All answers A–Z

Primary care role

• Growth and pubertal development at each visit
• Uveitis screening on schedule (every 3 months for high-risk children)
• Inactivated vaccines up to date; discuss live vaccines with rheumatology
• School participation, physical activity and mental health

Monitoring (ACR 2026)

• Methotrexate: CBC, liver tests and kidney function within the first 1–2 months, then every 3–4 months
• TNF inhibitors: CBC and liver tests yearly
• IL-6 inhibitors: within 1–2 months, then every 3–4 months, plus lipids every 6 months
• NSAIDs: every 6–12 months
• Hydroxychloroquine: CBC and liver tests yearly, plus baseline and yearly retinal screening

Contact rheumatology for new joint swelling, uveitis, slowing growth, abnormal labs or side effects.

Rule out the emergencies first: infection (fever, refusal to bear weight) and malignancy (night pain, abnormal counts, an ill child).

Then examine every joint, including the jaw, neck and hips. Children with JIA often don't complain of pain.

Reasonable first tests: CBC with differential and blood film, ESR, CRP, metabolic panel, LDH; ANA if JIA is possible (for uveitis risk).

Refer persistent swelling (6 weeks or more), morning stiffness or limp to pediatric rheumatology, and arrange an eye exam.

These antibodies carry diagnostic and prognostic meaning:

• Anti-dsDNA: lupus; higher levels are linked with nephritis
• Anti-Sm: highly specific for lupus
• Anti-U1 RNP: MCTD, lupus
• Anti-Scl-70 (topoisomerase I): diffuse systemic sclerosis, ILD
• Anti-centromere: limited systemic sclerosis, pulmonary hypertension
• Anti-RNA polymerase III: diffuse SSc, renal crisis, cancer association
• Anti-SSA/Ro, anti-SSB/La: Sjögren's disease, lupus, neonatal lupus and congenital heart block
• Anti-Jo-1 and other antisynthetase antibodies: myositis with ILD

Refer with CBC, metabolic panel, urinalysis with protein-to-creatinine ratio, C3/C4 and a list of symptoms. Urgency depends on the picture: urgent with symptoms, abnormal blood counts or urine findings; an isolated anti-SSA/Ro or anti-centromere in a well person can usually be a routine referral. SSA/Ro in pregnancy needs prompt coordination with maternal-fetal medicine.

Contact rheumatology promptly, and involve obstetrics. Uncontrolled inflammation carries more risk than most compatible treatments.

Options include prednisone or prednisolone at the lowest effective dose, intra-articular injections, hydroxychloroquine, sulfasalazine, azathioprine, tacrolimus and TNF inhibitors.

Avoid NSAIDs from 20 weeks.

In lupus, new hypertension or proteinuria needs urgent assessment to distinguish preeclampsia from nephritis.

A positive ANA is common in healthy children, and on its own does not diagnose JIA or lupus. It is often ordered for non-specific aches, which leads to unnecessary worry.

When it matters

• In a child with confirmed JIA, a positive ANA raises uveitis risk and changes the eye-screening schedule.
• With lupus features (rash, ulcers, cytopenias, proteinuria, arthritis, fever), it supports a referral.

Without symptoms: check CBC and urinalysis; if normal, reassure. Avoid ordering ANA for growing pains or hypermobility.

Signs of a flare: new joint swelling, longer morning stiffness, rising CRP or ESR, return of rash, ulcers, fevers or fatigue, or new organ symptoms.

First, check for other causes: infection (especially on immunosuppression), missed doses, drug interactions, or a new problem (gout, a mechanical injury).

Then

• Contact rheumatology, especially for organ symptoms (urgent in lupus with kidney or neurologic features).
• A short glucocorticoid course or a joint injection may help, ideally agreed with rheumatology so it fits the treatment plan.
• Avoid starting long glucocorticoid courses without a taper plan.

Most acute back pain is mechanical and improves within weeks.

Management: stay active, use heat, NSAIDs if appropriate, and physical therapy if not improving. Imaging isn't needed without red flags.

Re-evaluate if pain persists beyond 6–12 weeks, red flags appear, or inflammatory features develop (night pain, prolonged morning stiffness, improvement with exercise).

Diagnosis: joint aspiration showing urate crystals confirms gout. A typical first-MTP flare with a high urate can be diagnosed clinically, but aspirate if the presentation is atypical or infection is possible. Serum urate can be normal during a flare; recheck 2 or more weeks later.

Treat the flare early with one of:

• Colchicine (low-dose regimen; reduce in CKD and watch interactions)
• An NSAID at full dose if safe
• A glucocorticoid: oral, or intra-articular for one large joint

Then consider urate-lowering therapy. It is strongly recommended with tophi, radiographic damage, or 2 or more flares a year, and conditionally after a first flare with CKD stage 3 or worse, a urate above 9 mg/dL, or kidney stones.

Common causes

• Transient synovitis: young children, often after a viral illness, settles within days
• Perthes disease: ages about 4–8; hip, groin or knee pain with a limp
• Slipped capital femoral epiphysis (SCFE): adolescents, especially with obesity; hip or knee pain. Get hip X-rays, including frog-leg views.
• Fracture, including toddler's fracture
• Non-accidental injury when the history doesn't fit

Knee pain can be referred from the hip, so examine and image the hip.

Refer to pediatric orthopedics for structural causes. Consider JIA if swelling persists beyond 6 weeks, and infection or malignancy if the child is unwell.

Acute rheumatic fever follows group A streptococcal pharyngitis by 2–4 weeks. It causes migrating arthritis of large joints, carditis, chorea, erythema marginatum and subcutaneous nodules (revised Jones criteria, AHA 2015).

Tests: ASO and anti-DNase B, throat culture or rapid antigen test, ESR, CRP, CBC, ECG (prolonged PR interval) and an echocardiogram (subclinical carditis is common).

Management: treat the strep infection, coordinate with cardiology, and plan long-term secondary prophylaxis with penicillin. Arthritis usually responds dramatically to NSAIDs.

Reactive arthritis after strep (non-migratory, less NSAID-responsive) is a related condition.

Still's disease causes daily spiking fevers (often 39 °C or higher), an evanescent salmon-pink rash with the fever, sore throat, arthritis, lymph node and spleen enlargement, neutrophilia, raised liver tests and a very high ferritin.

It is a diagnosis of exclusion. Rule out infection, lymphoma and other cancers, and drug reactions.

Tests: CBC with differential, metabolic panel with liver tests, ferritin, CRP and ESR, LDH, blood cultures.

Treatment: EULAR/PReS 2024 favors early IL-1 or IL-6 blockade over prolonged glucocorticoids.

Emergent: falling blood counts, a rising ferritin or falling fibrinogen suggest macrophage activation syndrome.

Postpartum flares are common, especially in RA and lupus, often within the first 3 months. Plan follow-up and treatment before delivery.

Breastfeeding: many medicines are compatible, including hydroxychloroquine, sulfasalazine, azathioprine, tacrolimus, prednisone and all TNF inhibitors; most other biologics are considered compatible. Avoid leflunomide, mycophenolate, cyclophosphamide and JAK inhibitors.

Thrombosis risk is higher for about 6 weeks after delivery in APS.

Contraception: discuss before discharge; avoid estrogen-containing methods with antiphospholipid antibodies.

Less helpful: "Joint pains, positive ANA. Please see."

More helpful: "42-year-old woman with 8 weeks of painful swelling of both wrists and the 2nd–3rd MCPs, morning stiffness 90 minutes, now struggling to open jars. On exam: synovitis of the right wrist and MCPs 2–3 on both sides; squeeze test positive. CRP 22 mg/L, RF 45 IU/mL, anti-CCP pending, hand and foot X-rays normal. Ibuprofen gives partial relief; no glucocorticoids given. Hepatitis B and C sent. No rash, ulcers or eye symptoms. Not pregnant; uses an IUD. Question: possible early RA. Please assess for DMARD treatment. Happy to start therapy locally with your guidance."

The second version can be triaged correctly in seconds: it shows synovitis, duration, objective markers, and what has been done.

Some labs screen with ELISA or multiplex assays that report only positive or negative. These methods can differ from immunofluorescence (HEp-2 IFA), which remains the reference method.

Steps: ask the lab whether a titer and pattern by HEp-2 IFA are available, or whether reflex antibody results (ENA, dsDNA) were run.

Then use the same approach: symptoms first, then follow-up tests. A screen-positive result without symptoms, and with negative follow-up antibodies, rarely needs referral.

Higher titers are more likely to be clinically meaningful, but 1:160 is still found in about 5% of healthy people.

Steps

• ENA panel (Sm, RNP, SSA/Ro, SSB/La, Scl-70, centromere), anti-dsDNA, C3/C4
• CBC, metabolic panel, urinalysis with microscopy

Other causes of a positive ANA: autoimmune thyroid and liver disease, drugs (hydralazine, procainamide, minocycline, TNF inhibitors), infections, malignancy, and relatives of people with autoimmune disease.

If all follow-up tests are negative and there are no symptoms, reassure and review if symptoms appear. Refer if any specific antibody is positive, a test is abnormal, or symptoms fit a connective tissue disease.

Anti-SSA/Ro antibodies can cross the placenta and cause neonatal lupus, including congenital heart block (about 2% of first pregnancies, higher after a previously affected child).

Care

• Coordinate rheumatology and maternal-fetal medicine.
• Hydroxychloroquine is recommended, as it lowers the risk of heart block, especially after an affected pregnancy.
• Fetal heart rhythm monitoring (fetal echocardiography or Doppler PR interval), typically from about 16 to 26 weeks. Some centers add home fetal heart rate monitoring.
• After birth: an infant ECG, and watch for rash and low counts.

Persistent antiphospholipid antibodies without events: low-dose aspirin is often recommended during pregnancy.

Obstetric APS (prior pregnancy loss or placental complications): low-dose aspirin plus prophylactic-dose heparin (usually LMWH) is typical.

Thrombotic APS: therapeutic-dose LMWH plus low-dose aspirin. Warfarin is teratogenic, so switch before about 6 weeks of gestation; DOACs are not used in pregnancy.

Postpartum: thrombosis risk stays high for about 6 weeks; prophylaxis is usually continued.

APS is suggested by venous or arterial thrombosis (especially young, unprovoked or at unusual sites) or pregnancy morbidity, with antiphospholipid antibodies that persist for 12 weeks or more.

Testing

• Lupus anticoagulant, anticardiolipin IgG and IgM, anti-β2-glycoprotein I IgG and IgM
• Repeat any positive result after at least 12 weeks
• Note the anticoagulant at the time of testing; DOACs, warfarin and heparin all interfere with lupus anticoagulant assays

Treatment points

• Warfarin is preferred for confirmed thrombotic APS. DOACs, rivaroxaban in particular, are not recommended for triple-positive or arterial APS.
• Pregnancy needs specialist planning (usually low-dose aspirin, and heparin depending on history).

First priority: exclude infection. Aspirate when possible, before antibiotics, and send fluid for cell count, Gram stain, culture and crystals.

Also helpful: CBC, ESR, CRP, uric acid, blood cultures if febrile, and an X-ray of the joint.

Synovial fluid white cell count, roughly

• Under 2,000/µL: non-inflammatory (OA, trauma)
• 2,000–50,000/µL: inflammatory (crystals, inflammatory arthritis)
• Over 50,000/µL: septic until proven otherwise, though crystals can do this too

If you can't aspirate and infection is possible, send the patient to the emergency department or orthopedics the same day.

Red flags usually point to services other than rheumatology first.

• Cauda equina syndrome or cord compression (saddle anesthesia, new bladder or bowel dysfunction, progressive leg weakness): emergency department and spine surgery, immediately.
• Possible infection (fever, IV drug use, recent bacteremia, immunosuppression): urgent MRI and same-day assessment for discitis or epidural abscess.
• Possible malignancy (cancer history, weight loss, night pain at rest): MRI and the local cancer pathway.
• Possible fracture (osteoporosis, glucocorticoids, trauma, or a fused spine in ankylosing spondylitis, where minor trauma can cause unstable fractures): urgent imaging.

TNF inhibitors can be continued throughout pregnancy (EULAR 2024). Certolizumab crosses the placenta minimally. Other TNF inhibitors cross in the third trimester, so some teams adjust timing based on disease activity.

Infant vaccines after exposure in the womb

• Inactivated vaccines can be given on schedule to all infants.
• Live vaccines in the first 6 months (rotavirus, and BCG where used) depend on which biologic was used, how late in pregnancy, and how much crosses the placenta. Discuss with the pediatrician and rheumatology. Certolizumab exposure generally doesn't require a delay.

Rituximab late in pregnancy can deplete the newborn's B cells.

Before starting: TB screening, hepatitis B and C, vaccines updated, CBC and liver tests.

On treatment: infection awareness (fever needs prompt assessment), no live vaccines, skin checks, and labs depending on the class.

Around procedures: most need a short pause before major surgery; dental work rarely needs changes.

In pregnancy: TNF inhibitors can continue; plan the infant's live vaccines.

The DMARD table has class-by-class details.

Biosimilars are highly similar versions of reference biologics (adalimumab, etanercept, infliximab, rituximab, tocilizumab, ustekinumab and others), with no clinically meaningful differences in safety or effectiveness.

Switching from a reference product to a biosimilar is generally well tolerated; some patients notice a difference in injection devices or excipients. The 2026 ACR axSpA guideline conditionally prefers continuing the originator over switching for patients doing well, while acknowledging that payers often require switches.

Practical points: keep the same monitoring, record the product name and batch, and counsel patients about new devices.

DXA of the hip and spine for women 65 and older, younger postmenopausal women at increased risk, and people on long-term glucocorticoids or with other risk factors.

Vertebral fracture assessment (or lateral spine X-ray) when there is height loss, kyphosis or back pain, since vertebral fractures change management.

Repeat DXA every 1–3 years depending on risk and treatment. Use the same machine where possible.

Leukemia and other cancers (neuroblastoma, bone tumors) can mimic JIA.

Red flags: night pain or pain out of proportion to the exam, bone pain rather than joint pain, fever, weight loss, pallor, bruising, low blood counts or blasts, a high LDH or uric acid, and an ill-appearing child.

Same-day or urgent: CBC with blood film, LDH, uric acid, and imaging. Contact pediatric hematology-oncology urgently. Avoid glucocorticoids until malignancy is excluded; they can mask leukemia.

Compatible (EULAR 2024): hydroxychloroquine, sulfasalazine (healthy term infants), azathioprine, tacrolimus, cyclosporine, colchicine, prednisone and prednisolone, IVIG, non-selective NSAIDs, and all TNF inhibitors. Most other biologics are considered compatible, as they pass into milk in very small amounts.

Methotrexate: generally avoided; EULAR 2024 says it may be considered at 25 mg/week or less if there is no compatible alternative.

Avoid: leflunomide, mycophenolate, cyclophosphamide and JAK inhibitors.

LactMed is a useful, regularly updated reference for individual drugs.

CPPD causes acute attacks (often the knee or wrist in older adults, sometimes after illness or surgery), chronic inflammatory arthritis that resembles RA, or OA in unusual joints (MCPs, wrists, shoulders).

Diagnosis: CPP crystals in joint fluid; chondrocalcinosis on X-ray or ultrasound supports it.

Acute attack: aspirate (and culture) when possible. Treat with joint injection, an NSAID, colchicine or a short course of oral glucocorticoids.

If onset is before about 60, or disease is widespread, check calcium, phosphate, magnesium, ferritin and transferrin saturation (hemochromatosis), alkaline phosphatase and TSH.

Refer for recurrent attacks, chronic inflammatory CPPD, young onset, or diagnostic uncertainty.

EULAR 2024 points to consider support the use of targeted therapies after a cancer diagnosis in many situations, with decisions shared between rheumatology and oncology based on cancer type, stage, time since treatment and recurrence risk.

General points

• TNF inhibitors don't appear to increase the risk of most solid tumor recurrence, but skin cancer surveillance is important.
• Rituximab is often favored after lymphoma.
• JAK inhibitors carry a malignancy warning, particularly in older patients and smokers.

Checkpoint inhibitor patients who develop rheumatic side effects need joint rheumatology-oncology care.

Keep age-appropriate screening up to date for all patients.

Specific points

• Skin checks and sun protection for patients on azathioprine, TNF inhibitors and other immunosuppressants (higher non-melanoma skin cancer risk).
• Cervical screening may need to be more frequent in women with lupus or on immunosuppression; follow national guidance for immunocompromised patients.
• Sjögren's disease carries a raised lymphoma risk: watch for persistent gland swelling or lymph nodes.
• Dermatomyositis is associated with cancer; screening is tailored by risk.
• JAK inhibitors carry a malignancy warning, particularly in older adults and smokers.

RA, lupus, psoriatic arthritis, gout and other inflammatory diseases raise cardiovascular risk, and calculators often underestimate it.

Practical points

• In RA, EULAR suggests multiplying the calculated risk by about 1.5 if the tool doesn't include RA.
• Manage blood pressure, lipids, glucose and smoking as you would for a higher-risk patient.
• Controlling inflammation lowers risk; minimize long-term NSAIDs and glucocorticoids.
• Lupus and antiphospholipid syndrome carry particular risks of premature atherosclerosis and thrombosis.

CAPS causes thrombosis in three or more organs over days, often triggered by infection, surgery, stopping anticoagulation or pregnancy. Kidney failure, lung and brain involvement, skin necrosis and thrombocytopenia are common.

Same day: admit, usually to intensive care. Treatment generally combines anticoagulation, glucocorticoids and plasma exchange or IVIG. Involve hematology and rheumatology.

Anti-PD-1, anti-PD-L1 and anti-CTLA-4 cancer treatments can cause:

• Inflammatory arthritis (RA-like, oligoarticular or reactive-like), usually RF and anti-CCP negative
• A PMR-like illness, sicca, or vasculitis
• Myositis, which can overlap with myocarditis and myasthenia (weakness, ptosis, double vision, trouble swallowing, breathlessness, a troponin rise)

Many rheumatic side effects persist after the checkpoint inhibitor stops.

Steps: refer promptly and coordinate with oncology. Check CBC, metabolic panel, CRP/ESR, CK, RF, anti-CCP and ANA; troponin and an ECG if there is weakness or any cardiac symptom.

Suspected myositis or myocarditis is an emergency. Steroid-sparing DMARDs are often needed, chosen with the oncology team.

Childhood-onset lupus is usually more severe than adult lupus, with higher rates of nephritis, cytopenias and neuropsychiatric disease.

Features: rash, arthritis, fever, mouth ulcers, hair loss, cytopenias, proteinuria or hematuria, hypertension. Nearly all have a positive ANA, often with anti-dsDNA or anti-Sm and low complements.

Tests: ANA, anti-dsDNA, ENA, C3/C4, CBC, metabolic panel, urinalysis with microscopy, urine protein-to-creatinine ratio, and blood pressure.

Kidney, lung, brain or severe blood involvement is emergent. The 2025 ACR SLE guideline applies to children and adults.

CNO causes recurrent bone pain from sterile bone inflammation, often in several sites (metaphyses of long bones, clavicle, pelvis, spine). It can mimic infection or malignancy. It may come with psoriasis, palmoplantar pustulosis or IBD.

Steps: whole-body MRI is the preferred imaging. Biopsy is often needed to exclude infection and malignancy, especially with a single lesion. Inflammatory markers are normal or only mildly raised.

Treatment: NSAIDs first-line; bisphosphonates or TNF inhibitors for refractory or spinal disease.

EULAR/ACR classification criteria for pediatric CNO were published in 2025.

• Methotrexate: nausea, fatigue the day after dosing, mouth ulcers, hair thinning, mildly raised liver tests. Splitting the dose, taking it at night, switching to subcutaneous injection, or increasing folic acid often helps. New cough or breathlessness can be pneumonitis.
• Leflunomide: diarrhea, hypertension, raised liver tests, weight loss, hair thinning, neuropathy.
• Sulfasalazine: nausea, rash, headache, orange body fluids; rare blood dyscrasias, usually in the first 3 months.
• Hydroxychloroquine: GI upset, rash, rare skin pigmentation; retinal toxicity with long-term or high-dose use.
• Azathioprine: nausea, a flu-like hypersensitivity reaction early on, pancreatitis, low counts.
• Mycophenolate: diarrhea and GI upset, infections.
• Biologics: injection-site or infusion reactions, infections.
• JAK inhibitors: shingles, raised lipids, low lymphocytes.

These thresholds are widely used in shared-care protocols. Reaching one usually means pausing the drug and contacting the prescribing team:

• White cells below 3.5 × 10⁹/L
• Neutrophils below 1.6 × 10⁹/L
• Platelets below 140 × 10⁹/L
• ALT or AST above 100 U/L
• An unexplained fall in albumin below 30 g/L
• Creatinine up by more than 30% from baseline, or a falling eGFR
• MCV above 105 fL (check B12, folate and TSH)
• An unexplained eosinophilia above 0.5 × 10⁹/L

Trends matter. BSR 2025 emphasizes reviewing trends over time, as many isolated abnormalities are transient or unrelated to the drug.

COVID-19 vaccines are recommended for people on immunosuppression, following the current CDC schedule (which may include additional doses for moderately or severely immunocompromised people).

Responses are reduced on rituximab, mycophenolate, high-dose glucocorticoids and some other drugs. Timing doses before a rituximab cycle helps.

Medication holds: some guidance has suggested holding methotrexate for about 1–2 weeks after vaccination if disease allows (BSR 2025 includes this for adults); follow current guidance and the prescribing team's advice.

Cryoglobulins are immunoglobulins that precipitate in the cold. They can cause purpura, arthralgia, neuropathy, glomerulonephritis and skin ulcers.

Testing pitfalls: the blood must be kept at body temperature until the lab separates it, or false negatives are common. A low C4 and a positive RF are typical clues.

Causes: hepatitis C (most common), hepatitis B, HIV, Sjögren's disease, lupus, lymphoma and other B-cell disorders.

Next steps: hepatitis B and C, HIV, serum protein electrophoresis, urinalysis, creatinine, RF, C3/C4. Refer with vasculitic features; kidney involvement is urgent.

The dense fine speckled pattern is caused by antibodies to DFS70. It is relatively common in healthy people.

When anti-DFS70 is the only antibody present (no other ENA or dsDNA positivity) and there are no symptoms, it is less likely to indicate systemic autoimmune disease. Many labs can confirm anti-DFS70 specifically.

Refer only if symptoms or other antibodies suggest a connective tissue disease.

Routine dental work (cleaning, fillings, most extractions) generally doesn't require stopping DMARDs or biologics.

Bisphosphonates and denosumab: osteonecrosis of the jaw is rare; good dental care before starting and during treatment helps. Major dental surgery in patients on high-dose antiresorptives may need coordination with the dentist.

Antibiotic prophylaxis isn't routinely needed for patients on DMARDs; prosthetic joint prophylaxis follows dental and orthopedic guidance.

Skin signs of dermatomyositis include a violet heliotrope rash on the eyelids, Gottron papules over the knuckles, a V-sign or shawl rash, mechanic's hands, and ragged cuticles with dilated nailfold capillaries. Weakness may be mild or absent (clinically amyopathic dermatomyositis).

Tests: CK, aldolase, AST/ALT, LDH, CBC, metabolic panel, ANA, myositis antibody panel. A skin biopsy can help.

Why it matters

• Adult dermatomyositis is associated with cancer, so screening is part of the workup.
• Anti-MDA5 dermatomyositis (skin ulcers, little weakness) can cause rapidly progressive lung disease. New breathlessness is an emergency.

In children this is juvenile dermatomyositis; see the pediatric section.

Emergent: a persistently white, blue or black digit, severe pain at rest, or gangrene. This is critical ischemia and needs same-day assessment (emergency department or vascular surgery, with rheumatology). Consider emboli, vasculitis and antiphospholipid syndrome as well as systemic sclerosis.

Urgent: active digital ulcers or new pitting scars. Refer within days to a couple of weeks.

Meanwhile: keep warm, stop smoking, start or increase a calcium channel blocker if blood pressure allows, treat infected ulcers, and give analgesia. Check ANA with SSc antibodies, CBC, metabolic panel, ESR/CRP and antiphospholipid antibodies.

• Methotrexate + trimethoprim or trimethoprim-sulfamethoxazole: marrow suppression. Avoid.
• Methotrexate + NSAIDs or PPIs: usually fine at rheumatology doses, but watch kidney function.
• Azathioprine + allopurinol or febuxostat: dangerous marrow suppression. Febuxostat is contraindicated; allopurinol needs a large azathioprine dose reduction under specialist advice.
• Calcineurin inhibitors + azoles, macrolides, grapefruit, some anticonvulsants: large changes in drug levels.
• Colchicine + clarithromycin, some azoles, cyclosporine, verapamil or diltiazem: colchicine toxicity.
• Live vaccines + immunosuppressants: generally avoid.
• Hydroxychloroquine + other QT-prolonging drugs: consider an ECG.

The DMARD monitoring table on this site lists baseline tests, monitoring, key cautions, pregnancy and breastfeeding information and vaccine considerations for each drug and drug class.

The prescribing team's shared-care plan takes precedence. When in doubt about a result or side effect, pausing a csDMARD for a few days while you ask is rarely harmful. Abruptly stopping glucocorticoids can be.

• Drug-induced lupus: hydralazine, procainamide, minocycline, isoniazid, TNF inhibitors and others. Arthralgia, serositis and rash; anti-histone antibodies are common. Kidney and brain involvement are rare. It usually resolves within weeks to months of stopping the drug.
• Statin myopathy, including anti-HMGCR immune-mediated necrotizing myopathy
• ANCA vasculitis linked with hydralazine, propylthiouracil and levamisole-adulterated cocaine
• Arthralgia or arthritis from aromatase inhibitors, DPP-4 inhibitors and checkpoint inhibitors; tendinopathy from fluoroquinolones
• Gout from diuretics, cyclosporine and low-dose aspirin

Steps: stop or switch the drug where possible, with the prescriber. Refer if symptoms persist more than about a month after stopping, there is organ involvement, or it is unclear whether the disease is drug-induced.

Causes beyond Sjögren's disease: age, medicines, diabetes, mouth breathing, anxiety, thyroid eye disease, hepatitis C, HIV, IgG4-related disease, sarcoidosis, amyloidosis, graft-versus-host disease and radiation.

Tests: ANA, SSA/Ro, SSB/La, RF, CBC, metabolic panel, IgG or serum protein electrophoresis, hepatitis C. A Schirmer test, ophthalmology and dental review help.

A negative SSA/Ro doesn't fully exclude Sjögren's disease; a lip biopsy can help in specialist hands.

Many common medicines cause dry eyes and mouth:

• Anticholinergics, including bladder antispasmodics and some antiemetics
• Antihistamines and decongestants
• Tricyclic antidepressants, SSRIs and SNRIs
• Antipsychotics
• Diuretics and some antihypertensives (clonidine)
• Opioids
• Isotretinoin

Steps: review and, where possible, reduce or switch these medicines, and reassess after a few weeks. If dryness persists, check ANA, SSA/Ro, SSB/La and RF.

Continue: methotrexate, leflunomide, hydroxychloroquine, sulfasalazine and apremilast.

Hold biologics so that surgery falls at the end of the dosing interval (for example, surgery in week 3 for a biologic given every 2 weeks; week 5 for every 4 weeks). Restart about 14 days after surgery once the wound is healing and there is no infection.

Hold JAK inhibitors for 3 days before surgery.

Glucocorticoids: continue the usual daily dose; routine stress dosing isn't recommended.

The guideline was written for hip and knee replacement; other surgeons often apply similar principles.

Don't delay emergency surgery because of rheumatology medicines.

• Hold the biologic or JAK inhibitor after surgery until the wound is healing and there is no infection.
• Continue glucocorticoids at the usual dose; anesthesia may give additional cover per protocol.
• Inform rheumatology for advice on restarting.
• Watch closely for infection; signs can be muted on IL-6 inhibitors.

Tender, red, warm nodules, usually on the shins, that fade like bruises over weeks.

Common causes: streptococcal infection, sarcoidosis (Löfgren syndrome: with hilar lymphadenopathy and ankle periarthritis), inflammatory bowel disease, pregnancy and oral contraceptives, other drugs, TB and other infections, and idiopathic.

Tests: CBC, ESR or CRP, ASO or throat swab, chest X-ray (hilar nodes), TB testing where relevant, a pregnancy test, and questions about bowel symptoms.

Management: rest, elevation and NSAIDs; treat the cause. Most cases settle within 6–8 weeks.

Refer if recurrent or chronic, with arthritis, or with hilar lymphadenopathy (sarcoidosis).

CRP rises and falls within days and isn't affected by anemia or proteins, so it is better for tracking acute inflammation.

ESR changes slowly and is affected by age, sex, anemia, kidney disease and immunoglobulins.

Neither is specific. Infection, malignancy, obesity and smoking all raise them. Normal values don't exclude inflammatory disease; many people with psoriatic arthritis, axSpA or early RA have normal markers.

Use them to support a clinical picture, and for monitoring diseases where they track activity (PMR, GCA, RA).

Methotrexate is cleared by the kidneys; toxicity rises as function falls. A rise in creatinine of more than 30% from baseline, or an eGFR below 60, should prompt a repeat test and a call to the prescribing team. Methotrexate is generally avoided below an eGFR of 30.

Check for causes: dehydration, NSAIDs, ACE inhibitors or diuretics, infection, and urinary obstruction.

Calcineurin inhibitors (tacrolimus, cyclosporine, voclosporin) can also reduce kidney function. Check blood pressure, and drug levels for tacrolimus and cyclosporine. Voclosporin has no level monitoring; it is dosed by eGFR, checked every 2 weeks for the first month, then every 4 weeks.

Undifferentiated connective tissue disease describes a positive ANA plus one or more features (Raynaud's, arthralgia, rash, sicca, mild cytopenias) without enough to meet criteria for a defined disease. Most patients stay stable; a minority evolve, usually within the first few years.

Usual workup recommended before the referral is seen: ANA (titer and pattern), ENA panel, anti-dsDNA, C3/C4, CBC with differential, metabolic panel, urinalysis, ESR/CRP. Photos of any rash and a symptom diary help.

Raise urgency if organ features appear: proteinuria or hematuria, cytopenias, breathlessness, weakness or serositis.

Treat as possible meningococcal or other bacterial sepsis first. A febrile child (or adult) with a non-blanching petechial or purpuric rash, particularly one who looks unwell, needs emergency assessment and antibiotics without delay.

Once sepsis is excluded, consider IgA vasculitis (well child, purpura on the legs and buttocks, usually without high fever), other vasculitides, and hematologic causes (ITP, leukemia).

Basics for everyone: calcium (preferably from diet) and vitamin D, weight-bearing and balance exercise, fall prevention, stopping smoking and limiting alcohol.

First-line medicine: an oral bisphosphonate (alendronate or risedronate), or IV zoledronic acid if oral is unsuitable. Check kidney function and vitamin D first, and ask about dental health.

Denosumab is an alternative, but must not be stopped without a plan: stopping without follow-on therapy causes rebound vertebral fractures. In advanced CKD, especially on dialysis, an FDA boxed warning (2024) highlights severe, sometimes fatal hypocalcemia. There, decide with nephrology whether to use it; before treatment, check calcium, assess for CKD mineral and bone disorder, and correct low calcium (with calcium and activated vitamin D); afterwards, monitor calcium closely, especially 2–10 weeks after each dose.

Very high fracture risk (recent or multiple fractures, very low T-score) may warrant an anabolic agent first (teriparatide, abaloparatide, romosozumab), usually through a specialist.

Review after 3–5 years of bisphosphonate to consider a drug holiday in lower-risk patients.

• Metabolic: hyperglycemia (check glucose or HbA1c), weight gain, hypertension, dyslipidemia
• Bone and muscle: osteoporosis and fractures, osteonecrosis, myopathy
• Eyes: cataract and glaucoma (eye checks on long-term treatment)
• Infection: risk rises with dose and duration, including Pneumocystis
• Skin: thinning, bruising, poor wound healing
• Mood and sleep: insomnia, mood changes, occasionally psychosis
• GI: peptic ulcer risk, especially with NSAIDs
• Adrenal suppression after prolonged use

Use the lowest effective dose for the shortest time, and plan steroid-sparing treatment early with rheumatology.

ACR 2022 GIOP guideline

• Assess fracture risk (FRAX, adjusted for glucocorticoid dose, and bone density) as soon as possible after starting prednisone 2.5 mg daily or more for 3 months or more.
• Everyone: calcium and vitamin D, exercise, fall prevention, smoking cessation and limiting alcohol.
• Moderate risk: a bisphosphonate, denosumab or a PTH/PTHrP analog (teriparatide, abaloparatide), with no preferred order.
• High risk: denosumab or a PTH/PTHrP analog is conditionally preferred over a bisphosphonate, though an oral bisphosphonate is far better than no treatment.
• Very high risk: a PTH/PTHrP analog is preferred. Romosozumab or raloxifene only if other options aren't suitable.
• Repeat bone density with vertebral fracture assessment (or a spine X-ray) every 1–2 years while glucocorticoids continue.

Bone loss is fastest in the first months, so start protection early.

ACR/AAHKS 2022: for patients on long-term glucocorticoids having hip or knee replacement, continue the usual daily dose rather than giving supraphysiologic stress doses.

Practical points: make sure the morning dose is given on the day of surgery, monitor blood pressure and glucose, and be alert to adrenal insufficiency (unexplained hypotension). Other surgeries follow anesthesia protocols.

• Use the lowest effective dose for the shortest time.
• Plan bone protection, and monitor glucose, blood pressure and mood.
• Taper courses longer than about 3 weeks.
• Agree long-term steroid plans with rheumatology, and plan steroid-sparing treatment early.
• Don't stop long-term glucocorticoids abruptly, especially during illness.
• Suspected GCA is the main exception to "wait for the specialist": treat now.

Polyarticular gout and chronic CPPD can mimic RA. Polyarticular gout usually reflects long-standing, under-treated hyperuricemia and often comes with tophi.

Steps: aspirate an accessible joint for crystals and culture; X-rays of hands and feet; urate, kidney function, CBC, CRP. For CPPD, check calcium, magnesium, phosphate, iron studies and TSH if onset was before about 60.

Refer for tophaceous or polyarticular gout, or for chronic inflammatory CPPD. Start or optimize urate-lowering therapy for gout.

Allopurinol is still first-line in CKD. Start lower (for example, 50 mg daily in CKD 4 or worse) and titrate gradually to target; the ACR supports dose escalation above traditional kidney-based limits with monitoring.

Flares: avoid NSAIDs in significant CKD; reduce colchicine doses and avoid it in dialysis or with interacting drugs. Glucocorticoids are often the safest option.

Refer for CKD stage 4–5, transplant, dialysis, or inability to reach target.

Refer when

• Tophi or radiographic damage are present
• Flares continue despite a urate at target, or urate stays above 6 mg/dL despite titration
• Allopurinol causes intolerance or hypersensitivity
• CKD stage 4–5 or a transplant complicates treatment
• The diagnosis is uncertain (gout vs CPPD vs infection)

Before referring, check: adherence, the highest dose reached, interacting drugs (diuretics), and joint aspiration results if available.

Specialist options include higher allopurinol doses with monitoring, febuxostat, uricosurics such as probenecid, and pegloticase (usually with methotrexate) for refractory tophaceous gout.

Enthesitis-related arthritis and juvenile spondyloarthritis cause heel pain (Achilles or plantar fascia insertion), knee and hip arthritis, and later inflammatory back pain, most often in boys over 6. Acute anterior uveitis (a painful red eye) can occur.

Tests: ESR, CRP, HLA-B27.

Imaging (2026 ACR): SI joint MRI without contrast is preferred in children and adolescents with suspected axial disease; plain X-rays are less useful.

Refer within 2–4 weeks. Mechanical heel pain (Sever disease) is a common, benign alternative in active children.

Hereditary hemochromatosis can cause arthritis that looks like OA in unusual places: the 2nd and 3rd MCP joints ("iron fist"), wrists, hips and ankles. It is associated with CPPD (chondrocalcinosis).

Tests: ferritin and transferrin saturation (fasting), liver tests, and HFE genotyping if iron studies are raised.

Treatment: venesection treats the iron overload, though joint symptoms may not improve much. Refer to hepatology or hematology for iron overload, and to rheumatology for difficult arthritis.

Test all three: HBsAg, anti-HBc (total) and anti-HBs. CDC 2023 recommends this triple panel for adult screening.

Interpreting results

• HBsAg positive: chronic infection. Refer to hepatology or infectious disease; antiviral prophylaxis is needed before immunosuppression.
• HBsAg negative, anti-HBc positive: resolved infection. Reactivation risk depends on the drug, and is highest with rituximab (prophylaxis is often recommended). For other drugs, monitoring or prophylaxis per hepatology advice.
• All negative: vaccinate against hepatitis B.

Test: HCV antibody, with reflex HCV RNA if positive. Universal adult screening is recommended in the US.

If positive: refer for treatment; modern direct-acting antivirals cure most infections. Coordinate timing with rheumatology. Hepatitis C can also cause rheumatic symptoms (arthralgia, cryoglobulinemia, sicca, a positive RF).

The ESR depends on plasma proteins and red cells, so it can be raised without inflammation.

Common reasons: a paraprotein (myeloma, MGUS), polyclonal hypergammaglobulinemia (lupus, Sjögren's, liver disease), anemia, kidney disease, pregnancy, obesity, older age and female sex.

Lupus clue: CRP often stays normal in lupus flares unless there is serositis, arthritis or infection, while the ESR rises.

Tests: CBC, metabolic panel, serum protein electrophoresis with free light chains, immunoglobulins; ANA if lupus or Sjögren's features are present.

A rising MCV is common on methotrexate (folate antagonism) and azathioprine, and usually harmless on its own.

Above about 105 fL: check B12, folate and TSH, and consider alcohol and liver disease. Treat any deficiency. If they are normal, discuss with the prescribing team.

A rising MCV with falling counts can be an early sign of marrow toxicity, so look at the whole CBC.

Most people with high serum urate never develop gout. The ACR conditionally recommends against starting urate-lowering therapy for asymptomatic hyperuricemia.

Reasonable steps

• Look for contributors: alcohol, sugar-sweetened drinks, weight, kidney function, and medicines such as thiazide and loop diuretics.
• Manage cardiovascular and kidney risk factors.

Refer, or start treatment, if gout flares, tophi or urate kidney stones develop.

Ordinary hives come and go within hours. Lesions that last more than 24 hours, burn rather than itch, or leave bruising or pigmentation suggest urticarial vasculitis.

Associations: low complement levels (hypocomplementemic urticarial vasculitis, linked with lupus), infections, drugs, and paraproteins. In older adults with chronic hives, fevers and bone pain, consider Schnitzler syndrome (with an IgM monoclonal protein).

Tests: skin biopsy, CBC, ESR/CRP, C3, C4 (and C1q if available), ANA, urinalysis, serum protein electrophoresis.

Refer to dermatology or rheumatology, depending on systemic features.

HLA-B27 is present in roughly 6% of the US population, and most carriers never develop spondyloarthritis. It supports the diagnosis when symptoms fit; it doesn't make the diagnosis.

Useful when a patient has chronic back pain beginning before 45 with inflammatory features, enthesitis, anterior uveitis or reactive arthritis.

Not useful as a screening test without symptoms, and a negative result doesn't exclude axSpA.

Refer a positive result with inflammatory back pain, enthesitis, peripheral arthritis or uveitis (see axSpA). A positive result without symptoms doesn't need referral.

Synovitis is the finding that most changes urgency. Pain alone is not synovitis.

Clues on examination

• Soft, boggy or spongy swelling along the joint line, often warm
• Loss of the normal "valleys" between the knuckles when the patient makes a fist
• A positive squeeze test: pain when gently squeezing across the MCP or MTP joints
• Knee effusion: a bulge sign or patellar tap
• Reduced grip, or difficulty making a full fist

What synovitis is not

• Hard, bony enlargement (Heberden and Bouchard nodes in osteoarthritis)
• Tenderness without swelling, which is common in fibromyalgia and hypermobility

If you're still unsure: re-examine in 1–2 weeks, ask the patient to photograph any swelling when it is at its worst, and consider an ultrasound where one is available. Morning stiffness of more than 30–60 minutes and a positive squeeze test raise the likelihood of inflammatory arthritis. An e-consult can help decide whether the patient needs to be seen.

HPV vaccine (non-live) is recommended for eligible patients on immunosuppression. The ACR 2022 guideline conditionally recommends it for patients 27–45 on immunosuppressive treatment who weren't previously vaccinated, in addition to routine vaccination at younger ages.

Women with lupus and those on immunosuppression have higher rates of cervical dysplasia, so vaccination and cervical screening both matter.

AAO 2026 recommendations (revised November 2025)

• A baseline retinal exam with OCT and fundus autofluorescence soon after starting
• Annual screening with OCT plus wide-field autofluorescence after 5 years of use; visual fields and multifocal ERG are add-on tests
• Annual screening from the start if there are major risk factors: a dose above 5 mg/kg/day of actual body weight, kidney disease, tamoxifen, or starting at an older age

Dosing: 5 mg/kg/day of actual body weight or less. In severe obesity, start lower and keep to 400 mg/day or less. Lower risk comes with lower doses.

Retinal toxicity is rare in the first years at recommended doses, but irreversible once established, so screening matters.

IgA vasculitis is the most common childhood vasculitis (peak age 3–10). It causes palpable purpura on the legs and buttocks, with arthralgia or arthritis, colicky abdominal pain, and kidney involvement (hematuria or proteinuria) that can appear weeks to months later.

First, exclude infection. Fever, an ill-appearing child, or a rapidly spreading non-blanching rash needs emergency assessment for meningococcal or other bacterial sepsis before IgA vasculitis is considered.

Most well children recover within weeks. Manage pain supportively.

Monitor: urinalysis and blood pressure for at least 6–12 months from onset (SHARE 2019), more often in the first weeks. Involve pediatric nephrology once nephritis is confirmed (KDIGO 2025).

Refer urgently for significant proteinuria, nephrotic or nephritic features, a rising creatinine, hypertension, or severe abdominal pain (intussusception, bleeding). Refer for recurrent or atypical episodes.

IgG4-related disease causes swelling and fibrosis of organs: salivary and lacrimal glands, pancreas (autoimmune pancreatitis), bile ducts, retroperitoneum, aorta, orbits, lungs and kidneys. It can mimic cancer.

Tests: serum IgG4 and IgG subclasses (raised in many, but not all, patients), CBC with eosinophils, metabolic panel, lipase if relevant, C3/C4, urinalysis, and imaging of the affected area.

Biopsy is usually needed to exclude lymphoma and other cancers.

Urgent: obstructive jaundice, hydronephrosis or aortic involvement.

Treatment: glucocorticoids, rituximab, and inebilizumab (FDA-approved for IgG4-RD in 2025).

ACR/CHEST 2023 (screening in people with systemic autoimmune rheumatic disease at increased risk)

• Recommended: PFTs (spirometry, lung volumes, DLCO) and HRCT chest
• Conditionally not recommended for screening: chest X-ray, 6-minute walk, ambulatory desaturation testing and bronchoscopy

ERS/EULAR 2025: screen everyone with systemic sclerosis, MCTD and inflammatory myositis (except inclusion body myositis); screen people with RA or Sjögren's disease when risk factors are present.

Highest risk: systemic sclerosis (especially with Scl-70), myositis with antisynthetase or MDA5 antibodies, MCTD; RA in older male smokers with high-titer RF or anti-CCP.

2026 ACR/SAA/SPARTAN guideline (adults)

• First test: an AP pelvis radiograph. It is preferred over a lumbar spine radiograph, and over a dedicated SI joint radiograph.
• If plain films are non-diagnostic: SI joint MRI without contrast, preferred over lumbar MRI, low-dose CT and bone scan. PET is not recommended.

Children and adolescents: SI joint MRI without contrast is preferred (gadolinium is not needed).

Notes: a normal X-ray doesn't exclude axSpA. MRI findings need expert interpretation, as bone marrow edema can occur in athletes, after childbirth, and in mechanical back pain. Routine repeat spine or pelvis X-rays are not recommended.

Plain X-rays show established gout (punched-out erosions with overhanging edges, tophi) and chondrocalcinosis in CPPD. Early gout is often normal on X-ray.

Ultrasound can show the "double contour" sign of urate on cartilage, tophi, and CPPD deposits, in experienced hands.

Dual-energy CT can map urate deposits when the diagnosis is uncertain and aspiration isn't possible.

Aspiration remains the reference test, and none of these imaging tests exclude infection.

X-rays of both hands and both feet at baseline, even in early disease. They may be normal early on, but they set a baseline for erosions and can show other diagnoses (CPPD, gout, psoriatic changes). Feet often show erosions before hands.

Ultrasound (with power Doppler), where available, can confirm synovitis when the exam is equivocal. MRI is used selectively by specialists.

Don't delay referral for imaging when synovitis is evident.

MRI of the thighs (STIR or fat-suppressed sequences) shows muscle edema, guides biopsy site selection, and helps when CK is normal or the diagnosis is unclear. It is usually arranged by the specialist.

Also consider: chest HRCT and PFTs for ILD (especially with antisynthetase or MDA5 antibodies), an echocardiogram or cardiac MRI if myocarditis is possible, and age-appropriate cancer screening, which in dermatomyositis may include CT imaging.

OA can be diagnosed clinically in people 45 or older with use-related pain and no morning stiffness or stiffness of under 30 minutes (NICE). Imaging isn't needed for a typical presentation.

X-rays help when the presentation is atypical, symptoms change rapidly, another diagnosis is suspected, or joint replacement is being considered.

Radiographic severity often doesn't match symptoms, so treat the patient, not the X-ray.

Suspected GCA: ultrasound of the temporal and axillary arteries is the recommended first test where a fast-track service exists (EULAR 2023); temporal artery biopsy is an alternative. Arrange it quickly, since findings can fade within days of starting glucocorticoids. Don't delay treatment for imaging.

Large-vessel involvement (aorta and branches), in GCA or Takayasu: MRA, CTA or PET-CT, usually arranged by the specialist.

Long-term: aortic aneurysm can develop years later in GCA, so periodic imaging is often considered.

Most regional soft-tissue problems are diagnosed clinically.

Ultrasound is useful for rotator cuff tears, tendinopathy, bursitis, ganglia and nerve entrapment, and for guiding injections.

MRI is reserved for surgical planning, suspected internal derangement, or atypical features.

Inflammatory clues (multiple sites, enthesitis with back pain or psoriasis) should prompt consideration of spondyloarthritis.

X-rays remain the first test for most joint problems, and they set a baseline.

Ultrasound shows synovitis, effusions, tendons, crystal deposits and vascular wall inflammation, but depends on operator expertise.

MRI detects early inflammation (SI joints, muscle, bone marrow) and is best ordered with a clear question.

Avoid routine imaging for typical mechanical back pain or OA, and don't delay an urgent referral waiting for imaging.

Minor infections (a cold, an uncomplicated UTI treated with oral antibiotics): most patients can continue treatment, though some teams prefer a short pause of methotrexate. Follow the shared-care plan.

Serious infections (needing IV antibiotics or admission, or with sepsis): pause DMARDs, biologics and JAK inhibitors, and inform the prescribing team. Restart once the infection has resolved and antibiotics are complete. Don't stop glucocorticoids abruptly; adrenal suppression can make illness worse.

Watch for

• Fewer signs of infection: IL-6 inhibitors suppress CRP and fever
• TB and atypical infections on TNF inhibitors
• Shingles on JAK inhibitors
• Pneumocystis on high-dose glucocorticoids with other immunosuppressants

Fever on immunosuppression needs a low threshold for same-day assessment.

Inflammatory back pain typically begins before 40–45, comes on gradually, lasts 3 months or more, improves with exercise but not rest, and wakes the patient in the second half of the night. Morning stiffness often lasts more than 30 minutes, and buttock pain may alternate sides.

Look for: uveitis, psoriasis, IBD symptoms, heel pain (enthesitis), dactylitis, a family history, and a good response to NSAIDs.

Workup: CRP, ESR, HLA-B27, and an AP pelvis radiograph (the preferred first imaging test in the 2026 ACR guideline).

Yearly inactivated influenza vaccine for everyone on immunosuppression; avoid the live nasal vaccine.

ACR 2022 guideline

• High-dose or adjuvanted vaccine for patients 65 and older, and conditionally for patients 18–64 on immunosuppressive medicines
• Methotrexate: consider holding it for 2 weeks after the vaccine if disease activity allows
• Rituximab: give the influenza vaccine on schedule (don't wait), and time future rituximab doses so vaccines can be given at least 2 weeks before where possible
• Other medicines generally continue

Injection-site reactions (redness, itching, swelling) are common with subcutaneous biologics in the first months and usually settle. Rotating sites, letting the pen reach room temperature, and cold packs help.

Infusion reactions (infliximab, rituximab, tocilizumab IV) range from flushing and fever to rare anaphylaxis. They are managed by the infusion team with slowing the infusion, premedication, or treatment.

Delayed reactions (serum sickness-like rash, arthralgia and fever days later) should be reported to the prescribing team.

Ferritin is an acute-phase protein as well as an iron store.

Mild to moderate rises (hundreds to around 1,000 ng/mL): inflammation, infection, liver disease, alcohol, metabolic syndrome, kidney disease, iron overload (check transferrin saturation for hemochromatosis).

Very high levels (several thousand or more): Still's disease, macrophage activation syndrome or HLH, severe infection, liver injury, and some cancers.

Danger signs: a very high or rapidly rising ferritin with fever and falling blood counts suggests MAS. That is an emergency.

Myositis-specific antibodies help define the clinical picture:

• Antisynthetase (Jo-1, PL-7, PL-12, EJ, OJ): ILD, mechanic's hands, arthritis, fever, Raynaud's
• MDA5: skin ulcers, little weakness, rapidly progressive ILD risk
• TIF1-γ and NXP2: cancer-associated dermatomyositis in adults; NXP2 with calcinosis
• Mi-2: classic dermatomyositis, often responsive to treatment
• SRP and HMGCR: necrotizing myopathy; HMGCR is linked with statins

Myositis-associated antibodies (Ro52, PM/Scl, Ku, U1 RNP) are seen in overlap syndromes.

Caution: line immunoassays can give weak false positives. Interpret results with the clinical picture and CK, and discuss unexpected results with rheumatology.

Same day first

• A very high CK with dark (cola-colored) urine, a rising creatinine or a high potassium suggests rhabdomyolysis: same-day assessment, often in the emergency department. A urine dipstick positive for blood without red cells on microscopy suggests myoglobin.
• Weakness with trouble swallowing or breathing is an emergency.

Common explanations: recent exercise, intramuscular injections, falls or other injury, seizures, hypothyroidism, statins and other drugs. People of African ancestry and very muscular people often have higher normal ranges.

If the patient is well

• Repeat after about a week without strenuous exercise.
• Check TSH, a metabolic panel with potassium and creatinine, and a urinalysis, and review medicines.
• Examine strength carefully, including neck flexion and hip flexion.

Refer urgently with proximal weakness, a dermatomyositis rash, or a CK that stays high after stopping a statin. A CK in the thousands with weakness is urgent.

May not need referral: a modest, stable rise (under about 3–5 times normal) without weakness and with a benign explanation. An e-consult can help decide whether persistent, unexplained rises need a visit; neurology may be the right destination for some.

Test method matters. The 2017 international consensus recommends antigen-specific immunoassays for PR3- and MPO-ANCA as the primary test; immunofluorescence (c-ANCA, p-ANCA) alone is less specific.

PR3-ANCA is typical of granulomatosis with polyangiitis; MPO-ANCA of microscopic polyangiitis and some EGPA. With compatible features, a positive PR3 or MPO result strongly supports ANCA vasculitis.

False positives and look-alikes: atypical p-ANCA by immunofluorescence is common in inflammatory bowel disease, autoimmune liver disease and infections. Drugs (hydralazine, propylthiouracil, levamisole-adulterated cocaine) and endocarditis can cause PR3 or MPO positivity.

Next steps for a positive result: urinalysis with microscopy, creatinine, CBC, CRP and chest imaging. Kidney or lung involvement is an emergency.

Anti-dsDNA is fairly specific for lupus, especially by Crithidia or Farr assays. Low-level results by some ELISA or multiplex methods can be false positives, particularly with a negative ANA. Higher levels are linked with nephritis.

ENA panel

• Sm: highly specific for lupus
• U1 RNP: MCTD and lupus
• SSA/Ro and SSB/La: Sjögren's disease, lupus, neonatal lupus
• Scl-70 and centromere: systemic sclerosis
• Jo-1: antisynthetase syndrome

Next steps: a positive specific antibody usually warrants referral with CBC, metabolic panel, urinalysis with protein-to-creatinine ratio and C3/C4. SSA/Ro in pregnancy needs prompt coordination with maternal-fetal medicine.

The three tests: lupus anticoagulant, anticardiolipin (IgG, IgM) and anti-β2-glycoprotein I (IgG, IgM).

Persistence matters. Antibodies can be transiently positive after infection. Repeat positive tests at least 12 weeks apart.

Higher-risk profiles: lupus anticoagulant positivity, triple positivity, and persistently moderate to high titers.

Testing pitfalls: anticoagulants interfere with lupus anticoagulant assays (DOACs, warfarin and heparin). Testing during an acute clot can be misleading.

Refer persistently positive results with thrombosis or pregnancy morbidity, or triple positivity. A single low-titer result without events usually just needs repeating.

Low complement levels indicate consumption by immune complexes, or an inherited deficiency.

Low C3 and C4 together: active lupus (especially nephritis), cryoglobulinemia, hypocomplementemic urticarial vasculitis.

Low C3 with normal or mildly low C4: post-infectious glomerulonephritis, C3 glomerulopathy, and some forms of membranoproliferative glomerulonephritis.

Low C4 with normal C3: cryoglobulinemia (often hepatitis C), Sjögren's disease (a lymphoma risk marker), hereditary angioedema, or partial C4 deficiency.

In known lupus, falling complements with a rising anti-dsDNA often accompany a flare.

Next steps: ANA, anti-dsDNA, cryoglobulins, urinalysis, creatinine, hepatitis C. Refer with clinical features.

Anti-CCP is highly specific for RA (around 95%) and can appear years before arthritis. RF is less specific; it is found in some healthy older adults and in hepatitis C, Sjögren's disease, cryoglobulinemia, endocarditis and other chronic conditions.

With joint swelling: refer urgently, whatever the antibody results.

High-titer anti-CCP with joint pain but no swelling: a higher risk of developing RA. Routine referral is reasonable, especially with morning stiffness or a positive squeeze test. Ask the patient to return promptly if joints swell.

Low-titer RF alone, no swelling, negative anti-CCP: usually no referral needed.

Both antibodies being positive, at high titer, predicts more erosive disease.

Serum urate reflects the body's urate pool. Above about 6.8 mg/dL, urate can crystallize.

Key points

• Urate can be normal during a gout flare. Recheck 2 or more weeks afterward.
• A high urate alone doesn't diagnose gout, and asymptomatic hyperuricemia generally isn't treated.
• On urate-lowering therapy, the target is below 6 mg/dL (below 5 mg/dL in some guidelines for severe tophaceous disease).

Common causes of a high urate: CKD, diuretics, alcohol, sugar-sweetened drinks, obesity, metabolic syndrome, low-dose aspirin, cyclosporine and tacrolimus, and high cell turnover.

Highest risk: systemic sclerosis (especially with Scl-70), inflammatory myositis (especially antisynthetase and MDA5 antibodies) and MCTD; also RA and Sjögren's disease with risk factors.

Screening and evaluation (ACR/CHEST 2023): PFTs with spirometry, lung volumes and DLCO, plus HRCT chest. Chest X-ray or a 6-minute walk alone are not recommended for screening. ERS/EULAR 2025 recommends screening everyone with systemic sclerosis, MCTD or inflammatory myositis (except inclusion body myositis), and people with RA or Sjögren's disease when risk factors are present.

Warning signs: new exertional breathlessness, dry cough, crackles, a fall in FVC (about 10%) or DLCO (about 15%).

Refer to rheumatology and pulmonology; rapidly worsening breathlessness is an emergency.

FDA boxed warnings (2021, after the ORAL Surveillance trial in RA): serious infections, death, malignancy, major adverse cardiovascular events and thrombosis. In RA, JAK inhibitors are generally used after an inadequate response or intolerance to a TNF inhibitor.

Extra caution: age 50 or older with cardiovascular risk factors, current or past smokers, a history of VTE or cancer.

Practical points

• Recombinant zoster vaccine before starting where possible; shingles is more common than with biologics.
• Check CBC, liver tests and lipids.
• Hold before surgery (3 days before joint replacement, per ACR/AAHKS 2022).
• Avoid in pregnancy and breastfeeding.

JIA-associated uveitis is usually painless and silent, and can cause synechiae, cataract, glaucoma and permanent vision loss. It is found only by slit-lamp examination.

Highest risk: oligoarticular or RF-negative polyarticular JIA, ANA positive, onset before age 7, and within 4 years of onset.

Screening (ACR 2026): every 3 months for high-risk children. Arrange the first exam at diagnosis, without waiting for the rheumatology visit.

Treatment: short-term topical prednisolone acetate 1%; methotrexate is the preferred first DMARD and adalimumab the preferred biologic when topical steroids are still needed.

Intra-articular glucocorticoids help OA flares of the knee and hip (ultrasound guidance for the hip), inflammatory arthritis in a single joint while waiting for DMARDs, and gout or CPPD in one large joint.

Before injecting: exclude infection (aspirate and culture if in doubt), avoid injecting through infected or broken skin, and check anticoagulation.

Limits: repeated injections into the same joint are usually spaced at least about 3 months apart. Expect a transient glucose rise in people with diabetes.

Before surgery: avoid injecting a joint in the months before planned joint replacement.

Generalized joint hypermobility is common (roughly 10–30% of people, more often in young women and some ethnic groups). Many have no symptoms; some have widespread pain and fatigue.

Management: reassurance, physical therapy focused on strengthening and proprioception, activity pacing and pain management.

Consider referral for recurrent dislocations, skin fragility or unusual scarring, or arterial or organ rupture in the patient or family. These suggest a heritable connective tissue disorder (such as vascular Ehlers-Danlos syndrome), for which genetics is often the right destination. Signs of inflammatory arthritis need rheumatology.

Reactive arthritis typically causes asymmetric arthritis of the legs, enthesitis or dactylitis 1–4 weeks after a gut infection (Salmonella, Shigella, Campylobacter, Yersinia) or Chlamydia. Conjunctivitis, urethritis, mouth ulcers or skin changes may accompany it.

Steps: NSAIDs are first-line. Screen for sexually transmitted infections after genitourinary symptoms. Check ESR, CRP and HLA-B27. A hot single joint needs aspiration to exclude infection.

Most cases settle within weeks to months. Refer if swelling persists beyond about 6 weeks without clear improvement, keeps recurring, involves the eye (urgent ophthalmology), or the diagnosis is uncertain.

Arthralgia without synovitis is very common, and most causes are not inflammatory.

Common causes: osteoarthritis, fibromyalgia and widespread pain, hypermobility, hypothyroidism, tendinopathy, viral illness, and medicines (aromatase inhibitors, statins, fluoroquinolones, DPP-4 inhibitors).

Inflammatory causes to keep in mind: early RA (especially with morning stiffness and a positive squeeze test), PMR in older adults, lupus, and checkpoint inhibitor side effects.

Reasonable workup: CBC, metabolic panel, ESR, CRP and TSH. Add RF and anti-CCP if small hand and foot joints are involved with stiffness. An ANA is useful only when there are features of connective tissue disease.

Refer if swelling appears (urgent) or anti-CCP is high-titer (routine). If PMR features are present, see the PMR answer.

Swelling soon after trauma suggests a hemarthrosis, ligament or meniscal injury, or a fracture.

Steps: X-ray, and consider aspiration of a tense effusion (blood suggests a significant structural injury). Check anticoagulant use and bleeding disorders. Refer to orthopedics or sports medicine.

Consider rheumatology if swelling recurs without trauma, or inflammatory features persist after the injury settles.

JDM causes a heliotrope rash, Gottron papules, nailfold changes and proximal weakness (Gowers sign, trouble with stairs or getting off the floor), with fatigue. Muscle enzymes can be normal.

Tests: CK, aldolase, AST/ALT, LDH, CBC, metabolic panel, ANA and a myositis antibody panel. MRI of the thighs if the diagnosis is uncertain.

Emergent: trouble swallowing, voice change, breathing difficulty, or skin ulceration.

Calcinosis is more common than in adults; malignancy is much less common.

JIA is joint swelling lasting 6 weeks or more, starting before age 16, with no other cause. Children often don't complain of pain; look for morning stiffness, a limp, or reluctance to use a limb.

Refer within 2–4 weeks. Before the visit:

• CBC with differential, ESR, CRP, metabolic panel; LDH and a blood film if malignancy is possible
• ANA (for uveitis risk), RF and anti-CCP if several joints are involved, HLA-B27 with enthesitis or back pain
• Arrange an ophthalmology screening exam now. Uveitis is often silent.

Treatment (ACR 2026): DMARDs first-line for polyarthritis and intra-articular glucocorticoids first-line for oligoarthritis. Methotrexate is the preferred first csDMARD and a TNF inhibitor the preferred first biologic.

Suspect Kawasaki disease with fever for 5 days or more plus 4 or more of: bilateral non-exudative conjunctival injection; red, cracked lips or a strawberry tongue; a polymorphous rash; redness or swelling of the hands and feet (peeling later); and a cervical lymph node over 1.5 cm.

Incomplete Kawasaki disease (fewer features) is common in infants. Use the AHA algorithm with CRP, ESR and supplemental labs (albumin, ALT, platelets, white cells, urine white cells).

Same day: emergency department or admission. Treatment is IVIG 2 g/kg, ideally within 10 days of fever onset (and still indicated after day 10 with ongoing inflammation), plus aspirin. Echocardiograms at diagnosis and follow-up. High-risk children may need added treatment (AHA 2024).

Coughing blood, new lung infiltrates with a falling hemoglobin, or a rising creatinine with blood and protein in the urine can signal alveolar hemorrhage or rapidly progressive glomerulonephritis.

Causes: ANCA vasculitis, anti-GBM disease, lupus, and less often other vasculitides. Infection and heart failure are common mimics.

Same day: emergency department or direct admission. Contact rheumatology and nephrology. Send CBC, creatinine, urinalysis with microscopy, PR3/MPO-ANCA, anti-GBM antibodies, ANA, C3/C4, and chest imaging. Treatment often starts before all results are back.

Live vaccines include MMR, varicella (the live zoster vaccine is no longer used in the US), yellow fever, oral typhoid, live attenuated influenza (nasal) and rotavirus.

On immunosuppression: generally avoided, including on biologics, JAK inhibitors, and glucocorticoids at 20 mg/day or more for 2 weeks or longer. Some live vaccines may be considered on low-dose methotrexate, azathioprine or glucocorticoids after specialist discussion.

Timing: give needed live vaccines at least 4 weeks before starting immunosuppression. If they are needed during treatment, rheumatology may advise holding medicines before and after vaccination.

Travel: discuss yellow fever and other travel vaccines with a travel clinic and rheumatology well in advance.

Livedo reticularis is a regular, net-like, purple pattern that often appears with cold and fades with warming. It is usually benign.

Livedo racemosa is an irregular, broken pattern that persists with warming. It suggests an underlying cause:

• Antiphospholipid syndrome
• Vasculitis, especially polyarteritis nodosa
• Cholesterol emboli (after vascular procedures)
• Livedoid vasculopathy, cryoglobulinemia, calciphylaxis
• Sneddon syndrome (livedo racemosa with stroke)

Tests for livedo racemosa: antiphospholipid antibodies, CBC, metabolic panel, urinalysis, ANA, ANCA, cryoglobulins, hepatitis B and C. A skin biopsy can help.

Localized scleroderma causes patches or bands of skin thickening and color change. It is different from systemic sclerosis.

Why it matters: linear lesions on a limb can cause limb-length differences or contractures; facial lesions (en coup de sabre, Parry-Romberg syndrome) can involve the eye or brain.

Refer early, and urgently for linear, facial, deep, widespread or rapidly progressive disease. Methotrexate with initial glucocorticoids is the usual systemic treatment for active disease.

Helpful: photos with a ruler, location, and any limb-length difference. Facial disease needs an eye exam and sometimes brain MRI.

Rituximab can lower immunoglobulins, especially after repeated cycles or with other immunosuppressants.

Steps

• Check IgG, IgA and IgM before each cycle.
• Ask about recurrent or severe infections.
• Discuss significantly low IgG with the prescribing team, especially with recurrent infections. Options include delaying or stopping rituximab, vaccine response testing, antibiotic prophylaxis, or immunoglobulin replacement.

Commonly used threshold: platelets below 140 × 10⁹/L.

Steps: repeat the count, look at the trend, and ask about bruising or bleeding. If below threshold, pause the DMARD and contact the prescribing team.

Consider other causes: active lupus, antiphospholipid syndrome, liver disease, infection, heparin, and other drugs. Platelets below about 50 × 10⁹/L, or any bleeding, need same-day review.

Commonly used thresholds for action: white cells below 3.5 × 10⁹/L or neutrophils below 1.6 × 10⁹/L.

Steps

• Repeat the CBC promptly, and look at the trend; a steady fall matters even within the normal range.
• Ask about infection, mouth ulcers and new medicines (trimethoprim with methotrexate; allopurinol or febuxostat with azathioprine).
• If below threshold: pause the DMARD and contact the prescribing team.
• Neutrophils below about 1.0 × 10⁹/L, or any fever with neutropenia: same-day assessment.

Note: tocilizumab and sarilumab commonly lower neutrophils; rituximab can cause late-onset neutropenia.

Risks: flares, preeclampsia, pregnancy loss, preterm birth and growth restriction, especially with active disease, nephritis, antiphospholipid antibodies or hypertension.

Care

• Plan pregnancy during quiet disease, on compatible medicines.
• Continue hydroxychloroquine throughout pregnancy; stopping it raises flare risk.
• Low-dose aspirin from about 12 weeks.
• Joint care between rheumatology and maternal-fetal medicine, with regular blood pressure, urine protein and blood tests.
• Check SSA/Ro: if positive, fetal heart monitoring.

Telling preeclampsia from a lupus nephritis flare can be difficult and needs specialist input.

Severe lupus (for example, recent nephritis or other organ involvement): ACR/AAHKS 2022 suggests continuing mycophenolate, azathioprine, cyclosporine and tacrolimus through surgery. Biologics such as rituximab, belimumab and anifrolumab are timed with the surgical team.

Non-severe lupus: these medicines are usually held for about 1 week before surgery. Hydroxychloroquine is always continued.

Vasculitis and other conditions: decisions depend on disease activity. Coordinate with rheumatology, ideally well before the date.

At visits: blood pressure and a urinalysis; ask about rash, ulcers, joint swelling, chest pain, fevers, swelling of the legs, and neurologic symptoms.

Encourage: hydroxychloroquine adherence (it lowers flare risk and is recommended for nearly all patients), sun protection, smoking cessation, inactivated vaccines and cardiovascular risk management.

Plan pregnancies. Disease should ideally be quiet for about 6 months before conception, on compatible medicines. Estrogen-containing contraception is generally avoided with antiphospholipid antibodies.

Contact rheumatology promptly for new proteinuria or hematuria, a rising creatinine, new cytopenias, or new organ symptoms.

Call rheumatology the same day, or send to the emergency department, for

• Nephritis: a rising creatinine, nephrotic-range proteinuria, or active sediment with new hypertension
• Neuropsychiatric lupus: seizures, psychosis, confusion, transverse myelitis, stroke
• Severe cytopenias: hemolytic anemia, platelets below about 30,000, very low neutrophils
• Serositis with tamponade, myocarditis, or alveolar hemorrhage

Always consider infection, which is a leading cause of death in lupus and can mimic a flare. Thrombotic microangiopathy and antiphospholipid syndrome are other important causes of acute deterioration.

Lyme arthritis typically causes intermittent or persistent swelling of a large joint, most often the knee, weeks to months after a tick bite in an endemic area. The joint is often very swollen but less painful than septic arthritis.

First, exclude septic arthritis: a hot, very painful joint, fever, or an immunocompromised patient needs same-day aspiration (cell count, Gram stain, culture and crystals).

Testing: serology using the standard two-tier approach. Most patients with Lyme arthritis have strongly positive IgG results.

Treatment: oral antibiotics, typically doxycycline for 28 days (IDSA/AAN/ACR 2020). If swelling persists, options are a second oral course or observation for mild residual swelling, and IV ceftriaxone when there has been little or no response.

Refer if arthritis persists after oral and IV treatment (post-infectious or antibiotic-refractory Lyme arthritis), or if the diagnosis is uncertain.

MAS (secondary HLH) is a life-threatening cytokine storm. It can complicate Still's disease, lupus, infection or cancer.

Warning signs

• Persistent fever with new or worsening cytopenias
• A very high or rapidly rising ferritin (often above 5,000–10,000 ng/mL)
• Raised AST/ALT, LDH and triglycerides; falling fibrinogen
• A falling ESR despite a rising CRP (fibrinogen is being consumed)
• Enlarged liver or spleen, bleeding, confusion

Same day: emergency department, with rheumatology and hematology involved. Check CBC, ferritin, fibrinogen, triglycerides, liver tests, LDH, coagulation studies and blood cultures, and look for an infectious or malignant trigger.

MAS complicates systemic JIA, lupus, Kawasaki disease and infections.

2016 classification criteria (in sJIA): a febrile patient with ferritin above 684 ng/mL plus any 2 of: platelets 181,000/µL or less, AST above 48 U/L, triglycerides above 156 mg/dL, fibrinogen 360 mg/dL or less.

Emergency department and pediatric rheumatology today. ICU care is often needed. The 2026 ACR guideline recommends an IL-1 or IL-6 inhibitor plus systemic glucocorticoids for sJIA with MAS.

A malar rash of lupus is red, raised or flat, spares the nasolabial folds, and often follows sun exposure. Look-alikes are more common: rosacea, seborrheic dermatitis, contact dermatitis and photosensitive drug reactions.

Suggesting lupus: mouth or nose ulcers, hair loss, joint swelling, pleurisy, Raynaud's, fevers, low blood counts, or protein in the urine. Discoid lesions (scarring, with follicular plugging) suggest cutaneous lupus.

Tests: ANA, CBC, metabolic panel, urinalysis with microscopy; anti-dsDNA, ENA and C3/C4 if the ANA is positive. A dermatology review or skin biopsy can help.

Refer: urgent if systemic features are present; dermatology for isolated skin disease.

An ESR over 100 mm/h or a CRP over 100 mg/L usually has a serious cause.

Most common: infection (endocarditis, osteomyelitis, abscess, pneumonia, TB), malignancy (myeloma, lymphoma, metastatic disease), and GCA or PMR. Others include vasculitis, Still's disease and advanced kidney disease.

Prompt workup: CBC with smear, metabolic panel with liver tests, urinalysis, blood cultures if febrile, serum protein electrophoresis with free light chains, chest X-ray, and imaging guided by symptoms.

GCA symptoms make it an emergency. Otherwise, refer to rheumatology when the clinical features point there; many patients need an infection or cancer workup first.

Back pain that worsens with activity or posture and eases with rest, with short morning stiffness and no red flags, is usually mechanical.

Management

• Stay active; exercise and physical therapy have the best evidence.
• NSAIDs if appropriate. Avoid opioids for chronic low back pain where possible.
• Image only for red flags or if the pattern changes.

Refer to rheumatology if inflammatory features appear, or if there are features of spondyloarthritis such as uveitis, psoriasis or IBD.

EULAR 2024 lists as compatible: hydroxychloroquine, sulfasalazine (with folic acid), azathioprine, tacrolimus, cyclosporine, colchicine, prednisone and prednisolone (lowest effective dose), and all TNF inhibitors (which can be used throughout pregnancy).

May be used if needed: abatacept, anakinra, belimumab, canakinumab, ixekizumab, rituximab, sarilumab, secukinumab, tocilizumab and ustekinumab.

Only if there is no compatible alternative (limited data): anifrolumab, guselkumab and risankizumab, among others.

Hydroxychloroquine in lupus: continue through pregnancy; stopping it increases flare risk.

• Methotrexate: teratogenic. Stop 1–3 months before trying to conceive.
• Mycophenolate: teratogenic. Stop at least 6 weeks before.
• Cyclophosphamide: teratogenic and gonadotoxic. Stop at least 3 months before conception (EULAR 2024; this applies to men too). Offer fertility preservation counseling before treatment.
• Leflunomide: avoid. EULAR 2024: stop about 3.5 months (five half-lives) before, or use accelerated elimination with cholestyramine. The US label advises accelerated elimination and confirming teriflunomide levels below 0.02 mg/L, since levels can otherwise persist for up to 2 years.
• JAK inhibitors (tofacitinib, baricitinib, upadacitinib), apremilast, avacopan and voclosporin: insufficient data, so avoid; stop before conception with timing per agent.

Switch to a compatible drug to keep disease controlled.

Can be continued (EULAR 2024): methotrexate (25 mg/week or less), mycophenolate, leflunomide, azathioprine, hydroxychloroquine, sulfasalazine, tacrolimus, cyclosporine, colchicine, glucocorticoids, NSAIDs, and TNF and non-TNF biologics.

Mycophenolate in men: EULAR 2024 says it can be continued, but the US label advises effective contraception for male patients or their partners during treatment and for at least 90 days after, and no sperm donation. Discuss this with the patient.

Sulfasalazine can reversibly reduce sperm quality; consider stopping if conception is delayed.

Cyclophosphamide carries a dose-related risk of permanent infertility; offer sperm banking beforehand, and stop it at least 3 months before trying to conceive.

Limited data (consider switching): JAK inhibitors, apremilast, guselkumab and risankizumab, among others.

• Weekly dosing only. Daily dosing errors cause serious, sometimes fatal toxicity. Write "once weekly" and the day on prescriptions.
• Folic acid reduces side effects (often 1 mg daily, or 5 mg once weekly on a different day, per local practice).
• Avoid trimethoprim and trimethoprim-sulfamethoxazole, which can cause marrow suppression.
• Kidney function: reduce the dose in moderate CKD; generally avoid below an eGFR of 30.
• Alcohol: keep within low limits.
• Pregnancy: stop 1–3 months before trying to conceive; men may continue (EULAR 2024).
• Lungs: new cough, fever or breathlessness needs prompt assessment for pneumonitis or infection.
• Vaccines: consider holding for 2 weeks after influenza vaccination if disease allows.

• TNF inhibitors: CBC and liver tests periodically (for example every 3–6 months; yearly in JIA per ACR 2026). Repeat TB screening if exposure risk continues. Skin checks.
• IL-6 inhibitors: CBC and liver tests at 4–8 weeks, then about every 3 months; lipids. Remember CRP and fever are suppressed.
• Rituximab: CBC and immunoglobulins before each cycle.
• Abatacept, IL-17 and IL-23 inhibitors: few routine labs; clinical review.
• JAK inhibitors: CBC (lymphocytes, neutrophils, hemoglobin), liver tests and lipids at 4–8 weeks, then about every 3 months.

For everyone: vaccines up to date, infection awareness, cardiovascular risk management and age-appropriate cancer screening.

Prolonged morning stiffness (more than 30–60 minutes) is a feature of inflammatory disease, even before swelling is obvious.

Consider: early RA or psoriatic arthritis, PMR (age 50 or older with shoulder and hip girdle stiffness), axial spondyloarthritis (back stiffness), and hypothyroidism. OA usually causes stiffness of under 30 minutes.

Steps: look carefully for synovitis and do a squeeze test; check ESR, CRP, RF, anti-CCP, TSH and CK.

Refer

• Urgently if synovitis is found
• Routinely if anti-CCP is high-titer with joint symptoms (higher risk of developing RA)
• If age and girdle pattern fit PMR: semi-urgent, or manage in primary care if you are comfortable

Many young people are lost to follow-up during transfer, and flares and organ damage can follow.

Good transition

• Starts around age 12–14, with growing self-management skills: knowing their diagnosis and medicines, booking appointments, ordering refills.
• Includes a written medical summary and a named adult rheumatologist, ideally with a joint or warm-handoff visit.
• Keeps primary care involved; continuity is protective.

The ACR 2026 JIA guideline strongly recommends assessing transition readiness and creating a transition plan. Got Transition offers practical tools.

CDC case definition (2023): age under 21, fever of 38.0 °C or higher, CRP 3.0 mg/dL or higher, new involvement in at least 2 systems (cardiac, mucocutaneous, shock, gastrointestinal or hematologic), evidence of SARS-CoV-2 infection or exposure within the prior 60 days, illness needing hospitalization (or resulting in death), and no more likely alternative diagnosis (a final diagnosis of Kawasaki disease counts as an alternative).

Same day: admit for multidisciplinary care. Echocardiogram, ECG, troponin and BNP. Treatment usually includes IVIG and/or glucocorticoids, with antithrombotic therapy per protocol.

MIS-C can resemble Kawasaki disease, toxic shock and sepsis.

Most statin-associated muscle symptoms are aches with a normal or mildly raised CK, and they improve within weeks of stopping or switching.

A practical approach

• Check CK, TSH and kidney function, and review interacting drugs.
• Stop the statin if CK is more than 10 times normal or symptoms are intolerable; re-challenge or switch once settled.

Refer urgently if there is true proximal weakness, a CK in the thousands, or a CK that stays high or rises several weeks after stopping the statin. These suggest anti-HMGCR immune-mediated necrotizing myopathy, which needs immunosuppression. Ask for anti-HMGCR antibodies.

Weakness of the swallowing or breathing muscles can cause aspiration and respiratory failure.

Same day: emergency department or direct admission, and call rheumatology.

Warning signs: choking or coughing with meals, nasal speech, a weak cough, breathlessness lying flat, a falling vital capacity, chest pain or palpitations (myocarditis).

Checkpoint inhibitor patients: myositis can overlap with myocarditis and myasthenia (ptosis, double vision). Check troponin and an ECG, and contact oncology.

Neonatal lupus is caused by maternal anti-SSA/Ro (with or without anti-SSB/La) antibodies crossing the placenta. The mother may have no known autoimmune disease.

Features: congenital heart block (about 2% of first pregnancies in anti-Ro-positive mothers, higher after a previously affected child), an annular, photosensitive rash in the first months, cytopenias, and raised liver tests.

Steps: infant ECG, CBC and liver tests; pediatric cardiology for any conduction abnormality. The rash and blood changes usually resolve by 6–9 months as maternal antibodies clear.

Future pregnancies: fetal heart monitoring and hydroxychloroquine (which lowers recurrence risk) through rheumatology and maternal-fetal medicine.

Joint swelling with prolonged morning stiffness suggests inflammatory arthritis. Early treatment, ideally within about 12 weeks of symptom onset, improves long-term outcomes.

Refer urgently, within 2–4 weeks. Don't wait for results. NICE advises urgent referral even when ESR, CRP, RF and anti-CCP are normal, if small joints of the hands or feet are involved or more than one joint is swollen.

Usual workup recommended before the referral is seen

• CBC with differential, metabolic panel with liver tests
• ESR, CRP, RF, anti-CCP
• Hepatitis B (HBsAg, anti-HBc, anti-HBs) and hepatitis C, needed before most DMARDs
• X-rays of both hands and both feet

While waiting: an NSAID is reasonable if safe. If possible, avoid starting glucocorticoids, since they can mask synovitis. If symptoms are severe and the wait is long, call rheumatology to discuss a short course.

When the picture is unclear, a few steps help.

First, rule out an emergency. Call rheumatology or send to the emergency department for suspected GCA, a hot joint with fever, kidney and lung involvement, swallowing or breathing weakness, or a cold, discolored digit.

Then gather the basics: a careful joint exam (is there swelling?), CBC, metabolic panel, ESR and CRP, urinalysis, and targeted tests for the features you see. Broad autoantibody panels without specific features tend to create confusion rather than answers.

Ask before you send. Many rheumatology services offer an advice line or e-consult. These help decide whether the patient needs to be seen, how soon, and what to send first. They don't replace an in-person examination when one is needed.

If you do refer, state your question and level of concern clearly; it helps the triager place the patient correctly.

NSAIDs

• EULAR 2024: intermittent use only, and stop after 28 weeks (risk to the ductus arteriosus). The FDA advises avoiding NSAIDs from about 20 weeks unless necessary (low amniotic fluid and fetal kidney problems), using the lowest dose for the shortest time between 20 and 30 weeks, and avoiding them from 30 weeks.
• Earlier in pregnancy, intermittent use of short-acting non-selective NSAIDs is preferred. NSAIDs may also delay conception, so consider stopping them when conception is taking time.
• Low-dose aspirin for preeclampsia prevention is different and is often recommended.

Glucocorticoids: prednisone and prednisolone can be used; aim for 5 mg daily or less where possible. Higher doses raise the risk of gestational diabetes, hypertension and preterm birth.

Chronic monoarthritis has a broad differential:

• Infection: TB, fungal infection, Lyme disease, low-grade bacterial infection
• Inflammatory arthritis: psoriatic arthritis, spondyloarthritis, sarcoidosis; in children, oligoarticular JIA
• Crystal arthritis: CPPD, gout
• Structural: tenosynovial giant cell tumor, osteonecrosis, internal derangement
• Hemochromatosis and other metabolic causes

Steps: aspirate with cell count, crystals and cultures (including mycobacterial and fungal cultures if indicated); X-ray; CBC, ESR, CRP, uric acid; Lyme serology where relevant. MRI is often helpful.

Refer to rheumatology; synovial biopsy is sometimes needed.

Start with a question. Rheumatology tests have the most value when the pretest probability is reasonable. "Rheumatology panels" ordered for fatigue or widespread pain mostly produce false positives.

A sensible core: CBC with differential, metabolic panel with liver tests, ESR and CRP, and a urinalysis. Add targeted tests for the features you see:

• Synovitis: RF, anti-CCP
• Lupus features: ANA (then ENA, anti-dsDNA and C3/C4 if positive)
• Weakness: CK, TSH, myositis antibodies
• Vasculitis features: PR3/MPO-ANCA, urinalysis with microscopy
• Inflammatory back pain: HLA-B27, CRP

Don't wait for results to refer when the clinical picture is urgent.

OA is a clinical diagnosis: pain with use, morning stiffness under 30 minutes, bony enlargement, crepitus and normal inflammatory markers. Imaging isn't needed for a typical presentation.

What works (2026 ACR update)

• Exercise and weight loss for knee and hip OA (strong recommendations). For knee OA with obesity, a GLP-1 receptor agonist with diet and exercise (conditional, new in 2026).
• Topical NSAIDs for knee and hand OA (often tried before oral NSAIDs), oral NSAIDs where safe, intra-articular glucocorticoids for knee and hip.
• Duloxetine or acetaminophen (conditional); PT, OT, braces, hand orthoses, canes.

What doesn't: glucosamine or chondroitin, PRP, stem cell injections, hydroxychloroquine and bisphosphonates (strong recommendations against); opioids and hyaluronic acid injections (conditional against).

Refer to rheumatology if OA is atypical (young onset, MCP or wrist involvement, rapid progression), there is inflammatory swelling, or the patient has erosive hand OA (methotrexate is now a conditional option). Orthopedics for severe symptoms despite core treatment.

Consider a specialist (rheumatology, endocrinology or a bone clinic) for

• A fragility fracture while on treatment
• Very high fracture risk where anabolic therapy may be needed
• Atypical femoral fracture or osteonecrosis of the jaw
• Intolerance of, or contraindications to, standard options
• Young patients, men with unexplained osteoporosis, or suspected secondary causes
• Complex glucocorticoid-induced osteoporosis

Send: DXA reports with dates, FRAX, fracture history, treatments with dates (including the last denosumab dose), calcium, 25-OH vitamin D, creatinine, alkaline phosphatase and PTH if checked.

For many rashes, dermatology is the right first step, and a skin biopsy is often diagnostic.

Helpful details for any referral: photos (ideally over time), duration, distribution, triggers (sun, cold, drugs), and systemic symptoms.

Rashes that also need rheumatology: lupus-type rashes with systemic features, dermatomyositis, palpable purpura, skin thickening, psoriasis with joint symptoms, and livedo racemosa.

Biopsy tip: for suspected vasculitis, biopsy a lesion less than 48 hours old and ask for direct immunofluorescence.

Most childhood rashes are infectious or allergic. Consider a rheumatologic cause with persistent or recurrent rash plus fever, joint swelling, weakness, mouth ulcers, or abnormal blood counts or urine.

Helpful: photos over time, a fever diary, CBC, CRP, urinalysis, and targeted tests. Dermatology review and skin biopsy are often useful.

Growing pains: bilateral leg pain in the evening or night, in the thighs, calves or behind the knees, with a normal exam, normal activity during the day and normal growth. Massage and reassurance help.

Hypermobility: pain after activity, with a normal exam apart from hypermobility. Physical therapy for strength and proprioception helps.

Amplified musculoskeletal pain: widespread or localized pain out of proportion, often with allodynia and functional decline. A multidisciplinary rehabilitation approach works best.

Red flags that need evaluation: pain that is unilateral, in the joint itself, or present in the morning; swelling, limp, fever, weight loss, night waking, or abnormal counts.

Mechanical joint pain usually comes from osteoarthritis, internal derangement (meniscal or ligament problems), tendinopathy or bursitis.

Steps: a clinical diagnosis is usually enough. X-rays help when the presentation is atypical or surgery is being considered.

Management: exercise, weight management, topical NSAIDs and physical therapy. See osteoarthritis and soft-tissue problems for details.

Refer to rheumatology if inflammatory features develop, such as swelling, long morning stiffness or raised markers.

Fever or a patient who looks unwell: treat as possible sepsis or endocarditis first, with same-day emergency assessment and blood cultures.

Palpable, non-blanching purpura usually means small-vessel vasculitis. Causes include IgA vasculitis, cryoglobulinemia (often hepatitis C), drug-induced vasculitis, ANCA vasculitis, infection and urticarial vasculitis.

Tests

• Urinalysis with microscopy and creatinine (the most important first tests)
• CBC, ANCA, C3/C4, cryoglobulins (kept warm until processed), hepatitis B and C, HIV, blood cultures if febrile
• Skin biopsy with direct immunofluorescence, ideally from a lesion less than 48 hours old

Urgency: urgent if skin-limited and the patient is well; emergent with fever or systemic illness, kidney involvement, lung symptoms, gut bleeding or nerve involvement. Review recent new medicines.

Pediatric rheumatology is a small specialty, and many families travel far. A clear referral helps: the main problem, its duration, exam findings (which joints, rash, weakness), growth, and test results.

Always consider infection and malignancy in a child with musculoskeletal symptoms, especially with fever, night pain or abnormal counts.

Eye screening for any child with suspected JIA can be arranged before the rheumatology visit.

Pediatric versions of adult diseases (lupus, dermatomyositis, scleroderma, Sjögren's, vasculitis) are often more severe in children and need pediatric rheumatology.

PFAPA (the most common periodic fever in children): fevers every 3–8 weeks, starting before age 5, with aphthous ulcers, pharyngitis and cervical adenitis. The child is well and growing normally between episodes. A single dose of prednisone at onset usually stops an episode, though episodes may then come more often. Many pediatricians manage PFAPA; tonsillectomy can be curative for some children.

Consider other autoinflammatory syndromes with: onset after 5, rashes, abdominal pain or serositis (FMF), cold-triggered urticarial rash (CAPS), longer episodes with muscle pain (TRAPS), episodes after vaccines in infants (MKD), poor growth, or a family history.

Helpful: a fever diary, CBC and CRP during and between episodes, and photos of any rash. Colchicine is first-line for FMF (EULAR/PReS 2024).

Stereotyped episodes of fever with well intervals suggest an autoinflammatory syndrome.

• Familial Mediterranean fever (FMF): episodes of 1–3 days with abdominal or chest pain (serositis), arthritis or an erysipelas-like rash on the lower leg. More common with Mediterranean, Middle Eastern, Armenian and Jewish ancestry. Colchicine is first-line and prevents amyloidosis.
• CAPS: urticaria-like rash, often cold-triggered, conjunctivitis, hearing loss.
• TRAPS: longer episodes (often a week or more), migratory muscle pain, periorbital swelling.
• Schnitzler syndrome: chronic urticaria with an IgM monoclonal protein in older adults.

Helpful before referral: a fever diary, photos of rashes, CRP during an episode and when well, CBC, urinalysis (protein, for amyloidosis), and family history. Genetic testing is usually arranged by the specialist.

Plan with rheumatology, ideally 3–6 months ahead.

• Quiet disease first. In lupus, aim for about 6 months of low activity before conception; active disease, especially nephritis, raises the risk of preeclampsia, pregnancy loss and preterm birth.
• Switch medicines to compatible ones in time (see DMARDs in pregnancy).
• Check antibodies in lupus and related conditions: SSA/Ro, SSB/La and antiphospholipid antibodies.
• Low-dose aspirin is often recommended from about 12 weeks in lupus and with antiphospholipid antibodies, to lower preeclampsia risk.
• Baseline tests: blood pressure, creatinine and urine protein in lupus.
• Contraception until ready; avoid estrogen-containing methods with antiphospholipid antibodies.

Plan ahead with rheumatology, ideally 3–6 months before trying to conceive.

• Switch teratogenic drugs to compatible ones in time: methotrexate (stop 1–3 months before), mycophenolate (at least 6 weeks before), leflunomide (accelerated elimination with cholestyramine), cyclophosphamide (at least 3 months before).
• Continue compatible drugs that keep disease quiet: hydroxychloroquine, sulfasalazine, azathioprine, tacrolimus, and TNF inhibitors.
• Check SSA/Ro and SSB/La and antiphospholipid antibodies in women with lupus, Sjögren's or related disease.
• Low-dose aspirin is often recommended from about 12 weeks to reduce preeclampsia risk in lupus and APS.
• Folic acid as usual.

Active disease at conception carries more risk than most compatible medicines.

Recommended for adults on immunosuppressive treatment, regardless of age.

Current US options: a single dose of PCV20 or PCV21, or PCV15 followed by PPSV23, according to the current CDC schedule and any previous pneumococcal vaccines. PCV21 doesn't cover serotype 4, so in Alaska, Colorado, New Mexico, the Navajo Nation and Oregon, CDC notes that PCV20, or PCV15 then PPSV23, may give broader coverage.

Timing: ideally before immunosuppression, or at least 2 weeks before rituximab; otherwise give it during treatment.

Consider prophylaxis when patients receive high-dose glucocorticoids (often defined as about 20 mg prednisone daily or more for 4 weeks or longer), especially with another immunosuppressant such as cyclophosphamide or rituximab, or with low lymphocyte counts. This is common in ANCA vasculitis and severe lupus.

Options: trimethoprim-sulfamethoxazole is first-line, but check interactions; combining it with methotrexate needs particular caution because of marrow suppression, and the prescribing team may choose an alternative. Alternatives include atovaquone, dapsone (check G6PD) or inhaled pentamidine.

Follow the prescribing team's plan, which usually specifies when prophylaxis starts and stops.

Short-lived polyarthritis is often viral or post-infectious, but it can also be the first presentation of a chronic inflammatory arthritis.

Common causes

• Viral: parvovirus B19 (often with a rash or a sick child at home), hepatitis B and C, rubella, HIV, chikungunya and other travel-related viruses
• Reactive arthritis after a gut or genitourinary infection
• Serum sickness-like reactions to drugs
• Early RA, psoriatic arthritis or lupus

Reasonable first tests

• CBC, metabolic panel, ESR and CRP, urinalysis
• Parvovirus B19 IgM, hepatitis B and C serology, HIV if at risk
• RF and anti-CCP; ANA only if there are features of lupus

Plan

• Same day for fever with tenosynovitis, a pustular or petechial rash, or a new heart murmur: think disseminated gonococcal infection, endocarditis, septic arthritis or acute rheumatic fever.
• NSAIDs if safe.
• If a viral cause is likely (for example, a positive parvovirus IgM) and the swelling is settling, review within 2–4 weeks and refer if it persists.
• Otherwise refer urgently now, without waiting for 6 weeks, especially with small-joint swelling in the hands or feet, a positive anti-CCP, or systemic features. NICE advises urgent referral when more than one joint is affected, even with normal blood tests, and EULAR advises being seen within 6 weeks of symptom onset.

Acute (under 6 weeks): viral (parvovirus B19, hepatitis B and C, rubella, HIV, chikungunya), reactive arthritis, polyarticular crystal arthritis, drug reactions, acute rheumatic fever in young people, and early chronic inflammatory arthritis.

Chronic (6 weeks or more): RA (symmetric small joints), psoriatic arthritis (asymmetric, DIP joints, dactylitis), lupus (non-erosive, with systemic features), enteropathic arthritis, chronic CPPD, and sarcoidosis.

Clues that sort them out

• Distribution: symmetric or not; small or large joints; DIP involvement
• Extra-articular features: skin, nails, eyes, bowel, genitourinary symptoms, mouth ulcers
• Labs: RF, anti-CCP, ANA, urate, CRP; HLA-B27 for spondyloarthritis
• X-rays: erosions, chondrocalcinosis

Any persistent synovitis warrants an urgent referral.

PMR causes bilateral shoulder and/or hip girdle pain and stiffness (morning stiffness over 45 minutes) in people 50 or older, with raised ESR or CRP and a normal CK.

Always ask about GCA: new headache, jaw claudication, scalp tenderness, visual symptoms or limb claudication. Any of these makes this an emergency.

Without GCA features, PMR is semi-urgent. It can often be managed in primary care. If you're not comfortable with the diagnosis or treatment, refer: it's better for the patient to be seen sooner rather than later. Atypical features (age under 60, peripheral arthritis, normal markers, a poor response to glucocorticoids, or prominent systemic symptoms) also warrant referral.

Guidelines differ. EULAR 2025 recommends rapid specialist referral of all suspected PMR. The BSR 2026 guideline expects most PMR to be managed in primary care with specialist support, with referral for atypical features, after a second relapse, or after 18 months or more of glucocorticoids. Follow your local pathway.

Usual workup, before starting treatment or with a referral: ESR, CRP, CBC, metabolic panel, CK, TSH, RF/anti-CCP, and serum protein electrophoresis (mimics include RA, myeloma and other cancers, myopathy and hypothyroidism). A 'trial of steroids' shouldn't be used as a diagnostic test (EULAR 2025).

Treatment: prednisone 15–25 mg daily, tapering to 10 mg daily within about 2 months, then slowly, with bone protection. Relapse on taper, or difficulty tapering, needs specialist review; sarilumab, tocilizumab and methotrexate are steroid-sparing options.

A positive ANA matters when the clinical picture fits a connective tissue disease.

Features that raise concern: photosensitive rash, mouth or nose ulcers, hair loss, inflammatory arthritis, pleurisy or pericarditis, Raynaud's with puffy fingers or ulcers, proximal weakness, dry eyes and mouth with gland swelling, low blood counts, proteinuria or hematuria.

Steps: ENA panel, anti-dsDNA, C3/C4, CBC with differential, metabolic panel, urinalysis with microscopy, ESR/CRP.

Urgency depends on the features: organ involvement is emergent; suspected lupus, systemic sclerosis or myositis is urgent; mild, non-specific symptoms with negative follow-up tests are usually routine.

Non-specific symptoms alone (fatigue, widespread pain) with a low-titer ANA usually don't indicate autoimmune disease.

This is the most common source of unnecessary rheumatology referrals. In healthy people, about 32% test positive at 1:40, 13% at 1:80 and 5% at 1:160. A positive ANA alone does not diagnose any disease.

Reasonable steps

• Document why the test was ordered, and the titer and pattern.
• Check a CBC, metabolic panel and urinalysis. If these are normal and there are no symptoms, reassure the patient.
• At 1:160 or higher, check an ENA panel and anti-dsDNA once.
• Don't repeat the ANA; the titer doesn't track disease activity.

Refer if: a disease-specific antibody is positive (dsDNA, Sm, RNP, Scl-70, centromere, or SSA/Ro in pregnancy), there are unexplained cytopenias, proteinuria or hematuria, or new symptoms develop.

1. Why was it ordered? A test ordered for specific features means more than one ordered as a screen.

2. What are the titer and pattern? 1:40–1:80 is common in healthy people; 1:160 or higher is more often meaningful; a DFS70 pattern alone is usually benign.

3. Are there symptoms or abnormal basic tests? Check CBC, metabolic panel and urinalysis.

4. Are specific antibodies positive? Check ENA, anti-dsDNA and C3/C4 for titers of 1:160 or higher, or with symptoms.

Refer for symptoms of connective tissue disease, a positive specific antibody, or unexplained abnormal tests. Otherwise reassure, and review if symptoms develop.

RF is not specific. It is found in a meaningful minority of healthy older adults and in chronic infections (hepatitis C, endocarditis), Sjögren's disease, cryoglobulinemia, liver disease, sarcoidosis and lung disease.

Reasonable steps

• Examine carefully for synovitis.
• Check anti-CCP, which is much more specific for RA.
• Consider hepatitis C testing if risk factors are present.

Refer if synovitis is present (urgent), or with a high-titer anti-CCP and joint symptoms (routine). A low-titer RF with no joint swelling and a negative anti-CCP generally doesn't need referral.

ANCA vasculitis (GPA, MPA, EGPA) can damage the kidneys and lungs within days.

Emergent (same day, often admission): rising creatinine with blood and protein in the urine, coughing blood or new infiltrates with a falling hemoglobin, mononeuritis multiplex, stridor, or scleritis.

Urgent (within 2–4 weeks): limited disease such as chronic sinusitis, crusting, nosebleeds or lung nodules, with a normal urinalysis and creatinine. Recheck the urine every visit; kidney involvement can develop silently.

Tests

• PR3- and MPO-ANCA by antigen-specific immunoassay (preferred first test)
• Urinalysis with microscopy, urine protein-to-creatinine ratio, creatinine, CBC, CRP
• Chest imaging

Don't wait for ANCA results when the picture is compelling. About 1 in 10 people with GPA or MPA, and most people with EGPA, are ANCA-negative.

Behçet's is suggested by recurrent oral ulcers (3 or more episodes a year) with genital ulcers, eye inflammation, skin lesions (erythema nodosum, pseudofolliculitis), vascular events or neurologic symptoms.

Same-day ophthalmology for visual loss, floaters or a painful red eye: uveitis and retinal vasculitis can threaten sight. Coughing blood (possible pulmonary artery aneurysm) or sudden neurologic symptoms need emergency care.

Tests: CBC, metabolic panel, CRP or ESR, urinalysis. There is no diagnostic blood test.

Ulcer photos and a diary help. Care is often shared between rheumatology, ophthalmology and dermatology, and treatment depends on which organs are involved.

Inflammatory back pain is more likely when at least 4 of these 5 are present (ASAS criteria): onset before 40, insidious onset, improvement with exercise, no improvement with rest, and pain at night that improves on getting up.

A practical approach

• Check CRP and HLA-B27, and get an AP pelvis radiograph.
• Ask about uveitis, psoriasis, bowel symptoms, heel pain and family history.
• Try a full-dose NSAID for 2–4 weeks. A clear response supports axSpA.

Refer (semi-urgent) if chronic back pain began before 45 and there is at least one of: inflammatory back pain, HLA-B27, raised CRP, sacroiliitis on imaging, or another spondyloarthritis feature.

If none of these are present, mechanical back pain is more likely. Treat with activity and physical therapy and review if the pattern changes.

MCTD combines features of lupus, systemic sclerosis and myositis with a high-titer anti-U1 RNP antibody. Raynaud's and puffy hands are nearly universal.

Main long-term risks: interstitial lung disease and pulmonary hypertension.

Usual workup recommended before the referral is seen: ANA, anti-U1 RNP, CK, CBC, metabolic panel, urinalysis; PFTs with DLCO, HRCT chest and an echocardiogram (ERS/EULAR 2025 recommends ILD screening for everyone with MCTD).

Features can evolve over years into SLE, systemic sclerosis or myositis, so ongoing specialist follow-up is usually needed.

PAN is a medium-vessel vasculitis. Look for tender skin nodules, livedo racemosa, ulcers, mononeuritis multiplex (foot or wrist drop), testicular pain, new hypertension, and abdominal pain after meals.

Tests: ESR, CRP, CBC, metabolic panel, urinalysis, hepatitis B and C (PAN can be hepatitis B-related), and ANCA (usually negative; a positive result suggests another diagnosis).

Diagnosis usually needs a biopsy of affected skin, nerve or muscle, or angiography showing microaneurysms.

Urgency: urgent; mesenteric ischemia is emergent. In children and young adults, especially with stroke, ask about DADA2 testing.

A hot, swollen joint is septic arthritis until proven otherwise, especially with fever, immunosuppression, diabetes, a prosthetic joint, recent joint injection or IV drug use. Fever is absent in many patients.

Same day: emergency department or orthopedics.

• Aspirate before antibiotics if the patient is stable: cell count, Gram stain, culture and crystals.
• Blood cultures, CBC, CRP.
• Crystals don't exclude infection; gout and sepsis can coexist.
• Prosthetic joints should be aspirated by orthopedics.

Rheumatology can advise, but delay to a clinic appointment is unsafe.

A child with fever and an acutely painful joint or bone, or who refuses to bear weight, needs same-day assessment for infection: emergency department or pediatric orthopedics.

Tests usually include CBC, CRP, ESR, blood cultures, ultrasound for a hip effusion, and joint aspiration. MRI helps with osteomyelitis. Kingella kingae is a common cause in young children.

Rheumatology is involved later if infection is excluded and inflammation persists.

Large-vessel vasculitis in younger patients (classically women under 40) causes limb claudication, reduced or absent pulses, unequal arm blood pressures, bruits, carotid pain and hypertension, often with constitutional symptoms.

Tests: ESR, CRP, CBC, metabolic panel; blood pressure in both arms; CTA or MRA of the aorta and its branches.

Urgency: urgent referral. Ischemic symptoms such as stroke or TIA, mesenteric pain or a threatened limb are emergent.

In adults over 50, large-vessel GCA can look similar.

• TB: IGRA (preferred) or tuberculin skin test, plus a chest X-ray if positive or at high risk
• Hepatitis B: HBsAg, anti-HBc (total) and anti-HBs
• Hepatitis C: antibody, with RNA if positive
• HIV: USPSTF recommends screening everyone aged 15–65 at least once, and anyone younger or older at increased risk
• Baseline labs: CBC with differential, metabolic panel with liver tests; lipids before IL-6 or JAK inhibitors; immunoglobulins before rituximab
• Vaccines: update inactivated vaccines (pneumococcal, influenza, COVID-19, hepatitis B if non-immune, HPV where eligible); recombinant zoster vaccine, especially before JAK inhibitors; give any needed live vaccines (MMR, varicella) at least 4 weeks before starting
• Other: pregnancy plans, cancer screening up to date, history of heart failure or demyelinating disease (TNF inhibitors), diverticulitis (IL-6 inhibitors), and VTE and cardiovascular risk (JAK inhibitors)

• Most women with rheumatic disease can have successful pregnancies with planning.
• Aim for quiet disease on compatible medicines before conception.
• Hydroxychloroquine, sulfasalazine, azathioprine, tacrolimus and TNF inhibitors are commonly used in pregnancy.
• Stop methotrexate 1–3 months and mycophenolate at least 6 weeks before conception.
• Low-dose aspirin is often recommended for lupus and antiphospholipid antibodies.
• Test SSA/Ro and antiphospholipid antibodies in lupus and related diseases.
• Avoid NSAIDs from 20 weeks.

Primary Raynaud's typically starts between 15 and 30, with symmetric color changes (white, then blue, then red), no tissue injury, a negative or low-titer ANA and normal nailfold capillaries.

Management

• Keep the whole body warm, use gloves and hand warmers, stop smoking.
• Avoid vasoconstrictors where possible (decongestants, some migraine drugs, stimulants).
• A dihydropyridine calcium channel blocker (nifedipine or amlodipine) helps frequent or severe attacks.

Refer if secondary features appear: digital ulcers or pitting, puffy fingers, a positive specific antibody, abnormal capillaries, onset after about 30–40, or asymmetric attacks.

Most prolonged fevers in children are infections (often common infections with an unusual course), followed by inflammatory conditions and malignancy.

Rheumatologic causes: systemic JIA, Kawasaki disease (consider incomplete KD in infants), lupus, vasculitis, periodic fever syndromes and IBD.

Tests: CBC with blood film, ESR, CRP, ferritin, LDH, liver tests, urinalysis, blood cultures, and targeted infection testing and imaging.

Refer to pediatric rheumatology when the pattern suggests an inflammatory cause; involve infectious diseases and hematology-oncology as needed.

Fever of unknown origin is usually investigated by internal medicine or infectious diseases first. Rheumatologic causes are an important part of the differential:

• GCA in adults over 50, sometimes without headache
• Still's disease (fever, rash, arthritis, very high ferritin)
• Lupus, vasculitis, PMR, sarcoidosis

Common first tests: CBC with smear, metabolic panel with liver tests, ESR, CRP, ferritin, LDH, urinalysis, blood cultures, HIV, TB testing, and cross-sectional imaging. Temporal artery ultrasound or biopsy can be considered in older adults.

Refer to rheumatology when clues point to a rheumatic disease. Otherwise, an infectious diseases or general medicine evaluation is often the right first step.

Psoriatic arthritis can cause asymmetric arthritis, symmetric polyarthritis, DIP joint disease, dactylitis ("sausage digits"), enthesitis (heel pain) and inflammatory back pain. Psoriasis may be mild or hidden (scalp, ears, umbilicus, natal cleft, nails), and some patients only have a family history.

Usual workup recommended before the referral is seen: ESR and CRP (often normal in PsA), RF and anti-CCP (usually negative), CBC, metabolic panel, hepatitis B and C, and X-rays of affected hands and feet.

Refer within 2–4 weeks. Early treatment prevents irreversible damage. Treatment options keep expanding; deucravacitinib, a TYK2 inhibitor, was FDA-approved for PsA in March 2026.

Many women with RA improve during pregnancy and flare after delivery, but some stay active, and active disease is linked with smaller babies and preterm birth.

Care

• Plan with rheumatology; switch methotrexate or leflunomide to compatible drugs (sulfasalazine, hydroxychloroquine, TNF inhibitors).
• TNF inhibitors can be continued through pregnancy if needed (EULAR 2024).
• Avoid NSAIDs from 20 weeks; use low-dose prednisone if a flare needs it.
• Plan postpartum care early, as flares are common in the first months after delivery.

An isolated, mildly raised ESR or CRP is common and rarely due to rheumatic disease.

Common causes: infection, obesity, smoking, anemia, kidney disease, pregnancy, age (ESR rises with age), and malignancy. A rough upper limit for ESR is age ÷ 2 for men and (age + 10) ÷ 2 for women.

Reasonable steps

• Repeat in a few weeks, together with CRP.
• Check CBC, metabolic panel with liver tests, urinalysis; serum protein electrophoresis if the ESR is high and the CRP is normal.
• Review symptoms carefully, including age-appropriate cancer screening.

Refer if symptoms of PMR, GCA, inflammatory arthritis or vasculitis appear, or for a persistently very high ESR without explanation.

Tocilizumab, sarilumab and JAK inhibitors raise LDL and HDL cholesterol, usually within the first months.

Steps: check lipids about 4–12 weeks after starting, then periodically. Manage with standard cardiovascular risk guidance; statins are effective. Inflammatory disease itself raises cardiovascular risk, so assess overall risk rather than the lipid change alone.

Mild, transient rises are common, especially on methotrexate and leflunomide.

Commonly used thresholds: ALT or AST above 100 U/L (or a sustained rise above about 3 times normal) usually means pausing and contacting the prescribing team. Smaller rises (1–3 times normal) often settle with a dose review and a repeat test in 2–4 weeks.

Check for contributors: alcohol, fatty liver disease, viral hepatitis, other hepatotoxic drugs (including NSAIDs and supplements), and a falling albumin. BSR 2025 suggests FIB-4 scoring (and elastography when indicated) for patients with liver risk factors on methotrexate.

Breathlessness that worsens over days to weeks in a patient with myositis (especially anti-MDA5 or antisynthetase antibodies), systemic sclerosis or another CTD can be rapidly progressive ILD.

Anti-MDA5 dermatomyositis often has skin ulcers, palmar papules and little muscle weakness, and lung disease can progress quickly.

Same day: emergency assessment with oxygen saturation, HRCT chest, and exclusion of infection, pulmonary embolism and heart failure. Contact rheumatology and pulmonology. Early combination immunosuppression is often needed.

A positive ANA (especially anti-centromere, Scl-70 or RNA polymerase III) or abnormal nailfold capillaries (dilated loops, dropout, hemorrhages) raise the chance of an underlying connective tissue disease, most often systemic sclerosis.

Steps: ENA panel including SSc antibodies, CBC, metabolic panel, ESR/CRP, urinalysis. Ask about puffy fingers, reflux, breathlessness and skin changes.

Refer semi-urgently. Puffy fingers, skin thickening or ulcers make it urgent.

A dermatoscope or ophthalmoscope can give a rough look at nailfold capillaries if formal capillaroscopy isn't available.

Late onset (after about 30–40), asymmetric attacks or involvement of one digit suggest secondary Raynaud's.

Causes to consider

• Connective tissue disease: systemic sclerosis, lupus, MCTD, Sjögren's, myositis
• Vascular: atherosclerosis, thoracic outlet syndrome, emboli, vibration injury
• Blood: cryoglobulins, cold agglutinins, paraproteins
• Drugs: beta-blockers, ergots, stimulants, some chemotherapy
• Hypothyroidism

Workup: ANA with ENA, CBC, metabolic panel, ESR/CRP, urinalysis, TSH; cryoglobulins and SPEP where relevant; pulses and blood pressure in both arms.

Features of primary Raynaud's: onset between 15 and 30, symmetric attacks, no ulcers or pitting, normal nailfold capillaries, negative or low-titer ANA, normal ESR.

Features of secondary Raynaud's: later onset, asymmetry, digital ulcers or pitting, puffy fingers, abnormal capillaries, a positive specific antibody, or systemic symptoms.

A reasonable first panel: ANA, CBC, metabolic panel, ESR or CRP, urinalysis. Add SSc antibodies if the ANA is positive.

Reactive arthritis in children usually follows a gut infection (Salmonella, Shigella, Campylobacter, Yersinia), or Chlamydia in adolescents. It typically causes asymmetric arthritis of the legs, sometimes with enthesitis.

Steps: NSAIDs; check ESR, CRP and HLA-B27. Exclude septic arthritis if a single hot joint is present with fever.

Refer if it lasts more than 6 weeks (it may be JIA or enthesitis-related arthritis), recurs, or the diagnosis is uncertain.

Palindromic rheumatism causes attacks of pain and swelling in one or a few joints, or nearby soft tissue, lasting hours to days and resolving completely. A substantial proportion of patients later develop RA, especially those with anti-CCP antibodies.

Steps

• Check RF, anti-CCP, ESR and CRP (ideally during an attack), and uric acid.
• Ask the patient to photograph an attack.
• Consider gout and CPPD, which can also be episodic.

Refer routinely; more urgently if anti-CCP is positive or attacks are becoming more frequent or persistent.

Most recurrent mouth ulcers are simple aphthous ulcers.

Consider other causes when ulcers are frequent, large or come with other features

• Behçet's syndrome: plus genital ulcers, eye inflammation, skin lesions or thrombosis
• Lupus: often painless, on the hard palate
• Inflammatory bowel disease and celiac disease
• Low iron, B12 or folate
• Drugs: methotrexate toxicity (check a CBC), NSAIDs, nicorandil
• Herpes simplex
• In children: PFAPA (with fevers, sore throat and neck nodes)

Tests: CBC, ferritin, B12, folate, celiac serology; ANA if lupus features are present.

Refer if Behçet's or lupus features are present.

Relapsing polychondritis causes recurrent, painful, red swelling of cartilage: the ear (sparing the lobe), the nasal bridge (saddle nose) and the airway (hoarseness, cough, stridor). Inflammatory arthritis, eye inflammation, hearing loss and vertigo can occur.

Emergency: stridor, breathing difficulty or rapidly worsening hoarseness can mean airway narrowing. Arrange same-day emergency or ENT assessment.

Tests: ESR, CRP, CBC, metabolic panel. If there are stable respiratory symptoms, PFTs with flow-volume loops and CT of the airway; stable airway involvement is urgent.

In men over 50 with fevers, cytopenias or macrocytosis, consider VEXAS syndrome.

After surgery (ACR/AAHKS 2022, joint replacement): restart about 14 days after surgery if the wound is healing, sutures or staples are out, and there is no infection.

After an infection: restart once the infection has resolved and antibiotics are complete. After serious infections, discuss with the prescribing team.

After a long gap: some biologics (notably infliximab) carry a higher risk of infusion reactions when restarted after a long interruption. The prescribing team may adjust the plan.

Rheumatologic emergencies usually threaten an organ: sight (GCA), kidneys (vasculitis, lupus, scleroderma renal crisis), lungs (hemorrhage, rapidly progressive ILD), airway and swallowing (myositis), digits (critical ischemia), or life (MAS, CAPS, sepsis on immunosuppression).

Infection comes first. A hot joint with fever, or fever on immunosuppression, needs urgent assessment for infection before attributing symptoms to disease activity.

When in doubt, call. Most rheumatology services have an on-call physician. Send the patient to the emergency department if they are unstable or deteriorating.

Methotrexate, leflunomide, sulfasalazine, azathioprine and mycophenolate (typical schedule)

• Before starting: CBC, metabolic panel with creatinine and liver tests, hepatitis B and C (and the drug-specific tests in the DMARD table)
• First 3–6 months, or after a dose increase: CBC, creatinine and ALT/AST every 2–4 weeks at first, then about monthly (BSR 2025: week 2, then monthly for the first 3–6 months)
• Stable: about every 3 months. BSR 2025 allows longer intervals for some stable patients after an individual risk review.

Hydroxychloroquine: retinal screening rather than routine blood tests in adults (a baseline exam soon after starting, then yearly from 5 years, or from the start with risk factors). In children, ACR 2026 suggests a yearly CBC and liver tests, with baseline and annual retinal screening.

Leflunomide: also blood pressure and weight.

Biologics and JAK inhibitors: see the DMARD table; JAK inhibitors and IL-6 inhibitors need CBC, liver tests and lipids.

Always follow the shared-care plan from the prescribing team.

Löfgren syndrome (bilateral hilar lymphadenopathy, erythema nodosum and ankle periarthritis) usually settles with NSAIDs and time.

Other rheumatologic features: chronic arthritis, skin disease (lupus pernio), uveitis, hypercalcemia, bone lesions, and in children under 5, Blau syndrome or early-onset sarcoidosis (rash, arthritis, uveitis).

Tests: chest X-ray or CT, calcium, metabolic panel with liver tests, urinalysis, CBC, ECG. ACE levels have limited sensitivity and specificity. Biopsy of accessible tissue for non-caseating granulomas, except in classic Löfgren syndrome.

Coordinate with pulmonology, arrange an eye exam, and treat suspected cardiac or neurologic sarcoidosis as urgent.

Scleroderma renal crisis presents with new, often severe hypertension and acute kidney injury, sometimes with headache, visual change, seizures or hemolysis with low platelets. A minority have normal blood pressure.

Highest risk: early diffuse cutaneous systemic sclerosis, anti-RNA polymerase III antibodies, and high-dose glucocorticoids (prednisone above about 15 mg daily).

Same day: admit. Start an ACE inhibitor promptly (captopril is commonly used, titrated up), even if creatinine is rising. Avoid high-dose glucocorticoids. Contact rheumatology and nephrology.

Home blood pressure checks help patients at high risk catch it early.

Recombinant zoster vaccine (RZV) is non-live and safe on all immunosuppressants. Two doses, 2–6 months apart (a shorter interval is possible for people who are or will be immunosuppressed).

Who: the ACR 2022 guideline recommends RZV for patients 18 and older on immunosuppressive treatment; CDC recommends it for immunocompromised adults 19 and older and everyone 50 and older.

Priority: before starting JAK inhibitors, which carry the highest shingles risk, and for patients on combinations or glucocorticoids.

Systemic features include salivary or parotid swelling, lymphadenopathy, purpura, peripheral neuropathy, interstitial nephritis or renal tubular acidosis, interstitial lung disease, inflammatory arthritis and cytopenias.

Usual workup recommended before the referral is seen: ANA, SSA/Ro, SSB/La, RF, CBC, metabolic panel, urinalysis, IgG or serum protein electrophoresis, C3/C4; cryoglobulins if there is purpura or neuropathy.

Lymphoma risk: persistent parotid swelling, new lymphadenopathy, purpura, a low C4 or a monoclonal protein raise concern. Refer these promptly.

Persistent dry eyes and mouth with anti-SSA/Ro, and no systemic features, is often looked after with symptom care, dental and eye care, and periodic specialist review.

Symptom care

• Artificial tears; saliva substitutes; sugar-free lozenges or gum; humidifiers
• Regular dental care with fluoride; treat oral thrush
• Review drying medicines
• Pilocarpine or cevimeline for glandular dryness, if tolerated

Counseling: SSA/Ro-positive women considering pregnancy should know about neonatal lupus and congenital heart block (monitoring and hydroxychloroquine help).

Raise urgency for gland swelling, lymph nodes, purpura, neuropathy, cytopenias, a low C4 or a monoclonal protein.

Systemic sclerosis is suggested by Raynaud's with puffy fingers, skin thickening of the fingers (sclerodactyly) or beyond, digital pitting scars or ulcers, telangiectasias, reflux or swallowing problems, and breathlessness.

Usual workup recommended before the referral is seen

• ANA with pattern, anti-centromere, anti-Scl-70, anti-RNA polymerase III
• CBC, metabolic panel, urinalysis, blood pressure
• PFTs with DLCO and HRCT chest (recommended screening), and an echocardiogram

Important: avoid high-dose glucocorticoids, which raise the risk of scleroderma renal crisis. Rapidly spreading skin thickening is urgent. New severe hypertension with kidney injury is an emergency.

Not systemic sclerosis: isolated patches or bands of hard skin are usually localized scleroderma (morphea), which is managed differently.

Start now, without waiting: suspected GCA, and organ-threatening disease after discussion with rheumatology (vasculitis with kidney or lung involvement, severe lupus).

Try to avoid before the first visit where possible:

• Suspected inflammatory arthritis: steroids can mask synovitis and make diagnosis and classification harder.
• Suspected PMR: EULAR 2025 discourages a "trial of steroids" as a diagnostic test; complete the workup first.
• Suspected myositis: steroids can alter muscle biopsy findings.
• Undiagnosed fever or lymphadenopathy: steroids can mask lymphoma.
• Systemic sclerosis: high doses raise the risk of renal crisis.

If symptoms are severe and the wait is long, call rheumatology. A short course, or a joint injection, can be planned so it doesn't cloud the diagnosis. Document the dose and dates in the referral.

Indications (ACR 2020)

• Strongly recommended: tophi, radiographic damage, or 2 or more flares a year
• Conditionally recommended: more than one flare but fewer than 2 a year; after a first flare with CKD stage 3 or worse, a urate above 9 mg/dL, or kidney stones

How

• Allopurinol first-line: start at 100 mg daily or less (lower in CKD 3 or worse) and increase every few weeks (often every 2–5 weeks) until serum urate is below 6 mg/dL. Many patients need 300 mg or more.
• Consider HLA-B*58:01 testing first in patients of Southeast Asian descent and in African American patients.
• Flare prophylaxis (usually colchicine 0.6 mg once or twice daily, adjusted for kidney function) for 3–6 months.
• Febuxostat is an alternative; the ACR suggests switching from it if there is cardiovascular disease or a new CV event.

Check urate after each dose increase, then about every 6 months once at target. Continue treatment long term.

Stopping denosumab causes a rapid rebound in bone turnover, and multiple vertebral fractures can occur within months.

Never stop denosumab without a plan.

• Give injections on time, every 6 months.
• To stop, transition to a bisphosphonate (often zoledronic acid about 6 months after the last dose, or oral alendronate), and consider checking bone turnover markers.
• Seek specialist advice if a dose has been missed by several months or a transition is unclear.

Surgery: the ACR/AAHKS 2022 guideline recommends continuing the usual daily glucocorticoid dose rather than giving routine supraphysiologic "stress doses" for hip and knee replacement. Anesthesia teams follow their own protocols for other surgery.

Acute illness: patients on long-term glucocorticoids shouldn't stop them suddenly. "Sick-day rules" (temporarily increasing the dose during significant illness) are often advised, especially at physiologic doses after a long course.

Adrenal insufficiency can follow prolonged treatment. Suspect it with fatigue, nausea, low blood pressure, low sodium or hypoglycemia during a taper or after stopping. Check a morning cortisol and seek endocrine advice.

Chronic back pain that began before 45, with inflammatory features, suggests axial spondyloarthritis (axSpA). Diagnosis is often delayed by years.

Inflammatory features: insidious onset, morning stiffness over 30 minutes, improvement with exercise but not with rest, night pain (often in the second half of the night), alternating buttock pain.

Supporting features: HLA-B27, raised CRP, uveitis, psoriasis, inflammatory bowel disease, enthesitis or dactylitis, family history, a good response to NSAIDs.

Usual workup recommended before the referral is seen

• CRP, ESR, HLA-B27
• AP pelvis radiograph as the first imaging test (preferred over lumbar spine films or dedicated SI joint views in the 2026 ACR guideline)
• If X-rays are non-diagnostic, SI joint MRI without contrast is the next step

While waiting: a continuous full-dose NSAID trial if safe, and physical therapy.

GCA can cause sudden, permanent vision loss. Treat on suspicion.

Typical features: age 50 or older; new headache, scalp tenderness or jaw claudication; visual symptoms (transient loss, diplopia); PMR symptoms; fever, weight loss; arm claudication. ESR and CRP are usually raised, but normal values don't exclude GCA.

Same day

• Start glucocorticoids on clinical suspicion (typically prednisone 40–60 mg daily). Don't wait for biopsy or imaging.
• Any visual symptom: same-day emergency or ophthalmology assessment. IV methylprednisolone is often used.
• Call rheumatology. EULAR 2025 treats suspected cranial GCA as an emergency, with urgent specialist referral within 24 hours of presentation.
• Send ESR, CRP, CBC and a metabolic panel with glucose.

Confirming the diagnosis: temporal and axillary artery ultrasound (first-line where a fast-track service exists) or temporal artery biopsy. Ultrasound findings can fade within days of starting glucocorticoids, so arrange it quickly.

Symmetric proximal weakness (trouble rising from a chair, climbing stairs or lifting the arms) with a raised CK suggests myositis. AST, ALT and LDH are often raised too, which can be mistaken for liver disease.

Usual workup recommended before the referral is seen

• CK, aldolase, AST/ALT, LDH, TSH, CBC, metabolic panel, ESR/CRP
• ANA and a myositis-specific and myositis-associated antibody panel
• ECG and troponin if there are any cardiac symptoms; PFTs and HRCT if cough or breathlessness

Emergent: trouble swallowing or breathing, rapidly worsening lung disease, or myocarditis.

Cancer screening is part of the workup, especially in dermatomyositis, and is usually tailored by rheumatology using the IMACS 2023 guideline.

Lupus is suggested by a positive ANA with features such as photosensitive or malar rash, mouth or nose ulcers, non-scarring hair loss, inflammatory arthritis, pleurisy or pericarditis, low blood counts, or protein or blood in the urine.

Usual workup recommended before the referral is seen

• ANA (titer and pattern), anti-dsDNA, ENA panel (Sm, RNP, SSA/Ro, SSB/La), C3 and C4
• CBC with differential, metabolic panel
• Urinalysis with microscopy and urine protein-to-creatinine ratio
• Antiphospholipid antibodies if there have been clots or pregnancy losses

Emergent: nephritis (rising creatinine, heavy proteinuria, active sediment), lung hemorrhage, seizures or psychosis, or severe cytopenias.

Rheumatology may suggest starting hydroxychloroquine early; the 2025 ACR guideline recommends it for nearly everyone with SLE. Avoid starting glucocorticoids unless there is organ threat.

These are specialist decisions, but primary care often sees the triggers first: loss of response, side effects, infections, pregnancy plans, cancer, or surgery.

Principles

• After one biologic fails, switching to a different mechanism is often preferred (for example, the 2026 axSpA guideline).
• In sustained remission, rheumatology may taper rather than stop; abrupt withdrawal raises flare risk.
• Don't stop a biologic just because the patient feels well; discuss with the prescribing team.

Systemic JIA causes quotidian (daily, spiking) fevers for 2 weeks or more, an evanescent salmon-pink rash, arthritis (sometimes later), serositis, enlarged nodes, liver or spleen, and very high inflammatory markers.

Exclude infection and malignancy (leukemia, neuroblastoma) before diagnosing sJIA.

Contact pediatric rheumatology the same day. Macrophage activation syndrome is a life-threatening complication: falling platelets or white cells, a rising ferritin, liver test rise and falling fibrinogen.

Treatment (ACR 2026): IL-1 or IL-6 inhibitors first-line; avoid NSAIDs, csDMARDs or oral glucocorticoids alone.

General principles

• Courses shorter than about 3 weeks can usually be stopped without a taper.
• Longer courses: taper to reduce flare risk and allow adrenal recovery. Larger steps are fine at higher doses; slow down below about 10 mg, and below 5 mg (for example, 1 mg steps every 2–4 weeks).

Disease-specific examples (EULAR 2025)

• PMR: start at 15–25 mg, reach 10 mg daily within about 2 months, then taper slowly, aiming to stop within about a year.
• GCA: start at 40–60 mg, reach 15–20 mg daily by months 2–3, aiming to stop within 12–18 months.

If symptoms return, go back to the last effective dose and contact rheumatology. Repeated relapses suggest a steroid-sparing drug is needed.

Test: an interferon-gamma release assay (IGRA) is generally preferred, especially after BCG vaccination. A tuberculin skin test is an alternative.

If positive: chest X-ray and clinical assessment to exclude active TB, then latent TB treatment (often started at least about 1 month before the biologic, per local protocol and infectious disease advice).

Repeat testing is reasonable for patients with ongoing exposure risk (travel, healthcare work, high-incidence settings). TNF inhibitors carry the highest reactivation risk.

Rotator cuff disease, epicondylitis, de Quervain's tenosynovitis, trigger finger, trochanteric pain, plantar fasciitis and carpal tunnel syndrome are common and usually best served by MSK pathways.

Management: activity modification, physical or occupational therapy, splints or orthotics, and injections where appropriate. Sports medicine, orthopedics or hand surgery can help with persistent problems.

Consider rheumatology if several regions are involved, or there is swelling or enthesitis suggesting spondyloarthritis or another inflammatory disease. Bilateral carpal tunnel can be an early sign of RA, hypothyroidism or amyloidosis.

Treat early, ideally within 24 hours of onset. Choose based on comorbidities:

• Colchicine: a low-dose regimen (for example, 1.2 mg then 0.6 mg an hour later, then 0.6 mg once or twice daily). Reduce the dose in CKD, and avoid with strong CYP3A4 or P-glycoprotein inhibitors.
• An NSAID at full dose if kidney, GI and cardiovascular risks allow.
• A glucocorticoid: oral prednisone (for example, 30–40 mg daily, tapered over 5–10 days), or an intra-articular injection for one large joint.
• IL-1 inhibitors (canakinumab, anakinra) for patients who can't take the above, usually via rheumatology.

Continue urate-lowering therapy during a flare if the patient is already on it.

Act promptly but calmly.

• Stop methotrexate or mycophenolate immediately. For leflunomide, stop it and start accelerated elimination with cholestyramine.
• Start or continue folic acid (high-dose folic acid is often advised after methotrexate exposure).
• Contact rheumatology and obstetrics or maternal-fetal medicine the same week for counseling, early ultrasound and risk assessment.
• Switch to a compatible drug to keep the disease controlled.

The risk after exposure varies by drug, dose and timing. Many exposed pregnancies have normal outcomes, so specialist counseling is essential.

Where available, an e-consult or advice line is a quick way to decide whether a patient needs to be seen, how urgently, and what workup to send first.

Good questions for an e-consult

• "Does this lab result need a visit?" (for example, a positive ANA with few symptoms)
• "Can I start or adjust this treatment while the patient waits?"
• "What should I check before the visit so it is most useful?"
• Monitoring questions on a stable patient

Usually better as a referral or a call

• Suspected new synovitis, lupus or vasculitis, which needs an examination
• Anything organ-threatening (call)

An e-consult supports the decision about whether to see the patient; it doesn't replace an in-person examination when one is needed.

Methotrexate: consider holding for 2 weeks after influenza vaccination if disease activity allows (ACR 2022). BSR 2025 suggests withholding methotrexate for up to 2 weeks after influenza or COVID-19 vaccination in adults where disease allows.

Rituximab: vaccine responses are blunted for 6 months or more after a dose.

• Give non-influenza vaccines at least 2 weeks before the next rituximab dose where possible.
• Give influenza vaccine on schedule rather than delaying it.

Other medicines (TNF inhibitors, IL-6 and IL-17 inhibitors, hydroxychloroquine, sulfasalazine) generally continue around vaccination.

Best given before immunosuppression starts (responses are better, and live vaccines are possible):

• Pneumococcal vaccine (PCV20 or PCV21, or per current CDC schedule; where serotype 4 disease is common, such as Alaska, PCV20, or PCV15 then PPSV23, may give broader coverage)
• Recombinant zoster vaccine (2 doses), especially before JAK inhibitors
• Influenza and COVID-19 vaccines
• Hepatitis B vaccine if non-immune
• HPV vaccine where eligible
• Live vaccines (MMR, varicella) if non-immune: give at least 4 weeks before starting, if the patient isn't already immunosuppressed

Don't delay urgent treatment to complete vaccines; inactivated vaccines can be given during treatment.

Keep inactivated vaccines on schedule. They are safe on DMARDs and biologics.

Live vaccines (MMR, varicella) are best given before immunosuppression starts. During treatment, decisions are individualized with pediatric rheumatology; some children on low-dose methotrexate may receive booster live vaccines after discussion (EULAR/PReS 2021).

After high-dose IVIG (for example, Kawasaki disease): delay measles- and varicella-containing vaccines for 11 months.

Children on aspirin should receive inactivated influenza vaccine, not the live nasal vaccine.

Before starting csDMARDs, BSR 2025 suggests checking varicella and measles immunity in children.

Inactivated vaccines are safe on all DMARDs, biologics and JAK inhibitors: influenza, COVID-19, pneumococcal, recombinant zoster, hepatitis B, HPV, Tdap and others. Responses may be reduced on some treatments (rituximab, high-dose glucocorticoids, mycophenolate, abatacept), but vaccination is still recommended.

Live vaccines are generally avoided during immunosuppression; plan them before treatment where possible.

Best timing: before immunosuppression starts when possible, but don't delay urgent treatment for vaccines.

Vasculitis is uncommon, and its mimics are more common. Before labeling vasculitis, consider:

• Infection: endocarditis, sepsis, hepatitis B and C, HIV
• Emboli: cholesterol emboli after vascular procedures, atrial myxoma
• Drugs: cocaine (often levamisole-adulterated), hydralazine, propylthiouracil
• Clotting disorders: antiphospholipid syndrome
• Malignancy and calciphylaxis

A useful first panel: CBC, metabolic panel, urinalysis with microscopy (the single most useful test), ESR and CRP, PR3/MPO-ANCA, C3/C4, cryoglobulins, hepatitis B and C, HIV, blood cultures if febrile, CK, and chest imaging.

Call rheumatology the same day for any organ threat: kidney involvement, lung hemorrhage, mononeuritis, ischemic gut or digits, or visual symptoms.

VEXAS is an acquired (somatic) UBA1 mutation in blood cells. It causes recurrent inflammation, mostly in men over 50, and is estimated to affect about 1 in 4,000 men in that age group.

Clues: recurrent fevers, ear or nose chondritis (often labeled relapsing polychondritis), neutrophilic skin lesions (Sweet-like), vasculitis, lung infiltrates, venous thrombosis, macrocytic anemia, low platelets or myelodysplasia, and dependence on glucocorticoids.

Tests: CBC with smear (macrocytosis), CRP and ESR, metabolic panel. Diagnosis is by UBA1 testing, usually arranged by hematology or rheumatology.

Refer to rheumatology and hematology; severe cytopenias are urgent. The 2025 ACR guidance statement advises against B-cell depletion (rituximab) and recommends considering clot prevention when hospitalized and PJP and zoster prophylaxis. Women, especially with X-chromosome loss, are occasionally affected.

A normal CK makes most inflammatory myositis less likely, though not impossible (treated disease, some dermatomyositis, inclusion body myositis).

Consider

• Neurologic causes: myasthenia gravis (fatigable weakness, ptosis, diplopia), neuropathy, myelopathy, motor neuron disease
• Endocrine and metabolic: hypothyroidism, Cushing's or glucocorticoid myopathy, low potassium, calcium, magnesium or phosphate
• PMR: pain and stiffness that limit movement, rather than true weakness
• Inclusion body myositis: over 50, finger flexor and quadriceps weakness, slow progression
• Medicines and deconditioning

Tests: TSH, electrolytes including calcium, magnesium and phosphate, ESR/CRP, aldolase. Neurology referral and EMG are often the right next step.

In one clinic audit, 47% of referrals changed urgency grade after the consult, and 17% were upgraded to urgent. Referrals for those urgent patients often lacked a working diagnosis, symptom duration, or the joints involved.

Include

• Your question: diagnosis, treatment advice, a shared-care plan or a second opinion
• Your working diagnosis and level of concern
• Onset date and how symptoms are changing
• Examination findings: which joints are swollen, morning stiffness in minutes, rash, eye or nail findings, strength
• Red flags present or absent
• Results with dates, titers and reference ranges
• Treatments tried, with doses, dates and response (especially glucocorticoids)
• Pregnancy plans, infection history, kidney or liver disease, cancer history
• Photos of transient rashes or swelling (with consent)
• How to reach you

Explain why you are referring, roughly how long the wait may be, and what you have already arranged.

Ask the patient to

• Photograph any swelling, rash or color change when it is at its worst
• Keep a short diary of symptoms, morning stiffness and medicines tried
• Bring a list of all medicines and supplements to the appointment
• Stay active, and use an NSAID if you have advised one

Ask them to seek help sooner for new joint swelling, fever with a hot joint, new headache or visual symptoms (especially over 50), breathlessness, weakness, or a cold, painful digit.

A printable patient handout is available in the downloads.

Pick up the phone, or send the patient to the emergency department, rather than sending a routine referral, for:

• Suspected giant cell arteritis, especially with visual symptoms
• A hot, swollen joint with fever (septic arthritis until proven otherwise; usually ED or orthopedics)
• Kidney involvement or coughing blood in suspected vasculitis or lupus
• New severe hypertension or kidney injury in systemic sclerosis
• Weakness with trouble swallowing or breathing
• Persistent fever with falling blood counts and a very high ferritin
• A cold, painful or discolored finger or toe
• A child with suspected Kawasaki disease, MIS-C or MAS

An ANA is most useful when the pretest probability is reasonable.

Order it for: features of lupus (rash, ulcers, serositis, cytopenias, proteinuria), Raynaud's with puffy fingers or ulcers, suspected Sjögren's disease, myositis or systemic sclerosis, and uveitis risk assessment in children with JIA.

Avoid ordering it for: fatigue or widespread pain alone, osteoarthritis, or as part of a general screen.

Don't repeat a positive ANA; the titer doesn't track disease activity. Avoid ANA sub-serologies (ENA panel) when the ANA is negative and clinical suspicion is low.

USPSTF 2025: screen women 65 and older, and postmenopausal women under 65 at increased risk (using a risk tool). Evidence is insufficient for routine screening of men.

Also assess bone health in

• Anyone taking prednisone 2.5 mg daily or more for 3 months or more (ACR 2022 GIOP guideline)
• People with fragility fractures, RA, early menopause, low body weight, aromatase inhibitors or androgen deprivation

Use FRAX with or without bone density, and look for vertebral fractures (height loss, kyphosis).

Chronic widespread pain for 3 months or more, with fatigue, unrefreshing sleep and cognitive symptoms, a normal joint exam (apart from tenderness) and normal inflammatory markers, fits fibromyalgia.

Management

• Make and explain the diagnosis. More testing rarely helps and can increase anxiety.
• Graded aerobic exercise has the strongest evidence. Add sleep care, mood support and CBT-based approaches.
• Medicines with evidence: duloxetine, milnacipran, pregabalin, low-dose amitriptyline, and sublingual cyclobenzaprine (FDA-approved for fibromyalgia in 2025). Avoid opioids.

Refer if there is objective synovitis, raised inflammatory markers, or other signs of inflammatory disease, or if the diagnosis is genuinely uncertain. Fibromyalgia can coexist with RA, lupus and other conditions.

Raised markers with widespread pain point away from fibromyalgia.

Consider

• PMR (age 50 or older, girdle stiffness) and GCA
• Early inflammatory arthritis, lupus or myositis
• Infection (including endocarditis and spinal infection)
• Malignancy, including myeloma
• Vasculitis

Next steps: CBC, metabolic panel with liver tests, CK, TSH, urinalysis, serum protein electrophoresis, and targeted tests for the features present. Examine for synovitis, weakness and temporal artery tenderness.

A focused workup is enough for most patients:

• CBC, metabolic panel with liver tests and calcium
• ESR and CRP
• TSH
• CK if there is weakness or a statin

Avoid broad autoantibody panels (ANA, ENA, RF) without specific features. False positives are common and lead to unnecessary referrals and worry.

Also consider: sleep apnea, depression and anxiety, medication effects (statins, aromatase inhibitors), and deconditioning.

If the exam and these tests are normal, fibromyalgia is a positive diagnosis rather than a diagnosis of exclusion.