When to Refer

What to look for

• Age 50 or older with a new headache, scalp tenderness or jaw claudication
• Visual symptoms: transient monocular loss (amaurosis fugax), diplopia or sudden vision loss
• Shoulder and hip girdle aching (PMR symptoms), fever, weight loss or fatigue
• Arm claudication, unequal arm blood pressures or bruits suggest large-vessel involvement
• ESR and CRP are usually raised, but normal values do not rule GCA out

What to do

• Start glucocorticoids on the day of clinical suspicion; don't wait for biopsy or imaging. A typical starting dose is prednisone 40–60 mg daily.
• With visual loss or amaurosis, arrange same-day ophthalmology or emergency care. IV methylprednisolone is often used.
• Contact rheumatology the same day. EULAR 2025 treats suspected cranial GCA as an emergency, with urgent specialist referral within 24 hours of presentation, through a fast-track pathway where one exists.
• Confirm the diagnosis promptly. Use temporal and axillary artery ultrasound where a fast-track service exists, or temporal artery biopsy. Ultrasound changes can fade within days of starting glucocorticoids.
• Send ESR, CRP, CBC and a metabolic panel including glucose before or as treatment starts.

Good to know

• Ask every patient with PMR about headache, jaw pain and visual symptoms. Up to about 1 in 5 people with PMR may also have GCA, sometimes without cranial symptoms.
• A typical glucocorticoid plan tapers to 15–20 mg daily by months 2–3 (EULAR 2025). Steroid-sparing options include tocilizumab and upadacitinib (FDA-approved for GCA in 2025), with methotrexate as an alternative.

What to look for

• Rapidly progressive glomerulonephritis: rising creatinine, blood and protein on urinalysis, RBC casts
• Diffuse alveolar hemorrhage: hemoptysis, a falling hemoglobin, new infiltrates or hypoxia
• Mononeuritis multiplex (foot or wrist drop), scleritis, or stridor from subglottic stenosis
• GPA: chronic sinusitis, crusting, epistaxis, hearing loss, lung nodules or cavities
• EGPA: adult-onset asthma, eosinophilia, neuropathy, cardiac involvement

What to do

• Pulmonary hemorrhage or a rapidly rising creatinine needs the emergency department or admission. Contact rheumatology and nephrology directly.
• Order PR3- and MPO-ANCA by antigen-specific immunoassay, the preferred first test. Add urinalysis with microscopy, urine protein-to-creatinine ratio, creatinine, CBC, CRP and 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, and biopsy may be needed.

Good to know

• Treatment now commonly combines rituximab or cyclophosphamide with lower-dose glucocorticoid regimens and, in selected patients, avacopan.

What to look for

• Diffuse alveolar hemorrhage in SLE
• Rapidly progressive ILD, especially anti-MDA5 dermatomyositis (often with skin ulcers and little weakness)
• Scleroderma renal crisis: new severe hypertension and acute kidney injury, sometimes with microangiopathic hemolysis. Risk is highest in early diffuse SSc, with anti-RNA polymerase III, and with high-dose glucocorticoids.
• Severe lupus nephritis (nephrotic-range proteinuria, active sediment, rising creatinine) or neuropsychiatric lupus (seizures, psychosis, myelitis)
• Severe cytopenias such as hemolytic anemia or platelets below about 30,000
• Myositis with dysphagia, aspiration risk, respiratory muscle weakness or myocarditis
• Catastrophic antiphospholipid syndrome: thrombosis in several organs over days

What to do

• Emergency or inpatient evaluation is often needed. Contact rheumatology directly.
• Suspected scleroderma renal crisis: start an ACE inhibitor promptly (captopril is commonly used), admit, and avoid high-dose glucocorticoids.
• Suspected rapidly progressive ILD: urgent HRCT and admission. Early combination immunosuppression is usually needed.

What to look for

• Unremitting fever with new or worsening cytopenias
• Very high or rapidly rising ferritin (often above 5,000–10,000 ng/mL), raised AST/ALT, LDH and triglycerides
• Falling fibrinogen and ESR despite a rising CRP. This mismatch is a classic warning sign.
• Hepatosplenomegaly, coagulopathy, confusion or multiorgan dysfunction

What to do

• Send to the emergency department. Involve rheumatology and hematology the same day.
• Check CBC, ferritin, fibrinogen, triglycerides, liver tests, LDH, coagulation studies and blood cultures. Look for an infectious or malignant trigger.

Good to know

• Emapalumab was FDA-approved in June 2025 for HLH/MAS in known or suspected Still's disease (including systemic JIA), in adults and children, with an inadequate response or intolerance to glucocorticoids, or recurrent MAS.

What to look for

• Soft, boggy joint swelling (synovitis) of one or more joints, especially the small joints of the hands and feet
• Morning stiffness lasting 30–60 minutes or more, and pain that improves with use
• A positive squeeze test across the MCP or MTP joints
• RF or anti-CCP positive, or raised ESR/CRP. Normal blood tests do not exclude inflammatory arthritis.

What to do

• Refer as soon as synovitis is suspected; don't wait for test results. EULAR recommends that people with arthritis are seen by a rheumatologist within 6 weeks of symptom onset, and NICE advises urgent referral even when blood tests are normal.
• Send RF, anti-CCP, ESR, CRP, CBC with differential, and a metabolic panel with liver tests.
• Add hepatitis B (HBsAg, anti-HBc, anti-HBs) and hepatitis C antibody, which are needed before DMARDs. Add uric acid if gout is possible.
• Get X-rays of the hands and feet as a baseline for erosions.
• NSAIDs can help symptoms. If possible, avoid starting glucocorticoids before assessment, since they can mask synovitis. If symptoms are severe and the wait is long, discuss a short course with rheumatology.

What to look for

• Psoriasis now or in the past. Check the scalp, ears, umbilicus, gluteal cleft and nails (pitting, onycholysis).
• Patterns: asymmetric oligoarthritis, symmetric polyarthritis, DIP-predominant disease, axial disease, or arthritis mutilans
• Dactylitis ("sausage digit") and enthesitis (Achilles, plantar fascia)
• Uveitis or inflammatory bowel disease may coexist

What to do

• Refer within 2–4 weeks. Early treatment prevents irreversible joint damage.
• Send ESR, CRP, RF and anti-CCP (usually negative in PsA, which helps separate it from RA), CBC and a metabolic panel.
• Get X-rays of affected hands and feet.
• ESR and CRP are often normal in PsA, so normal results should not delay referral.

Good to know

• New treatment options keep arriving. Deucravacitinib (a TYK2 inhibitor) was FDA-approved for PsA in March 2026.

What to look for

• Positive ANA (usually 1:80 or higher by HEp-2 IFA; the entry criterion in the 2019 EULAR/ACR classification)
• Photosensitive or malar rash, discoid lesions, oral or nasal ulcers, non-scarring alopecia
• Inflammatory arthritis, serositis (pleurisy, pericarditis), fevers
• Cytopenias (leukopenia, lymphopenia, thrombocytopenia, hemolysis)
• Proteinuria or hematuria, low complements, anti-dsDNA or anti-Sm antibodies

What to do

• Send ANA titer and pattern, anti-dsDNA, ENA panel (Sm, RNP, SSA/Ro, SSB/La), C3/C4, CBC with differential, metabolic panel, urinalysis with microscopy and urine protein-to-creatinine ratio.
• Add antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) if there is a history of thrombosis or pregnancy loss.
• Nephritis, pulmonary hemorrhage, neuropsychiatric features or severe cytopenias are emergent.
• Rheumatology may advise starting hydroxychloroquine early, since the 2025 ACR guideline recommends it for nearly everyone with SLE. Avoid starting glucocorticoids unless there is organ threat.

What to look for

• Symmetric proximal weakness: trouble rising from a chair, climbing stairs or lifting the arms
• Raised CK. AST, ALT and LDH are also often high, which can be mistaken for liver disease.
• Dermatomyositis skin signs: heliotrope rash, Gottron papules, shawl or V-sign, mechanic's hands, periungual changes
• Dysphagia, dyspnea or cough (ILD), Raynaud's, arthritis
• On or after a statin, with weakness and a high CK that persists after stopping it (possible anti-HMGCR necrotizing myopathy)

What to do

• Send CK, aldolase, AST/ALT, LDH, TSH, CBC, metabolic panel, ESR/CRP, ANA, and a myositis-specific and myositis-associated antibody panel.
• Check an ECG and troponin if there are cardiac symptoms. Get PFTs and HRCT if there are respiratory symptoms.
• Cancer screening is part of the workup, especially in dermatomyositis. It is usually guided by rheumatology using IMACS 2023 risk stratification.
• Dysphagia, breathing weakness, rapidly progressive ILD or myocarditis are emergent.

What to look for

• Raynaud's with puffy or swollen fingers, sclerodactyly, digital pitting scars or ulcers
• Skin thickening proximal to the MCPs, telangiectasias, calcinosis
• Reflux, dysphagia, dyspnea, or a reduced DLCO
• ANA with an SSc-specific antibody: anti-centromere, anti-Scl-70 (topoisomerase I) or anti-RNA polymerase III
• Early disease can be just Raynaud's, puffy fingers and a positive ANA

What to do

• Send ANA with pattern, anti-centromere, anti-Scl-70, anti-RNA polymerase III, CBC, metabolic panel and urinalysis, and check blood pressure.
• Baseline PFTs with DLCO and HRCT are recommended for ILD screening (ACR/CHEST 2023). An echocardiogram helps screen for pulmonary hypertension.
• Avoid high-dose glucocorticoids, which raise the risk of renal crisis.
• Rapidly spreading skin thickening is urgent. New hypertension with AKI is emergent.

What to look for

• Persistent dry eyes and mouth, plus systemic features
• Salivary or parotid gland swelling, lymphadenopathy
• Purpura, peripheral neuropathy, interstitial nephritis or renal tubular acidosis, ILD, inflammatory arthritis
• Anti-SSA/Ro, RF, hypergammaglobulinemia, low C4, cryoglobulins

What to do

• Send ANA, SSA/Ro, SSB/La, RF, CBC, metabolic panel, urinalysis, serum protein electrophoresis or IgG, and C3/C4. Add cryoglobulins if there is purpura or neuropathy.
• Persistent parotid enlargement, new lymphadenopathy, purpura, low C4 or a monoclonal protein raise concern for lymphoma. Refer these promptly.
• Sicca alone with mild serology is a routine referral (see below).

What to look for

• Raynaud's (nearly universal) and puffy hands
• Arthritis, myositis, esophageal dysmotility
• ILD and pulmonary hypertension, the main long-term risks
• High-titer speckled ANA with anti-U1 RNP

What to do

• Send ANA, anti-U1 RNP, CK, CBC, metabolic panel and urinalysis.
• Get PFTs with DLCO and HRCT (MCTD is in the ACR/CHEST screening group), and an echocardiogram.
• Features can evolve into SLE, SSc or myositis over time, so ongoing specialist follow-up is usually needed.

What to look for

• Venous or arterial thrombosis, especially when young, unprovoked or at unusual sites
• Pregnancy morbidity: recurrent early loss, fetal death, or preterm delivery from preeclampsia or placental insufficiency
• Livedo, thrombocytopenia, heart valve thickening, microvascular kidney disease
• Lupus anticoagulant, anticardiolipin or anti-β2-glycoprotein I positive on two occasions at least 12 weeks apart

What to do

• Test lupus anticoagulant, anticardiolipin IgG/IgM and anti-β2-glycoprotein I IgG/IgM. Anticoagulants interfere with lupus anticoagulant testing, so note what the patient is taking.
• Repeat positive tests after at least 12 weeks.
• For confirmed thrombotic APS, warfarin is preferred. DOACs, rivaroxaban in particular, are not recommended for high-risk APS (triple-positive or arterial events).
• Pregnancy planning needs specialist input; LMWH and low-dose aspirin are typical.

What to look for

• Quotidian (daily, spiking) fevers, often 39 °C or higher
• Evanescent salmon-pink rash that comes with the fever
• Sore throat, arthralgia or arthritis, serositis, lymphadenopathy, splenomegaly
• Neutrophilic leukocytosis, raised liver tests, very high ferritin (glycosylated fraction under 20% if measured)

What to do

• Send CBC, metabolic panel with liver tests, ferritin, CRP/ESR and LDH.
• It is a diagnosis of exclusion. Rule out infection, malignancy (especially lymphoma) and drug reactions.
• EULAR/PReS 2024 favors early IL-1 or IL-6 blockade over prolonged glucocorticoids.
• Cytopenias with a rising ferritin may signal MAS, which is emergent.

What to look for

• Recurrent oral ulcers (3 or more episodes a year) plus genital ulcers
• Uveitis or retinal vasculitis. Eye involvement can threaten sight.
• Skin lesions: erythema nodosum, pseudofolliculitis, a positive pathergy test
• Venous thrombosis, arterial aneurysms, or neurologic involvement

What to do

• Same-day ophthalmology for visual loss, floaters or a painful red eye. Coughing blood (possible pulmonary artery aneurysm), sudden neurologic symptoms or sudden vision loss need emergency care.
• Send CBC, metabolic panel, CRP/ESR and urinalysis. There is no diagnostic blood test.
• Care is often multidisciplinary (rheumatology, ophthalmology, dermatology). Treatment depends on the organs involved.

What to look for

• Usually onset before age 40, though 2022 ACR/EULAR classification allows up to 60
• Arm or leg claudication, a reduced pulse, or a systolic BP difference between arms (20 mm Hg or more scores in the 2022 classification criteria)
• Carotid, subclavian or abdominal bruits, carotidynia, hypertension
• Constitutional symptoms and raised inflammatory markers

What to do

• Get CTA or MRA of the aorta and its branches. PET may be used by specialists.
• Send ESR, CRP, CBC and a metabolic panel.
• Ischemic symptoms (stroke or TIA, mesenteric or limb ischemia) are emergent.

What to look for

• Tender skin nodules, livedo racemosa, ulcers
• Mononeuritis multiplex, testicular pain, hypertension, renal infarcts
• Post-prandial abdominal pain from mesenteric involvement
• Associated with hepatitis B in some patients. ANCA is typically negative.

What to do

• Send ESR, CRP, CBC, metabolic panel, urinalysis, hepatitis B and C serology and ANCA (to exclude ANCA vasculitis).
• Biopsy of an affected tissue, or angiography showing microaneurysms, supports the diagnosis.
• Mesenteric ischemia is emergent. Consider DADA2 testing (ADA2 deficiency) in young-onset or stroke-associated PAN.

What to look for

• Palpable, non-blanching purpura, usually on the legs
• Arthralgia, abdominal pain, hematuria or proteinuria, neuropathy
• Causes include IgA vasculitis, cryoglobulinemic vasculitis (often hepatitis C), drug-induced vasculitis, ANCA vasculitis and urticarial vasculitis

What to do

• Fever or a patient who looks unwell: treat as possible sepsis or endocarditis first, with same-day emergency assessment and blood cultures.
• Send urinalysis with microscopy, creatinine, CBC, ANCA, C3/C4, cryoglobulins (drawn and kept warm), hepatitis B and C, and HIV.
• Skin biopsy with direct immunofluorescence is most useful from a lesion less than 48 hours old.
• Kidney, gut or nerve involvement raises the urgency. Pulmonary-renal features are emergent.

What to look for

• Inflammatory arthritis (RA-like, oligoarticular, or reactive-like). RF and anti-CCP are usually negative.
• PMR-like illness, sicca, or vasculitis
• Myositis, which can overlap with myocarditis and myasthenia (weakness, ptosis, dysphagia, dyspnea, troponin rise)
• These often persist after the checkpoint inhibitor stops, unlike many other irAEs

What to do

• Refer promptly and coordinate with oncology. Don't assume musculoskeletal symptoms come from the cancer.
• Send CBC, metabolic panel, CRP/ESR, CK, RF, anti-CCP and ANA. Add troponin and ECG if there is weakness or any cardiac symptom.
• Suspected myositis or myocarditis is emergent.
• Steroid-sparing DMARDs are often needed, chosen with the oncology team.

What to look for

• Exertional dyspnea, dry cough or inspiratory crackles in a patient with a systemic autoimmune rheumatic disease
• Highest risk: systemic sclerosis, myositis (especially antisynthetase and anti-MDA5), MCTD; also RA and Sjögren's with risk factors
• A falling FVC (about 10% or more, or 5–10% with worsening symptoms or imaging) or DLCO (about 15% or more)

What to do

• Get PFTs with spirometry, lung volumes and DLCO, plus HRCT chest. ACR/CHEST 2023 conditionally advises against chest X-ray or 6-minute walk alone for screening.
• Refer to rheumatology and pulmonology. Anti-MDA5 with ILD, or rapid decline, is emergent.
• ERS/EULAR 2025 strongly recommends HRCT screening for everyone with SSc or MCTD, and for myositis with risk factors such as antisynthetase or anti-MDA5 antibodies or amyopathic dermatomyositis.

What to look for

• Back pain for 3 months or more that began before age 45
• Inflammatory features: insidious onset, morning stiffness over 30 minutes, improves with exercise but not rest, night pain, alternating buttock pain
• Plus: HLA-B27, uveitis, psoriasis, IBD, dactylitis or enthesitis, family history, a good NSAID response, or a raised CRP

What to do

• Send CRP, ESR and HLA-B27.
• Get an AP pelvis radiograph as the first imaging test. The 2026 ACR guideline prefers it over lumbar spine films or dedicated SI joint views.
• If X-rays are non-diagnostic, SI joint MRI without contrast is the next test. Rheumatology often arranges this.
• Start a continuous NSAID trial and refer to physical therapy while waiting.

Good to know

• A normal X-ray does not rule out axSpA. Non-radiographic disease is common, especially in women.

What to look for

• Age 50 or older with bilateral shoulder and/or hip girdle pain, morning stiffness over 45 minutes
• Raised ESR or CRP, normal CK
• Usually a rapid, marked response to moderate-dose glucocorticoids, though response alone does not confirm the diagnosis
• Atypical: age under 60, peripheral arthritis, normal markers, poor steroid response, or prominent systemic symptoms

What to do

• Check for GCA features (headache, scalp tenderness, jaw claudication, visual symptoms, limb claudication). If present, treat as emergent.
• 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.
• Send ESR, CRP, CBC, metabolic panel, CK, TSH, RF/anti-CCP, and serum protein electrophoresis to look for mimics such as RA, myeloma and other cancers, myopathy and hypothyroidism. Complete the workup before glucocorticoids start; a 'trial of steroids' shouldn't be used as a diagnostic test (EULAR 2025).
• Guidelines differ on referral: EULAR 2025 recommends rapid specialist referral of all suspected PMR, while BSR 2026 expects most PMR to be managed in primary care with specialist support, referring atypical features, a second relapse, or 18 months or more of glucocorticoids. Follow your local pathway.
• Treatment: prednisone 15–25 mg daily, tapered to 10 mg daily within about 2 months, then slowly. Plan bone protection.
• Refer, or ask for advice, for atypical features, relapse on taper, or inability to taper. Sarilumab, tocilizumab and methotrexate are steroid-sparing options.

What to look for

• Tophaceous gout or radiographic damage
• Two or more flares a year despite adequately dosed urate-lowering therapy (ULT)
• Serum urate not below 6 mg/dL despite titration, or allopurinol hypersensitivity or intolerance
• CKD stage 4–5, transplant, or other comorbidity that makes ULT difficult
• Diagnostic uncertainty (gout vs CPPD vs septic or inflammatory arthritis), especially when aspiration isn't possible

What to do

• Send serum urate, creatinine/eGFR, CBC and liver tests, and include joint aspiration results if available.
• List ULT doses and duration, flare frequency and prophylaxis.
• Pegloticase (with methotrexate) is an option for refractory tophaceous gout.

What to look for

• Acute monoarthritis (knee, wrist) in older adults, often after illness or surgery
• Chronic inflammatory arthritis resembling RA, or OA in unusual joints (MCP, wrist, shoulder)
• Chondrocalcinosis on X-ray or ultrasound. CPP crystals (weakly positive birefringent) in synovial fluid confirm it.

What to do

• Aspirate and examine fluid for crystals and culture when possible.
• If onset is before about 60, or disease is polyarticular, screen for metabolic causes: calcium, phosphate, magnesium, ferritin and transferrin saturation (hemochromatosis), alkaline phosphatase, TSH.

What to look for

• Onset after about 30–40, asymmetric attacks, or thumb involvement
• Digital pitting scars, ulcers, or puffy fingers
• Abnormal nailfold capillaries (dilated loops, dropout, hemorrhages)
• Positive ANA, especially with anti-centromere, Scl-70 or RNA polymerase III

What to do

• Send ANA with pattern, an ENA panel including centromere and Scl-70, CBC, metabolic panel, ESR/CRP and urinalysis.
• Treat symptoms (warmth, smoking cessation, a dihydropyridine calcium channel blocker).
• Active digital ulcers are urgent. Critical ischemia or gangrene is emergent.

What to look for

• Asymmetric oligoarthritis of the legs, enthesitis, dactylitis
• Follows enteric infection (Salmonella, Shigella, Campylobacter, Yersinia) or Chlamydia
• Conjunctivitis, urethritis, oral ulcers or keratoderma

What to do

• NSAIDs are first-line. Most cases settle within weeks to months.
• Screen for STIs after GU symptoms. Check ESR, CRP and HLA-B27.
• Refer if swelling persists beyond about 6 weeks without clear improvement, recurs, involves the eye (urgent ophthalmology), or the diagnosis is uncertain.

What to look for

• Salivary or lacrimal gland enlargement, autoimmune pancreatitis or cholangitis
• Retroperitoneal fibrosis, aortitis, orbital disease, pachymeningitis
• Raised serum IgG4 in many patients. A normal level does not exclude it.

What to do

• Send serum IgG4 and IgG subclasses, CBC with eosinophils, metabolic panel, lipase if relevant, and C3/C4.
• Tissue biopsy is usually needed to exclude lymphoma or other cancers.
• Obstructive jaundice, hydronephrosis or aortic involvement is urgent.
• Inebilizumab became the first FDA-approved treatment in 2025. Glucocorticoids and rituximab are also used.

What to look for

• Löfgren syndrome: bilateral hilar lymphadenopathy, erythema nodosum and ankle periarthritis
• Chronic arthritis, lupus pernio, uveitis, hypercalcemia
• Cardiac or neurologic involvement

What to do

• Get a chest X-ray or CT. Send calcium, CBC, metabolic panel with liver tests, and urinalysis.
• ACE level has limited sensitivity and specificity.
• Biopsy accessible tissue to look for non-caseating granulomas, except in classic Löfgren.
• Arrange an eye exam. Coordinate with pulmonology. Suspected cardiac sarcoid is urgent; syncope, high-grade heart block or sustained ventricular arrhythmia is an emergency.

What to look for

• Drug-induced lupus: hydralazine, procainamide, minocycline, isoniazid, TNF inhibitors (anti-histone antibodies common)
• Statin myopathy, including anti-HMGCR necrotizing myopathy
• ANCA vasculitis linked to hydralazine, propylthiouracil, levamisole-adulterated cocaine
• Arthralgia or arthritis from aromatase inhibitors, retinoids, or fluoroquinolones (tendinopathy)

What to do

• Stop or switch the likely drug when possible. Most cases improve over weeks to months.
• Send ANA, anti-histone, anti-dsDNA, CK and ANCA as relevant to the presentation.
• Refer if symptoms persist more than about a month after stopping, if there is organ involvement, or if it is unclear whether the disease is drug-induced.

What to look for

• Usually men over 50 (about 1 in 4,000 men over 50). Women, especially with X-chromosome loss, are occasionally affected.
• Recurrent fevers, ear or nose chondritis, neutrophilic dermatosis (Sweet-like), vasculitis, lung infiltrates
• Macrocytic anemia, thrombocytopenia, or myelodysplasia
• Venous thromboembolism
• Often labeled relapsing polychondritis, Sweet syndrome, or MDS that doesn't fully fit

What to do

• Send CBC with smear (macrocytosis), CRP/ESR and a metabolic panel.
• Diagnosis is by UBA1 somatic mutation testing. Bone marrow often shows vacuoles in myeloid and erythroid precursors.
• Refer to rheumatology and hematology. Severe cytopenias are urgent.
• Treatment is specialist-led: glucocorticoids, IL-6 or JAK inhibitors (such as ruxolitinib), azacitidine in some, and stem cell transplant in selected patients. The 2025 ACR guidance advises against B-cell depletion and recommends considering clot prevention when hospitalized and PJP and zoster prophylaxis.

What to look for

• Auricular chondritis that spares the earlobe, and nasal chondritis (saddle nose)
• Tracheobronchial involvement: hoarseness, cough, stridor
• Inflammatory arthritis, eye inflammation, hearing loss or vertigo
• In men over 50 with cytopenias, consider VEXAS

What to do

• Send ESR, CRP, CBC and a metabolic panel.
• Stridor, breathing difficulty or rapidly worsening hoarseness can mean airway narrowing: same-day emergency or ENT assessment.
• With stable respiratory symptoms, assess the airway (PFTs with flow-volume loops, CT airway). Stable airway involvement is urgent.

What to look for

• Persistent disease activity despite DMARDs, or side effects
• Questions about biologics or targeted therapy, or tapering in sustained remission
• Pregnancy planning (this one is often urgent; see co-management)

What to do

• Continue the current DMARDs and monitoring.
• Document swollen and tender joints, morning stiffness, recent ESR/CRP, current and past DMARDs (doses, dates, reasons stopped), and the specific question.
• A flare with new joint swelling is more urgent. Call for advice.

What to look for

• Podagra or another typical flare, or crystal-proven gout
• Strong ULT indications: tophi, radiographic damage, or 2 or more flares a year
• Conditional indications: first flare with CKD stage 3 or worse, serum urate above 9 mg/dL, or urolithiasis

What to do

• Treat flares with colchicine, an NSAID or a glucocorticoid.
• Allopurinol is first-line ULT. Start at 100 mg or less daily (lower in CKD), increase every few weeks (often every 2–5 weeks), checking urate after each increase, until it is below 6 mg/dL, and give flare prophylaxis for 3–6 months.
• Consider HLA-B*58:01 testing before allopurinol in patients of Southeast Asian or African American descent.
• Refer if the practice prefers specialist initiation, if the diagnosis is uncertain, or if any complex feature appears.

What to look for

• Fragility fracture while on therapy, or multiple vertebral fractures
• T-score of −3.0 or lower, or very high FRAX risk
• Glucocorticoid-induced osteoporosis needing advanced therapy
• Atypical femoral fracture, osteonecrosis of the jaw, or bisphosphonate intolerance

What to do

• Most osteoporosis is treated in primary care. Send DXA results, fracture history, prior and current treatment, and calcium, 25-OH vitamin D, creatinine and PTH if checked.
• Never stop denosumab without a plan. Follow it with a bisphosphonate to prevent rebound vertebral fractures.
• In advanced CKD or on dialysis, decide on denosumab with nephrology: an FDA boxed warning (2024) highlights severe, sometimes fatal hypocalcemia.

What to look for

• Positive ANA plus at least one clinical feature
• No organ involvement and stable over time
• A minority evolve into a defined CTD, usually within the first few years

What to do

• Send ANA titer and pattern, ENA panel, anti-dsDNA, C3/C4, CBC, metabolic panel, urinalysis and ESR/CRP.
• Document all symptoms and photograph transient rashes.
• New organ symptoms, cytopenias or an abnormal urinalysis raise the urgency.

What to look for

• Persistent dry eyes and/or mouth, often with dental caries
• Anti-SSA/Ro positive, without purpura, neuropathy, cytopenias, gland swelling or organ involvement

What to do

• Treat dryness: artificial tears, saliva substitutes, sugar-free lozenges, dental care, and review of drying medications.
• Pilocarpine or cevimeline can help glandular dryness.
• SSA/Ro-positive women considering pregnancy need counseling about neonatal lupus and heart block.
• New systemic features raise the urgency.

What to look for

• Joint pain, often in the hands, without objective swelling
• Anti-CCP positive (especially high titer) or high-titer RF
• Morning stiffness, difficulty making a fist, or a positive squeeze test raise the risk

What to do

• Examine carefully for synovitis. Any objective swelling makes this an urgent new inflammatory arthritis referral.
• Refer for assessment and, if available, ultrasound. Ask the patient to return promptly if joints swell.

What to look for

• In healthy people, about 32% are positive at 1:40, 13% at 1:80 and 5% at 1:160 (Tan 1997)
• Low titers and a dense fine speckled (DFS70) pattern are common in healthy people
• No rash, arthritis, serositis, Raynaud's, cytopenias or abnormal urinalysis

What to do

• Document why the ANA was ordered, and the titer and pattern.
• Check a CBC, metabolic panel and urinalysis. If all are normal and there are no symptoms, reassure.
• At higher titer (1:160 or above), check an ENA panel and anti-dsDNA. Avoid ordering ANA sub-serologies when the ANA is negative and suspicion is low.

Refer if

• Disease-specific antibodies are positive (anti-dsDNA, Sm, RNP, Scl-70, centromere, or SSA/Ro in pregnancy)
• Unexplained cytopenias, proteinuria or hematuria
• New systemic symptoms develop

What to look for

• Pain with use, morning stiffness under 30 minutes
• Bony enlargement (Heberden and Bouchard nodes), crepitus, reduced range of motion
• Normal ESR/CRP. Imaging is not needed for a typical presentation.

What to do

• Exercise and weight loss for knee and hip OA carry strong recommendations. The 2026 ACR update adds a conditional recommendation for a GLP-1 receptor agonist, with diet and exercise, in knee OA with obesity.
• Topical NSAIDs for knee and hand OA (often tried before oral NSAIDs), oral NSAIDs if the risk profile allows, and intra-articular glucocorticoids for knee or hip (ultrasound-guided for the hip). Duloxetine and acetaminophen are conditional options. PT, OT, braces, hand orthoses and canes help many patients.
• The 2026 update strongly recommends against glucosamine or chondroitin, platelet-rich plasma, stem cell injections, hydroxychloroquine and bisphosphonates for OA, and conditionally against hyaluronic acid injections and opioids.

Refer if

• Young-onset OA, an atypical joint pattern (MCP, wrist, shoulder) or rapid progression, so CPPD, hemochromatosis or inflammatory arthritis can be excluded
• Joint swelling with features of inflammatory arthritis
• Erosive hand OA, where the 2026 update now conditionally recommends methotrexate

What to look for

• Widespread pain for 3 months or more, fatigue, unrefreshing sleep, cognitive difficulty
• Normal joint exam apart from tenderness, and normal inflammatory markers
• Often coexists with other conditions, including inflammatory disease

What to do

• A focused workup is enough: CBC, metabolic panel, ESR/CRP, TSH, plus CK if on a statin or weak.
• Avoid broad autoantibody panels without specific features.
• Graded aerobic exercise has the strongest evidence. Add sleep and mood care and CBT.
• Medication options include duloxetine, milnacipran, pregabalin, low-dose amitriptyline, and sublingual cyclobenzaprine (FDA-approved for fibromyalgia in 2025). Avoid opioids.

Refer if

• Objective joint swelling, raised inflammatory markers or other signs of inflammatory disease
• Real diagnostic uncertainty, or no response to several treatment steps

What to look for

• Pain worse with activity or posture, better with rest
• Short morning stiffness and no night waking from pain
• No uveitis, psoriasis, IBD or other extra-articular features. Onset is often after 45.

What to do

• Manage with activity, exercise and physical therapy, and NSAIDs if appropriate.
• Image only for red flags (cancer history, fever, weight loss, neurologic deficit, trauma, osteoporosis).

Refer if

• Inflammatory back pain features appear (see axial spondyloarthritis)

What to look for

• Localized pain from a tendon, bursa or entrapment, without features of inflammatory arthritis

What to do

• Manage through MSK pathways: physical or occupational therapy, splints or orthotics, and injections where appropriate.
• Sports medicine or orthopedics may also help.

Refer if

• Multiple regions are involved, or there is swelling suggesting inflammatory disease (for example, enthesitis in spondyloarthritis)

What to look for

• Raised urate with no flares, tophi or urate stones

What to do

• The ACR conditionally recommends against starting ULT for asymptomatic hyperuricemia.
• Address modifiable factors: alcohol, sugar-sweetened drinks, weight, and medications such as thiazide diuretics.

Refer if

• A gout flare, tophus or urate stones occur

What to look for

• Onset usually between 15 and 30, symmetric episodes (white, then blue, then red)
• No pitting, ulcers or puffy fingers
• Negative or low-titer ANA and normal nailfold capillaries

What to do

• Keep the whole body warm, use gloves, stop smoking, and avoid vasoconstrictors.
• A dihydropyridine calcium channel blocker (nifedipine or amlodipine) helps frequent attacks.

Refer if

• Secondary features appear: digital ulcers or pitting, a positive specific antibody, abnormal capillaries, onset after about 30–40, or asymmetry

What to look for

• Hypermobility with or without pain. No recurrent dislocations, skin fragility or vascular history.

What to do

• Reassure and refer to physical therapy for strengthening and proprioception.
• Manage pain and pace activity.

Refer if

• Recurrent dislocations, skin fragility or vascular events, which suggest a heritable connective tissue disorder. Genetics referral is often the right destination.
• Signs of inflammatory arthritis