10–20%
of healthy people have a positive ANA at 1:80 dilution. Ordering ANA without clinical pre-screening virtually guarantees false positives in primary care.
<5%
of positive ANAs in primary care settings lead to a confirmed autoimmune diagnosis. Indiscriminate testing creates patient anxiety and unnecessary specialist referrals.
3–5×
higher rheumatology referral rate from PCPs who order ANA without clinical pre-screening — the majority without a diagnosable autoimmune condition.
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Answer each question based on your symptoms. You'll see a summary of which autoimmune conditions your symptoms may relate to, and what tests your doctor might consider. This is not a diagnosis — it's a starting point for a conversation with your doctor.
Clinical decision support only. This tool estimates pre-test probability to guide test ordering decisions. It is not a diagnostic instrument and does not replace clinical judgment. Autoimmune serology has low positive predictive value in low-pretest-probability settings — features selected should reflect objective findings, not subjective symptoms alone.
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Constitutional Symptoms
Systemic inflammation — non-specific but raises suspicion when combined with organ-specific findings
Unexplained fatigue
Not explained by sleep disorder, anemia, depression, or thyroid disease
Unexplained fevers
Low-grade or episodic; no clear infectious etiology
Unintentional weight loss
Consider malignancy; raises suspicion alongside multi-system features
Lymphadenopathy
Generalized or regional; SLE, Sjögren's; rule out lymphoma
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Joint Symptoms
The most important discriminator — inflammatory pattern vs mechanical/OA must be established before ordering
Inflammatory joint pain pattern
Worse at rest / in morning, improves with activity — distinguishes from OA
Morning stiffness >45 minutes
Prolonged stiffness is a hallmark of synovitis; >1 hr is strongly inflammatory
Small joint involvement
MCPs, PIPs, wrists, MTPs — bilateral symmetric pattern favors RA or SLE
Objective joint swelling
Visible or palpable synovitis — not just tenderness; markedly raises probability
Inflammatory back pain
Improves with exercise not rest; wakes at night; onset <45 yrs — ASAS IBP criteria
Dactylitis ("sausage digit")
Diffuse swelling of entire finger or toe — highly specific for psoriatic arthritis
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Skin Findings
Cutaneous manifestations are often the most diagnostically specific — malar rash and purpura carry high LR+
Malar (butterfly) rash
Fixed erythema across cheeks and nasal bridge, spares nasolabial folds; worsened by sun
Photosensitivity
Rash or symptom flare after sun/UV exposure — documented or by history
Psoriasis (skin or nails)
Any subtype; nail pitting, onycholysis, or oil-drop sign also qualifies
Palpable purpura
Raised, non-blanching lesions (legs) — highly specific for small-vessel vasculitis
Livedo reticularis
Mottled purplish net-like pattern — antiphospholipid syndrome, vasculitis, SLE
Non-scarring alopecia
Diffuse thinning or hairline fragility ("lupus hair") — rule out thyroid, iron deficiency
Skin thickening or tightening
Sclerodactyly or proximal induration — hallmark of systemic sclerosis
Gottron's papules / heliotrope
Purple-red papules over knuckles or periorbital heliotrope discoloration — dermatomyositis
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Mucosal & Sicca Symptoms
Exocrine gland dysfunction — primary Sjögren's; also secondary in SLE, SSc, RA
Dry eyes (>3 months)
Gritty, sandy, or burning — persistent; not medication-related or age-appropriate alone
Dry mouth (>3 months)
Needs water to swallow food; accelerated dental caries; wakes at night to drink
Oral ulcers (recurrent)
In SLE typically painless on palate/buccal — distinct from painful aphthous ulcers
Parotid gland swelling
Bilateral, painless, recurrent — one of the most specific features for primary Sjögren's
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Raynaud's Phenomenon
Secondary Raynaud's: onset >30 yrs, asymmetric, digital ulcers, ANA+ — always evaluate for CTD
Triphasic color changes in digits
White (pallor) → blue (cyanosis) → red (hyperemia) with cold or emotional stress
Digital ulcers or pitting scars
Fingertip ulceration or pitted scars — highly specific for systemic sclerosis
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ENT / Upper Airway
GPA presents with upper airway disease in >90% of cases — often misattributed to recurrent sinusitis for years
Chronic or refractory sinusitis
Not responsive to antibiotics; bloody or crusted nasal discharge; recurrent episodes
Nasal crusting or recurrent epistaxis
Bloody crusts; septal perforation indicates advanced cartilage destruction in GPA
GPA clinical pearl: Refractory sinusitis in a younger patient — especially with any of bloody discharge, nasal crusting, or recurrent epistaxis — should prompt ANCA testing, not another course of antibiotics.
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Organ Involvement
Multi-system disease markedly raises pre-test probability — renal and pulmonary features may require urgent referral
Hematuria (micro or macro)
Perform UA + microscopy — RBC casts = GN; urgent evaluation for SLE and AAV
Proteinuria or rising creatinine
Nephrotic-range proteinuria in SLE; rapidly rising Cr in AAV — both urgent
Pleuritis or pericarditis
Unexplained serositis — SLE, RA, and inflammatory myopathy can all present this way
Peripheral neuropathy
Mononeuritis multiplex → vasculitis; small fiber neuropathy → Sjögren's
Hemoptysis or pulmonary infiltrates
Alveolar hemorrhage = emergency; pulmonary nodules in GPA; ILD in myositis/SSc
Proximal muscle weakness
Difficulty rising from chair or climbing stairs without arm support — order CK
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Incidental Lab Findings
Objective lab abnormalities that independently raise pre-test probability
Elevated ESR or CRP
Unexplained systemic inflammation — independently increases pre-test probability
Unexplained anemia or cytopenias
ACD, hemolytic anemia (Coombs+), leukopenia, thrombocytopenia — SLE criterion
Elevated creatine kinase (CK)
Without statin use or strenuous exercise — inflammatory myopathy until proven otherwise
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Family History & Epidemiology
Heritable risk and demographic factors that increase background pre-test probability
Autoimmune disease in 1st-degree relative
RA, SLE, thyroid disease, psoriasis, IBD, MS, T1DM — any autoimmune condition
Female sex, age 15–45
Peak epidemiologic risk: SLE (F:M 9:1), Sjögren's (9:1), myositis (2:1)
Evidence & References
  1. Slight-Webb S, et al. Autoantibody-positive healthy individuals display unique immune profiles that may predict future autoimmune disease. JCI Insight. 2016;1(7):e88311.
  2. Yazdany J, Schmajuk G, et al. American College of Rheumatology. Choosing Wisely: Five things physicians and patients should question in rheumatology. Arthritis Care Res. 2013;65(3):329–339.
  3. Aletaha D, et al. 2010 Rheumatoid Arthritis Classification Criteria. Arthritis Rheum. 2010;62(9):2569–2581.
  4. Aringer M, et al. 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019;71(9):1400–1412.
  5. Shiboski CH, et al. 2016 ACR/EULAR Classification Criteria for Primary Sjögren's Syndrome. Arthritis Rheumatol. 2017;69(1):35–45.
  6. Robson JC, et al. 2022 ACR/EULAR Classification Criteria for Granulomatosis with Polyangiitis. Ann Rheum Dis. 2022;81(3):315–320.
  7. Rudwaleit M, et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis. Ann Rheum Dis. 2011;70(1):25–31.
  8. Taylor W, et al. Classification criteria for psoriatic arthritis (CASPAR). Arthritis Rheum. 2006;54(8):2665–2673.