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The Big 5 Autoimmune Diseases

SLE, RA, Scleroderma, Dermatomyositis, Sjogren's. They all have joint pain. They all have fatigue. They all have autoantibodies. Here's how to never mix them up again.

A 32-year-old woman presents with fatigue, joint pain, and a facial rash that spares the nasolabial folds. Labs show ANA positive and low complement levels (C3, C4). She also reports pain in her fingers when exposed to cold.

What's the most likely diagnosis?
Rheumatoid Arthritis
Systemic Lupus Erythematosus
Scleroderma
Dermatomyositis
Sjogren's Syndrome
Malar rash sparing nasolabial folds + low complements = SLE until proven otherwise.

RA has symmetric joint involvement but no malar rash and doesn't consume complement. Scleroderma has skin tightening, not butterfly rash. Dermatomyositis has a heliotrope rash (on eyelids, not cheeks). Sjogren's has dry eyes and dry mouth as the hallmark.

The low complements are the real clincher — SLE consumes complement via immune complex deposition. None of the others do this.
Know Your Enemies

Each disease has a unique fingerprint. Tap through them. Notice what makes each one DIFFERENT.

SLE
RA
Scleroderma
Dermatomyositis
Sjogren's

Systemic Lupus Erythematosus

The Great Imitator

Who Gets It
Young women (15-45), 9:1 F:M. More severe in Black and Hispanic patients.
Signature Finding
Malar (butterfly) rash — spares nasolabial folds. Photosensitive.
Key Antibodies
Anti-dsDNA (specific, tracks disease activity), Anti-Smith (most specific but less sensitive). ANA positive in ~95%.
Unique Labs
Low C3/C4 (complement consumption). False-positive VDRL/RPR. Pancytopenia.
What It Attacks
Everything. Joints, skin, kidneys (lupus nephritis), brain, blood, serosa (pleuritis, pericarditis).
Joints
Symmetric polyarthritis but NON-erosive (unlike RA). Jaccoud's arthropathy = deformity without destruction.
Board Trap
Young woman + joint pain + rash + renal disease + low complements. Don't overthink it. Also: drug-induced lupus (hydralazine, procainamide, isoniazid) has anti-histone antibodies but SPARES kidneys and CNS.

Rheumatoid Arthritis

The Joint Destroyer

Who Gets It
Women 30-50, 3:1 F:M. Smoking is a major risk factor.
Signature Finding
Symmetric erosive polyarthritis of small joints (MCP, PIP, wrist). Morning stiffness >1 hour. Spares DIPs.
Key Antibodies
Anti-CCP (most specific, ~97%). RF (sensitive but not specific — also elevated in Sjogren's, HCV, endocarditis).
Unique Labs
Elevated ESR/CRP. Synovial fluid: inflammatory (WBC 2,000-75,000). No complement consumption.
What It Attacks
Primarily joints. Also: rheumatoid nodules (elbows), interstitial lung disease, Felty syndrome (splenomegaly + neutropenia), atlanto-axial subluxation.
Key Distinction
EROSIVE arthritis (see bony erosions on X-ray). SLE is non-erosive. This is the #1 differentiator.
Board Trap
Swan neck + boutonniere + ulnar deviation = RA. If they describe a deforming arthritis with bony erosions on imaging, it's RA, not SLE. Also: Caplan syndrome = RA + coal worker's pneumoconiosis.

Scleroderma (Systemic Sclerosis)

The Skin Tightener

Who Gets It
Women 30-50, 4:1 F:M. Two subtypes matter: limited (CREST) vs diffuse.
Signature Finding
Skin thickening/tightening. Mask-like facies. Sclerodactyly (tight skin on fingers). Raynaud's is often the FIRST symptom.
Key Antibodies
Limited/CREST: Anti-centromere. Diffuse: Anti-Scl-70 (topoisomerase I).
CREST Syndrome
Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, Telangiectasia. Better prognosis than diffuse.
Worst Complication
Diffuse: Renal crisis (malignant HTN, treat with ACEi). Limited: Pulmonary arterial hypertension.
GI Feature
Esophageal dysmotility (smooth muscle fibrosis) causing severe GERD and dysphagia.
Board Trap
Tight skin + Raynaud's + dysphagia = scleroderma. Anti-centromere = limited (CREST), Anti-Scl-70 = diffuse. Renal crisis in diffuse scleroderma is treated with ACEi, NOT steroids (steroids can precipitate crisis).

Dermatomyositis

The Muscle Melter

Who Gets It
Women 40-60, 2:1 F:M. Bimodal: children and adults. Adults: screen for malignancy.
Signature Finding
Heliotrope rash (purple discoloration around eyelids) + Gottron's papules (raised violaceous papules over knuckles). Proximal muscle weakness.
Key Antibodies
Anti-Jo-1 (antisynthetase syndrome: myositis + ILD + mechanic's hands). Anti-Mi-2 (classic dermatomyositis).
Unique Labs
Elevated CK (creatine kinase) — most important lab. Aldolase also elevated. Confirms muscle damage.
What It Attacks
Proximal muscles (can't climb stairs, can't brush hair). Skin. Lungs (ILD with anti-Jo-1). NOT distal muscles.
Cancer Link
Adult dermatomyositis = screen for occult malignancy. Ovarian, lung, GI cancers. This is the #1 board association.
Board Trap
Heliotrope rash (eyelids) vs Malar rash (cheeks) — both are facial rashes in autoimmune disease but they are NOT the same. Also: polymyositis = same muscle weakness, NO rash, NO cancer association.

Sjogren's Syndrome

The Dry One

Who Gets It
Women 40-60, 9:1 F:M. Often coexists with RA or SLE (secondary Sjogren's).
Signature Finding
Sicca symptoms: dry eyes (keratoconjunctivitis sicca) + dry mouth (xerostomia). Bilateral parotid gland enlargement.
Key Antibodies
Anti-SSA (Ro) and Anti-SSB (La). RF also elevated. Anti-SSA crosses the placenta!
Unique Labs
Positive Schirmer test (reduced tear production). Lip biopsy shows lymphocytic infiltration of minor salivary glands.
What It Attacks
Exocrine glands (lacrimal, salivary). Can also cause renal tubular acidosis (Type 1), peripheral neuropathy, and interstitial nephritis.
Cancer Link
44x increased risk of MALT lymphoma (mucosa-associated lymphoid tissue). Parotid gland swelling that becomes hard/fixed = biopsy immediately.
Board Trap
Anti-SSA (Ro) in a pregnant woman = risk of neonatal lupus and congenital heart block. The antibody crosses the placenta. They WILL test this. Also: dental caries from chronic dry mouth is a classic Sjogren's complication.
Antibody Match

Match each antibody to its disease. Wrong guesses shake. Right ones lock in.

Anti-dsDNA
→
SLE
RA
Scleroderma
Dermatomyositis
Sjogren's
Anti-CCP
→
SLE
RA
Scleroderma
Dermatomyositis
Sjogren's
Anti-Scl-70
→
SLE
RA
Scleroderma
Dermatomyositis
Sjogren's
Anti-Jo-1
→
SLE
RA
Scleroderma
Dermatomyositis
Sjogren's
Anti-SSA (Ro)
→
SLE
RA
Scleroderma
Dermatomyositis
Sjogren's
Anti-centromere
→
SLE
RA
Scleroderma
Dermatomyositis
Sjogren's
Anti-Smith
→
SLE
RA
Scleroderma
Dermatomyositis
Sjogren's
All matched. The antibody fingerprint is the fastest way to a diagnosis on boards. Anti-dsDNA tracks SLE activity, Anti-CCP is the most specific for RA, Anti-Scl-70 means diffuse scleroderma, Anti-centromere means CREST, Anti-Jo-1 is antisynthetase syndrome, and Anti-SSA crosses the placenta.
The Diagnostic Algorithm

A patient has fatigue, joint pain, and a positive ANA. Walk through the decision tree.

1
Does the patient have SKIN findings?
Yes - facial rash (butterfly pattern on cheeks)
Yes - skin tightening / sclerodactyly
Yes - purple eyelid rash / knuckle papules
No significant skin findings
2
The malar rash spares nasolabial folds. Are complements (C3/C4) low?
Yes - low complements
No - normal complements, patient on hydralazine/procainamide
2
Skin tightening detected. Is Raynaud's present? Where is the skin involvement?
Raynaud's + skin limited to distal extremities/face + dysphagia
Raynaud's + skin tightening spreading proximally (trunk) + renal issues
2
Heliotrope rash and/or Gottron's papules. Is CK elevated? Is the patient >40?
Yes - elevated CK + proximal weakness + age >40
Yes - elevated CK + proximal weakness + age <18
2
No skin findings. What are the main symptoms?
Dry eyes + dry mouth
Symmetric joint swelling with morning stiffness >1hr
Proximal muscle weakness without rash
3
Sicca symptoms (dry eyes + mouth). Which antibodies are positive?
Anti-SSA/Ro and/or Anti-SSB/La
Anti-SSA/Ro + Anti-CCP or Anti-dsDNA (secondary Sjogren's)
3
Symmetric polyarthritis. Are joints EROSIVE on imaging?
Yes - bony erosions + joint space narrowing on X-ray
No - non-erosive arthritis with multi-system involvement
3
Proximal weakness without rash. Elevated CK?
Yes - elevated CK, muscle biopsy shows endomysial inflammation
Memory Hooks

Tap each card to reveal the hook. These are meant to stick.

🦋
SLE
The butterfly rash is the logo. Lupus = wolf, but think butterfly on the face. She eats her own complement (low C3/C4) because she attacks everything, including herself. Double-stranded DNA for double the trouble.
tap to reveal
🔨
RA
RA destroys joints. SLE doesn't. That's the whole thing. Swan necks and hammer toes. If X-ray shows erosions, it's RA. Anti-CCP = Can Confirm Precisely (97% specific).
tap to reveal
🧊
Scleroderma
CREST = the mild version (think: a nice crest on a wave). Anti-centromere for the center of the cell = the milder, more contained form. Scl-70 for the one that goes everywhere (diffuse = worse).
tap to reveal
💪
Dermatomyositis
Heliotrope = eyelids turn purple like the heliotrope flower. Gottron's on the knuckles (imagine punching something and your knuckles go purple). In adults: the muscles are weak AND there might be a tumor hiding. Always screen.
tap to reveal
💧
Sjogren's
SSA and SSB = Sjogren's Syndrome Antibody (and B). Dry eyes, dry mouth, dry everything. The A antibody is the dangerous one in pregnancy — it crosses the placenta and blocks the baby's heart. MALT lymphoma = the glands went bad.
tap to reveal
Test Yourself

Board-style vignettes. No time pressure. Take your time.