STEPTRACKERGENERAL PRINCIPLES | IMMUNOLOGY + PATHOLOGY | HIGH-YIELD REVIEW

Autoimmune Disease II

Sjögren syndrome, systemic sclerosis (diffuse and limited), mixed connective tissue disease and Raynaud phenomenon.

FOCUS ON
Sjögren: dry eyes + dry mouth, anti-Ro/La, and a lymphoma risk. Systemic sclerosis: diffuse means anti-Scl-70, lung fibrosis and renal crisis. Limited means anticentromere, CREST features and pulmonary hypertension. Scleroderma renal crisis is treated with an ACE inhibitor.
DISEASE
PATHOLOGY · MECHANISM
CLINICAL FEATURES
ANTIBODIES · TESTS
Sjögren syndrome
exocrine glands
CD4 T-cell and B-cell infiltration of lacrimal and salivary glands → gland destruction. Primary, or secondary to RA/SLE.
Women 40–60: dry eyes (keratoconjunctivitis sicca), dry mouth, dental caries, bilateral parotid swelling; RTA, interstitial nephritis
Anti-Ro/SSA, anti-La/SSB, ANA, RF · lip biopsy: focal lymphocytic sialadenitis · Schirmer test
Sjögren complication
cancer risk
Chronic B-cell stimulation in glands.
New unilateral, firm parotid enlargement years later
Marginal zone (MALT) B-cell lymphoma
Systemic sclerosis — mechanism
vessels + fibrosis
Endothelial injury and autoimmune activation → TGF-β → fibroblasts lay down excess collagen; small arteries narrow.
Skin thickening, Raynaud, organ fibrosis
Women 30–50
Diffuse cutaneous SSc
fast, visceral
Skin thickening of proximal limbs and trunk; early organ involvement.
Interstitial lung disease (leading cause of death), scleroderma renal crisis, GI dysmotility, myocardial fibrosis
Anti-Scl-70 (topoisomerase I) · anti-RNA polymerase III (renal crisis)
Limited cutaneous SSc
CREST, slow
Skin of fingers, hands, forearms and face; late organ disease.
Calcinosis, Raynaud, esophageal dysmotility, sclerodactyly, telangiectasia; pulmonary arterial hypertension
Anticentromere
Scleroderma renal crisis
emergency
Intimal proliferation of renal arterioles → renin surge → malignant hypertension.
Sudden severe HTN, headache, AKI; "onion-skin" arterioles; steroids can precipitate
Treat with ACE inhibitor (captopril)
Mixed connective tissue disease
overlap
Overlapping features of SLE, systemic sclerosis and polymyositis.
Raynaud, puffy swollen hands, arthritis, myositis, esophageal dysmotility
Anti-U1 RNP
Raynaud phenomenon
vasospasm
Digital arteries spasm in cold or stress.
White (ischemia) → blue (cyanosis) → red (reperfusion). Primary: young women, benign. Secondary: SSc, SLE, MCTD → digital ulcers
Calcium-channel blockers
Inflammatory myopathy
overlap neighbor
Polymyositis (CD8 in fascicles) and dermatomyositis (CD4, perifascicular) — full detail on page 17.09.
Proximal weakness; heliotrope rash, Gottron papules; ILD
Anti-Jo-1 (ILD), anti-Mi-2; screen for cancer in DM

Mechanism — systemic sclerosis

Endothelial injuryAutoimmune trigger
→
VasculopathyRaynaud, PAH, renal crisis
→
Immune activationT cells, autoantibodies
→
TGF-β → fibroblastsCollagen in skin and organs

GI: smooth muscle fibrosis lowers LES tone → GERD, dysphagia, strictures, Barrett risk.

Antibody → disease

ANTIBODY
DISEASE · CLUE
Anti-Ro/SSA, anti-La/SSB
Sjögren (also SLE); neonatal heart block in babies
Anti-Scl-70
Diffuse SSc — interstitial lung disease
Anti-RNA polymerase III
Diffuse SSc — renal crisis risk
Anticentromere
Limited SSc (CREST) — pulmonary hypertension
Anti-U1 RNP
Mixed connective tissue disease
Anti-Jo-1
Myositis + interstitial lung disease

How it's tested

COMMON CONFUSIONDiffuse SSc kills through the lungs and kidneys. Limited SSc kills through pulmonary arterial hypertension, which comes late.
THE TRAPA scleroderma patient has sudden headache, BP 210/120 and rising creatinine. This is renal crisis, and the answer is an ACE inhibitor — not a β-blocker, and not dialysis first.
YOUR APPROACHDry eyes and mouth → Sjögren. Tight skin → check the extent (trunk = diffuse, distal = limited) → match the antibody and the organ to watch.

If you see… think…

Dry eyes, dry mouth, dental caries, parotid swelling → Sjögren
Long-standing Sjögren, new unilateral parotid mass → MALT lymphoma
Anticentromere + calcinosis + telangiectasias → limited SSc (CREST)
Anti-Scl-70 + trunk skin thickening + restrictive PFTs → diffuse SSc
SSc + abrupt severe hypertension + AKI → renal crisis — ACE inhibitor
SSc patient with heartburn and dysphagia → esophageal smooth muscle fibrosis
Puffy hands + Raynaud + myositis + anti-U1 RNP → MCTD
Fingers white → blue → red in the cold → Raynaud phenomenon
Lip biopsy with focal lymphocyte clusters → Sjögren