Dermatology MCQ - Inflammatory Dermatoses - Antiphospholipid antibody syndrome

A 40-year-old woman with a history of three first-trimester miscarriages presents with acute pain and cyanosis in the second and third digits of her right hand. Physical examination reveals livedo reticularis on her legs and cool, pulseless fingers with digital gangrene. Her laboratory workup is most likely to reveal which of the following?

A. Positive cryoglobulins
B. Elevated homocysteine level
C. Positive anticentromere antibodies
D. Lupus anticoagulant present
E. Positive anti-Jo-1 antibodies

Correct Answer: D. Lupus anticoagulant present

Explanation

This clinical scenario is highly suggestive of the catastrophic variant of antiphospholipid syndrome (CAPS), a life-threatening condition characterized by widespread thrombosis. Even without the catastrophic presentation, the history of recurrent pregnancy loss and current arterial thrombosis affecting the digits is classic for antiphospholipid antibody syndrome (APS).

• Diagnostic Criteria: The diagnosis of APS requires one clinical criterion (vascular thrombosis or pregnancy morbidity) and one laboratory criterion (persistently positive lupus anticoagulant, anticardiolipin antibodies, or anti-β2-glycoprotein I antibodies) on two or more occasions at least 12 weeks apart. The presence of lupus anticoagulant is the strongest risk factor for thrombosis.

Why other options are incorrect

• A. Positive cryoglobulins: This is associated with cryoglobulinemic vasculitis, which can cause purpura, arthralgias, and neuropathy, but it is not typically associated with recurrent miscarriage or large-vessel arterial thrombosis leading to digital gangrene.

• B. Elevated homocysteine level: This is a risk factor for hypercoagulability and can cause both arterial and venous thrombosis. However, it is not part of the specific diagnostic criteria for APS, and the classic triad of recurrent miscarriage, livedo reticularis, and arterial thrombosis is far more specific for APS.

• C. Positive anticentromere antibodies: This is a highly specific serologic marker for the limited cutaneous form of systemic sclerosis (CREST syndrome), which can cause digital ischemia and gangrene (scleroderma renal crisis is associated with anti-RNA polymerase III). However, it is not associated with recurrent pregnancy loss or the acute, widespread thrombotic picture described.

• E. Positive anti-Jo-1 antibodies: This is the classic serologic marker for antisynthetase syndrome, which presents with myositis, interstitial lung disease, fever, mechanic's hands, and polyarthritis. It is not associated with thrombosis.

Key Associations for Antiphospholipid Antibody Syndrome (APS)

• Pathogenesis: APS is an autoimmune thrombophilic disorder characterized by antibodies directed against phospholipid-binding proteins. These antibodies cause a prothrombotic state via multiple mechanisms, including endothelial activation, platelet aggregation, and complement activation.

• Clinical Features (Clinical Criteria):

  • Thrombosis: One or more episodes of arterial (e.g., stroke, digital gangrene), venous (e.g., DVT, PE), or small-vessel thrombosis.

  • Pregnancy Morbidity: Three or more unexplained consecutive miscarriages before 10 weeks, one or more unexplained fetal deaths beyond 10 weeks, or one or more premature births due to severe preeclampsia or placental insufficiency.

• Laboratory Diagnosis (Laboratory Criteria): Must be positive on two occasions >12 weeks apart.

  • Lupus Anticoagulant (LA): The most specific test (functional assay).

  • Anticardiolipin (aCL) antibodies: IgG or IgM isotype (ELISA).

  • Anti-β2-glycoprotein I (aβ2GPI) antibodies: IgG or IgM isotype (ELISA).

• Catastrophic APS (CAPS): A rare, severe form with thrombosis in three or more organs developing over a short period, often triggered by infection, surgery, or trauma. It has high mortality.

• Differential Diagnosis: Includes other inherited and acquired thrombophilias (e.g., Factor V Leiden, protein C/S deficiency), heparin-induced thrombocytopenia, thrombotic thrombocytopenic purpura, and vasculitis.

• Management & Prognosis:

  • Primary Prevention: In asymptomatic carriers of antiphospholipid antibodies (aPL) without prior thrombosis, treatment is usually not indicated unless the risk is very high (e.g., prior to major surgery).

  • Secondary Prevention (after a thrombotic event): Long-term anticoagulation with warfarin is the mainstay of therapy, typically with a target INR of 2.0-3.0 for venous thrombosis and 2.5-3.5 or higher for arterial thrombosis.

  • Pregnancy Management: Pregnant women with APS require treatment with low-dose aspirin and prophylactic or therapeutic dose low molecular weight heparin to prevent pregnancy loss and maternal thrombosis.

  • Prognosis is variable and depends on the severity of thrombotic events and adherence to anticoagulation.