Dermatology MCQ - Inflammatory Dermatoses - Thrombotic microangiopathy

A 30-year-old woman with a known history of SLE, currently on hydroxychloroquine, presents to the emergency department with a 24-hour history of high-grade fever, confusion, and a new, widespread purpuric rash. Her blood pressure is 85/50 mmHg. Laboratory studies reveal:
- Hemoglobin: 7.0 g/dL (previously 12 g/dL)
- Platelets: 30,000/μL
- Schistocytes present on peripheral smear
- Reticulocyte count: 12%
- Serum creatinine: 2.5 mg/dL (baseline 0.8 mg/dL)
- Coagulation panel: Normal PT/PTT
- Direct Coombs test: Negative

Which of the following is the most likely diagnosis?

A. Catastrophic Antiphospholipid Syndrome
B. Thrombotic Thrombocytopenic Purpura (TTP)
C. Disseminated Intravascular Coagulation (DIC)
D. Lupus Cerebritis
E. Severe Immune Thrombocytopenic Purpura (ITP)

Correct Answer: B. Thrombotic Thrombocytopenic Purpura (TTP)

Explanation

This clinical presentation describes a patient with SLE who has developed a classic thrombotic microangiopathy (TMA). The key features are the pentad of fever, neurological abnormalities (confusion), renal failure (acute kidney injury), microangiopathic hemolytic anemia (MAHA - evidenced by schistocytes and elevated reticulocytes with a falling hemoglobin), and thrombocytopenia.

• Distinguishing TTP from other TMAs: In a patient with SLE, the two primary considerations for TMA are TTP and Catastrophic Antiphospholipid Syndrome (CAPS). The normal PT/PTT and negative Coombs test rule out DIC and autoimmune hemolytic anemia, respectively. The critical distinguishing feature from CAPS is the lack of a history or current confirmation of antiphospholipid antibodies (though not provided, the clinical picture is more classic for TTP). TTP is caused by a severe deficiency of the enzyme ADAMTS13, leading to uncontrolled platelet aggregation. It is a well-recognized, life-threatening complication of SLE.

Why other options are incorrect

• A. Catastrophic Antiphospholipid Syndrome (CAPS): CAPS also presents with a TMA picture and can cause multi-organ failure. However, it is defined by the presence of persistent antiphospholipid antibodies and evidence of thrombosis in multiple organs. While it can look identical, the presentation here is the text-book pentad of TTP. In practice, both must be considered and tested for simultaneously.

• C. Disseminated Intravascular Coagulation (DIC): DIC is characterized by abnormal coagulation studies (elevated PT/PTT, elevated D-dimer, low fibrinogen) due to widespread consumption of coagulation factors. The normal PT/PTT in this case makes DIC very unlikely.

• D. Lupus Cerebritis: While this can explain the fever and confusion, it does not explain the concomitant hematologic findings of MAHA and severe thrombocytopenia. This is a multisystem process.

• E. Severe Immune Thrombocytopenic Purpura (ITP): ITP can cause severe thrombocytopenia, but it does not cause microangiopathic hemolytic anemia, schistocytes, acute kidney injury, or fever. It is an isolated platelet destruction.

Key Associations for SLE Complications

• Pathogenesis of TTP in SLE: The deficiency of ADAMTS13 can be congenital or acquired (due to autoantibodies inhibiting its function). SLE is an autoimmune state that predisposes to the formation of these inhibitory autoantibodies, triggering TTP.

• Diagnosis: This is a medical emergency. Diagnosis is primarily clinical based on the TMA pentad. A severely low ADAMTS13 activity level (<10%) confirms the diagnosis, but treatment must be initiated immediately based on clinical suspicion.

• Differential Diagnosis: As above, the main differentials in an SLE patient are CAPS, Scleroderma Renal Crisis, and Malignant Hypertension. The history and associated features help differentiate them.

• Management & Prognosis:

  • Therapy must be initiated emergently. The cornerstone of treatment is therapeutic plasma exchange (PLEX), which removes the inhibitory autoantibodies and replenishes ADAMTS13.

  • High-dose corticosteroids are used concurrently for their immunosuppressive effects.

  • Rituximab is often used early for refractory disease or as an adjunct to prevent relapse.

  • Without prompt treatment with PLEX, TTP has an extremely high mortality rate. With treatment, survival exceeds 80%. This complication signifies a severe flare of SLE and necessitates long-term, aggressive management of the underlying autoimmune condition.