Dermatology MCQ - Inflammatory Dermatoses - Acute graft-versus-host disease

A 25-year-old male patient is day +28 post allogeneic hematopoietic stem cell transplant for acute myeloid leukemia. He presents with a pruritic rash, nausea, and watery diarrhea. On examination, there is a widespread morbilliform eruption involving the palms and soles. The most specific cutaneous finding to confirm the diagnosis of acute graft-versus-host disease (GVHD) would be:

A. Confluent erythema and desquamation involving >30% of body surface area
B. The presence of numerous target-like lesions on the torso
C. An erythematous to violaceous maculopapular rash with follicular prominence
D. Bullae formation and skin sloughing on sun-exposed areas
E. A photodistributed eruption sparing all sun-protected sites

Correct Answer: A. Confluent erythema and desquamation involving >30% of body surface area

Explanation:

• Acute GVHD typically occurs within the first 100 days post-transplant. The clinical triad of rash, gastrointestinal symptoms (nausea, diarrhea, abdominal pain), and liver enzyme elevation is classic. The skin is the most commonly affected organ.

• Why option A is correct: The progression of the skin eruption in acute GVHD is staged. While it often begins as a morbilliform rash on the palms, soles, and pinnae, the most specific finding for established and significant acute GVHD is involvement of >30% of the body surface area with confluent erythema, often leading to bullae formation and desquamation. This corresponds to a Grade III (skin stage 3) or Grade IV (skin stage 4) severity, which is diagnostic in the correct clinical context.

• Why the other options are incorrect:

  • B. The presence of numerous target-like lesions on the torso: This is the hallmark of Erythema Multiforme, which is often triggered by infections (especially HSV) or drugs. While GVHD can sometimes mimic other eruptions, classic target lesions are not its primary presentation.

  • C. An erythematous to violaceous maculopapular rash with follicular prominence: While a maculopapular rash is the most common initial presentation of acute GVHD, follicular prominence is not a specific or hallmark feature. This description could fit several drug eruptions or viral exanthems.

  • D. Bullae formation and skin sloughing on sun-exposed areas: This describes a severe phototoxic reaction or perhaps a photo-aggravated autoimmune blistering disease. The distribution is key; GVHD is not primarily photodistributed.

  • E. A photodistributed eruption sparing all sun-protected sites: This is classic for a phototoxic or photoallergic drug eruption. GVHD, while it can be widespread, does not respect sun-exposed areas in this specific manner.

Key Points for Exams

• Pathogenesis: Acute GVHD results from donor T-cells (the graft) recognizing host (recipient) tissues as foreign and mounting an immune attack. The primary targets are the skin, gastrointestinal tract, and liver.

• Grading: The overall grade of acute GVHD (I-IV) is determined by the severity of involvement of these three organs. Grade I is mild (rash only), while Grade IV is life-threatening. The skin stage is a critical component of this grading.

• Histopathology: A skin biopsy is crucial for confirmation. The hallmark is an interface dermatitis with vacuolar degeneration of the basal layer and epidermal dyskeratosis (apoptotic keratinocytes, often called "sunburn cells").

• Prognosis: The prognosis is directly related to the grade. Grade I often has a good prognosis, while Grades III-IV carry significant mortality, often from infection or organ failure.

• Management:

  1. Prophylaxis: All patients receive immunosuppressive prophylaxis (e.g., calcineurin inhibitors like cyclosporine/tacrolimus, methotrexate).

  2. First-line treatment: For established disease, high-dose systemic corticosteroids (e.g., methylprednisolone) are the cornerstone of treatment.

  3. Second-line treatment: For steroid-refractory disease, options include extracorporeal photopheresis, monoclonal antibodies (e.g., infliximab, ruxolitinib), and other potent immunosuppressants.