Dermatology MCQ - Inflammatory Dermatoses - GVHD management

A 45-year-old man is 8 months post allogeneic stem cell transplant for acute myeloid leukemia. He presents with a widespread lichen planus-like eruption, xerostomia, and tightening of the skin on his arms. A diagnosis of chronic cutaneous lichenoid graft-versus-host disease is made. Which of the following is the most appropriate first-line systemic treatment for this patient?

A. Intravenous cyclophosphamide
B. Oral prednisone
C. Topical betamethasone dipropionate
D. Oral ruxolitinib
E. Extracorporeal photopheresis (ECP)

Correct Answer: B. Oral prednisone

Explanation

Chronic GVHD (cGVHD) is a multisystem autoimmune-like syndrome. The National Institutes of Health (NIH) consensus criteria provide guidelines for its management. For moderate to severe cGVHD, which this patient has (widespread cutaneous and oral involvement), systemic immunosuppression is required.

• First-Line Systemic Therapy: The established first-line treatment for moderate to severe cGVHD is systemic corticosteroids. The standard initial dose is prednisone 1 mg/kg/day. This is often used in combination with a calcineurin inhibitor (e.g., cyclosporine or tacrolimus), though monotherapy may also be used. The goal is to achieve disease control followed by a slow taper.

Why other options are incorrect

• A. Intravenous cyclophosphamide: Cyclophosphamide is a potent immunosuppressant typically reserved for severe, refractory cGVHD due to its significant toxicity profile (e.g., hemorrhagic cystitis, infertility, myelosuppression). It is not a first-line agent.

• C. Topical betamethasone dipropionate: High-potency topical corticosteroids are appropriate for mild, localized cGVHD. This patient has widespread skin involvement and oral disease, indicating a moderate-to-severe systemic process that requires systemic therapy.

• D. Oral ruxolitinib: Ruxolitinib, a JAK1/2 inhibitor, is a highly effective therapy but is currently approved for steroid-refractory cGVHD. It is a second-line agent, not first-line.

• E. Extracorporeal photopheresis (ECP): ECP is an effective and well-tolerated immunomodulatory therapy for cGVHD, particularly for sclerotic and lichenoid skin manifestations. However, it is generally considered a second-line treatment for patients who are steroid-refractory, steroid-dependent, or intolerant.

Key Associations for GVHD Management

• Staging and Grading: Management is guided by the NIH consensus criteria, which classify cGVHD as mild, moderate, or severe based on the number of organs involved and the severity of involvement.

• First-Line Therapy for cGVHD:

  • Mild cGVHD: Topical therapies (corticosteroids, calcineurin inhibitors).

  • Moderate to Severe cGVHD: Systemic corticosteroids are the cornerstone, with or without a calcineurin inhibitor.

• Second-Line & Refractory Disease: A wide range of options exists for steroid-refractory cGVHD, reflecting the challenging nature of this condition. These include:

  • Ruxolitinib (JAK inhibitor): Now a standard second-line option.

  • Ibrutinib (BTK inhibitor): Approved for cGVHD.

  • Extracorporeal Photopheresis (ECP): Especially good for skin and oral involvement.

  • Mycophenolate Mofetil

  • Rituximab (for features resembling autoimmune disorders)

  • Low-dose IL-2

• Prognosis & Complications: cGVHD is a major cause of non-relapse mortality and long-term morbidity after transplant. Management is a balance between controlling the alloimmune response and managing the profound immunosuppression, which leads to a high risk of infections. Other complications include organ dysfunction, contractures, and poor quality of life.