Acute and Chronic Cutaneous Graft-versus-Host Disease: Diagnosis, Treatment, and Emerging Directions

Cutaneous graft-versus-host disease (GVHD) is a frequent manifestation after allogeneic hematopoietic stem cell transplantation. This review synthesizes classification, pathophysiology, risk factors, and diagnostic frameworks for acute and chronic cutaneous GVHD. Acute cutaneous GVHD typically presents as a morbilliform eruption, with severe cases presenting with bullae and full-thickness desquamation. Chronic cutaneous GVHD presents in more protean ways, including both nonsclerotic and sclerotic phenotypes. We review current diagnostic criteria, staging, clinical and histopathologic features, and differential diagnoses of acute and chronic cutaneous GVHD. Additionally, we summarize management across the disease continuum, including skin-directed therapy, systemic therapy, and approved therapies for steroid-refractory GVHD such as ruxolitinib and remestemcel-L for acute GVHD and ibrutinib, ruxolitinib, belumosudil, and axatilimab for chronic GVHD. We also discuss emerging therapeutic strategies and areas of active investigation in GVHD therapeutics. However, despite therapeutic advances for chronic GVHD (cGVHD), nonresponse and relapse remain common. Early dermatologic involvement to diagnose, classify, and participate in multidisciplinary management is critical to improving outcomes for patients experiencing cutaneous GVHD. Biomarker-informed risk stratification and treatment selection, mechanistically informed combination regimens, and steroid-sparing first-line approaches for GVHD treatment are research priorities to enhance efficacy while minimizing toxicity.