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Tissue eosinophils and the perils of using skin biopsy specimens to distinguish between drug hypersensitivity and cutaneous graft-versus-host disease

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Abstract

Graft-versus-host disease (GvHD) is a frequent and serious complication of bone-marrow transplantation (BMT), and carries a high morbidity and mortality if not promptly recognized and treated. The rash of acute GvHD is often difficult to distinguish clinically from a drug eruption, and skin biopsies are often performed in an attempt to render a diagnosis. Histologically, eosinophils are classically associated with hypersensitivity reactions, and their presence in inflamed tissue is considered suggestive of a drug-induced dermatitis. We present 3 cases of acute exanthema in BMT recipients in whom the presence of eosinophils on skin biopsy specimen led to an initial diagnosis of drug eruption over GvHD. As a result, these patients experienced delays in the institution of definitive immunosuppressive therapy for GvHD. We review the growing literature suggesting that no single or combined histologic feature, including tissue eosinophils, is useful in differentiating GvHD from drug eruptions in BMT recipients. Indeed, in most cases, the cause of a new-onset blanchable erythematous rash in a BMT recipient is most accurately determined by close examination and follow-up of the clinical features without a skin biopsy.

Section snippets

Case 1

A 44-year-old woman with chronic lymphocytic leukemia underwent allogeneic-matched unrelated-donor peripheral blood stem cell transplant after conditioning with fludarabine and busulfan. She received GvHD prophylaxis with cyclosporine, prednisone, and mycophenolate mofetil. On post-BMT day 54 the patient developed fever of unclear origin, for which she received treatment with multiple antibiotics during the following weeks. Shortly after development of symptoms, prednisone and mycophenolate

Discussion

GvHD is a serious and frequent complication after BMT. Clinically relevant acute GvHD occurs in 35% to 50% of patients receiving HLA-identical grafts,1 and progressive GvHD may carry a mortality as high as 80%.2 Acute GvHD frequently begins in the skin, presenting as a morbilliform rash that involves the trunk, neck, cheeks, and ears.5 This rash is often difficult to distinguish clinically from drug eruptions or viral exanthems, and skin biopsies are frequently requested in an attempt to narrow

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