Prominence of hair follicles (whether overlying erythema is present or not) is typical of aGVHD [5]. Such prominence is often misdiagnosed as folliculitis, but it typically heralds the involvement of aGVHD within the follicular epithelium (Figs. 3.8 and 3.9).

Morbilliform aGVHD is among the most common presentations [6]. Eruptions are erythematous macules and papules that may coalesce into larger papules and plaques, which are symmetric and are often pruritic. This presentation may clinically mimic viral exanthema or drug eruptions (Figs. 3.10, 3.11, 3.12, and 3.13).

Erythrodermic aGVHD presents with confluent erythematous patches that mimic severe viral exanthema, drug reactions, psoriasis, eczematous dermatitis, cutaneous T-cell lymphoma, or staphylococcal scalded skin syndrome (SSSS) (Fig. 3.14). When mucous membrane lesions are present, there are no clinical or histologic differences between skin stage 4 aGVHD and toxic epidermal necrolysis (TEN) [7–9]. If extracutaneous features of aGVHD are present, diagnosis may be possible via tissue confirmation at involved sites. If extracutaneous features of aGVHD are absent, review of clinical symptoms and their development in relation to initiation of medications is mandatory. Viral serologies and/or quantification of viremia via polymerase chain reaction (PCR) testing of the blood may aid in the diagnosis of an erythrodermic viral exanthem, such as those caused by HHV-6. Concurrent empiric treatment of aGVHD, viral infection, and TEN may be necessary if a clear diagnosis cannot be rendered.