Acute Skin Graft-versus-Host Disease with Molecular Features Mimicking Herpes Simplex Virus-Associated Erythema Multiforme: Report of Three Cases

Abstract

Background: Acute skin erythematous lesions that follow allogeneic hematopoietic stem cell transplantation (HSCT) and are histologically diagnosed as graft-versus-host disease (GVHD) are often associated with reactivation of latent herpes simplex virus (HSV). Objective: To further examine the relationship between reactivated HSV and GVHD development. Methods: We present 3 patients with acute skin GVHD after allogeneic HSCT who were studied prospectively for expression of the HSV antigen Pol, which is involved in HSV-associated erythema multiforme. Results: Pol was expressed in the GVHD lesions but not the pre-HSCT normal skin or peripheral blood mononuclear cells. Lesion severity correlated with the Pol levels but not the histopathologically defined GVHD grade. Lesion development was accompanied by increased numbers of Pol+ circulating/skin-infiltrating CD34+ stem cells and CD1a+ and other dermal dendritic cells. Conclusions: Subclinical HSV infection of circulating CD34+ cells can contribute to some post-HSCT skin lesions histologically diagnosed as GVHD, with potential preventive and therapeutic implications.

Atypical cutaneous targetoid lesions after bone marrow transplant

“…This case highlights the importance of recognising atypical eruptions in patients post-BMT. Because of similarities between GVHD and EM, cutaneous reactions post-BMT may fall under a larger umbrella or spectrum of EM-reactive dermatoses 6 7. The timing of our patient’s eruption coinciding with the tapering of immunosuppression initially raised the possibility of GVHD, but the atypical morphology appreciated by his oncologist triggered a dermatology evaluation.…”

“…HSV genetic fragments may localise in stem cells, which can deliver the fragments to the skin on differentiation 6. Reactivated HSV can also increase the risk of GVHD through its ability to stimulate T-cell proliferation 7. Thus, underlying viral infections triggering both EM and GVHD can cause atypical cutaneous reactions seen post-BMT.…”

HSV‐associated erythema multiforme in a patient after hematopoietic stem cell transplantation

“…HAEM is rare in post-HSCT patients, and only three patients have been reported (Shvarsbeyn & Akpek, 2014). Infections due to HSV-1 and HSV-2 are mostly seen during the pre-engraftment phase (Sahin, Toprak, Atilla, Atilla, & Demirer, 2016).…”

Late-onset acute graft-versus-host disease mimicking hand, foot, and mouth disease

“…[1] Various atypical presentations of acute GVHD have been recently described like follicular type,[5] psoriasiform,[6] contact-dermatitis like,[6] type II pityriasis rubra pilaris-like,[6] eczema craquelé-like GVHD,[6] erythema-multiforme like,[7] erythematous nodules,[8] and pustular acral erythema. [9]…”