Chronic Cutaneous Graft versus Host Disease Mimicking Warts.

Dear Editor:

Chronic graft-versus-host disease (cGVHD) occurs in 60%~80% of allogeneic transplant recipients at some point in their post-transplant period. The skin is the most frequently involved organ at initial diagnosis (~75%)1. Frequently reported cutaneous manifestations of cGVHD include lichen planus-like, lichen sclerosus-like, morphea-like, poikiloderma, ichthyosis-like, keratosis pilaris-like, dyspigmentation, and sweat impairment2. Here, we report four cases of a rare manifestation of cutaneous cGVHD: cGVHD lesions resembling palmoplantar warts.

Between 2009 and 2011, four cases of wart-like palmoplantar hyperkeratotic papules were diagnosed as lichenoid cGVHD in our clinic (Table 1). In patient 1, the lesions were mainly distributed along the palmar creases and finger and toe webs (Fig. 1A), and in patient 2 on the finger-tips (Fig. 1B). Patient 3 had palmar erythematous papules and patches (Fig. 1C), and patient 4 had punctuated hyperkeratotic papules on the palms and soles (Fig. 1D). The disease duration was between 14 and 120 days, and the time interval between peripheral blood stem cell transplantation and the lesion onset was between 164 and 1,142 days. All of the skin biopsy specimens taken from the four patients showed hyperkeratosis, acanthosis, exocytosis, and apoptotic basal cells in the epidermis, with band-like lymphocytic infiltrations in the upper dermis. The pathology was consistent with chronic lichenoid GVHD.

Table 1

Clinical characteristics of the patients with wart-like cutaneous chronic GVHD

GVHD: graft-versus-host disease, HSCT: hematopoietic stem cell transplantation, MDS: myelodysplastic syndrome, alloPBSCT: allogenic peripheral stem cell transplantation, SAA: severe aplastic anemia, uPBSCT: unmatched peripheral blood stem cell transplantation, ALL: acute lymphoblastic leukemia, AML: acute myelocytic leukemia.

Fig. 1

(A) Skin-colored, flat-topped papules along the palmar creases in case 1. (B) Yellowish, hyperkeratotic papule on the finger tips in case 2. (C) Erythematous papules and patches on both palms in case 3. (D) Punctated hyperkeratotic papules on the soles in case 4.

The hyperkeratotic papules on the hands and feet of our patients were initially diagnosed as warts. Because these patients were immunocompromised due to hematologic diseases and immunosuppressants, the appearance of multiple warts that had spread widely in a short time did not seem unusual. However, the pathologic findings of the lesions in all four cases were consistent with chronic lichenoid GVHD. Findings suggestive of papillomavirus infection, such as papillomatosis and koilocytotic atypia, were absent. In addition, tissue human papilloma virus DNA polymerase chain reaction tests were negative in all patients.

GVHD involving the acral area usually manifests as palmoplantar erythema, particularly in its acute stage3. Also, lichenoid GVHD lesions are characterized by erythematous or violaceous papules and plaques with fine scales that usually coalesce on the dorsal aspects of the hands, forearms, and trunk4. However, palmoplantar hyperkeratotic papules have rarely been described. In a case of acral keratotic GVHD reported by Kossard and Ma3, the patient took hydroxychloroquine for 9 months before the lesion onset; the acral keratosis might have been induced by this medication. There is one report of quinacrine hydrochloride-induced keratoderma with underlying lichenoid reactions on the palms and soles5. However, none of our patients had a history of taking such drugs.

Wart-like cutaneous cGVHD can be misdiagnosed as palmoplantar warts because of their morphologic similarity; however, warts usually develop as a single lesion and spread slowly for months, whereas the wart-like cGVHD lesions spread within 4 months. In addition, the wart-like cGVHD showed symmetric distribution and a tendency to be distributed along palmar creases, whereas warts develop focally.

In conclusion, we suggest that acral wart-like hyperkeratotic papules should be included in the list of rare cutaneous manifestations of cGVHD.