Grover's Disease after Bone Marrow Transplantation

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after Bone Marrow. Transplantation. Skin rashes after allogeneic bone marrow transplan- tation (BMT) are not uncommon, and etiologies include.
Biology of Blood and Marrow Transplantation 13:1116-1117 (2007) 䊚 2007 American Society for Blood and Marrow Transplantation 1083-8791/07/1309-0001$32.00/0

LETTER

TO THE

EDITOR

Grover’s Disease after Bone Marrow Transplantation Skin rashes after allogeneic bone marrow transplantation (BMT) are not uncommon, and etiologies include graft-versus-host disease (GVHD), drug rashes, infections, etc. [1]. In this regard, transient acantholytic dermatosis or Grover’s disease has been uncommonly associated to oncologic patients [2] and rarely after allogeneic BMT [1,3]. After a first patient with Grover’s disease [4] was seen in consultation for suspected GVHD, we reviewed the records of 236 patients referred to the GVHD consultation service since October 2003, and found 3 other patients with Grover’s disease and no GVHD. The first patient was a 48-year-old white male, diagnosed with chronic lymphocytic leukemia. The patient progressed after several therapies, so he proceeded with a haploidentical nonmyeloablative BMT after total body irradiation (TBI), fludarabine and cyclophosphamide, and cyclophosphamide, tacrolimus, and mycophenolate mofetil (MMF) for GVHD prophylaxis [5]. By day 50 post-BMT, he developed a generalized pruritic rash with no gastrointestinal or liver abnormalities. A skin biopsy was obtained and he was started on immunosuppression for presumed GVHD. The biopsy had epidermal acantholysis occurring at multiple levels above the basal layer and no GVHD (Figure 1). Immunosuppression was discontinued and the rash resolved. The second patient was a 58-year-old gentleman with a plasma cell leukemia, who was 37 days postnonmyeloablative allogeneic BMT, and had received cyclophosphamide and MMF for GVHD prophylaxis. Chimerism studies obtained by restriction fragment length polymorphism (RFLP) 7 days earlier showed a mixed chimerism (66%-80% donor on peripheral blood). He presented with an extensive skin rash compatible with GVHD that when biopsied indicated Grover’s disease (similar to the one in Figure 2). He did not have gastrointestinal or liver abnormalities. The third patient was a 62-year-old white gentleman with myelodysplastic syndrome (MDS), who underwent a nonmyeloablative haploidentical BMT. Forty-nine days posttransplant he developed a generalized rash that showed skin GVHD, and was treated 1116

Figure 1. A, Features typical of Grover’s disease including dyskeratosis (short arrow), acantholysis (long arrows), and elongation of rete ridges are apparent in the biopsy (H&E 200⫻). B, In contrast, acute GVHD is histologically characterized by subtle interface inflammation, vacuolization of basal keratinocytes, and associated dyskeratosis. The overlying epidermis is of normal thickness, has minimal spongiosis, and an unremarkable cornified layer (H&E 200⫻).

with steroids, to which he responded promptly. Ninety days after BMT, he developed a new rash that was biopsied and it indicated Grover’s disease. Thirty days earlier he was a full chimera on peripheral blood by RFLP. He did not have gastrointestinal or liver abnormalities. The last patient was a 64-year-old gentleman who was admitted for his second cycle of R-EPOCH. He had received an allogeneic transplant 2 years earlier but relapsed. He developed a skin rash on day 2 of chemotherapy that was biopsied and indicated Grover’s disease. His chimerism studies obtained 1 month before showed mixed chimerism (92% donor on peripheral blood by RFLP). He also did not have gastrointestinal or liver abnormalities. To our knowledge, this is the largest series of patients with Grover’s disease after allogeneic transplant that has ever been reported. This self-limited process has been associated with heat and excessive sweating. In the past, there has been discussion about

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Letter to the Editor

REFERENCES

Figure 2. Typical appearance of Grover’s disease showing edematous papules with excoriation. This is indistinguishable from a rash induced by GVHD.

the need of obtaining biopsies in patients with skin rashes post-BMT [6]. The biopsy should be a part of the diagnostic workup of these patients, and the result of this biopsy should be considered when a diagnosis is made. A negative biopsy does not negate GVHD. However, when the biopsy is positive for another entity different from GVHD, as in these cases, assuming it is GVHD and treating it as such is problematic. Without a biopsy, these patients would have received aggressive immunosuppression for a prolonged period of time. As Grover’s disease is a self-limited condition, the use of immunosuppressants is not warranted, and can be deleterious in these patients. The relevance of this letter is to alert clinicians to another diagnosis in patients with rashes post-BMT, as not every rash in this setting is GVHD.

1. Bayer-Garner IB, Smoller BR. The spectrum of cutaneous disease in multiple myeloma. J Am Acad Dermatol. 2003;48:497-507. 2. Guana AL, Cohen PR. Transient acantholytic dermatosis in oncology patients. J Clin Oncol. 1994;12:1703-1709. 3. Harvell JD, Hashem C, Williford PL, White WL. Grover’s-like disease in the setting of bone marrow transplantation and autologous peripheral blood stem cell infusion. Am J Dermatopathol. 1998;20:179-184. 4. Grover RW. Transient acantholytic dermatosis. Electron microscope study. Arch Dermatol. 1971;104:26-37. 5. Fuchs EJ, Luznik L, Chen AR, et al. Post-transplantation cyclophosphamide (Cy) reduces graft rejection and graft-versus-host disease (GVHD) after non-myeloablative, partially HLA-mismatched (haploidentical) bone marrow transplantation (BMT). Blood. 2004;104:11. 6. Zhou Y, Barnett MJ, Rivers JK. Clinical significance of skin biopsies in the diagnosis and management of graft-vs-host disease in early postallogeneic bone marrow transplantation. Arch Dermatol. 2000;136:717-721.

Javier Bolaños-Meade1 Viki Anders1 Joshua Wisell2 Evan R. Farmer2 Georgia B. Vogelsang1 1 “George W. Santos” Bone Marrow Transplant Service Department of Oncology The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and Johns Hopkins University School of Medicine 2 Department of Dermatology Johns Hopkins Hospital and Johns Hopkins University School of Medicine Baltimore, Maryland

Biology of Blood and Marrow Transplantation 13:1116-1117 (2007)

doi:10.1016/j.bbmt.2007.06.002