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The Isomorphic Response in Morphealike Chronic Graft-vs-Host Disease
Asha R. Patel, BS;
Steven Z. Pavletic, MD;
Maria L. Turner, MD;
Edward W. Cowen, MD, MHSc
Arch Dermatol. 2008;144(9):1229-1231.
The isomorphic response of Koebner, also known as the Koebner phenomenon, is a well-recognized dermatologic manifestation first described in psoriasis. The isomorphic response occurs when a dermatologic disease develops at a site of normal-appearing skin that is injured in some manner.1
Chronic graft-vs-host disease (cGvHD) is a multisystem disorder that commonly affects the skin and may present with protean manifestations. Sclerotic cGvHD features are categorized as lichen sclerosus–like, morphealike, or sclerosis involving the subcutaneous tissue and fascia.2 Morphealike lesions of cGvHD are characterized by localized dyspigmented indurated plaques of skin thickening.
Methods
A retrospective analysis was performed of 110 consecutive patients with a diagnosis of cGvHD of any organ system evaluated in a cross-sectional cGvHD study at the National Institutes of Health (NIH).
Results
Eighty-one patients had evidence of cutaneous cGvHD, and 58 of these patients (72%) exhibited evidence of cutaneous sclerosis as defined by the NIH cGvHD consensus criteria.2 Eleven of 58 patients with cGvHD-associated sclerosis exhibited localized morphealike lesions involving the lower abdomen (the waistband area), often in a striking linear distribution (19%) (Table and Figure, A). Lesional skin biopsies were performed in 6 patients, and all findings were consistent with sclerotic cGvHD. Six of 11 patients with waistband involvement were women, and 3 of these 6 exhibited similar morphealike lesions in the inframammary/lateral torso region (the brassiere-band area) (Figure, B).
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Table. Characteristics of Patients With Morphealike cGvHD Exhibiting an Isomorphic Response
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Figure. Extensive linear hyperpigmentation and skin fibrosis in the lower abdomen waistband area (A) and lateral torso brassiere-band area (B) in a patient with morphealike chronic graft-vs-host disease.
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Comment
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Chronic graft-vs-host disease is an incompletely understood multisystem disorder with features of both alloimmunity and autoimmunity. We propose that the combination of irritation, friction, and pressure applied chronically to the waistband and brassiere-band areas of the torso is responsible for localization of cGvHD at these sites, consistent with an isomorphic response.
The mechanism by which relatively minor external trauma triggers the complex immunologic cascade that results in skin fibrosis is unclear. Interestingly, morphea and lichen sclerosus, 2 disorders that resemble cGvHD, are also associated with an isomorphic response,3 suggesting a common pathogenesis. Morphealike cGvHD is characterized histologically by prominent dermal sclerosis, but apoptotic keratinocytes in the overlying epidermis suggestive of typical cGvHD may also be present. Local infiltration of T cells is thought to initiate epithelial damage and propagate tissue injury through recruitment of natural killer cells, macrophages, and mast cells. Transforming growth factor β and platelet-derived growth factor (PDGF) have been implicated in the development of skin fibrosis in cGvHD.4 Recently, activating antibodies targeting the PDGF receptor were reported in a group of patients with extensive cGvHD, suggesting that targeted inhibition of PDGF receptor signaling with therapies such as imatinib may inhibit the fibrotic process associated with sclerotic cGvHD.5
Careful evaluation of the "high-risk" sites in the waistband area (and brassiere-band in women) may allow for early diagnosis of sclerotic cGvHD and appropriate intervention. Because it is not possible to predict which patients will develop sclerotic cGvHD, all patients at risk for cGvHD may wish to avoid excessively tight or binding garments that may irritate or apply significant pressure to the skin.
AUTHOR INFORMATION
Correspondence: Dr Cowen, Dermatology Branch, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1908, Bldg 10, Room 12N238, Bethesda, MD 20892 (cowene{at}mail.nih.gov).
Author Contributions: Dr Cowen had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Patel and Cowen. Acquisition of data: Patel, Pavletic, Turner, and Cowen. Analysis and interpretation of data: Patel, Pavletic, Turner, and Cowen. Drafting of the manuscript: Patel and Cowen. Critical revision of the manuscript for important intellectual content: Pavletic, Turner, and Cowen. Study supervision: Turner and Cowen.
Financial Disclosure: None reported.
Funding/Support: This study was supported in part by the Intramural Research Programs of the NIH, National Cancer Institute, Center for Cancer Research. Ms Patel was supported by the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer Inc).
REFERENCES
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1. Boyd AS, Neldner KH. The isomorphic response of Koebner. Int J Dermatol. 1990;29(6):401-410.
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2. Filipovich AH, Weisdorf D, Pavletic S; et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease, I: diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945-956.
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3. Rubin AI, Stiller MJ. A listing of skin conditions exhibiting the Koebner and pseudo-Koebner phenomena with eliciting stimuli. J Cutan Med Surg. 2002;6(1):29-34.
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4. Ochs LA, Blazar BR, Roy J, Rest EB, Weisdorf DJ. Cytokine expression in human cutaneous chronic graft-versus-host disease. Bone Marrow Transplant. 1996;17(6):1085-1092.
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5. Svegliati S, Olivieri A, Campelli N; et al. Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood. 2007;110(1):237-241.
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