Localization of Sclerotic-type Chronic Graft-vs-Host Disease to Sites of Skin Injury

Abstract

Background: The mechanisms responsible for the variable manifestations of chronic cutaneous graft-vs-host disease (cGVHD) are poorly understood. Localization of sclerotic-type chronic graft-vs-host disease to sites of skin injury (isomorphic and isotopic responses), a recognized phenomenon in morphea, suggests a potential common pathway between cGVHD and other sclerotic skin conditions. Observations: Four cases of sclerotic-type cGVHD developed at the site of disparate skin injuries (ionizing radiotherapy, repeated needle sticks, central catheter site, and varicella-zoster virus infection). We review the spectrum of previously reported cases of sclerotic and nonsclerotic cGVHD relating to external forces on the skin. Conclusions: Localization of sclerotic-type cGVHD may occur after many types of skin injury, including UV and ionizing radiotherapy, needle sticks, viral infection, and pressure or friction. Recognition of this phenomenon may be helpful for the early diagnosis of sclerotic disease. Recent insights into the immunological consequences of minor skin injury may provide important clues to the underlying pathogenesis of cGVHD-mediated skin disease.

The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease

“…Second, tissue damage incurred during acute GVHD may persist, as evidenced by progressive onset chronic GVHD or overlap syndrome. Even restricted areas of mild cell damage (waistband pressure, varicella zoster virus reactivation) can trigger localized sclerotic cutaneous chronic GVHD (71). Th1/Tc1 and Th17 cells are the dominant T-cell effectors in lichenoid infiltrates of the skin and mucosa (62, 72–77) (Figure 3).…”

Upregulation of IFN-Inducible and Damage-Response Pathways in Chronic Graft-versus-Host Disease

“…AGVHD and CMV infection, both sources of cell destruction and induction of Type I and Type II IFN, are established cofactors in the development of CGVHD (47, 48). Indeed, localized areas of minor tissue damage after allo-HSCT – mild pressure from waistbands and bra straps, repeated blood draws, targeted irradiation and localized skin lesions from varicella – have all been associated with localized sclerotic CGVHD (49). Effects of earlier immune activation by these factors may not be apparent clinically.…”

The role of skin trauma in the distribution of morphea lesions: A cross-sectional survey of the Morphea in Adults and Children cohort IV

“…Sclerotic type cGVHD has been shown to occur in an isotopic fashion with ionizing radiation, repeated needle sticks, and varicella-zoster virus infection as well as in an isomorphic fashion at areas of skin friction (waistband and brassiere line). 7, 8 As seen in Table IV, greater than 40% of patients with trauma induced lesions had them on the breast implying a potential preferential distribution, however its significance is difficult to ascertain due to the strong female predominance of affected patients who would be more likely to have procedures in those areas. Also of interest, children, in which the subtype is predominantly linear, were underrepresented in the trauma induced morphea group relative to the overall MAC cohort.…”

“…These classifications were based on definitions in the literature 5, 6 and recent studies of sclerotic-type GVHD. 7, 8 …”