Chronic Graft-Versus-Host Disease Presenting as Eosinophilic Fasciitis

Abstract

Chronic graft-versus-host disease (cGVHD) is one of the main late complications of allogeneic hematopoietic stem cell transplant and a major contributor to the mortality and morbidity in surviving recipients. Skin is the most common involved organ in cGVHD and may mimic a wide spectrum of dermatological conditions in its clinical and histopathologic manifestations. Some of the commonly simulated diseases are scleroderma, morphea, and lichen sclerosus. Chronic GVHD simulating eosinophilic fasciitis (EF) is relatively rare, frequently presenting with skin induration, a typical "peau d'orange" appearance, peripheral blood eosinophilia, myalgia, arthralgia, and arthritis leading to joint contractures in severe cases.Diagnosis is based on clinical manifestations and histopathology. Treatment is challenging because most cases are refractory to first-line therapy of glucocorticoids and calcineurin inhibitors (CNIs), and there is no standard second-line therapy.We report a comprehensive review of literature on all reported cases of CGVHD presenting as EF. We also describe an additional interesting case of cGVHD presenting as EF that was resistant to traditional therapy of high-dose glucocorticoids and cyclosporin A, but showed complete resolution of skin manifestations after addition of imatinib.Chronic GVHD presenting as EF is a rare variant of sclerodermatous cGVHD. Diagnosis is difficult, and treatment of cGVHD mimicking EF remains a therapeutic challenge because of obscure pathogenesis and poor response to traditional immunosuppressive medications. Emerging insights into the pathogenesis of cGVHD have resulted in the development of novel targeted therapies, which may improve outcomes and should be attempted in this subset of the disease. Larger studies are warranted to substantiate these preliminary findings.

Diffuse skin thickening, myalgias and joint stiffness in a 41-year-old man

“…3 In addition, chronic cutaneous graftversus-host disease has also been associated with this disorder. 4 The earliest phase of diffuse fasciitis with eosinophilia is often characterized by edema and erythema in the extremities, soon followed by woody induration, frequently associated with a peau d'orange appearance, as seen in our patient. Elevation of an affected extremity leads to reduction of the distending venous pressure, causing indentation along the course of the superficial veins -the characteristic "groove sign" shown in Figure 1B.…”

Graft versus host disease-related eosinophilic fasciitis: cohort description and literature review

“…Studies and reviews specifically of cGVHD-related fasciitis are limited. Most of them are descriptions of isolated cases [21,[27][28][29][30][31][32][33][34][35] or case series with small sample sizes [19,20,[36][37][38], or uncontrolled series [19,26]. For this reason, the cohort of our hospital is the second largest series to be reported in the literature after that of the Seattle group [26], whose publication extended the data they published in 2014 [19].…”

“…5). This included 10 individual case reports [21,[27][28][29][30][31][32][33][34][35], five retrospective case series [19,20,[36][37][38] and one extension of a single prospective observational study [26]. EF-like cGVHD was first reported in 1987 by van den Bergh et al [34] and later in 1990by Markusse et al [34].…”

Chronic Graft Versus Host Disease: An Update on the Clinical Characterization and Diagnostic Assessment of Cutaneous and Articular Sclerotic Forms

“…Moreover, multiple studies have presented strong correlation between joint and skin symptoms during the course of GVHD (15). According to Vukiç, joints change appeared in 83,3% of subjects with coexisting erythematous lesions, superficial o deep sclerosis [30] Unfortunately, it is not known what clinical, genetic and biological factors are specifically involved in the musculoskeletal and joint involvement of GVHD patients [31][32][33]. The search for serum biomarkers in this fibrous entity, such as specific autoantibodies, has so far proved unsuccessful.…”