Nephrogenic fibrosing dermopathy: A rare entity in patients awaiting liver transplantation

A 56-year-old Caucasian female with end-stage liver disease secondary to α1-antitrypsin deficiency and end-stage renal disease secondary to idiopathic membranous nephropathy presented with a one-week history of increased bilateral lower extremity edema and anasarca. On admission, the patient complained of raised hardened areas especially prominent on the upper medial thighs that were painful, warm, and non-pruritic. She denied any constitutional symptoms and denied using any new medications. On exam, the patient was found to be afebrile with stable oxygen saturation. The abdomen was distended with evidence of hepatomegaly. Bilateral lower extremity edema to the groin were present, and hyperpigmented plaques (Fig. 1) (tender, indurated, and warm) were noted on the upper medial aspects of her thighs, but not involving the groin. There was no visible face or upper extremity involvement. Hyperpigmented confluent plaques on the inner thighs of a patient with NFD. Laboratory tests did not reveal leukocytosis or eosinophilia. ESR was 40 and ANA test was negative. Serum protein electrophoresis was negative for paraproteinemia. Doppler ultrasound did not reveal deep venous thromboses. The patient received a short course of antibiotics without any clinical improvement. A skin punch biopsy revealed increased dermal fibroblast proliferation, thick collagen bundles with surrounding clefts, elastic fibers, and increased mucin deposition consistent with NFD (Fig. 2 and 3). The patient declined any steroid treatment and was subsequently discharged. (H&E). Thickened, haphazardly arranged collagen bundles separated by clefts and associated with a proliferation of fibroblasts and dendritic cells. The subcutaneous septa also show thickened collagen bundles and fibroblast. No significant inflammation is seen. (Colloidal Iron Stain). Note the widened spaces between collagen bundles due to the increased position of mucin, which is stained blue by the colloidal iron stain. Eventually the patient underwent liver transplant and received oral prednisone as part of the immunosuppression regimen, which has led to some improvement of the cutaneous lesions. Currently she has extensive skin contraction involving her calves and shins with decreased range of motion, and she has become largely wheelchair bound. Nephrogenic Fibrosing Dermopathy (NFD) is a recently described dermatologic condition characterized by large indurated plaques and papules with several key histopathologic features generally seen in patients with renal failure. These lesions predominantly affect the extremities and trunk, and tend to be large, hardened, hyperpigmented, and are often warm, pruritic, and painful with flexion contractures resulting in limited range of motion. Presentation may mimic scleromyxedema but NFD tends to lack paraproteinemia, systemic or facial involvement, or inflammatory cells on histology. The diagnosis is made mainly by skin biopsy.1 As of July 2003, only a few cases in the United States and Europe had been identified.2 Three liver transplant patients with NFD have been described.3 The etiology, pathogenesis, and disease course have not been clearly defined. NFD, a rare condition seen in patients on hemodialysis, needs to be considered in the differential diagnosis of skin lesions, along with other conditions like scleromyxedema, scleroderma, eosinophilic fasciitis, or toxic syndromes in those with end-stage liver disease or recent liver transplantation. Onset tends to be acute but may progress to a functional impairment of the lower extremities.4 Management with corticosteroids has been largely ineffective, although successful treatment with plasmapheresis (decreasing circulating levels of TGF-β and other cytokines) following liver transplantation has been described.3 One proposed mechanism suggests NFD is an aberrant and protracted tissue injury response, in which certain cytokines like TGF-β may mediate the characteristic florid fibroblastic proliferation of NFD.4