Dermatology Online Journal

Nephrogenic fibrosing dermopathy: Case report and review
Dornechia E George MD, Rebecca Lu MD, Saira J George MD, Sylvia Hsu MD
Dermatology Online Journal 12 (3): 7

Department of Dermatology, Baylor College of Medicine, Houston, Texas. shsu@bcm.edu

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Nephrogenic fibrosing dermopathy (NFD) is a newly recognized idiopathic fibrotic disorder that occurs in patients with renal failure [1, 2]. The lesions of NFD appear as scleroderma-like plaques, most often involving the extremities. In order to highlight the salient features of the condition, we present two illustrative cases of NFD and a brief review of the literature.

Case 1

A 75-year-old woman with diabetes, hypertension, and end-stage renal disease on hemodialysis for 6 months, was seen in consultation for progressive redness, induration, and pain of her upper extremities. The patient was admitted for presumed cellulitis and treated empirically with vancomycin. A bilateral upper extremity ultrasound was performed to rule out deep-venous thrombosis and showed a right internal jugular vein thrombus near the tip of a right subclavian intravenous catheter. Dermatology was consulted when her skin changes did not improve following vancomycin therapy and the removal of her subclavian catheter. On physical exam, she was noted to have symmetric, ill-defined, erythematous, indurated plaques on her arms, forearms, and anterior thighs. The plaques were tender to palpation. Punch biopsy of the left forearm skin showed dermal fibrosis, fibroblastic proliferation extending to the subcutaneous adipose tissue, and an increase in dermal mucin consistent with nephrogenic fibrosing dermopathy.

Case 2

A 77-year-old man who was undergoing inpatient treatment for metastatic prostate cancer was seen in consultation for evaluation of newly formed, firm, red plaques on his arms and legs. One month prior, he had required 2 weeks of hemodialysis for acute renal failure secondary to obstructive nephropathy. Physical examination showed erythematous, indurated plaques on his bilateral upper arms and anterior thighs. Punch biopsy performed on the right upper arm showed a diffuse fibroblastic and histiocytic proliferation, sclerotic collagen, and mucin deposition consistent with nephrogenic fibrosing dermopathy.

Discussion

First recognized as a distinct entity by Cowper et al. in 2001, NFD has since been reported in both adults and children with renal disease [1, 2, 3, 4]. Although increasingly recognized, the disorder still appears to be uncommon. To date, the International Center for Nephrogenic Fibrosing Dermopathy Research at Yale University reports approximately 170 cases in its registry. The lesions of NFD appear as symmetric, brawny or erythematous, indurated plaques with a thickened or peau d'orange appearance [2]. The lower extremities are almost always affected. Lesions can also occur on the upper extremities or trunk [1, 2, 5, 6, 7, 8]. The plaques are ill defined and may contain islands of sparing and finger-like projections [9]. Involvement of the head and neck is uncommon [1, 7, 10]; however, yellow plaques on the sclerae have been observed in affected patients [6]. Patients may complain of severe pain, a burning sensation, or intractable pruritus in affected areas [2, 5, 7, 8]. Edema may precede the cutaneous eruption [5, 7, 8]. As in our first case, these plaques may be initially mistaken for cellulitis [9]. Painful joint contractures may develop and, in severe cases, limit mobility as the fibrosis progresses [2, 6, 8, 11]. Patients may become wheelchair dependent or bed-bound within a matter of weeks because of contractures. Previously thought to be limited to the skin, systemic involvement is now reported, including fibrosis and calcification of skeletal muscle, myocardium, lungs, renal tubules, and testes [8, 11, 12].

NFD is characterized histologically by a proliferation of spindle-shaped fibrohistiocytic cells and small-caliber blood vessels in the dermis [1, 9, 13]. Collagen bundles are thickened, [1, 9, 13, 14] and they are surrounded or infiltrated by dendritic cells [1]. An increase in elastic fibers and interstitial mucin deposition is also seen [1, 9, 13, 14].

NFD occurs only in the setting of renal failure. The majority of cases occur in patients who have been treated with hemodialysis although the disease may also develop in peritoneal dialysis patients [5, 7] and in patients with renal insufficiency who never have received dialysis [1, 5, 7, 15]. Several cases have been also reported in renal transplant recipients [15, 16]. The onset of NFD is variable and may occur days, months, or years after the onset of renal failure or the start of dialysis.

The etiology of renal disease in patients with NFD is highly variable as well; neither the etiology nor the severity of renal dysfunction correlate with severity of NFD [2]. Embolic events, vasculopathy, primary kidney diseases, diabetes mellitus, hypertension, cyclosporine nephrotoxicity, and systemic autoimmune diseases have all been reported as causes of renal failure in patients with NFD[1, 5].

Beyond the requirement of renal failure, the pathogenesis of NFD is still poorly understood. Although an unidentified infectious or toxic etiology has been proposed, none have been identified [2]. Current hypotheses implicate a possible role for circulating fibrocytes, a subset of newly identified peripheral blood cells involved in wound healing and tissue remodeling that are CD34+, CD45RO+, and Type-I procollagen+. [20,21,22] Dermal dendritic cells with a similar immunophenotype have also been identified in NFD lesions [19]. Others suggest that increased expression of the profibrotic growth factor TGF-β by CD68+/factor XIIIa+ dendritic cells may be involved [8, 9]. The presence of antiphospholipid antibodies has been demonstrated, but their role in the development of NFD is unclear [7]. It is also hypothesized that chronic renal failure patients not taking angiotensin-converting enzyme inhibitors may be at increased risk of NFD [23].

Treatment options for NFD have been unsatisfactory. Plasmapheresis [9], intravenous immunoglobulins [24], cyclophosphamide [25], cyclosporine [7, 11], intralesional steroids [26], intralesional interferon-α [26], psoralen plus ultraviolet A [11], and photopheresis [7, 11, 27] all have been used to treat NFD, with inconsistent responses. Shmook et al. report success with use of photodynamic therapy with topical methylaminolaevulinate [16]. Correction of renal function may improve cutaneous lesions, but many cases of NFD persist despite normalization of blood urea nitrogen and creatinine levels [5, 11]. The condition is typically chronic and progressive, although spontaneous resolution of skin lesions rarely has been reported [7, 14].

The association between renal insufficiency and NFD is certain [2]. The correct identification of this disorder is pertinent to reduction of morbidity associated with erroneous treatment, for recognition of patterns surrounding its occurrence and resolution, and for identification of functional treatment modalities.

References

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