Nephrogenic fibrosing dermopathy

A 75-year-old woman with end-stage renal disease on hemodialysis presented with a 2-month history of progressive skin thickening of the lower extremities. A punch biopsy specimen showed plump fibroblasts entrapping collagen bundles and positive staining for CD34 and procollagen. These changes were consistent with a diagnosis of nephrogenic fibrosing dermopathy (NFD). Nephrogenic fibrosing dermopathy is a rare, sclerosing disorder in patients with renal failure, which may be mistaken for scleromyxedema. The etiology of NFD is unclear but may be associated with systemic involvement, antecedent surgical procedures, gadolinium, or an underlying hypercoagulable state. The treatment is limited, and only a few reported cases have shown remission after stopping dialysis in transient renal failure.     

Nephrogenic fibrosing dermopathy

Nephrogenic fibrosing dermopathy (NFD) is an uncommon, recently described fibrotic skin disorder that has been observed in patients with end-stage renal disease. We describe a 81-year-old man with end-stage renal disease who developed NFD in the seventh year of haemodialysis. Laboratory investigations revealed considerably increased circulating immune complexes and anti double stranded DNA antibodies. Because the pathogenesis of NFD may not entirely be attributable to haemodialysis, the role of circulating factors in the development of cutaneous manifestations requires further investigation.     

肾源性纤维性皮病

报告1例肾源性纤维性皮病.患者男,66岁.双下肢皮肤僵硬、色素沉着1年余.皮肤科检查示双下肢皮肤干燥、僵硬伴明显色素沉着.组织病理学检查示真皮全层及皮下成纤维细胞增生、胶原增生,脂肪间隔明显增厚.患者既往有糖尿病病史11年,糖尿病肾病病史2年.根据临床资料及组织病理学检查,该例是典型的并发糖尿病肾病的肾源性纤维性皮病患者.     

Nephrogenic fibrosing dermopathy.

This report details the histopathologic findings in a unique fibrosing disorder that recently emerged among patients with renal disease. The affected patients were initially identified among recipients of renal transplants at a single institution, but later cases at other centers were identified, and included patients receiving renal dialysis for a variety of different kidney diseases. The cutaneous changes consisted largely of indurated plaques and papules on the extremities and trunk. Systemic findings seen in scleromyxedema, which the condition resembles in some respects, were absent. By routine microscopy, the findings range from a very subtle proliferation of dermal fibroblasts in early lesions, to a florid proliferation of fibroblasts and dendritic cells in fully developed cases. Thick collagen bundles with surrounding clefts are a prominent finding, and a variable increase in dermal mucin and elastic fibers was usually evident with special stains. CD-34 positive dermal dendrocytes were floridly abundant, with dendritic processes aligned with elastic fibers and around collagen bundles in a dense network. Factor XIIIa and CD-68 positive mono-and multinucleated cells are also present in increased numbers. Electron microscopy highlighted increased elastic fibers closely apposed to dendritic cell processes. The entire dermis was commonly involved, with increased spindle cells, collagen, mucin, and elastic fibers extending through the subcutis along the septa of fatty lobules. In some instances, the process resembled a sarcoma on histopathologic examination. The recent emergence of this condition and the apparent clustering of cases in specific dialysis centers initially suggested a possible infectious and/or toxic agent. To date, however, no such agent has been identified. We propose the term "nephrogenic fibrosing dermopathy (NFD)" until a specific cause can be identified.     

Nephrogenic fibrosing dermopathy: first Colombian case

A 67-year-old woman with acute renal insufficiency, who was on hemodialysis, developed progressive skin lesions consistent with thickening and hardening of the skin in both the back and extremities without contracture upon flexure. Her face was not affected. Laboratory evaluation was unremarkable and a skin biopsy showed an increase in collagen and interstitial mucin with no inflammatory infiltrate. These clinical features resemble a new recently reported disorder, nephrogenic fibrosing dermopathy. This disorder manifests itself as scleromyxedema-like skin lesions without associated paraproteinemia, occurring in the setting of renal disease. The incidence, prevalence and etiology of the disease are unknown and currently no effective treatment is available. This is the first case reported in Colombia.     

Nephrogenic fibrosing dermopathy with systemic involvement

BACKGROUND: There is a growing literature regarding sclerotic and panniculitic cutaneous conditions seen in patients with end-stage renal disease (eg, calciphylaxis and soft tissue calcification). Nephrogenic fibrosing dermopathy (NFD) is a recent designation to describe cutaneous findings in patients with end-stage renal disease who developed sclerotic plaques with scleromyxedema-like histologic features. Soft tissue calcification is rare in patients with NFD and systemic involvement has not been reported. OBSERVATIONS: We describe a patient with end-stage renal disease who developed diffuse indurated woody plaques consistent with NFD in association with soft tissue calcification with catastrophic sequelae. A deep excisional biopsy specimen from the patient revealed thickened collagen bundles in the reticular dermis, plump bipolar spindle cells, and increased mucin. Focally, there were zones of calcium deposition in dermal collagen without vessel calcification. Autopsy of the patient revealed extensive fibrosis and calcification of the diaphragm, psoas muscle, renal tubules, and rete testes. The patient died 11 months after developing NFD. CONCLUSION: A subset of patients with NFD may have significant systemic involvement.     

Nephrogenic fibrosing dermopathy: report of two cases

Nephrogenic fibrosing dermopathy is a recently described fibrosing disorder that emerges in different settings of renal insufficiency. The degree and cause of the underlying renal impairment seem not to be related to the severity of the nephrogenic fibrosing dermopathy. Lesions are typically symmetrical and usually develop on the limbs and trunk. These are characterized by skin-coloured to erythematous papules that coalesce into plaques markedly thickened in texture. Flexion contractures of the joints may be a feature of the disease. There is no consistently effective therapy for nephrogenic fibrosing dermopathy. We report here 2 Brazilian patients in connection with a short review. Remission was recorded in one case after plasmapheresis.     

Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis

Nephrogenic fibrosing dermopathy (NFD) is a rare fibrosing skin disease of unknown etiology occurring in patients with terminal renal disease. It was first described in the year 2000. The histology of NFD shows an increased number of dendritic cells, fibroblasts and thickened collagen fibers resembling scleromyxedema. It can be distinguished from scleromyxedema by a different distribution pattern of the skin lesions with indurated plaques mainly on the extremities and the absence of paraproteinemia. As yet, no treatment for NFD has been proven to be uniformly efficient. We describe the case of a 40-year old patient with renal insufficiency who was treated with hemodialysis and who had undergone kidney transplantation. Two years after transplantation, she developed sclerodermiform brownish plaques on her extremities. The induration improved significantly after 4 cycles of extracorporeal photopheresis.     

Nephrogenic fibrosing dermopathy after liver transplantation successfully treated with plasmapheresis

Nephrogenic fibrosing dermopathy (NFD) is a recently described cutaneous fibrosing disorder associated with renal dysfunction. It appears similar to scleromyxedema but with some notable exceptions, including the lack of involvement of the face and absence of plasma cells on histology, systemic involvement, and paraproteinemia. Patients can present with thickened or edematous skin with indurated papules and plaques involving the extremities and the trunk. We report the first three cases of NFD after liver transplantation successfully treated with plasmapheresis. Two patients underwent liver transplantation for hepatitis C virus-induced cirrhosis and one for hepatitis B virus-induced cirrhosis. All the patients had encephalopathy, refractory ascites, and malnutrition prior to transplantation. Like those patients with NFD, all three of our patients had renal dysfunction and required hemodialysis before and after transplantation. Two were not dependent on dialysis at the time of diagnosis, however. These patients had excellent liver allograft function, but the other patient had allograft failure secondary to recurrent hepatitis C. Immunosuppression therapy consisted of basiliximab, mycophenolate mofetil, calcineurin inhibitor, and prednisone. The patients developed "woody" skin induration of the distal extremities, erythematous papules, and contractures at 1, 2, and 120 months after transplantation. Skin biopsies resembled NFD. No paraproteinemia was evident. One to three 5-day courses of plasmapheresis resulted in moderate to marked clinical improvement. The improvement of the kidney function in two of our patients did not appear to correlate with that of the skin disorder, because the kidney function was improving at the time the diagnosis of NFD was made. In conclusion, we report the first three cases of NFD after liver transplantation. Plasmapheresis was moderately successful in resolving the skin-indurated papules, severe skin induration, and associated joint contractures. Preliminary studies (unpublished data) show that decreasing plasma levels of transforming growth factor-beta1 after plasmapheresis appear to correlate with the amelioration of this clinical condition.     

Nephrogenic fibrosing dermopathy in a renal transplant recipient with tubulointerstitial nephritis and uveitis

We report a patient with nephrogenic fibrosing dermopathy. He had chronic renal failure with arthritis, uveitis and histologically severe tubulointerstitial nephritis for which he received a renal transplant from a family relative. After an episode of acute renal failure with the transplant he developed painful, erythematous, firm papules and plaques with geographic borders on the legs, anterior thorax and elbow. A skin biopsy revealed increased fibroblast and collagen fiber content of the dermis and subcutaneous septae. Mucin deposition, sparse smooth-muscle-actin-positive cells and an increased number of CD34-positive cells in the deep dermis were found. After several weeks of hemodialysis, the lesions changed from an inflammatory to a purely sclerotic phase. The fibrocyte, a recently described circulating cell type, that is deposited in scar tissue may be involved in the pathogenesis of this novel pseudosclerodermatous skin disorder.     

Nephrogenic fibrosing dermopathy in a patient with acute renal failure never requiring dialysis

Nephrogenic fibrosing dermopathy (NFD) is a newly recognized cutaneous fibrosing disorder. To date the etiology, pathogenesis, and clinical course remains unknown. The majority of cases have been in renal dialysis or renal transplant patients. Only four cases have been reported in which patients had acute renal failure and never required dialysis. Currently, there is no effective treatment. A 65-year-old man was hospitalized for pneumonia. During hospitalization he developed acute renal failure secondary to acute tubular necrosis. The patient had woody indurated plaques on his upper extremities and trunk, and brown indurated plaques on his trunk. Histopathological examination revealed a spindle cell proliferation infiltrating through the dermis and subcutis with mild mucin deposition. Nephrogenic fibrosing dermopathy is a novel fibrosing disorder diagnosed clinically and histopatholigically. Currently no risk factors other than renal failure have been identified. Our patient is a unique example of NFD observed in acute renal failure secondary to acute tubular necrosis, never requiring dialysis. We also review the four other cases of acute NFD never requiring dialysis that have been reported in the literature.     

Nephrogenic fibrosing dermopathy in a patient with systemic lupus erythematosus and acute lupus nephritis

Abstract:  Nephrogenic fibrosing dermopathy is a recently recognized skin disorder similar in appearance to scleromyxedema but without the systemic involvement. We describe a 14-year-old girl with new-onset systemic lupus erythematosus and acute lupus nephritis who developed on the lower extremities confluent hyperpigmented, woody, indurated plaques that contained groups of coalescing erythematous papules. Nephrogenic fibrosing dermopathy was diagnosed histologically. Possible etiologies are discussed.     

Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis: a case series of nine patients and review of the literature

BACKGROUND: Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NFD/NSF) is a fibrosing cutaneous disorder recently recognized to have systemic manifestations. The disease is characterized clinically by an acute onset of hardening and thickening of the skin of the extremities and trunk, often resulting in flexion contractures, and histologically by an increase in spindle-shaped cells, collagen, and sometimes mucin deposition in the dermis. The only common exposure amongst patients is acute or chronic renal failure. The pathophysiology of the disease remains to be elucidated, and there is currently no consistently effective treatment for this unremitting disease. METHODS: We report a case series of nine patients seen at the University of Pennsylvania between 1998 and mid-2004. The clinical, laboratory, and pathologic data of these patients are reviewed. RESULTS: All patients had renal disease, received peritoneal or hemodialysis, and five had received at least one renal transplant. All patients had characteristic fibrotic cutaneous lesions involving the trunk, extremities, or both, and eight of the nine patients had scleral plaques. There were no other common findings amongst the histories, medications, or laboratory results of the patients. CONCLUSION: Our report confirms the clinical and histologic characteristics of NFD that have been described previously, and raises new issues regarding the possible subtypes. A review of the current literature stresses that further basic science and translational studies are necessary to understand the disease mechanism and to propose effective therapy, and emphasizes the importance of recognizing the systemic effects of NFD.     

肾源性纤维组织增生性皮肤病一例

患者男,50岁,因双下肢暗红斑、硬肿、皮下结节、剧烈瘙痒4月余,于2006年12月14日来我科就诊.4个月前发现双大腿中上部内侧及曲侧暗红斑、硬肿,可扪及皮肤硬结,伴剧烈瘙痒,皮损迅速扩大,当地医院诊断不详,外搽曲安奈德益康唑乳膏,无明显效果.1976年10月曾患急性肾小球肾炎,乙肝病史10年,高血压病史3年,戒烟酒10年.6个月前,无明显诱因出现乏力、纳差、全身皮肤瘙痒,肌酐1279.6 mmol/L,诊断为慢性肾功能衰竭.在当地医院行血液透析,每周2次.3个月前.出现恶心、呕吐、腹胀,行肝脏磁共振平扫加增强扫描、B超检查,见肝占位性病变、脾大,腹腔穿刺液涂片见非典型细胞,考虑为肝硬化腹水、肝癌.2个月前出现尿少,每日200～300 mL,开始在进行血液透析的同时,反复腹腔穿刺抽腹水.     

Gadolinium deposition in nephrogenic fibrosing dermopathy

There is growing recognition of the association between the use of gadolinium-containing radiocontrast agents for magnetic resonance imaging and the serious dermal and systemic disease nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NFD/NSF). The pathogenesis of this entity remains unclear; however, our recent observations suggest a likely mechanism for the initial dermal manifestations of this gadolinium toxicity.