Cases Of Nephrogenic Fibrosing Dermopathy Research Articles

Nephrogenic systemic fibrosis: The need for accurate case reporting

We have read with great interest the recent editorial by Dr. Peter Dawson entitled “Nephrogenic Systemic Fibrosis: Possible Mechanisms and Imaging Management Strategies” which appeared in the October issue of the Journal of Magnetic Resonance Imaging (1). Although the article is well written, there are shortcomings which should be brought to the attention of the readers of JMRI to prevent misconceptions and misunderstandings. Above all, Table 1 indicates that there have been cases of nephrogenic systemic fibrosis (NSF) with certain gadolinium-based contrast agents (GBCAs) only. Unfortunately, it is not clear whether Table 1 refers to cases spontaneously reported by healthcare professionals or by consumers to the healthcare authorities (“spontaneous reports”) or cases described in peer-reviewed articles. In our experience, several spontaneous reports, especially those reported by consumers, turn out not to be NSF, many are not biopsy-proven, and duplications of the same report are possible. Nevertheless, all spontaneous reports are promptly submitted to the healthcare authorities, independently of their quality or accuracy. The quality of NSF cases reported in peer-reviewed articles is usually more reliable, even if a few cases are not biopsy-proven (2). Besides, it is not clear whether Table 1 refers solely to “unconfounded” cases of NSF (ie, NSF occurring following documented administration of one GBCA alone) or “confounded” cases (ie, when patients developed NSF after undergoing MRI examinations with two or more GBCAs). In either case, Table 1 is incorrect. As for spontaneous reports, there have been confounded NSF cases with the majority of the GBCAs, the macrocyclic GBCAs Dotarem, ProHance, and Gadovist included (3-7). Most of the unconfounded cases have been reported after the administration of Omniscan, followed by Magnevist and OptiMARK. There is one unconfounded case, reported as a “mild case of nephrogenic fibrosing dermopathy,” also with the macrocyclic ProHance. As for cases reported in peer-reviewed articles, Broome (7) recently completed a thorough analysis and summary of the medical literature. According to the results of this extensive analysis, as of February 1, 2008, there were 186 biopsy-proven cases of NSF published in the peer-reviewed literature with the following unconfounded associations: 157 Omniscan, 8 Magnevist, 3 OptiMARK, and 18 unspecified GBCAs. A further four cases were confounded with more than one GBCA, while five additional cases were not associated with any GBCA. It is important to underline that it is still unclear whether GBCAs trigger NSF. Nevertheless, it is appropriate to assume for now that a potential association might exist for all GBCAs, macrocyclic agents included. Preventive measures, above all the prompt identification of patients at risk, may minimize the risk of developing NSF (4). Alberto Spinazzi MD*, Miles A. Kirchin PhD , Gianpaolo Pirovano MD*, * Worldwide Medical & Regulatory Affairs, Bracco Diagnostics Inc., Princeton, NJ, USA, Worldwide Medical & Regulatory Affairs Bracco Imaging SpA Milan, Italy.

A case of nephrogenic fibrosing dermopathy in a liver transplant recipient

A case of nephrogenic fibrosing dermopathy in a liver transplant recipient

A pediatric case of nephrogenic fibrosing dermopathy: Improvement after combination therapy

To the Editor: Nephrogenic fibrosing dermopathy (NFD) is a rare, recently described clinicopathologic entity characterized by indurated cutaneous plaques that develop in patients undergoing renal dialysis or those with end-stage renal disease.1 To our knowledge, there have only been 4 previously described pediatric cases.2,3 We report an additional pediatric case of NFD that is notable for partial improvement of the skin lesions with local topical therapy and the use of leg compression stockings.

Description of 12 Cases of Nephrogenic Fibrosing Dermopathy and Review of the Literature

To review the clinical and laboratory features of 12 cases of nephrogenic fibrosing dermopathy (NFD) studied at our institution and of 70 previously described cases in the literature. Clinical evaluation and laboratory studies of 12 patients with NFD associated with chronic hemodialysis or peritoneal dialysis for end-stage renal disease and a review of 23 previous publications describing 70 patients with this disease. Eleven patients undergoing chronic hemodialysis and 1 patient undergoing chronic peritoneal dialysis for end-stage renal failure developed a severe and progressive cutaneous fibrotic process with woody induration of legs, thighs, hands, and forearms, and severe loss of motion and flexion contractures in multiple joints. Several patients displayed systemic involvement including fibrosis of muscles, myocardium, and lungs and marked elevations of the erythrocyte sedimentation rate and/or C-reactive protein. Three patients died within 2 years of symptom onset. A review of previously published reports of this disorder confirmed the presence of systemic involvement and a poor prognosis with a high mortality rate. NFD is a severe and usually progressive systemic fibrotic disease affecting the dermis, subcutaneous fascia, and striated muscles. It also appears that the disease can cause fibrosis of lungs, myocardium, and other organs.

Nephrogenic fibrosing dermopathy: A series in a non-Western population

Nephrogenic fibrosing dermopathy (NFD) is a newly proposed clinical entity resembling scleromyxedema. This is mainly found in patients with chronic renal failure who have undergone hemodialysis. Nearly all cases have been reported in the Western population. We sought to assess whether NFD cases occurred in a non-Western population and to ascertain the frequency, clinical characteristics, histopathology, and natural history of the condition in the event of its occurrence. Patients postdialysis in the nephrology department of a tertiary referral hospital in Kolkata, India, were evaluated clinically and histopathologic assessment was done on the basis of a clinical scoring to ascertain the frequency of the condition and its characteristics. This report is based on the findings of the first 3 years of an ongoing study. NFD was diagnosed in 6 of 2146 patients postdialysis 0.28%). In transplant recipients undergoing dialysis, NFD was diagnosed in 2 of 43 patients (4.65%). The average number of dialyses undergone by the patients was 7.2 (range: 2-16). Of the 6 cases of NFD, 5 conformed to the diagnosis of chronic kidney disease-V. Among them, 3 were noninsulin-dependent diabetes mellitus and one each were cases of chronic glomerulonephritis and systemic lupus erythematosus. One case followed dialysis in acute tubular necrosis. All cases clinically showed circumscribed thickening, roughened texture, hardening, xerosis, and infiltrated papules, plaques, or both. One case showed rippled pigmentation, four showed varied hyperpigmentation, two demonstrated localized fibrosis, and one resembled papular mucinosis. Increased thickness of dermis, increased number of plump spindle cells, abundance of thick collagen bundles with prominent clefts, and sparse small, multinucleated histiocytes were the hallmark of microscopic findings. The inherent nature of the study precluded the inclusion of NFD cases without any background of dialysis, which have now been reported. No statistical conclusions may be established from our small series. To our knowledge, this is the first reported series of NFD outside North America and Europe.

Successful treatment of three cases of nephrogenic fibrosing dermopathy with extracorporeal photopheresis

Nephrogenic fibrosing dermopathy (NFD) is a recently described cutaneous fibrosing disorder associated with renal dysfunction. Patients present with thickened skin or oedematous skin with indurated papules and plaques involving extremities and trunk, and often associated with disabling contracture of the adjacent joints. The aetiology and pathogenesis remain largely unknown. As a consequence, therapeutic measures with proven efficacy are nonexistent to date. To consider treatment with extracorporal photopheresis (ECP) in three patients. Patients We report three new cases of NFD with the characteristic clinical and pathological features. Two patients required haemodialysis due to end-stage renal failure, despite prior renal transplantation. One patient had renal dysfunction but was never on dialysis, nor had she been transplanted. ECP treatment was administered at intervals of 2-4 weeks. All three patients showed a softening of the skin lesions and a marked improvement of the joint motility starting after four cycles of ECP. One patient developed a complete regression of her skin lesions after 16 cycles of ECP, and response to therapy was observed despite constantly elevated renal values. These data indicate that ECP may represent a valuable therapeutic option for NFD.

Nephrogenic Fibrosing Dermopathy

Nephrogenic fibrosing dermopathy is a rare, recently described fibrotic skin condition that primarily affects patients with a history of renal disease.We report 2 cases of nephrogenic fibrosing dermopathy and review clinical and histopathologic features with differential diagnosis and more.Case #1 was a 64‐year‐old black male with chronic renal insufficiency which progressed to end stage renal disease requiring hemodialysis. After two days, he developed blisters on both his hands. By a month, his blister lesions resolved leaving scaly skin with some skin thickening and tightening in the hands and forearms. Over the course of one month, skin over above‐mentioned areas began to harden and stiffen. His fingers began to coalesce and contract resulting in fixation of hand grip. He also developed flexing contracts at the elbows bilaterally. Skin biopsy revealed the diagnosis of nephrogenic fibrosing dermopathy with giant cells reaction. Case #2 was a 44‐year‐old black male with a hx of nephropathy. He eventually developed end stage renal disease requiring hemodialysis. One month after, he was found to have thickened, sclerotic appearing skin involving the upper back, hands, and forearms with flexing contracts of the all the small joints. Histopathology was most consistent with nephrogenic fibrosing dermopathy.

Nephrogenic Fibrosing Dermopathy with Osteoid Metaplasia

Nephrogenic fibrosing dermopathy is a rare and recently described disease which occurs in patients with a history of renal disease and is often associated with hemodialysis or renal transplants. The usual presentation is multiple indurated plaque lesions resembling scleromyxedema on the extremities and trunk. Nephrogenic fibrosing dermopathy has been described in association with calciphylaxis and metastatic calcification, however, to our knowledge, the occurrence of osteoid metaplasia has not been previously reported. We report a case of nephrogenic fibrosing dermopathy with osteoid metaplasia in a 78‐year‐old female patient with chronic renal failure on dialysis. The patient had a relatively acute onset (a few months) of lesions with irritation and pruritis of the lower extremities. Biopsies showed fibrous thickening of the dermis with islands of osteoid tissue with osteoblastic rimming. Calcification and lamellar bone formation were not seen. An Alcian blue stain demonstrated increased dermal mucin. Elastic stains showed prominent elongated elastic fibers between collagen fibers and within osteoid areas. The differential diagnosis included scleromyxedema and other fibrotic disorders. The pathogenesis of this disorder is unknown. Although rare patients improve with correction of renal abnormalities, currently no effective treatment is available.

Histologic Comparison of Scleromyxedema and Nephrogenic Fibrosing Dermopathy

Background: Nephrogenic fibrosing dermopathy (NFD), can be strikingly similar, if not indistinguishable, histologically from scleromyxedema. Both disorders consist of a dermal and subcutaneous proliferation of fibroblast‐like cells with mucin production. NFD has been shown to contain an increased number of dual positive CD34 and procollagen cells, as well as an increased number of factor XIIIa positive cells. To our knowledge, there has been no direct comparison between the histologic and immunophenotypic properties of scleromyxedema and NFD. Design: Nine biopsies from eight cases of NFD and eight biopsies from eight cases of scleromyxedema were identified. Standard immunohistochemical techniques for antibodies toward CD34, procollagen I, CD31, SMA, and factor XIIIa were applied. A colloidal iron stain was used to evaluate for dermal mucin. Amount of antibody expression and mucin production were then evaluated using a grading scale of 0–3. Results: Both NFD and scleromyxedema were found to have similar immunophenotypic expression. Both demonstrated increased numbers of CD34 and procollagen‐positive fibroblast‐like cells, as well as increased numbers of factor XIIIa positive cells. Increased vessels and stromal mucin were identified in both diseases without significant differences. Conclusions: Although scleromyxedema and NFD are clinically distinct diseases, their morphologic and immunophenotypic appearances are likely to be similar.

A report on four new cases of nephrogenic fibrosing dermopathy in chronic hemodialysis patients

Nephrogenic fibrosing dermopathy (NFD) is a rare clinical entity affecting patients with renal failure, often on chronic dialysis or after transplantation. The patient profile at risk for this debilitating condition is undefined. Lack of awareness of the condition has hampered epidemiologic work in identifying the etiology. We present four chronic hemodialysis (HD) patients who developed this disease. The patients' ages ranged from 26 to 75 years, and they had received HD from between 20 months and 10 years before the diagnosis of NFD. Two patients had a history of renal transplantation. All patients had progressive thickening and woody induration of the skin associated with contractures, leading to difficult ambulation, and permanent disability within weeks of the diagnosis. In one case, the diaphragm, psoas muscle, and pericardium were involved. The latter is likely the first report of pericardial involvement of NFD. In all four patients, the skin findings were restricted to the extremities, sparing the trunk and face. Skin biopsy findings included thickened dermis with particularly thickened collagen bundles, fibroblast proliferation, minimal mucin deposition, and nearly absent inflammation. The pathologic findings were distinct from scleromyxedema and scleroderma. We found no laboratory evidence of autoimmune disease or thyroid dysfunction to account for alternate etiologies. CD34-positive cells were documented in the skin biopsies as well as in the diaphragm, psoas muscle, and pericardial tissue of the concerned case. NFD is a novel fibrosing disorder of progressively debilitating nature which needs further clinical characterization and recognition to guide investigation of its pathogenesis.

Nephrogenic fibrosing dermopathy: A unique fibrosing skin condition of renal insufficiency associated with CD34/procollagen dual positive circulating fibrocytes

Rationale Nephrogenic fibrosing dermopathy (NFD) is a recently described fibrosing skin condition with only about 100 cases reported between USA and Europe. Methods We report a case of a 52-year old kidney transplant patient who developed NFD three weeks after the onset of acute renal insufficiency. NFD is characterized by erythematous, brownish coalescent plaques that manifest as “woody” skin. The lesions may be itchy, painful, typically symmetrical with a predilection for extremities. Results The skin biopsy, typical for NFD, showed increased fibroblast-like cells in the dermis, some myofibroblasts, thickened collagen bundles separated by small clefts, and minimal inflammatory infiltrate. Systemic sclerosis was excluded clinically and histologically. The patient partially improved with oral corticosteroids and topical vitamin D. Hemodialysis was initiated. He is being evaluated for another kidney transplantation. The pathophysiology of NFD is incompletely understood, the histopathology suggests that fibrogenic cytokines like transforming growth factor-β1 may be involved in the disease. Recent dual immunohistochemical studies have shown that a unique cell known as circulating fibrocyte (CF) produces the characteristic histologic findings. It is unknown whether the CFs of NFD are aberrant in function, quantity, or merely stimulated by cytokines that are abnormally elevated in renal insufficiency. Conclusions To our knowledge, this is the first case of NFD outside Europe and USA. Since this is a new and rare condition, there is no standard treatment, but in almost all cases, resolution was associated with the return of normal kidney function. The collection and organization of information from NFD cases is crucial to the development of targeted therapeutic efforts.44

Nephrogenic fibrosing dermopathy: two pediatric cases

We report two pediatric cases of nephrogenic fibrosing dermopathy (NFD), first described in 2000. NFD is a condition in which individuals with renal dysfunction have development of extensive skin hardening and histopathologic evidence of a scleromyxedema-like condition.

Nephrogenic Fibrosing Dermopathy and Alpha-1 Antitrypsin Deficiency: A Case Report of a Hemodialysis Dependent Man

Nephrogenic fibrosing dermopathy (NFD) is a rare newly described scleromyxedema-like cutaneous disease that occurs in renal failure patients. Since the year 2000, NFD has been identified in patients on hemodialysis, peritoneal dialysis, renal transplantation and no dialysis. Objective: To discuss the clinical presentation of a case of NFD, which compounded the course of alpha-1 antitrypsin (A1AT) deficiency. This 23-year-old man on hemodialysis thrice weekly had rapid deterioration of functional abilities. The patient was previously ambulatory, but he became contracted and bedridden over several weeks. He had a brawny thickening of his skin over his arms, legs and chest. He complained of intolerable burning joint pain during hemodialysis. After a failed trial of steroid therapy NFD was diagnosed by biopsy. He subsequently became hypercalcemic secondary to immobilization. His existing A1AT deficiency presented as liver failure, hyperammonemia and encephalopathy. He was cachetic and his nutritional status was difficult to manage due to medically induced diarrhea, poor appetite, confused mental state and infected total parenteral nutrition lines. A dual liver-kidney transplant was considered, but several factors prevented surgery including: poor nutritional status, scant data to suggest resolution of NFD after transplantation and lack of profound liver failure. His nutritional status, contractures, mental status and liver function never recovered, and six months after diagnosis of NFD the patient died. Conclusions: This case of NFD resulted in a rapid decline of function from ambulatory young man to contracted and bedridden invalid. The NFD did not respond to therapy and compounded the course of A1AT. NFD contributed to hypercalcemia of immobility, intolerance of hemodialysis and cachexia.

Nephrogenic fibrosing dermopathy (scleromyxedema-like illness of renal disease)

Nephrogenic fibrosing dermopathy or scleromyxedema-like illness of renal disease is a recently reported disorder. It manifests as scleromyxedema-like skin lesions without associated paraproteinemia, occurring in the setting of renal disease. In the majority of cases skin lesions of nephrogenic fibrosing dermopathy develop after hemodialysis or renal transplantation; however, the origin is still unknown. We report 4 new cases of nephrogenic fibrosing dermopathy and review the literature. The clinical and histopathologic features, differential diagnosis, possible etiology, and treatment options are reviewed. (J Am Acad Dermatol 2003;48:55-60.)