Shawn E. Cowper

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: the first 6 years.

Purpose of reviewNephrogenic fibrosing dermopathy (NFD) is a newly recognized scleroderma-like fibrosing skin condition. It develops in patients with renal insufficiency. This review summarizes recent case reports and examines theories of disease pathogenesis. Information from the Yale University NFD Registry Project, as well as published case reports, is included to provide a contextual framework upon which to base these theories. Recent findingsRecent studies have contributed to a clearer definition of the clinical spectrum, epidemiology, and pathogenesis of NFD. The findings of yellow scleral plaques and circulating antiphospholipid antibodies have been proposed as markers of NFD in recent case reports. In addition, epidemiologic data have yielded several distinct clinical patterns of disease onset. Lastly, dual immunohistochemical staining for CD34 and procollagen in the spindle cells of NFD suggest that the dermal cells of NFD may represent circulating fibrocytes recruited to the dermis—a finding previously undescribed in normal skin. SummaryScenario classification of NFD is a means for simplifying the search for multifactorial disease triggers, and may be helpful in predicting prognosis and response to therapy. The technique of dual immunolabeling, although not yet fully characterized as a diagnostic test, may provide a sensitive and specific method of diagnosis, as well as a starting point in the investigation of other cutaneous fibrosing disorders. The postulate that NFD may represent a systemic disorder mediated by aberrantly functioning circulating fibroblast precursor fibrocytes is explored.

Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy).

Purpose of reviewNephrogenic systemic fibrosis, also known as nephrogenic fibrosing dermopathy, was first documented in 1997 as a scleroderma-like fibrosing entity of the skin in association with renal insufficiency. Rheumatologists, along with other specialists, may be the first to encounter these patients; and both a familiarity with the disorder and vigilance for its cardinal features is in order. This review provides an update and highlights recent theories, achievements and ongoing research in understanding this emerging and enigmatic disorder. Recent findingsClinical reports support the evidence of nephrogenic systemic fibrosis as a systemic disease and emphasize an increase in its recognition in the United States, Europe and Asia. The most recent work supports a model whereby circulating fibrocytes together with fibrogenic factors lead to the evolution of this disabling and sometimes fatal disorder. SummaryWhile a specific cause of nephrogenic systemic fibrosis remains to be established, the pathogenesis seems to be multifactorial, with the postulated involvement of the circulating fibrocytes. Recent published data including information from the Yale University NSF Registry has shed light on the clinical spectrum, cause, pathogenesis and treatment options. Clinical awareness of nephrogenic systemic fibrosis is still emerging and future studies are warranted to clarify its etiopathogenesis and effective therapies.

Clinical and histological findings in nephrogenic systemic fibrosis

Nephrogenic systemic fibrosis (NSF) is a relative newcomer to the world of medicine. NSF was introduced just over 10 years ago as nephrogenic fibrosing dermopathy, but with further investigation, its systemic nature was determined. The strict adherence to a definition requiring both clinical and pathological concordance has allowed for careful separation of this entity from other fibrosing disorders, leading eventually to the realization that gadolinium-based contrast agents were closely associated with its onset. As planned prospective studies get underway, it is of paramount importance that researchers and clinicians realize that NSF remains a very challenging diagnosis, and that both clinical and histopathological criteria must be employed to reach the most accurate diagnosis possible.

Solitary fibrous tumor of the skin.

Solitary fibrous tumor (SFT) is an uncommon mesenchymal tumor that typically arises in the pleural cavity. Comprised of spindled cells characteristically arranged in diverse architectural patterns, SFT histologically simulates a variety of benign and malignant mesenchymal tumors. The diagnosis of SFT has been refined by the availability of newer immunohistochemical markers such as CD-34 and factor XIIIa, facilitating the identification of SFTs arising in multiple extrapleural sites, including the skin. We describe three cases of primary cutaneous SFT, review the literature, and discuss the histologic and immunohistochemical differential of other cutaneous tumors that SFT can mimic.

Nephrogenic systemic fibrosis: early recognition and treatment.

Nephrogenic systemic fibrosis (NSF) is a progressive, debilitating, and emotionally distressing disease that can affect patients with renal dysfunction. Prevention, early recognition and early treatment are essential to limiting its impact. The most significant risk factors for developing NSF are chronic or significant acute kidney disease (usually necessitating dialysis) and the administration of gadolinium‐containing contrast agents (GCCA). Early symptoms include swelling, redness, pruritus, and pain in the limbs, sometimes with muscle weakness. Early signs are edema, erythema, and occasionally palpable warmth of the involved extremities; there may be florid scleral telangiectasia resembling conjunctivitis. We must redouble our efforts to avoid the administration of GCCA to patients with renal insufficiency. The most effective treatment for NSF to date is maximization of renal function via medical therapy or transplantation. There are data to support a beneficial effect from extracorporeal photopheresis, and all patients can gain from physical therapy.

Nephrogenic Systemic Fibrosis: An Overview

In 1997, a new fibrosing skin disorder became apparent among patients with renal disease. Nephrogenic systemic fibrosis, as this disorder has come to be known, has recently been tied to the administration of contrast agents containing gadolinium. This overview examines the discovery and elucidation of the major research accomplishments to date. It was presented as the keynote address at the First Annual Scientific Symposium on Nephrogenic Systemic Fibrosis and MRI Contrast, conducted at Yale University on May 4, 2007.

Nephrogenic systemic fibrosis: a case series suggesting gadolinium as a possible aetiological factor

Nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy is a rare fibrotic condition that presents in patients with a history of renal disease. The aetiology is unknown, but it has recently been proposed that gadolinium, a paramagnetic contrast agent, may be a trigger of this disease. We report three patients with NSF with a history of use of gadolinium in magnetic resonance angiography a few weeks before the onset of symptoms. In the future, gadolinium should probably be avoided as much as possible in renal insufficiency patients until its role in the development of NSF is clarified.

Nephrogenic systemic fibrosis: an emerging threat among renal patients.

Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy, is a scleroderma‐like disease of the skin observed in patients with renal insufficiency. Since its recognition in 1997, relatively little has been published in the nephrology literature, despite indications that the disorder is becoming increasingly recognized in the United States and abroad. As nephrology professionals may be the first to encounter newly developing cases of NSF, it becomes imperative that they be able to recognize the symptoms and comorbidities and initiate tests and treatment. To date, the cause of NSF has not been established. Recent observations indicate that specific cells normally involved in wound repair and tissue remodeling may be aberrantly recruited to the skin and soft tissues of NSF patients.

Cellular digital fibromas: distinctive CD34-positive lesions that may mimic dermatofibrosarcoma protuberans.

Background:  Digital fibromas are common benign acral tumors typically reported as angiofibromas (AFs) or acquired digital fibrokeratomas (ADFs). Cellular variants are not well recognized.