Nephrogenic Systemic Fibrosis Workup

Updated: Sep 18, 2020
  • Author: Shawn Cowper, MD; Chief Editor: Dirk M Elston, MD  more...
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Laboratory Studies

Scleromyxedemalike skin lesions occur without associated paraproteinemia. Serum protein electrophoresis and immunoelectrophoresis results are negative.

Nephrogenic systemic fibrosis (NSF) occurs in the setting of renal disease. Thus, abnormal values of BUN and creatinine are typically present.

Thyroid studies produce normal findings in patients with nephrogenic systemic fibrosis.

In rare cases, peripheral eosinophilia has been noted.

In some cases, a positive antinuclear antibody test result has been reported.

Some patients with nephrogenic systemic fibrosis have anticardiolipin or antiphospholipid antibodies.

Rheumatoid factor and other autoantibodies are typically absent.

Many patients have an associated hypercoagulable state.

Some patients have hepatitis B or C.

In summary, no particular laboratory abnormality is consistently linked to nephrogenic systemic fibrosis.


Imaging Studies

No imaging study is indicated to assess nephrogenic systemic fibrosis. However, although no imaging study is indicated to assess nephrogenic systemic fibrosis, many authors have described soft tissue calcifications.


Other Tests

Abnormalities of nerve conduction have been described in some patients.

Thakral and Abraham [60] developed an automated quantitative scanning electron microscopy and energy dispersive x-ray spectroscopy method for documenting gadolinium in tissue of patients with nephrogenic systemic fibrosis. They examined, under standardized conditions, freshly cut tissue in paraffin block using the variable pressure mode. This allowed them to perform a random search of the tissue area to conduct in situ detection and semiquantitative morphometric (volumetric) analysis of insoluble, higher–atomic number features using backscattered electron imaging.

Paraffin-embedded tissue, lesional, nonlesional, and fresh tissue, as well as serum, can all show elevated levels of gadolinium in nephrogenic systemic fibrosis. [61]

Thakral and Abraham detected gadolinium ranging from 1-2270 cps/mm2 in 57 cutaneous biopsy specimens of nephrogenic systemic fibrosis. Gadolinium was associated with phosphate, calcium, and sodium in the tissues. This method reproducibly determines the elemental composition, relative concentration, and spatial distribution of detected features within the tissue; however, they could not detect features below their spatial resolution or concentrations below the detection limit of the scanning electron microscopy and energy dispersive x-ray spectroscopy system.



A skin biopsy is indicated for this condition. A deep biopsy, such as an incisional biopsy or a deep punch biopsy, should be performed. A sample of dermis, subcutaneous fat, and fascia should be obtained, if possible.


Histologic Findings

In 2001, Cowper et al [38] described the unique histopathologic features of nephrogenic systemic fibrosis, specifically, thickened collagen bundles with surrounding clefts, mucin deposition, and a proliferation of fibroblasts and elastic fibers.

Early lesions (within 20 wk of clinic onset) demonstrate reticular, dermal, large, and epithelioid or stellate spindle cells. These cells can extend into and widen the subcutaneous fat lobule septa. The spindle cells are diffusely arranged among thickened collagen bundles.

Clefts can encompass some spindle cells. Most of the spindle cells are CD34/procollagen dual-positive cells that form a dense interconnecting network.

Because this condition is not commonly reported, diagnostic errors abound. Spindle cell proliferation can be confused with dermatofibrosarcoma protuberans or even spindle cell melanoma. Alcian blue, mucicarmine, or Movat pentachrome stains can be used to detect variable amounts of mucin. Thick elastic fibers oriented parallel to collagen bundles are usually present.

Some cases of nephrogenic systemic fibrosis have manifested with a scant superficial and deep lymphocytic infiltrate, although inflammation is usually absent, and this finding should prompt consideration of an alternative diagnosis. Multinucleated cells positive for CD68 and factor XIIIa–positive cells are commonly present.

Late lesions (>20 wk of clinical onset) typically have less prominent clefting, less mucin, and fewer CD34/procollagen–positive cells. Calcification, which is described in some patients and which has been interpreted as dystrophic in nature, can be present.

Histopathologically, nephrogenic systemic fibrosis resembles scleromyxedema in that it manifests with a proliferation of dermal fibroblasts and dendritic cells, thickened collagen bundles, increased elastic fibers, and mucin deposition. Tram tracking of CD34+ dendrocytes is noted on either side of elastic fibers. Osteoid may form around elastic fibers (lollipop bodies). See the images below.

Osteoid in dermis. Courtesy of Dirk M Elston, MD. Osteoid in dermis. Courtesy of Dirk M Elston, MD.
Hypercellular dermis. Courtesy of Dirk M Elston, M Hypercellular dermis. Courtesy of Dirk M Elston, MD.
Lollipop bodies (osteoid with protruding elastic f Lollipop bodies (osteoid with protruding elastic fibers). Courtesy of Dirk M Elston, MD.