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Nephrogenic Fibrosing Dermopathy: Suspect Identified, Motive Unclear

Cowper, Shawn E. MD; Bucala, Richard MD, PhD

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The American Journal of Dermatopathology: August 2003 - Volume 25 - Issue 4 - p 358

To the Editor:

Nephrogenic fibrosing dermopathy (NFD), a fibrosing disorder of renal patients, was thoroughly defined as a clinical and histopathological entity in this journal in 2001. 1 Since then, several case reports 2–4 have been published, and scores of reports have been histopathologically confirmed and tracked in the NFD Registry at Yale University. 5

While no cases of NFD have been reported in persons with normal renal function, a specific cause has yet to be elucidated. Clues in that comprehensive report, however, have led to some intriguing theories that are currently under investigation.

The remarkable resemblance to wound healing, and the expression of CD34 and procollagen markers in the majority of dermal spindle cells piqued the interest of investigators in the rheumatologic community, who suggested that the cells may be a CD34+/procollagen+ population. With dual staining techniques, this theory has been borne out, and a new suspect has been identified (Fig. 1).

Double immunoperoxidase staining for CD34 (brown) and procollagen (red) shows staining for CD34 is most marked along the dendritic processes while that for procollagen is localized to the cytoplasm.

Circulating fibrocytes are collagen+/CD34+ cells that are involved in wound repair and tissue remodeling. When isolated from blood, they express markers of both connective tissue cells and circulating leukocytes, hence the appellation “fibrocyte”. While most dermatopathologists are unfamiliar with this cell, those in the research community have been characterizing it since it was first described in 1994. 6 Fibrocytes enter sites of inflammation and tissue injury, secrete growth factors and cytokines, and contribute to connective tissue matrix production. In experimental studies, fibrocytes have been found to localize to dermal scars and to granulomas, and they have the capacity to present antigens to T cells. 7,8

Besides dual positivity for collagen and CD34, several other clues suggest circulating fibrocytes may, in fact, be involved in NFD: (1) the symmetry of lesions suggests a circulating (intrinsic) factor is involved, (2) the rapidity of development of lesions (with concurrent absence of mitotic figures among the spindle cells) suggests the recruitment of a blood-borne cell, (3) the concurrence of histiocytes in varying proportions in the infiltrate suggests a common origin for these cells (circulating fibrocytes are known to differentiate from monocytic precursors under certain conditions), 9 (4) the cellular composition of an active case of NFD closely resembles a wound healing reaction (including angiogenesis), 10 and (5) the resolved lesions of NFD are histologically indistinguishable from those of a healed wound.

While complete substantiation of this theory is lacking, the clues are sufficient to promote further research into this possible disease mechanism. The originally described circulating fibrocyte, if confirmed in the etiopathogenesis of disease, may be considered in this context to be a dermal, “differentiated” fibrocyte.

Shawn E. Cowper, MD

Richard Bucala, MD, PhD


1. Cowper SE, Su LD, Bhawan J, et al. Nephrogenic fibrosing dermopathy. Am J Dermatopathol. 2001; 23:383–393.
2. McNeill AM, Barr RJ. Scleromyxedema-like fibromucinosis in a patient undergoing hemodialysis. Int J Dermatol. 2002; 41:364–367.
3. Mackay-Wiggan JM, Cohen DJ, Hardy MA, et al. Nephrogenic fibrosing dermopathy (scleromyxedema-like illness of renal disease). J Am Acad Dermatol. 2003; 48:55–60.
4. Streams BN, Liu V, Liegeois N, et al. Clinical and pathological features of nephrogenic fibrosing dermopathy. J Am Acad Dermatol. 2003; 48:42–47.
5. Cowper SE. Nephrogenic Fibrosing Dermopathy [NFD web site]. 2001. Available at Accessed May 6, 2003.
6. Chesney J, Bucala R. Peripheral blood fibrocytes, mesenchymal precursor cells and the pathogenesis of fibrosis. Curr Rheumatol Rep. 2000; 2:501–505.
7. Chesney J, Metz C, Stavitsky AB, et al. Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes. J Immunol. 1998; 160:419–425.
8. Chesney J, Bacher M, Bender A, et al. The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T-cells in situ. Proc Natl Acad Sci U S A. 1997; 94:6307–6312.
9. Abe R, Donnelly SC, Peng T, et al. Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol. 2001; 166:7556–7562.
10. Hartlapp I, Abe R, Saeed RW, et al. Fibrocytes induce an angiogenic phenotype in cultured endothelial cells and promote angiogenesis. FASEB J. 2001; 15:2215–2224.
© 2003 Lippincott Williams & Wilkins, Inc.