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Shawn Cowper, MD

Professor of Dermatology

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Shawn Cowper, MD

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Mailing Address

  • Dermatology

    PO Box 208059

    New Haven, CT 06520-8059

    United States

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Research Summary

Nephrogenic systemic fibrosis (NSF) is a disease marked by skin stiffening in the setting of a patient with kidney disease. The disease has been linked with MRI Contrast Agents. There is no evidence to suggest that patients without kidney disease can develop NSF.

Evidence gathered through our primary research efforts was presented to the Food and Drug Administration, which later modified labeling and warnings on MRI contrast agents to reflect the risk. The result has been a near disappearance of new cases of NSF since the warnings went into place. In addition the FDA accelerated approval of less-risky contrast agents, allowing for the introduction of new products in the US which, to date, have not proven to carry the same risks for NSF as the earlier generation of MRI contrast agents.

One outcome of this victory is that my primary research has necessarily shifted to other topics in fibrosis. While I am still very interested in learning about putative new cases of NSF, I have (thus far) been convinced that NSF may be a former disease, rather than a current one.

Specialized Terms: Alopecia; Cutaneous lymphoma; Pathology informatics; Nephrogenic fibrosing dermopathy; Nephrogenic systemic fibrosis

Extensive Research Description

Nephrogenic Systemic Fibrosis and its relevance in other fibrosing disorders

My initial research interest (from 1999 to 2010) was in the mechanism of nephrogenic systemic fibrosis (formerly nephrogenic fibrosing dermopathy). This was an emerging fibrosing disorder seen in patients with renal disease. Compelling epidemiological, microanalytical, and animal studies linked the disease to the use of gadolinium-based contrast agents (GBCA) used in MRI imaging. Evidence presented to the US FDA led to changes in contrast agent labeling as well as accelerated approval of less risky GBCAs. Because of these interventions, NSF has essentially disappeared.

The mechanism of fibrosis induction in NSF remains of interest as it may offer insights into pathways activated in other fibrosing conditions. Current thinking continues to suggest that these renally-excreted compounds are ineffectively removed in the renally-impaired, leading to a novel toxicity reaction. The findings manifest themselves most dramatically in the skin and soft-tissue of affected patients by increased production of matrix elements (collagen, elastin, mucin). These excess components reduce the flexibility and compliance of skin, leading to decreased range of motion in affected limbs. Questions still being examined include effects in non-cutaneous tissues and factors that may contribute to a propensity to develop NSF (genetic, medical cofactors, other toxicities, etc).
Yale remains the home of the International NSF Registry, housing clinical records and pathology specimens from nearly 400 NSF patients. This registry serves as a source of basic information for investigations into the clinical and histological aspects of NSF.

Yale is also the home base for a core of interested clinical and basic science researchers actively engaged in understanding all aspects of fibrosis. Periodically, this team hosts the Yale Fibrosis Symposium.


Dermatohematopathology and Alopecia

Beyond NSF, I am interested in cutaneous lymphomas and alopecias, and the appropriate use of histopathology in diagnosing these disorders. I regularly speak and teach on the topic of the biopsy diagnosis of alopecia and have created a four hour curriculum on the topic that is part of the basic education of dermatology residents at Yale. In addition, specialized in-depth training on this topic is provided to Yale dermatopathology fellows. Lastly, I have coauthored a book on the subject and look forward to spearheading the next edition of this book in the near future.

The birth of pathology informatics and "virtual" slides

My primary and preferred instructional tool is the networked computer. I have been involved with web-based pathology education for some time. My largest project Pathmax, was one of the first web-based resource for pathology professionals on the internet. Beginning in 1997, this site ran continuously until 2018. I am also one of the cofounders of the Dermatopathology Master Class Series, a web-based streaming lecture series on topics of relevance in dermatopathology. In recent years I have been the chairman of the Virtual Slide Library of the American Society of Dermatopathology (ASDP) where I manage 50 volunteers interested in optimizing and vetting over 10,000 scanned dermatopathology whole slide images. This virtual library serves as one of the core teaching tools of the ASDP.

Coauthors

Research Interests

Alopecia; Dermatology; Fibrosis; Medical Informatics; Pathology; Scleroderma, Systemic; Skin Neoplasms; Nephrogenic Fibrosing Dermopathy

Research Images

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An indurated erythematous leg from a patient with NSF

Selected Publications

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