Magro, C, Xuan, W., Shapiro, L., et al (2013) The Effects of Eculizumab on the Pathology of Degos Disease. Orphanet Journal of Rare Diseases, in press.
Chung, L., Shapiro, L., Fiorentino, D., et al. (2009) MQX, A Novel Formulation of Nitroglycerin, Improves Severity of Raynaud's Phenomenon: A randomized, Controlled Trial. Arthritis and Rheumatism 60: 870-877
Magro, C, Kim, C, Shapiro, L et al (2011) Degos Disease: A C5B-9/Interferon Alpha Mediated Endothelipathy Syndrome. American Journal of Clinical Pathology, in press.
Garrett-Bakelman, F, Magro, C, Toledo-Garcia, A, Shapiro, L, Desancho, M (2011) Primary Degos Disease: A C5B-9 Mediated Microvascular Injury Syndrome Effectively Treated with Eculizumab.
Submitted to New England Journal of Medicine.
Shapiro, L, Farrell, J, Borhani-Haghighi, A. (2012) Tocilizumab treatment of neuro-Behcet's., the first
Report. In Press, Clinical Neurology and Neurosurgery
Toledo, A, Cavaliere, L, Carlson, J, White, C., Shapiro, L. Degos Disease: Possible Lessons for Scleroderma Treatment . Presented at the 11th International Workshop on Scleroderma Research, Boston, Massachusetts, 2010.
Polito, J., Toledo A, Shapiro, L. Early Detection of Systemic Degos Disease (DD) or Malignant Atrophic Papulosis May Increase Survival. Presented at annual meeting of the American College of Gastroenterology, San Antonio, Texas, 2010.
Shapiro, L, Toledo, A, Farrell, J. Effective Treatment of Degos Disease with Trepostinil: Early Experience, accepted for presentation at 2nd Systemic Sclerosis World Congress, 2012.
Degos Disease, possible lessons for Scleroderma treatment?
A.E. Toledo¹, L. F. Cavaliere¹, J.A. Carlson¹, C. Whyte¹, L.S. Shapiro². ¹ Albany Medical College, ²The Center for Rheumatology, Albany, NY
Background: Degos Disease (DD) or Malignant Atrophic Papulosis (MAP) is a rare thrombo occlusive vasculopathy with increased deposition of C5b-9 deposition in affected tissues. Small vessel obliterative vasculopathy is a shared feature of MAP and Scleroderma. Increased C5b-9 deposition in tissue has also been seen in Scleroderma. This similarity might significantly influence future treatment for Scleroderma patients with Degos like lesions. We wish to present two patient histories, one with DD and a second one with Scleroderma, SLE overlap with new onset DD like lesions. The first patient was febrile, hypertensive, tachycardic and had required laparotomy for acute abdomen with evidence of perforation and peritonitis. After the first dose of eculizumab was given he immediately showed signs of improvement, vital signs normalized; eventually was discharged home and he restarted school. Eculizumab is a monoclonal Antibody against C5, which prevents C5b-9 deposition in tissues. The classical evolution of Systemic DD is death from repeated small bowel perforation within two to three years. It almost always presents with quite characteristic cutaneous lesions. On histology the lesions look similar independent of the organ involved. The CNS, pericardium and other organs have been affected to a lesser degree. There are about 200 cases reported in the literature and there are a few cases with Scleroderma and DD like lesions proven by biopsy, concomitantly in the same patient. Both diseases tend to be histologicaly pauci immune, they have been linked to a possible endotheliotropic virus triggering the complement cascade with subsequent MAC deposition and tissue destruction, along with autoantibody formation. There is evidence of ischemia in both diseases. The primary aim of this report is to compare MAP and Scleroderma with DD like lesions, with the hypothesis that that patients with scleroderma-DD overlap may benefit from C5 inhibitor therapy.
Materials and Methods: Case Reports: A 17 year old male presented with acute abdomen and a 2 year history of skin lesions typical for MAP. He had a small bowel obstruction with multiple DD like lesions seen on exploratory laparotomy. Due to peritonitis and impending perforation he went through 3 exploratory laparotomies during the same hospitalization; had abdominal compartment syndrome from severe swelling and was critically ill until the eculizumab was started. From then on very quickly and consistently he improved.
More recently a 40 year old female with a prior history of Scleroderma and lupus overlap has developed DD like lesions over the course of one year along with more recent abdominal pain which is getting progressively worse. Her systemic sclerosis was diagnosed in 2006 followed by lupus in 2009. Both diagnoses are supported by serology and biopsy. A year ago she developed pericardial effusion leading to tamponade without clear etiology. The biopsy of pericardial tissue was revised very recently and it does show evidence of a possible Degos like reaction.
Conclusion: The primary Degos patient had an immediate, dramatic and sustained response to eculizumab. The second patient displays very similar pathology but in the setting of an already diagnosed connective tissue disease. She does have C5b-9 deposition and confirmed DD like lesions on biopsy. Lessons learned from treatment of a very rare disease with similar vascular pathology may have applications to some patients with systemic sclerosis. Efforts are underway to identify patients with systemic sclerosis who may be appropriate candidates for eculizumab therapy.