Lee Shapiro

Linear scleroderma “en coup de sabre” (LSES) variant is a cephalic subtype of localized scleroderma that can be associated with extracutaneous stigmata, such as epilepsy, dementia syndromes, as well as focal central nervous system neurologic deficits. While the pathophysiology of cutaneous linear scleroderma includes endothelial cell injury and up regulation of pro-fibrogenic pathways, the basis of LSES-associated neurologic complications is largely unknown. We report a patient with a history of LSES who developed intractable epilepsy and cognitive decline. Magnetic resonance imaging (MRI) of the brain exhibited numerous persistently enhancing brain lesions. Due to progressive neurologic deterioration over a period of 7 years, despite interventional therapy, a brain biopsy was performed. Neuropathologic analysis exhibited acute and chronic cortical ischemia associated with a small vessel lymphocytic vasculitis. Direct immunofluorescent studies showed C5b-9 and IgG deposition on endothelium while indirect immunofluorescent studies demonstrated reactivity of the patient’s serum with the microvasculature of the patient’s own brain tissue and generic human umbilical vein endothelial cells indicative of anti-endothelial cell antibodies. Therapy focusing on damaged endothelium was implemented. The interleukin-6 (IL-6) receptor inhibitor tocilizumab was used and the patient improved dramatically, likely reflecting the drug’s effect on the replenishment of endothelial progenitor cells.

The malignant form of atrophic papulosis (Köhlmeier-Degos disease) is a rare thrombo-occlusive vasculopathy that can affect multiple organ systems. Patients typically present with distinctive skin lesions reflective of vascular drop out. The small bowel is the most common internal organ involved, resulting in considerable morbidity and mortality attributable to ischemic microperforations. Determination of the presence of gastrointestinal lesions is critical in distinguishing systemic from the benign, cutaneous only disease and in identifying candidates for treatment. We describe an 18 year old male who first presented with cutaneous atrophic papulosis but became critically ill from small bowel microperforations. He had an almost immediate and dramatic response to treatment. Prior to his presentation with acute abdomen he had upper and lower endoscopy showing areas of nonspecific patchy erythema. At laparotomy, innumerable characteristic lesions with central pearly hue and erythematous border were seen. PubMed was used for a literature search using the keywords malignant atrophic papulosis, Degos disease, endoscopy, laparoscopy and laparotomy. This search yielded 200 articles which were further analyzed for diagnostic procedures and findings. Among the 200 articles we identified only 11 cases in which endoscopy was performed. Results of endoscopy and laparotomy in our patient with malignant atrophic papulosis were compared to those in the literature. Endoscopy of the gastrointestinal tract has shown gastritis and non-specific inflammation whereas laparoscopy shows white plaques with red borders on the serosal surface of the small bowel and the peritoneum. From personal communications with other physicians worldwide, we identified three additional unpublished cases in which endoscopy revealed only minimal changes while laparoscopy showed dramatic lesions. From our experience the endoscopic findings are often subtle and nonspecific, whereas laparascopy or laparotomy will reveal pathognomic lesions on the serosal surface of the intestine. Our report contrasts the endoscopic and laparoscopic findings in malignant atrophic papulosis which suggest laparoscopy is the more powerful means of detecting gastrointestinal involvement. Imaging studies may serve as a key indicator of systemic progression. Based on our experience, laparoscopy should be performed when there is a high index of suspicion for gastrointestinal malignant atrophic papulosis, even if endoscopic examination is non-diagnostic or normal.

Malignant atrophic papulosis (Köhlmeier-Degos disease; MAP) is an uncommon endotheliopathy with pathological findings similar to the vascular lesions of systemic sclerosis. These two disorders can overlap. When associated with visceral lesions, MAP has been considered almost universally and rapidly fatal. A recent report described dramatic response to treatment with eculizumab, but disease progression after initial response to therapy has occurred.

Degos disease is a frequently fatal and incurable occlusive vasculopathy most commonly affecting the skin, gastrointestinal tract and brain. Vascular C5b-9 deposition and a type I interferon (IFN) rich microenvironment are held to be pathogenetically important in the evolution of the vascular changes. We recently discovered the use of eculizumab as a salvage drug in the treatment of near fatal Malignant atrophic papulosis (MAP). The effects of eculizumab on the pathology of MAP are explored.