A case of Degos disease: demonstration of C5b-9-mediated vascular injury

Umemura, Masayu; Miwa, Yusuke; Yanai, Ryo; Isojima, Sakiko; Tokunaga, Tohru; Tsukamoto, Hiroyuki; Takahashi, Ryo; Yajima, Nobuyuki; Kasama, Tsuyoshi; Takahashi, Nanako; Sueki, Hirohiko; Yamaguchi, Sayaka; Arai, Kumiko; Takeuchi, Yoji; Ohike, Nobuyuki; Norose, Tomoko; Yamochi-Onizuka, Toshiko; Takimoto, Masafumi

doi:10.3109/14397595.2013.874761

Cited by 8 publications

(4 citation statements)

References 10 publications

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“…High levels of interferons administered exogenously as a therapeutic agent can be directly damaging to the endothelium and are known to result in TMA. [43][44][45][46][47] BK virus has been shown to trigger high interferon-g production in renal transplant recipients and also to be associated with an increased risk of complement mediated TA-TMA in HSCT recipients. 48 In addition, BK virus can directly injure endothelial cells and promote release of interferon-g. 49 Inflammatory cytokines like IL-6, IL-8, and interferong are also released from circulating activated T cells, NK cells, monocytes, and tissue macrophages as a result of BK virus infection, GVHD and in disorders like hemophagocytic lymphohistiocytosis, with high interferon production resulting in thrombotic microangiopathy.…”

Section: Discussionmentioning

confidence: 99%

Interferon-complement loop in transplant-associated thrombotic microangiopathy

et al. 2020

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Transplant-associated thrombotic microangiopathy (TA-TMA) is an important cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The complement inhibitor eculizumab improves TA-TMA, but not all patients respond to therapy, prompting a search for additional targetable pathways of endothelial injury. TA-TMA is relatively common after HSCT and can serve as a model to study mechanisms of tissue injury in other thrombotic microangiopathies. In this work, we performed transcriptome analyses of peripheral blood mononuclear cells collected before HSCT, at onset of TA-TMA, and after resolution of TA-TMA in children with and without TA-TMA after HSCT. We observed significant upregulation of the classical, alternative, and lectin complement pathways during active TA-TMA. Essentially all upregulated genes and pathways returned to baseline expression levels at resolution of TA-TMA after eculizumab therapy, supporting the clinical practice of discontinuing complement blockade after resolution of TA-TMA. Further analysis of the global transcriptional regulatory network showed a notable interferon signature associated with TA-TMA with increased STAT1 and STAT2 signaling that resolved after complement blockade. In summary, we observed activation of multiple complement pathways in TA-TMA, in contrast to atypical hemolytic uremic syndrome (aHUS), where complement activation occurs largely via the alternative pathway. Our data also suggest a key relationship between increased interferon signaling, complement activation, and TA-TMA. We propose a model of an “interferon-complement loop” that can perpetuate endothelial injury and thrombotic microangiopathy. These findings open opportunities to study novel complement blockers and combined anti-complement and anti-interferon therapies in patients with TA-TMA and other microangiopathies like aHUS and lupus-associated TMAs.

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Section: Discussionmentioning

confidence: 99%

Interferon-complement loop in transplant-associated thrombotic microangiopathy

et al. 2020

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“…MAP vascular diseases include thrombotic microangiopathies targeting capillaries and venules and stenotic fibrointimal arteriopathy involving small and medium arteries ( 20 , 21 ). One possibility for the thrombotic mechanism in MAP is the increased intima-media thickness (IMT), as it is currently seen in other microthrombotic diseases like antiphospholipid syndrome ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Malignant atrophic papulosis treated with eculizumab and hirudin: a fatal case report and literature review

Yu,

Wang,

Tang

et al. 2024

Front. Cardiovasc. Med.

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BackgroundMalignant atrophic papulosis (MAP) is a rare obliterative vasculopathy whose etiology and pathophysiological mechanisms remain unknown, and the treatment is still empirical. It can involve multiple systems, especially the gastrointestinal tract and central nervous system, and has a poor prognosis.Case presentationA 20-year-old Chinese male appeared to have Widespread atrophic papules and plaques, intermittent abdominal pain, recurrent bowel perforation, and psoas abscess. The clinical diagnosis of MAP was supported by skin biopsy. He was then treated with anticoagulants, antiplatelets, glucocorticoids, and immunosuppressants and started on eculizumab and hirudin after the first surgical interventions. Despite the aggressive immunosuppression, anticoagulant, antiplatelet, humanized monoclonal antibodies, and surgery therapy, he died five months after presentation.ConclusionsMAP is an extremely rare obliterative vasculopathy manifesting as benign cutaneous involvement or potentially malignant systemic involvement. MAP patients who exhibit any abdominal symptoms should undergo laparoscopy and evaluation in time and start on eculizumab and treprostinil as soon as possible, as the combination of them is presently the most effective treatment option for gastrointestinal MAP and hopefully reduce mortality.

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“…Deaths from gastrointestinal K-D resulted from recurrent bowel perforation, with hemorrhage, hypotension, and sepsis. In our review, 59% (19/32) of those with gastrointestinal perforations died of sepsis or severe peritonitis [ 2 , 4 – 6 , 10 , 15 , 17 , 19 , 20 , 24 , 27 , 30 , 31 , 55 ].…”

Section: Treatmentmentioning

confidence: 99%

Gastrointestinal Kohlmeier–Degos disease: a narrative review

Sattler

Magro

Shapiro

et al. 2022

Orphanet J Rare Dis

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Introduction Kohlmeier-Degos (K-D) disease is a rare obliterative vasculopathy that can present as a benign cutaneous form or with potentially malignant systemic involvement. The gastrointestinal tract is most frequently involved in systemic disease and mortality is often related to bowel perforations. Herein, we provide information to providers and patients regarding gastrointestinal K-D symptomology, pathology, treatment, and diagnosis, with a focus on the importance of timely diagnostic laparoscopy. We present three new cases of gastrointestinal K-D to highlight varying disease presentations and outcomes. Body Based on reviewed reports, perforation is preceded by at least one gastrointestinal symptom: abdominal pain/cramping, anorexia/weight loss, vomiting, diarrhea, nausea, gastrointestinal bleeding, obstipation, constipation, and abdominal fullness. Perforation most commonly occurs in the small intestine and often results in sepsis and death. Although underutilized, laparoscopy is the most sensitive and specific diagnostic technique, demonstrating serosal porcelain plaques similar to those on the skin and characteristic for K–D. The combination of eculizumab and treprostinil is presently the most effective treatment option for gastrointestinal K–D. The pathology of gastrointestinal K-D is characterized by an obliterative intimal arteriopathy eventuating in occlusive acellular deposits of mucin and collagen along with an extravascular pauci-cellular sclerosing process resembling scleroderma confined to the subserosal fat. C5b-9 and interferon-alpha are both expressed in all caliber of vessels in the affected intestine. While C5b-9 blockade does not prevent the intimal expansion, enhanced type I interferon signaling is likely a key determinant to intimal expansion by, causing an influx of monocytes which transdifferentiate into procollagen-producing myofibroblast-like cells. Conclusion Prompt laparoscopic evaluation is necessary in any K–D patient with an abdominal symptom to facilitate diagnosis and treatment initiation, as well as to hopefully decrease mortality. Those with gastrointestinal K–D should start on eculizumab as soon as possible, as onset of action is immediate.

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A case of Degos disease: demonstration of C5b-9-mediated vascular injury

Cited by 8 publications

References 10 publications

Interferon-complement loop in transplant-associated thrombotic microangiopathy

Interferon-complement loop in transplant-associated thrombotic microangiopathy

Malignant atrophic papulosis treated with eculizumab and hirudin: a fatal case report and literature review

Gastrointestinal Kohlmeier–Degos disease: a narrative review

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