Pyoderma gangrenosum‐like necrotizing panniculitis associated with alpha‐1 antitrypsin deficiency: a lethal course

Vigl, Kornelia; Itzinger-Monshi, Babak; Vujic, Igor; Rappersberger, Klemens

doi:10.1111/ddg.12830

Cited by 10 publications

(14 citation statements)

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“…augmentation therapy with the alpha-1 proteinase inhibitor Prolastin ® (60 mg/kg every other weeks) [2][3][4][5][6]. On this regimen, there was rapid clinical improvement with respect to the swelling of the extremities and gradual stabilization of the perianal inflammatory process.…”

Section: Correspondence Clinical Lettermentioning

confidence: 99%

Disseminated panniculitis with subcutaneous abscesses and fat necrosis associated with alpha‐1 antitrypsin deficiency

Schöfl

Koch‐Thalhammer

Jabkowski

et al. 2020

J Deutsche Derma Gesell

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Section: Correspondence Clinical Lettermentioning

confidence: 99%

Disseminated panniculitis with subcutaneous abscesses and fat necrosis associated with alpha‐1 antitrypsin deficiency

Schöfl

Koch‐Thalhammer

Jabkowski

et al. 2020

J Deutsche Derma Gesell

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“…Although other locally acting elastase inhibitors (e.g., secretory leukocyte SLPI and elafin) provide some protection against NE and PR3 in humans, only decreased levels of plasma a1PI are known to be associated with chronic diseases. Gene mutations in a1PI with reduced inhibitory plasma levels frequently cause emphysema and COPD, more rarely cause liver disease (Duvoix et al, 2014), and occasionally cause a skin disease presenting as necrotizing panniculitis (Vigl et al, 2015). a1PI dysfunction has also been associated with an increased risk of ANCA-associated vasculitis (Mahr et al, 2010).…”

Section: Proteinase 3-targeting Inhibitors and Antibodies As Theramentioning

confidence: 99%

Inhibitors and Antibody Fragments as Potential Anti-Inflammatory Therapeutics Targeting Neutrophil Proteinase 3 in Human Disease

Korkmaz¹,

Lesner²,

Guarino³

et al. 2016

Pharmacol Rev

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Proteinase 3 (PR3) has received great scientific attention after its identification as the essential antigenic target of antineutrophil cytoplasm antibodies in Wegener's granulomatosis (now called granulomatosis with polyangiitis). Despite many structural and functional similarities between neutrophil elastase (NE) and PR3 during biosynthesis, storage, and extracellular release, unique properties and pathobiological functions have emerged from detailed studies in recent years. The development of highly sensitive substrates and inhibitors of human PR3 and the creation of PR3-selective single knockout mice led to the identification of nonredundant roles of PR3 in cell death induction via procaspase-3 activation in cell cultures and in mouse models. According to a study in knockout mice, PR3 shortens the lifespan of infiltrating neutrophils in tissues and accelerates the clearance of aged neutrophils in mice. Membrane exposure of active human PR3 on apoptotic neutrophils reprograms the response of macrophages to phagocytosed neutrophils, triggers secretion of proinflammatory cytokines, and undermines immune silencing and tissue regeneration. PR3-induced disruption of the anti-inflammatory effect of efferocytosis may be relevant for not only granulomatosis with polyangiitis but also for other autoimmune diseases with high neutrophil turnover. Inhibition of membrane-bound PR3 by endogenous inhibitors such as the alpha-1-protease inhibitor is comparatively weaker than that of NE, suggesting that the adverse effects of unopposed PR3 activity resurface earlier than those of NE in individuals with alpha-1-protease inhibitor deficiency. Effective coverage of PR3 by anti-inflammatory tools and simultaneous inhibition of both PR3 and NE should be most promising in the future

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“…Given that these disorders are characterized by a dysregulation of the innate immune system, this has opened up new therapeutic approaches, such as the use of certain biologics (TNFα inhibitors, IL‐1β antibodies). Experimental studies have demonstrated Th1‐weighted overexpression of interleukin (IL)‐1β, IL‐1α, tumor necrosis factor‐α (TNFα), IL‐6, IL‐8, IL‐17, IL‐23, IL‐36α, CXCL1/2/3, RANTES, and Fas ligands .…”

Section: Introductionmentioning

confidence: 99%

Treatment options for pyoderma gangrenosum

Quist

Kraas

2017

J Deutsche Derma Gesell

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SummaryPyoderma gangrenosum (PG) is an orphan disease. While research on such disorders is based on only few randomized multicenter as well as retrospective studies, most of the data comes from case series of small patient groups. Apart from topical and intralesional therapeutic options for early stages and mild disease courses, treatment predominantly involves systemic therapeutic agents. Besides systemic corticosteroids and cyclosporine A (CsA), options also include intravenous immunoglobulins (IVIG) and biologics such as the TNF α inhibitors infliximab, adalimumab, and etanercept; the interleukin (IL) 12/23 antibody ustekinumab; the IL-1 receptor antagonist anakinra; and the IL-1 β antibody canakinumab. The best evidence-based study data is available for CsA, prednisolone, and infliximab; the latter especially in patients with concomitant ulcerative colitis or Crohn's disease. A response to IVIG and canakinumab has been reported in smaller case series. First described by Brocq almost 100 years ago, it was soon recognized that PG did in fact require treatment. To this day, however, such treatment remains a clinical challenge. Despite the severe -albeit rare -clinical picture, improvement in therapeutic options may be expected in the future, primarily due to further clinical studies -especially with a greater number of patients, a better understanding of the etiopathogenesis, as well as the use of modern targeted therapies with higher efficacy and a lower rate of side effects than conventional immunosuppressants such as prednisolone and CsA.

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Pyoderma gangrenosum‐like necrotizing panniculitis associated with alpha‐1 antitrypsin deficiency: a lethal course

Cited by 10 publications

References 0 publications

Disseminated panniculitis with subcutaneous abscesses and fat necrosis associated with alpha‐1 antitrypsin deficiency

Disseminated panniculitis with subcutaneous abscesses and fat necrosis associated with alpha‐1 antitrypsin deficiency

Inhibitors and Antibody Fragments as Potential Anti-Inflammatory Therapeutics Targeting Neutrophil Proteinase 3 in Human Disease

Treatment options for pyoderma gangrenosum

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