Anakinra Improves Pyoderma Gangrenosum in Psoriatic Arthritis: A Case Report

Acquitter, M.; Plantin, P.; Kupfer, I.; Auvinet, Henri; Marhadour, Thierry

doi:10.7326/l15-5107

Cited by 28 publications

(12 citation statements)

References 4 publications

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“…[1][2][3] Interleukin-1 (IL-1) has been reported at high concentrations in the lesions of SS patients, and IL-1 neutralizing therapies have shown promising outcomes in SS, PG, and PG patients with psoriatic arthritis. [4][5][6][7][8][9] Coding and transcript variants of protein tyrosine phosphatase-6 (PTPN6, or Src homology region 2 domain-containing phosphatase-1, SHP1) are a feature of SS and PG, consistent with the findings that mutations in murine Ptpn6 cause spontaneous skin inflammation that is dependent on the IL-1 receptor (IL-1R), granulocyte-colony stimulating factor (G-CSF), and neutrophils. [10][11][12][13] Ptpn6 regulates the activity of more than 50 cytoplasmic signaling proteins and cell surface receptors.…”

Section: Introductionsupporting

confidence: 59%

Ptpn6 inhibits caspase-8- and Ripk3/Mlkl-dependent inflammation

Speir

Nowell²,

Chen

et al. 2019

Nat Immunol

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Ptpn6 is a cytoplasmic phosphatase that functions to prevent autoimmune and interleukin 1 receptor (IL-1R)-dependent caspase-1-independent inflammatory disease. Conditional deletion of Ptpn6 in neutrophils (Ptpn6 ΔPMN ) is sufficient to initiate IL-1R-dependent cutaneous inflammatory disease, but the source of IL-1 and the mechanisms behind IL-1 release remain unclear. Here, we investigated the mechanisms controlling IL-1α/β release from neutrophils by inhibiting caspase-8-dependent apoptosis and Ripk1-Ripk3-Mlkl-regulated necroptosis. Loss of Ripk1 accelerated disease onset, whereas combined deletion of caspase-8, and either Ripk3 or Mlkl, strongly protected Ptpn6 ΔPMN mice. Ptpn6 ΔPMN neutrophils displayed increased p38 MAP kinase-dependent Ripk1-independent IL-1 and tumor necrosis factor (TNF) production, and were prone to cell death. Together, these data emphasize dual functions for Ptpn6 in the negative regulation of p38 MAP kinase activation to control TNF and IL-1α/β expression, and in maintaining Ripk1 function to prevent caspase-8-and Ripk3-Mlkl-dependent cell death and concomitant IL-1α/β release.

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Section: Introductionsupporting

confidence: 59%

Ptpn6 inhibits caspase-8- and Ripk3/Mlkl-dependent inflammation

Speir

Nowell²,

Chen

et al. 2019

Nat Immunol

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“…Two weeks after discontinuation of etoposide therapy, the progression of both HLH and PG was noted. In March 2020, the rescue treatment with anakinra (100 mg subcutaneously once a day) was started, in addition to previous treatment with steroids and cyclosporin, as its effectiveness was reported in both PG and HLH [18][19][20][21][22][23][24][25]. However, no clinical improvement was observed and the patient's condition gradually deteriorated.…”

Section: Case Reportmentioning

confidence: 99%

Multifocal Pyoderma Gangrenosum with an Underlying Hemophagocytic Lymphohistiocytosis: Case Report and the Review of the Literature

Opalińska

Kwiatkowska

Burdacki

et al. 2021

Dermatol Ther (Heidelb)

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Pyoderma gangrenosum (PG) is an uncommon, serious, ulcerating skin disease of uncertain etiology. It manifests as a noninfectious, progressive necrosis of the skin characterized by sterile neutrophilic infiltrates. It seems to be a disorder of the immune system. PG is associated with certain underlying conditions in at least 50% of cases. Therefore, it is important to look carefully for comorbidities in every patient with PG and treat them adequately to improve the prognosis. Here, we demonstrate a 35-year-old man diagnosed with multifocal PG and hemophagocytic lymphohistiocytosis (HLH) with fatal outcome, despite combined, longterm, intensive dermatological and hematological treatment with high doses of steroids, cyclosporin, intravenous immunoglobulins (IVIG), HLH-2004 protocol with intravenously administered etoposide, and anakinra. This case is presented owing to the extremely rare coexistence of PG and HLH and the related diagnostic and therapeutic difficulties. It is also worth underlying that the diagnosis of HLH should perhaps be considered in the presence of a high percentage of double-negative T lymphocytes (DNTs) in flow cytometry, after excluding the diagnosis of lymphoma and leukemia. In this article we have also performed and present the critical literature review of local and systemic options in the management of PG lesions based on a detailed search of the PubMed database.

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“…Case reports of improvement in pustular psoriasis(40) and pyoderma gangrenosum(41) with IL-1 blockade support a role for this cytokine in their pathogenesis. A recent small randomized control trial also documented some benefit for anakinra in the treatment of hidradenitis supperativa(42)*.…”

Section: Treatment Of Autoinflammatory Diseasementioning

confidence: 97%

Anti-inflammatory panacea? The expanding therapeutics of interleukin-1 blockade

Kahlenberg

2016

Current Opinion in Rheumatology

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Purpose of review Blockade of IL-1 signaling is one of the oldest biologic therapies, yet the use of these agents is on the rise as the role of IL-1 activation is being recognized in a wide spectrum of inflammatory disorders. This review will cover established and emerging uses of IL-1 antagonism in rheumatic diseases. Recent findings Expanding off-label indications for IL-1 blockade include neutrophil-dominant skin diseases including pyoderma gangrenosum, hidradenitis supperativa, and pustular psoriasis. There is also increasing evidence for the use of IL-1 blockade in heart failure associated with rheumatic diseases. Somatic mosaicism in NLRP3 may explain the onset of later-in-life presentations of periodic fevers which are responsive to IL-1 blockade. Of importance, clinical response to anti-IL-1 therapy does not always denote protection from autoinflammatory disease complications such as macrophage activation syndrome or amyloidosis. Summary Indications for IL-1 blocking therapies will likely continue to broaden, but given the rarity of many rheumatic diseases which respond to such treatment, rigorous, large clinical trials for each indication are unlikely to occur. Thus, recommended use of these medications will often fall to the discretion of the astute physician. However, medication cost and hurdles of insurance approval, rather than drug efficacy, may be the primary limitation for more widespread use.

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Anakinra Improves Pyoderma Gangrenosum in Psoriatic Arthritis: A Case Report

Cited by 28 publications

References 4 publications

Ptpn6 inhibits caspase-8- and Ripk3/Mlkl-dependent inflammation

Ptpn6 inhibits caspase-8- and Ripk3/Mlkl-dependent inflammation

Multifocal Pyoderma Gangrenosum with an Underlying Hemophagocytic Lymphohistiocytosis: Case Report and the Review of the Literature

Anti-inflammatory panacea? The expanding therapeutics of interleukin-1 blockade

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