Failure of Anti-Interleukin-1 Therapy in Severe Hidradenitis Suppurativa: A Case Report

Zee, Hessel H. van der; Prens, Errol P.

doi:10.1159/000343221

Cited by 60 publications

(41 citation statements)

References 18 publications

(20 reference statements)

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“…Several case studies support the use of anakinra in HS, although outcomes are variable. 35,36 Other groups have suggested that targeting IL-23/IL-12p40 may benefit HS. 37 TNF-a inhibitors are effective therapies for HS.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa

et al. 2015

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SummaryBackground There is a dearth of information on the precise pathogenesis of hidradenitis suppurativa (HS), but immune dysregulation is implicated. Objectives To determine the nature of the immune response in HS. Methods Skin biopsies -lesional, perilesional (2 cm away) and uninvolved (10 cm away) -were obtained from patients with HS and healthy controls. The expression of various cytokines was determined by enzyme-linked immunosorbent assay, flow cytometry and real-time polymerase chain reaction. Results The expression of the inflammatory cytokines interleukin (IL)-17, IL-1b and tumour necrosis factor-a was enhanced in lesional skin of patients with HS. In addition, IL17A and IL1B mRNA were enhanced in clinically normal perilesional skin. CD4 + T cells produced IL-17 in HS, while CD11c + CD1a À CD14

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Section: Discussionmentioning

confidence: 99%

Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa

et al. 2015

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“…Cytokine-mediated inflammation has been considered as immunosuppressive agents have been used. Blocking TNFα is effective in some patients but TNFα failures have been reported [144]. Elevated levels of TNFα as well as IL-1β are released from 24 h cultures of skin from these patients; the elevated levels are not only in lesional skin biopsies but also in the unaffected peripheral skin of the lesions [145].…”

Section: Chronic Inflammatory Diseasesmentioning

confidence: 99%

Treating inflammation by blocking interleukin-1 in humans

Dinarello¹,

Meer²

2013

Seminars in Immunology

476

349

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IL-1 is a master cytokine of local and systemic inflammation. With the availability of specific IL-1 targeting therapies, a broadening list of diseases has revealed the pathologic role of IL-1-mediated inflammation. Although IL-1, either IL-1α or IL-1β, was administered to patients in order to improve bone marrow function or increase host immune responses to cancer, these patients experienced unacceptable toxicity with fever, anorexia, myalgias, arthralgias, fatigue, gastrointestinal upset and sleep disturbances; frank hypotension occurred. Thus it was not unexpected that specific pharmacological blockade of IL-1 activity in inflammatory diseases would be beneficial. Monotherapy blocking IL-1 activity in a broad spectrum of inflammatory syndromes results in a rapid and sustained reduction in disease severity. In common conditions such as heart failure and gout arthritis, IL-1 blockade can be effective therapy. Three IL-1blockers have been approved: the IL-1 receptor antagonist, anakinra, blocks the IL-1 receptor and therefore reduces the activity of IL-1α and IL-1β. A soluble decoy receptor, rilonacept, and a neutralizing monoclonal anti-interleukin-1β antibody, canakinumab, are also approved. A monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α are in clinical trials. By specifically blocking IL-1, we have learned a great deal about the role of this cytokine in inflammation but equally important, reducing IL-1 activity has lifted the burden of disease for many patients.

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“…The use and success of Anakinra for the treatment of HS has been a matter of controversy (van der Zee and Prens, 2013; Zarchi et al, 2013; Leslie et al, 2014; Menis et al, 2015; Russo and Alikhan, 2016). However, in a recent double-blind, randomized, placebo controlled trial, 20 patients were treated with Anakinra or placebo daily for 12 weeks.…”

Section: Skin Diseases With Il-1 Involvementmentioning

confidence: 99%

Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases

2017

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In 2002, intracellular protein complexes known as the inflammasomes were discovered and were shown to have a crucial role in the sensing of intracellular pathogen- and danger-associated molecular patterns (PAMPs and DAMPs). Activation of the inflammasomes results in the processing and subsequent secretion of the pro-inflammatory cytokines IL-1β and IL-18. Several autoinflammatory disorders such as cryopyrin-associated periodic syndromes and Familial Mediterranean Fever have been associated with mutations of genes encoding inflammasome components. Moreover, the importance of IL-1 has been reported for an increasing number of autoinflammatory skin diseases including but not limited to deficiency of IL-1 receptor antagonist, mevalonate kinase deficiency and PAPA syndrome. Recent findings have revealed that excessive IL-1 release induced by harmful stimuli likely contributes to the pathogenesis of common dermatological diseases such as acne vulgaris or seborrheic dermatitis. A key pathogenic feature of these diseases is IL-1β-induced neutrophil recruitment to the skin. IL-1β blockade may therefore represent a promising therapeutic approach. Several case reports and clinical trials have demonstrated the efficacy of IL-1 inhibition in the treatment of these skin disorders. Next to the recombinant IL-1 receptor antagonist (IL-1Ra) Anakinra and the soluble decoy Rilonacept, the anti-IL-1α monoclonal antibody MABp1 and anti-IL-1β Canakinumab but also Gevokizumab, LY2189102 and P2D7KK, offer valid alternatives to target IL-1. Although less thoroughly investigated, an involvement of IL-18 in the development of cutaneous inflammatory disorders is also suspected. The present review describes the role of IL-1 in diseases with skin involvement and gives an overview of the relevant studies discussing the therapeutic potential of modulating the secretion and activity of IL-1 and IL-18 in such diseases.

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Failure of Anti-Interleukin-1 Therapy in Severe Hidradenitis Suppurativa: A Case Report

Cited by 60 publications

References 18 publications

Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa

Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa

Treating inflammation by blocking interleukin-1 in humans

Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases

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