SAPHO Syndrome: Current Developments and Approaches to Clinical Treatment

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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“…Skin manifestations include palmoplantar pustulosis, psoriasis, severe acne and HS (Firinu et al, 2016). …”

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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“…Therefore, intra-articular or systemic corticosteroids, disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, sulfasalazine, cyclosporine, and lelunomide are the treatment options but there are no randomized controlled clinical trials for the treatment. Doxycycline can also be thought as a treatment option for P. acnes eradication [33] Inliximab (INFX), an anti-TNF-α monoclonal antibody, has been showed efective for the treatment SAPHO patients especially unresponsive or refractory to conventional drugs. In recent case series, remarkable improvement of bone, joints, and skin inlammatory manifestations was observed with Inliximab (INFX) therapy.…”

Section: Synovitis Acne Pustulosis Hyperostosis and Osteitis (Sapmentioning

confidence: 99%

Acne-Associated Syndromes

Emiroğlu¹

2017

Acne and Acneiform Eruptions

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Introduction: Acne, a chronic inlammatory disorder of pilosebaceous unit, is characterized by comedones, pustules, papules, nodules, cysts, and scars. It afects nearly 85% of adolescents. High sebaceous gland secretion, follicular hyperproliferation, high androgen efects, propionibacterium acnes colonization, and inlammation are major pathogenic factors. Systemic disease or syndromes that are associated with acne are less commonly deined. Therefore, these syndromes may not be usually recognized easily.Research methods: Acne-associated syndromes prove the nature of these diseases and are indicative of pathogenesis of acne. Polycystic ovary (PCOS), synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO), hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN), pyogenic arthritis-pyoderma gangrenosum-acne (PAPA), pyoderma gangrenosum-acne vulgaris-hidradenitis suppurativa-ankylosing spondylitis (PASS), pyoderma gangrenosum-acne conglobate-hidradenitis suppurativa (PASH), seborrhea-acne-hirsutism-androgenic alopecia (SAHA), and Apert syndromes are wellknown acne-associated syndromes. Endocrine disorders (insulin resistance, obesity, hyperandrogenism, etc.) can be commonly seen in these syndromes, and there are too many unknown factors that must be investigated in the formation of these syndromes.Conclusion-key results: If we are aware of the component of these syndromes, we will recognize those easily during dermatological examination. Knowledge of clinical manifestations and molecular mechanisms of these syndromes will help us to understand acne pathogenesis. When acne pathogenesis is explained clearly, new treatment modalities will be developed.

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“…Understanding of SAPHO pathogenesis is still limited. Proinflammatory cytokines such as TNF‐α and IL‐1 seem to play a central role, and the recombinant IL‐1 receptor antagonist anakinra has proven rapidly effective in a limited number of patients with SAPHO syndrome (Table ).…”

Section: Cases Of Sapho Syndrome Treated With Anakinramentioning

confidence: 99%