Hidradenitis suppurativa and Mediterranean fever gene mutations

İlgen, Ufuk; Yayla, Müçteba Enes; Eyupoglu, Sahin; Karahan, İrfan

doi:10.1016/j.jdcr.2019.06.035

Cited by 5 publications

(5 citation statements)

References 9 publications

(12 reference statements)

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“…HS can present as a component of systemic autoinflammatory syndromes like pyoderma gangrenosum, acne, pyogenic arthritis, and HS (PAPASH) and pyoderma gangrenosum, acne, and HS (PASH), which are caused by mutations in PSTPIP1 (46,47). HS may also be presented by patients with familial Mediterranean fever carrying MEFV mutations (48)(49)(50). Notably, the frequency of MEFV mutations in the group of patients with HS was higher than that in healthy controls (49), suggesting that MEFV mutations may contribute to the pathogenesis of HS.…”

Section: More Genes Associated With Hsmentioning

confidence: 99%

Hidradenitis Suppurativa as a Potential Subtype of Autoinflammatory Keratinization Disease

Nomura

2020

Front. Immunol.

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Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition, clinically characterized by boiled cysts, comedones, abscesses, hypertrophic scars, and/or sinus tracts typically in the apocrine-gland-rich areas such as the axillae, groin, and/or buttocks. Although its precise pathogenic mechanisms remain unknown, I herein emphasize the importance of the following three recent discoveries in the pathogenesis of HS: First, heterozygous loss-of-function mutations in the genes encoding γ-secretase, including NCSTN, PSENEN, and PSEN1, have been identified in some patients with HS. Such genetic alterations result in hyperkeratosis, dysregulated hair follicle differentiation, and cyst formation via aberrant Notch signaling. Furthermore, Psen1-/Psen2-, Psen1-, Ncstn+/-, and Notch1-/Notch2-mice share common phenotypes of human HS, suggesting a role of aberrant keratinization in the development of HS. Second, upregulation of interleukin 1β, interleukin-36, caspase-1, and NLRP3 and dysregulation of the Th17:Treg cell axis have been demonstrated in HS samples, suggesting that autoinflammation is a key event in the pathophysiology of the disease. Notably, HS may be complicated with other autoinflammatory diseases such as inflammatory bowel diseases and pyoderma gangrenosum, again highlighting the importance of autoinflammation in HS. Last, biologics such as adalimumab, infliximab, anakinra, ustekinumab, and secukinumab are reportedly effective for moderate-to-severe HS. These findings collectively suggest that HS is closely linked with aberrant keratinization and autoinflammation, raising the question whether it represents an autoinflammatory keratinization disease, a recently proposed disease entity. In this mini review, I introduce the concept of autoinflammatory keratinization disease and attempt to address this clinically important question.

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Section: More Genes Associated With Hsmentioning

confidence: 99%

Hidradenitis Suppurativa as a Potential Subtype of Autoinflammatory Keratinization Disease

Nomura

2020

Front. Immunol.

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“…However, discrepancy between a positive family history and γ-secretase mutations in affected individuals implies that genes other than PSENEN are also likely involved in the pathogenesis 6 . Although the γ-secretase–Notch signaling pathway is the best described genetic association, HS is also a known component of other systemic autoinflammatory syndromes including the combination of pyoderma gangrenosum, acne, and suppurative hidradenitis, which is associated with monogenic mutations in the proline-serine-threonine phosphatase interacting protein 1 gene leading to defective inflammasome function 14 …”

Section: Genetic Perturbations In Hsmentioning

confidence: 99%

“…6 Although the g-secretase-Notch signaling pathway is the best described genetic association, HS is also a known component of other systemic autoinflammatory syndromes including the combination of pyoderma gangrenosum, acne, and suppurative hidradenitis, which is associated with monogenic mutations in the proline-serine-threonine phosphatase interacting protein 1 gene leading to defective inflammasome function. 14 Although a positive family history has been noted in approximately one-third of patients with HS, suggesting a genetic basis of the disease, Pink et al 15 found that only 7% of patients exhibited a monogenetic mutation with autosomal dominant inheritance. 15,16 The most commonly involved monogenic mutations are within either the Notch or phosphatase interacting protein 1 gene signaling pathway.…”

Section: Genetic Perturbations In Hsmentioning

confidence: 99%

Hidradenitis Suppurativa: An Exploration of Genetic Perturbations and Immune Dysregulation

Preda-Naumescu

Ahmed

Mayo

et al. 2021

Int J Dermatol Venereol

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Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition that poses a significant diagnostic and therapeutic challenge for clinicians, as the underlying etiology and pathogenesis remains unclear. The host of genetic mutations and immune dysfunction has been identified to be involved in the pathogenesis of HS during recent years. These genetic defects, including monogenetic mutations altering subunits of g-secretase, a protease that functions through Notch signaling to maintain skin appendages, promote epithelial stability, suppress/terminate innate immune responses (ie, Toll-receptors), further have the propensity to induce aberrant cytokine responses that create to a proinflammatory environment, consequently induce hyperkeratosis and promote expression of pro-inflammatory, locally destructive matrix metalloproteinases. Cytokine-driven inflammation propagates the disease state of HS and contributes to the formation of painful subcutaneous nodules, abscesses, and eventually, fistulas and draining sinus tracts. A closer look at genetic mutations linked to the disease may explain the immune perturbations seen in HS. An understanding of the immune cells and inflammatory markers expressed in affected individuals provides insight into disease pathogenesis and can help identify therapeutic targets.

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“…Su base inmunogenética no está completamente aclarada, y no siempre están ligados a mutaciones del complejo gamma-secretasa, como se ha descrito en ciertas formas familiares de HS. Se han descrito previamente mutaciones en el gen de la fiebre mediterránea familiar (MEFV) en la HS 3 . Dicho gen regula la pirina, una proteína con una función capital en la respuesta inflamatoria.…”

Section: Comentariounclassified