Follicular occlusion tetrad in a male patient with pachyonychia congenita: clinical and genetic analysis

Musumeci, Maria Letizia; Fiorentini, Federica; Bianchi, Luca; Cascella, Raffaella; Giardina, Emiliano; Caputo, Valerio; Micali, Giuseppe

doi:10.1111/jdv.15851

Cited by 13 publications

(8 citation statements)

References 26 publications

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“…PC and HS have previously been reported to coexist, [19][20][21][22] but it is unclear to date whether this association is serendipitous or reflects a common pathogenesis. The high prevalence of HS among patients with PC demonstrated in this study (25Á9%), which is significantly higher than the prevalence of HS in the general population, 28 argues in favour of a specific association.…”

Section: Discussionmentioning

confidence: 99%

“…Given previous results [19][20][21][22] supporting an association between KRT17 variants and the propensity to develop HS, we circulated a questionnaire among a cohort of 815 patients with PC (Figure S1). In total, 278 patients with PC replied, with the distribution of keratin gene mutations being similar to that in previous reports based on the IPCRR 13 (Figure 4a, b).…”

Section: Hidradenitis Suppurativa Is Prevalent Among Patients With Pa...mentioning

confidence: 99%

“…An association of HS with PC was first described by McDonald and Reed in 1976 18 and has since been further confirmed in several case reports. [19][20][21][22] The molecular basis for this association and its magnitude are currently not known.…”

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confidence: 99%

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Coexistence of pachyonychia congenita and hidradenitis suppurativa: more than a coincidence

Pavlovsky

Peled

Sarig

et al. 2022

British Journal of Dermatology

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Background The coexistence of pachyonychia congenita (PC) and hidradenitis suppurativa (HS) has been described in case reports. However, the pathomechanism underlying this association and its true prevalence are unknown. Objectives To determine the genetic defect underlying the coexistence of PC and HS in a large kindred, to delineate a pathophysiological signalling defect jointly leading to both phenotypes, and to estimate the prevalence of HS in PC. Methods We used direct sequencing and a NOTCH luciferase reporter assay to characterize the pathophysiological basis of the familial coexistence of HS and PC. A questionnaire was distributed to patients with PC registered with the International Pachyonychia Congenita Research Registry (IPCRR) to assess the prevalence of HS among patients with PC. Results Direct sequencing of DNA samples obtained from family members displaying both PC and HS demonstrated a missense variant (c.275A>G) in KRT17, encoding keratin 17. Abnormal NOTCH signalling has been suggested to contribute to HS pathogenesis. Accordingly, the KRT17 c.275A>G variant resulted in a significant decrease in NOTCH activity. To ascertain the clinical importance of the association of HS with PC, we distributed a questionnaire to all patients with PC registered with the IPCRR. Seventy-two of 278 responders reported HSassociated clinical features (25Á9%). Disease-causing mutations in KRT17 were most prevalent among patients with a dual phenotype of PC and HS (43%). Conclusions The coexistence of HS and KRT17-associated PC is more common than previously thought. Impaired NOTCH signalling as a result of KRT17 mutations may predispose patients with PC to HS.What is already known about this topic?• The coexistence of pachyonychia congenita (PC) and hidradenitis suppurativa (HS) has been described in case reports. • However, the pathomechanism underlying this association and its true prevalence are unknown.What does this study add?• A dual phenotype consisting of PC and HS was found to be associated with a pathogenic variant in KRT17. • This variant was found to affect NOTCH signalling, which has been previously implicated in HS pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Hidradenitis Suppurativa Is Prevalent Among Patients With Pa...mentioning

confidence: 99%

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Coexistence of pachyonychia congenita and hidradenitis suppurativa: more than a coincidence

Pavlovsky

Peled

Sarig

et al. 2022

British Journal of Dermatology

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“…Several HS or HS-like cases have been described in association with pachyonychia congenita or steatocystoma multiplex caused by mutations in KRT17 or KRT6A (40,41). Mutations in FGFR2 also underlie nevus comedonicus and HS-like skin lesions (42).…”

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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“…PCAS may occur along with hidradenitis suppurativa (HS), acne conglobate and pilonidal sinus, termed the follicular occlusion tetrad. These four different clinical conditions appear to have common pathogenic events including follicular hyperkeratosis, poral obstruction, dilation and rupture, followed by neutrophilic and granulomatous inflammatory response, bacterial overgrowth, scarring, and sinus tract formations 2 . Treatment of PCAS is challenging and clinical practice varies a lot, while evidence‐based treatment guidelines for PCAS are quite rare.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic options for perifolliculitis capitis abscedens et suffodens: A review

Zhang

et al. 2022

Dermatologic Therapy

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Perifolliculitis capitis abscedens et suffodiens (PCAS) is a chronic skin inflammatory disease characterized by relapsing folliculitis and painful, fluctuant abscesses, sinus tracts, and scars. The treatment of PCAS is challenging and clinical practice varies a lot, and how to choose the best treatment for PCAS is a real problem for clinicians. We reviewed articles providing treatment options for patients with PCAS in different databases. Dermatologists may find this review helpful to meet the challenges of PCAS management, but there is still a lack of authoritative guidelines. In the future, more robust randomized control trials are needed to determine the best treatment for PCAS. K E Y W O R D S biologics, dissecting cellulitis of the scalp (DCS), perifolliculitis capitis abscedens et suffodiens (PCAS), retinoids, treatment option 1 | INTRODUCTION Perifolliculitis capitis abscedens et suffodiens (PCAS), also known as dissecting cellulitis of the scalp (DCS) or Hoffman's disease, is a chronic skin inflammatory disease characterized by relapsing folliculitis and painful, fluctuant abscesses in the scalp that lead to the formation of sinus tracts and scarring. 1 PCAS may occur along with hidradenitis suppurativa (HS), acne conglobate and pilonidal sinus, termed the follicular occlusion tetrad. These four different clinical conditions appear to have common pathogenic events including follicular hyperkeratosis, poral obstruction, dilation and rupture, followed by neutrophilic and granulomatous inflammatory response, bacterial overgrowth, scarring, and sinus tract formations. 2 Treatment of PCAS is challenging and clinical practice varies a lot, while evidence-based treatment guidelines for PCAS are quite rare. Despite a paucity of robust and high-quality data on PCAS, this review focuses on different aspects of PCAS, especially on treatment options for PCAS, providing clinical inspirations for dermatologists. | CLINICAL MANIFESTATIONS AND HISTOPATHOLOGIC FEATURESLesions of PCAS are folliculitis at an early stage and becoming nodules and abscesses later, primarily on the occipital scalp or vertex, with symptoms of pain, itching or swelling. The nodules and abscesses rapidly develop into interconnecting, fluctuant, boggy sinus tracts, which discharge purulent and bloody secretions with a foul smell. With time, irreversible atrophic or hypertrophic scarring and cicatricial alopecia occur. PCAS presents as a chronic process with frequent episodes. 1,3 The histopathologic characteristics of PCAS usually depend on the clinical manifestation, which can range from early folliculitis, nodules or abscesses to sinus tracts or scars. In the early stage, histopathology findings show an infiltrate of lymphocytes and neutrophils involving the lower half of the dermis and gradually extended downward to subcutaneous fat. The disease progressed with vascular hyperplasia. In the late stage, the deep dermis and subcutaneous fat layer show the histologic characteristics of granuloma and eventually sinus tract and fibrosis develop. 4,5

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Follicular occlusion tetrad in a male patient with pachyonychia congenita: clinical and genetic analysis

Cited by 13 publications

References 26 publications

Coexistence of pachyonychia congenita and hidradenitis suppurativa: more than a coincidence

Coexistence of pachyonychia congenita and hidradenitis suppurativa: more than a coincidence

Hidradenitis Suppurativa as a Potential Subtype of Autoinflammatory Keratinization Disease

Therapeutic options for perifolliculitis capitis abscedens et suffodens: A review

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