Phenotypes and Pathophysiology of Syndromic Hidradenitis Suppurativa: Different Faces of the Same Disease? A Systematic Review

Abstract

<b><i>Background:</i></b> There is growing evidence that (certain) hidradenitis suppurativa (HS) comorbidities comprise syndromes including HS as a key cutaneous manifestation. These apparently autoinflammatory syndromes and their diagnostic delay might have detrimental effects on affected patients. <b><i>Methods:</i></b> A systematic review was performed on the databases MEDLINE, EMBASE, and CENTRAL utilizing a standardized extraction form according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. <b><i>Results:</i></b> Sixty-four eligible articles on syndromic HS were retrieved. The identified syndromes included already described ones (pyoderma gangrenosum-acne-suppurative hidradenitis, pyogenic arthritis-pyoderma gangrenosum-acne-suppurative hidradenitis, psoriatic arthritis-pyoderma gangrenosum-acne-suppurative hidradenitis, pyoderma gangrenosum-acne vulgaris-hidradenitis suppurativa-ankylosing spondylitis, synovitis-acne-pustulosis-hyperostosis-osteitis) and further novel symptom constellations. Cutaneous signs, including HS lesions, usually precede signs from other organs. The cutaneous signs of a considerable proportion of patients appear refractory to conventional treatment, and monotherapy with biologics does not suffice to sustain remission. <b><i>Conclusion:</i></b> The results are subsequently discussed with focus on the pathophysiology and treatment of the detected syndromes. The dermatologist’s role in the precise diagnosis and early treatment administration of HS is pivotal. The purpose of the treatment should be the effective prevention or delay of the autoinflammatory march and its irreversible consequences.

A case of PAPASH syndrome in a young man carrying a novel heterozygote missense variant in PSTPIP1

“…3 PSTPIP1 variants, as found in our patient, have been associated with a decreased inhibition of the inflammasome 4 and were reported to have a causative role in PAPA syndrome, 5 the main variants here being p.E250Q as well as p.A230T. 6 Interestingly, a single PSTPIP1 missense variant (c.831G>T, p.E277D) was identified in only one of 6 PAPASH cases reviewed by Nikolalis et al 7 To our knowledge, this is the first time that the missense variant c.748G>C, p.E250Q in exon 11 has been described in a PAPASH patient. The clinical course of PAPASH is mostly similar to PAPA.…”

Follicular Occlusion Triad: A Case Report

“…With proinflammatory cytokines being prominently associated with HS skin lesions and the same gene mutations appearing between HS and other autoinflammatory diseases, it is known that autoinflammation reaction plays a leading role in the pathogenesis of HS [9]. SAPHO syndrome, pyoderma gangrenosum-acne-suppurative hidradenitis (PASH) syndrome, pyoderma acne-pyoderma gangrenosum-acne-suppurative hidradenitis (PAPASH) syndrome, and pyoderma gangrenosum-acne vulgaris-suppurative hidradenitis-ankylosing spondylitis (PASS) syndrome have been reported as autoinflammatory syndromes related with HS and AC [6,10]. Since skin symptoms, such as HS lesion, are usually a leading sign of Fig.…”

Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab

“…Twelve years after being diagnosed with HS, the patient developed acne conglobata (AC), which was treated without systemic therapy. In addition, she underwent numerous incisions and radical excisions, antibiotic treatment with doxycycline, and the combination of clindamycin and rifampicin over 3 months, according to the HS treatment guidelines, 1 , 2 without sustained remission of the lesions. A previous 1-year therapy with isotretinoin did not improve the HS lesions.…”

“…Significant increase of proinflammatory cytokines IL-1β, TNF-α, IL-17 and the antiinflammatory cytokine IL-10 has been detected in lesional and perilesional skin. 2 , 3 Apart from sporadic cases, there is a genetic background for certain HS patients, correlating with mutations in the γ-secretase genes nicastrin, presenilin enhancer 2 and presenilin. 4 HS has been described in association with several clinical syndromes that include comorbid disorders, such as pyogenic arthritis (PA), pyoderma gangrenosum (PG), acne, ulcerative colitis (UC) and psoriatic arthritis.…”