The co-existence of pachyonychia congenita (PC) and hidradenitis suppurativa (HS) has been reported in case reports. However, the pathomechanism underlying this association and its true prevalence are unknown. Here, we studied a large kindred in which HS was diagnosed concomitantly with PC. Direct sequencing of DNA samples obtained from affected family members demonstrated a missense variant (c.275A>G) in KRT17, encoding keratin 17. In contrast, no mutations were identified in genes previously reported to be associated with HS. Abnormal NOTCH signaling has been suggested to contribute to HS pathogenesis. Interestingly, transfection of the KRT17 c.275A>G variant in HaCaT cells resulted in a significant decrease in NOTCH activity. NOTCH activity was also reduced in primary keratinocytes obtained from a patient carrying the KRT17 c.275A>G variant. To ascertain the clinical importance of HS association with PC, we distributed a questionnaire to 815 PC patients registered with the International PC Research Registry (IPCRR). Seventy two out of 278 responders reported clinical features consistent with a diagnosis of HS (25.9%). KRT17 mutations were most commonly associated with HS (86%). In conclusion, the co-existence of HS and KRT17-associated PC may be more common than previously thought. Impaired NOTCH signaling as a result of KRT17 mutations may predispose PC patients to HS.

ESDR166 - Co-existence of pachyonychia congenita and hidradenitis suppurativa: more than a coincidence

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING