Hidradenitis Suppurativa (HS) is a chronic autoinflammatory disease (AID) with variable phenotypic presentation. The triad of HS, pyoderma gangrenosum (PG) and acne form the rare syndrome PASH, which has significant overlap with PAPA syndrome - the association of pyogenic arthritis, PG, and acne1 . A further syndrome named PAPASH has been described in which mutations of the PSTPIP1 gene are present as in PAPA2 . The only current genetic abnormality found in PASH is an increased number of CCTG microsatellite repeats in the PSTPIP1 promoter region3 . Proposed pathogenesis of AIDs is complex and unclear, and appears to involve activation of the inflammasome with contributing exogenous factors3 .
We present a patient and affected kindred with clinically severe HS manifest as a widespread truncal comedonal eruption, characteristic of the affected males in this kindred. Over a thirty-five year period no evidence of PG or joint symptoms have been recorded. Genetic sequencing detected a PSTPIP1 gene mutation indicating a diagnosis of PASH. Therapy with retinoids and the biologic agents Infliximab, Adalimumab and Anakinra failed to produce a response.
Rationalisation of this mismatched genotype-phenotype raises questions of current classification systems. His genotype is consistent with PASH syndrome, but his phenotype is atypical. In particular he does not have PG and his apparent HS is clinically atypical.
Does this kindred represent a new entity on the spectrum of AIDs related to PASH with a genetic mutation not yet classified? We also consider that the HS in this kindred is unique and undescribed in its morphological similarity to acne, reinforcing the suggestion that acne is an AID. These issues will be explored and elaborated.