The association of
pyoderma gangrenosum,
acne, and
suppurative hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile
inflammation, without circulating
autoantibodies and autoreactive T-cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (
AIDs), and
cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of
interleukin (IL)-1β and its receptors I and II were significantly higher in PASH (P = 0.028, 0.047, and 0.050, respectively) than in controls. In PASH patients,
chemokines such as
IL-8 (P = 0.004), C-X-C motif
ligand (CXCL) 1/2/3 (P = 0.028), CXCL 16 (P = 0.008), and regulated on activation, normal T cell expressed and secreted (
RANTES) (P = 0.005) were overexpressed. Fas/
Fas ligand and cluster of differentiation (CD)40/
CD40 ligand systems were also overexpressed (P = 0.016 for Fas, P = 0.006 for
Fas ligand, P = 0.005 for CD40, and P = 0.004 for
CD40 ligand), contributing to tissue damage and
inflammation. In peripheral blood, serum levels of the main proinflammatory
cytokines, that is, IL-1β,
tumor necrosis factor-α, and
IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical of well-known
AIDs, including
inflammatory bowel diseases, and the only patient lacking genetic changes had clinically evident
Crohn disease. In conclusion, overexpression of
cytokines/
chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin.