Autoinflammation has recently been suggested in the pathogenesis of neutrophilic
dermatoses but systematic studies on their
cytokine profile are lacking. Notably, amicrobial pustulosis of the folds (APF), classified among neutrophilic
dermatoses, has been studied only in small case series. In our University Hospital, we conducted an observational study on 15 APF patients, analyzing their clinical and laboratory features with a follow-up of 9 months to 20 years. Skin
cytokine pattern of 9 of them was compared to that of 6 normal controls. In all patients, primary lesions were pustules symmetrically involving the skin folds and anogenital region with a chronic-relapsing course and responding to
corticosteroids.
Dapsone,
cyclosporine, and
tumor necrosis factor blockers were effective in refractory cases. In skin samples, the expressions of
interleukin (IL)-1β, pivotal
cytokine in autoinflammation, and its receptors I and II were significantly higher in APF (P = 0.005, 0.018, and 0.034, respectively) than in controls.
Chemokines responsible for neutrophil recruitment such as
IL-8 (P = 0.003), CXCL 1/2/3 (C-X-C motif
ligand 1/2/3) (P = 0.010), CXCL 16 (P = 0.045), and
RANTES (regulated on activation, normal T cell expressed and secreted) (P = 0.034) were overexpressed. Molecules involved in tissue damage like
matrix metalloproteinase-2 (MMP-2) (P = 0.010) and MMP-9 (P = 0.003) were increased. APF is a pustular neutrophilic
dermatosis with a typical distribution in all patients. The disorder may coexist with an underlying autoimmune/dysimmune disease but is often associated only with a few
autoantibodies without a clear autoimmunity. The overexpression of
cytokines/
chemokines and molecules amplifying the inflammatory network supports the view that APF has an important autoinflammatory component.