Hidradenitis suppurativa (HS) (also designated acne inversa) is a chronic inflammatory disease characterized by painful purulent skin lesions and progressive destruction of skin architecture. Despite the high burden for the patients, pathogenetic pathways underlying HS alterations remain obscure. When we examined the HS cytokine pattern, IL-1b turned out to be a highly prominent cytokine, overexpressed even compared with psoriatic lesions. Analyses of IL-1beinduced transcriptome in various cell types showed overlapping profiles, with upregulations of molecules causing immune cell infiltration and extracellular matrix degradation, and of specific cytokines including IL-6, IL-32, and IL-36. Matching cellular IL-1 receptor levels, dermal fibroblasts showed both the strongest and broadest IL-1b response, which was not clearly shared or strengthened by other cytokines. The IL-1b signature was specifically present in HS lesions and could be reversed by application of IL-1 receptor antagonist. Search for blood parameters associated with IL-1b pathway activity in HS identified serum amyloid A, which was synergistically induced by IL-1b and IL-6 in hepatocytes. Consequently, strongly elevated blood serum amyloid A levels in HS correlated positively with the extent of inflammatory skin alterations. In summary, the IL-1b pathway represents a pathogenetic cascade, whose activity may be therapeutically targeted and monitored by blood SAA levels.

LCN2 might serve as a blood biomarker for the objective assessment of inflammatory activity in AI. We suggest a self-amplification loop comprising TNF-α, neutrophilic granulocytes and LCN2, which contributes to the recurrent skin neutrophil infiltration in AI, clinically evident as pus.

Acne inversa (AI; also designated as hidradenitis suppurativa) is a chronic inflammatory disease with still unknown pathogenesis that affects the intertriginous skin of perianal, inguinal, and axillary sites. It leads to painful nodules, abscesses, and fistulas with malodorous secretion and is frequently associated with metabolic alterations. Here, we demonstrate that one of the most highly upregulated molecules in AI lesions is matrix metalloproteinase 8 (MMP8), an enzyme specialized in the degradation of extracellular matrix components and the HDL component apolipoprotein A-I. Granulocytes, which were present in AI lesions, secreted high amounts of MMP8 especially after TNF-α stimulation. Furthermore, activated fibroblasts but not keratinocytes were found to express MMP8. The high lesional MMP8 levels were accompanied by elevated blood levels that positively correlated with TNF-α blood levels and disease severity assessed by Sartorius score, especially with the number of regions with inflammatory nodules/abscesses and fistulas. Additionally, we found a negative correlation between blood MMP8 and HDL-cholesterol levels, suggesting a contributory role of MMP8 in metabolic alterations in AI. In summary, we demonstrate elevated MMP8 levels in AI lesions, suggest their role in skin destruction and metabolic alterations, and recommend the use of MMP8 as blood biomarker for AI disease activity assessment.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with an adverse impact on patients' quality of life (QoL).Objectives: To quantify QoL impairment in patients in Germany suffering from HS and to identify the parameters associated with QoL impairment.Methods: A non-interventional, cross-sectional, mono-centric study with 500 HS patients. QoL data (measured using the Dermatology Life Quality Index; DLQI) and demographic, anamnestic, clinical, and blood parameters were collected. All patients were examined by dermatologists that documented the skin alterations. QoL data from 462 HS patients were available and evaluated.Results: The mean (± standard deviation) DLQI score of HS patients was 13.18 ± 7.99. Approximately 40% and 20% of HS patients declared very large and extremely large QoL impairment, respectively. The degree of QoL disturbance correlated with the severity of skin alterations, blood leucocyte count and, in particular, with anogenital localization and the presence of nodules and fistulas. Furthermore, QoL impairment was associated with specific comorbidities, such as adiposity and back pain, but not with HS family history. QoL impairment was not influenced by whether or not the patients had undergone resection surgery or antibiotic treatment but was more severe in HS patients that had undergone abscess lancing compared to patients without such treatment in the past.Limitations: It was a mono-centric study and most data were obtained from self-administered patient questionnaires. The association of QoL with type of treatment was analyzed for abscess lancing, resection surgery, and antibiotic treatment. Further therapeutic modalities recommended in the guidelines were not investigated.Conclusion: A profound impairment in QoL was present in patients with HS, and this was higher than that observed in other studied dermatoses. The degree of impairment correlated with the extent of cutaneous and some extra-cutaneous alterations. Surgical and conventional medicamentous therapies of HS were not associated with long-lasting reduction of QoL impairment. Our data support the implementation of patient-reported outcome measures for the assessment of therapy responses.

Acne inversa (AI)/hidradenitis suppurativa is a chronic, recurrent, immune-mediated dermatosis characterized by deep inflammatory nodules, abscesses, fistulas, and undermined scars in skin areas bearing apocrine glands. In addition to the cutaneous manifestation, numerous AI patients show metabolic changes, spondyloarthritis, and depression. AI leads to a strong reduction in the quality of life and an impairment of the sexual life of affected individuals and often culminates in social withdrawal, stigmatization, unemployment, and suicidal thoughts. In this overview, we summarized the most important facts about AI and propose a simple algorithm for therapy.