Abstract
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.
Highlights
Acne inversa (AI, referred to as hidradenitis suppurativa) is a chronic inflammatory skin disease with common onset in the second or third decade of life [1, 2]
Increased matrix metalloproteinase 8 (MMP8) expression was specific for AI lesions and not observed in affected skin of patients with psoriasis, a chronic inflammatory skin disease without sinus tract development (Figure 1(b))
We show a strong upregulation of MMP8 in AI lesion compared to skin from healthy controls and psoriasis patients
Summary
Acne inversa (AI, referred to as hidradenitis suppurativa) is a chronic inflammatory skin disease with common onset in the second or third decade of life [1, 2]. The axilla and the inguinal, gluteal, and perianal area are the most common affected sites. The inner thighs, perineal areas, sub- and inframammary skin, and gluteal cleft are additional sites for involvement [1, 2]. The associated pain, large amount of purulent exudate, malodor, and disfigurement contribute to a profound psychosocial impact of the disease on affected patients [3, 5, 6]. An early and accurate diagnosis would allow the initiation of a treatment plan aimed at minimizing the risk of progression to disabling, end-stage disease. As of today, on average 12 years pass between first symptoms and accurate diagnosis [9]
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