Sylke Schneider-Burrus

Deficiency of IL-22 Contributes to a Chronic Inflammatory Disease: Pathogenetic Mechanisms in Acne Inversa

Overexpression of the T cell cytokine IL-22 is linked to the development of some chronic diseases, but little is known about IL-22 deficiency in humans. As demonstrated in this study, acne inversa (AI; also designated as Hidradenitis suppurativa) lesions show a relative deficiency of IL-22 and IL-20, but not of IL-17A, IL-26, IFN-γ, IL-24, or IL-1β. Moreover, AI lesions had reduced expression of membranous IL-22 and IL-20 receptors and increased expression of the natural IL-22 inhibitor, IL-22 binding protein. AI is a chronic inflammatory skin disease with prevalence up to 4% of the population and in which cutaneous bacterial persistence represents an important pathogenetic factor. Accordingly, we also found a relative deficiency of antimicrobial proteins (AMPs) in AI lesions and a positive correlation between lesional IL-22 and IL-20 versus AMP levels. IL-22, like its tissue cell downstream mediator IL-20, upregulated AMPs in reconstituted human epidermis and was critical for increased AMP levels under inflammatory conditions. The relative IL-22 deficiency in AI was not linked to lesional T cell numbers or Th22/Th1/Th17 subset markers and -inducing cytokines. However, IL-10 was highly expressed in AI lesions and correlated negatively with IL-22 expression. Moreover, IL-10 inhibited IL-22 but not IL-17 production in vitro. The IL-10 overexpression, in turn, was not associated with an elevated presence of regulatory T cells but with the enhanced presence of an IL-10–inducing cytokine. We conclude that IL-22 deficiency may contribute to the pathogenesis of certain chronic disorders as postulated in this paper for AI.

Increased Prevalence of Metabolic Syndrome in Patients with Acne Inversa

Background Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored. Methods and Findings A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL-cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients. Conclusions This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend monitoring of AI patients in order to correct their modifiable cardiovascular risk factors.

Profound disturbances of sexual health in patients with acne inversa

BACKGROUNDnAcne inversa (AI) leads chronically to painful eruptions and extensive scarring in predominantly intimate areas. We hypothesized an impairment of sexual life caused by the disease.nnnOBJECTIVESnBy means of validated questionnaires, sexual health and quality of life were assessed in patients with AI and in healthy control subjects.nnnMETHODSnA self-administered questionnaire was given to 85 voluntary study participants. In all, 45 women (24 patients vs 21 control subjects) and 40 men (20 patients vs 20 control subjects) were enrolled in the study. The Female Sexual Function Index, the International Index of Erectile Function, and the Frankfurt Self-Concept Scale for Sexuality were used to assess sexual health. Quality of life was measured with the Dermatology Life Quality Index.nnnRESULTSnThis study demonstrated, for the first time to our knowledge, that patients with AI have sexual dysfunctions and sexual distress in comparison with matched control subjects. Sexual distress was particularly higher in female than in male patients with AI. Surprisingly, severity of cutaneous alterations correlated neither with sexual dysfunctions nor with sexual distress. However, the sexual dysfunction and sexual distress negatively correlated with the quality of life in female patients with AI who had a lower quality of life compared with gender-matched control subjects and male patients.nnnLIMITATIONSnSmall sample size is the main limitation of this study.nnnCONCLUSIONSnSexual health is diminished in patients with AI. We underscore the need for physicians to implement attention on the impact of AI on sexual health and quality of life when treating patients for this disease.

Depression is a frequent co-morbidity in patients with acne inversa

Acne inversa (AI) is a common chronic inflammatory disease that has a profound impact on the patientsí quality of life. We hypothesized a higher level of depression in AI patients compared to controls.

Development and validation of the International Hidradenitis Suppurativa Severity Score System (IHS4), a novel dynamic scoring system to assess HS severity

A validated tool for the dynamic severity assessment of hidradenitis suppurativa/acne inversa (HS) is lacking.

High Prevalence of Back Pain and Axial Spondyloarthropathy in Patients with Hidradenitis Suppurativa.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease, causing fistulating sinuses in the intertriginous skin of axillary, genitofemoral and perianal sites. Objective: As other chronic inflammatory diseases, e.g. psoriasis, are frequently associated with spondyloarthropathies (SpA), the goal of this study was to quantify the prevalence of back pain and SpA in HS patients. Methods: A prospective questionnaire survey in 100 HS patients and a retrospective evaluation of pelvic magnetic resonance imaging (MRI) scans in 46 HS patients were conducted. Results: 71% of HS patients were suffering from back pain. There was no difference between age at onset of HS, disease duration, body mass index (BMI), or disease severity between HS patients with and without back pain. Evaluating pelvic MRI scans, 32.6% of HS patients showed signs of chronic SpA and 39.1% signs of active SpA. Again, no significant differences between patients with/without SpA were found regarding age at time of MRI, age at onset of HS, disease duration, smoking habits, and BMI. Furthermore, there was no correlation between these parameters and the degree of SpA. Limitations: Only patients with moderate/severe HS (Hurley stage II and III) in genitofemoral/perianal sites were analysed via MRI scans. Conclusion: Back pain and SpA are very common among patients with moderate/severe HS. Neither medical history nor clinical parameters provide hints for the presence of SpA.

Lipocalin-2 is expressed by activated granulocytes and keratinocytes in affected skin and reflects disease activity in acne inversa / hidradenitis suppurativa

Acne inversa (AI)/hidradenitis suppurativa is a chronic inflammatory disease characterized by painful axillary, inguinal and perianal skin lesions with deep‐seated nodules, abscesses and fistulae.

MMP8 Is Increased in Lesions and Blood of Acne Inversa Patients: A Potential Link to Skin Destruction and Metabolic Alterations

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.

Prevalence of the MspI and Ile462Val SNPs of Cytochrome P-450 1A1 in Hidradenitis Suppurativa

Please cite this paper as: Prevalence of the MspI and Ile462Val SNPs of Cytochrome P‐450 1A1 in Hidradenitis Suppurativa. Experimental Dermatology 2010; 19: 541–542.

Acne inversa/Hidradenitis suppurativa: Ein Update

ZusammenfassungAcne inversa (AI)/Hidradenitis suppurativa ist eine chronisch rezidivierende, immunvermittelte Dermatose mit dem Charakter einer Systemerkrankung, die durch tief sitzende entzündliche Knoten, Abszesse, Fisteln und unterminierte Narben in Hautarealen mit apokrinen Drüsen gekennzeichnet ist. Neben den Hautveränderungen zeigen zahlreiche AI-Patienten metabolische Veränderungen, Spondylarthritis und Depressionen. AI führt zu einer massiven Einschränkung der Lebensqualität und des Sexuallebens der Betroffenen und mündet oft in sozialem Rückzug, Stigmatisierung, Arbeitsplatzverlust und Suizidgedanken. In diesem Übersichtsbeitrag haben wir die wichtigsten Fakten zu AI zusammengefasst und schlagen einen einfachen Algorithmus für die Behandlung dieser Erkrankung vor.AbstractAcne inversa (AI)/hidradenitis suppurativa is axa0chronic, 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 axa0strong 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 axa0simple algorithm for therapy.