Neutrophilic granulocyte-derived B-cell activating factor supports B cells in skin lesions in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by painful inflamed nodules, abscesses, and pus-draining tunnels appearing in axillary, inguinal, and perianal skin areas. HS lesions contain various types of immigrated immune cells. OBJECTIVE: This study aimed to characterize mediators that support lesional B/plasma cell persistence in HS. METHODS: Skin samples from several cohorts of HS patients and control cohorts were assessed by mRNA sequencing, quantitative PCR on reverse-transcribed RNA, flow cytometry, and immunohistofluorescence. Blood plasma and cultured skin biopsy samples, keratinocytes, dermal fibroblasts, neutrophilic granulocytes (neutrophils), monocytes, and B cells were analyzed. Complex systems biology approaches were used to evaluate bulk and single-cell RNA sequencing data. RESULTS: Proportions of B/plasma cells, neutrophils, CD8+ T cells, and M0 and M1 macrophages were elevated in HS lesions compared to skin of healthy and perilesional intertriginous areas. There was an association between B/plasma cells, neutrophils, and B-cell activating factor (BAFF, aka TNFSF13B). BAFF was abundant in HS lesions, particularly in nodules and abscesses. Among the cell types present in HS lesions, myeloid cells were the main BAFF producers. Mechanistically, granulocyte colony-stimulating factor in the presence of bacterial products was the major stimulus for neutrophils' BAFF secretion. Lesional upregulation of BAFF receptors was attributed to B cells (TNFRSF13C/BAFFR and TNFRSF13B/TACI) and plasma cells (TNFRSF17/BCMA). Characterization of the lesional BAFF pathway revealed molecules involved in migration/adhesion (eg, CXCR4, CD37, CD53, SELL), proliferation/survival (eg, BST2), activation (eg, KLF2, PRKCB), and reactive oxygen species production (eg, NCF1, CYBC1) of B/plasma cells. CONCLUSION: Neutrophil-derived BAFF supports B/plasma cell persistence and function in HS lesions.

The impact of hidradenitis suppurativa on professional life.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that affects intertriginous skin. OBJECTIVES: To determine the extent of work ability and productivity impairment as a result of HS in Germany. METHODS: A prospective, multicentre, epidemiological, noninterventional study of patients with HS was conducted. Medical history, medical examination performed by dermatologists and patient-reported outcomes [Work Ability Index (WAI) and Work Productivity and Activity Impairment (WPAI)] were collected. RESULTS: Of the 481 patients with HS included in the study, 99% were below the current statutory retirement age. In total, 53·3% of patients were working full time, 16·8% part time and 7·3% had retired. The unemployment rate was 12·6%, two times higher than in the general German population. Medical leave because of HS, within the last 6 months, was reported in 41·4% [95% confidence interval (CI) 36·9-46·0], with a duration of 39·3 days on average (95% CI 32·4-46·1). The mean HS-related WPAI absenteeism was 13.3% (95% CI 9·7-16·8), and the loss in productivity because of HS during working hours (WPAI presenteeism) was 25.2% (95% CI 21·8-28·6). Presenteeism was associated with HS disease severity. Overall work impairment because of HS was 33·4% (95% CI 29·3-37·6). The WAI score for patients was 32·2, ∼20% lower than for the average German employee. Only 62·8% of patients were relatively certain that they would be able to perform their work in the coming 2 years. Being more depressed and having more severe pain were associated with lower work ability and overall work impairment. The estimated annual loss of gross value added because of HS for Germany was ∼€12.6 billion (€3.3 billion related to a lower employment rate, €3.5 billion related to absenteeism and €5.8 billion related to presenteeism). CONCLUSIONS: HS leads to a substantial decrease in work ability and productivity and considerable loss of gross value added. Impairment during working hours correlates with disease severity, underlining the socioeconomic importance of early and adequate treatment. Furthermore, decreased work ability and productivity is linked to depressed mood and severe pain, aspects that need more attention in patient care.

Blood T Helper Memory Cells: A Tool for Studying Skin Inflammation in HS?

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful lesions on intertriginous body areas such as the axillary, inguinal, and perianal sites. Given the limited treatment options for HS, expanding our knowledge of its pathogenetic mechanisms is a prerequisite for novel therapeutic developments. T cells are assumed to play a crucial role in HS pathogenesis. However, it is currently unknown whether blood T cells show specific molecular alterations in HS. To address this, we studied the molecular profile of CD4+ memory T (Thmem) cells purified from the blood of patients with HS and matched healthy participants. About 2.0% and 1.9% of protein-coding transcripts were found to be up- and down-regulated in blood HS Thmem cells, respectively. These differentially expressed transcripts (DETs) are known to be involved in nucleoside triphosphate/nucleotide metabolic processes, mitochondrion organization, and oxidative phosphorylation. The detected down-regulation of transcripts involved in oxidative phosphorylation suggest a metabolic shift of HS Thmem cells towards glycolysis. The inclusion of transcriptome data from skin from HS patients and healthy participants in the analyses revealed that in HS skin lesions, the expression pattern of transcripts identified as DETs in blood HS Thmem cells was very similar to the expression pattern of the totality of protein-coding transcripts. Furthermore, there was no significant association between the extent of the expressional changes in the DETs of blood HS Thmem cells and the extent of the expressional changes in these transcripts in HS skin lesions compared to healthy donor skin. Additionally, a gene ontology enrichment analysis did not demonstrate any association of the DETs of blood HS Thmem cells with skin disorders. Instead, there were associations with different neurological diseases, non-alcoholic fatty liver disease, and thermogenesis. The levels of most DETs linked to neurological diseases showed a positive correlation to each other, suggesting common regulatory mechanisms. In summary, the transcriptomic changes in blood Thmem cells observed in patients with manifest cutaneous HS lesions do not appear to be characteristic of the molecular changes in the skin. Instead, they could be useful for studying comorbidities and identifying corresponding blood biomarkers in these patients.

Interleukin-19 Levels Are Increased in Palmoplantar Pustulosis and Reduced following Apremilast Treatment.

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease characterised by neutrophilic granulocyte (neutrophil)-filled pustules on the palms and soles. The pathogenesis of PPP is poorly understood. This study conducted an identification of the immune mediators associated with PPP and an exploration of apremilast treatment effects on them. We screened for immune mediators elevated in blood taken from 68 patients with PPP versus control participants and included the most promising parameters in the protocol of phase the 2, multicentre study of apremilast (PDE4 inhibitor) in 21 patients with moderate-to-severe PPP (APLANTUS; EudraCT 2016-005122-11) for respective analysis of blood and skin samples of study patients. We investigated stimulated neutrophils and three-dimensional reconstituted epidermis cultures. Interleukin (IL)-19 was found to be the most upregulated immune mediator in the blood of PPP patients. IL-19 serum levels were independent of patients' age, gender, and BMI but were associated with strongly upregulated cutaneous IL-19 expression and correlated with the number of palmoplantar pustules. In patients participating in the APLANTUS study, apremilast reduced pustules more effectively than erythema and scaling. Moreover, this treatment significantly reduced IL-19 blood and skin levels. The reduction in IL-19 blood levels at week 4 correlated with the reduction in pustule counts at week 20 (end of treatment). IL-19 was expressed by neutrophils activated in vitro and induced CXCL6, a neutrophil-attracting chemokine, in epidermis models. This work demonstrates elevated IL-19 levels in the blood and skin of PPP patients and suggests a relevant role of this cytokine in the appearance of pustules in this disorder. It also suggests the suitability of IL-19 blood levels as a predictive biomarker for the treatment response of PPP patients, which should be validated in further studies.

The impact of surgical interventions on the psychosocial well-being of patients with hidradenitis suppurativa.

BACKGROUND AND OBJECTIVES: Hidradenitis suppurativa is a chronic inflammatory skin disease. Depending on disease severity, a combination of conservative and surgical treatments is necessary. This analysis aimed to determine the impact of surgical interventions on patient psychosocial well-being. PATIENTS AND METHODS: This is a prospective, noninterventional, multicenter study. The medical history, medical examination, and patient-reported outcomes, including the Hospital Anxiety and Depression Scale, Dermatology Life Quality Index, and the Short Form-12 Health Survey, were collected from 481 patients with hidradenitis suppurativa. RESULTS: Among all patients with hidradenitis suppurativa included in this study, 74.2% reported surgery before study inclusion, of whom 92.4% could identify surgery type and location. Although adjusted for confounding factors, such as disease severity and activity, the aforementioned patient reported outcomes, did not vary significantly between groups of patients with different techniques and number of prior surgical intervention. However, patients without any prior surgical intervention yielded significantly better scores. CONCLUSIONS: In patients with hidradenitis suppurativa, previous surgery was associated with worse outcomes in anxiety, depression, and quality of life, showing the apparent need of psychological support. It remains unclear whether the morbidity of surgical procedures or a possible higher severity score in patients undergoing surgery is responsible.

Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis.

Psoriasis is a chronic inflammatory disease characterised by sharply demarcated erythematous and scaly skin lesions accompanied by systemic manifestations. Classified by WHO as one of the most serious non-infectious diseases, psoriasis affects 2-3% of the global population. Mechanistically, psoriatic lesions result from hyperproliferation and disturbed differentiation of epidermal keratinocytes that are provoked by immune mediators of the IL-23 and IL-17 pathway. Translational immunology has had impressive success in understanding and controlling psoriasis. Psoriasis is the first disease to have been successfully treated with therapeutics that directly block the action of the cytokines of this pathway; in fact, therapeutics that specifically target IL-23, IL-17, and IL-17RA are approved for clinical use and show excellent efficacy. Furthermore, inhibitors of IL-23 and IL-17 intracellular signalling, such as TYK2 or RORγt, are in clinical development. Although therapies that target the IL-23 and IL-17 pathway also improve psoriatic arthritis symptoms, their effects on long-term disease modification and psoriasis-associated comorbidities still need to be explored.

Tumor necrosis factor receptor signaling in keratinocytes triggers interleukin-24-dependent psoriasis-like skin inflammation in mice.

Psoriasis is a common chronic inflammatory skin disease with a prevalence of about 2% in the Caucasian population. Tumor necrosis factor (TNF) plays an essential role in the pathogenesis of psoriasis, but its mechanism of action remains poorly understood. Here we report that the development of psoriasis-like skin inflammation in mice with epidermis-specific inhibition of the transcription factor NF-κB was triggered by TNF receptor 1 (TNFR1)-dependent upregulation of interleukin-24 (IL-24) and activation of signal transducer and activator of transcription 3 (STAT3) signaling in keratinocytes. IL-24 was strongly expressed in human psoriatic epidermis, and pharmacological inhibition of NF-κB increased IL-24 expression in TNF-stimulated human primary keratinocytes, suggesting that this mechanism is relevant for human psoriasis. Therefore, our results expand current views on psoriasis pathogenesis by revealing a new keratinocyte-intrinsic mechanism that links TNFR1, NF-κB, ERK, IL-24, IL-22R1, and STAT3 signaling to disease initiation.

Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?

Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disease characterized by painful skin lesions that occur in the axillary, inguinal, gluteal and perianal areas of the body. These lesions contain recurring deep-seated, inflamed nodules and pus-discharging abscesses and fistulas. Affecting about 1% of the population, this common disease has gained appropriate clinical attention in the last years. Associated with numerous comorbidities including metabolic syndrome, HS is considered a systemic disease that severely impairs the quality of life and shortens life expectancy. Therapeutic options for HS are limited, comprising long-term antibiotic treatment, the surgical removal of affected skin areas, and neutralization of TNF-α, the only approved systemic treatment. Novel treatment options are needed to close the therapeutic gap. HS pathogenesis is increasingly better understood. In fact, neutrophilic granulocytes (neutrophils) seem to be decisive for the development of the purulent destructive skin inflammation in HS. Recent findings suggest a key role of the immune mediators IL-1ß, IL-17A and G-CSF in the migration into and activation of neutrophils in the skin. Although phytomedical drugs display potent immunoregulatory properties and have been suggested as complementary therapy in several chronic disorders, their application in HS has not been considered so far. In this review, we describe the IL-1/IL-17/G-CSF axis and evaluate it as potential target for an integrated phytomedical treatment of HS.

Risk factors for Epstein-Barr virus reactivation after renal transplantation: Results of a large, multi-centre study.

Epstein-Barr virus (EBV) reactivation is a very common and potentially lethal complication of renal transplantation. However, its risk factors and effects on transplant outcome are not well known. Here, we have analysed a large, multi-centre cohort (N = 512) in which 18.4% of the patients experienced EBV reactivation during the first post-transplant year. The patients were characterized pre-transplant and two weeks post-transplant by a multi-level biomarker panel. EBV reactivation was episodic for most patients, only 12 patients showed prolonged viraemia for over four months. Pre-transplant EBV shedding and male sex were associated with significantly increased incidence of post-transplant EBV reactivation. Importantly, we also identified a significant association of post-transplant EBV with acute rejection and with decreased haemoglobin levels. No further severe complications associated with EBV, either episodic or chronic, could be detected. Our data suggest that despite relatively frequent EBV reactivation, it had no association with serious complications during the first post-transplantation year. EBV shedding prior to transplantation could be employed as biomarkers for personalized immunosuppressive therapy. In summary, our results support the employed immunosuppressive regimes as relatively safe with regard to EBV. However, long-term studies are paramount to support these conclusions.

Ambivalent Effects of Tumor Necrosis Factor Alpha on Apoptosis of Malignant and Normal Human Keratinocytes.

INTRODUCTION: Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that may paradoxically induce either apoptosis or cell survival. It mediates its activity through binding of TNF-receptor (TNFR) 1 or 2. TNFR1 is mainly responsible for transmitting apoptotic signals. The activation of apoptotic mechanisms can either be intrinsic (mitochondrial) or extrinsic (death receptors). Death ligands such as TNF-related apoptosis-inducing ligand (TRAIL) specifically induce extrinsic apoptosis, while cytostatic drugs such as 5-fluorouracil (5FU) induce intrinsic apoptosis. OBJECTIVES: To investigate the effects of TNFα on apoptosis in malignant and normal human keratinocytes. METHODS: Human cutaneous squamous cell carcinoma (SCC) cell line SCC-13 and immortalized human keratinocytes HaCaT as well as primary normal human keratinocytes (PNHK) were stimulated with TNFα and then treated either with TRAIL or 5FU. Cell viability and cell proliferation, DNA fragmentation, apoptosis, and cytotoxicity were determined by WST-1 proliferation assay, ELISA, flow cytometry, and colorimetric analysis of lactate dehydrogenase, respectively. In addition, Western blotting was performed for analysis of caspase-3. RESULTS: TNFα affected viability of SCC-13 and HaCaT cells in combination with 5FU or TRAIL. In contrast, TNFα did not influence cell viability of PNHK. It enhanced the apoptotic effects of both extrinsic and intrinsic stimuli in SCC-13 and HaCaT. In clear contrast, TNFα protected PNHK against TRAIL- and 5FU-induced apoptosis. The effects were dose-dependent and TNFα-specific; furthermore, the apoptosis pathway was caspase-dependent. CONCLUSIONS: In summary, opposing effects of TNFα in malignant versus normal human keratinocytes were observed with possibly relevant clinical implications, when patients are treated with TNFα inhibitors.

Delayed Diagnosis of Hidradenitis Suppurativa and Its Effect on Patients and Healthcare System.

BACKGROUND: Hidradenitis suppurativa (HS) is a neglected chronic inflammatory disease with long delay in diagnosis. Besides pain, purulent discharge, and destruction of skin architecture, HS patients experience metabolic, musculoskeletal, and psychological disorders. OBJECTIVES: To determine the delay in HS diagnosis and its consequences for patients and the healthcare system. METHODS: This was a prospective, multicenter, epidemiologic, non-interventional cross-sectional trial carried out in Germany and based on self-reported questionnaires and medical examinations performed by dermatologists. In total, data of 394 adult HS patients were evaluated. RESULTS: The average duration from manifestation of first symptoms until HS diagnosis was 10.0 ± 9.6 (mean ± SD) years. During this time, HS patients consulted on average more than 3 different physicians - most frequently general practitioners, dermatologists, surgeons, gynecologists - and faced more than 3 misdiagnoses. Diagnosis delay was longer in younger and non-smoking patients. In most cases, HS was correctly diagnosed by dermatologists. The longer the delay of diagnosis, the greater the disease severity at diagnosis. Delayed HS diagnosis was also associated with an increased number of surgically treated sites, concomitant diseases, and days of work missed. CONCLUSION: This study demonstrates an enormous delay in the diagnosis of HS, which results in more severe disease. It also shows for the first time that a delay in diagnosis of a chronic inflammatory disease leads to a higher number of concomitant systemic disorders. In addition to the impaired health status, delayed diagnosis of HS was associated with impairment of the professional life of affected people.

Efficacy of Adalimumab for Nail Psoriasis During 24 Months of Continuous Therapy.

Psoriatic nail symptoms are frequent in psoriasis, affecting up to 80% of patients. Therapy responses to nail symptoms are often limited. In this multicentre non-interventional prospective study, 267 patients with nail involvement were treated with adalimumab for a period of 24 months. The efficacy of adalimumab for nail psoriasis was evaluated and predictors for better response were identified. For statistical analysis Kolmogorov-Smirnoff, Mann-Whitney U, Wilcoxon, χ2 and two-tailed Spearman's rank correlation tests were applied. After 3 and 6 months, reductions in Nail Psoriasis Severity Index (NAPSI) of 32.8% (p < 0.001) and almost 50% (p < 0.001), respectively, were observed, compared with baseline scores (mean NAPSI score, 34.2 ± 1.3). In 6 months, 60.0% of patients achieved NAPSI50, 36.4% NAPSI75, and 21.7% NAPSI90. Approximately 42% and 60% of patients achieved NAPSI90 after 12 and 24 months, respectively. At month 12, reduction in NAPSI significantly correlated with improvement in Dermatological Life Quality Index. Stratification by age, sex, and body mass index indicated that treatment was more effective in younger patients and those with higher body mass index. Adalimumab is an effective long-term therapy for nail psoriasis. The amelioration of nail symptoms correlates with an improvements in the skin disease and quality of life.

A novel approach reveals that HLA class 1 single antigen bead-signatures provide a means of high-accuracy pre-transplant risk assessment of acute cellular rejection in renal transplantation.

BACKGROUND: Acute cellular rejection (ACR) is associated with complications after kidney transplantation, such as graft dysfunction and graft loss. Early risk assessment is therefore critical for the improvement of transplantation outcomes. In this work, we retrospectively analyzed a pre-transplant HLA antigen bead assay data set that was acquired by the e:KID consortium as part of a systems medicine approach. RESULTS: The data set included single antigen bead (SAB) reactivity profiles of 52 low-risk graft recipients (negative complement dependent cytotoxicity crossmatch, PRA < 30%) who showed detectable pre-transplant anti-HLA 1 antibodies. To assess whether the reactivity profiles provide a means for ACR risk assessment, we established a novel approach which differs from standard approaches in two aspects: the use of quantitative continuous data and the use of a multiparameter classification method. Remarkably, it achieved significant prediction of the 38 graft recipients who experienced ACR with a balanced accuracy of 82.7% (sensitivity = 76.5%, specificity = 88.9%). CONCLUSIONS: The resultant classifier achieved one of the highest prediction accuracies in the literature for pre-transplant risk assessment of ACR. Importantly, it can facilitate risk assessment in non-sensitized patients who lack donor-specific antibodies. As the classifier is based on continuous data and includes weak signals, our results emphasize that not only strong but also weak binding interactions of antibodies and HLA 1 antigens contain predictive information. TRIAL REGISTRATION: ClinicalTrials.gov NCT00724022 . Retrospectively registered July 2008.

Limited Presence of IL-22 Binding Protein, a Natural IL-22 Inhibitor, Strengthens Psoriatic Skin Inflammation.

Psoriasis is a chronic inflammatory disease resulting from dysregulated immune activation associated with a large local secretion of cytokines. Among them, IL-22 largely contributes to epithelial remodeling and inflammation through inhibiting the terminal differentiation of keratinocytes and inducing antimicrobial peptides and selected chemokines. The activity of IL-22 is regulated by IL-22 binding protein (IL-22BP); however, the expression and role of IL-22BP in psoriatic skin has remained unknown so far. Here we showed that nonaffected skin of psoriasis patients displayed lower expression of IL-22BP than skin of healthy controls. Furthermore, the strong IL-22 increase in lesional psoriatic skin was accompanied by a moderate induction of IL-22BP. To investigate the role of IL-22BP in controlling IL-22 during skin inflammation, we used imiquimod-induced skin disease in rodents and showed that rats with genetic IL-22BP deficiency (Il22ra2-/-) displayed exacerbated disease that associated with enhanced expression of IL-22-inducible antimicrobial peptides. We further recapitulated these findings in mice injected with an anti-IL-22BP neutralizing Ab. Hypothesizing that the IL-22/IL-22BP expression ratio reflects the level of bioactive IL-22 in psoriasis skin, we found positive correlations with the expression of IL-22-inducible molecules (IL-20, IL-24, IL-36γ, CXCL1, and BD2) in keratinocytes. Finally, we observed that serum IL-22/IL-22BP protein ratio strongly correlated with psoriasis severity. In conclusion, we propose that although IL-22BP can control deleterious actions of IL-22 in the skin, its limited production prevents a sufficient neutralization of IL-22 and contributes to the development and maintenance of epidermal alterations in psoriasis.

Systemic therapies of pityriasis rubra pilaris: a systematic review.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous disorder. Treatment is challenging; the armamentarium consists of topical corticosteroids, phototherapy, classic systemic treatments such as retinoids or immunosuppressive drugs, and most recently biologicals. However, the relative effectiveness of therapies is unclear. Our objective was to review the published literature on systemic treatment of PRP. A systematic review was conducted on PubMed and the Cochrane Library up to 5 September 2017. Studies evaluating any systemic treatments of PRP (except for historical treatments) were included. Overall, 182 studies met the predefined inclusion criteria, and reported on 475 patients and 652 courses of treatment. 42.0 % (225/514) of all patients treated with retinoids achieved an excellent response (isotretinoin: 61.1 % [102/167], etretinate: 47 % [54/115], and acitretin: 24.7 % [43/174]) compared to an excellent response rate of 33.1 % (53/160) with methotrexate. Therapy with biologicals was successful in 51.0 % of patients (71/133) (ustekinumab: 62.5 % [10/16], infliximab: 57.1 % [28/49], etanercept: 53.3 % [16/30], and adalimumab: 46.4 % [13/28]). This review balances effectiveness, side effects, experience, and drug costs in order to suggest a treatment regimen starting with isotretinoin as first-line, methotrexate as second-line and biologicals as third-line treatment for this difficult-to-treat dermatosis.

Adipokines in psoriasis: An important link between skin inflammation and metabolic alterations.

Psoriasis is a chronic inflammatory skin disease most common in Europe, North America, and Australia. The etiology and pathomechanisms underlying the evolution and persistence of the skin alterations are increasingly being understood and have led to the development of effective anti-psoriatic therapies. Apart from the skin manifestations, psoriasis is associated with the metabolic syndrome (MetS), known to increase the risk of type 2 diabetes mellitus and cardiovascular disorders. Research of the last years demonstrated a dysregulated adipokine balance as an important link between inflammation, MetS, and consequential disorders. This article describes selected adipokines and their potential role in both metabolic comorbidity and skin inflammation in psoriasis.

Hidradenitis suppurativa/Acne inversa: an endocrine skin disorder?

Hidradenitis suppurativa / acne inversa (HS) is a chronic inflammatory, debilitating skin disorder with a largely unknown etiology. However, many observations such as the typical onset of the disease after puberty, the female predominance, the pre-menstrual flare ups and the improvement during pregnancy suggest a contribution of endocrinological factors to the emergence of the disease. In addition, the reported efficacy of anti-androgen treatment on HS indicates a possible involvement of androgens in the pathogenesis. Furthermore, the common comorbidity with metabolic syndrome points to possible interactions between endocrinological and metabolic alterations in the development of HS. Taking into account the endocrine functions of the human skin, several studies investigated the effects of hormones and the behavior of the pilosebaceous unit in the skin of patients with HS. In this review we describe the current view on the hormonal dysregulation and metabolic syndrome and their role in HS.

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.

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.