Hidradenitis Suppurativa Is Associated with Severe Sexual Impairment.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of the pilosebaceous unit, often affecting and deforming intimate regions. HS is associated with severe pain, pruritus, and constant, purulent, malodorous discharge expected to impair sexual health of patients. METHODS: We performed a cross-sectional, multicentric study involving 199 German patients from the health services research project "Epidemiology and Care in Acne inversa (EpiCAi)." The sexual health, HS severity, and quality of life of the studied group were evaluated using a specially designed questionnaire. RESULTS: Regardless of gender, HS has an enormous impact on patients' sexual health. The patients scored, on average, 28.8 ± 5.3 points on the Relation and Sexuality Scale (RSS). Multiple linear regression revealed that females and patients with Hurley III stage had higher sexual dysfunction (p = 0.012). Sexual dysfunction is associated with pain (ß = 0.25), the number of active lesions, the affected areas (ß = 0.14), and psychosocial aspects, including low quality of life (ß = 0.404), stigmatization (ß = 0.411), depression (ß = 0.413), and anxiety (ß = 0.300). Patients already see a substantial decrease in sexual frequency in the early stages of HS, while functional impairment and fear increase with the severity of the disease. CONCLUSION: Sexual health and management of its dysfunctions should be part of a holistic approach to HS patients.

Systematic review: Impact of stem cells-based therapy, and platelet-rich plasma in hair loss and telogen effluvium related to COVID-19.

Background: The incidence of hair loss (HL) and telogen effluvium (TE) in COVID-19 patients has been reported in several studies. Objectives: Evaluate both the increased incidence of HL and TE in COVID-19 and the effectiveness of Platelet-Rich Plasma (PRP), Adipose-derived Mesenchymal Stem Cells (AD-MSCs), and Human Follicle Stem Cells (HFSCs) in these patients. Methods: The protocol was developed by the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of PubMed, MEDLINE, Embase, Clinicaltrials. gov, Scopus, and Cochrane databases has been performed to identify papers focusing on HL and TE COVID-19 related, and papers focusing on AD-MSCs, HFSC, and PRP use. Results: Of the 404 articles initially identified focusing on HL and TE, 44 were related to COVID-19, and finally, only 6 were analyzed. On the other way, 331 articles focusing on AD-MSCs, HFSC, and PRP were initially identified. Of these, only 6 articles PRP (n = 3), AD-MSCs, and HFSCs (n = 3) have been analyzed. Conclusion: Collected data confirmed both an increased incidence of HL and TE in COVID-19 patients, preliminarily, the related effectiveness of AD-MSCs, HFSCs, and PRP without major side effects.

Systematic Review: Platelet-Rich Plasma Use in Facial Rejuvenation.

BACKGROUND: An increasing interest in maintaining a youthful appearance has led to the development of innovative and noninvasive aesthetic procedures for the treatment of facial aging, such as the recent use of autologous platelet-rich plasma (PRP). This article aims to review the literature and critically appraise the available evidence regarding the efficacy of autologous activated PRP and/or nonactivated PRP injection used for facial rejuvenation. METHODS: A systematic review regarding the clinical use of autologous activated PRP and autologous nonactivated PRP injection in facial rejuvenation against signs of aging was performed using the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov , Scopus, and Cochrane databases. The protocol was developed following the Preferred Reporting for Items for Systematic Reviews-Protocols guidelines. The included studies had to match predetermined criteria according to the patients, intervention, comparator, outcomes, and study design approach. RESULTS: Eleven of the 12 studies identified, including three randomized split-face trials, showed improved results despite differences in study design and outcome measures, many of which were subjective. CONCLUSION: Further randomized controlled trials and related systematic reviews need to be performed, as evidence-based medicine studies of level I are required to confirm PRP injection efficacy in facial rejuvenation, to consolidate the promising results of the studies identified in this systematic review.

Similar Levels of Efficacy of Two Different Maintenance Doses of Adalimumab on Clinical Severity and Quality of Life of Patients with Hidradenitis Suppurativa.

Adalimumab is the only biologic agent approved for the treatment of moderate-to-severe hidradenitis suppurativa (HS) patients (i.e., with Hurley II or III), which is recommended in two different maintenance doses (i.e., 40 mg weekly or 80 mg every two weeks). We conducted a prospective multicentric study to measure outcomes related to the severity of disease and quality of life (QoL) of patients affected by moderate-to-severe HS, treated with adalimumab at a maintenance dosing of 40 mg or 80 mg. Assessments were performed at baseline (T0) and after 32 weeks of treatment (T32). We enrolled 85 moderate-to-severe HS Italian patients, 43 men (50.6%) and 42 women, aged between 16 and 62 years (median 31 years, interquartile range 24.4-43.8). Statistically significant improvements were observed for clinical status (with a mean reduction of 7.1 points for the International Hidradenitis Suppurativa Severity Score System (IHS4)), pain levels (3.1 mean decrease in VAS), and QoL (3.4 mean improvement in DLQI score). Patients with no comorbidities, and those with higher levels of perceived pain showed significantly greater improvement in QoL than their counterpart from T0 to T32. As for the proportion of patients who at follow-up reached the minimal clinical important difference (MCID) in QoL, significantly higher proportions of success were observed for age (patients in the 29-39 category), pain (patients with higher reported pain), and Hurley stage III. While both treatment regimen groups (i.e., 40 vs. 80 mg) improved significantly, no statistical differences were observed when comparing the two treatment dosages.

Whole-Exome Sequencing in 10 Unrelated Patients with Syndromic Hidradenitis Suppurativa: A Preliminary Step for a Genotype-Phenotype Correlation.

BACKGROUND: The genetics of syndromic hidradenitis suppurativa (HS), an immune-mediated condition associated with systemic comorbidities such as inflammatory bowel diseases and arthritis, has not been completely elucidated. OBJECTIVE: To describe clinical features and genetic signature of patients with the main syndromic HS forms, i.e., PASH, PAPASH, and PASH/SAPHO overlapping. METHODS: Whole-exome sequencing (WES) approach was performed in ten patients with syndromic HS. RESULTS: Three clinical settings have been identified based on presence/absence of gut and joint inflammation. Four PASH patients who had also gut inflammation showed three different variants in NOD2 gene, two variants in OTULIN, and a variant in GJB2, respectively. Three PAPASH and three PASH/SAPHO overlapping patients who had also joint inflammation showed two different variants in NCSTN, one in WDR1 and PSTPIP1, and two variants in NLRC4, one of whom was present in a patient with a mixed phenotype characterized by gut and joint inflammation. LIMITATIONS: Limited number of patients that can be counterbalanced by the rarity of syndromic HS. CONCLUSION: Syndromic HS can be considered as a polygenic autoinflammatory condition; currently WES is a diagnostic tool allowing more accurate genotype-phenotype correlation.

Pediatric Hidradenitis Suppurativa: A Cross-Sectional Study on Clinical Features and Treatment Approaches.

BACKGROUND: Hidradenitis suppurativa is uncommon in patients of pediatric age, and differentiation with adult-onset disease is controversial. Treatment of pediatric hidradenitis suppurativa is scarcely standardized, and specific guidelines are lacking. OBJECTIVE: We report the clinical features, relevant risk-factors, comorbidity profile, and treatment patterns of a hospital-based cohort of pediatric hidradenitis suppurativa. METHODS: In a cross-sectional study data on patients' demographics, disease-specific characteristics, early/pre-pubertal onset of disease, comorbidities, and treatment management were retrieved. Reference population data and clinical data from the national hidradenitis suppurativa disease registry were used for comparison. RESULTS: From a database of 870 patients with hidradenitis, 71 (15 males and 56 females) patients aged <18 years (mean age: 15.3 years; range 8-17 years), with mild (Hurley I, 45.1%) and moderate-severe disease (Hurley II-III, 54.9%), were retrieved. Smoking (23.9%) and overweight/obese frequencies (59.2%) were higher than reference population standards. Patient's older age at baseline (OR 1.43, 95% CI: 1.01 to 2.02) and higher BMI (OR 1.26, 95% CI: 1.07-1.48) were the only factors associated with moderate-severe disease. Family history and early/pre-pubertal onset of disease were not associated with severity or extent of disease. Sebaceous-follicular comorbid conditions were associated with cigarette smoking (P = .002). Among 81 treatment courses, clindamycin-based and zinc-sulphate-based combination regimens were most frequently used (59.3%). Female preponderance, family history of disease and extensive involvement were significantly different from the general hidradenitis suppurativa population. CONCLUSIONS: Pediatric hidradenitis suppurativa presents a clinical spectrum comparable to adult-onset disease. Increased preventive measures should target obesity and smoking in this population.

Systematic review: The platelet-rich plasma use in female androgenetic alopecia as effective autologous treatment of regenerative plastic surgery.

BACKGROUND: The number of clinical trials evaluating platelet-rich plasma (PRP) efficacy in female androgenetic alopecia (F-AGA) has exponentially increased during the last five years. A systematic review focused on this specific field has been performed by assessing the local infiltrations of PRP compared with any control for F-AGA in the selected studies. OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of the use of PRP in F-AGA. METHODS: The protocol was developed in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. A multistep search of PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on female pattern hair loss (FPHL) treatment with PRP. Of the 63 articles initially identified, 11 articles focusing on AGA were selected and, consequently, only 5 articles focused exclusively on F-AGA were analyzed. Of this amount, 3 articles were randomized-controlled trials (RCTs), 1 clinical trial, and 1 double-blind placebo-controlled pilot study (DBPCPS). The studies included had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. RESULTS: Eight percent of the articles selected and analyzed, reported a positive effect of PRP for F-AGA treatment. The information analyzed highlights the positive effects of PRP on F-AGA, without major side effects and thus, it may be considered as a safe and effective alternative procedure to treat hair loss compared with traditional drugs as Minoxidil® and Finasteride®. CONCLUSIONS: The use of PRP in F-AGA was safe and effective for F-AGA.

The Effectiveness of Low-Level Light/Laser Therapy on Hair Loss.

Background: A systematic review on low-level light/laser therapy (LLLT) in male pattern hair loss (MPHL) and female pattern hair loss (FPHL) has been performed. Objectives: Compare the reported effectiveness of LLLT in MPHL and FPHL with any control, through randomized controlled trials (RCTs) analysis. Methods: The protocol was developed in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify articles on MPHL and/or FPHL treatment with LLLT. Results: Of the 298 articles initially identified, 136 articles focusing on MPHL and FPHL were selected and, consequently, only 36 articles focused exclusively on LLLT. Of this amount, 23 articles were clinical trials while 13 articles were systematic reviews. Systematic reviews were excluded, and only seven articles were analyzed as RCTs. Conclusions: All the articles selected and analyzed reported a positive effect of LLLT for MPHL and/or FPHL treatment without side effects.

PASH, PAPASH, PsAPASH, and PASS: The autoinflammatory syndromes of hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease usually involving the major skin folds characterized by a multifactorial pathogenesis and a wide spectrum of clinical manifestations. It can also rarely present in association with other diseases as complex clinical syndromes, causing additional diagnostic and therapeutic challenges. Different etiopathologic factors contribute to follicular inflammation and suppurative lesions of syndromic HS, including follicular hyperkeratinization and plugging, as well as activation of autoinflammatory pathways. Patients with syndromic HS frequently have a severe disease course, presenting with atypical skin involvement, signs of systemic inflammation, and resistance to conventional treatments. Systematic classification of syndromic HS is based on clinical, pathogenetic, and genetic factors, but it is constantly evolving due to increased disease awareness. Treatment of syndromic HS is difficult and should be personalized on a case-by-case basis. Investigating syndromic HS can lead to useful insights on genetics and pathogenesis, translating into new clinical approaches for sporadic hidradenitis. We review the classification, clinical presentation, disease associations, and therapeutic management of syndromic HS, focusing mainly on its autoinflammatory syndromes PASH, PAPASH, PsAPASH, and PASS.

Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) against Ultraviolet (UV) Radiation Effects and the Skin Photoaging.

The skin is a natural barrier against the ultraviolet (UV) radiation of sunlight. The long-term and/or repetitive exposure to the sunlight and related UV radiation may change the skin structure, decreasing collagen production, promoting premature skin aging, which is termed "photoaging". The signs of photoaging include wrinkle formation, mottled pigmentation, and/or cancerous changes. For many years, adipose-derived mesenchymal stem cells (AD-MSCs) and fat grafting (F-GRF) have been used to combat photoaging signs, wrinkles, loss of elasticity, and face soft tissue defects. Several studies have analyzed in vitro actions of AD-MSCs against photoaging's effects, thanks to their migratory activity, paracrine actions, and related in vivo-ex vivo outcomes. In fact, AD-MSCs act against skin photoaging in vitro via activation of dermal fibroblast proliferation, antioxidant effect, and matrix metalloproteinases (MMPs) reduction. In vivo and ex vivo outcomes regard the local injection of AD-MSCs, F-GRF, and/or enriched-F-GRF with AD-MSCs directly in the wrinkles and the face's soft tissue defects. This concise review summarizes the most recent in vitro, in vivo and ex vivo outcomes and developments on the effects of AD-MSCs and F-GRF against photoaging.

Systematic review: Advances of fat tissue engineering as bioactive scaffold, bioactive material, and source for adipose-derived mesenchymal stem cells in wound and scar treatment.

Fat tissue (FT) has been used for many years in regenerative surgery as a bioactive material through the lipofilling/fat graft (F-GRF)-nano-fat technique, as a bioactive scaffold when it was enriched with adipose-derived mesenchymal stem cells (AD-MSCs) contained in the stromal vascular fraction (SVF), and as a direct source of AD-MSCs used in wound healing (WH) and scar treatment (ST). This systematic review aims to describe the advances in FT engineering applied to regenerative surgery (from bench to clinic), through the use of AD-MSCs, SVF contained in F-GRF in WH and ST. The work has been performed by assessing in the selected studies autologous graft of AD-MSCs, SVF, and F-GRF compared to any control for ST and WH. The protocol was developed following the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov , Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, SVF, and F-GRF use in WH and ST in which FT was used as bioactive material-scaffold and source of AD-MSCs. Of the 714 articles initially identified, 453 articles focusing on regenerative strategies in WH and ST were selected and, consequently, only 84 articles that apparently related to AD-MSC, SVF, and F-GRF were analyzed. Of these, 61 articles identified as pre-clinical, experimental, and in vitro, and 5 articles identified as a comment and systematic review were excluded. Only 18 original articles which strictly and exclusively focused on autologous AD-MSCs, SVF, and F-GRF in ST and WH were analyzed. The included studies had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. The identified studies described microscopic and clinical outcomes in patients treated with AD-MSCs, SVF, and F-GRF. Collected data confirmed the safety and efficacy of FT both as bioactive material-scaffold and source of AD-MSCs in WH and ST without major side effects.

Pruritus as a Distinctive Feature of Type 2 Inflammation.

Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients' quality of life and strongly interfere with sleep, social, and work activities. We review the role of type-2 inflammation and immunity in the pathogenesis of chronic pruritic conditions of the skin. Type 2 cytokines, including IL-4, IL-13, thymic stromal lymphopoietin, periostin, IL-31, IL-25, and IL-33 are released by mast cells, innate lymphoid cells 2, keratinocytes, and type 2 T lymphocytes, and are master regulators of chronic itch. These cytokines might act as direct pruritogen on primary sensory neurons (pruriceptors) or alter the sensitivity to other itch mediators Type 2 inflammation- and immunity-dominated skin diseases, including atopic dermatitis, prurigo nodularis, bullous pemphigoid, scabies, parasitic diseases, urticaria, and Sézary syndrome are indeed conditions associated with most severe pruritus. In contrast, in other skin diseases, such as scleroderma, lupus erythematosus, hidradenitis suppurativa, and acne, type 2 inflammation is less represented, and pruritus is milder or variable. Th2 inflammation and immunity evolved to protect against parasites, and thus, the scratching response evoked by pruritus might have developed to alert about the presence and to remove parasites from the skin surface.

Systematic Review: Adipose-Derived Mesenchymal Stem Cells, Platelet-Rich Plasma and Biomaterials as New Regenerative Strategies in Chronic Skin Wounds and Soft Tissue Defects.

The number of clinical trials evaluating adipose-derived mesenchymal stem cells (AD-MSCs), platelet-rich plasma (PRP), and biomaterials efficacy in regenerative plastic surgery has exponentially increased during the last ten years. AD-MSCs are easily accessible from various fat depots and show intrinsic plasticity in giving rise to cell types involved in wound healing and angiogenesis. AD-MSCs have been used in the treatment of soft tissue defects and chronic wounds, employed in conjunction with a fat grafting technique or with dermal substitute scaffolds and platelet-rich plasma. In this systematic review, an overview of the current knowledge on this topic has been provided, based on existing studies and the authors' experience. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, PRP, and biomaterials used in soft tissue defects and chronic wounds. Of the 2136 articles initially identified, 422 articles focusing on regenerative strategies in wound healing were selected and, consequently, only 278 articles apparently related to AD-MSC, PRP, and biomaterials were initially assessed for eligibility. Of these, 85 articles were excluded as pre-clinical, experimental, and in vitro studies. For the above-mentioned reasons, 193 articles were selected; of this amount, 121 letters, expert opinions, commentary, and editorials were removed. The remaining 72 articles, strictly regarding the use of AD-MSCs, PRP, and biomaterials in chronic skin wounds and soft tissue defects, were analyzed. The studies included had to match predetermined criteria according to the patients, intervention, comparator, outcomes, and study design (PICOS) approach. The information analyzed highlights the safety and efficacy of AD-MSCs, PRP, and biomaterials on soft tissue defects and chronic wounds, without major side effects.

Chronic Nodular Prurigo: A European Cross-sectional Study of Patient Perspectives on Therapeutic Goals and Satisfaction.

Chronic nodular prurigo is characterized by recalcitrant itch. Patient perspectives on therapeutic goals, satisfaction with therapy and efficacy of therapeutic regimens for this condition are unknown. This questionnaire study examined these issues in 406 patients with chronic nodular prurigo from 15 European dermatological centres. Improvements in itch, skin lesions and sleep were the most important goals. Emollients, topical corticosteroids and antihistamines were the most frequently used treatments, while a minority of patients were prescribed potent medications, such as systemic immunosuppressants and gabapentinoids. Most patients were not satisfied with their previous therapy (56.8%), while 9.8% did not receive any therapy despite having active disease. A substantial number of respondents (28.7%) considered none of the therapeutic options effective. Although chronic nodular prurigo is a severe disease, most patients were not treated with potent systemic drugs, which may contribute to the high levels of dissatisfaction and disbelief in available therapies. Specific guidelines for chronic nodular prurigo and the development of novel therapies are necessary to improve care.

Prevalence of Neuropathic Pain and Related Characteristics in Hidradenitis Suppurativa: A Cross-Sectional Study.

BACKGROUND: Pain is a core symptom of hidradenitis suppurativa (HS) and is of complex, multifactorial origin. HS patients frequently report typical neuropathic pain qualities, but its prevalence has been poorly described. METHODS: In this cross-sectional study, we examine the prevalence of neuropathic pain (NP) component and related pain-characteristics of a hospital-based cohort of patients with symptomatic HS. We administered the pain-DETECT tool (PDQ), a validated screening tool for NP, collecting clinical and patient-reported data on pain, pruritus and pain-management. We obtained 110 complete datasets from symptomatic HS patients (49.1% females; Hurley I (27.3%])-II (45.5%)-III (27.3%)). According to the PDQ tool, 30% of patients were classified with a high probability (>90%) of neuropathic pain (LNP). LNP status was significantly associated with increased pain severity, disease activity, pruritus intensity and use of pain medication. Regression analysis showed a significant impact of the PDQ score on patient-reported outcomes, including pain severity and the dimensions of activity and affective pain interference. HS patients may present a mixed chronic pain phenotype with a neuropathic component, thus requiring additional pain-assessments. A multi-modal approach to pain management, in combination with disease-specific treatment, should be implemented in future interventional studies.

Research progress on Mesenchymal Stem Cells (MSCs), Adipose-Derived Mesenchymal Stem Cells (AD-MSCs), Drugs, and Vaccines in Inhibiting COVID-19 Disease.

Mesenchymal Stem Cells (MSCs), and Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) have been used for many years in regenerative medicine for clinical and surgical applications. Additionally, recent studies reported improved respiratory activity after intravenous administration of MSCs into patients affected by coronavirus disease 2019 (COVID-19) caused by the Coronavirus 2 (SARS-CoV-2) suggesting their role as anti-viral therapy. Severe COVID-19 patients usually progress to acute respiratory distress syndrome, sepsis, metabolic acidosis that is difficult to correct, coagulation dysfunction, multiple organ failure, and even death in a short period after onset. Currently, there is still a lack of clinically effective drugs for such patients. The high secretory activity, the immune-modulatory effect, and the homing ability make MSCs and in particular AD-MSCs both a potential tool for the anti-viral drug-delivery in the virus microenvironment and potential cellular therapy. AD-MSCs as the most important exponent of MSCs are expected to reduce the risk of complications and death of patients due to their strong anti-inflammatory and immune-modulatory capabilities, which can improve microenvironment, promote neovascularization and enhance tissue repair capabilities. In this literature review, the role of regenerative strategies through MSCs, AD-MSCs, and adipocyte-secreted exosomal microRNAs (A-SE-miRs) as a potential antiviral therapy was reported, comparing the results found with current research progress on drugs and vaccines in COVID-19 disease.