New Insight into the Molecular Pathomechanism and Immunomodulatory Treatments of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is an immune-mediated inflammatory disorder characterized by deep-seated nodules, abscesses, sinus tracts and scars localized in the intertriginous areas. It is accompanied by pain, malodourous secretion and a dramatically decreased quality of life. Although the pathogenesis has not been entirely elucidated, the primary event is follicular hyperkeratosis of the pilosebaceous apocrine unit. Since the registration of the tumor necrosis factor-alpha inhibitor Adalimumab in 2015, several cytokines have been implicated in the pathomechanism of HS and the research of novel therapeutic targets has been intensified. We provide an update on the inflammatory cytokines with a central role in HS pathogenesis and the most promising target molecules of future HS management.

Efficacy and safety of topical resorcinol 15% versus topical clindamycin 1% in the management of mild-to-moderate hidradenitis suppurativa: A retrospective study.

Topical and systemic antibiotic therapy remains the first-line treatment for mild-to-moderate hidradenitis suppurativa (HS). However, literature data on antibiotic resistance in HS are growing. A total of 134 patients with mild-to-moderate HS were retrospectively evaluated. Seventy-three patients (group A) received topical clindamycin 1% and 61 patients (group B) received topical resorcinol 15%. We evaluated the efficacy and tolerability of topical 15% resorcinol versus topical 1% clindamycin in mild-to-moderate HS, comparing the clinical response at 12 weeks of treatment. Patients treated with resorcinol 15% showed a significant improvement in Hidradenitis Suppurativa Clinical Response, International Hidradenitis Suppurativa Severity Score System, and Pain Visual Analogue Scale score from baseline compared to patients treated with clindamycin 1%. Topical resorcinol 15% could be a valid alternative to clindamycin in the management of acute and long-standing HS, limiting antibiotic use and antimicrobial resistance.

Management of patients with hidradenitis suppurativa during the COVID-19 pandemic: Risk and benefit of immunomodulatory therapy.

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Italy has been the first nation affected by the coronavirus pandemic and is the second in the number of reported deaths in the European Union. In the United Hospital of Ancona, a specialist outpatient clinic dealing with diagnosis and treatment of immunomediated skin diseases has been operating since 1985, and 291 patients with hidradenitis suppurativa (HS) are currently being treated. Several cutaneous immunomediated diseases, including HS, are treated with biologic and nonbiologic immunosuppressive and immunomodulatory drugs. Since the end of February 2020, when the SARS-CoV-2 pandemic had already spread in most of Italy, a task force comprised of seven specialists has been set up with the aim of addressing problems relating to the specific risk for this class of patients in relation to SARS-CoV-2 infection and immunosuppressive ongoing therapy. In this article, the management of HS disease during the COVID-19 pandemic is discussed. The main goal was to evaluate the risk/benefit in modulating treatment taking into consideration patients' risk of exposure to SARS-CoV-2 virus.

Global coronavirus pandemic (SARS-CoV-2): Past, present, and future of pediatric dermatology.

Two months have passed since the World Health Organization (WHO) declared the pandemic of the Coronavirus Disease 19 (COVID-19), caused by the SARS-CoV-2 virus, on 11 March 2020. Medical and healthcare workers have continued to be on the frontline to defeat this disease, however, continual changes are being made to their working habits which are proving to be difficult. Although the skin is not the main target of the SARS-CoV-2 infection, it is strongly involved both directly and indirectly, in many aspects of dermatological disease management, and particularly in pediatric dermatology. In this manuscript, our goal was to provide a "up-to-date" account on this topic, through analysis of current literature and sharing our experiences during this pandemic.

Systemic Antibiotic Therapy in Hidradenitis Suppurativa: A Review on Treatment Landscape and Current Issues.

Hidradenitis suppurativa (HS) is a chronic, recurrent, and inflammatory skin disease characterized by painful, deep-seated, nodules, abscesses, and sinus tracts in sensitive areas of the body, including axillary, inguinal, and anogenital regions. Antibiotics represent the first-line pharmacological treatment of HS because of their anti-inflammatory properties and antimicrobial effects. This narrative review summarizes the most significant current issues on the role of systemic antibiotics in the management of HS, critically analyzing the main limits of their use (antibiotic resistance and toxicity). Although, in the last decades, several cytokines have been implicated in the pathomechanism of HS and the research on the use of novel biologic agents in HS has been intensified, antibiotics remain a valid therapeutic approach. Future challenges regarding antibiotic therapy in HS comprise their use in association with biologics in the management of acute flare or as a bridge therapy to surgery.

Melanoma and subcutaneous adipose tissue: Role of peritumoral adipokines in disease characterization and prognosis.

In the last decades, the concept of adipose organ has emerged, giving adipose tissue an active endocrine and immunologic function through the secretion of multiple cytokines and chemokines that seem to be implicated in the development and progression of several cancer, including cutaneous melanoma. In this pilot experimental study, we analyzed the expression in the peritumor subcutaneous adipose tissue of the most significant adipokines involved in the processes of carcinogenesis and metastasis in a population of melanoma patients and in two control groups composed of melanocytic nevi and epidermoid cysts, respectively. We correlated the results obtained with the main disease prognostic factors observing a statistically significant increase in the expression of PAI1, LEP, CXCL1, NAMPT, and TNF-α at the level of the peritumor tissue of the melanoma samples compared to the control groups and a correlation of the same with the histopathological prognostic factor of melanoma. Our preliminary study shows that the overexpression of PAI1, LEP, CXCL1, NAMPT, and TNF-α may contribute to the growth and to the local aggressiveness of cutaneous melanoma. It opens the hypothesis of a direct oncogenic role of subcutaneous adipose tissue and adipokines in the tumorigenesis of melanoma.

The Effect of Dalbavancin in Moderate to Severe Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by painful nodules, abscesses, and fistulas, localized to the areas of the folds where apocrine glands are present: the armpits, groin, inframammary region, and genital or perineal region. The management is still challenging, and it includes mainly systemic antibiotics, immunosuppressors, and biologic agents. Antibiotics are frequently used in the management of HS for their anti-inflammatory, immunomodulatory, and antimicrobial properties, but no data have been reported regarding the use of dalbavancin in HS. The aim of our practice was to evaluate efficacy, flare, and disease-free survival after dalbavancin therapy in a selected population with HS. We report the experience of the Ancona Dermatology Clinic in treating HS flare-ups with dalbavancin and its rationale for use. Our observation shows that the use of dalbavancin is an effective and well-tolerated treatment for the management of Hurley stage II-III HS; currently, dalbavancin should be considered as a supportive therapy for selected patients.

The effect of dupilumab in an HBV-HIV coinfected atopic patient: a case report.

Atopic dermatitis (AD) is a chronic immune-mediated inflammatory disease typical of childhood that can also affect adults. AD is clinically characterized by intensely pruritic eczematous lesions. The burden of this disease and its impact on quality of life are often substantial. Dupilumab is a fully humanized monoclonal antibody against interleukin 4 (IL-4) receptor α, capable of blocking IL-4 and IL-13 signaling. This novel therapy represents the first biologic approved for the treatment of moderate to severe AD. Our report describes the case of a 39-year-old adult patient affected by severe chronic AD with associated allergic and viral comorbidities for whom conventional systemic therapies proved ineffective or contraindicated. The main source of interest in this case is hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection because, to our knowledge, this is the first case of an adult atopic patient treated with dupilumab in the simultaneous presence of these comorbidities. Regarding coinfections, the patient was on antiretroviral therapy for HBV and HIV before starting dupilumab. Efficacy and safety data after 24 weeks of therapy are reported in detail.

Metabolic, pharmacokinetic, and toxicological issues of biologic therapies currently used in the treatment of hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa is a chronic, relapsing, debilitating inflammatory dermatologic disease of the terminal hair follicles at intertriginous sites clinically characterized by painful inflammatory nodules, abscesses, draining sinus tracts, and dermal fibrosis. The management of hidradenitis suppurativa is a challenge and usually consists of both medical and surgical approaches, which must often be combined for best outcome. The introduction of biological therapies, specifically TNFα-inhibitors such as adalimumab, has profoundly changed the therapeutic armamentarium of the disease. AREAS COVERED: The PubMed database was searched using combinations of the following keywords: hidradentis suppurativa, biologic therapy, TNF-α inhibitors, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, adverse effects, pharmacodynamics, pharmacology, adverse events, pharmacokinetics, drug interaction. This article reviews and updates the chemistry, pharmacokinetics, mechanism of action, adverse effects, drug interactions of on-label and off-label use of TNF-α inhibitors in HS. EXPERT OPINION: Biologic agents, particularly adalimumab, exhibit clinical efficacy in patients with hidradenitis suppurativa. Careful patient selection and close monitoring during treatment are mandatory to provide safe and effective use of the TNF-α inhibitor. Familiarity with biologic agents is crucial because these agents could become a consolidated treatment option in the clinician's therapeutic approaches.

Efficacy and Safety of Topical Calcipotriol 0.005% Versus Topical Clobetasol 0.05% in the Management of Alopecia Areata: An Intrasubject Pilot Study.

INTRODUCTION: Alopecia areata (AA) is a chronic inflammatory non-scarring type of hair loss. Current therapies for alopecia areata are rather limited and mainly involve the use of topical, intra-lesional or systemic steroids and topical immunotherapy, with variable benefit. Recent studies have demonstrated that vitamin D analogues could potentially promote hair growth in patients with patchy AA. METHODS: We investigated the efficacy and safety of treatment with calcipotriol, a synthetic derivative of vitamin D (calcipotriol 0.005% ointment), versus treatment with the corticosteroid clobetasol (topical clobetasol 0.05% formulation), in a series of 35 patients with scalp AA, using an intrasubject design. RESULTS: Patches treated with calcipotriol ointment showed greater and faster response rates than did those treated with topical clobetasol, although the differences were not statistically significant. The main strength of the study is its prospective design; the main limitation is the small number of participants. CONCLUSIONS: Treatment with the calcipotriol would appear to be reasonably effective in patients with mild to moderate patchy AA and was associated with only limited and reversible side effects.

Bullous Sweet's syndrome in a patient with ulcerative colitis: a rare case report.

Bullous Sweet's syndrome is an uncommon clinical presentation of classical Sweet's syndrome, often associated with various kinds of tumors, infections, and active inflammatory bowel diseases (IBDs), namely Crohn's disease and ulcerative colitis. Only a few cases of bullous Sweet's syndrome associated with ulcerative colitis are described in the literature. We report a case of a 62-year-old female patient with acute exacerbation of ulcerative colitis associated with infiltrating purple-erythematous skin plaques, which were partly vesicular, and oral ulcerative stomatitis. Biopsy was consistent with bullous Sweet's syndrome. Treatment with betamethasone sodium phosphate, starting at 5.5 mg, followed by gradual dose tapering for 12 weeks, resulted in improvement of the ulcerative colitis and disappearance of the cutaneous lesions. Bullous Sweet's syndrome most commonly occurs in the setting of hematologic malignancies, suggesting that physicians should perform long-term screening for early diagnosis of hematological and solid malignancies.

Buschke-Ollendorff syndrome in a 6-year-old patient: clinical and histopathological aspects of a rare disease.

Buschke-Ollendorff syndrome (BOS) is a rare genetic hereditary genodermatosis characterized by benign skeletal and cutaneous lesions. Skeletal alterations known as osteopoikilosis (OPK) or "spotted bone disease" are asymptomatic areas of sclerosing dysplasia. Two skin lesion patterns have been described because they may be of either elastic tissue (juvenile elastoma) or collagenous composition (dermatofibrosis lenticularis disseminata). We present the case of a 6-year-old male patient with yellowish papules that coalesced to form plaques localized on both thighs and on the upper limbs consistent with a connective tissue nevus (CTN) diagnosis. X-ray examination of the skeletal system revealed the presence of multiple small areas (measuring between 1 and 7 mm) of increased bone density (OPK) bilaterally. A skin biopsy was performed and did not show striking alterations in the number or dimension of the extracellular matrix fibers, but it showed mucin deposition between them, which is compatible with a CTN. This study reports on the clinical presentation and histological examination of this unusual disease.