Nuovi farmaci antivirali e preminente ruolo del dermatologo: un caso emblematico.

La disponibilità di farmaci innovativi in svariati ambiti della medicina vede il dermatologo impegnato nella valutazione e nella gestione dei possibili effetti collaterali cutanei. L’insorgenza di reazioni avverse cutanee di grado severo (severe cutaneous adverse reactions, SCAR) può essere determinante per la sospensione definitiva del trattamento, oltre che pericolosa per l’incolumità del paziente. Si presenta il caso di un paziente affetto da epatite C cronica trattato con telaprevir, inibitore della proteasi NS3/4A del virus dell'epatite C, in associazione a peginterferone alfa e ribavirina, che ha sviluppato una reazione cutanea di severità progressivamente crescente. L’estensione della manifestazioni cutanee a oltre il 50% della superficie corporea, la comparsa di febbre e sintomatologia sistemica e le alterazioni della formula leucocitaria hanno imposto la sospensione del trattamento prima delle 12 settimane previste, esponendo, d’altro canto, il paziente al rischio di una mancata risposta virologica. Si discutono l’inquadramento diagnostico del caso clinico in esame, i provvedimenti terapeutici attuati e i criteri di severità delle SCAR

A case of subcutaneous sarcoidosis: Considerations on genetic characterization, clinical presentation and course

Sarcoidosis is a systemic granulomatous disorder of unknown etiology, which can involve the skin. Subcutaneous sarcoidosis is a rare variant of the cutaneous sarcoidosis, typically presenting as single or multiple indurated plaques on the upper extremities. It is closely associated with systemic manifestations, mainly lung involvement, although response to treatment and prognosis remain good. We report the case of a 58 year-old woman with subcutaneous manifestations associated with lung infiltrates and mediastinal and paratracheal adenopathy. Cutaneous and pulmonary involvement as well as mediastinal lymphadenopathy rapidly regressed without any systemic treatment. HLA typing was performed to evaluate the potential role of an immunogenetic predisposition factor

P2X7 receptor involvement in the pathogenesis of Hidradenitis Suppurativa

The P2X7 receptor (P2X7R) is an ATP-gated plasma membrane ion channel widely distributed in human tissues, the highest expression being in cells of the immune and inflammatory systems, especially of the myeloid lineage [1]. The P2X7R plays different functions depending on the cell type and agonist concentration. One of the most relevant P2X7R activities consists in the regulation of inflammatory responses mainly through NLRP3 inflammasome activation and IL-1β processing and release [2]. Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent, painful nodules and abscesses of apocrine glands. Follicular occlusion and subsequent rupture are central events in HS. HS pathogenesis is not yet understood and many researches have recently focused on possible involvement of components of the immune system, mainly cytokines. Indeed, dysregulated cytokine expression, e.g. IL-1β, TNF-α, IL-6, was found in skin, plasma and immune cells of HS patients [3-6]. The aim of this study was to investigate a possible role of P2X7R in the pathogenesis of HS, also in view of a possible use of P2X7R antagonists in the treatment of this pathology with few options for effective therapy. For this 30 HS patients compared to 30 matched healthy control subjects, have been studied as regard skin biopsies, plasma and peripheral blood mononuclear cells (PBMC). Results show increased P2X7R expression in skin biopsies of HS patients respect to healthy controls (Fig. 1). Higher P2X7R immunostaining was shown by cheratinocytes as well as by some inflammatory cells in the derma, mainly macrophages and plasma cells. Plasma IL-1β levels were increased in HS patients respect to healthy controls suggesting a role for this cytokine in disease development. In apparent contrast with the last finding, PBMC from HS patients appeared defective in IL-1β release upon P2X7R stimulation. This is in agreement with deregulated and compartmentalized cytokine responses found by other authors [3,6]. Further research is necessary to identify the main source of circulating IL-1β as well as the expression of inflammasome components in HS lesional and possibly perilesional skin. Open image in new window Figure 1. Increased P2X7 immunostaining of skin section from HS patient (A) compared to control subject (B). 1. Bours MJ, Dagnelie PC, Giuliani AL, Wesselius A, Di Virgilio F (2011) P2 receptors and extracellular ATP: a novel homeostatic pathway in inflammation. Front Biosci (Schol Ed) 3:1443-1456. 2. Giuliani AL, Sarti AC, Falzoni S, Di Virgilio F (2017) The P2X7 receptor-interleukin-1 liaison. Front Pharmacol 8:123. 3. Kelly G, Hughes R, Mc Garry T, van den Born M, Adamzik K, Fitzgerald R, Lawlor C, Tobin AM, Sweeney CM, Kirby B (2015) Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa. Br J Dermatol 173:1431-1439. 4. Xu H, Xiao X, He Y, Zhang X, Li C, Mao Q, Wu X, Wang B (2017) Increased serum interleuikin-6 levels in patients with hidradenitis suppurativa. Postepy Dermatol Alergol 34:82-84. 5. Van der Zee HH, de Ruiter L, van der Broecke DG, Dik WA, Laman JD, Pren EP (2011) Elevated levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-alpha and IL-1beta. Br J Dermatol 164:1292-1298. 6. Kanni T, Tzanetakou V, Savva A, Kersten B, Pistiki A, van der Veerdonk FL, Netea MG, van der Meer J, Giamarellos-Bourboulis EJ (2015) Compartimentalized cytokine responses in hidradenitis suppurativa. PLoS One 10:e0130522

Hidradenitis Suppurativa in a Large Cohort of Italian Patients: Evaluation of the Burden of Disease

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually occurs after puberty with painful, deep-seated, inflamed nodules and sinus tracts in the apocrine gland-bearing areas of the body, most commonly the axillae and inguinal and anogenital regions, with a relevant impact on patients' quality of life (QoL). Objective: To evaluate how the burden of HS disease impacts on patient well-being and working activities in a large Italian population over a period of 9 months. Methods: A multicenter, prospective, epidemiologic cohort study was conducted in adult Italian patients with HS. HS severity was assessed through Hurley stage and HS Physician's Global Assessment (HS-PGA), clinical improvement by HS Clinical Response (HiSCR) and partial response, and disease burden through QoL questionnaires (HIDRAdisk, Skindex-16, Dermatology Life Quality Index [DLQI]), and Work Productivity and Activity Impairment - General Health (WPAI:GH). Results: A total of 308 patients (56.2% women; mean age 35.2 +/- 12.9 years) were enrolled in 27 dermatologic clinics. Men were older (37.4 years vs. 33.5), more smoking addicted (74.1% vs. 60.1%), and alcohol consumer (34.1% vs. 13.9%), while more women were obese (34.10% vs. 22.22%). At baseline, most patients had a Hurley severity stage of 2 (43.9%), a moderate HS-PGA score (57.1%), and poor QoL (HIDRAdisk: 65.7 +/- 23.3, Skindex-16: 60.3 +/- 26.9, and DLQI: 10.8 +/- 8.1). Patients with more severe disease showed worse QoL. Mean values for the variables related to HS severity decreased during the study period. The achievement of HiSCR and partial response increased during the study. Conclusion: This study offers insight into the disease burden of HS in an Italian population. Our results underline the impact of QoL evaluation, also with the use of the HIDRAdisk, in clinical routine as a support to validated severity clinical and instrumental indexes for a "360-degree" assessment of HS patient's burden of disease

Hidradenitis Suppurativa in a Large Cohort of Italian Patients: Evaluation of the Burden of Disease

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually occurs after puberty with painful, deep-seated, inflamed nodules and sinus tracts in the apocrine gland-bearing areas of the body, most commonly the axillae and inguinal and anogenital regions, with a relevant impact on patients' quality of life (QoL). Objective: To evaluate how the burden of HS disease impacts on patient well-being and working activities in a large Italian population over a period of 9 months. Methods: A multicenter, prospective, epidemiologic cohort study was conducted in adult Italian patients with HS. HS severity was assessed through Hurley stage and HS Physician's Global Assessment (HS-PGA), clinical improvement by HS Clinical Response (HiSCR) and partial response, and disease burden through QoL questionnaires (HIDRAdisk, Skindex-16, Dermatology Life Quality Index [DLQI]), and Work Productivity and Activity Impairment - General Health (WPAI:GH). Results: A total of 308 patients (56.2% women; mean age 35.2 +/- 12.9 years) were enrolled in 27 dermatologic clinics. Men were older (37.4 years vs. 33.5), more smoking addicted (74.1% vs. 60.1%), and alcohol consumer (34.1% vs. 13.9%), while more women were obese (34.10% vs. 22.22%). At baseline, most patients had a Hurley severity stage of 2 (43.9%), a moderate HS-PGA score (57.1%), and poor QoL (HIDRAdisk: 65.7 +/- 23.3, Skindex-16: 60.3 +/- 26.9, and DLQI: 10.8 +/- 8.1). Patients with more severe disease showed worse QoL. Mean values for the variables related to HS severity decreased during the study period. The achievement of HiSCR and partial response increased during the study. Conclusion: This study offers insight into the disease burden of HS in an Italian population. Our results underline the impact of QoL evaluation, also with the use of the HIDRAdisk, in clinical routine as a support to validated severity clinical and instrumental indexes for a "360-degree" assessment of HS patient's burden of disease