From regulatory limitations to new opportunities: Real-life experience on the effectiveness of short courses of omalizumab in the treatment of chronic idiopatic urticaria.

Economic sustainability of long-term continuous treatment of antihistamine refractory chronic urticaria with omalizumab may be an issue. We assessed the efficacy of relatively short courses (5-6 months) of omalizumab in patients with chronic idiopathic urticaria (CIU). We retrospectively studied 40 patients (observed between June 2015 and January 2019) affected by moderate-to-severe CIU refractory to anti-H1 antihistamines (up to fourfold doses). Omalizumab was administered every 4 weeks for 24 weeks, then for 20 weeks in case of a relapse of moderate-to-severe degree, then again for 24 weeks in case of a second relapse. Monthly clinical evaluations were performed. Mean disease severity significantly dropped after 1 month and further decreased thereafter, with 30 complete remissions after the first course of treatment. In 2-4 months, 18 patients had a relapse of moderate-to-severe degree. The profile of response to the second course of omalizumab was similar to the first. A third course was necessary for seven patients. No adverse effects were recorded. Courses of 5-6 months of omalizumab may induce rapid significant improvement of urticaria and many prolonged complete remissions. In case of relapse, further courses show a similar profile of response and may induce additional long-term complete remissions.

Malignant melanoma in HIV: Epidemiology, pathogenesis, and management.

People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV-infected people is 2.6-fold higher than in uninfected ones. In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV-negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV-positive patients regardless of their CD4+ count and the use of standard surgical margins for re-excision procedures. In case of diagnosis of melanoma in HIV-positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV-positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow-up, every 3 months, for the first 2 years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint-based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV.

Dominant pretibial dystrophic epidermolysis bullosa in an Italian family.

We describe a case of pretibial dystrophic epidermolysis bullosa in a 5-year-old girl, her mother, and maternal great aunt. All subjects had trauma-induced blisters and erosions, with scarring, on the knees and lower legs, and nail dystrophy of variable severity. Genetic analysis in all three patients showed a 6849del18 mutation in the COL7A1 gene, causing the production of shortened collagen VII polypeptides and resulting in a mild phenotype, with localized acral blisters and nail involvement.

Adalimumab in severe plaque psoriasis of childhood: A multi-center, retrospective real-life study up to 52 weeks observation.

The objective of this study is to determine drug effectiveness and safety of the tumor necrosis factor-alpha blocker monoclonal antibody adalimumab in a real-life cohort of 54 children and/or adolescents with severe plaque psoriasis. Retrospective, multicenter analysis over a 52-week period is discussed in this study. Efficacy was determined by the percentage of patients achieving Psoriasis Area Severity Index (PASI 75) and PASI 90 at weeks 16, 24, and 52 and the response in biologic-naïve versus non-naïve patients. Safety was assessed by the number of patients experiencing at least one adverse event. At week 16, 29.6% of patients achieved a 90% PASI score reduction (PASI 90), while 55.5% of patients achieved a 75% PASI score reduction (PASI 75). Effectiveness was sustained through week 24, since PASI 90 response increased to 55.5% and PASI 75 response increased to 74.0% of patients. The PASI response rates did not differ between biologic-naïve and non-naïve patients. The drug was well tolerated and no serious infections were observed. Adalimumab was effective and safe in this cohort of children with severe plaque psoriasis in a 52-week observation. Effectiveness did not differ between biologic-naïve and non-naïve patients.

Auditory System Involvement in Psoriasis.

Psoriasis is a systemic inflammatory disorder associated with many other chronic and progressive diseases. There are few studies on the association of psoriasis with alterations in auditory function. A clinical and instrumental pilot study of auditory function was performed with 77 psoriatic patients and 77 age- and sex-matched healthy controls. The main results were: (i) hearing loss, mostly of sensorineural type, was significantly more frequent in patients than in controls; (ii) conductive and mixed hearing loss were more frequent in arthropathic than in non-arthropathic psoriatic patients; (iii) duration of psoriasis > 10 years or smoking were associated with higher frequency of hearing loss; (iv) psoriasis was more severe in patients with hearing loss than in those without hearing loss. Tympanogram abnormalities were found in patients more often than in controls. These data expand the list of extracutaneous conditions associated with psoriasis, and support the need for further basic and clinical research in this field.

Living with Chronic Spontaneous Urticaria in Italy: A Narrative Medicine Project to Improve the Pathway of Patient Care.

Chronic spontaneous urticaria (CSU) is perceived as a difficult to manage disease with negative impact on quality of life. The aim of this study was to highlight how to improve the care of people with CSU, using the methodology of narrative medicine. From June 2014 to March 2015, CSU-diagnosed patients and their physicians were asked to record their experiences of the condition in writing. Fourteen healthcare teams participated: 41% considered CSU as a challenge to overcome, while 22% experienced CSU as a big commitment. The number of professional involved was evaluated as insufficient in 11 hospitals. Seventy-five percent of the 190 Italian patients had visited 3 or more physicians before receiving a final diagnosis, with a perceived waste of time and resources. The therapeutic pathways were described as unsatisfactory in 83% of cases. As a result, anger and frustration were life-dominant emotions in 92% of patients. The critical points of the care pathway are related to organizational issues and lack of awareness.

Release of nickel and chromium in common foods during cooking in 18/10 (grade 316) stainless steel pots.

BACKGROUND: Literature data on the release of nickel and chromium from stainless steel cookware during food preparation are contrasting, have often been obtained with uncommon foods and/or procedures, and are thus not widely applicable. OBJECTIVES: To assess the release of nickel and chromium from 18/10 (grade 316) stainless steel pots in cooking conditions that are common in an urban lifestyle. METHODS: Tomato sauce and lemon marmalade were cooked for 1 h, alone or with added EDTA, in used or unused stainless steel pots from different manufacturers. Additionally, aqueous solutions at pH 2.3, 7.7 and 9 were boiled for 1 h in the same pots. Metal release was assessed with inductively coupled plasma mass spectrometry. RESULTS: The release of nickel and chromium increased with cooking/boiling time, was higher with unused pots, at low pH or with EDTA, and was sometimes remarkably different between manufacturers. In all experiments, the amounts released were below known allergy-triggering thresholds. CONCLUSIONS: Under common conditions, the use of 18/10 stainless steel pots is considered to be safe for the majority of nickel-allergic and/or chromium-allergic subjects. However, the total amount of nickel contained in foods and released from pots may exceed the individual threshold for triggering allergy, potentially causing problems for highly sensitive patients, or, conversely, contribute to induction of immunotolerance by oral low-dose exposure.

Differential Expression of Nitric Oxide Synthase Isoforms nNOS and iNOS in Patients with Non-Segmental Generalized Vitiligo.

Nitric oxide (NO) is involved in several biological processes, but its role in human melanogenesis is still not well understood. Exposure to UVA and UVB induces nitric oxide production in keratinocytes and melanocytes through the activation of constitutive nitric oxide synthase, increasing tyrosinase activity and melanin synthesis, whereas inducible nitric oxide synthase over expression might be involved in hypopigmentary disorders. The aim of this study was to evaluate whether inducible nitric oxide synthase and neuronal nitric oxide synthase expression were modified in vitiligo skin compared to healthy controls. Skin biopsies were obtained from inflammatory/lesional and white/lesional skin in 12 patients with active, non-segmental vitiligo; site-matched biopsies of normal skin from eight patients were used as controls. Nitric oxide synthase isoforms expression was evaluated by confocal laser scanning microscopy and Western Blot analysis. Inducible nitric oxide synthase expression was significantly increased in inflammatory/lesional skin compared to healthy skin; melanocytes showed a moderate neuronal nitric oxide synthase expression in white/lesional skin, demonstrating that metabolic function still goes on. The obtained data demonstrated that vitiligo lesions were characterized by modifications of nitric oxide synthase isoforms, thus confirming the hypothesis that nitric oxide imbalance is involved in vitiligo and supporting the idea that nitric oxide synthase inhibitors might be used as a possible therapeutic approach for the management of vitiligo.

Photodynamic therapy in lupus miliaris disseminatus faciei's scars.

Lupus miliaris disseminatus faciei is an uncommon granulomatous inflammatory disease, characterized by multiple, monomorphic, reddish translucent papules and nodules, mainly located on the face. Several therapeutic options have been employed with variable results, leaving residual disfiguring scars. On this topic, we report a case of significant improvement of red-atrophic scars in a 54-year-old male after three sessions of photodynamic therapy with 10% aminolevulinic acid. Owing to the high safety profile and the excellent cosmetic result, photodynamic therapy may be considered a useful tool to both prevent and treat undesirable scarring.

COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Serum levels of miRNA-21-5p in vitiligo patients and effects of miRNA-21-5p on SOX5, beta-catenin, CDK2 and MITF protein expression in normal human melanocytes.

BACKGROUND: Epigenetics of vitiligo was evaluated in few studies. In particular, the role of miR-21, a microRNA involved in various processes, including melanogenesis, was never investigated. OBJECTIVE: Evaluation of serum levels of miR-21-5p in vitiligo patients and miR-21-5p effects on melanogenesis. METHODS: We measured serum levels of miR-21-5p in 40 patients affected by nonsegmental vitiligo and 40 sex- and age-matched healthy controls. Next, normal human melanocytes were transfected with miR-21-5p to study the effects of this microRNA, which targeted some proteins involved in melanogenesis pathway like SOX5, beta-catenin, cyclin-dependent kinase 2 (CDK2), and MITF. RESULTS: The expression of miR-21-5p in vitiligo patients was 3.6-4454.4 fold (mean 990.4 ± 1397.9) higher than in controls. The relative expression of miR-21-5p was directly and significantly correlated with disease severity, defined by VASI (Vitiligo Area and Severity Index) score (Rho = 0.89, p = 10-7), but not other individual or clinical characteristics. In the second part of the study, a significant reduction of SOX5, beta-catenin and CDK2 protein expression and increase of MITF protein expression was observed in cultured melanocytes after 24 h trasfection with miR-21-5p. CONCLUSION: According to literature, miR-21-5p upregulation and consequent SOX5 downregulation should upregulate melanogenesis, while vitiligo is characterized by skin depigmentation. Our results suggest that current knowledge of the pathogenesis of vitiligo is probably incomplete. Clinical manifestations could result from an altered balance between metabolic pathways with contrasting effects. In this view, miR-21-5p upregulation might be a tentative compensation mechanism. Further studies appear necessary to confirm and better understand our results and their importance.