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.

Effectiveness and Safety of Upadacitinib in the Treatment of Moderate-Severe Atopic Dermatitis: A Multicentric, Prospective, Real-World, Cohort Study.

BACKGROUND: The efficacy and safety of upadacitinib in atopic dermatitis (AD) have been defined in clinical trials, but no real-world data are currently available. We aimed to assess the safety and effectiveness of upadacitinib in a real-world AD patient cohort that mostly included patients who failed the available systemic therapies, including dupilumab. METHODS: Prospective cohort study collecting data on upadacitinib-treated AD adult patients completing at least 16 weeks of therapy. RESULTS: Forty-three patients showed rapid and marked response to upadacitinib with significant reduction of all disease severity scores since the first follow-up visit. At week 16, Eczema Area and Severity Index (EASI) 75, EASI 90, and EASI 100 response was observed in 97.5%, 82.1%, and 69.2% of patients, respectively. EASI 90 response reflected the achievement of a clear or almost clear condition (POEM 0-2), self-evaluated by 79.5% of patients. Patients' quality of life improved as suggested by the achievement of DLQI 0/1 by 38.5% of patients at week 4, and by 76.9% at week 16. CONCLUSION: Elevated effectiveness and favorable safety of upadacitinib were confirmed in patients unresponsive to dupilumab, who were not included in upadacitinib trials.

Management of patients with atopic dermatitis undergoing systemic therapy during COVID-19 pandemic in Italy: Data from the DA-COVID-19 registry.

BACKGROUND: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. METHODS: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. RESULTS: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. CONCLUSIONS: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.

Do we have serological evidences that chilblain-like lesions are related to SARS-CoV-2? A review of the literature.

The outbreak of chilblain-like lesions (CLL) coincidentally to the COVID-19 pandemic is a topic of great concern. SARS-CoV-2 was initially hypothesized as the etiologic agent of CLL, but, since nasopharyngeal swabs seldom resulted positive, dermatologists' attention focused on the search for specific SARS-CoV-2 antibodies. Many papers were published contemporarily on this topic, reporting limited case series. We reviewed the English literature up to the first July 2020 and, excluding single case reports, we considered 13 studies that serologically investigated 220 patients. The presence of specific antibodies was detected in 18 subjects (8.2%): isolated IgA were found in 6 patients, IgA and IgG in 1, isolated IgG in 5, and IgM in 2. In 4 patients, isotypes were not specified. Our review demonstrated a high prevalence of negative serological results in CLL: antibodies were observed only in a few patients, that are even less excluding those with positive IgA, not clearly involved in the pathogenesis of the disease. In conclusion, although it is still uncertain whether CLL are related to SARS-CoV-2 infection, patients affected by CLL seem not to be prone to shedding the virus, hence, if they are asymptomatic, we can reassure them, thus avoiding hospital referral.