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.

Successful Management of Erythema Dyschromicum Perstans Following Topical Ruxolitinib Therapy.

Erythema dyschromicum perstans (EDP) is a rare cutaneous disorder in which patients develop gray or blue-brown macules or patches on their bodies.1 This condition does not appear to have a gender or age predilection. The diagnosis of EDP is essentially clinical, with histopathology findings being nonspecific. To date, treatment for EDP varies. The use of several therapies, including dapsone, clofazimine, retinoid A, tacrolimus, and ultraviolet light have been reported but with minimal effectiveness.5 We report a case of EDP occurring in a patient following the COVID-19 vaccine that was given topical ruxolitinib with success in treatment. To our knowledge, this is the first report of the use of topical ruxolitinib in treatment of EDP with successful management. J Drugs Dermatol. 2022;22(3): doi:10.36849/JDD.7156.

Generalized Pustular Figurate Erythema in Patients with COVID-19 Treated with Hydroxychloroquine: A Systematic Review.

severe distinctive cutaneous drug reaction, generalized pustular figurate erythema, closely linked with hydroxychloroquine (HCQ), has been documented. It is distinguishable from AGEP by its longer incubation, more varied morphology (initially urticarial and later targetoid, arcuate plaques), recalcitrance to therapy and longer disease course. Aim of the article is to review the recognized entity associated with ingestion of hydroxychloroquine in patients infected with COVID-19. A systematic review using electronic search was performed. Inclusion criteria: n patients with COVID-19 demonstrated by PCR, with typical clinical features of AGEP/GPFE or atypical features associated with typical histopathology. We used the (JBI) Critical Appraisal Checklist for Case Reports for the qualitive assessment. We included 13 publications. Their overall quality was good to moderate. Only 27.3% of the patients had a severe COVID-19 course. The mean lag time between trigger exposure and rash development was 24 days. Only 15.38% of the reported AGEP were clinically typical, while the remaining 69.23 % were suggestive of GPFE. Unfortunately, 2 patients died secondary to massive pulmonary embolism. In COVID-19 infection, we suggest reconsidering treating established COVID-19 empirically with HCQ, as both triggers can augment the subsequent cytokine storm, inducing a severe drug reaction and possibly increasing the risk of thrombo-embolic events.

[Multiform exudative erythema caused by hydroxychloroquine, diagnosed by epicutaneous tests: A case report]. / Eritema exudativo multiforme provocado por hidroxicloroquina, diagnosticado mediante pruebas epicutáneas: reporte de un caso.

INTRODUCTION: Multiform exudative erythema is a rare delayed hypersensitivity reaction associated with medications. The manifestations caused by hydroxychloroquine are exceptional; however, due to the increase in its prescription due to the recent SARS-CoV-2 pandemic, adverse reactions have been exacerbated. CASE REPORT: A 60-year-old female patient, who attended the Emergency Department for a picture of erythematous rash of one week of evolution, with involvement of the trunk, face and palms of the hands. Laboratory studies reported: leukocytosis with neutrophilia and lymphopenia, without eosinophilia or abnormal liver enzymes. The lesions continued to descend towards her extremities, with subsequent desquamation. She was prescribed prednisone 15 mg/24 h for three days, tapering to 10 mg/24 h, until her new assessment, in addition to antihistamines. Two days later, new macular lesions appeared in the presternal area and on the oral mucosa. Control laboratory studies did not show alterations. Skin biopsy reported: vacuolar interface dermatitis with spongiosis and parakeratosis, compatible with erythema multiforme. Epicutaneous tests were carried out with meloxicam and 30% hydroxychloroquine in water and vaseline, occluded for two days and interpreted at 48 and 96 hours, with a positive result for the latter. The diagnosis of multiform exudative erythema due to hydroxychloroquine was established. CONCLUSIONS: This study confirms the efficacy of patch tests in patients with delayed hypersensitivity reactions to hydroxychloroquine.

INTRODUCCIÓN: El eritema exudativo multiforme es una reacción de hipersensibilidad retardada poco frecuente asociada con medicamentos. Las manifestaciones provocadas por hidroxicloroquina son excepcionales; sin embargo, debido al incremento de su prescripción, por la reciente pandemia de SARS-CoV-2, las reacciones adversas se han exacerbado. REPORTE DE CASO: Paciente femenina de 60 años, que acudió al servicio de Urgencias por un cuadro de exantema eritematoso de una semana de evolución, con afectación hacia el tronco, la cara y las palmas de las manos. Los estudios de laboratorio informaron: leucocitosis con neutrofilia y linfopenia, sin eosinofilia ni alteración de las enzimas hepáticas. Las lesiones continuaron descendiendo hacia las extremidades, con posterior descamación. Se le indicó prednisona 15 mg/24 h durante tres días, con disminución a 10 mg/24 h, hasta su nueva valoración, además de antihistamínicos. Dos días posteriores aparecieron nuevas lesiones maculares en la zona preesternal y en la mucosa oral. Los estudios de laboratorio de control no mostraron alteraciones. La biopsia cutánea informó: dermatitis de interfase vacuolar con espongiosis y paraqueratosis, compatible con eritema multiforme. Se llevaron a cabo pruebas epicutáneas con meloxicam e hidroxicloroquina al 30% en agua y vaselina, ocluidos dos días e interpretados a las 48 y 96 horas, con resultado positivo para esta última. Se estableció el diagnóstico de eritema exudativo multiforme por hidroxicloroquina. CONCLUSIONES: Este estudio confirma la eficacia de las pruebas epicutáneas en pacientes con reacciones de hipersensibilidad retardada a hidroxicloroquina.

A 25-Year-Old Patient With Chest Wall Erythema and Tenderness Who Was Ventilated Mechanically.

CASE PRESENTATION: A 25-year-old man with cerebral palsy, scoliosis, and ventilator dependence since SARS-CoV-2 infection 11 months earlier presented with a 2-week history of chest redness and swelling. The area of erythema and edema was located on the left side of the anterior chest and had grown to approximately 9 cm in diameter over the 2 weeks. It was tender to palpation. There was no history of trauma, injury, or bug bites at that site. He had not had a rash or similar lesions elsewhere on his body and had not taken any new medications. He did have increased, thick, yellow secretions from his tracheostomy, but no fevers. He was born in the Dominican Republic and moved to the United States as a child. He had not traveled anywhere outside the United States in more than a decade.

Autoimmunity-related neutrophilic dermatosis after coronavirus disease 2019 vaccination: A case report and literature review.

Autoimmune diseases triggered by coronavirus disease 2019 (COVID-19) mRNA vaccination have been emerging. Here, we report the case of a 27-year-old Japanese man with autoimmunity-related neutrophilic dermatosis, occurring as an initial cutaneous manifestation of systemic lupus erythematosus with Sjögren syndrome after the second dose of the Pfizer/BioNTech COVID-19 vaccination. The patient presented with urticarial erythema and partially annular erythema on the trunk and extremities with severe pruritus. Histopathological analysis showed vacuolar degeneration at the dermo-epidermal junction and interstitial neutrophil infiltration. We reviewed eight patients, including the aforementioned patient, with exacerbation or new-onset of SLE after COVID-19 vaccination and found the patient had relatively mild symptoms, itchy annular erythema, and positive anti-SS-A/SS-B antibodies. COVID-19 mRNA vaccination can induce the production of type-I interferon, which plays a crucial role in the pathogenesis of SLE and may cause autoimmunity-related neutrophilic dermatosis in susceptible individuals. In the case that itchy annular erythema develops approximately 2 weeks after the vaccination, the possibility of systemic or cutaneous lupus erythematosus should be considered. For an accurate diagnosis, dermatologists should obtain a recent vaccination history and perform complete antibody profiling and skin biopsy for patients presenting with annular or erythema multiforme-like lesions.

A Phase 2/3 observer-blind, randomized, controlled study to determine the safety and immunogenicity of SARS-CoV-2 recombinant spike protein vaccine in Indian children and adolescents aged 2 to 17 years (preprint)

Background: A recombinant, adjuvanted COVID-19 vaccine, SII-NVX-CoV2373 was manufactured in India and evaluated in Indian children and adolescents to assess safety and immunogenicity. Methods: This was a Phase 2/3 observer-blind, randomized, controlled study in children and adolescents aged 2 to 17 years. Participants were randomly assigned in 3:1 ratio to receive two doses of SII-NVX-CoV2373 or placebo on day 1 and day 22. Solicited adverse events (AEs) were collected for 7 days after each vaccination. Unsolicited AEs were collected for 35 days following first dose and serious AEs (SAEs) and adverse events of special interest (AESI) were collected throughout the study. Anti S IgG and neutralizing antibodies against the SARS-CoV-2 were measured at baseline, day 22, day 36 and day 180. Variant immune responses were assessed in a subset of participants at baseline, day 36 and day 180. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 in each pediatric age group (12 to 17 years and 2 to 11 years, separately) to that in adults in terms of ratio of titers of both anti-S IgG and neutralizing antibodies 14 days after the second dose (day 36). Non-inferiority was to be concluded if the lower bound of 95% CI of the ratio was >0.67. Results: A total of 920 children and adolescents (460 in each age cohort; 12 to 17 years and 2 to 11 years) were randomized and vaccinated. The demographic and baseline characteristics between the two groups were comparable in both age groups. After the second dose, there were more than 100-fold rise in anti-S IgG GMEUs and more than 84-fold rise in neutralizing antibodies GMTs from baseline in the participants who received SII-NVX-CoV2373. The GMTs in both age groups were non-inferior to those observed in Indian adults. The seroconversion rate was [≥] 98% (anti-S IgG) and [≥] 97.9% (neutralizing antibodies) in both age groups, respectively. Similar findings were seen in the baseline seronegative participants. SII-NVX-CoV2373 also showed robust responses against various variants of concern. Injection site pain, tenderness, swelling, erythema and fever, headache, malaise, fatigue, myalgia, arthralgia, nausea and vomiting were the common solicited adverse events which were transient and resolved without any sequelae. Throughout the study, only two causally unrelated SAEs and no AESI were reported. Conclusion: SII-NVX-CoV2373 has been found safe and well tolerated in children and adolescents of 2 to 17 years. The vaccine was highly immunogenic and the immune response was non-inferior to that in adults.

A Histologic Timeline of a Delayed Hypersensitivity Reaction after the COVID-19 Pfizer Booster.

A 54-year-old man presented with worsening bilateral rashes on legs and arms 7 days after receiving his BNT162b2 mRNA COVID-19 (Pfizer) vaccine booster. He developed burning on his palms about 5 days after receiving the booster. On day 6, he observed significant edema on his fingers and palms in addition to thin erythematous papules on his forearms. On day 7, he developed edema on his bilateral dorsal feet, and thin erythematous plaques on his shins. He stated that the rashes were pruritic. He had no rashes following the first two doses of the Pfizer vaccine. He denied having any history of skin disease, autoimmune disease, or allergies. Physical examination revealed multiple thin erythematous papules coalescing into thin plaques on his flexor forearms, and thin erythematous plaques on his dorsal feet (Figure 1). Three 4-mm punch biopsies were performed on his left flexor forearm. The biopsies were carried out at papules present for different lengths of time. Papules at biopsy sites "A," "B," and "C" were present for approximately 24-36 hours, 12-18 hours, and 3-6 hours, respectively (Figure 1).

Preliminary report: Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, KD-414, in healthy adult participants: a non-randomized, open-label phase 2/3 clinical study in Japan (preprint)

Abstract: Background: In the prolonged COVID-19 pandemic, there remains a high need for the development of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine that can be used more safely and effectively to prevents the disease onset or severe disease. To satisfy such unmet need, we are currently developing the inactivated whole particle SARS-CoV-2 vaccine (KD-414) and conducted a phase 2/3 study in healthy adults in Japan to accumulate more immunogenicity and safety data of KD-414 using the dose selected based on the results of the phase 1/2 study. Methods: In an open-label uncontrolled phase 2/3 study, adults aged 18 years or older without a history of COVID-19 or COVID-19 vaccination received two intramuscular doses of KD-414 at a 28-day intervals, followed by one intramuscular dose 13 weeks after the second dose as the primary immunization. Safety data were collected after the first dose of KD-414 in all participants to evaluate the safety profile. In predetermined immunogenicity analysis subjects, the neutralizing antibody titers against the pseudovirus SARS-CoV-2 (Wuhan) before the first vaccination and after each vaccination with KD-414 were evaluated. Results: A total of 2500 adults aged 18 years or older were enrolled; 2474 of them received the vaccination up to the second dose, and 2081 completed the third vaccination. Regarding the safety, no deaths or serious adverse reactions were recorded from the first vaccination until 28 days after the third vaccination with KD-414. The incidence of adverse reactions (number of participants with onsets/number of participants in the safety analysis set) was 80.6% (2015/2500). Adverse reactions with an incidence of 10% or more included injection site pain, malaise, headache, injection site erythema, myalgia, and injection site induration. A total of 11 events of grade 3 or higher adverse reactions that prevented daily activities in 9 participants. There was no increasing tendency in the incidence of adverse reactions responding to the vaccinations. To evaluate immunogenicity, 295 first comers enrolled from five age ranges were allocated to the immunogenicity analysis subjects; 291 participants received the vaccination up to the second dose, and 249 participants completed the third vaccination. The geometric mean titers (95% confidence interval [CI]) of neutralizing antibody titers against pseudovirus SARS-CoV-2 (Wuhan) 28 days after the second vaccination and 28 days after the third vaccination with KD-414 were 139.6 (118.9 - 164.0) and 285.6 (244.3 - 334.0), respectively, showing an approximately two-fold increase after the third vaccination compared to that after the second vaccination. The geometric mean titers (95% CI) of neutralizing antibody titers after the third vaccination were 327.6 (269.8 - 397.9), 272.2 (211.5 - 350.4) and 128.0 (51.6 - 317.7) in participants aged 18 to 40 years, 41 to 64 years, and 65 years or older, respectively, showing an age-dependency. Conclusion: This study confirmed the favorable safety profile of KD-414 as a result of three vaccinations of KD-414 administered to over 2000 healthy Japanese participants aged 18 years or older. There were no particular differences in the types and incidences of adverse reactions between vaccinations, and no tendency of an increase in adverse reactions with an increase in the number of vaccinations. Similar to the phase 1/2 study, neutralizing antibody responses appeared to be age-dependent and the highest titers were observed in the age group of 18 - 40 years. A phase 3 study in adults aged 18 - 40 years (jRCT2031210679) and a phase 2/3 study in children aged 6 months - 18 years (jRCT2031220032) are currently ongoing.

A 14-Year-Old Boy With Neck Pain, Fevers, and Diffuse Erythematous Rash.

A previously healthy 14-year-old boy developed right-sided neck pain, tachycardia, a diffuse erythematous rash, and subjective fevers over 2 days. He sought medical attention in a local urgent care clinic, where he had a negative Sars-CoV-2 antigen test and was referred to the local emergency department (ED) for persistent tachycardia and further workup. After fluid resuscitation, his tachycardia was not improved, so he was admitted to the Pediatric Hospital Medicine Service. Physical examination showed large areas of erythema and erythroderma of multiple body sites, perioral sparing, increased erythema in flexor skin folds, posterior soft palate petechiae, and a white strawberry tongue. There was a small, tender lesion with surrounding erythema without discharge on his right neck thought to be a possible entry point for infection. Laboratory results showed thrombocytopenia, normal white blood cell count, normal hemoglobin concentration, absolute lymphopenia, and an elevated C-reactive protein (CRP) to 130 mg/L. He was started on intravenous fluids and antibiotics for a presumed infectious cause of the rash and laboratory findings. The next morning, an expanded diagnostic workup was undertaken including electrocardiogram, echocardiogram, ferritin, triglycerides, liver enzymes, lactate dehydrogenase (LDH), brain natriuretic peptide, coagulation studies, and fibrinogen. With treatment and supportive care, his tachycardia and energy improved, so he was discharged with oral antibiotics and follow-up with the Infectious Disease Clinic in 2 days. When seen in follow-up, he was immediately admitted to the hospital for worsening fatigue, tachycardia, and new findings that prompted multiple consultations, and transfer to pediatric critical care services.

Exposure to solar UV radiation of Polish teenagers after the first COVID-19 lockdown in March-April 2020.

In Poland, schools were closed from March to June 2020 due to the COVID-19 epidemic. During the lockdown (March-April), everyone was advised to stay at home. From May, students were allowed to spend time outdoors. We examine their exposure to solar UV radiation during the period of virtual learning at schools (May-June), vacations (July-August) and the first month of typical learning (September). Primary and high school students aged 12-18 completed a questionnaire on the details of their outdoor activities and the weather at the exposure site. A total of 146 anonymous questionnaires were registered for the study. The survey responses provided input to a radiative transfer model to estimate erythemal and vitamin D doses obtained by teenagers during outdoor activities. The results from 48% of the questionnaires indicated that students' exposure exceeded 1 minimal erythema dose (MED) during the day. Corresponding doses of sun-synthesized vitamin D, in excess of 1000 international units (IU) and 2000 IU, were found in 77% and 66% of the surveys, respectively. Only 12% of the teenagers declared that they use sunscreen. The overexposure (> 1 MED) increased with age. It was found in 72% and 26% of surveys among the students aged 17-18 and 12-14, respectively. Teenagers seem to have tried to compensate for the lack of sunlight during the lockdown by engaging in outdoor activities permitted since May. While those activities could have improved their vitamin D levels, they also put them at a higher risk of developing erythema.

Types and prevalence of adverse skin reactions associated with prolonged N95 and simple mask usage during the COVID-19 pandemic.

BACKGROUND: As the coronavirus 2019 (COVID-19) pandemic persists on a global level, the chronic daily use of face masks within the healthcare system remains an important component of disease prevention and transmission. Increased use of personal protective equipment (PPE) may result in increased rates of occupational dermatoses and adverse skin reactions. OBJECTIVES: The purpose of this study is to explore how chronic, prolonged use of N95 masks or simple surgical masks affects the prevalence of adverse skin reactions in Healthcare Workers (HCWs). METHODS: An optional, quantitative, web-based survey was administered to patient-facing HCWs across six network hospitals in a large metropolitan city. Data were analysed to assess the types and sites of adverse skin reactions, and to evaluate correlations between single mask use duration and adverse skin reactions. RESULTS: A total of 230 HCWs responded with 192 endorsing occupational dermatoses. Among the healthcare responders, (n = 192, 83.5%) experienced at least one adverse skin reaction. The most common occupational adverse skin reactions were acne (n = 133, 57.8%), dryness (n = 108, 47.0%) and redness (n = 105, 45.7%). Anatomical areas most commonly affected included the nasal bridge (n = 92, 40.0%), cheeks (n = 92, 40.0%) and chin (n = 91, 39.6%). Acne (P = 0.002), dryness/scaling (P = 0.002), increased pore size (0.003), itch (P = 0.003), nasal bridge scarring (P < 0.001), redness (P < 0.001), frictional erosions (P = 0.001) and ulcerations (P = 0.002) showed a positive correlation to duration of mask use. CONCLUSIONS: Prolonged, daily usage of PPE is associated with numerous adverse skin reactions among HCWs with acne being the most commonly seen adverse reaction. Many adverse reactions are associated with prolonged use of single mask.

The effects of wearing a face mask and of subsequent moisturizer use on the characteristics of sensitive skin.

BACKGROUND: COVID-19 is a serious respiratory disease, and wearing masks has become essential in daily life. Nevertheless, the number of people complaining of skin problems caused by wearing masks is increasing. Therefore, we investigated the characteristics of changes in sensitive skin caused by wearing a mask. MATERIALS AND METHODS: Twenty healthy Korean women with sensitive skin participated in this study. To determine any skin-related changes caused by mask-wearing, we evaluated redness, hydration, transepidermal water loss (TEWL), and moisture at 2.5 mm below the surface before and 4 h after wearing a Korea Filter 94 mask. In addition, we tested whether applying a moisturizer for 30 min after mask removal could reverse any mask-induced changes. RESULTS: Skin redness and TEWL were significantly increased at 4 h after wearing a mask (p < 0.05), otherwise skin hydration and the 2.5 mm moisture were significantly decreased (p < 0.05). After applying the moisturizer, skin redness and TEWL were significantly decreased compared to their values 4 h after wearing masks (p < 0.05), whereas skin hydration and the 2.5 mm moisture were significantly increased (p < 0.05). Moreover, after applying the moisturizer, skin redness and TEWL were significantly reduced compared to the pre-masking baseline (p < 0.05), whereas skin hydration was significantly increased (p < 0.05); the 2.5 mm moisture showed no significant change. CONCLUSION: We observed that wearing masks causes physiological changes in sensitive skin, whereas applying a moisturizer after removing the mask improved skin conditions.

Histopathological analysis of skin reactions after coronavirus disease 2019 vaccination: Increment in number of infiltrated plasmacytoid dendritic cell.

Skin disorders are frequent adverse events after coronavirus disease 2019 (COVID-19) vaccination. However, the pathogenesis of these disorders is not fully understood. Here, we report a case series of cutaneous adverse events following COVID-19 vaccination, and the results of our investigation reveal the underlying mechanism. Case 1: a 47-year-old female developed a wheal, confined to the COVID-19 vaccination site, 2 days after her first injection. She was treated with topical steroids and oral antihistamines. Case 2: a 51-year-old female showed generalized petechial erythema accompanied by fever, genital bleeding, thrombocytopenia, liver dysfunction, and disseminated intravascular coagulation, 2 days after her second injection. She was diagnosed with vaccine-induced macrophage activation syndrome and treated with anti-inflammatory therapy. Immunohistological analysis of the skin eruption, in both these cases, showed infiltration of CD123+ BDCA2+ plasmacytoid dendritic cells (p-DC). Despite the distinctive clinical features in these two cases, this finding suggests that p-DC might be involved in different cutaneous adverse events after COVID-19 vaccination.