key: cord-1032457-2f7unbms authors: Castelo‐Soccio, Leslie; Lara‐Corrales, Irene; Paller, Amy S.; Bean, Eric; Rangu, Sneha; Oboite, Michelle; Flohr, Carsten; Ahmad, Regina‐Celeste; Calberg, Valerie; Gilliam, Amy; Pope, Elena; Reynolds, Sean; Sibbald, Cathryn; Shin, Helen T.; Berger, Emily; Schaffer, Julie; Siegel, Michael P.; Cordoro, Kelly M. title: Acral Changes in pediatric patients during COVID 19 pandemic: Registry report from the COVID 19 response task force of the society of pediatric dermatology (SPD) and pediatric dermatology research alliance (PeDRA) date: 2021-03-20 journal: Pediatr Dermatol DOI: 10.1111/pde.14566 sha: d82c9a1b4b37d677b25e9e401f5e10410c14d3f5 doc_id: 1032457 cord_uid: 2f7unbms BACKGROUND/OBJECTIVE: In spring 2020, high numbers of children presented with acral pernio‐like skin rashes, concurrent with the coronavirus disease 2019 (COVID‐19) pandemic. Understanding their clinical characteristics/ infection status may provide prognostic information and facilitate decisions about management. METHODS: A pediatric‐specific dermatology registry was created by the Pediatric Dermatology COVID‐19 Response Task Force of the Society for Pediatric Dermatology (SPD) and Pediatric Dermatology Research Alliance (PeDRA) and was managed by Children's Hospital of Philadelphia using REDCap. RESULTS: Data from 378 children 0‐18 years entered into the registry between April 13 and July 17, 2020 were analyzed. Data were drawn from a standardized questionnaire completed by clinicians which asked for demographics, description of acral lesions, symptoms before and after acral changes, COVID‐19 positive contacts, treatment, duration of skin changes, laboratory testing including SARS‐CoV‐2 PCR and antibody testing, as well as histopathology. 229 (60.6%) were male with mean age of 13.0 years (± 3.6 years). Six (1.6%) tested positive for SARS‐CoV‐2. Pedal lesions (often with pruritus and/or pain) were present in 96%. 30% (114/378) had COVID‐19 symptoms during the 30 days prior to presentation. Most (69%) had no other symptoms and an uneventful course with complete recovery. CONCLUSIONS AND RELEVANCE: Children with acral pernio‐like changes were healthy and all recovered with no short‐term sequelae. We believe these acral changes are not just a temporal epiphenomenon of shelter in place during the spring months of the first wave of the COVID‐19 pandemic and may be a late phase reaction that needs further study. The registry compiled 384 individual cases of patients with acral skin changes between April 13, 2020 and July 17, 2020. Six subjects were excluded due to age greater than 18 years, and 378 (age 2 months to 18 years, mean 13 years ± 3.6 years) were evaluated (Table 1) . Most were male (60.6%) and white/Caucasian (72%) ( Table 2) . Potential exposure to SARS-CoV-2 prior to the acral changes was noted by 33.6% (127/378), most often by those living in a community with high rates (16.7%; 63/378) or contact with a family member exposed through work (7.7%; 29/378). Close contact with a SARS-CoV-2-positive individual was reported by 2.6% (10/378) ( Table 2) . Of 378 subjects, 1.6% had SARS-COV-2 infection confirmed by PCR or antibody testing, while 134 (35.4%) had negative testing for the virus by PCR or tested negative for antibodies (8) . 47.4% confirmed they had no SARS-CoV-2 testing. None were hospitalized or died. Some subjects (~35%) had additional blood testing. Among these subjects, abnormalities were demonstrated in complete blood counts, antinuclear (typically speckled) and anti-phospholipid antibodies, complement, D-dimer, fibrinogen, and inflammatory markers ( Table 3) . The lesions lasted an average of 21.6 days and were virtually always on the feet (96.3%). Some subjects also had lesions on the hands (11.9%) or head/neck (11.4%) ( Table 2 and Supplemental Table S1 ). Toes were most commonly affected, but changes on the dorsal feet, heels, and periungual area were also reported. The skin changes were the first wave of the COVID-19 pandemic and may be a late phase reaction that needs further study. exanthems, infection-viral, skin signs of systemic disease largely described as pink or red macules/patches (91.3%), bullae (6.1%), vesicles (11.6%), erosions (14.8%), and ulcers (3.7%). In 5.3% (20/378), desquamation was noted. Thirteen cases had associated histopathology. Among these, the most common changes were a superficial and deep lymphocytic infiltrate with vacuolar change and purpura as well as hemorrhagic parakeratosis in the stratum corneum (Table S2 ). We present a large collection of children and adolescents with acral skin manifestations that presented in the initial phases of the SARS-CoV-2 pandemic. Although most cases were in adolescent males, several cases occurred in infants (youngest just 2 months of age). The age and male predominance noted here are atypical for classical pernio, but similar to reports in primarily adult COVID registries. 2, 3 We hypothesized a connection between SARS-Cov-2 exposure/infection and these changes but found it difficult to confirm showed SARS-CoV-2 RNA in skin biopsy samples from patients who previously had negative nasopharyngeal PCR testing. 6, 13 Still, there is no agreement. A few argue that pernio is solely the result of greater exposure (such as by being barefoot in unheated homes) during the period of sheltering in place. 16, 17 We disagree with this because there has been no evidence of unseasonably cold and wet weather that would explain the higher incidence of pernio observed. 18 In a retrospective study of 3. data from Philadelphia shows that 2020 was not statistically colder (or warmer), nor did it have more precipitation during these months than over the same months during the previous 5 years. Still, many children reported doing schoolwork at desks or tables without socks or shoes, which would be unusual in the school environment. 19 Despite this, there is no evidence that home schooling or bare feet can explain the male adolescent predominance or why infants/toddlers would have increased numbers of cases. 18, 19 The second wave of increased acral pernio cases many reported in the early fall underscores a direct relationship to the virus rather than a temporal coincidence. Since our first analysis, 56 additional cases were added to the registry in the late summer, fall, and winter and mostly similar trends were observed with slightly higher rates of positive testing. Of these 56 cases, 5 tested positive by PCR for SARS-CoV-2 (Supplemental Table S3 ). One subject was hospitalized due to COVID-19. We also reached out to those who had We were limited by selection and confirmation bias. At the time of data collection, SARS-COV-2 diagnostic testing was not widespread and even currently available testing may be inadequate. Media exposure to the idea of "COVID toes" likely introduced recruitment bias. Differences in the ability to recognize acral changes in dark skin tones and/or decreased access to care may explain why few Black patients were added to registry. Prospective studies with improved antibody-based immunoassays, diagnostic lesional PCR, and inflammatory biomarkers are needed. Longitudinal studies would help to determine long-term sequelae. In the short term, it appears that patients with acral changes had full recovery. 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