Chilblain-like lesions (CLL), known in the lay press as "COVID toes," increased significantly during the COVID-19 pandemic. The phenotypic similarity of chilblains in the monogenic type 1 interferonopathies, coupled with the consistent clinical phenotype across multiple countries and temporospatial association with COVID-19 spread, suggest a SARS-CoV-2 triggered immune phenomenon. Yet direct evidence of this relationship has been limited due to low rates of SARS-CoV-2 positivity utilizing conventional testing. We prospectively enrolled a cohort of 79 patients with CLL across 4 waves of the SARS-CoV-2 pandemic in Wisconsin collecting serial blood samples and lesional skin biopsies. Immunophenotyping including the type 1 interferon (IFN-1) signature was investigated utilizing multiplex immunohistochemistry in affected tissue. Proteomics and RNA sequencing were performed on the peripheral blood at serial time points. RNAscope for S gene and depositional immunohistochemistry for evidence of SARS-CoV-2 were performed on tissue. Antibody responses and T-cell specific responses to SARS-CoV-2 were performed and an animal model (golden hamster) provided mechanistic evidence of dissemination of viral RNA to acral sites with local IFN-1 activation. Our results support an inducible local and peripheral IFN-1 signature, which abrogates within weeks, with evidence of viral SARS-CoV-2 RNA as the trigger.

Coincident with the start of the COVID-19 pandemic, dermatologists worldwide have reported an uncharacteristic increase in pernio or chilblains (aka ‘COVID toes’). However, the lack of systemic illness, low PCR positivity and lack of consistent seroconversion have led some authors to postulate an epiphenomenon. SARS-CoV-2 spike protein has been identified in a limited number of skin biopsies in few publications, yet there remain conflicting reports regarding other SARS-CoV-2 associated proteins, the presence or absence of viral RNA, and a unifying pathophysiology. In cooperation with the COVID Human Genome Effort, our “COVID toes” biobank was established to identify both the genetic and immunologic basis and provide clinically relevant insights into targeted therapeutics. As of March 2021, we have enrolled 96 patients, creating a prospective biorepository with clinical data, saliva, serial blood collection, and skin biopsies. Here we aim to comprehensively investigate the conflicting findings, detail the inflammatory response, and identify the source of interferon signaling with multiplex immunofluorescence (IFA) and the RNAscope fluorescent assay to detect viral mRNA. Median patient age was 17 (range 2 – 72) and 44/96 (46%) were male. Preliminary IFA results demonstrate detection of SARS-CoV-2 components, robust MxA detection and plasmacytoid dendritic cell (pDC) colocalization, identifying PDCs as the likely primary source of IFN-I production and implicates an excessive localized IFN-I response in affected patients.

术语“红斑狼疮”指的是一系列相关疾病。盘状红斑狼疮 (DLE) 是一种在儿童中罕见的皮肤红斑狼疮。其可导致毁容性瘢痕。某些患者出现系统性红斑狼疮 (SLE),这是一种影响全身的红斑狼疮,其可导致多器官损害。多项小型研究表明,25 ‐ 30% 的 DLE 儿童患者随时间推移出现 SLE,但与此相关的风险因素尚不明确。SLE 早期诊断和治疗很有帮助。本研究采用一种调查方法来比较美国和加拿大两个医学专业(学术型风湿科医师和皮肤科医师)为 DLE 儿童患者提供护理的实践模式。本研究的目的在于识别两组间的一致方面,以及基于实践的差异。若两个专业达到 70% 或更多的一致,则出现共识(一致)。作者发现了应在所有儿童诊断为 DLE 时查看某些实验室研究的共识。两组都同意,存在“除 ANA 以外的其他自身抗体”、关节炎或肾炎是 SLE 的高风险特性,对此应增加系统性疾病的筛查。没有其他一致同意的 SLE 风险因素,包括先前在 DLE 成人患者中显示的风险因素。两组都同意,泛发性 DLE 的一线系统性疗法(全身治疗)应为羟氯喹。作者未就哪些药物可用于治疗耐药性皮肤病达成一致。总而言之,本研究发现某些一致方面,但许多方面存在基于实践的差异。需要有关 DLE 儿童患者的更多数据来确定最佳实践方法。作者正在开展一项回顾性队列研究,该研究可能有助于填补这一空白。

The term ‘lupus’ refers to a range of related disorders. Discoid lupus erythematosus (DLE) is a form of lupus in the skin, which is rare in children. It can lead to disfiguring scarring. Some patients develop systemic lupus (SLE), a type of lupus that affects the whole body, which can lead to damage to multiple organs. Small studies have suggested that 25 to 30% of children with DLE develop SLE over time, but risk factors for this are not known. Early diagnosis and treatment of SLE are helpful. This study used a survey approach to compare practice patterns between two medical specialties, academic rheumatologists and dermatologists, in the United States and Canada, caring for children with DLE. The study aimed to identify areas of agreement but also practice-based differences between groups. Consensus (agreement) occurred when 70% or more of both specialties agreed. The authors found consensus that certain laboratory studies should be checked for all children at diagnosis of DLE. Both groups agreed that the presence of “other auto-antibodies besides ANA”, arthritis, or nephritis were high-risk features for SLE that should increase screening for systemic disease. There were no other agreed-upon risk factors for SLE, including those that have previously been shown in adults with DLE. Both groups agreed that first-line systemic therapy (whole body treatment) for widespread DLE should be hydroxychloroquine. The authors could not agree on which medications to use for resistant skin disease. Overall, the study found some areas of agreement but many areas of practice-based difference. More data in children with DLE is necessary to determine best practice approaches. The authors are completing a type of study called a retrospective cohort study that may help to fill these gaps.

If linear morphea represents a form of keratinocyte mosaicism, then it should reflect Blaschko’s lines in the skin. Using data from our group’s 14-site retrospective study of pediatric-onset morphea, comprised of 2534 lesions from 829 subjects, we mapped lesions to standardized templates using custom web-based software. After completing a training module, 3 investigators independently categorized linear lesions from only the face and neck as blaschkoid, not blaschkoid, or too small to assess. Of 261 lesions (across 239 subjects), 35 were excluded because they were considered too small by at least 1 investigator. Of the remaining, 164 of 226 (73%) lesions were called blaschkoid by at least one investigator, 127 by two (56%) and 74 (33%) by all investigators. The concordance rate was 60% (free-marginal κ=0.59, moderate agreement). Non-blaschkoid lesions primarily coursed perpendicular to or lacked the curvilinear nature of Blaschko’s lines. These results suggest that factors beyond segmental mosaicism must underlie linear morphea patterning. Further analysis is planned to gain consensus and seek “morpheatomes” that better characterize disease patterning.

Morphea is a sclerosing disease that can affect any body site though its distribution is incompletely understood. This 14-site retrospective study was performed to characterize morphea lesional distribution. Patients with pediatric-onset morphea (including extragenital lichen sclerosus and atrophoderma but excluding pansclerotic morphea) and adequate lesional photographs were included. Lesions were mapped using a custom web-based software, linked to demographic and clinical data stored in a REDCap database. Overall, 829 subjects and 2534 lesions were included. Consistent with prior reports, female sex (73%) and the linear morphea subtype (69%) were most prevalent. Lesions were most frequent on the extremities (56%) than trunk (48%) and head/neck (23%). Lesions were more common on extensor (55%) than flexor (45%) extremities (χ2 =19.6 p <0.0001). The right upper extremity (57%) was more likely affected than the left (43%) (χ2 =13.6, p=0.0002);this difference was not seen on the lower extremity. Lesions were found more often on the posterior (58%) vs anterior (42%) trunk (χ2 =34.0, p<0.0001), as well as upper (62%) vs lower face (38%) (χ2 =28.4, p<0.0001). Morpheas predilection for the extremities, especially the extensor surfaces and right upper extremity (which is more commonly the dominant hand and arm), back, and upper face supports the theory that trauma may be an inciting factor.