Cutaneous Pathology of COVID-19 as a Window into Immunologic Mechanisms of Disease.

Many skin manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection reflect activation of cutaneous and systemic immune responses involving effector pathways of both the innate and adaptive arms of the immune system. This article reviews evidence from the recent clinical and scientific literature that informs the current understanding of the consequences of coronavirus disease 2019 (COVID-19)-induced immune cell activation, as relevant to dermatology. Topics include the clinical consequences of autoantibody production in patients with COVID-19, immunologic evidence for chilblains as a manifestation of SARS-CoV-2 infection, and the relationship between type I interferons and COVID-19 disease severity.

Distinguishing active pediatric COVID-19 pneumonia from MIS-C.

IMPORTANCE: Active pediatric COVID-19 pneumonia and MIS-C are two disease processes requiring rapid diagnosis and different treatment protocols. OBJECTIVE: To distinguish active pediatric COVID-19 pneumonia and MIS-C using presenting signs and symptoms, patient characteristics, and laboratory values. DESIGN: Patients diagnosed and hospitalized with active COVID-19 pneumonia or MIS-C at Children's of Alabama Hospital in Birmingham, AL from April 1 through September 1, 2020 were identified retrospectively. Active COVID-19 and MIS-C cases were defined using diagnostic codes and verified for accuracy using current US Centers for Disease Control case definitions. All clinical notes were reviewed for documentation of COVID-19 pneumonia or MIS-C, and clinical notes and electronic medical records were reviewed for patient demographics, presenting signs and symptoms, prior exposure to or testing for the SARS-CoV-2 virus, laboratory data, imaging, treatment modalities and response to treatment. FINDINGS: 111 patients were identified, with 74 classified as mild COVID-19, 8 patients as moderate COVID-19, 8 patients as severe COVID-19, 10 as mild MIS-C and 11 as severe MIS-C. All groups had a male predominance, with Black and Hispanic patients overrepresented as compared to the demographics of Alabama. Most MIS-C patients were healthy at baseline, with most COVID-19 patients having at least one underlying illness. Fever, rash, conjunctivitis, and gastrointestinal symptoms were predominant in the MIS-C population whereas COVID-19 patients presented with predominantly respiratory symptoms. The two groups were similar in duration of symptomatic prodrome and exposure history to the SARS-CoV-2 virus, but MIS-C patients had a longer duration between presentation and exposure history. COVID-19 patients were more likely to have a positive SAR-CoV-2 PCR and to require respiratory support on admission. MIS-C patients had lower sodium levels, higher levels of C-reactive protein, erythrocyte sedimentation rate, d-dimer and procalcitonin. COVID-19 patients had higher lactate dehydrogenase levels on admission. MIS-C patients had coronary artery changes on echocardiography more often than COVID-19 patients. CONCLUSIONS AND RELEVANCE: This study is one of the first to directly compare COVID-19 and MIS-C in the pediatric population. The significant differences found between symptoms at presentation, demographics, and laboratory findings will aide health-care providers in distinguishing the two disease entities.

Cutaneous manifestations of COVID-19.

The severe acute respiratory syndrome coronavirus two (SARS-CoV-2), which causes the 2019 coronavirus disease (COVID-19), has infected patients worldwide. Physicians have increasingly identified cutaneous findings as a significant clinical manifestation of COVID-19. In this review, we describe the clinical presentation, onset, duration, associated symptoms, treatment, and outcome of cutaneous manifestations thus far reported to be related to COVID-19. We have included data from 63 studies and subdivided reported cutaneous manifestations into the categories of viral exanthem, urticarial, vesicular, chilblains/chilblains-like, non-chilblains vasculopathy-related, pityriasis rosea-like, erythema multiforme-like, Kawasaki/Kawasaki-like disease, and others. Physicians should be aware of the known common cutaneous manifestations of COVID-19 and future research is required to better understand the pathophysiology and prognosis of each COVID-19-related skin manifestation.

Reversible splenial lesion syndrome associated with SARS-CoV-2 infection in two children.

BACKGROUND: Reversible splenial lesion syndrome (RESLES) is characterized by a temporary lesion in the splenium of the corpus callosum, emerging related to encephalitis, seizures, antiepileptic drug withdrawal, or metabolic disturbances. Among RESLES, mild encephalitis/encephalopathy with reversible splenial lesion (MERS) has been defined as a distinct clinicoradiologic syndrome associated with viral infections. CASE PRESENTATION: We report two children with multisystem inflammatory syndrome-children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who developed RESLES during the disease course. Encephalopathy was the main central nervous system symptom. Both of the children showed a rapid recovery, and brain magnetic resonance imaging revealed complete resolution of the splenial lesion within 1 week. CONCLUSION: The complete resolution of the splenial lesion and rapid recovery from encephalopathy in RESLES associated with SARS CoV-2 were similar to observed in MERS.

Equine coital exanthema caused by equid alphaherpesvirus 3: a report of an outbreak in northeastern Brazil / Exantema coital equino causado pelo alphaherpesvirus equídeo tipo 3: relato de um surto no nordeste do Brasil

Equine coital exanthema is a venereal infectious disease poorly reported in horses in Brazil and was never described in the northeastern region of the country. This work aims to describe the clinical and pathological aspects of an outbreak of equine coital exanthema caused by equid alphaherpesvirus 3, occurred in a herd of horses at the semiarid region of the State of Rio Grande do Norte. Main clinical signs consisted of anorexia, hiporexia, fibrinous or purulent secretion in the penis mucosa and vagina. Two mares presented mild to minimal lesions that consisted of scars in the mucosa of the vagina and in the perivulvar region. In a stallion the disease consisted of severe, multifocal, umbilicated-exanthematous ulcers of approximately 1cm in diameter on the penis mucosa. Other areas where ulcers and crusts were focally observed included the skin of the scrotum and on the lips and mucocutaneous junctions of the oral cavity. Histologically, the main lesion consisted of multifocal severe ulcerative and fibrinous necrotizing balanoposthitis and mild multifocal necrotizing, lymphocytic dermatitis in the lips and scrotum. The equide alphaherpesvirus 3 DNA was amplified in blood samples and penis mucosa using the PCR technique. This is the first report of molecular diagnosis of equine coital exanthema affecting horses in northeastern Brazil. Further studies should be carried out in order to investigate the epidemiology and the importance of this herpetic disease in the country.(AU)

O exantema coital equino é uma doença infecciosa venérea pouco relatada em equinos no Brasil e nunca descrita na região Nordeste do país. Este trabalho tem como objetivo descrever os aspectos clínicos e patológicos de um surto de exantema coital equino causado pelo alphaherpesvirus equídeo 3, que ocorreu em um haras na região semiárida do Estado do Rio Grande do Norte. Os principais sinais clínicos consistiram em anorexia, hiporexia, secreção fibrinosa ou purulenta na mucosa do pênis e vagina. Duas éguas apresentavam lesões discretas que consistiam em cicatrizes na mucosa da vagina e na região perivulvar. Em um garanhão, a doença consistia em úlceras umbilicadas-exantematosas severas, multifocais, de aproximadamente 1 cm de diâmetro na mucosa do pênis. Outras áreas onde úlceras e crostas foram observadas focalmente incluíram a pele do escroto, lábios e junções mucocutâneas da cavidade oral. Histologicamente, as principais lesões consistiam em balanopostite multifocal ulcerativa e necrosante fibrinosa grave e dermatite linfocítica necrosante multifocal leve nos lábios e escroto. O DNA do alphaherpesvirus equídeo tipo 3 foi amplificado em amostras de sangue e mucosa do pênis pela técnica de PCR. Este é o primeiro relato de diagnóstico molecular de exantema coital equino afetando cavalos no nordeste do Brasil. Novos estudos devem ser realizados a fim de investigar a epidemiologia e a importância dessa doença herpética no país.(AU)

Assessment of Risk Factors and Outcomes of Severe Ehrlichiosis Infection.

Importance: Ehrlichiosis cases in the US have increased more than 8-fold since 2000. Up to 57% of patients with ehrlichiosis require hospitalization and 11% develop a life-threatening complication; however, risk factors for serious disease are not well documented. Objective: To examine risk factors associated with severe ehrlichiosis. Design, Setting, and Participants: An analytic cross-sectional study of patients diagnosed with ehrlichiosis by polymerase chain reaction (PCR) between January 1, 2007, and December 31, 2017, was conducted in a single tertiary-care center in a region endemic for ehrlichiosis. Analysis was performed from February 27, 2018, to September 9, 2020. A total of 407 positive Ehrlichia PCR results were identified from 383 unique patients, with 155 unique patients meeting study criteria. Patients hospitalized at other institutions who had a positive Ehrlichia PCR performed as a reference test (n = 222) were excluded as no clinical data were available. Electronic medical record review was performed to collect demographic, clinical, laboratory, treatment, and outcomes data. Cases were excluded when there were insufficient clinical data to assess the severity of illness (n = 3) and when the clinical illness did not meet the case definition for ehrlichiosis (n = 3). Exposures: Date of presentation, onset of symptoms, date of PCR testing, date of treatment initiation, site of care, age, birth sex, race/ethnicity, Charlson Comorbidity Index, trimethoprim with sulfamethoxazole use within the prior 2 weeks, and immunosuppression. Main Outcomes and Measures: Requirement for intensive care unit (ICU) admission. Results: Of the 155 patients who met inclusion criteria, 99 patients (63.9%) were men, and 145 patients (93.5%) identified as non-Hispanic White; median age was 50 years (interquartile range, 23-64 years). Intensive care unit admission was indicated in 43 patients (27.7%), 94 patients (60.6%) were hospitalized on general medical floors, and 18 patients (11.6%) received care as outpatients. In adjusted analysis, time to treatment initiation was independently associated with an increased risk for ICU admission (adjusted prevalence ratio [aPR], 1.09; 95% CI, 1.04-1.14; P < .001). Documentation of tick exposure was independently associated with a decreased risk for ICU admission (aPR, 0.54; 95% CI, 0.34-0.86; P = .01). There appeared to be a nonsignificant change toward a decreased need for ICU care among immunosuppressed persons (aPR, 0.51; 95% CI, 0.26-1.00; P = .05). Conclusions and Relevance: This study suggests that delay in initiation of doxycycline therapy is a significant factor associated with severe ehrlichiosis. Increased recognition of infection by front-line clinicians to promote early treatment may improve outcomes associated with this increasingly common and life-threatening infection.

The Impact of COVID-19 on the Faces of Frontline Healthcare Workers.

As the coronavirus epidemic continues, a host of new cutaneous complications is seen on the faces of frontline healthcare workers wearing personal protective equipment on a daily basis. To minimize the risk of COVID-19 infection, healthcare workers wear tight-fitting masks that lead to an excessive amount of pressure on the facial skin. Mechanical pressure, mask materials, and perspiration can all lead to various types of cutaneous lesions such as indentations of the face, skin tears, post-inflammatory hyperpigmentation, ulceration, crusting, erythema, and infection. The objective of this article is to provide effective and straightforward recommendations to those health care providers using facial masks in order to prevent skin-related complications. J Drugs Dermatol. 2020;19(9):858-864. doi:10.36849/JDD.2020.5259.

Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis.

OBJECTIVE: To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. METHODS: The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. RESULTS: A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. CONCLUSION: The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.

Comparison of clinical features and outcomes between patients with early and delayed lupus nephritis.

BACKGROUND: Lupus nephritis is associated with increased risk of end-stage renal disease (ESRD) and all-cause mortality. We evaluated the clinical features and outcomes of patients with early and delayed lupus nephritis. METHODS: The medical records of 171 patients who met the 1997 revised classification criteria for systemic lupus erythematosus (SLE) with pathologic confirmation of lupus nephritis were reviewed. Early lupus nephritis was defined when lupus nephritis was histopathologically confirmed as the first clinical manifestation of SLE, whereas delayed lupus nephritis was defined as lupus nephritis that was identified after the diagnosis of SLE. Clinical and laboratory data, as well as kidney histopathology and medication usage were investigated. Kaplan-Meier and Cox-proportional hazard analysis was performed to compare the outcomes of early and delayed lupus nephritis and evaluate factors associated with ESRD and all-cause mortality. RESULTS: Patients with early lupus nephritis had higher disease activity (median non-renal SLE disease activity index-2000, 6.0 vs. 4.0; p < 0.001) and more frequent skin rash, oral ulcer and serositis; however, the proportion of patients with higher renal chronicity index was greater in the delayed lupus nephritis group (p = 0.007). Nevertheless, no difference was found regarding ESRD and all-cause mortality between the groups. In Cox-proportional hazard analysis, C-reactive protein level, creatinine level and chronicity index were factors associated with ESRD, while age and haemoglobin level were associated with all-cause mortality. CONCLUSIONS: In conclusion, clinical outcomes of early and delayed lupus nephritis are not significantly different. Rigorous adherence to current treatment recommendations is essential for the treatment of lupus nephritis.

Gestational outcomes in women infected by Zika virus during pregnancy in Mato Grosso do Sul, Brazil: A cross-sectional study.

OBJECTIVES: This study aimed to describe the demographic and clinical parameters of women infected by Zika virus who had infants with stigmata of Congenital Zika Syndrome (CZS) versus those who had normal-appearing infants at birth, thereby providing further details on the clinical caveats of neonatal ZIKV infection. METHODOLOGY: This cross-sectional study was performed in the state of Mato Grosso do Sul, Central-West region of Brazil, and included 117 mother-infant pairs who were interviewed and 120 gestational outcomes. All mothers had laboratory confirmation by qRT-PCR of ZIKV infection during pregnancy. RESULTS: The prevalence of congenital abnormalities related to ZIKV was 2.69 cases per 10,000 live births during this period. Exanthem was the main clinical finding, observed in 92.5% of the mothers in this study. Regarding the timing of ZIKV infection, the first trimester was the most frequent time of infection among mothers of infants with CZS (54.55%) (p=0.0007). The case fatality rate was 5% (n=6). Among the 23 children who were classified as having CZS, 13 (56.52%) of them presented with microcephaly. Only 13 (56.52%) children with CZS were tested by qRT-PCR for ZIKV infection at birth, five (38%) were positive. CONCLUSIONS: This study highlights the congenital alterations of ZIKV infection during pregnancy in an epidemic burst, demonstrating that the alterations found in other studies are similar to the present research.

Clindamycin-induced acute generalized exanthematous pustulosis: A case report.

RATIONALE: Acute generalized exanthematous pustulosis (AGEP) is a severe pustular cutaneous adverse drug reaction. Sterile, non-follicular pustules overlying the erythematous skin characterize this reaction. PATIENT CONCERNS: A 30-year-old Asian women presented with sterile, non-follicular lesions with pus-fluid levels on her back 2 days after taking clindamycin. Skin biopsy revealed a spongiotic change in the epidermis with a focal subcorneal pustule and perivascular eosinophil and lymphocyte infiltration. DIAGNOSIS: Clindamycin-induced AGEP. INTERVENTIONS: We discontinued clindamycin treatment and prescribed systemic corticosteroids. OUTCOMES: The pustule stopped spreading within 1 day and the rash improved within 2 days. LESSONS: AGEP is a pustular cutaneous adverse drug reaction that can appear with pus-fluid levels, clinically mimicking Sneddon-Wilkinson disease. The differentiation between both conditions is a history of drug use, characteristic skin lesions and histopathology.

Heart transplant recipient patient with COVID-19 treated with tocilizumab.

A heart transplant 62-year-old patient referred for coronavirus-19 disease (COVID-19) pneumonia. At admission, he was febrile, tachypnoeic, and mild hypoxic with dry cough; during hospitalization, a diffuse morbilliform skin rash appeared. He was treated with tocilizumab with symptoms improvement, without a complete pulmonary function recovery. Skin rash, highly suggestive for COVID-19 cutaneous involvement, persisted for ten days despite tocilizumab administration.

The association of MEFV gene mutations with the disease risk and severity of systemic juvenile idiopathic arthritis.

BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) has many clinical features overlapping with familial Mediterranean fever (FMF), which is caused by mutations in MEFV gene. And FMF patients were easily misdiagnosed as sJIA in China. So we speculate that MEFV is critical genetic background for sJIA and influences patients' severity. In this study, we aim to figure out whether MEFV mutations are risk factor for the occurrence of sJIA and to study the association of MEFV mutations with disease severity of sJIA patients. METHODS: The present study includes 57 sJIA children and 2573 healthy controls. Odd ratio with 95% confidence interval based on allelic frequency of MEFV mutations or variants was used to evaluate their contribution to sJIA susceptibility. Meta-analysis was then performed to reach comprehensive conclusion. All included sJIA patients were grouped by presence and number of MEFV mutations. Clinical data and indicators of disease severity were compared among different groups. Multiple linear regression method was used to find out whether the number of MEFV variants is associated with the severity of sJIA. Kaplan-Meier curves and log rank test were used to estimate the probability of the first relapse. RESULTS: The MEFV mutations of our subjects predominantly existed in exons 2 and 3. No significant difference was found in allelic frequency between sJIA children and healthy controls. Meta-analysis demonstrated that p.M694V/I was a risk factor for sJIA (pooled OR: 7.13, 95% CI: 3.01-16.89). The relative period of activity was significantly lower in the one mutation group than those with more than one mutation (p = 0.0194). However, no relevance was found in multiple linear regression models. CONCLUSIONS: The mutation p.M694V/I in MEFV might be a risk factor for sJIA. SJIA patients carrying more than one heterozygous mutation in MEFV tend to be more severe than those containing only one, but studies in other cohort of patients need to be performed to validate it.