Dermatological Involvement Research Articles

Unraveling a history of overlap: A phenotypic comparison of RBCK1-related disease and glycogen storage disease type IV.

RBCK1-related disease is a rare, multisystemic disorder for which our current understanding of the natural history is limited. A number of individuals initially carried clinical diagnoses of glycogen storage disease IV (GSD IV), but were later found to harbor RBCK1 pathogenic variants, demonstrating challenges of correctly diagnosing RBCK1-related disease. This study carried out a phenotypic comparison between RBCK1-related disease and GSD IV to identify features that clinically differentiate these diagnoses. Literature review and retrospective chart review identified 25 individuals with RBCK1-related disease and 36 with the neuromuscular subtype of GSD IV. Clinical features were evaluated to assess for statistically significant differences between the conditions. At a system level, any cardiac, autoinflammation, immunodeficiency, growth, or dermatologic involvement were suggestive of RBCK1, whereas any respiratory involvement suggested GSD IV. Several features warrant further exploration as predictors of RBCK1, such as generalized weakness, heart transplant, and recurrent infections, among others. Distinguishing RBCK1-related disease will facilitate correct diagnoses and pave the way for accurately identifying affected individuals, as well as for developing management recommendations, treatment, and an enhanced understanding of the natural history. This knowledge may also inform which individuals thought to have GSD IV should undergo reevaluation for RBCK1.

Casuística de atendimento de caninos e felinos da Clínica Veterinária Escola da UFSC Curitibanos, Santa Catarina, Brasil, entre 2015 e 2022

This study aimed to conduct a casuistry survey based on the analysis of clinical records of canines and felines treated between 2015 and 2022 at the School Veterinary Clinic of UFSC (SVC/UFSC) to study disease prevalence associated with patient review data. This is the first clinical prevalence study in the state of Santa Catarina. Diseases were diagnosed in seven organ systems, including skeletal muscle, respiratory, digestive, reproductive, urinary, nervous, and endocrine, and five specialties, including dermatology, ophthalmology, infectious diseases, dentistry, and oncology, considering the first seven years of care. Of the 1419 animals treated, 74.21% (1053) were canine and 25.79% (366) feline. Of the 1053 dogs, 23.67% (250) were purebred and 76.36% (803) were mixed breeds. Among the cats, 89.61% (328) presented no defined breed, and 10.39% (38) were pure breeds. Most canines are between 10 months and four years old, whereas in felines, most are up to 1 year of age. Canines presented a higher prevalence of dermatological involvement, corresponding to 26.59%, whereas urinary system problems prevailed in felines (15.30%). Casuistry studies indicate the predominant diseases in a given area and their risk factors, considering differential diagnosis and future prevention programs for animal welfare and health.

Remitting seronegative symmetrical synovitis with pitting edema syndrome: case report of an atypical presentation of a rare syndrome and literature review

BackgroundRemitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare syndrome. The following case shows an atypical course of the disease with successful treatment. In addition, the accompanied review highlights current findings in the pathogenesis and treatment. Clinicians should be aware of the differential diagnosis of RS3PE syndrome.Case presentationA 67-year-old female patient with recurrent, asymmetric, and painful swelling of both hands with pitting edema, predominantly affecting the dorsal right hand, presented at our in-patient clinic. Over the years of her disease, first diagnosed as rheumatoid arthritis and then psoriatic arthritis, prednisolone treatment had the most favorable effects over various disease-modifying antirheumatic drugs.Subsequent diagnostic evaluation confirmed RS3PE syndrome, a rare inflammatory disorder primarily affecting the elderly population. Manifesting as symmetrical joint inflammation of small joints with pitting edema, RS3PE syndrome typically onsets suddenly and may be accompanied by systemic symptoms like fever, fatigue, and weight loss. Although the precise etiology remains enigmatic, both the innate and the adaptive immune system seem to play a pathogenic role. Treatment is conventionally based on prednisolone, which effectively mitigates symptoms.Ultimately, RS3PE was diagnosed in the context of psoriatic arthritis without dermatological or nail involvement. Given the unusual presentation marked by female gender, asymmetry, and prolonged and extensive disease with various prior treatments and in the context of psoriatic arthritis, a tumor necrosis factor alpha inhibitor was initiated in addition to low-dose prednisolone resulting in clinical remission for the first time.ConclusionsIn conclusion, the aforementioned atypical manifestation highlights the significance of including RS3PE syndrome as a potential differential diagnosis, particularly in instances where specific diagnostic criteria for rheumatoid arthritis, polymyalgia rheumatica, or psoriatic arthritis are absent. RS3PE responds well to the administration of prednisolone. In refractory cases, a therapeutic trial with tumor necrosis factor alpha inhibitors can be conducted.

Juvenile dermatomyositis with Anti-SAE antibodies in a Moroccan child associated with pseudo-angioedema: a case report

BackgroundJuvenile Dermatomyositis (JDM) is the leading cause of non-infectious inflammatory myopathy in children. It is a heterogeneous group of autoimmune diseases characterized by a variable combination of muscular, dermatological, and visceral involvement. Myositis-specific autoantibodies help define homogeneous subgroups with common clinical characteristics and prognoses. Anti-SAE (small ubiquitin-like modifier 1 (SUMO-1) activating enzyme) antibodies are among the most recently discovered specific autoantibodies. The presence of these antibodies is very rare, making it challenging to define clinical features and prognosis in the juvenile form. We report the first case of an African patient with juvenile dermatomyositis and positive anti-SAE antibodies.Case ReportA 5-year-3-month-old Moroccan boy presented to the pediatric emergency department with dysphagia that had been evolving for two days, preceded two months earlier by facial erythema associated with fatigue, lower limb pain, difficulty walking, and progressive inflammatory polyarthralgia. On admission, the child had a heliotrope rash with predominant pseudo-angioedema on the lips, periungual telangiectasia, and Gottron’s papules over the bilateral interphalangeal and metatarsophalangeal joints. The patient had a more pronounced proximal muscle weakness in the lower limbs. He had no urticaria, fever, arthritis, calcinosis, cutaneous ulcers, or lipodystrophy. The Joint examination was normal, as was the pleuropulmonary examination. The electroneuromyography showed myogenic changes in all four limbs. Laboratory findings showed elevated levels of creatine phosphokinase and lactate dehydrogenase and a mild inflammatory syndrome. The electrocardiogram was normal. The anti-SAE antibodies were positive. The boy was diagnosed with juvenile dermatomyositis. He received methylprednisolone bolus therapy followed by oral prednisone. The latter was gradually tapered in combination with weekly intramuscular methotrexate. As a result, dysphagia disappeared within 48 h. After two weeks, there was an improvement in the muscular score and a significant regression of facial pseudo-angioedema.ConclusionWe report the first African patient with anti-SAE autoantibody-positive JDM. He had a typical dermatological manifestation of JDM associated with pseudo-angioedema predominant on the lips; a rarely reported sign in DM and JDM patients. The patient responded well to corticosteroid therapy and methotrexate.

P020 Clinical characteristics, disease trajectories and management of Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review

Abstract Background/Aims VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an autoinflammatory condition, characterised by somatic mutation of UBA1 gene. To date, no systematic literature review (SLR) has been undertaken to summarise the clinical manifestations, genotypes and treatment of VEXAS. We undertook a SLR to evaluate the multisystem characteristics and genotypes associated with VEXAS syndrome. Methods Articles discussing VEXAS syndrome, published 1946 until May 2023, were included. The protocol was registered in the PROSPERO database of systematic reviews (CRD42023407547). Medline, Embase and Cochrane Databases were searched. The research questions were: 1) What are the clinical characteristics of patients diagnosed with VEXAS? 2) What are the genotypes associated with VEXAS? 3) What are the effective treatments for VEXAS? Articles meeting inclusion criteria were examined by two authors at abstract and full paper stage. Information was extracted on: demographics, type and prevalence of clinical manifestations, genetic mutations, and treatment. Meta-analysis using a random effects model was used to determine pooled estimates of serum markers. Results From 214 articles, 64 were included, comprising 273 patients with VEXAS. 96.3% were male, with a mean age of 67.2 years (SD 6.8) at disease onset. Study cohorts were from: Europe (n = 25); North America (n = 18); South America (n = 1); Asia (n = 16); Australasia (n = 4). The most frequent diagnoses made prior to VEXAS were: relapsing polychondritis (n = 48); Sweet’s syndrome (n = 24); polyarteritis nodosa (n = 11); myelodysplastic syndrome (n = 10). Fever was reported in 195 cases (71.4%) and weight loss in 69 (25.3%). Most patients had pulmonary (n = 231; 84.6%), haematological (n = 228; 83.5%) dermatological (n = 217; 79.5%) and musculoskeletal (n = 138; 50.5%) involvement, although other organ manifestations of varying prevalence were also recorded. Pooled estimates of serological investigations were: ESR 101.3 mm/hr (SE 4.8; n = 246); CRP 144.2 mg/L (SE 14.1; n = 258); Hb 91.0 g/L (SE 3.2; n = 265); MCV 107.3 fL (SE 2.3; n = 265). The most commonly reported mutations were “c.122T>C pMET41Thr” (n = 71), “c.121A>G pMET41Val” (n = 35) and “c.121A>C pMet41Leu” (n = 33). Most patients received glucocorticoids (n = 133, 48.7%) followed by methotrexate (n = 55, 20.1%) and IL-6 inhibitors (n = 47, 17.2%). One patient underwent splenectomy; six received bone marrow transplants. Regarding mortality, 44 patients were reported to have died due to manifestations of VEXAS syndrome. Conclusion This is the first SLR to capture clinical manifestations, genetics and treatment of cases of VEXAS reported to date. Diagnosis remains clinically challenging, as evidenced by the multiple prior diagnoses ascribed to patients, most commonly relapsing polychondritis and Sweet’s syndrome. Most patients present with haematological disorders, fever, pulmonary and dermatological involvement. Reported mortality was consistent with genetic variants strongly associated with reduced survival rates. Genetics and treatment of VEXAS continue to be an active area of research. Future studies are needed to better understand these as well as optimize treatment for people with this rare condition. Disclosure K. Kouranloo: None. M. Dey: None. J. Almutawa: None. N. Myall: None. A. Nune: None.

Clinical characteristics, disease trajectories and management of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly discovered autoinflammatory condition characterised by somatic mutation of the UBA1 gene. The syndrome leads to multi-system inflammation affecting predominantly the skin, lungs and bone marrow. We undertook a systematic review of the multisystem features and genotypes observed in VEXAS syndrome. Articles discussing VEXAS syndrome were included. Medline, Embase and Cochrane databases were searched. Information was extracted on: demographics, type and prevalence of clinical manifestations, genetic mutations and treatment. Meta-analysis using a random effects model was used to determine pooled estimates of serum markers. From 303 articles, 90 were included, comprising 394 patients with VEXAS. 99.2% were male, with a mean age of 67.1 years (SD 8.5) at disease onset. The most frequent diagnoses made prior to VEXAS were: relapsing polychondritis (n = 59); Sweet's syndrome (n = 24); polyarteritis nodosa (n = 11); and myelodysplastic syndrome (n = 10). Fever was reported in 270 cases (68.5%) and weight loss in 79 (20.1%). Most patients had haematological (n = 342; 86.8%), dermatological (n = 321; 81.5%), pulmonary (n = 297; 75.4%%) and musculoskeletal (n = 172; 43.7%) involvement, although other organ manifestations of varying prevalence were also recorded. The most commonly reported mutations were "c.122T > C pMET41Thr" (n = 124), "c.121A > G pMET41Val" (n = 62) and "c.121A > C pMet41Leu" (n = 52). Most patients received glucocorticoids (n = 240; 60.9%) followed by methotrexate (n = 82; 20.8%) and IL-6 inhibitors (n = 61, 15.4%). One patient underwent splenectomy; 24 received bone marrow transplants. VEXAS syndrome is a rare disorder affecting predominantly middle-aged men. This is the first systematic review to capture clinical manifestations, genetics and treatment of reported cases. Further studies are needed to optimise treatment and subsequently reduce morbidity and mortality.

SAPHO syndrome: current clinical, diagnostic and treatment approaches.

This review provides an overview of SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis), a rare autoinflammatory disease that primarily affects bones, skin, and joints. We conducted a search on Medline/PubMed using keywords such as SAPHO syndrome, chronic recurrent multifocal osteitis/osteomyelitis, and related terms. SAPHO syndrome is rare, with a reported frequency of 1 in 10,000 in the Caucasian population. However, the actual incidence of SAPHO syndrome is unknown, and the incidence of the disease is likely higher. The pathogenesis of SAPHO syndrome remains incompletely understood. Current evidence suggests that SAPHO results from a complex interplay between immune dysregulation, genetic susceptibility, and environmental factors. It's not clear if SAPHO syndrome is an autoimmune disease or an autoinflammatory disease, but current evidence suggests that it's more likely an autoinflammatory disease because of things like neutrophil hyperactivity, fewer natural killer (NK) cells, high levels of interleukin (IL)-1, and a good response to treatments that block IL-1. Osteo-articular (OA) involvement is a key clinical feature of SAPHO. It affects the anterior chest wall, axial skeleton, peripheral joints, mandible, long bones of the extremities, and pelvis. Dermatological involvement is a common target in SAPHO, with lesions observed in 60-90% of cases. Common skin lesions include psoriasis and acne, with hidradenitis suppurativa and neutrophilic dermatoses being less commonly seen. Other clinical findings include constitutional symptoms caused by systemic inflammation, such as fever, weight loss, and fatigue. There is no specific laboratory finding for SAPHO syndrome. However, during active disease, there may be an increase in positive acute phase markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement levels, mild leukocytosis, and thrombocytosis. Diagnosis is crucial for SAPHO syndrome, which lacks a specific diagnostic finding and is often underrecognized. A comprehensive evaluation of a patient's medical history and physical examination is crucial. Treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional and synthetic disease-modifying agents (cDMARDs and sDMARDs), biological therapies, bisphosphonates, and antibiotics. Biological treatments have emerged as a viable alternative for SAPHO patients who do not respond to conventional treatments.

Neurological and Dermatological Manifestations of Tuberous Sclerosis Complex: Report from a Romanian Tertiary Hospital Cohort.

Tuberous sclerosis complex is a rare multisystem genetic disorder characterized by multiorgan involvement, frequently associated with intellectual impairment and epilepsy. The aim of our study was to describe the neurological and dermatological manifestations of TSC in 32 adult patients (of whom 19 were females) who attended the Neurology and Nephrology Clinics of Fundeni Clinical Institute in Romania from 2015 to 2020. Seventeen patients were diagnosed with epilepsy, nine patients had intellectual impairment, and complete neuroimaging was available for twenty-two patients. As expected, the most frequent dermatological lesions were cutaneous angiofibromas in 20 patients, but with a lower frequency than described in the current literature. Statistical analysis was performed considering the small number of patients. Cortical tubers in neuroimaging seemed to be associated with the diagnosis of epilepsy, while subependymal nodules represented a risk factor for intellectual impairment. Males showed a larger number of dermatological types of lesions, especially café -au-lait patches. Interestingly, we found a statistically significant positive association between epilepsy and the presence of cutaneous angiofibromas, as well as total dermatological involvement. Females had significantly higher Charlson comorbidity index scores, indicating a higher burden of disease. Everolimus seemed to be a well-tolerated treatment and showed promising results in controlling epileptic seizures alone in two patients. More studies, with the inclusion of a larger number of patients, are needed to confirm these results.

A neonatal lupus syndrome with pericardial tamponade due to maternal Sjögren’s syndrome

Neonatal lupus syndrome (NLS) is a rare disease with dermatological, cardiac, hepatic and hematologic involvement due to placental transfer of anti-Ro/ SSA and anti-La/ SSB antibodies in infants of mothers with autoimmune diseases. Multisystemic involvement is common in infants. Here we present a baby with neonatal lupus syndrome whose mother had Sjögren's syndrome. He presented with thrombocytopenia, then convulsion and cardiac arrest due to pericardial tamponade. So, the risk of NLS should be kept in mind in infants of mothers with autoimmune diseases.

Efficacy of Dupilumab in STAT6 GOF disease: 30 months follow-up of a single patient

Signal transducer and activator of transcription 6 (STAT6) gain-of-function (GOF) disease is a novel inborn error of immunity (IEI) characterised by early-onset severe allergic disease with dermatological, respiratory, and gastrointestinal involvement, accompanied by hypereosinophilia and hyperIgE. We diagnosed one such patient in Hong Kong, who now is a young man in his 20 s, and has had lifelong struggle with debilitating recalcitrant eczema and short stature among other issues. Exome sequencing identified a heterozygous mutation in STAT6 NM_001178078.1:c.1256A>G; p.(Asp419Gly), which we demonstrated to cause gain-of-function in luciferase promoter assays. Knowing the diagnosis, the patient was started on a biologic, Dupilumab, which is a monoclonal targeting IL4RA, the receptor upstream of STAT6. The patient experienced dramatic reduction in eczema disease activity as quantified by EASI and SCORAD scores, and had sharp reduction in peripheral eosinophilia without normalising his IgE levels. Dupilumab also potentiated the effect of his growth hormone replacement as he experienced dramatic height and weight gain since initiating Dupilumab. Transcriptomic analyses on bulk and single-cell levels also demonstrated reduced immune cell perturbation compared to healthy controls after treatment. The clinical effect of Dupilumab was sustained up to the last follow up more than 2 years after initiation. Dupilumab use was not associated with safety concerns. To conclude, Dupilumab appears to be a safe and effective treatment option for patients with STAT6 GOF disease.

Prevalence of lymphedema among Anderson-Fabry disease patients: A report from the Fabry registry.

Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease due to a genetic variation in the α-galactosidase A (GLA) gene. As a result, the activity of the α-galactosidase A (AGAL-A) enzyme is reduced or absent, which causes sphingolipid deposition within different body parts. AFD typically manifests with cardiovascular, renal, cerebrovascular, and dermatologic involvement. Lymphedema is caused by sphingolipid deposition within lymphatics. Lymphedema can cause intolerable pain and limit daily activities. Very limited data exist on lymphedema in AFD patients. Using data from the Fabry Registry (NCT00196742) with 7671 patients included (44% males and 56% females), we analyzed the prevalence of lymphedema among AFD patients who were ever assessed for lymphedema and studied the age of first reported lymphedema. Additionally, we assessed whether patients received AFD-specific treatment at some point during their clinical course. The data was stratified by gender and phenotype. Our study showed that lymphedema occurred in 16.5% of the Fabry Registry patients who were ever assessed for lymphedema (n = 5487). Male patients when compared to female patient have higher prevalence (21.7% vs 12.7%) and experienced lymphedema at a younger age (median age at first reported lymphedema of 43.7 vs 51.7 years). When compared to other phenotypes, classic phenotype has the highest prevalence of lymphedema with the earliest reported lymphedema. Among those who reported lymphedema, 84.5% received AFD-specific treatment during their clinical course. Lymphedema is a common manifestation of AFD in both genders, with a tendency to present later in female patients. Recognition of lymphedema can offer an important opportunity for intervention and potential impact on associated morbidity. Additional future studies are needed to characterize the clinical implications of lymphedema in AFD patients and identify additional treatment options for this growing population.

A Broad Characterization of Glycogen Storage Disease IV Patients: A Clinical, Genetic, and Histopathological Study.

Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disease caused by variants in the GBE1 gene, which encodes the glycogen branching enzyme (GBE). GSD IV accounts for approximately 3% of all GSD. The phenotype of GSD IV ranges from neonatal death to mild adult-onset disease with variable hepatic, muscular, neurologic, dermatologic, and cardiac involvement. There is a paucity of literature and clinical and dietary management in GSD IV, and liver transplantation (LT) is described to correct the primary hepatic enzyme defect. Objectives: We herein describe five cases of patients with GSD IV with different ages of onset and outcomes as well as a novel GBE1 variant. Methods: This is a descriptive case series of patients receiving care for GSD IV at Reference Centers for Rare Diseases in Brazil and in the United States of America. Patients were selected based on confirmatory GBE1 genotypes performed after strong clinical suspicion. Results: Pt #1 is a Latin male with the chief complaints of hepatosplenomegaly, failure to thrive, and elevated liver enzymes starting at the age of 5 months. Before LT at the age of two, empirical treatment with corn starch (CS) and high protein therapy was performed with subjective improvement in his overall disposition and liver size. Pt #2 is a 30-month-old Afro-American descent patient with the chief complaints of failure to gain adequate weight, hypotonia, and hepatosplenomegaly at the age of 15 months. Treatment with CS was initiated without overall improvement of the symptoms. Pt #3.1 is a female Latin patient, sister to pt #3.2, with onset of symptoms at the age of 3 months with bloody diarrhea, abdominal distention, and splenomegaly. There was no attempt of treatment with CS. Pt #4 is an 8-year-old male patient of European descent who had his initial evaluation at 12 months, which was remarkable for hepatosplenomegaly, elevated ALT and AST levels, and a moderate dilatation of the left ventricle with normal systolic function that improved after LT. Pt #1, #3.2 and #4 presented with high levels of chitotriosidase. Pt #2 was found to have the novel variant c.826G > C p.(Ala276Pro). Conclusions: GSD IV is a rare disease with different ages of presentation and different cardiac phenotypes, which is associated with high levels of chitotriosidase. Attempts of dietary intervention with CS did not show a clear improvement in our case series.

An atypical presentation of dermatomyositis sine dermatitis

Dermatomyositis (DM) is a rare autoimmune disorder. This idiopathic inflammatory myopathy (IIM) is characterized by overexpression of major histocompatibility complex I and the formation of autoantibodies. Apart from muscle weakness, dermatological involvement is classically seen in DM. Recently, a few articles have been published documenting a subset of DM with no skin involvement – DM sine dermatitis. Here, we present a 37-year-old male with progressive proximal weakness with no skin involvement. Unlike classical DM, neither muscle enzymes (creatinine phosphokinase and aldolase) were elevated nor myositis-specific autoantibodies were detected. Muscle biopsy, however, was characteristic for DM with positivity for CD3, CD4, CD8, CD20, and CD68. The patient improved with initiation of immunosuppressants. Screening for malignancy and interstitial lung disease was unremarkable.

Study of Dermatological manifestations of Dengue fever in Andhra Population

Background: Dengue fever is a major health problem in all age groups especially in tropical countries like India.Dengue fever (DF) may present with dermatological manifestations but enough data is not available for justificationhence this study was conducted to correlate DF with dermatological manifestation.Method: 80 (Eighty) patients aged between 16 to 60 years having DF positive by ELISA test were studied toevaluate dermatological manifestation.Results: 44 (55%) had only cutaneous involvement, 19 (23.7%) had muco-cutaneous involvement, 17 (21.7%) hadno dermatological involvement. Among those with skin involvement, 38 (47.5%) had generalized rash, 27 (33.7%)truncal, 15 (18.7%) had rash in the extremities. Out of 80, 55 (68.7%) had pruritus and 25 (31.7%) had no pruritus.Conclusion: Dermatological manifestations are common clinical feature in DF patients but not observed in all DFpatients. Identification of skin involvement help the clinician in early diagnosis and better management of patientsto avoid morbidity and mortality.

1865. Analysis of National Surveillance Data to Support Case Definition Revisions for Multisystem Inflammatory Syndrome in Children (MIS-C), United States, February 2020–April 2022

Abstract Background Classification of MIS-C, COVID-19, and other pediatric inflammatory conditions is challenged by phenotypic overlap and absence of diagnostic laboratory evidence. Due to public health need and based on limited data from early cases, CDC developed a necessarily broad MIS-C surveillance case definition in May 2020. Studies have since shown that some criteria do not distinguish between MIS-C and other conditions and may contribute to misclassification. To inform planned revision to the CDC definition, we evaluated the impact of narrowing these criteria on case inclusion in national MIS-C surveillance. Methods Of state and local health-department reported cases meeting the current MIS-C case definition as of 04/14/2022, we describe the proportion that met revised criteria under consideration including fever duration, C-reactive protein (CRP) elevation using a defined cutoff, and organ involvement represented by specific criteria. We also evaluated cases identified using potential combinations of revised criteria. Results Of 8,096 MIS-C cases fulfilling the original case definition, 6,332 (78%) had sufficient data for evaluation of criteria. Of these, 96% had fever for ≥2 days and 94% had a CRP ≥ 3.0 mg/dL (Table 1). Cardiac involvement defined by key features of MIS-C was present in 84% of cases (62% if BNP/proBNP elevation was excluded); 43% had shock. Dermatologic, gastrointestinal (GI) and hematologic involvement were present in 75%, 89% and 37% of cases, respectively. Neurologic (excluding headache), renal, and respiratory involvement were present in 16%, 20%, and 63% of cases, respectively. The number of cases with ≥ 2 of cardiac (without BNP/proBNP elevation), shock, dermatologic, GI, or hematologic involvement was 5,733 (91%). SARS-CoV-2 testing results are shown in Table 2. Conclusion The CDC MIS-C case definition is intentionally broad. Using national surveillance data, we evaluated case inclusion under narrower criteria, prioritizing features of MIS-C that distinguish it from similar pediatric inflammatory conditions. A surveillance case definition may not capture all cases and is not intended to replace clinical judgment. We plan to assess additional criteria combinations, describe potentially excluded cases, and incorporate findings into a revised definition. Disclosures All Authors: No reported disclosures.

Hospitalized children with SARS-CoV-2 infection and MIS-C in Jamaica: A dive into the first 15 months of the novel pandemic.

ObjectivesCOVID-19 in children was initially mild until the emergence of Multisystem Inflammatory Syndrome in Children (MIS-C). We describe pediatric COVID-19 in a developing country within the Caribbean.MethodsJamaican children who were hospitalized with SARS-CoV-2 infection, in one Caribbean regional academic referral center from April 2020 through June 2021 were included. Prospective surveillance and pediatric infectious disease consultations were performed using the CDC's MIS-C case definition. Data were extracted from patients' hospital charts using WHO's reporting form, entered into the RedCap database, and SPSS 28 was used for analysis. MIS-C and non-MIS-C patients were compared using independent sample t-tests for continuous variables and Fisher's exact test for categorical variables, p values < 0.05 were statistically significant.ResultsSeventy-nine children with COVID-19 with/without MIS-C presented to UHWI. Thirty-eight (48%) were mild ambulatory cases. Hospitalizations occurred in 41 (52%) children, with median age of 10 years. SARS-CoV-2 RT-PCR positivity was present in 26 (63%), Immunoglobulin M, or Immunoglobulin G (IgM/IgG) positivity in 8 (20%), with community exposures in 7 (17%). Eighteen (44%) MIS-C positive patients were significantly more likely than 23 MIS-C negative patients (56%) to present with fever (94% vs. 30%; p < 0.001), fatigue/lethargy (41% vs. 4%; p = 0.006), lymphadenopathy (33% vs. 0%; p = 0.003), elevated neutrophils (100% vs. 87%; p = 0.024), and ESR (78% vs. 9%; p = 0.002). Involvement of > two organ systems occurred more frequently in MIS-C positive cases (100% vs. 34%; p < 0.001), including gastrointestinal (72% vs. 17%; p < 0.001); vomiting/nausea (39% vs. 9%; p < 0.028); hematological/coagulopathic (67% vs. 4%; p < 0.001); dermatologic involvement (56% vs. 0%; p < 0.001); and mucositis (28% vs. 0%; p = 0.001). MIS-C patients had Kawasaki syndrome (44%), cardiac involvement (17%), and pleural effusions (17%). MIS-C patients had >4 abnormal inflammatory biomarkers including D-dimers, C-reactive protein, ESR, ferritin, troponins, lactate dehydrogenase, neutrophils, platelets, lymphocytes, and albumen (72%). MIS-C patients were treated with intravenous immune gamma globulin (78%), aspirin (68%), steroids (50%), and non-invasive ventilation (11%). None required inotropes/vasopressors. MIS-C negative patients received standard care. All recovered except one child who was receiving renal replacement therapy and developed myocardial complications.ConclusionsIn this first report of COVID-19 from the Caribbean, children and adolescents with and without MIS-C were not very severe. Critical care interventions were minimal and outcomes were excellent.

A study of Mucocutaneous Manifestations of HIV infections &amp; its relation with CD4 Count

AIDS was first recognized in the United States in 1981. In 1983, HIV was isolated and by 1984 it was demonstrated clearly to be the causative agent of AIDS. All countries in the world are facing HIV/AIDS occurrence as a major health problem. Dermatological involvement in AIDS has been appreciated since the days the disease was recognized as a cryptic acquired immune deficiency illness in homosexual men and before the causative virus was identified. HIV has been demonstrated in the dermis of infected individuals and may be present in langerhans cells. It is estimated that more than 90% of HIV- infected patients develop skin or mucous membrane disorders at some time during their infection. The knowledge of skin manifestations such as bacillary angiomatosis, Kaposi‘s sarcoma, oral candidiasis and hairy leukoplakia, may provide a clue for diagnosing a previously undetected HIV positive status. CD4 cell count is extremely important in staging of HIV infection and a revised classification of the center for disease control (CDC), Atlanta, USA (1993) divides HIV positive persons into three CD4 count categories: 1) 1&amp;#62;500/Ml; 2) 200- 499/Ml, 3) Pneumocystis carinii pneumonia: In general a CD4 cell count of 200/mL is roughly equivalent to 20% of the lymphocyte count. The normal range for CD4 values vary between laboratories but they are around 500- 1300/mL for the absolute count and 38%- 65% for the percentage. The CD4 T lymphocytes; a subpopulation of the lymphocytes also known as T helper cells, are coordinators of the body‘s immune response, e.g. providing help to B cells in the production of antibody, as wells as in augmenting cellular immune response to antigens. Within hours of exposure to HIV, CD4 T lymphocytes are found to be infected showing active viral replication.

EP263: A pathogenic deletion at 13q32.1q33.1 presenting with bilateral sensorineural hearing loss and pigmentation anomalies, mimicking Waardenburg syndrome

13q deletion syndrome is caused by structural and functional monosomy of the long arm of chromosome 13. Individuals with partial deletions of 13q have a wide spectrum of clinical phenotypes, including mild to severe intellectual disability, growth retardation, craniofacial dysmorphism, hand and foot anomalies, brain, cardiac and renal defects. Previous reports suggest that deletions including the 13q32 band are associated with severe congenital malformations. The ZIC2 gene maps to this critical distal region at 13q32.2 and has been considered a possible candidate for brain malformations, such as holoprosencephaly and Dandy-Walker malformation. We present an individual with a 7.9 Mb deletion on chromosome 13, encompassing almost all of band q32, with a relatively mild phenotype. An 11-month-old term male was seen in the medical genetic clinic regarding concerns for possible Waardenburg Syndrome. He presented with bilateral sensorineural hearing loss at 9 months of age and was noted to have multiple hypopigmented lesions on both his feet and chest. Prenatal and post- natal course was unremarkable with normal growth and development. Physical examination revealed mild dysmorphic features such as borderline, low set and posteriorly rotated ears with folded upper helixes and a broad nasal bridge. Hypopigmented lesions consistent with leukoderma was noted over the anterior chest wall, abdominal wall and medial aspect of his right thigh. Family history was positive for a maternal cousin with similar hypopigmented lesions and maternal great, great grandmother with early premature graying of hair. There was no family history of congenital hearing loss or birth defects. A chromosomal microarray (CMA) was performed and revealed a 7.9 megabase pathogenic deletion at chromosome 13q32.1q33.1, involving 65 genes. This deletion encompasses the ZIC2 gene which is associated with holoprosencephaly. This was an unexpected finding and further imaging studies to evaluate for cardiac, renal and brain malformations have been planned. Deletions of 13q are rare and additional cases are needed to better understand the genotype-phenotype correlation. We present an atypical case of a 13q deletion syndrome associated with mild dysmorphism, bilateral sensorineural hearing loss and leukoderma. There have been suggestions that distal deletions are associated with a more severe clinical phenotype and proximal deletions causes less severe major anomalies. This case broadens the clinical spectrum of 13q deletion syndrome as hearing loss is an uncommon finding and dermatological involvement has not been previously reported. There have been one prior report indicating that the loss of Zic2 function results in impaired inner ear development in mice and may be a candidate gene that contributes to the genetics of hearing loss in humans. Additionally, although the region deleted on the long arm of chromosome 13 involves the ZIC2 gene, this patient appears to be growing and developing normally. These findings suggest regions outside of band 13q32 likely contribute to the severe congenital malformations previously associated with distal 13q deletions.

Mammalian target of rapamycin inhibitors for the treatment of astrocytic hamartoma in tuberous sclerosis complex (TSC).

Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder. Fifty percent of patients with TSC will develop retinal astrocytic hamartoma (RAH). The mammalian target of rapamycin (mTOR) inhibitors interferes with the pathological mechanisms of TSC. Treatment of RAH with mTOR inhibitors has been described in only a few isolated case reports. The purpose of this study was to assess the effect of mTOR inhibitors on RAH in a small cohort of patients. The medical records of all consecutive patients with ocular manifestations of TSC that were treated with mTOR inhibitors at the Sheba Medical Center from January 2014 to December 2018 were retrospectively reviewed. Data collection included demographics, medical history, ocular presentation, ocular treatment, and treatment outcome. Tumor size was assessed by a masked observer, before and after treatment. Lesion measurements were made with Heidelberg SD-OCT (HRA + OCT SPECTRALIS), and fundus photos were taken with RetCam3® (Natus, USA) and analyzed by "ImageJ" software. Eleven patients with tuberous sclerosis and astrocytic hamartoma were treated with mTOR inhibitors in the study period. Of them, 6 children (11 eyes, 20 tumors) had proper imaging of tumor size before and after treatment. The analysis included these 11 eyes. All six patients had non-ocular manifestations of TSC, including dermatologic (n = 5), neurologic (n = 5), and renal (n = 3) involvement. Ocular involvement included in five eyes (45%) tumors near the optic disc and in four eyes (37%) foveal tumors. The mean follow-up duration was 2.15 ± 1.4years (range 10months to 4.5years). The average tumor base reduction in the treated group was 17.8% ± 15.9. The average maximal thickness at baseline was 414 ± 174μm (range 152-686μm). There was a 14% ± 7.1 reduction after treatment. None of the tumors showed evidence of growth at the final follow-up. The findings of this study suggest that mTOR inhibitors can reduce tumor size and that they can be considered as an optional treatment in certain conditions. This preliminary report is the first to quantitatively assess pre- and posttreatment tumor size, in young patients.

Dilated Cardiomyopathy Revealing a Henoch-Schönlein Purpura in a Young Patient: About a Case and Review of the Literature…

Schönlein-Henoch purpura is a non-thrombocytopenic systemic vasculitis of small-caliber vessels due to immune complexes. We report the case of an adult 30 year old man admitted for a generalized edematous syndrome with purpuric lesions in the 2 lower limbs revealing a dilated cardiomyopathy whose etiological assessment was in favor of a Schönlein-Henoch purpura with cardiac, renal, dermatological involvement. The diagnosis was difficult to establish given the clinical polymorphism. Also, management was complicated given the multifocal involvement. The treatment was based on corticosteroid therapy and rituximab but the evolution was, unfortunately, not satisfactory.