COVID-19 associated multisystem inflammatory syndrome in a neonate with atypical coronary artery involvement.

Objective The study aimed to report a COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) in a neonate found to have an atypical diffuse thickening in coronary artery walls, whose diagnosis required a multi-imaging approach. Study Design A neonate presented at birth with multiple organ involvement and coronary artery anomalies. A diagnosis of MIS-C associated to COVID-19 was supported by maternal Sars-CoV-2 infection during pregnancy, and by the presence of both IgG against Sars-CoV-2 and Spike-specific memory B cells response in the neonatal blood. Other plausible causes of the multiple organ involvement were excluded. Result At admission, a severe coronary artery dilatation was identified on echocardiography, supporting the diagnosis of MIS-C Kawasaki-like disease; however, coronary artery internal diameters were found to be normal using cardiac computed tomography angiography. At discharge, comparing the two imaging techniques each other, the correct diagnosis resulted to be an abnormal thickening in coronary arterial walls. These findings suggest that the inflammatory process affecting the coronary arterial wall in MIS-C could result not only in typical coronary artery lesions such as dilatation of the lumen or aneurysms development, but also in abnormal thickening of the coronary artery wall. Conclusion. Our case provides an alert for paediatric cardiologists about the complexity to assess coronary artery involvement in MIS-C, and raises the question of whether an abnormal vascular remodeling, with normal inner diameters, is to be considered like coronary artery dilatation for risk stratification.

Associations between cardiac and pulmonary involvement in patients with juvenile dermatomyositis—a cross-sectional study

This study aimed at exploring the association between detectable cardiac and pulmonary involvement in long-term juvenile dermatomyositis (JDM) and to assess if patients with cardiac and pulmonary involvement differ with regard to clinical characteristics. 57 JDM patients were examined mean 17.3 (10.5) years after disease onset; this included clinical examination, myositis specific/associated autoantibodies (immunoblot), echocardiography, pulmonary function tests and high-resolution computed tomography. Cardiac involvement was defined as diastolic and/or systolic left ventricular dysfunction and pulmonary involvement as low diffusing capacity for carbon monoxide, low total lung capacity and/or high-resolution computed tomography abnormalities. Patients were stratified into the following four groups: (i) no organ involvement, (ii) pulmonary only, (iii) cardiac only, and (iv) co-existing pulmonary and cardiac involvement. Mean age was 25.7 (12.4) years and 37% were males. One patient had coronary artery disease, seven had a history of pericarditis, seven had hypertension and three had known interstitial lung disease prior to follow-up. There was no association between cardiac (10/57;18%) and pulmonary (41/57;72%) involvement (p = 0.83). After stratifying by organ involvement, 21% of patients had no organ involvement; 61% had pulmonary involvement only; 7% had cardiac involvement only and 11% had co-existing pulmonary or cardiac involvement. Patients with co-existing pulmonary or cardiac involvement had higher disease burden than the remaining patients. Patients with either cardiac or pulmonary involvement only, differed in clinical and autoantibody characteristics. We found no increased risk of developing concomitant cardiac/pulmonary involvement in JDM. Our results shed light upon possible different underlying mechanisms behind pulmonary and cardiac involvement in JDM.

Cutaneous manifestations of systemic lupus erythematosus: experience from a tertiary care hospital of Bangladesh

Background: Systemic lupus erythematosus (SLE) is a chronic, multisystem disorder that can affect any organ of the body. Approximately 80 percent of patients develop skin disease at some point in their disease course. The association with SLE varies among the subtypes of cutaneous lupus erythematosus (LE). Better understanding of cutaneous manifestations can help in more effective management. This study aimed to evaluate the pattern of cutaneous manifestations of SLE and to find out association with organ involvement. Methods: This cross-sectional observational study was conducted in the Green Life Medical College Hospital from January 2019 to December 2020. Sixty four lupus patients who fulfilled the SLICC 2012 classification criteria and having new onset or preexisting skin complaints were enrolled. Mixed connective tissue disease and other overlap syndromes were excluded. All patients were evaluated by a dermatologist and diagnosis was done as per modified Gilliam Classification criteria. Results: Out of 64 patients, 56 were female and 8 were male. Female and male ratio was 7:1. Mean age was 28.4±9.6 years. Among the cutaneous manifestations, LE specific was 38 (59.4%), LE non-specific was 41 (64.1%). Among LE specific, 66% were acute (ACLE), 42% were sub-acute (SCLE) and 37% patients were chronic (CCLE). Among ACLE, 72% had malar rash and 84% had photosensitivity. Among SCLE, most common was papulosqumous (68%). DLE (86%) was the most common CCLE. Among LE non-specific, 85% had non-scarring alopecia, 52% had vascular abnormalities. Most common organ involvement was musculoskeletal (84%), then renal (56%). DLE had negative association with renal involvement [OR (-0.04)]. No other cutaneous manifestations showed any significant association with any other organ involvement. Conclusion: Cutaneous manifestations are important feature in SLE. LE non-specific was more common than LE specific manifestations in this study. Better understanding can help in efficient diagnosis and management. BIRDEM Med J 2022; 12(1): 57-61

Clues To Mortality Trends And Their Related Factors In IgG4-Related Disease: A Japanese Single-Center Retrospective Study

Background: Few observations on the long-term prognosis have been conducted in immunoglobulin G4-related disease (IgG4-RD) patients with various organ involvement, not limited to autoimmune pancreatitis. Especially, mortality and its related factors in patients with IgG4-RD with various organ involvement are not well known. This study aimed to clarify mortality trends and its related factors in IgG4-RD with various organ involvement.Methods: We retrospectively reviewed the medical records of patients with IgG4-RD at a single center in Japan. We calculated the crude mortality rate and the standardized mortality ratio (SMR) using national Japan mortality statistics and investigated the cause of death. We performed Cox regression analyses to assess mortality-related factors.Results: A total of 179 patients with IgG4-RD were included and the median follow-up from diagnosis was 47 months (IQR 19-96). Ten patients (5.6%) in our cohort died during the follow-up period. The crude mortality rate was 11.1 per 1,000 person-years. According to national Japan mortality statistics, 11.6 age- and sex-matched deaths would have been expected to occur within the follow-up period, resulting in an SMR of 0.86 (95% confidence interval [CI] 0.41-1.59). Univariate Cox regression analyses indicated that the number of affected organs at diagnosis (hazard ratio [HR] 1.45, 95% CI 1.02-2.05), eGFR <45 mL/min/1.73m2 at diagnosis (vs. ≥45, HR 8.48, 95% CI 2.42-29.79), and the presence of malignancy during the clinical course (HR 3.93, 95% CI 1.10-14.02) had a significant impact on the time to death.Conclusions: Our findings suggested that IgG4-RD does not significantly affect long-term patient survival. On the other hand, multi-organ involvement and renal dysfunction as well as malignancy might be associated with higher mortality trends in IgG4-RD. Early detection and appropriate management of risk factors may improve the long-term prognosis of IgG4-RD.

Performance of 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus in Children and Adults : A Retrospective Observational Study

Background: The European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) recently developed a systemic lupus erythematosus (SLE) classification criteria (EULAR/ACR-2019) with high sensitivity and specificity. The aim of this study was to validate and compare the performance of the newly developed criteria to that of the ACR-1997 and the 2012 Systemic Lupus International Collaborating Clinics (SLICC-2012) criteria in juvenile-onset SLE (jSLE) and adult-onset SLE (aSLE) patients.Methods: We conducted a retrospective study of SLE patients (221 children and adult) and controls (214 children and adult) with defined rheumatic diseases to establish the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria. The performance of the three criteria was statistically analyzed.Results: For jSLE, sensitivities of ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria were 63.3%, 94.6% and 98.2% (P < 0.001), with specificities 99.5%, 98.6% and 93.5% (P < 0.001), respectively. For aSLE, sensitivities of ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria were 72.9%, 96.8% and 99.1% (P < 0.001), with specificities 97.2%, 92.5% and 90.2% (P = 0.013), respectively. In ANA positive juvenile patients, a EULAR/ACR score ≥13 instead of a score ≥10 resulted in higher specificity (93.1% vs. 75.9%), despite slightly lower sensitivity (92.2% vs. 99.5%). In both jSLE and aSLE patients, the SLICC-2012 and EULAR/ACR-2019 criteria had increased sensitivity for major organ involvement than ACR-1997.Conclusion: The EULAR/ACR-2019 criteria showed similar sensitivity to jSLE and aSLE patients and was more sensitive than ACR-1997 and SLICC-2012 criteria, allowing earlier recognition of patients with single or major organ involvement. The adoption of a EULAR/ACR total score ≥13 in this study, instead of the initially proposed ≥10 score, was more appropriate to classify jSLE.

Fatal Neonatal DOLK-CDG as a Rare Form of Syndromic Ichthyosis

Neonatal collodion baby or ichthyosis can pose a diagnostic challenge, and in many cases, only additional organ involvement or the course of the disease will help differentiate between non-syndromic and syndromic forms. Skin abnormalities are described in about 20% of the congenital disorders of glycosylation (CDG). Among those, some rare CDG forms constitute a special group among the syndromic ichthyoses and can initially misdirect the diagnosis towards non-syndromic genodermatosis. DOLK-CDG is such a rare subtype, resulting from a defect in dolichol kinase, in which the congenital skin phenotype (often ichthyosis) is later associated with variable extracutaneous features such as dilatative cardiomyopathy, epilepsy, microcephaly, visual impairment, and hypoglycemia and may lead to a fatal course. We report two neonatal cases of lethal ichthyosis from the same family, with distal digital constrictions and a progressive course leading to multi-organ failure and death. Postmortem trio whole-exome sequencing revealed the compound heterozygous variants NM_014908.3: c.1342G&gt;A, p.(Gly448Arg) and NM_014908.3: c.1558A&gt;G, p.(Thr520Ala) in the DOLK gene in the first affected child, which were confirmed in the affected sibling. Reduced staining with anti-α-Dystroglycan antibody was observed in frozen heart tissue of the second child as an expression of reduced O-mannosylation due to the dolichol kinase deficiency. In addition to the detailed dermatopathological changes, both cases presented hepatic and extrahepatic hemosiderosis on histological examination. Our patients represent an early and fatal form of DOLK-CDG with a striking presentation at birth resembling severe collodion baby. Both cases emphasize the phenotypic variability of glycosylation disorders and the importance to broaden the differential diagnosis of ichthyosis and to actively search for organ involvement in neonates with ichthyosis.

Immunocompetent Mice Infected by Two Lineages of Dengue Virus Type 2: Observations on the Pathology of the Lung, Heart and Skeletal Muscle

Dengue virus (DENV) infection by one of the four serotypes (DENV-1 to 4) may result in a wide spectrum of clinical manifestations, with unpredictable evolution and organ involvement. Due to its association with severe epidemics and clinical manifestations, DENV-2 has been substantially investigated. In fact, the first emergence of a new lineage of the DENV-2 Asian/American genotype in Brazil (Lineage II) in 2008 was associated with severe cases and increased mortality related to organ involvement. A major challenge for dengue pathogenesis studies has been a suitable animal model, but the use of immune-competent mice, although sometimes controversial, has proven to be useful, as histological observations in infected animals reveal tissue alterations consistent to those observed in dengue human cases. Here, we aimed to investigate the outcomes caused by two distinct lineages of the DENV-2 Asian/American genotype in the lung, heart and skeletal muscle tissues of infected BALB/c mice. Tissues were submitted to histopathology, immunohistochemistry, histomorphometry and transmission electron microscopy (TEM) analysis. The viral genome was detected in heart and skeletal muscle samples. The viral antigen was detected in cardiomyocytes and endothelial cells of heart tissue. Heart and lung tissue samples presented morphological alterations comparable to those seen in dengue human cases. Creatine kinase serum levels were higher in mice infected with both lineages of DENV-2. Additionally, statistically significant differences, concerning alveolar septa thickening and heart weight, were observed between BALB/c mice infected with both DENV-2 lineages, which was demonstrated to be an appropriate experimental model for dengue pathogenesis studies on lung, heart and skeletal muscle tissues.

749 Clinical profile and outcome of patients with Anderson–Fabry disease followed at a multidisciplinary cardiomyopathy centre

Aims Anderson–Fabry disease (AFD) is a rare genetic lysosomal storage disorder which often goes unnoticed until the onset of symptoms requires aggressive treatment. Prompt diagnosis remains crucial. Dedicated centres may offer a remarkable opportunity to develop early detection strategies and prompt appropriate multidisciplinary management. To describe the long-term outcomes of patients diagnosed with AFD followed at a national Cardiomyopathy Referral Center according to phenotype (clinical involvement vs. sub-clinical involvement). Methods and results Consecutive patients visited at our Cardiomyopathy Unit from 1989 to 2020 with &gt;1-year follow-up were retrospectively reviewed. Clinical involvement was defined by the presence of one among left ventricular hypertrophy (LVH)&gt;15 mm, presence of conduction blocks or cardiac implantable electronic devices (CIED), atrial fibrillation, kidney disease (glomerular filtration rate &lt;60 ml/min/m2, dialysis or kidney transplant), stroke or transient ischaemic attack (TIA). Disease progression was defined by either de novo CIED implantation, de novo LVH &gt; 15mm or increased IVS, de novo Stroke/TIA, or progression of kidney disease. Overall, 110 were diagnosed with AFD [first via α galactosidase (αGAL) activity and then confirmed via genetic exam], and 86 (78%) with &gt;1-year follow-up were selected. Clinical involvement was present in 60 (70%) patients. Age at diagnosis was similar between patients with clinical and subclinical phenotype (42 ± 17 vs. 39 ± 15, P = 0.277). Patients manifesting clinical involvement compatible with AFD were more frequently men [N = 25 (42%) vs. 4 (15%), P = 0.025] and probands (P = 0.01). Overall, one organ involvement was present in 31 (52%) patients, two organ involvement in 24 (40%) patients, and three organs in 5 (8%). A total of 46 (77%) patients were referred for enzyme replacement therapy (ERT): 52% received agalsidase α, 26% agalsidase β, and 22% migalastat. Among those with a clinical involvement not on ERT, nine (15%) were scheduled for ERT initiation, three (5%) were considered old for ERT, one (1.5%) refused ERT, and one (1.5%) had an allergic reaction to ERT. At 7 (3–12) years follow-up, both study cohorts manifested signs and symptoms of disease progression, although its incidence was higher in patients with clinical involvement [N = 28 (47%, 4.7%/year) vs. N = 4 (15%, 1.5%/year), in clinical vs. subclinical involvement, respectively, P = 0.01]. The main causes for diseases progression were increase in LVH (28%), de novo LVH (13%), progression of kidney disease (7%), and CIED implantation (5%). All patients with disease progression in the subclinical involvement group had been diagnosed with family screening; among these, two were men and one had a late onset phenotype. Three developed LVH &gt; 15mm and one kidney disease. Conclusions Clinical involvement in AFD is frequent irrespective of age at diagnosis, being present in more than 1-in-2 patients at baseline. Prompt referral to dedicated centres is warranted for appropriate care as disease may progress in both patients with and without initial clinical involvement despite optimal medical management.

Gynecologic organ involvement and incidental gynecologic organ neoplasms in female patients with urothelial carcinoma of the bladder undergoing anterior pelvic exenteration in Rajavithi Hospital

Objective: To evaluate the pathological data of the bladder and gynecologic organs obtained from anterior pelvic exenteration and review the incidence of gynecologic organ involvement and primary gynecologic tumor. Materials and Methods: The clinicopathological data of 70 patients who were diagnosed with bladder transitional cell carcinoma and underwent anterior pelvic exenteration in Rajavithi Hospital between January 2008 and October 2020 were analyzed to examine and determine any correlations. Results: Thirteen (18.5%) patients had gynecologic organ involvement. This consisted of 4 cases (5.7%) involving the uterus, 7 (10%) involving the vagina, 2 (2.8%) involving the ovaries, and 10 (14.2%) involving the cervix. Female patients with gynecologic organ invasion were more likely to have a high pathological T stage (p < 0.001), and have pre-operative hydronephrosis (p = 0.002). From multivariate logistic regression, pre-operative hydronephrosis was associated with increased risk of gynecologic organ invasion (odds ratio 9.57; 95% confidence interval, 1.86 - 49.18; p = 0.007). There were 23 (32%) female patients incidentally diagnosed with benign gynecologic tumors, specifically 16 (22%) cases of myoma uteri, 7 (10%) of adenomyosis and 4 (2.8%) with ovarian cysts. No patient was diagnosed as having primary gynecologic malignancy. Conclusions: The incidence of gynecologic organ involvement in female patients who had undergone anterior pelvic exenteration for urothelial carcinoma of the bladder was 18.5%. Pre-operative hydronephrosis was a risk factor associated with increased risk of gynecologic organ involvement. Information from this study may allow better identification of candidates for gynecologic organ sparing surgery.

SARS-CoV-2-related Multisystem Inflammatory Syndrome in Adults

Adults infected with SARS-CoV-2 may develop a multisystem inflammatory syndrome (MIS-A) characterized by elevated inflammatory markers and multisystem organ involvement. We report the case of a patient who presented with fever and vomiting at hospital admission. He tested positive for SARS-CoV-2 infection and blood tests showed elevated inflammatory markers. The patient developed acute cardiac dysfunction and shock in less than 24 hours and the echocardiogram revealed an LVEF of 30%. He was discharged 3 weeks later fully recovered. MIS-A should be considered if a compatible syndrome is observed in patients with evidence of SARS-CoV-2 infection by PCR test or serology.