Pediatric multisystem inflammatory syndrome associated with COVID-19: Insights in pathogenesis and clinical management

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a major challenge to be faced in recent years. While adults suffered the highest morbidity and mortality rates of coronavirus disease 2019, children were thought to be exclusively asymptomatic or to present with mild conditions. However, around April 2020, there was an outbreak of a new clinical syndrome related to SARS-CoV-2 in children - multisystemic inflammatory syndrome in children (MIS-C) - which comprises a severe and uncon-trolled hyperinflammatory response with multiorgan involvement. The Centers for Disease Control and Prevention considers a suspected case of MIS-C an individual aged < 21 years presenting with fever, high inflammatory markers levels, and evidence of clinically severe illness, with multisystem (> 2) organ involvement, no alternative plausible diagnoses, and positive for recent SARS-CoV-2 infection. Despite its severity, there are no definitive disease management guidelines for this condition. Conversely, the complex pathogenesis of MIS-C is still not completely understood, although it seems to rely upon immune dysregulation. Hence, in this study, we aim to bring together current evidence regarding the pathogenic mechanisms of MIS-C, clinical picture and management, in order to provide insights for clinical practice and implications for future research directions.     

Respiratory complications of Ehlers-Danlos syndrome type IV

Pulmonary complications are described in a case of Ehlers-Danlos syndrome type IV, established by studies of collagen biosynthesis. At age 20.5 years the patient, who had previously suffered a spontaneous colonic perforation, developed intermittent recurrent hemoptysis and had a spontaneous hemopneumothorax. At presentation, imaging studies revealed multiple scattered cavitary lesions in both lungs. On separate occasions large parenchymal cysts ensued and subsequently regressed. Reviews of other reported patients indicate that pulmonary complications do occur in patients with Ehlers-Danlos syndrome type IV but have not resulted directly in patient mortality.     

Cardiovascular complications in the Ehlers-Danlos syndrome with minimal external findings

Ehlers-Danlos syndrome (EDS) is clinically and genetically a heterogeneous disorder of connective tissue. Eleven different types of EDS have been documented, several of which have major cardiovascular complications as part of their clinical manifestations. The purpose of this report is to call attention to a form of EDS with minimal external features but severe internal vascular complications.     

Type III tracheal agenesis with familial tetralogy of Fallot and absent pulmonary value syndrome

We describe a female infant born at 33 weeks gestation diagnosed postnatally with a previously unreported phenotype consisting of Type III tracheal agenesis plus tetralogy of Fallot with absent pulmonary valve. She was delivered to a mother who had the same congenital heart malformation, but no detectable tracheal abnormality. We discuss possible etiologies of these malformations. © 1996 Wiley-Liss, Inc.     

Multisystem Inflammatory Syndrome in Adults and Adolescents Associated with COVID-19 Infection: A Single-center Experience

How to cite this article: Arjun R, Niyas VKM, Thomas SM, Raman M, Thomas A, Aloysius W, et al. Multisystem Inflammatory Syndrome in Adults and Adolescents Associated with COVID-19 Infection: A Single-center Experience. Indian J Crit Care Med 2022;26(1):145–148.     

Sudden death caused by pulmonary thromboembolism in Proteus syndrome

We report 3 patients with Proteus syndrome (PS) who died suddenly from pulmonary embolism (PE). The first patient was a male diagnosed with PS at 12 years who had varicose veins, portal vein thrombosis, right iliac vein occlusion and recurrent PE. At age 25 years, he was admitted to the hospital with a severe headache. Despite therapeutic doses of warfarin, investigations for an acute episode of breathlessness showed PE and he was unable to be resuscitated. The second case was a 9-year-old male with PS who collapsed at home and could not be revived. Autopsy revealed that the cause of death was a PE associated with thrombosis of the deep veins (DVT). The third patient was a 17-year-old female undergoing inpatient treatment for sinusitis when she unexpectedly arrested. She could not be revived and a full autopsy revealed a large PE with no identified DVT. We conclude that PE is a serious complication of PS and recommend vigilance concerning the signs and symptoms of thrombosis and PE in individuals with PS, including children. Aggressive evaluation and treatment should be considered urgently in patients with PS and signs or symptoms of DVT.     

Stevens-Johnson syndrome/toxic epidermal necrolysis with severe ocular complications

Introduction: Stevens-Johnson syndrome (SJS) and its severe phenotype, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucosa. Approximately 50% of SJS/TEN patients diagnosed by dermatologists and in burn units suffer from severe ocular complications (SOC) in the acute stage.

Areas covered: Earlier studies on patients with SJS/TEN with SOC identified cold medicines including multi-ingredient cold medications and non-steroidal anti-inflammatory drugs as the main eliciting drugs. HLA analyzes showed that genetic predisposition might play a role in the response to these drugs. Our analysis of the association between HLA genotypes and cold medicine-related SJS/TEN (CM-SJS/TEN) with SOC revealed that certain HLA genotypes play a role in the development of SJS/TEN with SOC. Genetic predisposition and other factors contributing to the elicitation of CM-SJS/TEN with SOC and the management of patients in the acute and chronic stage of the disease are discussed.

Expert opinion: The main sequelae of SJS/TEN are ocular sequelae with visual disturbance. SJS/TEN with SOC needs ophthalmic treatment in addition to systemic treatment from the onset time to reduce the ophthalmic sequelae. In addition, HLA examination and public awareness of SJS/TEN with SOC due to cold medicine use might contribute to preventing visual disturbance due to SJS/TEN.

Abbreviations: SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis; SOC: severe ocular complications     

FIZZ1在炎症相关性肺动脉高压中的作用

低氧诱导促有丝分裂因子(hypoxia-induced mitogenic factor,HIMF)是一类富含半胱氨酸的分泌蛋白.HIMF首先在炎症区域被发现,并且扮演着炎症细胞标志物的角色,HIMF同时又称作发现于炎症区域1(found in inflammatory zone 1,FIZZ1).由于该蛋白家族成员在低氧与炎症相关生理病理过程中起不可忽视的作用,国内外对该蛋白家族的研究越来越多.目前该因子在血管生长、平滑肌增殖、气道炎症、肠道免疫等方面的作用已有相关研究.     

POEMS综合征合并肺动脉高压临床分析

目的 分析POEMS综合征合并肺动脉高压患者的临床特点.方法 回顾性分析北京协和医院确诊POEMS综合征患者的临床资料,并将超声心动图证实合并肺动脉高压的患者与肺动脉压正常的患者以及未行超声心动检查的患者的临床表现进行比较,描述合并肺动脉高压的POEMS综合征患者的临床特点.结果 POEMS综合征117例,合并肺动脉高压49例,肺动脉压正常33例,未行超声心动检查35例;肺动脉高压患病率41.9%.肺动脉高压组临床表现主要为胸闷、憋气,发生率42.9%(21/49),显著高于另外两组(P≤0.05),但一半以上患者无明显胸闷、憋气;肺动脉高压组并发胸水、腹水、心包积液发生率较另外两组高(P≤0.01),其他临床表现无显著差异.结论 POEMS综合征超声心动图检测肺动脉高压患病率高达40%以上,但半数以上患者无胸闷、憋气,提示在POEMS综合征诊治过程中应重视肺动脉高压的筛查和早期发现.     

Autosomal dominant duplication of the renal collecting system,hearing loss,and external ear anomalies: A new syndrome?

We report two families in which propositi had severe bilateral sensorineural hearing loss, a preauricular pit or tag, and duplication of the ureters or bifid renal pelvices. Other relatives had one or more of these anomalies in a pattern suggesting autosomal dominant inheritance with reduced penetrance and variable expressivity. We suggest the term “branchio-oto-ureteral syndrome” to designate this condition.     

Regulation of the Na,K-ATPase: Special implications for cardiovascular complications of metabolic syndrome

Skeletal muscle contains one of the largest pools of Na,K-ATPase in the body, and therefore plays a central role in the clearance of [K⁺] from the blood during the ingestion or infusion of K⁺. In the case of major hyperkalaemia (i.e. pathological increase of plasma [K⁺]), skeletal muscle can rapidly accumulate significant amounts (up to 50%) of extracellular K⁺. Thus, skeletal muscle is an important temporary storage for K⁺. Hyperkalaemia and impaired K⁺-tolerance frequently occurs in people who present features of the metabolic syndrome, concomitant with impaired activity of the sodium pump and decreased expression of the Na,K-ATPase subunits. These pathological conditions may lead to membrane depolarization in excitable tissues and to the development of cardiac arrhythmia or other cardiovascular complications that are a major consequence of metabolic syndrome. Thus, increasing Na,K-ATPase activity in skeletal muscle may protect from these complications.     

Multiple mitochondrial dysfunctions syndrome 1: An unusual cause of developmental pulmonary hypertension

Pulmonary hypertension (pHTN) is a severe, life‐threatening disease, which can be idiopathic or associated with an underlying syndrome or genetic diagnosis. Here we discuss a patient who presented with severe pHTN and was later found to be compound heterozygous for pathogenic variants in the NFU1 gene causing multiple mitochondrial dysfunctions syndrome 1 (MMDS1). Review of autopsy slides from an older sibling revealed the same diagnosis along with pulmonary findings consistent with a developmental lung disorder. In particular, these postmortem, autopsy findings have not been described previously in humans with this mitochondrial syndrome and suggest a possible developmental basis for the severe pHTN seen in this disease. Given the rarity of patients reported with MMDS1, we review the current state of knowledge of this disease and our novel management strategies for pHTN and MMDS1‐associated complications in this population.     

Multisystem inflammatory syndrome in children: A dysregulated autoimmune disorder following COVID-19

Multisystem inflammatory syndrome in children (MIS-C) is a dysregulated autoimmune-mediated illness in genetically susceptible patients following COVID-19 with an interval of 2–6 weeks. The median age of patients with MIS-C is 6–11 years. Most common manifestations are involvement of gastrointestinal tract, cardiovascular system, hematological system, and mucocutaneous system. Respiratory tract, neurological system, musculoskeletal system, and kidney are less frequently affected. Mucocutaneous manifestations and coronary artery abnormalities characteristic for Kawasaki disease (KD) may be observed in a significant proportion of MIS-C patients that may make the differential diagnosis be difficult for some patients, especially in the post-pandemic era. The mortality rate is 1–3%. Management and prognosis of MIS-C are similar to that of KD. MIS-C and KD may share a common pathogenic process. Based on the observation of MIS-C-like illness in uninfected neonates, i.e. multisystem inflammatory syndrome in neonates, both MIS-C and KD may be a consequence of dysregulated, over-exaggerated humoral immune responses triggered by a specific infectious agent.     

Congenital pulmonary lymphangiectasis: Report of an autopsy case masquerading as pulmonary interstitial emphysema

We describe the clinicopathologic features of a case of congenital pulmonary lymphangiectasis (CPL). A male Japanese infant born prematurely at 34 weeks of gestation developed a severe moaning sound, dyspnea, and prominent respiratory acidosis about 10 min after delivery. A chest X-ray film showed bilateral frosted glass-like infiltrates with an air bronchogram and an air leak around the cardiac shadow, suggesting pneumomediastinum. The patient died of hypoxemic respiratory failure 13 h after birth. The death was complicated by bilateral pneumothorax, despite the initiation of artificial ventilation and administration of a surfactant. At autopsy, small cystic lesions were noted in the visceral pleura, interlobular septa, and hilum of both lungs. A histologic examination of the lungs showed diffuse and marked dilation of the lymphatic channels in the subpleural, peribronchial, interlobular, and hilar areas. The channels were lined with flattened endothelium, which was immunohistochemically positive for D2-40. In addition, lymphangiectasis was found around the thymus and intra-abdominal organs, but no cardiovascular anomalies were seen. The findings conformed to a primary form of CPL, Noonan Group 3. Although pulmonary interstitial emphysema (PIE) was considered an important differential diagnosis because of the overlapping clinicopathologic features, a giant cell reaction surrounding the interstitial cystic lesions, a histologic hallmark of PIE, was absent in the present case.     

Management of inflammatory complications in third molar surgery: a review of the literature

Background

Pain, swelling and trismus are common complications associated with third molar surgery. These complications have been reported to have an adverse effect on the quality of life of patients undergoing third molar surgery.

Objective

To review the different modalities of minimizing inflammatory complications in third molar surgery.

Methods

A medline literature search was performed to identify articles on management of inflammatory complications in third molar surgery. Standard textbooks of Oral and Maxillofacial Surgery were also consulted and some local scientific publications on the subject were reviewed.

Results

Methods ranges from surgical closure techniques, use of drains, physical therapy and pharmacological means. Studies reviewed have shown that no single modality effectively minimizes postoperative pain, swelling and trismus without undesirable effects.

Conclusion

Inflammatory complications after third molar surgery still remains an important factor in quality of life of patients at the early postoperative periods. Oral surgeons should be aware of the different modalities of alleviation of these complications to make postoperative recovery more comfortable for patients.     

Total anomalous pulmonary vein drainage: report of an autopsy case associated with atresia of the common pulmonary vein and left superior pulmonary vein

We describe the clinicopathological features of a case of total anomalous pulmonary vein drainage (TAPVD) associated with atresia of the common pulmonary vein (ACPV). A male Japanese infant born at 37 weeks of gestation demonstrated apnea and severe respiratory acidosis immediately after delivery. The patient died of hypoxemic respiratory failure 6 days after birth despite the initiation of artificial ventilation and administration of a surfactant. Autopsy showed the bilateral inferior pulmonary veins joined with a blind confluence, representing ACPV, accompanied by atresia of the left superior pulmonary vein. Moreover, the anomalous and small right superior pulmonary vein drained into the superior vena cava, consistent with partial and supracardiac type TAPVD. A histological examination of the lungs exhibited diffuse dilation of the lymphatic channels in the peribronchial, interlobular, hilar and focally, subpleural areas. The channels were lined with flattened endothelium which was immunohistochemically positive for D2-40. These findings conformed to a secondary form of pulmonary lymphangiectasis due to the congenital cardiovascular anomalies, including TAPVD and ACPV. To the authors' knowledge, this is the first case of TAPVD associated with ACPV, atresia of left superior pulmonary vein and pulmonary lymphangiectasis.