Longitudinal Echocardiographic Follow-Up of a Pediatric Multisystem Inflammatory Syndrome Cohort.

OBJECTIVE: Significant involvement of the cardiovascular system is known in multisystem inflammatory syndrome in children (MIS-C). This study aimed to examine the recovery of affected cardiovascular parameters over a medium-term follow-up. METHODS: A cohort of 69 children was studied prospectively. Assessments of left ventricular (LV) function and coronary artery abnormalities (CAA) were conducted at admission, 1.5 months, and 3 months. Coronavirus Disease 2019 (COVID-19) antibody titers were assessed at these three time points. Echocardiographic and antibody parameters (rising/decreasing) were analyzed for correlation. Outcomes were assessed using logistic regression. RESULTS: At admission, among the 78.2% of patients who were tested, 88.9% tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A quarter of the patients had pericardial effusion, and half had valvulitis. Decreased ejection fraction, global circumferential strain (GCS), and global longitudinal strain (GLS) were seen in 54.4%, 68.6%, and 35.8% of patients, respectively. CAAs were observed in 27.78% of patients. Systolic dysfunction was significantly associated with older age. During follow-up, severe LV dysfunction normalized within 6-7 weeks, while mild to moderate dysfunction reached normalcy by two weeks. Both GCS and GLS reached normalcy within a median of two weeks. Diastolic parameters recovered by six weeks. Most small and moderate coronary aneurysms resolved, but a giant aneurysm in an infant remained large even after 15 months. Trends in antibodies and ejection fraction (EF) at three months were significantly correlated. Admission EF, GLS (at 6 weeks) and deceleration time (at 3 months) were significantly associated with intensive care unit (ICU) admission. The median segmental strain of the cohort remained low in certain segments at three months. CONCLUSION: Smaller CAAs resolve, whereas giant CAAs persist. EF and GLS are important predictors of Pediatric Intensive Care Unit (PICU) stay. The residual impairment of median segmental strain and persistent diastolic dysfunction at three months indicate the need for long-term follow-up.

A rare case of congenital insensitivity to pain with anhidrosis.

A 22-month-old girl of consanguineous parents was admitted with a high-grade fever. She was found to have insensitivity to painful stimuli and an absence of perspiration. She also displayed self-mutilating behaviour and was insensitive to cold/hot water on her body. On examination, there was loss of the tip of the tongue, missing teeth, generalised xerosis, and several ulcers at sites of minor trauma. She also had dysplastic nails and digital ulcers. Sensory examination demonstrated a complete lack of awareness of pain and temperature, vibration and fine touch were intact and lacrimation was normal. Differential diagnoses of hereditary sensory and autonomic neuropathy (HSAN), Lesch-Nyhan syndrome, hypohidrotic ectodermal dysplasia and leprosy were considered. Results of routine blood investigations including serum uric acid were normal. On performing clinical exome sequencing, the diagnosis of congenital insensitivity to pain with anhidrosis (CIPA) of autosomal recessive inheritance was confirmed. A novel, predicted to be pathogenic variant detected at exon 16 of the NTRK1 gene resulting in congenital insensitivity to pain with anhidrosis is reported.Abbreviations: CIPA: congenital Insensitivity to pain with anhidrosis; HSAN: hereditary sensory and autonomic neuropathy; NGF: nerve growth factor; NTRK1: neurotrophic tyrosine kinase receptor 1 gene; TrKA: tropomyosin receptor kinase A.

Extensive perineal ecthyma gangrenosum in leukocyte adhesion deficiency type 1 associated with Staphylococcus hominis bacteremia.

Leukocyte adhesion deficiency (LAD), a disorder of neutrophil function, is characterized by a defect in leukocyte adhesion to the endothelium. Recurrent infections in the skin, soft tissue, gingiva, and lungs due to Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella sp. are common in these patients. Ecthyma gangrenosum (EG) is an ulcer of skin and subcutaneous tissue with a black eschar and surrounding erythematous halo secondary to a bacterial infection. Here, we report an unusual presentation of LAD type-1 with extensive EG of perineum secondary to Staphylococcus hominis bacteremia treated successfully with combination of granulocyte transfusion and diversion colostomy.

Genetic Studies in Infants with Congenital Nephrotic Syndrome: A Case Series.

Information on the genetic profile of congenital nephrotic syndrome (CNS) from India is scarce. The management of CNS is largely supportive of the setting of developing countries, mainly via the administration of intravenous albumin infusions, angiotensin-converting enzyme inhibitors, and levothyroxine. Inadequate infrastructure and management facilities, including genetic analyses, further hamper the outcome. These infants may progress to end-stage renal disease, and mortality is high in infancy. Here, we report a case series of four infants (aged 14-60 days) with CNS from our center with genetic mutations (including mutations in the NPHS1 and LAMB2 genes) that were not described in previous reports from India. Although responsiveness to enalapril has been documented in anecdotal reports of NPHS1 mutations, our case series of four infants did not exhibit any response to enalapril. Our case series adds to the existing literature regarding the genetic profile of CNS in India.

Etiology and Outcomes of Rapidly Progressive Glomerulonephritis in Children: A Retrospective Cohort Study.

OBJECTIVE: To study the clinico-etiological spectrum and outcomes of children with rapidly progressive glomerulonephritis (RPGN). METHODS: This retrospective cohort study evaluated patients <18 years with RPGN, over an 8-year period (2014-2022), for etiology and kidney outcomes. RESULTS: Among 68 RPGN cases [median age 10 (7,12) years], 23 (33.8%) had lupus nephritis, 21 (30.9%) C3 glomerulopathy, and 15 (22.1%) infection-related glomerulonephritis (IRGN). At presentation, 18 (26.4%) patients had pulmonary edema, 20 (29.4%) had hypertensive emergency and 22 (32.4%) required dialysis. Median (IQR) follow-up duration was 24.5 (12,48) months. The median (IQR) admission eGFR was 19 (10.93, 38.60) mL/min/1.73 m2, which increased to 126 (102.7,142) mL/min/1.73m2 at the last follow-up. At the last follow-up, 39 (57.3%) and 13 (19.1%) patients attained complete and partial renal recovery, respectively; while 16 (23.5%) progressed to CKD stage 2 and beyond. The prevalence of end stage kidney disease (ESKD) was 7.3% at 1-year and 7.7% at the last follow-up. Factors predicting kidney survival were duration of symptoms prior to presentation ≥7 days, crescents ≥37.5%, and presence of fibrous crescents/segmental sclerosis. CONCLUSION: Lupus nephritis, was the commonest etiology of RPGN in children. Renal outcomes were determined by pre-admission symptoms, and percentage and stage of crescents.

Etiology and outcomes of acute kidney disease in children: a cohort study.

BACKGROUND: There is paucity of information regarding the etiology and outcomes of Acute Kidney Disease (AKD) in children. METHODS: The objectives of this cohort study were to evaluate the etiology and outcomes of AKD; and analyze predictors of kidney survival (defined as free of CKD 2, 3a, 3b, 4 or 5). Patients aged 1 month to 18 years who developed AKD over a 4-year-period (January 2018-December 2021) were enrolled. Survivors were followed-up at the pediatric nephrology clinic, and screened for residual kidney injury. RESULTS: Among 5710 children who developed AKI, 200 who developed AKD were enrolled. The median (IQR) eGFR was 17.03 (10.98, 28) mL/min/1.73 m2. Acute glomerulonephritis, acute tubular necrosis (ATN), hemolytic uremic syndrome (HUS), sepsis-associated AKD, and snake envenomation comprised of 69 (34.5%), 39 (19.5%), 24 (12%), 23 (11.5%) and 15 (7.5%) of the patients respectively. Overall, 88 (44%) children required kidney replacement therapy (KRT). There were 37 (18.5%) deaths within the AKD period. At a follow-up of 90 days, 32 (16%) progressed to chronic kidney disease stage-G2 or greater. At a median (IQR) follow-up of 24 (6, 36.5) months (n = 154), 27 (17.5%) had subnormal eGFR, and 20 (12.9%) had persistent proteinuria and/or hypertension. Requirement of KRT predicted kidney survival (free of CKD 2, 3a, 3b, 4 or 5) in AKD (HR 6.7, 95% CI 1.2, 46.4) (p 0.04). CONCLUSIONS: Acute glomerulonephritis, ATN, HUS, sepsis-associated AKD and snake envenomation were common causes of AKD. Mortality in AKD was 18.5%, and 16% progressed to CKD-G2 or greater at 90-day follow-up.

Clinical profile and outcomes of multisystem inflammatory syndrome in children (MIS-C): Hospital-based prospective observational study from a tertiary care hospital in South India.

AIM: To study the clinical profile and outcomes in children with multisystem inflammatory syndrome in children (MIS-C). METHODS: Children aged 1 month to 15 years presenting with MIS-C (May 2020 to November 2021) were enrolled. Clinical, laboratory, echocardiography parameters and outcomes were analysed. RESULTS: Eighty-one children (median age 60 months (24-100)) were enrolled. Median duration of fever was 5 days (3-7). Twenty-nine (35.8%) had shock (severe MIS-C) including 23 (28.3%) requiring inotropes (median duration = 25 h (7.5-33)). Ten required mechanical ventilation, 12 had acute kidney injury and 1 child died. Left ventricular (LV) dysfunction was seen in 38 (46.9%), 16 (19.7%) had coronary artery abnormalities (CAA) and 13 (20%) had macrophage activation syndrome. Sixty-one (75.3%) were SARS CoV-2 positive (10 by RT-PCR and 51 by serology). Sixty-eight (83.9%) received immunomodulators. Younger age was significantly associated with CAA (P value = 0.05). Older age, LV dysfunction, SARS CoV-2 positivity, low platelet count and elevated serum ferritin were significantly associated with severe MIS-C (univariate analysis). Younger age was an independent predictor of CAA (P = 0.05); older age (P = 0.043) and low platelet count (P = 0.032) were independent predictors of severe MIS-C (multivariate logistic regression analysis). CONCLUSION: Our patients had diverse clinical manifestations with a good outcome. Younger age was significantly associated with CAA. Older age, LV dysfunction, low platelet count and elevated serum ferritin were significantly associated with severe MIS-C. Younger age is an independent predictor of CAA. Older age and low platelet count are independent predictors of severe MIS-C.

Atypical manifestations of infantile-onset nephropathic cystinosis: a diagnostic challenge.

A 7-month-old male infant was referred to us for evaluation of hypercalcemia and failure to thrive. He was the second-born child to third-degree consanguineous parents with a birth weight of 3.5 kg. The index child was severely underweight. Initial laboratory investigations showed hypercalcemia (13.6 mg/dL), hypophosphatemia, hyponatremia, hypokalemia and hypochloremia. The initial serum bicarbonate level was 20.9 mEq/L. The urine calcium: creatinine ratio (0.05) was normal. He was noted to have polyuria (6 mL/kg/hr) and required intravenous fluids to maintain intravascular volume and manage hypercalcemia, along with potassium chloride supplements. The serum calcium decreased to 9.7 mg/dL after hydration for 48 h. At this juncture, the child was noted to exhibit metabolic acidosis (serum bicarbonate 16 mEq/L) for the first time. Thereafter, fractional excretion of bicarbonate was estimated to be 16.5% while the tubular threshold maximum for phosphorus per glomerular filtration rate was 1.2 mg/dL; indicating bicarbonaturia and phosphaturia, respectively. Glycosuria with aminoaciduria were also noted. Clinical exome sequencing revealed a NM_004937.3:c.809_811del in exon 10 of the CTNS gene that resulted in in-frame deletion of amino acids [NP_004928.2:p.Ser270del] at the protein level. The child is now growing well on oral potassium citrate, neutral phosphate and sodium bicarbonate supplements. This case was notable for absence of metabolic acidosis at admission. Instead, severe hypercalcemia was a striking presenting manifestation, that has not been reported previously in literature. Cystinosis has been earlier described in association with metabolic acidosis, hypocalcemia and hypomagnesemia. However, typical features like metabolic acidosis were masked in early stages of the disease in our case posing a diagnostic challenge. This atypical initial presentation adds to the constellation of clinical features in this condition.

Incidence and predictive risk factors for ophthalmological complications in children with nephrotic syndrome receiving long-term oral corticosteroids: a cohort study.

BACKGROUND: There is a paucity of data from India on ophthalmological complications in children on long-term oral corticosteroids for idiopathic nephrotic syndrome. METHODS: All children aged 4-18 years with idiopathic nephrotic syndrome who had received long-term oral steroids for >6 months  and who attended the paediatric nephrology clinic between January 2019 and January 2021 were included. The majority of them (95/110) were being followed up in the paediatric nephrology clinic which was functioning from 2010.   The children were screened for ophthalmological complications at 6-month intervals. RESULTS: Overall, 110 children with nephrotic syndrome  were enrolled. Their median (IQR) age was 9.4 (7.0-12.8) years, and the median (range) duration of follow-up following onset of nephrotic syndrome was 5 years (1.0-16). The incidence of cataract was 18.1% (20 of 110 cases).  Visual acuity was impaired in seven (35%) of the children with cataract.  Children with cataract were younger as compared to those without cataract [Median (IQR) age at onset of nephrotic syndrome [2.5 (2.0-4.0) yrs vs 4 (2.1-6.0) yrs] (p=0.03)]. Children with cataract also had higher cumulative dose of prednisolone intake (mg/m2) [28,669 (21,329-33,500) vs 14,995 (10,492-19,687)] (p<0.01)] and greater cumulative duration of prednisolone intake [4.3 (3.1-5.2) vs 2.25 (1.3-3.7) yrs] (p<0.01). The incidence of raised IOP was 9.1% (10 of 110 cases). CONCLUSIONS: The incidence of cataract and raised IOP was high. The risk factors for the development of cataract were age at onset of nephrotic syndrome, cumulative dose and cumulative duration of steroid intake.