Clinical and Laboratory Profile of Macrophage Activation Syndrome in Kawasaki Disease: A Single Centre Cross-Sectional Study.

OBJECTIVE: To study the prevalence of Macrophage Activation Syndrome (MAS) in children with Kawasaki disease (KD) and to devise a classification tree for predicting MAS in early KD based on easily available clinical and laboratory information using artificial intelligence (AI) technology. METHODS: A prospective cross-sectional observational study was conducted (March 2020 - October 2021) during which hospitalized children aged 1-18 years with KD were consecutively enrolled. Those with positive RTPCR test or IgM/IgG serology for COVID-19 were excluded. The clinical and laboratory profiles of children with and without MAS were studied. A multivariable logistic regression (LR) model was developed utilizing backward elimination method to determine the relationship between select candidate predictor variables and MAS in patients with KD. A classification tree was created based on these using artificial intelligence algorithms. RESULTS: Sixty-two children were diagnosed with KD during the study period, of these, 42 children with KD were included; 14 (33.3 %) were diagnosed with MAS. The median (IQR) duration of fever (days) was significantly more in MAS than those without MAS [7 (5, 15) vs 5 (5, 9), P < 0.05]. Serum albumin (g/dL) was significantly lower in those with MAS [2.3 (2.2, 2.7) vs 2.8 (2.3, 3.1), P = 0.03]. The classification tree constructed by the AI-based algorithm predicted that in children with KD who had myocardial dysfunction, serum albumin ≤ 2.8 g/dL and fever > 6 days duration at admission had increased likelihood of developing MAS. In children without myocardial dysfunction, alanine transaminase (ALT) levels > 70 U/L and fever > 5 days were equally predictive of MAS. CONCLUSION: Nearly one-third of the children with KD had MAS. Clinicians should consider screening all children with KD for MAS at admission. A classification tree based on the presence of myocardial dysfunction, duration of fever > 6 days, ALT levels and hypoalbuminemia can identify MAS in the course of KD.

Mucolipidosis: A mimicker of juvenile idiopathic arthritis.

Juvenile idiopathic arthritis is the most common form of chronic arthritis in children and at times misdiagnosed in those presenting with arthropathy secondary to non-inflammatory causes. The overlap of symptoms often pose a diagnostic challenge for clinicians. This mostly results in a delayed diagnosis subjecting children to unnecessary use of long-term immunosuppressants and disease-modifying drugs. We present the case of a 9-year-old boy who was previously misdiagnosed as a case of juvenile idiopathic arthritis. Detailed evaluation later led to the diagnosis of mucolipidosis (type III) which was confirmed on genetic testing. Emphasis on detailed history and clinical examination including the subtle hints like lack of signs of inflammation, family history, no morning stiffness and normal inflammatory markers should be picked up to make a timely diagnosis. In today's era of genetic testing and diagnosis, it is prudent to offer these tests for such patients to make an accurate diagnosis and prognosticate them for the long-term outcome.

Serum Calprotectin Levels in Different Subtypes of Juvenile Idiopathic Arthritis (JIA) and Its Correlation with Quantitative CRP and JADAS-27.

OBJECTIVE: To study the serum calprotectin levels in children with juvenile idiopathic arthritis (JIA) and correlate it with C-reactive protein (CRP) and the Juvenile Arthritis Disease Activity Score-27 (JADAS-27). METHODS: This was a cross-sectional observational study done between November 2017 and March 2019. Fifty treatment-naive children, aged 1 to 18 y with the diagnosis of JIA as per the International League of Associations of Rheumatology (ILAR) criteria were enrolled. Assessment of disease activity was done according to the Juvenile Arthritis Disease Activity Score (JADAS-27). Determination of serum calprotectin and CRP levels was done by immunoassay. The correlation between calprotectin levels with CRP and JADAS-27 was calculated. RESULTS: Of the 50 patients with JIA included in the study, there were 18 female and 32 male children. The median age of presentation to the hospital was 9 y (IQR 5.82-13). The median JADAS-27 was 14 (IQR 6, 20.25). The median serum calprotectin level was 45,375 ng/mL (IQR 30,725, 52,270; range 8,560-63,160 ng/mL). The median CRP was 35.4 mg/L (IQR 3.48, 80.3; range 0.02 and 107.4 mg/L). The levels of calprotectin in different JIA subtypes were not statistically different using Kruskal-Wallis test. The study also demonstrated a positive correlation between serum calprotectin with CRP and the JADAS-27 (r = 0.418). CONCLUSION: The calprotectin levels in JIA were significantly higher than those reported in the literature irrespective of the subtype. Serum calprotectin positively correlated with CRP and JADAS-27 in children with JIA.

Kawasaki Disease with Peripheral and Facial Gangrene: A Case report and review of literature.

With the onset of the SARS-CoV-2 pandemic, Kawasaki Disease (KD) has come to the fore with its many atypical manifestations. Atypical clinical neurological, ophthalmological, musculoskeletal, gastrointestinal and pulmonary manifestations in a febrile child with raised markers should prompt the clinician to think of Kawasaki disease. Peripheral gangrene is a rare atypical manifestation of KD reported in infancy. We present a three-and-a-half-year-old boy with extensive gangrene all four limbs and face along with purpura fulminans. He was successfully treated with two doses of intravenous immunoglobulin (IVIG) and infliximab, with no residual gangrene. This case highlights that very severe forms of Kawasaki disease require IVIG, pulse steroids as well as infliximab for adequate control and complete resolution of the disease.

Clinical Profile of COVID-19 Illness in Children-Experience from a Tertiary Care Hospital.

OBJECTIVE: To detail clinical profile and outcome in children infected with SARS-CoV-2. METHODS: This retrospective study was undertaken at a tertiary care pediatric teaching hospital in Northern India. The data on clinical characteristics and outcome of children (< 18 y) with COVID-19 illness from April 2020-October 2020 were reviewed and analyzed. RESULTS: A total of 2919 children with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness were tested for novel COVID-19 virus in the flu emergency (n = 1744), severe acute respiratory infection (SARI) ward (n = 825), and non-COVID area (n = 350) of the hospital. 8.73% (255/2919) children tested positive for SARS-CoV-2 infection. Of the 255 positive cases, 144 (56.47%) were managed on an outpatient basis and 100 (59 boys) required admission in COVID ward. The mortality rate of patients with SARS-CoV-2 was 11.4% (29/255). Majority of children admitted with COVID-19 had severe to critical illness due to the presence of malnutrition and underlying comorbidities. CONCLUSIONS: Children of all age groups were susceptible to COVID-19 illness with a slight male preponderance. Amongst infected, two-third were asymptomatic or had mild symptoms that required outpatient management and home isolation. The adverse outcomes were more commonly seen in infants and children > 10 y of age with malnutrition and comorbid illness.

Comparison of clinical and laboratory profile of survivors and non-survivors of SARS-CoV-2-related multisystem inflammatory syndrome of childhood in India: An observational study.

AIM: The SARS-CoV-2 pandemic is characterised by multiple reports of paediatric multisystem inflammatory disease or multisystem inflammatory syndrome in children (MIS-C) with Kawasaki disease-like features often complicated by myocarditis, shock and macrophage activation syndrome. Certain clinical and laboratory markers may be used to identify high risk cases. METHODS: All sequentially admitted patients hospitalised between April 2020 and October 2020, who met the WHO case definition for MIS-C were included. Data included patient demographic information, presenting symptoms, organ dysfunction and laboratory parameters. SARS-CoV-2 infection was diagnosed by nasopharyngeal swab real-time reverse transcription-polymerase chain reaction and/or rapid antibody test for SARS-CoV-2 as recommended. The clinical and laboratory criteria were compared in the survival and non-survival groups. RESULTS: A total of 29 patients with MIS-C were treated during the study period. There were 21 survivors and 8 non-survivors. The non-survivors had more neurocognitive and respiratory symptoms along with increased incidence of myocarditis compared with survivors. The serum levels of CPK-MB, D-dimer, ferritin and triglyceride were significantly raised in non-survivors as compared to survivors. CONCLUSION: The non-survivor group had higher CPK and greater proportion of children with troponin-T elevation indicating higher incidence of myocardial injury and necrosis. The D-dimer, ferritin and triglyceride were also higher in the mortality group, indicating the greater extent of inflammatory damage in this group.

Profile of Children with Kawasaki Disease Associated with Tropical Infections.

OBJECTIVE: To describe various infectious triggers for Kawasaki disease (KD) in India. METHODS: A series of 10 children with diagnosed infections who developed KD during their course of illness has been presented. They were diagnosed by the American Heart Association (AHA) 2017 guidelines. Echocardiography was done to check for coronary artery dilation. Treatment was instituted as per standard protocol. RESULTS: Kawasaki disease was diagnosed in 8 boys and 2 girls, aged 1 mo to 11 y. These children were being treated for dengue, chikungunya, SARS-CoV-2, hepatitis A, tuberculosis, brucellosis, disseminated staphylococcal sepsis, scrub typhus, and enteric fever. CONCLUSIONS: Kawasaki disease has been associated with infectious triggers. It should be considered in febrile patients with mucocutaneous involvement or in nonresponsive sepsis, despite adequate therapy.

Efficacy and Safety of Combined Oral Chelation With Deferiprone and Deferasirox in Children With ß-Thalassemia Major: An Experience From North India.

OBJECTIVE: A combination of desferrioxamine with either deferiprone (DFP) or deferasirox (DFX) for patients with ß-thalassemia major who do not achieve negative iron balance with monotherapy has been studied widely. However, poor compliance resulting from the need for parentral administration of desferrioxamine and its cost necessicitates combining 2 oral chelators. METHODS: A prospective study was conducted in patients with transfusion-dependent ß-thalassemia major in a tertiary care center over 2 years. Patients on either DFP or DFX who were not improving on monotherapy over a long period and persistently maintaining serum ferritin >2500 µg/L were enrolled. Efficacy was assessed by serum ferritin levels assessed at 12 months and 2 years. Complete blood counts and liver and kidney function tests were monitored to assess the safety of the combination of drugs. RESULTS: In total, 33 patients with a mean age of 12.67 years (7.5 to 17.5 y) and a mean ferritin of 4835.2394±1443.85 µg/L formed the study cohort.In total, 28 patients completed the 1-year study period; and 12 patients completed 2 years. Mean serum ferritin reduction at 1 and 2 years was 34.99%±18.13% (range, -34.36% to 56.17%) and 44.67%±13.78% (range, 22.17% to 62.74%), respectively. The combination therapy was well tolerated. CONCLUSIONS: Combined oral chelation with DFP and DFX has better efficacy than either drug used alone. The combination of drugs was well tolerated and no new adverse effects were observed.

Thalassemia Major: how do we improve quality of life?

BACKGROUND: Thalassemia Major is a preventable genetic disorder characterized by abnormal hemoglobin synthesis and lifelong blood transfusions. The children suffering from Thalassemia Major have poor quality of life. This study was conducted to assess the factors influencing quality of life of these children and how it can be improved. METHODS: A descriptive cross sectional study was conducted in 2014 at Thalassemia Day Care Centre of a tertiary level children's hospital in Delhi, to assess quality of life of children suffering from Thalassemia Major. A total of 241 eligible children (age 2-18 years) were enrolled in the study. Socio demographic and clinical characteristics were collected from interview and existing medical records. The PedsQL 4.0 generic core scale was used for assessing the quality of life of the children. RESULTS: The mean age of children was 8.69 ± 4.98 years. Two-thirds (63.5%) were boys. The total mean QoL score of the children was 82.0 ± 14.4. The quality of life scores were better for boys as compared to girls. The most affected domain was the emotional domain which showed statistically significant (p = 0.025) difference between boys and girls. The total QoL scores were significantly affected by the current age of the child (p = 0.000) and presence of co-morbidity (p = 0.026). Children not on any form of iron chelation therapy (p = 0.003) and fewer hospital visits (p = 0.044) had better QoL scores. CONCLUSIONS: Factors improving the quality of life were control of iron overload and adverse effects of ICTs, management of co morbidities and fewer hospital visits.

Neurological Complications and Cataract in a Child With Thalassemia Major Treated With Deferiprone.

The oral iron chelator deferiprone is associated with various side effects including agranulocytosis, arthropathy, and deranged liver function tests. Rarely, neurological and visual side effects have been reported with high doses. The authors describe rare neurological manifestations of cerebellar ataxia, hypertonia, and bilateral cataract in an 11-year-old boy with thalassemia major on recommended therapeutic doses of deferiprone. The neurological abnormalities resolved with stoppage of deferiprone. Central nervous system toxicity and lenticular opacities may be attributed to the low molecular weight of deferiprone and its ability to cross the blood-brain and blood-ocular barrier, respectively. Clinicians should be alert to the possibility of neurological abnormalities that may occur during deferiprone therapy.

Inflammatory myofibroblastic tumor: an unusual mimicker of childhood intrathoracic tuberculosis.

Inflammatory myofibroblastic tumors are rare lesions of uncertain etiology that are often difficult to diagnose because of their myriad clinical presentations. Not uncommon, they mimic persistent pneumonia. We report a 4-year-old girl who presented with prolonged pyrexia, weight loss, severe anemia, hepatosplenomegaly, and nonresolving pneumonia. Initial investigations including flexible bronchoscopy and bronchial washing for usual causes of persistent pneumonia, such as tuberculosis and other infections, were negative. Chest computed tomography revealed a well-defined lesion involving the lingula and left upper lobe with extension into the subpleural space. Pleural tap and biopsy was also noncontributory. Thoracoscopic biopsy was suggestive of an inflammatory myofibroblastic tumor. As the lesion was encasing the major vessels, it was considered inoperable. The patient did not respond to steroid therapy and etoricoxib and later succumbed to the illness. This uncommon tumor should be considered in the differential diagnosis of children who presented with unresolving consolidation with pyrexia.

Central pontine myelinolysis presenting with tremor in a child with celiac disease.

A 4-year-old boy presented with a history of tremor for 7 days. He also had recurrent diarrhea for the previous 1 year, and poor weight gain. Magnetic resonance of the brain was suggestive of central pontine myelinolysis. There was no evidence of electrolyte abnormalities. The serum tissue transglutaminase level was markedly elevated, and the duodenal biopsy revealed features of celiac disease. The patient was started on gluten-free diet. The tremor resolved within 3 months. Repeat imaging of the brain done 3 months after starting gluten-free diet showed complete resolution of the lesion. This case highlights the unusual presentation of central pontine myelinosis as tremor in a malnourished child with celiac disease.

A Rare Case Report of Fatal Fulminant Hepatic Failure in a Child due to Mixed vivax and falciparum Infection.

Malaria remains an overwhelming problem in the tropical developing countries, with 300 to 500 million new cases and about a million deaths per year (Mishra et al., 2003). Malaria is a potentially life-threatening disease in the tropics. Jaundice is one of the severe manifestations of falciparum malaria. Its incidence (Mishra et al., 2003). varies between 10 and 45% in different reports and is seen more in adults than in children. Jaundice may vary from mild to very severe. However, clinical signs of hepatic encephalopathy (such as liver flaps) are never seen unless there is presence of concomitant viral hepatitis (WHO, 2000). Our case is a 6-year-old female child presented with fever, jaundice, and anasarca. Peripheral smear showed trophozoites and schizonts of Plasmodium (P.) vivax and trophozoites and gametocytes of P. falciparum. Viral markers for hepatitis were negative. She developed fulminant hepatic failure and expired after 26 hours of admission.