Thrombocytopenia in Children: A Large Prospective Study on Clinical Manifestations, Seasonal Variation, Etiology, and Outcome.

AIM: To study the clinico-etiological profile of children with thrombocytopeniaMethods: This prospective hospital-based study included all children (<18 years) with thrombocytopenia at the time of hospitalization and/or thrombocytopenia during the course of their hospital stay. A detailed history was recorded and appropriate laboratory investigations were carried out Results: The study group comprised 246 children (mean age, 9.29 years; median age, 10 years) with male to female ratio of 1.5:1. Nearly 45% of children were above 10 years of age. Trends of admissions showed that the majority of children with thrombocytopenia (n = 115) got hospitalized during the rainy season, followed by summer (n = 84). Fever (72.8%), pallor (52.8%), bleeding manifestations (22%), lymphadenopathy (20.3%), and splenomegaly (20.3%) were common clinical features. Petechiae was the most common bleeding manifestation (63%). Septicemia (24%) was the most common etiology, followed by megaloblastic anemia (14.6%), undiagnosed fever (10.2%), local infection (9.3%), hepatitis (6.5%), and scrub typhus (6.1%). About nine children died. All those who died had septicemia and multi-organ dysfunction (MOD). On logistic regression analysis, age >10 years, presence of bleeding, arthralgia, rash, pallor, gastrointestinal (GI) symptoms, hematological disorders, and malignancy were associated with severe thrombocytopeniaConclusion: Thrombocytopenia is a common hematological observation. This study revealed seasonal variation in the occurrence of thrombocytopenia in children, with the maximum number of cases in the rainy season. Septicemia is the commonest etiology. The majority of children with thrombocytopenia have no bleeding manifestations. Age >10 years, presence of bleeding, arthralgia, rash, pallor, GI symptoms, hematological disorders, and malignancy are associated with severe thrombocytopenia.

Clinician's dilemma: Naproxen-induced liver injury.

Naproxen is a widely used nonsteroidal anti-inflammatory drug (NSAID) in pediatric population, used for mild-to-moderate pains, arthritis, and other immune-mediated disorders. It rarely causes clinically apparent liver injury in the adult population taking high doses of the drug over a prolonged period and is reported even rarer in pediatric population. We present a case of drug-induced liver injury (DILI) in a 13-year-old girl taking naproxen in therapeutic doses for juvenile rheumatoid arthritis. There was a complete recovery of liver function following discontinuation of naproxen therapy.

Distal coronary artery abnormalities in Kawasaki disease: experience on CT coronary angiography in 176 children.

OBJECTIVE: Precise evaluation of coronary artery abnormalities (CAAs) in Kawasaki disease (KD) is essential. The aim of this study is to determine role of CT coronary angiography (CTCA) for detection of CAAs in distal segments of coronary arteries in patients with KD. METHODS: CTCA findings of KD patients with distal coronary artery involvement were compared with those on transthoracic echocardiography (TTE) during the period 2013-21. RESULTS: Among 176 patients with KD who underwent CTCA (128-Slice Dual Source scanner), 23 (13.06%) had distal CAAs (right coronary-15/23; left anterior descending-14/23; left circumflex-4/23 patients). CTCA identified 60 aneurysms-37 proximal (36 fusiform; 1 saccular) and 23 distal (17 fusiform; 6 saccular); 11 patients with proximal aneurysms had distal contiguous extension; 9 patients showed non-contiguous aneurysms in both proximal and distal segments; 4 patients showed distal segment aneurysms in absence of proximal involvement of same coronary artery; 4 patients had isolated distal CAAs. On TTE, only 40 aneurysms could be identified. Further, distal CAAs could not be identified on TTE. CTCA also identified complications (thrombosis, mural calcification and stenosis) that were missed on TTE. CONCLUSIONS: CAAs can, at times, occur in distal segments in isolation and also in association with, or extension of, proximal CAAs. CTCA demonstrates CAAs in distal segments of coronary arteries, including branches, in a significant number of children with KD-these cannot be detected on TTE. CTCA may therefore be considered as a complimentary imaging modality in children with KD who have CAAs on TTE.

Uncommon histopathological features of cytomegalovirus encephalitis and measles inclusion body encephalitis on autopsy in two patients with primary immunodeficiency.

PURPOSE: To describe the neuropathological findings in two patients with primary immunodeficiency who had fatal viral encephalitis. MATERIALS AND METHODS: Severe combined immunodeficiency (SCID) was confirmed in case 1 by genetic testing, while case 2 had features suggestive of combined immunodeficiency; however, whole exome sequencing showed no pathogenic variants. Autopsies were performed in both cases after an informed consent. A detailed sampling of the brain including extracranial organs was conducted. Immunohistochemistry and electron microscopy was also performed to confirm the presence of viruses. RESULTS: Besides evidence of cystic encephalomalacia observed in both cases, the brain in case 1 revealed cytomegalovirus (CMV) ventriculoencephalitis accompanied by an exuberant gemistocytic response in the entire white matter. Nuclei of gemistocytes were loaded with several CMV nuclear inclusions, which was confirmed by immunohistochemistry. Case 2 demonstrated features of measles inclusion body encephalitis with several viral inclusions within neurons and astrocytes. Rare giant cells were also seen. Measles virus was confirmed on immunohistochemistry and electron microscopy. Plausibly, there was paucity of microglial nodules in both cases. Superadded bacterial pneumonia with diffuse alveolar damage was also seen in both cases. CONCLUSION: These cases add to the spectrum of unusual histological features of viral encephalitis seen in patients with underlying primary immunodeficiency diseases.

Clinical profile, long-term follow-up and outcome of juvenile systemic scleroderma: 25 years of clinical experience from North-West India.

OBJECTIVES: To describe the clinical profile, long-term follow-up and outcome of juvenile systemic scleroderma (JSSc) from a tertiary care referral hospital in North-West India. METHODS: A review of case records was performed and children with JSSc (disease onset <14 years of age) were analysed. Diagnosis was based on the Paediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for JSSc. RESULTS: Forty patients (28 girls and 12 boys; F:M ratio= 2.3:1) were diagnosed with JSSc (including 22 children with overlap) in the last 25 years. Mean age at symptom onset was 7.75±3.19 years with a mean delay in diagnosis of 2.275±2.09 years. Raynaud's phenomenon was seen in 26/40 (65%) patients at presentation. Lung involvement was noted in 40% patients. Methotrexate was the most commonly used therapy, followed by oral prednisolone. Patients without overlap had higher incidence of cutaneous ulcers as compared to patients with overlap (55% vs. 18%; p-value: 0.01). Patients with overlap required significantly higher oral prednisolone (81% vs. 22%), methotrexate (72% vs. 38%) and hydroxychloroquine (54% vs. 5%) while cyclophosphamide (13% vs. 44%) and azathioprine (9% vs. 44%) were used relatively less in this group. Mortality was 15% at a mean follow-up of 51.75 months. Infections were noted to be the most common cause of death. There was no significant difference in the mortality between patients with and without lung disease or patients with or without overlap. CONCLUSIONS: We describe the largest single-centre cohort with longest follow-up of juvenile systemic scleroderma from India.

Autoantibody Profile of Children with Juvenile Dermatomyositis.

OBJECTIVE: To study autoantibody profile in juvenile dermatomyositis (JDM) and to look for phenotypic associations of these autoantibodies, if any. METHODS: Thirty-four children with JDM with a minimum follow-up duration of 24 mo were enrolled. Clinical findings and investigations at the time of diagnosis were noted from the clinic records. At inclusion, they were clinically evaluated for residual disease, disease activity and complications. All the enrolled patients were tested for antinuclear antibodies (ANA), muscle specific antibodies (MSA) and myositis associated autoantibodies (MAA). RESULTS: ANA positivity was seen in 14/34 children. At least one MSA or MAA was present in 8/34 children. Anti-SRP, anti-MDA-5, and anti-Mi-2 antibodies were present in 4, 3, and 1 patient, respectively. Anti-SSA/Ro52 antibody was positive in 1 child. All four children with anti-SRP antibody were girls, who had polycyclic course. Two of them developed calcinosis. Prominent skin involvement with less severe muscle involvement and monocyclic course were seen in patients with anti-MDA-5 antibody. Two of them had arthritis/arthralgia at initial presentation. The only patient with anti-Mi-2 had normal muscle strength at enrollment. None of the patients had anti-synthetase antibodies (anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ), anti-Ku, anti-Scl-70, anti-NXP-2 or anti-HMG CoA. CONCLUSION: Eight patients tested positive for at least one MSA or MAA. The prevalence of autoantibodies was low. Positivity for anti-SRP, anti-MDA-5, anti-Mi-2 and anti-SSA/Ro52 antibodies was seen in 4, 3, 1 and 1 patients, respectively. Ethnic differences and testing for autoantibodies during/after therapy could be responsible for the low positivity rate for autoantibodies.

Liver Abscess in Chronic Granulomatous Disease-Two Decades of Experience from a Tertiary Care Centre in North-West India.

PURPOSE: Most of the literature on liver abscess in chronic granulomatous disease (CGD) emanates from developed countries. Data from developing countries are scarce. In this study, we report clinical features, microbiological profile, and treatment difficulties encountered while managing liver abscesses in patients with CGD at a tertiary care centre in North-West India. METHODOLOGY: Case records of children with CGD and liver abscesses at Pediatric Immunodeficiency Clinic, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India were analyzed. RESULTS: Seven of 68 patients (10.29%) with CGD presented with hepatic abscess. One patient had 2 recurrences. All were males and age-range at presentation was 7 months-22 years. Mutation analysis was carried out in all patients-3 had defects in CYBB gene; 2 in NCF1; 2 in NCF2 gene. Staphylococcus aureus was isolated from 5 patients. Duration of antimicrobial treatment ranged from 3 weeks to 7 months. Open drainage was required in 1 patient, and 1 patient was treated with a prolonged course of prednisolone. Two children succumbed to the illness. CONCLUSIONS: This is the largest reported experience of liver abscesses in patients with CGD from the developing world. Staphylococcus aureus was the commonest pathogen isolated. In our experience, prolonged courses of antimicrobials are usually necessary in these patients. Glucocorticoids can reduce inflammatory response and facilitate early resolution of abscesses in CGD.

Chronic non-bacterial osteomyelitis: a retrospective international study on clinical manifestations and response to treatment.

OBJECTIVES: Chronic non-bacterial osteomyelitis (CNO) is a rare non-infectious bone inflammatory disorder; when multifocal, it is referred to as Chronic Recurrent Multifocal Osteomyelitis (CRMO). This study evaluates the demographic, clinical and radiological characteristics of a multi-centre cohort of patients with CNO/CRMO. METHODS: Demographic and clinical data of patients with an established diagnosis of CNO/CRMO followed at paediatric rheumatology centres across Europe (Italy, France, Slovenia) and India were retrospectively collected. RESULTS: There were no demographic differences across countries, but time to diagnosis was significantly longer in India (p=0.041). Pain was almost invariably present at disease onset; functional impairment was more frequent among Italian and Slovenian patients (p=0.001). The number of sites of bone involvement was similar between genders and countries, with long bone metaphises being the most common site. Raised acute phase reactants, detected in >50% of patients, were not associated with clinical manifestations or response to treatment. Comorbidities, evinced in 37% of patients, were equally distributed between genders and nationalities. Imaging approach was similar across countries, without any association between radiological findings and clinical manifestations. NSAIDs were almost invariably used as first-line treatment, but response rate was significantly lower in Italy (p=0.02). Methotrexate was used in 28% of case, with an overall rate of response of 82%. Health conditions and rate of permanent deformities were similar across different countries. CONCLUSIONS: The differences in clinical presentation, radiological features and response to treatment described in this multinational cohort of CNO/CRMO might provide novel insights into this still elusive disease.

Retinal vasculopathy in children with systemic lupus erythematosus: report of two cases.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune, multisystem disease associated with a variable clinical course. SLE is more severe and is associated with higher mortality in children compared to adults. Eye involvement may be seen in up to a third of patients. Retinal vasculopathy is rare in children with SLE. We report two such cases. Both patients in this series had cotton-wool spots on fundus examination, and fundus fluorescein angiography revealed findings of occlusive micro-angiopathy. These findings are characteristic of lupus retinal vasculopathy. Fundus examination is crucial in diagnosing retinal vasculopathy. All children with SLE must be evaluated in detail to detect any retinal abnormalities and should be managed with aggressive immunosuppression to save their vision.

An uncommon overlap of two common rheumatological disorders.

Juvenile systemic lupus erythematosus (SLE) is a heterogeneous multisystem autoimmune disease. Kawasaki disease is a common vasculitic disorder in children that manifests with fever and mucocutaneous involvement. While overlap of childhood SLE with other rheumatological disorders has been described, it is extremely unusual in the context of Kawasaki disease. We report two children who had SLE and developed features of Kawasaki disease simultaneously, and the second child had myocarditis which could be a manifestation of Kawasaki disease rather than SLE. Two or more rheumatological diseases may coexist at the same time and one must always be vigilant.

Familial macro thrombocytopenia: role of genetics where morphology fails.

: Myosin heavy chain 9 (MYH9)-related disorders are rare inherited platelet disorders that are accompanied by a wide variety of systemic abnormalities. The persistent thrombocytopenia is usually asymptomatic and these patients are often misdiagnosed and treated as immune thrombocytopenia. MYH9 gene has been studied in association with solid organ malignancies. We report a young girl with family history of thrombocytopenia and hearing loss who presented with kidney dysfunction and later developed acute lymphoblastic leukemia. She lacked the characteristic inclusion bodies in her blood granulocytes, however a diagnosis of MYH9-related Epstein syndrome was confirmed on genetic testing. In the background of known causal association of MYH9 gene in solid organ malignancies, the role of MYH9 gene variant in malignant transformation in the index case remains conjectural.

Platelets in Kawasaki disease: Is this only a numbers game or something beyond?

Kawasaki disease (KD) is a medium vessel vasculitis with predilection to cause coronary artery abnormalities. KD is now the most common cause of acquired heart disease in developed countries. Thrombocytosis is consistently found in patients with KD, usually in 2nd to 3rd week of illness. Thrombocytopenia has occasionally been reported in the acute phase of KD. An increase or decrease in platelet number in patients with KD was initially considered to be a benign phenomenon. However, recent literature on platelet biology in KD has suggested that platelets are not only increasing but are rather activated. This phenomenon has been found to increase the risk of thrombosis in these patients. Similarly a fall in platelet counts during acute stage of KD has also been found to be associated with increased severity of disease. In this review, we update on the current best understanding about pathogenic role of platelets in patients with KD.

Kawasaki Disease in Children Older Than 10 Years: A Clinical Experience From Northwest India.

Background: Kawasaki disease (KD) is predominantly seen in young children (<5 years). Diagnosis of KD is often delayed in older children and adolescents, leading to a higher risk of coronary artery abnormalities (CAAs). There is a paucity of literature on KD in older children. Methods: Data were collated from a review of records of patients diagnosed with KD who were aged ≥10 years at the time of diagnosis, during the period from January 1994 to June 2019. Results: Eight hundred and sixty five patients were diagnosed with KD during this period. Of these, 46 (5.3%; 26 boys and 20 girls) were aged 10 years or older at the time of diagnosis. The median age at diagnosis was 11 years (range of 10-30 years). The median interval between the of fever and the diagnosis of KD was 12 days (range of 4-30 days). Eight patients (17.4%) presented with hypotensive shock. Coronary artery abnormalities (CAAs) were seen in six patients (13.04%), and three patients had myocarditis. Patients with CAAs were found to have significantly higher median platelet counts and higher median C-reactive protein levels. First-line treatment included intravenous immunoglobulin. Adjunctive therapy was given in five patients (infliximab in four patients and steroids in one patient). The median time between the onset of fever and the administration of IVIg was 13.5 days (range of 6-2). The total duration of follow up is 2,014.5 patient-months. Conclusion: Diagnosis of KD in children older than 10 years is usually delayed, and these patients are thus at a higher risk of CAAs.

Clinico-laboratory profile of Kawasaki disease with arthritis in children.

Kawasaki disease (KD) is associated with several musculoskeletal manifestations. Although arthritis has been reported to occur in 2.3-31% of children with KD, there is paucity of detailed studies on the subject. We report our experience on arthritis in children with KD. Data were collated from a review of records of patients diagnosed with KD and arthritis during the period January 1994-June 2019. Eight hundred sixty-five children (male:female 29:11) were diagnosed with KD during this period-of these, 40 (4.6%) had arthritis. Median day of diagnosis of KD was 17 days. Twenty-nine (72.5%), 8 (20%), and 3 (8.6%) children developed arthritis in acute, subacute, and convalescent phases of KD, respectively. Oligoarticular involvement was observed in 32 (80%) children and among these, 7 (20%) had monoarthritis. Predominant joints involved were knee (74.3%), ankle (40%), and hip (28.6%). Thirty-two children (80%) were treated with non-steroidal anti-inflammatory drugs (NSAIDs). Median duration of arthritis was 10 days (range, 2-180 days) with uneventful recovery in all cases. Three (7.5%) children had coronary artery ectasia which regressed on follow-up.Conclusion: Arthritis in KD is usually non-erosive, self-limiting, and responds well to a short course of NSAIDs.What is Known:• Arthritis has been reported to occur in 2.3-31% of children with KD.• Arthritis in KD is usually oligoarticular, non-erosive, and responds well to short course of non-steroidal anti-inflammatory drugs.What is New:• Children with KD and arthritis do not appear to be at increased risk of development of coronary artery abnormalities.• Arthritis in children with KD can result in diagnostic confusion, and diagnosis of KD may get delayed.