Deepti Suri

Quantification of κ-deleting recombination excision circles in Guthrie cards for the identification of early B-cell maturation defects

In conclusion, the associations among asthma, biofilmforming bacteria, and revision ESS are strong and robust after adjusting for other factors in patients with CRS from a tertiary medical center. Despite its limitations, this study may improve our understanding of refractory CRS pathogenesis, possibly leading to more effective treatment strategies, such as incorporating the treatments of asthma and biofilm infection into conventional CRS therapies. Prospective cohort studies in diverse populations are needed to assess the causality of these associations.

Is Kawasaki disease incidence rising in Chandigarh, North India?

Objective To estimate incidence of Kawasaki disease (KD) over time among children in the city of Chandigarh, North India. Patients and methods We analysed records of all children with KD below 15 years of age at the Pediatric Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, from January 1994 to December 2008. Diagnosis and treatment of KD were based on American Heart Association criteria. Among these cases, children residing in Chandigarh were identified. Yearly incidence was calculated and compared from 1994 to 2008. Results During this period, 196 children were diagnosed as KD. Of these, 80 (40.8%; 48 boys, 32 girls) resided in Chandigarh. Four among these had coronary artery abnormalities (CAA) on echocardiography, while two had mitral regurgitation. Comparison of yearly data revealed increasing incidence of disease from 0.51 cases in 1994 to 4.54 cases per 100 000 children below 15 years of age in 2007. Majority (93.7%) of cases occurred in children ≤10 years of age with the highest incidence reported in the seventh year of life. Monthly distribution of disease showed two peaks with a maximum number of cases presenting in October followed by a second peak in May with a nadir in the month of February. Conclusion Increasing incidence of KD in Chandigarh could be due to increasing clinical recognition as a result of greater awareness among paediatricians in the city, or may represent an actual increase in numbers. Striking differences from KD series reported from other countries include the older median age of our patients, low rate of CAA and a different bimodal seasonality, which may be epidemiologic clues to the nature of this vasculitis.

Arthritic presentation of childhood malignancy: beware of normal blood counts

Some children with malignancy (e.g. acute lymphoblastic leukemia) who initially present with musculoskeletal complaints may be misdiagnosed as having a rheumatological disorder. In the literature, importance has been given to subtle changes in blood counts, which may point toward an underlying malignancy. We report 3 children with malignancy, who had an arthritic presentation but had normal blood counts at presentation. Atypical clinical pattern, significant nocturnal pain, pain out of proportion to joint involvement and prominent systemic features in these children prompted us to do a bone marrow examination that revealed a malignancy. Pediatricians must be aware of the arthritic presentation of childhood malignancy. If the clinical features point toward a malignancy, bone marrow examination should always be performed even if the blood counts are normal.

Clinical profile of 516 children affected by HIV in a tertiary care centre in northern India: 14 years of experience

Increasing numbers of children affected by HIV are being recognised in northern India. The present study aimed to evaluate the clinical profile of 516 children affected by HIV at the Pediatric Allergy and Immunology Unit, Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India, during the period January 1994 to May 2008. In total, 454 children (327 boys and 127 girls) infected by HIV were analysed. The median age at presentation was 54 months. Of these children, 401 (88.3%) acquired the infection vertically and 26 (5.7%) acquired it through transfusion of blood/blood products. Moreover, 156 children (34.4%) were asymptomatic at presentation to hospital. Common clinical features included fever (36.6%), respiratory infections (31.7%), lymphadenopathy (30.0%), hepatosplenomegaly (21.8%) and diarrhoea (18.1%); 299 children (65.9%) were malnourished. Triple drug antiretroviral therapy was initiated in 205 children. Children receiving such therapy showed significant improvement in clinical and immunological parameters. Furthermore, follow-up rates improved markedly following free supply of the drug. Therapy was very well tolerated. To conclude, physicians looking after children need to be familiar with the varying clinical presentation of HIV infection. To the best of our knowledge, this is the largest paediatric series on HIV infection from a single centre from any developing country.

Dengue fever and Kawasaki disease: a clinical dilemma

There are several pediatric conditions which can present with fever and rash; however, it is uncommon to have two diseases occurring in a patient at the same time. We report a young child with fever and rash. He was initially diagnosed to have dengue fever based on clinical features and serological tests. Later in the course of illness he developed findings consistent with Kawasaki disease. This is extremely unusual and has rarely been reported before.

Kawasaki disease in infants below 6 months: a clinical conundrum?

Kawasaki disease (KD) is a medium vessel vasculitis of childhood. In infancy KD is often characterized by incomplete and atypical forms. There is paucity of literature on KD in children below 6 months and there are no data from any developing country. This study defines the profile of children with KD below 6 months at our centre.

Rituximab in childhood lupus myocarditis

Sir, Myocarditis is a life-threatening complication of systemic lupus erythematosus (SLE) [1]. Myocardial involvement demonstrable as reduction in left ventricular ejection fraction can be seen in 8–25% of patients with active SLE [2]. Symptomatic myocarditis, however, with signs of frank congestive heart failure is extremely uncommon especially in childhood lupus [3, 4]. We report a young girl with lupus myocarditis, who had severe congestive cardiac failure while on maximal immunosuppression. R, a 12-year-old girl, presented with complaints of polyarticular arthritis, fever, edema, and painless oral ulcers. She had pallor, pitting pedal edema, hypertension, and arthritis involving knee, ankle, and proximal interphalangeal joints. On investigation, urine examination revealed many red blood cells, and 24-h urine protein was 136 mg/m/h. Blood urea was 56 mg/dl and serum creatinine 1.4 mg/dl. Antinuclear antibody was 4+, diVuse pattern and antidsDNA antibody titer was 760 IU/ml (N < 55). Lupus anticoagulant was positive. Renal biopsy revealed class IV/V lupus nephritis. She was administered Wve daily methylprednisolone pulses (30 mg/kg/dose) followed by oral prednisolone (2 mg/kg/ day). She was also started on intravenous monthly cyclophosphamide pulses (750 mg/m/dose). Within a month, she was readmitted with fever, increasing edema, and respiratory distress. She had persistent disease activity, nonoliguric renal failure (creatinine 3.4 mg/dl), and hypertension. She was treated again with intravenous pulse methylprednisolone, and cyclophosphamide pulses were continued. With above treatment, renal functions normalized and blood pressure got controlled with antihypertensive medications—amlodipine (0.3 mg/kg/day) and carvedilol (0.6 mg/kg/day). Three months later, she presented with loose stools, vomiting for 2 days, and respiratory distress for a day. On examination, she had tachycardia, tachypnoea, and hypotension. She developed basal crepts, hepatomegaly, and gallop rhythm. For hemodynamic stability, she required inotropic support. Chest X-ray showed cardiomegaly (cardio thoracic ratio 64%) and bilateral basal inWltrates. Ventilation/perfusion (V/Q) scan was normal. Echocardiography showed dilated right and left ventricles, decreased myocardial contractility with left ventricular ejection fraction of only 30%. A clinical diagnosis of lupus myocarditis was made. As she had already received two courses of intravenous methylprednisolone and was on monthly cyclophosphamide pulses, a decision was made to start her on rituximab (375 mg/m/dose). She showed prompt clinical recovery, and we were able to taper oV her inotropes. The gallop disappeared. Repeat echocardiogram done after 1 week showed ejection fraction of 50%. She was treated with weekly doses of rituximab (375 mg/m/dose) for 4 weeks. Cyclophosphamide was given every month for 6 months and thereafter every 3 months. After 12 months of follow-up patient, she is asymptomatic and on tapering doses of oral prednisolone along with hydroxychloroquine. Cardiac involvement represents one of the most important clinical manifestations of SLE and contributes signiWcantly to the morbidity and P. Aggarwal · S. Singh (&) · D. Suri · A. Rawat Pediatric Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India e-mail: surjitsinghpgi@rediffmail.com

Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication

Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

X-linked Agammaglobulinemia

X-linked agammaglobulinemia (XLA) is one of the commonest primary immune deficiencies encountered in pediatric clinical practice. In adults, common variable immunodeficiency (CVID) is the most common primary immunodeficiency disease (PID). It is an X-linked disorder characterized by increased susceptibility to encapsulated bacteria, severe hypergammaglobulinemia and absent circulating B cells in the peripheral blood. Replacement immunoglobulin therapy is the main cornerstone of treatment. Aggressive management of intercurrent infections and prophylactic antimicrobials are needed. This review attempts to highlight varied clinical manifestations and management of XLA, especially in the context of developing country.

Hyper-IgE syndrome with a novel STAT3 mutation-a single center study from India.

BACKGROUND Hyper IgE syndrome (HIES) is a rare primary immunodeficiency disorder characterized by the triad of elevated IgE and eosinophilia, eczema and recurrent skin and pulmonary infections. Mutation in the STAT3 gene accounts for majority of the autosomal dominant and sporadic forms of HIES. OBJECTIVE To report clinical and molecular analyses of patients with Hyper IgE syndrome from a single tertiary care center in India. METHODS Four patients with suspected HIES were studied. Flowcytometry for T(H)17 cell numbers and phosphoSTAT3, and STAT3 gene sequencing were performed. RESULTS T(H)17 cells were significantly reduced. Mutations were found in the DNA-binding domain in three and a mutation in the transactivation domain in one patient. One of the mutations detected was a novel mutation (g54792 c.1018A> C p.K340Q) in the DNA binding domain. Mycobacterial infection, which is usually not commonly associated with HIES was found in two of our cases, one with a cutaneous abscess in the shoulder, and the other with BCG site reactivation. CONCLUSIONS A novel mutation in the STAT3 is reported. Mycobacterial infections can be seen in the spectrum of HIES related infections.