Ankur Kumar

Prevalence of Autism Spectrum Disorders in Siblings of Indian Children With Autism Spectrum Disorders

This study determined the prevalence of autism spectrum disorders in 201 siblings of children with autism spectrum disorders. Siblings were screened using Modified Checklist for Autism in Toddlers and Social Responsiveness Scale, parent version. Screen-positive siblings were assessed using Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. The risk of autism spectrum disorder in siblings was correlated with various familial and disease characteristics of the index case. Prevalence of autism spectrum disorder in siblings was 4.97%. There was a significant effect of the presence of aggressive behavior, externalizing problems and total problems in the proband, assessed using Childhood Behavior Checklist, and the young age of the father at conception on sibling risk of autism spectrum disorder. Results of our study are in line with previous studies reporting similar prevalence but have also brought up the association with behavioral problems as a possible risk factor. Siblings of children with autism spectrum disorder should be routinely screened, and genetic counseling for this increased risk should be explained to the family.

BCG Site Reactivation in Kawasaki Disease.

1a expression in capillaries and major histocompatibility complex class I expression in type II muscle fibers from polymyositis and dermatomyositis patients: important pathogenic features independent of inflammatory cell clusters in muscle tissue. Arthritis Rheum 2002;46:1044–55. 41. Pandya JM, Fasth AE, Zong M, Arnardottir S, Dani L, Lindroos E, et al. Expanded T cell receptor Vb–restricted T cells from patients with sporadic inclusion body myositis are proinflammatory and cytotoxic CD28 T cells. Arthritis Rheum 2010;62: 3457–66. 42. Namekawa T, Snyder MR, Yen JH, Goehring BE, Leibson PJ, Weyand CM, et al. Killer cell activating receptors function as costimulatory molecules on CD4CD28 T cells clonally expanded in rheumatoid arthritis. J Immunol 2000;165:1138–45. 43. Fagnoni FF, Vescovini R, Mazzola M, Bologna G, Nigro E, Lavagetto G, et al. Expansion of cytotoxic CD8 CD28 T cells in healthy ageing people, including centenarians. Immunology 1996;88:501–7. 44. Nakajima T, Schulte S, Warrington KJ, Kopecky SL, Frye RL, Goronzy JJ, et al. T-cell-mediated lysis of endothelial cells in acute coronary syndromes. Circulation 2002;105:570–5. 45. Scheler M, Irmler M, Lehr S, Hartwig S, Staiger H, Al-Hasani H, et al. Cytokine response of primary human myotubes in an in vitro exercise model. Am J Physiol Cell Physiol 2013;305:C877–86. 46. Ritter M, Huber C, Aubock J, Pohl-Markl H, Troppmair J, Herold M, et al. Lytic susceptibility of target cells to cytotoxic T cells is determined by their constitutive major histocompatibility complex class I antigen expression and cytokine-induced activation status. Immunology 1994;81:569–77. 47. Nakajima T, Goek O, Zhang X, Kopecky SL, Frye RL, Goronzy JJ, et al. De novo expression of killer immunoglobulin-like receptors and signaling proteins regulates the cytotoxic function of CD4 T cells in acute coronary syndromes. Circ Res 2003;93:106–13. 48. Hodge G, Hodge S, Ahern J, Holmes-Liew CL, Reynolds PN, Holmes M. Up-regulation of alternate co-stimulatory molecules on proinflammatory CD28 T cells in bronchiolitis obliterans syndrome. Clin Exp Immunol 2013;173:150–60.

The Expanding Spectrum of Gottron Papules in Juvenile Dermatomyositis

To the Editor: Juvenile dermatomyositis (JDMS) is the most common inflammatory myopathy of childhood and is associated with a variety of cutaneous manifestations. Gottron papules and heliotrope rash are the two most common skin abnormalities in patients with JDMS. Gottron papules are typically seen over the extensor surface of joints. We describe a 9-y-old boy who presented with complaints of rash over face and upper extremities for last 2 y. He had erythematous non-itchy lesions over malar area and nasolabial folds along with heliotrope rash. He also had prominent atrophic Gottron papules on knuckles (Fig. 1a), dorsum of hands and extensor aspect of both forearms (Fig. 1b and c). There was, however, no associated muscle weakness. Investigations revealed the following: hemoglobin 126 g/L, white blood cell count 6.4 × 10 cells/L, platelet count 209 × 10/L, erythrocyte sedimentation rate 5 mm in 1st hour, C-reactive protein 4 mg/L (normal <6 mg/L), anti-nuclear antibody not detectable and muscle enzymes (CPK, AST, LDH) within normal limits. Magnetic resonance imaging of thighs did not reveal muscle edema or inflammation. In view of typical Gottron papules and heliotrope rash, with no overt feature of muscle involvement , a diagnosis of amyopathic juvenile dermatomyositis (JDMS) was proffered. He was initiated on subcutaneous methotrexate therapy. On follow up after 2 y, he has had no muscular weakness and his lesions have healed completely. Gottron papules are the hallmark of JDMS and may be seen in >80% patients [1]. These are erythematous, scaly papular lesions distributed over extensor surfaces of joints typically over dorsal aspect of metacarpophalangeal and interphalangeal joints, elbow and knee joints [2]. Later in disease course or because of

Factors influencing the propensity of nurses to counsel patients for eye donation: a pilot study in a tertiary care hospital in north India

• What motivates the nurses to counsel the attendants of patients under their care for eye donation?

Recent advances in pediatric rheumatology: October to December 2016

1. Enthesitis-related arthritis: time to re-define? Bryan AR, Rabinovich CE Curr Rheumatol Rep 2014 Dec; 16(12), 466. doi:10.1007/s 11926-014-466-z It is becoming increasingly clear that enthesitis-related arthritis (ERA) subtype of juvenile idiopathic arthritis (JIA) in the International League of Associations for Rheumatology (ILAR) classification is far more complex than previously thought. ERA, as defined in the ILAR classification at present, does not include all subsets of spondyloarthropathy and many children may end up in the undifferentiated category of the ILAR classification. The authors highlight the pitfalls in classifying ERA as one single type of JIA, thereby implying that children given this label have a uniform and predictable clinical presentation. ERA is now known to be a heterogeneous group containing, as it does, at least two subgroups of arthritides – axial and peripheral, which vary in presentation, prognosis and therapeutic requirements. It is clear that axial disease is more common in children than previously thought and may occur much earlier. However, the current ILAR nomenclature does not have a mechanism to distinguish between axial and peripheral disease types of ERA. There is little doubt that that the ILAR classification needs to be revisited and the classification criteria redefined to encompass the expanded spectrum of conditions included in the term JIA. ILAR classification perhaps also needs to be simplified and made more user-friendly! 2. The new histopathologic classification of ANCAassociated glomerulonephritis and its association with renal outcomes in childhood Noone DG, Twilt M, Hayes WN, Thorner PS, Benseler S, Laxer RM, Parekh RS, Hebert D Clin J Am Soc Nephrol. 2014 Oct; 9, 1684–91 There is a paucity of published literature on longterm follow-up of children with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Noone et al. report a single-centre study on 40 children with ANCA-associated glomerulonephritis (GN) carried out over 25 years. Affected children were followed up until they transitioned to adult care. Renal biopsy specimens were categorized as: focal GN, 13 patients (32.5%); crescentic GN, 20 patients (50%); mixed, two patients (5%); and sclerotic, five patients (12.5%). The mixed and crescentic subgroups were combined for follow-up analyses. The authors show that the probability of having a glomerular filtration rate (GFR) > 60 mL/min per 1.73 m at 2 years was 100% for the group with focal GN, 56.5% for the mixed/crescentic subgroups and 0% for the group with sclerotic changes. This study shows how findings on renal biopsy in children with ANCA-associated GN can be correlated with their clinical outcomes and long-term prognosis, akin to what has hitherto been known for lupus. 3. Childhood-onset bullous systemic lupus erythematosus Lourenc o DM, Gomes RC, Aikawa NE, Campos LM, Romiti R, Silva CA Lupus. 2014 Nov; 23, 1422–5 Correspondence: Dr Surjit Singh, Pediatric Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, 160012 Chandigarh, India. Emails: surjitsinghpgi@rediffmail.com; surjitsinghapc@ gmail.com

365 Profile of henoch schonlein purpura (hsp) nephritis: 23 years experience at a tertiary care centre in north india

Background and aims Henoch Schonlein Purpura (HSP) is one of the most common vasculitides of childhood. Glomerulonephritis is seen in approximately 30%–50% of the patients and is the principal cause of morbidity and mortality in HSP patients. Methods 314 children were diagnosed with HSP from 1993–2015 based on EULAR/PRINTO/PRES criteria. A retrospective case review of all patients with HSP Nephritis (HSPN) was done. HSPN was defined based on urine erythrocyte >5/HPF and proteinuria. Patients were divided into four clinical types (Table 1). The severity of renal pathological findings was determined based on the classification of International Study of Kidney Disease (ISKDC), from grades I – VI. Abstract 365 Table 1 Clinical subtypes of HSPN. Results Renal involvement was seen in 64 patients after a mean duration of 32.3 days from the onset of symptoms of HSP. Details of patients with HSPN is summarised in table 2, 3 and figure 1. Three fourth of the patients had histological grade II or IIIa (Figure 2). 75% of patients with grade ≥ IV had gross hematuria at presentation. Treatment details are shown in figure 3. Patients were followed up for a mean period of 42.9 months during which 13 were lost to follow up and 1 expired. Nephritis resolved in 48 patients (75%). 13 patients developed renal relapse manifesting as albuminuria with microscopic hematuria in 77% patients followed by isolated albuminuria (23%). Abstract 365 Table 2 Details of patients with HSPN Abstract 365 Table 3 Percentage of various clinical subtypes of HSPN. Abstract 365 Figure 1 Timing of renal involvement from onset of HSP Abstract 365 Figure 2 Percentage of various histological grades on renal biopsy. Abstract 365 Figure 3 Treatment in patients with HSPN. Conclusions Renal involvement was noted in 20.4% of children with HSP. Massive proteinuria was the most common clinical feature. Grade II and IIIa were the most common renal pathological grades.

132 Systemic lupus erythematosus and antiphospholipid antibodies in a child with noonan syndrome

Background and Aims Autoimmune dysfunction has been described in patients with Noonan Syndrome (NS). Till date, 9 patients with systemic lupus erythematosus (SLE) and NS have been reported. However, exact relationship between SLE and NS is not known. Methods To describe the clinical presentation of a child with SLE and NS. Results A 10-years-old boy presented with fever, gradually progressive dyspnoea, pain in bilateral elbow and knee joints for 8 months. His past and family history was normal. Weight and height were <−3 z-score for his age. He had a long face with relatively large ears, down slanting palpebral fissure and livedo reticularis over lower limbs. Grade III ejection systolic murmur was present at pulmonary area along with loud second heart sound. He had hypertonia with brisk deep tendon reflexes in bilateral lower limbs, bilateral ankle clonus and extensor plantar response. Investigations revealed anaemia, thrombocytopenia, leucopenia, elevated acute phase reactants and aPTT prolongation. His antinuclear antibody was positive by indirect immunofluorescence (4+ homogenous), anti-double stranded deoxyribonucleic acid was elevated and direct coomb test and lupus anticoagulant were positive along with low serum complement 3 level. Echocardiography revealed mitral valve prolapse and mitral regurgitation. Magnetic resonance imaging of brain revealed chronic lacunar infarct in medial aspect of right thalamus. A diagnosis of SLE, APLA and NS was made and treatment with oral prednisolone, hydroxychloroquine, acetyl salicylate and low molecular weight heparin was initiated. Conclusions Autoimmune conditions including SLE are being increasingly described in patients with NS requiring close monitoring and long term follow up.

Chronic Granulomatous Disease Due to Neutrophil Cytosolic Factor (NCF2) Gene Mutations in Three Unrelated Families

Chronic granulomatous disease (CGD) is an inheritable and genetically heterogeneous disease resulting from mutations in different subcomponents of the NADPH oxidase system. Mutations in the NCF2 gene account for <5% of all cases of CGD. We analyzed the clinical and laboratory findings of CGD with mutations in the NCF2 gene from amongst our cohort of CGD patients. A homozygous mutation (c.835_836delAC, p.T279fsX294), a deletion in NCF2 gene was found in two cases. In the third case, two heterozygous mutations were detected, IVS13-2A>T on one allele and c.1099C>T (p.) on the other allele. The mother of this child was a carrier for the IVS13-2A>T mutation. All three cases had colitis, and it was the initial symptom in two patients. One of the patients also developed a lung abscess due to Nocardia cyriacigeorgica.

Melanonychia following cyclophosphamide therapy

Figure 2 | Pigmentation is limited to the distal part of the nails 11 weeks after onset of melanonychia. A n 8-year-old-boy with steroid-dependent nephrotic syndrome presented with bilateral thumbnail discoloration. After treatment with oral prednisolone for 18 months, he was started on oral cyclophosphamide. Eleven weeks later, nail pigmentation was noted. The nails were colored black, were nonblanchable, and involved the whole nail plate (Figure 1). There was no skin or mucous membrane pigmentation. His blood counts and renal and liver function tests results were normal. Melanonychia in our patient was attributed to cyclophosphamide, given the temporal association. Follow-up examination after 11 weeks revealed pigmentation moving distally with nail growth (Figure 2). Melanonychia, brown to black pigmentation of nails, is the most frequent pattern of nail discoloration associated with chemotherapeutic drugs including doxorubicin, after starting cyclophosphamide therapy.

Brain Abscess in a Child with Leukocyte Adhesion Defect: An Unusual Association

Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency caused by a defect in the adherence of neutrophils to the wall of blood vessels. This failure in adherence results in an inability of transmigration of neutrophils through the endothelium to the site of inflammation [1]. Patients with LAD are predisposed to severe and life-threatening bacterial infections from birth. Three types of LAD have been identified thus far [2], namely (i) LAD type I with defect in the ITGB2 gene encoding for CD18, (ii) LAD type II with defect in the SLC35C1 gene encoding for CD15, and (iii) LAD Type III with defect in the FERMT3 gene encoding the Kindlin 3 protein. Patients with LAD fail to develop pus at the site of infection because of an inability of neutrophils and monocytes to egress the circulation and reach the site of inflammation. The most common clinical manifestations include recurrent infections, poor wound healing, ulcers in the oral cavity, and skin abscesses [3]. Delayed separation of the umbilical cord (usually 3 weeks after birth) and omphalitis is a hallmark clinical manifestation of this immunodeficiency albeit not always present. Marked neutrophilic leukocytosis in the peripheral blood is the hallmark laboratory abnormality. Besides, patients with LAD III also have defective platelet aggregation leading to bleeding manifestations and an osteopetrosis phenotype because of a defect in osteoclasts [2]. We report brain abscess in a child with LAD type I, a hitherto unreported clinical presentation in LAD. The index case, a girl, born to non-consanguineously married couple, presented at 1 month of age with failure to thrive, cutaneous ulcers, cough, and respiratory distress. Her birth and perinatal events were uneventful, and umbilical cord normally fell on day 10 of life. On evaluation, she was afebrile, had pulse rate (PR)—140/min and respiratory rate (RR)—68/ min, was grossly malnourished, and had necrotic ulcers without any pus formation in the left submandibular region, left axilla, and the left inguinal region; crepitations in the right side of the chest were suggestive of pneumonia. Initial investigations revealed severe anemia, neutrophilic leukocytosis, and thrombocytosis (Table 1). Flow cytometry showed a markedly decreased expression of CD18 (<1 % on gated neutrophils), suggestive of leukocyte adhesion deficiency type 1. Scrapings from ulcerative lesion revealed Pseudomonas aeruginosa on culture. She was treated with 3 weeks of intravenous cefoperazone. The ulcers healed, and respiratory distress settled. She was discharged on prophylactic doses of cotrimoxazole and remained well for another 20 days. She presented to us again at 3 months of age with irritability and a new ulcer in the perianal region. On initial evaluation, she was active but irritable with HR—130/min and RR— 32/min. An ulcer was observed in the left side of the perianal region, measuring around 4 × 3 cm in size, with a necrotic base, an elevated edge but no pus formation. Scar marks were present in the left inguinal region, left axilla, and the left submandibular region, reminiscent of healed ulcers. She had hepatosplenomegaly and left side lower motor neuron (LMN) facial palsy. Investigations during this admission also revealed severe anemia with polymorphonuclear leukocytosis and thrombocytosis (Table 1). CSF examination was done with the suspicion of meningitis, and it showed features suggestive * Amit Rawat rawatamit@yahoo.com