FEBRILE CHILD - WHEN TO SUSPECT AND HOW TO WORK UP FOR CONNECTIVE TISSUE DISORDERS

*Mahesh Janarthanan

Abstract: Connective tissue disorders are rare compared to common infectious diseases in children. Making a diagnosis of connective tissue disorder may sometimes be easy when they have classical manifestations such as Kawasaki disease or Henoch Schonlein purpura. However at times fever may be the only manifestation or children may present with rare or atypical manifestations of a disease. A meticulous clinical examination and analysis of basic blood tests may provide a clue to the diagnosis or the need for further specific investigations in these situations.

Keywords: Febrile child, Connective Tissue disorder, Work up

Points to Remember

•When children present with prolonged fever, connective tissue disorders should be considered as differential diagnosis.

•Most diagnosis in rheumatology is clinical and blood tests should be used as corroborative evidence and not as screening tool.

•A complete clinical examination is vital

•Connective tissue disorders may evolve over time.

References

1.Chow A, Robinson JL.Fever of unknown origin in children a systematic review. World J Pediatr2011;7:5-10.

2.Liza J McCann, Lucy R Wedderburn and Nathan Hasson. Juvenile Idiopathic Arthritis. Arch Dis Child Educ Pract 2006; 91:29-36.

3.Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet 2007;369:767-778.

4.Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al.Derivation and Validation of Systemic Lupus International Collaborating Clinics Classification Criteria for Systemic Lupus Erythematosus.Arthritis Rheum 2012; 64:2677-2686.

5.Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J Med1975; 292:344-347.

6.Brown VE,Pilkington CA, Feldman BM, Davidson JE and on behalf of the Network for Juvenile Dermatomyositis, a working party of the Paediatric Rheumatology European Society (PReS).An international consensus survey of the diagnosticcriteria for juvenile dermatomyositis (JDM). Rheumatology 2006;45: 990-993.

7.Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, et al.Diagnosis, Treatment, and Long- Term Management of Kawasaki Disease. Circulation 2004;110:2747-2771.

8.Ozen S, Ruperto N, Dillon MJ, Bagga A, Barron K, Davin JC, et al.EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis 2006; 65: 936–941.

9.Eleftheriou D, Batu ED, Ozen S, Brogan PA. Vasculitis in children. Nephrol Dial Transplant 2015;30: i94–i103.

JUVENILE IDIOPATHIC ARTHRITIS

*Chitra Sundaramurthy

Abstract: Juvenile idiopathic arthritis comprises a heterogeneous group of inflammatory arthritides of unknown etiology with onset before 16 years of age and persisting for longer than 6 weeks. Several genetic associations have been identified but the etiopathogenesis is still unclear. The different subtypes have distinct clinical presentations and varied prognosis. Although none of the treatments available are curative, recent advances, particularly the introduction of biologics, have greatly improved outcomes. Continued research to understand the pathogenesis and identify specific molecules or pathways that need to be targeted will further improve the outlook for these patients in the future.

Keywords: Juvenile idiopathic arthritis, Classification, Management, Biologics

Points to Remember

•Juvenile idiopathic arthritis is a diagnosis of exclusion.

•Anti-nuclear antibody and rheumatoid factor are not screening or diagnostic tests for Juvenile idiopathic arthritis.

•Uveitis screening at diagnosis is mandatory for all children with Juvenile idiopathic arthritis.

•Radiographic joint damage occurs early in the disease course. Early referral to specialized care to initiate aggressive treatment will improve outcomes and prevent permanent joint damage.

•Macrophage activation syndrome is a serious lifethreatening complication of Systemic onset Juvenile idiopathic arthritis and needs prompt aggressive treatment.

•In children with unacceptable side effects or inadequate response to first line drugs biologics may be considered.

*Consultant Pediatric Rheumatologist, Apollo Children’s Hospital, Chennai.

email: chitra41275@hotmail.com

1.Manners PJ, Bower C. Worldwide prevalence of juvenile arthritis why does it vary so much? J Rheumatol 2002; 29:1520-1530.

2.Abujam B, Mishra R, Agarwal A. Prevalence of musculoskeletal complaints and juvenile idiopathic arthritis in children from a developing country: a school based study. Int J Rheum Dis 2014;17:256-260.doi: 10.1111/ 1756-185X.12276.Epub 2014 Jan 10.

3.Haersh AO, Prahalad S. Immunogenetics of juvenile idiopathic arthritis: A comprehensive review. JAutoimmun 2015;64:113-124. Doi:10.1016/j.jaut.2015.08.002.

4.Berkun Y, Padeh S. Environmental factors and geoepidemiology of juvenile idiopathic arthritis. Autoimmune Rev 2010;9:A31924.doi:10.1016/j. autrev. 2009.11.018. Epub 2009 Nov22.

5.Petty RE, Southwood TR, Baum J, Bhettay E, Glass DN, Manners P, et al. Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol 1998;25:1991-1994.

6.Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations

Indian Journal of Practical Pediatrics

for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004;31:390-392.

7.Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet 2007; 369(9563): 767-778.

8.Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, et al. 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/ Paediatric Rheumatology International Trials Organisation Collaborative Initiative.Ann Rheum Dis 2016;75;481-489.

9.Gutiérrez-Suárez R, Pistorio A, Cespedes Cruz A, Norambuena X, Flato B, Rumba I, et al and Pediatric Rheumatology International Trials Organisation (PRINTO). Health-related quality of life of patients with juvenile idiopathic arthritis coming from 3 different geographic areas. The PRINTO multinational quality of life cohort study. Rheumatology (Oxford) 2007; 46: 314- 320.

10.Packham JC, Hall MA. Long-term follow-up of 246 adults with juvenile idiopathic arthritis: functional outcome. Rheumatology (Oxford) 2002;41: 1428-1435.

11.Packham JC, Hall MA. Long-term follow-up of 246 adults with juvenile idiopathic arthritis: education and employment. Rheumatology (Oxford) 2002;41:1436-1439.

12.Mason T, Reed AM, Nelson AM, Thomas KB, Patton A, Hoffman AD, et al. Frequency of abnormal hand and wrist radiographs at time of diagnosis of polyarticular juvenile rheumatoid arthritis. J Rheumatol 2002;29:2214-2218.

13.Magni-Manzoni S, Rossi F, Pistorio A, Temporini F, Viola S, Beluffi G, et al. Prognostic factors for radiographic progression, radiographic damage, and disability in juvenile idiopathic arthritis. Arthritis Rheum 2003;48: 3509-3517.

14.Albers HM. Wessels JA. van der Straaten RJ. Brinkman DM. Suijlekom-Smit LW. Kamphuis SS, et al. Time to treatment as an important factor for the response to methotrexate in juvenile idiopathic arthritis. Arthritis Rheumatol 2009; 61:46-51.

15.Magnani A, Pistorio A, Magni-Manzoni S, Falcone A, Lombardini G, Bandeira M, et al. Achievement of a state of inactive disease at least once in the first 5 years predicts better outcome of patients with polyarticular juvenile idiopathic arthritis. Journal of Rheumatology 2009;36:628- 634.

16.van Rossum MA, van Soesbergen RM, Boers M, Zwinderman AH, Fiselier TJ, Franssen MJ, et al. Long- term outcome of juvenile idiopathic arthritis following a placebo-controlled trial: sustained benefits of early sulfasalazine treatment. Ann Rheum Dis 2007;66:1518– 1524.

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17.Wallace CA, Ruperto N, Giannini E. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. Childhood Arthritis and Rheumatology Research Alliance; Pediatric Rheumatology International Trials Organization; Pediatric Rheumatology Collaborative Study Group. J Rheumatol 2004;31:2290-2294.

18.Wallace CA, Giannini EH, Huang B, Itert L, Ruperto N. Childhood Arthritis Rheumatology Research Alliance; Pediatric Rheumatology Collaborative Study Group; Paediatric Rheumatology International Trials Organisation. American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken) 2011;63:929-936. doi: 10.1002/acr.20497.

19.Beresford MW, Baildam EM. New advances in the management of juvenile idiopathic arthritis-1: non- biological therapy. Arch Dis Child Educ Pract Ed 2009;94:144-150.

20.Hashkes PJ, Uziel Y, Laxer RM. “The safety profile of biologic therapies for juvenile idiopathic arthritis.” Nat Rev Rheumatol 2010;6: 561-571.

21.Tynjälä P, Vähäsalo P, Tarkiainen M, Kröger L, Aalto K, Malin M, et al. Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial. Ann Rheum Dis 2011;70:1605-1612. Epub 2011 May 28.

22.Wallace CA, Giannini EH, Spalding SJ, Hashkes PJ, O’Neil KM, ZeftAS, et al. Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis. Arthritis Rheum 2012;64:2012-2021.

23.Vilca I, Munitis PG, Pistorio A, Ravelli A, Buoncompagni A, Bica B. Pediatric Rheumatology International Trials Organisation (PRINTO). Predictors of poor response to methotrexate in polyarticular-course juvenile idiopathic arthritis: analysis of the PRINTO methotrexate trial.Annals of the Rheumatic Diseases 2010; 69: 1479-1483.

24.Flatø B, Lien G, Smerdel A, Vinje O, Dale K, Johnston V, et al. Prognostic factors in Juvenile Rheumatoid arthritis: a case-control study revealing early predictors and outcome after 14.9years. J Rheumatol 2003;30386-393.

SYSTEMIC LUPUS ERYTHEMATOSUS

*Anand P Rao **Jyothi Raghuram

Abstract: Pediatric systemic lupus erythematosus (pSLE) is a rare autoimmune disorder which tends to have multisystemic involvement characterized by chronic course interspersed with remissions and exacerbations. It is caused by immune dysregulation in both innate and adaptive immunity and has a female preponderance. Renal involvement more often than not tends to determine the prognosis. With newer drugs and more aggressive treatment regimens the prognosis of this otherwise dreadful condition has undergone a paradigm shift with more and more pSLE patients having a near normal life expectancy.

Keywords: Pediatric systemic lupus erythematosus, Lupus nephritis, Immune complex

*Consultant Pediatrician with Special interest in Pediatric Rheumatology,

Indira Gandhi Institute of Child Health and Manipal Hospital,

Bangalore.

email : dranand15@gmail.com

**Consultant Pediatrician with Special interest in Pediatric Rheumatology,

Indira Gandhi Institute of Child Health and Columbia Asia Hospital, Bangalore.

Points to Remember

•Pediatric systemic lupus erythematosus is a multisystem, chronic disease with remissions and exacerbations.

•It tends to affect more preadolescent and adolescent girls than boys.

•Lupus nephritis is more often seen in the first 2 years of disease onset.

•Early diagnosis and treatment can prevent organ damage and improve the disease outcomes significantly.

References

1.Aggarwal A, Srivastava P. Childhood onset systemic lupus erythematosus: how is it different from adult SLE? International journal of rheumatic diseases 2015; 18:182- 91.

2.Marisa Klein-Gitelman, Jerome Charles Lane. Systemic lupus erythematosus. In: Petty RE, Laxer RM, Lindsley CB, Wedderburn LR editors. Seventh edition, Textbook of Pediatric Rheumatology. Philadelphia, PA: Elsiever Saunders; 2016; pp285-317.

3.Pineles D, Valente A, Warren B, Peterson MG, Lehman TJ, Moorthy LN. Worldwide incidence and prevalence of pediatric onset systemic lupus erythematosus. Lupus 2011; 20:1187-1192.

4.Slingsby JH, Norsworthy P, Pearce G, Vaishnaw AK, Issler H, Morley BJ, et al. Homozygous hereditary C1q deficiency and systemic lupus erythematosus.Anew family and the molecular basis of C1q deficiency in three families. Arthritis Rheum 1996; 39:663-670.

5.Niewold TB. Interferon alpha as a primary pathogeic factor in human lupus. J Interferon Cytokine Res 2011; 31:887- 892.

6.Muñoz LE, Lauber K, Schiller M, Manfredi AA, Herrmann M. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol 2010; 6:280-289.

7.Belot A, Cimaz R. Monogenic forms of systemic lupus erythematosus: new insights into SLE pathogenesis. Pediatr Rheumatol Online J 2012; 10:21.

KAWASAKI DISEASE - UPDATE

* Surjit Singh ** Ankur Kumar Jindal

Abstract: Kawasaki disease is the commonest form of vasculitis in children with predilection to involve coronary arteries. The etiology of this disease is not well known but it is believed to be triggered in a genetically susceptible host by an infectious agent. This update describes the recent advances in Kawasaki disease with an emphasis on its etiopathogenesis, newer laboratory and radiological investigations and therapeutic options. IVIg and aspirin remain the mainstay of treatment in acute stage. Infliximab is an effective and safe treatment option in IVIg resistant cases.

Keywords: Coronary artery aneurysm, Intravenous immunoglobulin, Kawasaki disease, Update

Points to Remember

•Kawasaki disease is the commonest form of vasculitis and the most common cause of acquired heart disease in children.

•The etiopathogenesis is believed to be triggered by an infectious agent in genetically predisposed individuals.

•Diagnosis is essentially clinical and can be challenging in infants and young children as they often present with incomplete form of the disease.

•Two-dimensional echocardiography is a useful diagnostic modality during acute stage as well as on follow-up.

•Intravenous immunoglobulin (IVIg) is the standard first line therapy and should be administered as early as possible.

•If left untreated, the risk of developing coronary artery aneurysms is up to 25%. With prompt diagnosis and appropriate treatment, this risk can be brought down to 3%-5%.

•Patients with KD must be kept on long-term follow up as they are at a higher risk of cardiovascular events later in life.

*Professor, Allergy Immunology Unit, Department of Pediatrics

email: surjitsinghpgi@rediffmail.com

**DM Fellow in Pediatric Clinical Immunology and Rheumatology,

Advanced Pediatrics Centre, PGIMER, Chandigarh.

References

1.Newburger JW, Takahashi M, Burns JC. Kawasaki Disease. J Am Coll Cardiol 2016; 67:1738–1749.

2.Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children]. Arerugî 1967;16: 178–222.

3.Burns JC. Commentary: translation of Dr. Tomisaku Kawasaki’s original report of fifty patients in 1967. Pediatr Infect Dis J 2002; 21:993–995.

4.Makino N, Nakamura Y, Yashiro M, Ae R, Tsuboi S,

Aoyama Y, et al. Descriptive epidemiology of Kawasaki disease in Japan, 2011-2012: from the results of the 22nd nationwide survey. J Epidemiol Jpn EpidemiolAssoc 2015; 25(3):239–245.

5.Kim GB, Han JW, Park YW, Song MS, Hong YM, Cha SH, et al. Epidemiologic features of Kawasaki disease

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in South Korea: data from nationwide survey, 2009-2011. Pediatr Infect Dis J 2014; 33:24–27.

6.Huang WC, Huang LM, Chang IS, Chang LY, Chiang BL, Chen PJ, et al. Epidemiologic features of Kawasaki disease in Taiwan, 2003-2006. Pediatrics 2009; 123:e401-405.

7.Singh S, Aulakh R, Bhalla AK, Suri D, Manojkumar R, Narula N, et al. Is Kawasaki disease incidence rising in Chandigarh, North India? Arch Dis Child 2011; 96: 137–140.

8.Singh S, Bhattad S. Kawasaki disease incidence at Chandigarh, North India, during 2009-2014. Rheumatol Int 2016; 36:1391-1397.

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11.Yoon KL. Update of genetic susceptibility in patients with Kawasaki disease. Korean J Pediatr 2015; 58:84–88.

12.Onouchi Y, Gunji T, Burns JC, Shimizu C, Newburger JW, Yashiro M, et al. ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat Genet 2008; 40:35–42.

13.Onouchi Y. Genetics of Kawasaki disease: what we know and don’t know. Circ J Off J Jpn Circ Soc 2012; 76:1581– 1586.

14.Rowley AH. Kawasaki Disease: Novel Insights into Etiology and Genetic Susceptibility. Annu Rev Med 2011; 62:69–77.

15.Rowley AH, Baker SC, Shulman ST, Rand KH, Tretiakova MS, Perlman EJ, et al. Ultrastructural, Immunofluorescence, and RNA Evidence Support the Hypothesis of a “New” Virus Associated With Kawasaki Disease. J Infect Dis 2011; 203:1021-1030.

16.Rodó X, Curcoll R, Robinson M, Ballester J, Burns JC, Cayan DR, et al. Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan. Proc Natl Acad Sci 2014; 111:7952– 7957.

17.Brown TJ, Crawford SE, Cornwall ML, Garcia F, Shulman ST, Rowley AH. CD8 T Lymphocytes and Macrophages Infiltrate Coronary Artery Aneurysms in Acute Kawasaki Disease. J Infect Dis 2001; 184:940–943.

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Kiyosawa N, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int 2005; 47:232–234.

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32.Tseng HC, Ho JC, Guo MMH, Lo MH, Hsieh KS, Tsai WC, et al. Bull’s eye dermatoscopy pattern at bacillus Calmette-Guérin inoculation site correlates with systemic involvements in patients with Kawasaki disease. J Dermatol 2016; 43:1044–1050.

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I.Diagnosis, clinical features, and pathogenesis. J AmAcad Dermatol 2013; 69:501.e1-11; quiz 511-512.

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42.Lin KH, Chang SS, Yu CW, Lin SC, Liu SC, Chao HY, et al. Usefulness of natriuretic peptide for the diagnosis of Kawasaki disease: a systematic review and meta-analysis. BMJ Open. 2015; 5(4):e006703. doi: 10.1136/bmjopen- 2014-006703.

43.Ye Q, Shao W, Shang S, Zhang T, Hu J, Zhang C.

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44.Reddy M, Singh S, Rawat A, Sharma A, Suri D, Rohit MK. Pro-brain natriuretic peptide (ProBNP) levels in North Indian children with Kawasaki disease. Rheumatol Int 2016; 36:551–559.

45.Dionne A, Meloche-Dumas L, Desjardins L, Turgeon J, Saint-Cyr C, Autmizguine J, et al. NT-proBNP diagnostic algorithm for Kawasaki Disease compared to AHA Algorithm. Pediatr Int Off J Jpn Pediatr Soc 2016; doi: 10.1111/ped.13154 [Epub ahead of print].

46.Kawamura Y, Takeshita S, Kanai T, Yoshida Y, Nonoyama S. The Combined Usefulness of the Neutrophil- to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Predicting Intravenous Immunoglobulin Resistance with Kawasaki Disease. J Pediatr 2016;doi: 10.1016/j.jpeds. 2016.07.035 [Epub ahead of print].

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47.Ha KS, Lee J, Jang GY, Lee J, Lee KC, Son CS, et al. Value of neutrophil-lymphocyte ratio in predicting outcomes in Kawasaki disease. Am J Cardiol 2015; 116:301–306.

48.Demir F, Karadeniz C, Özdemir R, Yozgat Y, Çelegen K, Karaaslan U, et al. Usefulness of Neutrophil to Lymphocyte Ratio in Prediction of Coronary Artery Lesions in Patients with Kawasaki Disease. Balk Med J 2015; 32:371–376.

49.Manlhiot C, Millar K, Golding F, McCrindle BW. Improved classification of coronary artery abnormalities based only on coronary artery z-scores after Kawasaki disease. Pediatr Cardiol 2010; 31:242–249.

50.Dietz SM, Tacke CE, Kuipers IM, Wiegman A, de Winter RJ, Burns JC, et al. Cardiovascular imaging in children and adults following Kawasaki disease. Insights Imaging 2015; 6:697–705.

51.Tacke CE, Kuipers IM, Groenink M, Spijkerboer AM, Kuijpers TW. Cardiac magnetic resonance imaging for noninvasive assessment of cardiovascular disease during the follow-up of patients with Kawasaki disease. Circ Cardiovasc Imaging 2011; 4:712–720.

52.Kuo HC, Hsu YW, Wu MS, Chien SC, Liu SF, Chang WC. Intravenous immunoglobulin, pharmacogenomics and Kawasaki disease. J Microbiol Immunol Infect 2016; 49:1–7.

53.Alexoudi I, Kanakis M, Kapsimali V, Vaiopoulos G. Kawasaki disease: current aspects on aetiopathogenesis and therapeutic management. Autoimmun Rev 2011; 10:544–547.

54.Bayers S, Shulman ST, Paller AS. Kawasaki disease: part II. Complications and treatment. J Am Acad Dermatol 2013; 69: 521-522.

55.Muta H, Ishii M, Yashiro M, Uehara R, Nakamura Y. Late intravenous immunoglobulin treatment in patients with Kawasaki disease. Pediatrics 2012; 129:e291-297.

56.Rahbarimanesh A, Taghavi-goodarzi M. Comparison of High-Dose versus Low-Dose Aspirin in the Management of Kawasaki Disease. Indian J Pediatr 2014;81:12098

57.Su D, Wang K, Qin S, Pang Y. Safety and efficacy of warfarin plus aspirin combination therapy for giant coronary artery aneurysm secondary to Kawasaki disease: a meta-analysis. Cardiology 2014; 129:55–64.

58.Manlhiot C, Brandão LR, Somji Z, Chesney AL, MacDonald C, Gurofsky RC, et al. Long-Term Anticoagulation in Kawasaki Disease: Initial Use of Low Molecular Weight Heparin is a Viable Option for Patients with Severe Coronary Artery Abnormalities. Pediatr Cardiol 2010; 31:834–842.

59.Adler AC, Kodavatiganti R. Kawasaki disease and giant coronary artery aneurysms: the role of echocardiography from diagnosis through follow-up. Echocardiography 2016; 33:1245–1250.

60.Dimitriades VR, Brown AG, Gedalia A. Kawasaki disease:

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pathophysiology, clinical manifestations, and management. Curr Rheumatol Rep 2014; 16:423.

61.Newburger JW, Sleeper LA, McCrindle BW, Minich LL, Gersony W, Vetter VL, et al. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med 2007; 356:663–675.

62.Kobayashi T, Saji T, Otani T, Takeuchi K, Nakamura T, Arakawa H, et al. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial. Lancet Lond Engl 2012; 379(9826):1613–1620.

63.Furukawa T, Kishiro M, Akimoto K, Nagata S, Shimizu T, Yamashiro Y. Effects of steroid pulse therapy on immunoglobulin-resistant Kawasaki disease. Arch Dis Child 2008; 93:142–146.

64.Ogata S, Ogihara Y, Honda T, Kon S, Akiyama K, Ishii M. Corticosteroid pulse combination therapy for refractory Kawasaki disease: a randomized trial. Pediatrics 2012;129:e17-23.

65.Saneeymehri S, Baker K, So TY. Overview of Pharmacological Treatment Options for Pediatric Patients with Refractory Kawasaki Disease. J Pediatr Pharmacol Ther 2015; 20:163–177.

66.Singh S, Sharma D, Suri D, Gupta A, Rawat A, Rohit MK. Infliximab is the new kid on the block in Kawasaki disease: a single-centre study over 8 years from North India. Clin Exp Rheumatol. 2016; 34:S134-138.

67.Xue LJ, Wu R, Du GL, Xu Y, Yuan KY, Feng ZC, et al. Effect and Safety of TNF Inhibitors in Immunoglobulin- Resistant Kawasaki Disease: a Meta-analysis. Clin Rev Allergy Immunol 2016 Aug 23;[Epub ahead of print].

68.Burns JC, Best BM, Mejias A, Mahony L, Fixler DE, Jafri HS, et al. Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease. J Pediatr 2008; 153:833–838.

69.Son MB, Gauvreau K, Burns JC, Corinaldesi E, TremouletAH, Watson VE, et al. Infliximab for intravenous immunoglobulin resistance in Kawasaki disease: a retrospective study. J Pediatr 2011; 158:644–649.

70.Mori M, Imagawa T, Hara R, Kikuchi M, Hara T, Nozawa T, et al. Efficacy and limitation of infliximab treatment for children with Kawasaki disease intractable to intravenous immunoglobulin therapy: report of an open- label case series. J Rheumatol 2012; 39:864–867.

71.Hamada H, Suzuki H, Abe J, Suzuki Y, Suenaga T, Takeuchi T, et al. Inflammatory cytokine profiles during Cyclosporin treatment for immunoglobulin-resistant Kawasaki disease. Cytokine 2012; 60:681–685.

72.Wallace CA, French JW, Kahn SJ, Sherry DD. Initial intravenous gammaglobulin treatment failure in Kawasaki disease. Pediatrics 2000; 105:E78.

73.Lee TJ, Kim KH, Chun JK, Kim DS. Low-dose

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methotrexate therapy for intravenous immunoglobulin- resistant Kawasaki disease. Yonsei Med J 2008; 49:714– 718.

74.Matsui M, Okuma Y, Yamanaka J, Uryu H, Sato N, Shichino H, et al. Kawasaki disease refractory to standard treatments that responds to a combination of pulsed methylprednisolone and plasma exchange: Cytokine profiling and literature review. Cytokine 2015; 74:339–

75.Fujimaru T, Ito S, Masuda H, Oana S, Kamei K, Ishiguro A, et al. Decreased levels of inflammatory cytokines in immunoglobulin-resistant Kawasaki disease after plasma exchange. Cytokine 2014; 70:156–160.

76.Mostafavi N, Haghjooy-Javanmard S, Presidend N, Manssori NS, Kelishadi R. Persistence of endothelial cell damage late after Kawasaki disease in patients without coronary artery complications. Adv Biomed Res 2015; doi: 10.4103/2277-9175.150393.

77.Cheung YF. Vascular health late after Kawasaki disease: implications for accelerated atherosclerosis. Korean J Pediatr 2014; 57:472–478.

78.Dhillon R, Clarkson P, Donald AE, Powe AJ, Nash M, Novelli V, et al. Endothelial dysfunction late after Kawasaki disease. Circulation 1996; 94:2103–2106.

79.Furuyama H, Odagawa Y, Katoh C, Iwado Y, Ito Y, Noriyasu K, et al. Altered myocardial flow reserve and endothelial function late after Kawasaki disease. J Pediatr 2003; 142:149–154.

80.Yamakawa R, Ishii M, Sugimura T, Akagi T, Eto G, Iemura M, et al. Coronary endothelial dysfunction after Kawasaki disease: evaluation by intracoronary injection of acetylcholine. J Am Coll Cardiol 1998; 31:1074–1080.

81.Narsaria P, Singh S, Gupta A, Khullar M, Bhalla A. Lipid profile and fat patterning in children at a mean of

8.8years after Kawasaki disease: a study from Northern India. Clin Exp Rheumatol 2015; 33:S171-175.

82.Meena RS, Rohit M, Gupta A, Singh S. Carotid intima- media thickness in children with Kawasaki disease. Rheumatol Int 2014; 34:1117–1121.

83.Mitra A, Singh S, Devidayal, Khullar M. Serum lipids in north Indian children treated for kawasaki disease. Int Heart J 2005; 46:811–817.

84.Kato H, Ichinose E, Kawasaki T. Myocardial infarction in Kawasaki disease: clinical analyses in 195 cases. J Pediatr 1986; 108:923–927.

85.Serpytis P, Petrulioniene Z, Gargalskaite U, Gedminaite A, Panaviene V. Myocardial infarction associated with Kawasaki disease in adult man: case report and review of literature. Am J Med 2015; 128:e1-3.

86.Bhagwat A, Mukhedkar S, Ekbote S, Gordon JB. Missed Kawasaki disease in childhood presenting as myocardial infarction in adults. Indian Heart J 2015; 67: 385-388.

VASCULITIS SYNDROMES

*Sathish Kumar T

Abstract: Childhood vasculitis is a challenging and complex group of conditions that are multisystem in nature and often require integrated care from multiple subspecialties including rheumatology, dermatology, cardiology, nephrology, neurology and gastroenterology. Primary systemic vasculitides of the young are relatively rare diseases, but are associated with significant morbidity and mortality, particularly if there is a delay in diagnosis. The site of vessel involvement, size of the affected vessels, extent of vascular injury and underlying pathology determine the disease phenotype and severity. This review explores the classification and general features of pediatric vasculitis as well as the clinical presentation, diagnostic evaluation and therapeutic options for the common vasculitides.

Keywords: Vasculitis, Primary, Children.

*Professor of Pediatrics, Christian Medical College, Vellore.

email: sathishkumar1973@yahoo.com

Points to Remember

•The two most common types of primary pediatric vasculitides are Henoch-Schonlein purpura and Kawasaki disease. The clinical expression and severity of the vasculitis are determined by the size of involved vessels, type of pathologic change, organs involved and systemic extent of the vascular injury.

•European League Against Rheumatism (EULAR)/ Pediatric Rheumatology European Society (PRES) classification criteria for childhood vasculitis are currently used to classify primary vasculitis in children.

•Advances in imaging techniques such as CT and MR angiography have revolutionized the imaging approach to large and medium vessel vasculitis.

•Controlled data are lacking to guide therapeutic decisions for children with systemic vasculitis, with the noticeable exception of Kawasaki disease.

References

1.Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR. Incidence of Henoch-Schönlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet 2002; 360: 1197-1202.

2.Ozen S, Ruperto N, Dillon MJ, Bagga A, Barron K, Davin JC, et al. EULAR/PReS endorsed consensus criteria for the clas-sification of childhood vasculitides. Ann Rheum Dis 2006; 65: 936-941.

3.Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, et al. EULAR/PRINTO/PReS criteria for Henoch- Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis 2010; 69: 798-806.

4.Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65: 1-11.

5.Waller R, Ahmed A, Patel I, Luqmani R. Update on the classification of vasculitis. Best Pract Res Clin Rheumatol 2013; 27: 3–17.

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6.Peru H, Soylemezoglu O, Bakkaloglu SA, Elmas S, Bozkaya D, Elmaci AM, et al. HenochSchonlein purpura in child-hood: clinical analysis of 254 cases over a 3-year period. Clin Rheumatol 2008; 27: 1087-1092.

7.Narchi H. Risk of long term renal impairment and duration of follow up recommended for Henoch-Schonlein purpura with normal or minimal urinary findings: a systematic review. Arch Dis Child 2005; 90: 916-920.

8.Davin JC. Henoch-Schönlein purpura nephritis: pathophys- iology, treatment and future strategy. Clin J Am Soc Nephrol 2011; 6: 679-689.

9.Bayrakci US, Baskin E, Ozen S. Treatment of Henoch- Schonlein purpura: what evidence do we have? Int J Clin Rheumatol 2010; 5: 669–676.

10.Bosch X, GuilabertA, Font J. Anti-neutrophil cytoplasmic antibodies. Lancet 2006; 368: 404-418.

11.Finkielman JD, Merkel PA, Schroeder D, Hoffman GS, Spiera R, St Clair EW, et al. Antiproteinase 3 Anti- neutrophil cytoplasmic antibodies and disease activity in Wegener granu-lomatosis. Ann Intern Med 2007; 147: 611- 619.

12.Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010; 363: 221-232.

13.De Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, et al. Randomized trial of cyclo- phosphamide versus methotrexate for induction of remission in early systemic Anti-neutrophil cytoplasmic antibody-associ-ated vasculitis.Arthritis Rheum 2005; 52: 2461-2469.

14.Agard C, Mouthon L, Mahr A, Guillevin L. Microscopic polyangiitis and polyarteritis nodosa: how and when do they start? Arthritis Rheum 2003; 49: 709-715.

15.Eleftheriou D, Levin M, Shingadia D, Tulloh R, Klein NJ, Brogan PA. Management of Kawasaki disease. Arch Dis Child 2014; 99: 74–83.

16.Tse SM, Silverman ED, McCrindle BW, Yeung RS. Early treatment with intravenous immunoglobulin in patients with Kawasaki disease. J Pediatr 2002; 140: 450-455.

17.Burns JC, Mason WH, Hauger SB, Janai H, Bastian JF, Wohrley JD, et al. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr 2005; 146: 662-667.

18.Eleftheriou D, Dillon MJ, Tullus K, Marks SD, Pilkington CA, Roebuck DJ, Klein NJ, Brogan PA.Systemic polyarteritis nodosa in the young: a single-center experience over thirty-two years. Arthritis Rheum 2013;65:2476-2485.

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19.Matteoda MA, Stefano PC, Bocián M, Katsicas MM, Sala J, Cervini AB. Cutaneous polyarteritis nodosa. An Bras Dermatol 2015;90:188-190.

20.Brunner J, Feldman BM, Tyrrell PN, Kuemmerle-Deschner JB, Zimmerhackl LB, Gassner I, et al. Takayasu arteritis in children and adolescents. Rheumatology 2010; 49: 1806- 1814.

21.Mavrogeni S, Dimitroulas T, Chatziioannou SN, Kitas G. The role of multimodality imaging in the evaluation of Takayasu arteritis. Semin Arthritis Rheum 2013;42;401- 412.

MACROPHAGE ACTIVATION SYNDROME

*Aruna Bhat

Abstract: Macrophage activation syndrome (MAS) is a life threatening complication that may arise in chronic rheumatic diseases of childhood. It closely resembles hemophagocytic lymphohistiocytosis (HLH). Infections are common triggers. It is often a challenge to diagnose MAS as the features closely mimic sepsis and may rapidly progress to multiorgan dysfunction, unless prompt action is taken. Unremitting fever, cytopenia, liver dysfunction, coagulopathy, high levels of ferritin and hemophagocytosis in tissues are some of the cardinal features of this illness. MAS is associated with high mortality.

References

1.Grom AA. Macrophage activation syndrome. In:

Cassidy JT, Petty RE, Laxer RM, Lindsley CB. Textbook of pediatric rheumatology, 6thedn, Saunders Elsevier, Philadelphia, 2011; pp674-681.

2.Grom AA. NK dysfunction: A common pathway in systemic onset juvenile rheumatoid arthritis, macrophage activation syndrome, and hemophagocyticlympho- histiocytosis. Arthritis Rheum 2004; 50:689-698.

3.Sawhney S, Woo P, Murray KJ. Macrophage activation syndrome: A potentially fatal complication of rheumatic disorders. Arch Dis Child 2001; 85:421-426.

4.Ramanan AV, Baildam EM. Macrophage activation syndrome is hemophagocyticlymphohistiocytosis-need for the right terminology. J Rheumatol 2002; 29:1105.

Keywords: Macrophage activation syndrome, Hemophagocytic lymphohistiocytosis, Sepsis mimic, Chronic rheumatic diseases of childhood.

Points to Remember

•Macrophage activation syndrome is a potentially fatal complication that occurs in rheumatological conditions due to overwhelming inflammatory response caused by dysregulated immune system

•A suspicion of MAS should be raised when there is a change in the fever pattern to high grade and unremittingwith new onset lymphadenopathy, hepatosplenomegaly and rash.

•Persistent fever, splenomegaly, bicytopenias, hypertriglyceridemia, and hemophagocytosis in the bone marrow are cardinal features of MAS.

•Various treatment options include intravenous methylprednisolone pulses, cyclosporine, etoposide, rituximab, anti-thymocytegloulin or TNF alpha inhibitors

•MAS is a potentially fatal disease with mortality rates of up to 20%. Severe renal dysfunction or multiorgan dysfunction carry poor prognosis.

*Consultant Pediatric Rheumatologist, Narayana Health City, Bangalore. email: hegdearuna@hotmail.com

5.Favara BE, Feller AC, Pauli M, Jaffe ES, Weiss LM, Arico M, et al., Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocytic Society, Med Pediatr Oncol 1997; 29:157-166.

6.Filipovich HA.Hemophagocyticlymphohistiocytosis, Immunol Allergy Clin N Am 2002; 22:281-300.

7.Behrens EM, Beukelman T, Paessler M, Cron RQ. Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J Rheumatol 2007; 34:1133- 1138.

8.Stephan JL, Kone-Paut I, Galambrun C, Mouy R, Bader- Meunier B, Prieur AM. Reactive Hemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients. Rheumatology (Oxford) 2001; 40:1285-1292.

9.Muise A, Tallett SE, Silverman ED. Are children with Kawasaki disease and prolonged fever at risk of macrophage activation syndrome? Paediatrics 2003; 112:e495-e497.

10.Avcin T,Tse SM, Schneider R, Ngan B, Silverman ED. Macrophage activation syndrome as the presenting manifestation of rheumatic diseases in childhood.J Pediatr 2006; 148:683-686.

11.Risdall RJ, McKenna RW, Nesbit ME, Krivit W, Balfour HH Jr, Simmons RL, et al. Virus-associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis. Cancer1979; 44:993-1002.

12.Grom AA, Villanueva J, Lee S, Goldmuntz EA, Passo MH, Filipovich AH. Natural killer cell dysfunction in patients

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with systemic-onset juvenile rheumatoid arthritis and macrophage activation syndrome. J Peds 2003;142;292- 296.

13.Vastert SJ, van Wijk R, D’Urbano LE, de Vooght KM, de Jager W, Ravelli A, et al. Mutations in the perforin gene can be linked to macrophage activation syndrome in patients with systemic onset juvenile idiopathic arthritis. Rheumatology (Oxford). 2010;49:441-449.

14.Stepp SE, Dufourcq-Lagelouse R, Le Deist F, Bhawan S, Certain S, Mathew PA, et al. Perforin gene defects in familial hemophagocyticlymphohistiocytosis. Science 1999;286:1957-1959.

15.Feldmann J, Callebaut I, Raposo G, Certain S, Bacq D, Dumont C, et al. MUNC13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocyticlymphohistiocytosis (FHL3). Cell 2003; 115:461-473.

16.Davies SV, Dean JD, Wardrop CA, Jones JH. Epstein-Barr virus-associated haemophagocytic syndrome in a patient with juvenile chronic arthritis. Br J Rheumatol 1994; 33:495-497.

17.Fishman D, Rooney M, Woo P. Successful management of reactive haemophagocytic syndrome in systemic-onset juvenile chronic arthritis (letter). Br J Rheumatol 1995; 34:888.

18.FardetL, Coppo P, Kettaneh A, Dehoux M, Cabane J, Lambotte O. Low glycosylated ferritin, a good marker for the diagnosis of hemophagocytic syndrome.Arthritis Rheum 2008; 58:1521-1527.

19.Bleesing J, Prada A, Siegel DM, Villanueva J, Olson J, Ilowite NT, et al. The diagnostic significance of soluble CD163and soluble interleukin-2 receptor alpha -chains in macrophage activation syndrome and untreated new onset systemic juvenile idiopathic arthritis. Arthritis Rheum 2007; 56:965-971.

20.Moller HJ, Aerts, H, Gronbaek, Peterslund NA, Hyltoft Petersen P, Hornung N, et al. Soluble CD163: a marker molecule for monocyte/macrophage activity in disease.Scand J Clin Lab Investsuppl2002; 237:29-33.

21.Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, et al.HLH-2004: diagnostic and therapeutic guidelines for hemophagocyticlymphohistiocytosis. Pediatr Blood Cancer 2007:48:124-131.

22.Ravelli A, Magni-Manzoni S, Pistorio A, Bensana C, Foti T, Ruperto N, et al. Preliminary diagnostic guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. J Pediatr 2005; 146:598-604.

23.Ravelli A, Minoia F, Davi S, Anna Carin Horne, Angela Pistorio, Francesca Bovis, et al. 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis. Ann Rheum Dis 2016;75:481-489.

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24.Mouy R, Stephan JL, Pillet P, Haddad E, Hubert P, Prieur AM. Efficacy of cyclosporine A in the treatment of macrophage activation syndrome in juvenile arthritis: Report of five cases. JPaediatr1996; 129:750-754.

25.Coca A,BundyKW, Marston B, Huggins J, Looney RJ. Macrophage activation syndrome: serological markers and treatment with anti-thymocyte globulin.ClinImmunol 2009; 132:10-18.

26.BalamuthNJ, Nichols KE, Paessler M, Teachey DT. Use of Rituximab in conjunction with immunosuppressive chemotherapy for EBV-associated hemophagocyticlympho histiocytosis. J Paediatr Hematol Oncol 2007; 29:569-573.

PITFALLS OF LABORATORY INVESTIGATIONS IN RHEUMATOLOGY

*Raju Khubchandani **Anita Dhanrajani

Abstract: Laboratory tests are important adjuncts to a thorough history and physical examination in pediatric rheumatology. The importance of frugal ordering and cautious interpretation of tests cannot be overemphasized. This review describes laboratory tests used to assist diagnosis and monitoring of various paediatric rheumatologic diseases and the common errors in their interpretation.

Keywords: Rheumatology, Acute Phase Reactants, Autoantibodies, HLA-B27, Synovial fluid

Points to Remember

•Laboratory tests are not meant to replace a careful history and directed physical examination in pediatric rheumatology. They are valuable in assisting the physician in diagnosis and monitoring of complex rheumatological conditions.

•Extensive ordering of a ‘Rheumatological Panel’ can lead to confusion with regards to the diagnosis as well as unnecessary financial and emotional burden to the patient and family.

•Interpretation of the results must be done with extreme caution, bearing in mind normal physiological variations and contributory pathological conditions that can affect the test results. When in doubt, an expert consultation should be sought in the best interest of the patient.

*Director Pediatrics and in charge, Pediatric Rheumatology Clinic,

Jaslok Hospital and Research Centre, Mumbai. email: rajukhubchandani@yahoo.co.in

**Research fellow in Vasculitis, Hospital for Sick Children, University of Toronto, Canada.

References

1.Greer JP, Foerster J, Lukens NJ, Rodgers MG,

Paraskevas F, Glader B (Eds). Wintrobe’s Clinical Hematology. 11th Edn. Philadelphia: Lippincott Williams & Wilkins; 2003;p998.

2.Bridgen ML. Clinical utility of the Erythrocyte Sedimentation Rate. Am Fam Physician 1999; 60:1443- 1450.

3.Ravelli A, Minoia F, Davì S, Horne AC, Bovis F, Pistorio A, et al. 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis. Arthritis Rheumatol 2016; 68:566-576.

4.Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, et al. Diagnosis, Treatment, and Long- Term Management of Kawasaki Disease. Circulation 2004;110:2747-2771.

5.Ross E. Petty, Ronald M. Laxer, Carol B. Lindsley,

Lucy Wedderburn (Eds). Laboratory investigations. In: Textbook of pediatric rheumatology. 7th edn. Elsevier, Philadelphia 2016;pp117-126.

6.Position Statement, American College of Rheumatology. Methodology of testing for antinuclear antibodies. 2016. https://www.clinicalkey.com.ezproxy.library.ubc.ca/ www.rheumatology.org/practice/clinical/position/ ana_position_stmt.pdf .

7.Mehta J. Laboratory Testing in Pediatric Rheumatology. Pediatr Clin N Am 2012; 59:263-284.

BIOLOGIC DRUGS IN PEDIATRIC RHEUMATOLOGY

*Sathish Kumar T

Abstract: The past decade has seen growing use of biologic drugs for the treatment of pediatric rheumatic diseases. The widest range of such treatments is used for juvenile idiopathic arthritis (JIA), although biologics are sometimes given in more refractory cases of juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM) and vasculitis. The discovery of biologic therapies, their efficacy and relative safety in treating multiple rheumatologic conditions, improve quality of life for the patients. This review summarizes the current state of biologic drugs, their clinical application and their efficacy and safety in the pediatric age group.

Keywords: Biologic drugs, Pediatric rheumatology, Efficacy, Safety

Points to Remember

•‘Biologicals’ is a name for a pharmacological group of specific proteins with high molecular weight specifically targeting pro-inflammatory cytokines or cell surface antigens.

•TNF α blockers now are approved for rheumatoid factor positive and negative polyarthritis, extended oligoarthritis, enthesitis related arthritis and psoriatic arthritis.

•Abatacept is approved for polyarticular JIA refractory to TNF inhibitors.

•Systemic onset JIA can be treated with tocilizumab or on an off label basis with the IL1 inhibitors anakinra or canakinumab.

•Biologicals are used in other pediatric rheumatic disease like periodic fever syndromes, refractory cases of SLE, juvenile dermatomyositis and vasculitis.

*Professor of Pediatrics, Department of Pediatrics, Christian Medical College, Vellore.

email: sathishkumar@cmcvellore.ac.in

1.Isaacs JD. Antibody engineering to develop new antirheumatic therapies. Arthritis Res Ther 2009; 11:225.

2.Breda L, Del Torto M, De Sanctis S, Chiarelli F. Biologics in children’s autoimmune disorders: efficacy and safety. Eur J Pediatr 2011; 170:157-167.

3.Lovell DJ, Giannini EH, ReiffAet al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med 2000; 342:763–769.

4.Lovell DJ, Reiff A, Jones OY. Pediatric Rheumatology Collaborative Study Group. Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis.Arthritis Rheum 2006; 54:1987–1994.

5.Gerloni V, Pontikaki I, Gattinara M, Desiati F, Lupi E, Lurati A, et al. Efficacy of repeated intravenous infusions of an anti-tumor necrosis factor-á monoclonal antibody, infliximab, in persistently active, refractory juvenile idiopathic arthritis: results of an open-label prospective study. Arthritis Rheum 2005; 52:548–553.

6.Simonini G, Druce K, Cimaz R, Macfarlane GJ, Jones GT. Current evidence of anti-tumor necrosis factor α treatment efficacy in childhood chronic uveitis: a systematic review

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and meta-analysis approach of individual drugs. Arthritis Care Res 2014; 66:1073–1084.

7.Singh S, Sharma D, Suri D, Gupta A, Rawat A, Rohit MK. Infliximab is the new kid on the block in Kawasaki disease: a single-centre study over 8 years from North India.ClinExp Rheumatol 2016; 34: S134-138.

8.Sorrentino D, Marino M, Dassopoulos T, Zarifi D, Del Bianco T. Low dose Infliximab for Prevention of Postoperative Recurrence of Crohn’s Disease: Long Term Follow-Up and Impact of Infliximab Trough Levels and Antibodies to Infliximab. PLoS One 2015; 10: e0144900.

9.Ruperto N, Lovell DJ, Cuttica R, Woo P, Meiorin S, Wouters C, et al. Long-term efficacy and safety of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis: findings from an open-label treatment extension. Ann Rheum Dis 2010; 69:718–722.

10.Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K, et al. Pediatric Rheumatology Collaborative Study Group; Pediatric Rheumatology International Trials Organisation. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med 2008; 359: 810–820.

11.Ramanan AV, Dick AD, Benton D, Lacassagne SC, Dawoud D, Hardwick B, et al. A randomised controlled trial of the clinical effectiveness, safety and cost- effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis (SYCAMORE Trial). Trials 2014;15:14.

12.Pardeo M, Marafon DP, Insalaco A, Bracaglia C, Nicolai R, Messia V, De Benedetti F.Anakinra in Systemic Juvenile Idiopathic Arthritis: A Single-center Experience. J Rheumatol 2015; 42:1523-1527.

13.Koné-Paut I, Galeotti C. Anakinra for cryopyrin-associated periodic syndrome. Expert Rev ClinImmunol 2014;10: 7-18.

14.Lovell DJ, Gianinni EH, Kimura Y, Suzanne Li, Hashkes PJ, Reiff AO, et al. Preliminary evidence for bioactivity of IL-1 trap. (Rilonacept), a long acting il-1 inhibitor, in systemic juvenile idiopathic arthritis (SoJIA). Arthritis Rheum 2006;54:S325

15.Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB et al. Canakinumab in CAPS Study Group. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med 2009; 360:2416–2425.

16.Nicolino R, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med 2012; 367:2396–2406.

17.De Benedetti F, Brunner HI, Nicolino R, Kenwright A, Wright S, Calvo S, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med 2012; 367:2385–2395.

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18.Brunner HI, Nicolino R, Zbigniew Z, Caroline K, Olivier H, Andrew K, et al. Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis 2015;74:1110–1117.

19.Ruperto N, Lovell DJ, Quartier P, et al. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebocontrolled withdrawal trial. Lancet 2008;372:383–391.

20.Brunner H, Ruperto N, Tzaribachev N, Horneff G, Wouters C, Panaviene V, et al. A148: A multi-center, double-blind, randomized-withdrawal trial of subcutaneous golimumab in pediatric patients with active polyarticular course juvenile idiopathic arthritis despite methotrexate therapy: week 48 results. Arthritis Rheum 2014;66:S191–92.

21.PediatricArthritis Study of Certolizumab Pegol (PASCAL). Available from:https://clinicaltrials.gov/ct2/show/study/ NCT01550003?show_locs=Y%23locn. Initial trial of certolizumab in pediatric rheumatology- unpublished results. Accessed on 10.12.2016.

22.Alexeeva EI, Valieva SI, Bzarova TM, Semikina EL, Isaeva KB, Lisitsyn AO, et al. Efficacy and safety of repeat courses of rituximab treatment in patients with severe refractory juvenile idiopathic arthritis. Clin Rheumatol 2011; 30:1163–1172.

23.Lehman TJ, Singh C, Ramanathan A, Alperin R, Adams A, Barinstein L, et al. Prolonged improvement of childhood onset systemic lupus erythematosus following systematic administration of rituximab and cyclophosphamide. Pediatric Rheumatol Online J 2014;12:3.

24.Dale RC, Brilot F, Duffy LV, Twilt M, Waldman AT, Narula S, et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology 2014;83:142–150.

25.Bader-Meunier B, Decaluwe H, Barnerias C, Gherardi R, Quartier P, Faye A, et al. Safety and efficacy of rituximab in severe juvenile dermatomyositis: results from 9 patients from the French Autoimmunity and Rituximab Registry. J Rheumatol 2011; 38:1436–1440.

MANAGEMENT OF ADOLESCENT ANXIETY DISORDERS

Venkateswaran R

Abstract: Anxiety disorder is one of the most common mental health problemsamong adolescents. The types of anxiety disorders include generalized anxiety disorder, specific phobia, social phobia, selective mutism, panic disorder and agoraphobia. They commonly present with fear, worry, physical symptoms, avoidance and cognitive symptoms. It should be differentiated from developmentally normal fear. The varied presentation creates challenges in diagnosis and hence, a high index of suspicion is required to diagnose anxiety disorders. Early identification and treatment results in good clinical outcomes. Both psychotherapy and medications have been found to be beneficial in their management.

Keywords: Anxiety disorders, Adolescents, Child psychiatry.

*Consultant Child and Adolescent Psychiatrist, Dr.Mehta’s Children’s Hospital, Chennai. email: venkateswaranrajaraman@gmail.com

Points to Remember

•Anxiety disorder in adolescents is a common psychological problem, where high index of suspicion is required for early diagnosis and reduction of morbidity.

•It can present as unexplained physical symptoms, unnecessary worries, academic deterioration and school refusal.

•Diagnosis is mainly clinical though thyroid disorders, cardiac arrhythmias and complex partial seizures are to be considered in differential diagnosis.

•Cognitive behavioural therapy is the first line of treatment.

•Medications commonly used are SSRIs including sertraline, fluoxetine and escitalopram.

References

1.Connolly SD, Bernstein GA, Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with anxiety disorders. J Am Acad Child Adolesc Psychiatry 2007;46:267–283.

2.APA. Diagnostic and Statistical Manual of Mental Disorders. 5thedn. Washington: American Psychiatric Association; 2013.

3.Nair MKC, Russell PSS, Krishnan R, Russell S, Subramaniam VS, Nazeema S, et al. ADad 4: the symptomatology and clinical presentation of Anxiety Disorders among adolescents in a rural community population in India. Indian J Pediatr 2013;80:S149–154.

4.Nair MKC, Russell PSS, Mammen P, Abhiram Chandran R, Krishnan R, Nazeema S, et al. A Dad 3: The Epidemiology of Anxiety Disorders Among Adolescents in a Rural Community Population in India. Indian J Pediatr 2013;80(S2):144–148.

5.Russell PSS, Nair MKC, Mammen P, Chembagam N, Vineetha KS, Shankar SR, et al. ADad 5: the co-morbidity in Anxiety Disorders among adolescents in a rural community population in India. Indian J Pediatr 2013;80Suppl 2:S155–159.

6.McGrath LM, Weill S, Robinson EB, Macrae R, Smoller JW. Bringing a developmental perspective to anxiety genetics. DevPsychopathol 2012;24:1179–1193.

Indian Journal of Practical Pediatrics

7.Svihra M, Katzman MA. Behavioural inhibition: A predictor of anxiety. Paediatr Child Health 2004;9:547– 550.

8.Muris P, van BrakelAML,ArntzA, Schouten E. Behavioral Inhibition as a Risk Factor for the Development of Childhood Anxiety Disorders: A Longitudinal Study. J Child Fam Stud 2011;20:157–170.

9.Rapee RM, Heimberg RG. A cognitive-behavioral model of anxiety in social phobia. Behav Res Ther 1997;35:741– 756.

10.Brumariu LE, Kerns KA. Mother-Child Attachment and Social Anxiety Symptoms in Middle Childhood. J Appl Dev Psychol 2008;29:393–402.

11.Muris P, Meesters C, Merckelbach H, Sermon A, Zwakhalen S. Worry in normal children. J Am Acad Child Adolesc Psychiatry 1998;37:703–710.

12.Masi G, Mucci M, Favilla L, Romano R, Poli P. Symptomatology and comorbidity of generalized anxiety disorder in children and adolescents. Compr Psychiatry 1999;40:210–215.

13.Bergman RL, Piacentini J, McCracken JT. Prevalence and description of selective mutism in a school-based sample. J Am Acad Child Adolesc Psychiatry 2002;41:938–946.

14.Woodward LJ, Fergusson DM. Life course outcomes of young people with anxiety disorders in adolescence. J Am Acad Child Adolesc Psychiatry 2001;40:1086–1093.

15.Russell PSS, Nair MKC, Russell S, Mammen P, Tsheringla S, Chandran A, et al. ADad 10: the impairment in Anxiety Disorders among adolescents in a rural community population in India. Indian J Pediatr 2013;80 Suppl 2:S181–185.

16.Storch EA, Ehrenreich May J, Wood JJ, Jones AM, De Nadai AS, Lewin AB, et al. Multiple informant agreement on the anxiety disorders interview schedule in youth with autism spectrum disorders. J Child Adolesc Psychopharmacol 2012;22:292–299.

17.Larson MK, Walker EF, Compton MT. Early signs, diagnosis and therapeutics of the prodromal phase of schizophrenia and related psychotic disorders. Expert Rev Neurother 2010;10:1347–1359.

18.Spence SH, Donovan C, Brechman-Toussaint M. The treatment of childhood social phobia: the effectiveness of a social skills training-based, cognitive-behavioural intervention, with and without parental involvement. J Child Psychol Psychiatry2000;41:713–726.

19.Dow SP, Sonies BC, Scheib D, Moss SE, Leonard HL. Practical guidelines for the assessment and treatment of selective mutism. J Am Acad Child Adolesc Psychiatry 1995;34:836–846.

20.Kodish I, Rockhill C, Varley C. Pharmacotherapy for anxiety disorders in children and adolescents. Dialogues ClinNeurosci 2011;13:439–452.

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21.Fluvoxamine for the treatment of anxiety disorders in children and adolescents. The Research Unit on Pediatric Psychopharmacology Anxiety Study Group. N Engl J Med 2001;344:1279–1285.

22.Compton SN, Walkup JT, Albano AM, Piacentini JC, Birmaher B, Sherrill JT, et al. Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods. Child Adolesc Psychiatry Ment Health 2010;4:1.

DIAGNOSIS AND MANAGEMENT OF INFANTS LESS THAN SIX MONTHS OLD WITH SEVERE ACUTE MALNUTRITION

*Praveen Kumar **Shivani Rohatgi

Abstract: Severe acute malnutrition (SAM) is increasingly being recognized in infants who are less than 6 months of age with a higher risk of mortality and intellectual impairment compared to older children. There are fundamental differences in criteria for identification and admission due to physiological differences between young infants and older children. Principles of management essentially remain the same as for children more than 6 months with the exception of feeding management. All possible efforts should be directed towards establishment of exclusive breastfeeding by improving feeding practices and relactation by supplementary suckling techniques (SST) in these infants. If there are no prospects of breastfeeding, rehabilitation with diluted F-100 (F-100D) in place of F-100 should be done.

Keywords: Severe acute malnutrition, Infant less than six months, Supplementary suckling technique

*Professor,

Department of Pediatrics

*Consultant

NRC, PPMU

Kalawati Saran Children’s Hospital, New Delhi. email: pkpaed@gmail.com

Points to Remember

•Severe acute malnutrition (SAM) is increasingly being recognized in infants who are less than 6 months of age.

•Infants less than 6 months with SAM are identified by their W/L < - 3SD score and or presence of bilateral pitting edema. MUAC cut off is not well defined for this age group.

•Basic principles of management (Ten steps) remain same as for more than 6 months old age, however focus is on establishing exclusive breastfeeding unless there is no prospect of breastfeeding.

References

1.UNICEF, WHO, World Bank. UNICEF-WHO-World Bank Joint child malnutrition estimates. New York, Geneva & Washington DC, UNICEF, WHO & World Bank, 2012.

2.Caballero B. Early nutrition and risk of disease in the adult. Public Health Nutr.2001;4: 1335-1336.

3.WHO. Guideline: Updates on the management of severe acute malnutrition in infants and children. Geneva, World Health Organization; 2013. http://www.who.int/nutrition/ publications/guidelines/updates_management_SAM_ infantandchildren/en/

4.Kerac M, Blencowe H, Grijalva-Eternod C, McGrath M, Shoham J, Cole TJ, et al. Prevalence of wasting among under 6-month-old infants in developing countries and implications of new case definitions using WHO growth standards: a secondary data analysis. Arch Dis Child 2011; 96:1008-1013.

5.Patwari AK, Kumar S, Beard J.Undernutrition among infants less than 6 months of age: an underestimated public health problem in India. Matern Child Nutr 2015;11(1): 119-126.

6.Singh P, Kumar P, Rohatgi R, Basu S, Aneja S. Experience and Outcome of Children with Severe Acute Malnutrition Using Locally Prepared Therapeutic Diet. Indian J Pediatr 2016; 83:3-8.

7.Ministry of Health and Family Welfare, Government of India. Operational guidelines on facility-based management of children with severe acute malnutrition. National Rural Health Mission, Ministry of Health and Family Welfare, New Delhi, India, 2011.

8.Briend A, Maire B, Fontaine O, Garenne M. Mid- upper arm circumference and weight for height to identify high-

VITAMINS AND MINERALS SUPPLEMEN- TATION IN PEDIATRICS

*Jeeson C Unni **Ranjit Baby Joseph **Bijal Jitendrabhai Rughani

Abstract: Deficiency of vitamins and minerals is common in children in India. Pediatricians tend to use vitamin and mineral supplement empirically and these medications are available over the counter without prescription. There are no definite guidelines regarding the dose of many of the vitamins required and different preparations come with different composition which makes it difficult to standardise. This article reviews the evidence for use of vitamins and minerals in children, a survey of preparations available in the Indian market and their relevance in regular supplementation.

Keywords: Multivitamins, Minerals, RDA

*Editor-in-Chief, IAP Drug Formulary,

Associate Consultant in Pediatrics e-mail: jeeson955@gmail.com

**Specialist in Pediatrics, Aster Medcity, Kochi.

References

1.Kotecha PV, Lahariya C. Micronutrient Supplementation and Child Survival in India. Indian J Pediatr 2010; 77 (4): 419-424.

2.Sanghvi T, Ameringen MV, Baker J, John Fiedler J, guest editors. Vitamin and mineral deficiencies technical situation analysis: a report for the Ten Year Strategy for the Reduction of Vitamin and Mineral Deficiencies. http://www.gainhealth.org/wp-content/uploads/2014/05/ 10.-Food-and-Nutrition-Bulletin.-10-Year-Strategy- Supplement.pdf.

3.UNICEF. State of the world children 2008: Child Survival:

UNICEF; New York: 2008

4.Nutrient requirements and recommended dietary allowances for Indian. A report of the expert group of the Indian Council of the Medical Research 2009; pp332.

5.Nair KM, Iyengar V. Iron content, bioavailability & factors affecting iron status of Indians. Indian J Med Res 2009; 130: 634-645.

6.Kotecha PV. Nutritional anemia in young children with focus on Asia and India. Indian J Community Med 2011; 36:8-16.

7.IAP Drug Formulary 2015. 4th edn. (eds) Jeeson C Unni, Menon PSN, Nair MKC, Bansal CP. Publication of IAP. Pixel Studio, Cochin: 2015;p139.

8.Bayraktar UD, Soley Bayraktar S. Treatment of iron deficiency anemia associated with gastrointestinal diseases. World J Gastroenterol 2010; 16(22): 2720–2725.

9.Holick MF, Vitamin D deficiency. N Engl J Med 2007; 357:266-281.

10.Harinarayanan CV, Joshi SR. Vitamin D status in India – Its implications and remedial measures. J Assoc Physicians 2009; 57: 40-48.

11.Marwaha RK, Sripathy G. Vitamin D and Bone mineral density of healthy school children in northern India. Indian J Med Res 2008; 127:239-244.

12.Ritu G, Gupta A. Vitamin D Deficiency in India: Prevalence, Causalities and Interventions. Nutrients 2014; 6:729–775.

13.Balasubramanian S, Dhanalakshmi K, Amperayani S. Vitamin D deficiency in childhood- A review of current guidelines in the diagnosis and management. Indian Pediatr 2013; 50: 669-675.

Indian Journal of Practical Pediatrics

14.Balasubramanian S. Vitamin D deficiency in breast fed infants & need for routine vitamin D supplementation. Indian J Med Res. 2011; 133:250–252.

15.IAP Drug Formulary 2015. 4th edn. eds Jeeson C Unni, Menon PSN, Nair MKC, Bansal CP. Publication of IAP. Pixel Studio, Cochin: 2015;p527.

16.Teotia SPS, Teotia M. Nutritional bone disease in Indian population. Indian J Med Res. 2008; 127(3):219-228.

17.Bhatia V. Dietary calcium intake- a critical reappraisal. Indian J Med Res 2008; 127: 269-273.

18.Khounnorath S, Chamberlain K, Taylor AM, Soukaloun D, Mayxay M, Lee SJ, Phengdy B, Luangxay K, Sisouk K, Soumphonphakdy B, Latsavong K, Akkhavong K, Nicholas J, White, Paul N. Newton Clinically Unapparent Infantile Thiamin Deficiency in Vientiane, Laos. PLoS Negl Trop Dis 2011; 5: e969. 10.1371/journal.pntd.0000969

19.Rao SN, Chandak GR. Cardiac beriberi: often a missed

diagnosis. J Trop Pediatr 2010; 56(4): 284–285.10.1093/ tropej/fmp108.

20.Fattal-Valevski A, Kesler A, Sela BA, Nitzan-Kaluski D, Rotstein M, Mesterman R, et al. Outbreak of life- threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula. Pediatrics 2005; 115(2): e233–238.10.1542/peds.2004-1255.

21.Barennes H, Sengkhamyong K, René JP, Phimmasane M. Beriberi (Thiamine deficiency) and high infant mortality in Northern Laos. PLoS Negl Trop Dis 2015; 9(3) : e0003581.10.1371/journal.pntd.0003581.

22.Sriram K, Manzanares W, Joseph K. Thiamine in nutrition therapy. Nutr Clin Pract 2012; 27(1): 41–50.10.1177/ 0884533611426149.

23.Luxemburger C, White NJ, ter Kuile F, Singh HM, Allier- Frachon I, Ohn M, et al. Beri-beri: the major cause of infant mortality in Karen refugees. Trans R Soc Trop Med Hyg 2003; 97: 251–255.10.1016/S0035-9203(03)90134-9

24.Taneja S, Strand TA, Kumar T, Mahesh M, Mohan S, Manger MS, Refsum H, Yajnik CS, Bhandari N. Folic acid and vitamin B-12 supplementation and common infections in 6-30-mo-old children in India: A randomized placebo-controlled trial. J Clin Nutr 2013; 98:731-737.

25.Kvestad I, Taneja S, Kumar T, Hysing M, Refsum H, Yajnik CS, et al. PLoS One 2015; 10(6): e0129915. doi: 10.1371/journal.pone.0129915. eCollection 2015.

26.Tandon S, Moulik NR, Kumar A, Mahdi AA, Kumar A. Effect of Pre-treatment Nutritional Status, Folate and Vitamin B12 Levels on Induction Chemotherapy in Children with Acute Lymphoblastic Leukemia. Indian Pediatr 2015; 52:385-389

27.Chandra J. Megaloblastic anemia: back in focus. Indian J Pediatr 2010; 77:795-799.

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28.IAP Drug Formulary 2015. 4th edn. (eds) Jeeson C Unni, Menon PSN, Nair MKC, Bansal CP. Publication of IAP. Pixel Studio, Cochin: 2015;p526.

29.Bhan MK, Sommenfelt H, Strand T. Micronutrient Deficiency in children. Br J Nutr 2001; 85:S199-S203.

30.Gibson RS, Ferguson EL. Nutrition intervention strategies to combat zinc deficiency in developing countries. Nut Res Rev 1998; 11:115-131.

31.Bhandari N, Bahl R, Taneja S. Effect of micronutrient supplementation on linear growth of children. Br J Nutr 2001; 85: Supp 2:S131-S137.

32.WHO. Clinical management of acute diarrhoea. WHO, Geneva, 2004.

33.IAP Drug Formulary 2015. 4th edn. (eds) Jeeson C Unni, Menon PSN, Nair MKC, Bansal CP. Publication of IAP. Pixel Studio, Cochin: 2015;p530.

34.Haider BA, Bhutta ZA. Neonatal vitamin A supplementation for the prevention of mortality and morbidity in term neonates in developing countries. Cochrane Database Syst Rev 2011; 10: CD006980. doi: 10.1002/14651858.CD006980.pub2.

35.IAP Drug Formulary 2015. 4th edn. (eds) Jeeson C Unni, Menon PSN, Nair MKC, Bansal CP. 2015, Publication of IAP. Pixel Studio, Cochin: p36

36.Current index of medical specialties. UBM Medica India Private Limited; Oct 2015-Jan 2016:pp379-420.

CUTANEOUS MANIFESTATIONS OF CONNECTIVE TISSUE DISORDERS

*Madhu R

Abstract: Connective tissue disorders or collagen vascular disorders are inflammatory disorders of the connective tissue with multisystem involvement.They are characterized by the presence of specific and non-specific cutaneous manifestations. These disorders which may present with vague symptoms like prolonged fever and fatigue, tend to have a chronic course with remissions and exacerbations. Specific dermatological findings pave the way for early diagnosis and prompt treatment. This article focuses on the dermatological manifestations and treatment of the most common rheumatic diseasesof childhood namely lupus erythematosus, systemic sclerosis, dermatomyositis and juvenile idiopathic arthritis.

Keywords: Childhood lupus erythematosus, Juvenile systemic sclerosis, Dermatomyositis, Juvenile idiopathic arthritis, Cutaneous manifestations

Points to Remember

•Systemic lupus erythematosus, systemic sclerosis, dermatomyositis and juvenile idiopathic arthritis are connective disorders which have many specific cutaneous manifestations.

•Malar rash, discoid rash and photosensitivity reaction are specific for systemic lupus erythematosus.

•Induration of the skin, morphea and vascular lesions are pathognomonic of juvenilesystemic sclerosis.

•Gottron’s papules and heliotrope rashare characteristic skin lesions of juvenile dermatomyositis.

•Awareness of the specific and non-specific dermatological features of these conditions will enable the pediatrician to refer the child early for prompt diagnosis and treatment.

References

1.Chiewchengchol D, Murphy R, Edwards SW, Beresford MW.Mucocutaneousmanifestations in juvenile-onset systemic lupus erythematosus: A reviewof literature. Pediatr Rheumatolonline J 2015; 13:1.Available from: URL:http://www.ped-rheum.com/content/13/1/1

2.Laxser RM, Benseler SM. Pediatric systemic lupus erythematosus, dermatomyositis, scleroderma and vasculitis. In: Firestein GS, Budd RC, Gabriel SE, Mcinnes

IB, O’Dell JR (eds). Kelley’sTextbook of Rheumatology, vol 2, 9th edn. Elsevier Saunders, Philadelphia 2011;pp1771-1800e9.

3.HabibiS, Saleem Ma, Ramanan AV. Juvenile Systemic Lupus Erythematosus: Review of clinical features and management. Indian Pediatr 2011;48:879-887.

4.Barnett NK, Weston WL, Krol A, Shishov M, Ede K, Shulman ST, et al. Rheumatic diseases in children, autoinflammatory syndromes in children, and selected

systemic diseases with skin manifestations. In: Schachner LA, Hansen RC, (eds). Pediatric dermatology, vol.2, 4th edn. Mosby Elsevier,Philadelphia2011;pp1269-1330.

Indian Journal of Practical Pediatrics

5.Dung NTN,Loan HT, Nielsen SA, Zak M, Petersen FK. Juvenile systemic lupus erythematosus onset patterns in Vietnamese children: A descriptive study of 45 children. Pediatr Rheumatol 2012; 10:38.1-5. Available from: URL:http://www.ped-rheum.com/content/10/1/38.

6.Collagen vascular diseases.In: PallerAS, Mancini AJ (eds). Hurwitz clinical pediatric dermatology. 4th edn. Elsevier Saunders, 2011; pp 497-527.

7.Gulay and Dans: Clinical presentations and outcomesof Filipino juvenile systemic lupus erythematosus. Pediatric Rheumatology2011; 9:7.Available from:URL:http:// www.pedrheum.com/content/9/1/7

8.LevyDM, Kamphuis S. Systemic Lupus Erythematosus in Children and Adolescents Pediatr Clin North Am 2012; 59(2): 345–364.

9.Dickey BZ, Holland KE, Drolet BA, Galbraith SS, Lyon VB, Siegel DH, et al. Demographic and clinical characteristics of cutaneous lupus erythematosus at a pediatric dermatology referral centre. BrJDermatol 2013; 169:428-433.

10.Thabet Y, Mankaï A, Achour A, Sakly W, Trabelsi A, Harbi A, et al. Systemic Lupus Erythematosus in Children: A Study about 37 Tunisian Cases. J Clin Cell Immunol 2014 5: 192.

11.Misra R, Singh G, Aggarwal P, Aggarwal A. Juvenile onset systemic sclerosis: a single center experienceof 23 cases from Asia. Clin Rheumatol 2007; 26:1259–1262.

12.Hedrich CM, Fiebig B, Hahn G, Suttorp M, Gahr M. Presentations and Treatment of Childhood Scleroderma: Localized Scleroderma, Eosinophilic Fasciitis, Systemic Sclerosis, and Graft-Versus-Host Disease. Clin Pediatr 2011;50: 604–614.

13.Denton ECP, Smith CD. Juvenile-Onset Systemic Sclerosis: Children are not small adults. Rheumatology 2009; 48:96–97.

14.Yuen LK, Lai WM, Tse KC, MC Chiu. Two Cases of Juvenile Systemic Sclerosis andLiterature Review. HK J Paediatr (new series) 2007; 12:221-226.

15.Russo RAG, Katsicas MM. Clinical characteristics of children with Juvenile Systemic Sclerosis:follow-up of 23 patients in a single tertiary center. Pediatr Rheumatol 2007, 5:6. Available from:URL:http://www.ped-rheum.com/ content/5/1/6

16.Torok KS. Pediatric Scleroderma -Systemic and Localized Forms. Pediatr Clin North Am 2012; 59(2): 381–405.

17.Martini G, Foeldvari I, Russo R, Cuttica R, Eberhard A, Ravelli A, et al. Systemic sclerosis in childhood: clinical and immunologic features of 153 patients in an international database. Arthritis Rheum 2006;54:3971- 3978.

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18.YadavA, Yadav TP, Gupta V. Juvenile Systemic Sclerosis.J Indian Acad Clin Med2011; 12: 128-133.

19.Dolijanovic SP, Damjanov N, Ostojic P, Gordana Sus¡ic´, Stojanovic R , Gacic D, et al. The Prognostic value of nailfold capillary changes for the development of connectiveTissue Disease in Children and Adolescents withPrimary Raynaud Phenomenon: A Follow-up Study of 250 Patients. Pediatr Dermatol 2006; 23: 437–442.

20.Wedderburn LR, Rider LG. Juvenile dermatomyositis: New developments inpathogenesis, assessment and treatment. Best Pract Res Clin Rheumatol 2009;23: 665–678.

21.Rider LG, Lindsley CB, Cassidy JT. Juvenile

dermatomyositis. In: Cassidy JT, Petty RE, Laser RM, Lindsley CB(eds) Textbook of Pediatric dermatology. 6th edn. Saunders Elsevier health sciences; Philadelphia 2010;pp375-414.

22.Gordon P, Creamer D. Dermatomyositis. Griffiths CEM,

Barker J, Bleiker T, Chalmers R, Creamer D.(eds). Rook’s Textbook of dermatology. 9th edn. West Sussex: Wiley Blackwell; 2016; pp 118.1– 118.17.

23.Tansley SL, McHugh NJ, Wedderburn LR. Adult and juvenile dermatomyositis: are the distinct clinical features explained by our current understanding of serological subgroups and pathogenic mechanisms?Arthritis Res Ther 2013, 15:211. Available from: URL:http://arthritis- research.com/content/15/2/211.

24.Gowdie PJ, Allen RC,Kornberg AJ, Akikusa JD. Clinical features and disease course of patients with juveniledermatomyositis.Int J Rheum Dis 2013; 16: 561– 67.

25.Mahesh A, Rajendran CP, Rukmangatharajan S, Rajeswari, Vasanthy N,Parthiban M. Juvenile dermatomyositis- Clinical and laboratory profile. J Indian Rheumatol Assoc 2005; 13:4-7.

26.Chickermane PR, Mankad D, Khubchandani RP. Disease Patterns of Juvenile Dermatomyositis from Western India. Indian Pediatr2013; 50:961-963.

27.Singh S, Bansal A. Twelve years’ experience of Juvenile dermatomyositis in North India. Rheumatol Int 2006; 26:510–515.

28.Viswanathakumar HM, Kumar GV. Study of clinical spectrum of juvenile idiopathic arthritis in children in atertiary referral hospital.Curr Pediatr Res 2014;18:21-25.

LOCAL ANESTHETICS FOR BEDSIDE PEDIATRIC SURGICAL PROCEDURES

*Krishnan N **Shanthimalar R

Abstract: Pain control is an important part in the management of children with injuries. Proper understanding of the commonly available local anesthetic drugs, their common complications, early detection of toxicity and safe management are essential. The purpose of the present review is to discussand to inform non- anesthesiologist physicians and other medical persons who may be using local anesthetic drugs for childrento alleviate pain for minor procedures.

Keywords: Local anesthesia, Lignocaine, Bupivacaine, Intra lipids, Toxicity.

Points to Remember

•Calculate the maximal dose of local anesthetic that you are going to use before starting the procedure.

•Always aspirate very slowly before injecting

•Keep resuscitating equipments like ambu bag, drugs ready before even small procedure.

Bibliography

1.Lönnqvist PA. Toxicity of local anesthetic drugs: a pediatric perspective. Paediatr Anaesth 2012;22:39-43.

2.A Practice of Anesthesia for Infants and Children. Coté CJ, Lerman J, Toders D (eds), 4thedn, Elesevier, Philadelphia 2009.

3.Stoelting’s Handbook of Pharmacology and Physiology

in Anesthetic Practice. Stoelting RK, Flood P, Rathmell JP, Shafer S (eds), 3rdedn, Wolters Kluwer Health, Philadelphia 2015.

4.Jankovic. Use of Local Anesthetics in Regional Anesthesia and Pain Therapy. In : Regional Nerve Blocks in Anesthesia

and Pain Therapy Traditional and Ultrasound-Guided Techniques, Jankovic, Danilo, Peng, Philip (eds), 4thedn, Springer International publishing, Switzerland, 2015; pp3-16.

5.Smith’sAnesthesia for Infants and Children. Davis PJ, Cladis FP, Motoyama EK, (eds), 8thedn, Elsevier, Philadelphia, 2011.

6.Local anesthetics. In: Morgan and Mikhail’s Clinical

Anesthesiology. Butterworth J, Mackey DC, Wasnick J (eds), 5thedn, Mc Graw Hill Education, Lange, US, 2013.

7.Cave G, Griffiths WH, Harvey M, Meek T, Picard J, Short T, Weinberg G (working group). AAGBI Safety Guideline. The Association of Anaesthetists of Great Britain & Ireland, 2010.

A RARE CASE OF VIRGINAL BREAST HYPERTROPHY IN A 12-YEAR-CHILD TREATED WITH REDUCTION MAMMO- PLASTY

*Supriya Kushwah **Anitha S Prabhu **Nithu N

***Satish Bhat

Abstract: Virginal breast hypertrophy is an idiopathic rare condition found in peri-pubertal period and is characterized by massive breast hypertrophy without any hormonal or CNS cause.

Virginal breast hypertrophy should be one of differential diagnosis of massive breast hypertrophy. Both physical, psychological symptoms and growth phase should be the basis of consideration in management.

Keywords:Virginal breast hypertrophy, Reduction mammoplasty, Gigantomastia

References

1.Grifth JR. Virginal breast hypertrophy. J Adolesc Health Care 1989;10:423–432.

2.Durston, W. Concerning a very sudden and excessive swelling of a women‘s breasts. (Phil Trans, vol. IV, for Anno 1669, pp 1047–1049) Royal Society, London; 1670.

3.Fisher W, Smith J W. Macromastia during puberty. PlastReconstr Surg. 1971;47:445–451.

4.Gliosci A, Presutti F. Virginal gigantomastia: validity of combined surgical and hormonal treatments. Aesthetic PlastSurg 1993;17:61-65.

5.Uribe Barreto A. Juvenile mammary hypertrophy. PlastReconstrSurg 1991;87:583–584.

6.Craig HR. Penicillamine induced mammary hyperplasia: report of a case and review of the literature. J Rheumatol 1988;15:1294-1297.

7.Ali E, Athanasopoulos PG, Forouhi P, Malata CM. Cowden syndrome and reconstructive breast surgery: case reports and review of the literature. JPlast Reconstr Aesthet Surg 2011;64:545–549.

8.Ryan RF, Pernoll ML. Virginal hypertrophy. Plast Reconstr Surg 1985;75:737-742.

9.Ship AG, Shulman J. Virginal and gravid mammary gigantism: recurrence after reduction mammaplasty. Br J PlastSurg 1971;24:396-401.

10.Hedberg K, Karlsson K, Lindstedt G, Gigantomastia during pregnancy: effect of a dopamine agonist. Am J Obstet Gynecol 1979;133:928-931.

SEXUALLY TRANSMITTED IN TEENS - REPORT OF THREE CASES

*Kumar Parimalam **Hemamalini R

References

1.Stamm WE, Handsfield HH, Rompalo AM, Ashley RL, Roberts PL, Corey L. The association between genital ulcer disease and acquisition of HIV infection in homosexual men. J Am Med Assoc 1988; 260:1429-1433.

Abstract: Teenagers have special health related vulnerabilities and the recognition of adolescent healthcare has been growing in the recent years. According to WHO, sexual and reproductive ill health is one of the major causes of morbidity and mortality among this age group. Many adolescents are sexually active and at risk of contracting sexually transmitted infection [STI]. STIs are associated with an increased risk of acquiring HIV infection. Awareness about STIs will help detect and treat them early to prevent complications and spread of infection to the society. We report three adolescent school boys with STI in whom early diagnosis was missed.

Keywords: Adolescent, STI, Wart, Chancre

2.Silber TJ, Niland NF. The clinical spectrum of syphilis in adolescence. J Adolesc Health Care 1984; 5:112-116.

3.Youk EG, Ku JL, Park JG. Detection and typing of human papillomavirus in anal epidermoid carcinomas: sequence variation in the E7 gene or human papillomavarius type

16.Dis Colon Rectum 2001; 44: 236–242.

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of progress. JAMA 1988; 259: 570–572.

6.Widdice LE, Moscicki AB. Updated guidelines for Papanicolaou tests, colposcopy, and human papillomavirus testing in adolescents. J Adolesc Health 2008;43: S41–S51.

7.Conley LJ, Ellerbrock TV, Bush TJ, Chiasson MA, Sawo D, Wright TC. HIV-1 infection and risk of vulvovaginal and perianal condylomataacuminata and intraepithelial neoplasia: a prospective cohort study. Lancet 2002; 359:108-113.

8.LeBlanc KA, Cole P, Grafton W, Goldman LI. Perianal squamous cell carcinoma in situ. Sur Rounds 1985;8:72-

ACUTE PANCREATITIS: A RARE COMPLICATION IN AN EPILEPTIC CHILD ON VALPROATE THERAPY

*Sangeetha Yoganathan **Suresh Babu Pasangulapati

***Maya Thomas

*Associate Professor **Assistant Professor

***Professor

Department of Neurological Sciences Christian Medical College Vellore, Tamil Nadu.

References

1.Camfield PR, Bagnell P, Camfield CS. Pancreatitis due to valproate acid. Lancet 1979; 1:1198-1199.

2.Hamad AE, Fawzi ME. Valproate associated acute pancreatitis. Neurosciences (Riyadh). 2000; 5:156-158.

3.Werlin SL, Fish DL. The spectrum of valproic acid- associated pancreatitis. Pediatrics. 2006; 118:1660-663.

4.Binek J, Hany A, Heer M. Valproic-acid-induced pancreatitis: Case report and review of the literature. J Clin Gastroenterol. 1991;13:690-693.

5.Gerstner T, Busing D, Bell N,Longin E, Kasper JM, Klostermann W, et al. Valproic acid-induced pancreatitis: 16 new cases and a review of the literature. J Gastroenterol. 2007;42:39-48.

Acute flaccid paralysis - Approach (101)

Acute kidney injury (43)

Anti Epileptic drugs (36)

Asthma - GINA 2015 guidelines (5)

Ataxia – Approach (109)

Biologic drugs in rheumatology (347)

Bleeding child - Approach (237)

Breast hypertrophy (387)

Chikungunya (270)

Cholelithiasis - Fetal (212)

Demyelinating disorders (122)

Dermatology

-Hair loss (78)

-Cutaneous adverse drug reactions (279)

-Cutaneous manifestations connective tissue disorders ( )

-Nutritional dermatosis (204)

Developmental disorders – Early recognition (57)

Severe acute malnutrition infants less than six months old (361)

Difficult pediatric airway (193)

Drug profile

-Antacids and H2 antagonists (200)

-Proton pump inhibitors (74)

-Suppositories (274)

-Vitamins and minerals supplementation in pediatrics (367)

Dysfunctional voiding (83) Epileptic encephalopathies (151)

Febrile child - work up for connective tissue disorders (299) Feeding - low birth weight neonates (21) Hemophagocytic lymphohistiocytosis (243) Hirschsprung’s disease (89)

Waardenburg syndrome (89)

Humidified highflow nasal cannula oxygen therapy (52) Hydrocephalus (144)

Hypoxic ischemic encephalopathy (180) Inflammatory bowel disease (29)

Intestinal strongyloidiasis - in immunocompetent (288) Juvenile idiopathic arthritis (306)

Kawasaki disease - update (320)

Leukemia treatment - Management of common problems (254)

Local anesthetics bedside surgical procedures (380) Macrophage activation syndrome (335) Malignancies - Atypical presentation (249) Adolescent anxiety disorders management (354) Migraine (186)

Muscle disorders - Approach (136)

Neurometabolic disorders - diagnostic approach (158) Nutritional anemia (227)

Laboratory investigations in rheumatology (——) Pitfalls (340)

Primary immunodeficiency disorders (266) Rabies Vaccine (67)

Radiology

-Dysplasias (87)

-Osteomyelitis (286, 384)

-Acutely swollen limb (210)

Solid tumors - Recent advances in managment (258)

A rare case of virginal breast hypertrophy treated with reduction mammoplasty (387)

Sexually trasmitted infections in teens (390) Systemic lupus erythematosus Thalasssemia – Prevention (232) Tracheomalacia - vascular anomaly (290) Traumatic brain injury (171)

Vasculitis syndromes (328) WHO dengue guidelines (13) Zinc - health and disease (62)