NUTRITIONAL ANEMIA

*Thilagavathi V

Abstract: Nutritional anemia in children is a common deficiency disorder and iron deficiency is the most common cause manifesting as either isolated or combined deficiency. Iron plays an essential role in hemoglobin synthesis and B 12 and folate in DNA synthesis. Inadequate intake of foods rich in iron, B12 and folate, malabsorption, infections and inflammation cause the state of deficiency. It is important to identify the specific cause of anemia and treat appropriately.

Keywords: Anemia, Nutritional, Iron, Folate, B12, Child.

Points to Remember

•Iron deficiency is the most common cause of nutritional anemia both as isolated or as combined deficiency.

•Serum ferritin along with C-reactive protein serves as the best indicator of body iron stores.

•Iron deficiency anemia is treated with oral iron supplements in appropriate form, dose and duration.

•Folate and B12 deficiency during infancy have adverse impact on the developing brain.

•Oral vitamin B 12 is as effective as parenteral B12.

References

*Prof. of Pediatrics,

SRM Medical College Hospital and Research Centre and Retired Associate Prof. of Pediatric Hematology, Institute of Child Health and Hospital for Children, Chennai.

email: drthilagavathi@gmail.com

1.Mother and child nutrition in the tropics and subtropics; Nutritional Anemias. Chapter 9, J Trop Pediatr 339-355.

2.Gomber S, Bhawna, Madan N, Lal A, Kela K. Prevalence and etiology of nutritional anemia among school children of urban slums; Indian J Med Res 2003;118: 167 -171.

3.Koury MJ, Ponka P. New insights into erythropoiesis: The roles of folate, vitamin B-12 and iron. Annu Rev Nutr 2004; 24:105-131.

4.Canadian Paediatric Society Nutrition Committee. Iron needs of babies and children. Paediatr Child Health 2007; 12(4): 333–334.

5.Baker RD, Greer FR. Committee on Nutrition American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron deficiency anemia in infants, and young children (0-3 years of age). Pediatrics 2010; 126:1040- 1050.

6.Lozoff B, Jimeneze E, Hagen J, Mollen E, Wolf AW. Poorer behaviour and development outcome more than 10yrs after treatment for iron deficiency in infancy. Pediatrics 2000;105: e51.

7.Lukowski AF, Koss M, Burden MJ, Jonides J, Nelson CA, Kaciroti N, et al. Iron deficiency in infancy and neuro cognitive functioning at 19 yrs: evidence of long term deficits in executive function and recognition memory. Nutr Neurosci 2010;13: 54-70.

8.Wayne Thomas D, Rod f.Hinchliffe, Carol Briggs, Iain C.Macdougall,Tim Littlewood andIvor cavill-British committeefor standards in Haematology. Guidelines for the laboratory diagnosis of functional iron deficiency. Br J Haematol 2013;161:639 -648.

PREVENTIVE STRATEGIES FOR THALASSEMIA

*Anupam Sachdeva **Arun S Danewa

Abstract: Thalassemias are group of autosomal recessive disorders of hemoglobin chain production. This inherited disorder requires life-long management in the form of regular blood transfusions and chelation therapy imposing a great burden on the family as well as the country. Various strategies for thalassemia prevention including genetic counselling, carrier detection and prenatal diagnosis have decreased the burden of disease but there is a need to increase awareness about the preventive strategies with special focus on pregnant women.

Keywords: Prenatal diagnosis, Preventive strategies, Thalassemia

*Director, Pediatric Hematology Oncology and Bone Marrow Transplantation

email: anupamace@yahoo.co.in

**Fellow in Pediatric Hematology Oncology and Bone Marrow Transplantation,

Sir Ganga Ram Hospital, New Delhi.

Points to Remember

•Thalassemias are a group of autosomal recessive disorders with defective or absent hemoglobin chain synthesis.

•Management includes life-long packed red cell transfusions, chelation therapy and management of complications with iron overload.

•Prenatal diagnosis should be advised when both partners are carriers of β-thalassemia which includes chorionic villus sampling, amniocentesis and fetal cord blood sampling.

•More efforts are needed to increase awareness about the preventive strategies.

References

1.Winichagoon P, Saechan V, Sripanich R, Nopparatana C,

Kanokpongsakdi S, Maggio A. Prenatal diagnosis of β-thalassemia by reverse dot blot hybridization. Prenatal Diagn 1999; 19:428–435.

2.Weathrall DJ, Clegg JB. Inherited Haemoglobin Disorders: an increasing global problem. Bull World Health Organ 2001;79:704-712.

3.Verma IC, Choudhry VP, Jain PK. Prevention of thalassemia: A necessity in India. Indian J Pediatr 1992; 59: 649-654.

4.Orofino MG, Argiolu F, Sanna MA, Rosatelli MC,

Tuveri T, Scalas MT, et al. Fetal HLA typing in β-thalassemia: Implications for hemopoietic stem-cell transplantation. Lancet 2003; 362: 41–42.

5.Ahmed S, Saleem M, Modell B, Petrou M. Screening extended families for genetic hemoglobin disorders in Pakistan. N Engl J Med 2002; 347: 1162–1168.

6.Angastiniotis MA, Hadjiminas MG. Prevention of thalassemia in Cyprus. Lancet 1981; 1:369–371.

7.Cao A, Rosatelli MC, Galanello R. Control of β-thalassemia by carrier screening, genetic counselling and prenatal diagnosis: The Sardinian experience. Ciba Found Symp 1996;197:137–155.

8.Loukopoulos D. Current status of thalassemia and the sickle cell syndromes in Greece. Semin Hematol 1996;33:76–86.

9.Koren A, Profeta L, Zalman L, Palmor H, Levin C, Zamir RB, et al. Prevention of â Thalassemia in Northern

Indian Journal of Practical Pediatrics

Israel - a Cost-BenefitAnalysis. Mediterr J Hematol Infect Dis 2014;6:e2014012. doi: 10.4084/MJHID.2014.012. eCollection 2014.

10.Weatherall DJ, Clegg JB. The thalassemia syndromes. 4th edn, Blackwell Science, Oxford., UK, 2001.

11.Mehta BC, Iyer PD, Gandhi SG, Ramnath SR, Patel JC. Diagnosis of heterozygous beta-thalassemia in a population with high prevalence of iron deficiency. Indian J Med Sci 1973;27:832-835.

12.Gomber S, Madan N. Validity of Nestroft in screening and diagnosis of β-thalassemia trait. J Trop Pediatr 1997;43:363-366.

13.Gonzalez-Redondo JM, Stoming TA, Kutlar A, Kutlar F, Lanclos KD, Howard EF, et al. A C!T substitution at nt

2101 in a conserved DNA sequence of the promotor region of the β-globin gene is associated with “silent” β-thalassemia. Blood 1989;73:1705–1711.

14.Galanello R, Barella S, Ideo A, Gasperini D, Rosatelli C,

Paderi L, et al. Genotype of subjects with borderline hemoglobin A2 levels: Implication for β-thalassemia carrier screening. Am J Hematol 1994;46:79–81.

15.Saiki RK, Walsh PS, Levenson CH, Erlich HA. Genetic analysis of amplified DNA with immobilized sequence specific oligonucleotide probes. Proc Natl Acad Sci 1989;86: 6230–6234.

16.Kokkali G, Synodinos JT, Vrettou C, Stavrou D, Jones GM, Cram DS, et al Blastocyst biopsy versus cleavage stage

biopsy and blastocyst transfer for preimplantation genetic diagnosis of β-thalassemia: A pilot study. Hum Reprod 2007;22:1443–1449.

17.Verlinsky Y, Ginsberg N, Lifchez A, Valle J, Moise J, Strom CM. Analysis of the first polar body: Preconception genetic diagnosis. Hum Reprod 1990;5:826–829.

18.Cheung MC, Goldberg JD, Kan YW. Prenatal diagnosis of sickle cell anaemia and thalassemia by analysis of fetal cells in maternal blood. Nat Genet 1996;14:264–268.

19.Bianchi DW, Williams JM, Sullivan LM, Hanson FW, Klinger KW, Shuber AP. PCR quantitation of fetal cells in maternal blood in normal and aneuploid pregnancies. Am J Hum Genet 1997;61:822–829.

20.Cao A, Galanello R, Rosatelli MC. Prenatal diagnosis and screening of the haemoglobinopathies. Baillieres Clin Haematol 1998;11:215-238.

21.Samavat A, Modell B. Iranian national thalassemia screening programme. BMJ 2004; 329:1134-1137.

22.Indian Red Cross Society (IRCS), Gujarat State Branch. Annual Report 2009-2010. Ahmedabad: IRCS, Gujarat State Branch; 2010.

23.Mohanty D, Colah R, Gorakshakar A, editors. Report of the Jai Vigyan S & T Mission Project on community control of thalassaemia syndromes -Awareness, screening, genetic counselling and prevention. A National Multicentric Task

2016;18(3) : 228

Force Study of Indian Council of Medical Research-New Delhi, 2008. New Delhi, ICMR, 2008.

24.Colah R, Surve R, Wadia M, Solanki P, Mayekar P, Thomas M, et al. Carrier screening for beta-thalassemia during pregnancy in India: a 7-year evaluation. Genet Test 2008;12: 181-185.

25.Colah R, Thomas M, Mayekar P. Assessing the impact of

screening and counselling high school children for β-thalassemia in India. J Med Screen 2007;14:158.

26.Tamhankar PM, Agarwal S, Arya V, Kumar R, Gupta UR, Agarwal SS. Prevention of homozygous beta thalassemia by premarital screening and prenatal diagnosis in India. Prenat Diagn 2009;29:83-88.

27.Muralitharan S, Srivastava A, Shaji RV, Mathai M, Srivastava VM, Dennison D, et al. Prenatal diagnosis of beta-thalassemia mutations using the reverse dot blot technique. Natl Med J India 1996;9:70-71.

28.Thakur (Mahadik) C, Vaz F, Banerjee M, Kapadia C, Natrajan PG, Yagnik H, et al. Prenatal diagnosis of beta- thalassemia and other haemoglobinopathies in India. Prenat Diagn 2000;20:194-201.

29.Saxena R, Jain PK, Thomas E, Verma IC. Prenatal diagnosis of beta-thalassemia: experience in a developing country. Prenat Diagn 1998;18:1-7.

APPROACH TO A BLEEDING CHILD

*Nitin Shah

Abstract: Hemostasis is a perfect balance between fluidity of flowing blood on one hand and clotting when required on other hand. Vessel wall, platelets, coagulation factors and their regulators as well as fibrinolytic processes play a role in this balance. While approaching a child with bleeding, systematic approach starting with clinical history, detailed examination, screening laboratory tests and at the end confirmatory test is essential. Clinical clues also at times help to clinch the diagnosis. Newer laboratory tests have helped further diagnosis of rare bleeding disorders.

Keywords: Bleeding child, Approach, Screening tests, Confirmatory tests

Points to remember

•Ascertain whether bleeding is due to local cause or systemic cause, inherited cause or acquired cause, vascular/platelet defect or coagulation defect.

•Clinical clues at times help clinch the diagnosis in a syndromic child with bleeding.

•Bleeding time is rarely required and clotting time is given up as a screening test.

•CBC, PS, PT, aPTT and TCT form the screening tests in a bleeding child.

•Prolonged aPTT can be also due to presence of inhibitors.

•Normal screening tests for bleeding do not rule out bleeding disorders always.

•Keep battered baby or fictitious purpura as a cause of bleeding in mind in a given clinical background.

References

*Consultant Pediatrician, P.D.Hinduja National Hospital & Hon. Pediatric Hematologist Oncologist, BJ Wadia Hospital for Children, Mumbai email: drnitinshah@hotmail.com

1.Khair K, Liesner R. Bruising and bleeding in infants and children-a practical approach. Br J Haematol 2006; 133:221-231.

2.Hoyer LW. Hemophilia A. N Engl J Med 1994;330: 38-47.

3.Haitjema T, Westermann CJ, Overtoom TT, Timmer R, Disch F, Mauser H, et al. Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease): new insights in pathogenesis, complications, and treatment. Arch Intern Med 1996;156:714-719.

4.Warrier I, Lusher JM. Congenital thrombocytopenias. Curr Opin Hematol 1995; 2:395.

5.Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. et al. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet 1998;77:31-37.

6.Neunert C, Lim W, Crowther M, Cohen A, Lawrence Solberg Jr, Mark A. Crowther. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011;117:4190-4207.

7.Hsieh L, Nugent D. Factor XIII deficiency. Haemophilia 2008; 14:11901200.

HEMOPHAGOCYTIC

LYMPHOHISTIOCYTOSIS

*Balasubramanian S

Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a life threatening illness often associated with malignancy, rheumatologic and infectious diseases. HLH presents with fever and involvement of many organ systems with hepatosplenomegaly, lymphadenopathy, rash and neurologic manifestations. Anemia and thrombocytopenia along with elevated ferritin, abnormal liver enzymes level and deranged coagulation profile should point towards HLH. Though hemophagocytosis on bone marrow examination is not seen in all cases, infiltration of the bone marrow by activated macrophages is consistent with the diagnosis. Immunological investigations are not essential for initiation of therapy. Treatment aim is to interrupt the amplification cascades of cytokines and suppress the hyperinflammation.

Keywords: Hemophagocytic lymphohistiocytosis, Children, Pathogenesis, Management

*Head - Department of Pediatrics,

Kanchi Kamakoti CHILDS Trust Hospital & CHILDS Trust Medical Research Foundation, Chennai.

email: sbsped@gmail.com

Points to Remember

•Hemophagocytic lymphohistiocytosis (HLH) is a frequently fatal but underdiagnosed condition.

•Clinical features mimic many illnesses.

•Fever, lymphadenopathy, hepatosplenomegaly, rash along with bicytopenia, elevated liver enzymes and ferritin should make one suspect HLH.

•Well defined criteria help in making a definitive diagnosis of HLH.

•Corticosteroids, etoposide and cyclosporine A form the basis of the treatment.

•Hematopoietic stem cell transplant will be needed in primary cases to correct the underlying immune defect and to prevent recurrence.

•Supportive care is essential.

References

1.Freeman HR, Ramanan AV. Review of haemophagocytic lymphohistiocytosis, Arch Dis Child 2011; 96: 688–693.

2.Filipovich A, McClain K, Grom A. Histiocytic disorders: recent insights into pathophysiology and practical guidelines. Biol Blood Marrow Transplant 2010;16: S82-S89.

3.Fall N, Barnes M, Thornton S, Luyrink L, Olson J, Ilowite NT, et al. Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome.Arthritis Rheum 2007; 56: 3793-3804.

4.Behrens EM, Canna SW, Slade K, Rao S, Kreiger PA, Paessler M, et al. Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice. J Clin Invest 2011; 121: 2264-2277.

5.Henter JI, Elinder G, Söder O, Hansson M, Andersson B, Andersson U. Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. Blood 1991; 78: 2918-2922.

6.Osugi Y, Hara J, Tagawa S, Takai K, Hosoi G, Matsuda Y, et al. Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis. Blood 1997; 89: 4100-41003.

ATYPICAL PRESENTATION OF PEDIATRIC MALIGNANCIES IN OFFICE PRACTICE

*Aruna Rajendran

Abstract: Pediatric malignancies have a variable presentation. These may be in the form of proptosis, lytic bone lesions, testicular swelling endocrine dysfunction or simply as pyrexia of unknown origin. The diagnosis may get delayed with the use of corticosteriods and concomitant severe infection. A through knowledge of these unusual presentations and continued observation and follow up will help in arriving at the correct diagnosis. Sometimes repeating the tests like bone marrow examination on strong clinical suspicion will yield the diagnosis. Some of the variations in clinical presentation of pediatric malignancies are discussed with illustrative cases.

Keywords: Atypical presentation, malignancies, childhood

*Assistant Professor,

Division of Pediatric Hematology Oncology, Department of Pediatrics,

Sri Ramachandra Medical College and Research Institute, Chennai.

email: deararuna@yahoo.com

Points to Rembember

•Pediatric malignancies may present with clinical features of other common childhood problems, such as infection, endocrine problems, rheumatologic disorders etc.

•The diagnosis may also get delayed due to iatrogenic factors such as even a single dose of steroids.

•In clincally suspected cases, continuous reexamination and repeating the tests like bone marrow examination will help in the diagnosis.

•Appropriate tissue should be sampled for accurate diagnosis.

•Knowledge about the atypical presentation will help the pediatrician to suspect malignancy in the appropriate clinical circumstances.

References

1.Golai S, Nimbeni B, Patil SD, Kakanur M, Paul S. Langerhans histiocytosis in a child -diagnosed by oral manifestations. J Clin Diagn Res 2015;9:9-11.

2.Kalapurakal JA, Dome JS, Perlman EJ, Malogolowkin M, Haase GM, Grundy P, et al. Management of Wilms’tumour: current practice and future goals. Lancet Oncol 2004; 5: 37–46.

3.Sargent JT, Smith OP. Haematological emergencies managing hypercalcaemia in adults and children with haematological disorders. Br J Haematol 2010; 149:465- 477.

4.Rajendran A, Trehan A, Ahluwalia J, Marwaha RK. Severe Systemic Infection Masking Underlying Childhood Leukemia. Indian J Hematol Blood Transfus 2013; 29:167– 170.

5.Margolin JF, Rabin KR, Steuber CP, Poplack DG. Acute

lymphoblastic leukemia. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 6th edn. Philadelphia Pa: Lippincott Williams & Wilkins, 2011.

6.El-Osta HE, Salyers WJ Jr, Palko W, Hagan ME, El-Haddad B, Schulz TK. Anaplastic large-cell lymphoma with leukemoid reaction. J Clin Oncol 2008;26: 4356-4358.

7.Lew T, Chauhan A, Vasquez R, Warrier R. Massive Hepatomegaly with Respiratory Distress in a Newborn. Clin Pediatr 2015; 54:907-909.

MANAGEMENT OF COMMON PROBLEMS DURING LEUKEMIA TREATMENT

*Anupama Borker **Pooja Balasubramanian

Abstract: Leukemia is the most common and curable of childhood cancers. The treatment of acute leukemia in children is intense and prolonged. Chemotherapy-induced myelosuppression leads to anemia, neutropenia and thrombocytopenia. The prompt treatment of bacterial and fungal infections, rational use of blood components and the availability of potent anti-emetics and analgesics have made leukemia treatment safer. Malnutrition, depression and physical disability during leukemia therapy can be effectively treated with nutritional rehabilitation, physiotherapy and psychosocial support respectively.

Points to Remember

•Febrile neutropenia is an oncological emergency requiring timely action with antibacterial and antifungal therapy to avoid mortality.

•Transfusion with leucodepleted and irradiated blood products helps to prevent alloimmunisation and transfusion associated graft versus host disease in children with leukemia.

•Aggressive nutritional rehabilitation must be initiated from the time of diagnosis to withstand chemotherapy and reduce morbidity and mortality.

•Along with physical problems, emotional and social needs of the child must also be addressed with establishment of a normal routine with age appropriate activities.

Keywords: Leukemia, Chemotherapy, Neutropenia, Anemia.

*Consultant, Pediatric Hematologist and Oncologist

**Junior Consultant, Pediatric Hematologist and Oncologist, Department of Medical and Pediatric Oncology, Somaiya Ayurvihar - Asian Cancer Institute,

Mumbai.

email: dranupamasb@gmail.com

References

1.Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002;34: 730-751.

2.Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America. Clinical Infect Dis 2011;52: e56–e93.

3.Hammond SP, Marty FM, Bryar JM, DeAngelo DJ, Baden LR. Invasive fungal disease in patients treated for newly diagnosed acute leukemia. Am J Hematol 2010; 85: 695–699.

4.Prentice HG, Kibbler CC, Prentice AG. Towards a targeted, risk-based, antifungal strategy in neutropenic patients. Br J Haematol 2000; 110: 273–284.

5.Pazos C, Ponton J, Del Palacio A. Contribution of (1→3)- beta-D-glucan chromogenic assay to diagnosis and therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: A comparison with serial screening for circulating galactomannan. J Clin Microbiol 2005; 43: 299–305.

6.Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F et al. Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer; Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. Defining

RECENT ADVANCES IN THE MANAGE- MENT OF PEDIATRIC SOLID TUMORS

*Prakash Agarwal

Abstract: Solid tumors make up about 30% of all pediatric cancers. The most common types of solid tumors in children include brain tumors, neuroblastoma, rhabdomyosarcoma, Wilms’ tumor and osteosarcoma. In the last decade substantial progress has been made in the treatment of pediatric solid tumors. Better understanding of the natural history of the various tumors, improved histologic classifications, new techniques to define extent of disease accurately, effective chemotherapy and improved radiation, surgical and supportive therapies have contributed to improved survival. This article reviews some of the common childhood tumors, emphasizing on current management and future directions.

Keywords: Pediatric solid tumors, Recent advances.

*Professor and HOD, Pediatric Surgery, Sri Ramachandra University, Chennai.

email: agarwal_prakash@hotmail.com

Points to Remember

•Improved understanding of the molecular genetic basis of tumorigenesis has translated into diagnostic assays to identify abnormalities of gene or chromosome structure in patient tissues and as a means of supporting standard histopathologic and immunohistochemical diagnostic methods.

•Advances in imaging have helped in better diagnosis and prognostication of pediatric solid tumors.

•Targeted chemotherapy including monoclonal antibodies and adjuvant chemotherapy has revolutionized the treatment.

•Advent of central venous lines to administer chemotherapy has made care of the child easier.

References

1.Stiller AC. Epidemiology of Childhood Tumors.

In: Surgery of Childhood tumors. Carachi R, Grosfeld JL, AzmyAF (eds) 2nd edn, Springer-Verlag Berlin Heidelberg, 2008;pp3-16.

2.Green DM, Jaffe N. Wilms’ tumor-model of a curable pediatric malignant solid tumor. Cancer Treat Rev 1978; 5:143-172.

3.DavidoffAM, Krasin MJ. Principles of pediatric oncology/

genetics of cancer. In: Pediatric surgery Grosfeld JL, O’Neill JA, Coran AG (eds), 6th edn. Mosby, Philadelphia, 2006;pp411-436.

4.Brodeur GM, Maris JM, Yamashiro DJ, Hogarty MD, White PS. Biology and genetics of human neuroblastomas. J Pediatr Hematol Oncol 1997;19:93-101.

5.Hoffer FA. Magnetic resonance imaging of abdominal masses in the pediatric patient. Semin Ultrasound CT MR 2005;26:212-223.

6.Kellenberger CJ, Epelman M, Miller SF, Babyn PS. Fast stir whole-body MR imaging in children. RadioGraphics 2004;24:1317–1330.

7.Pashankar FD, O’dorisio MS, Menda Y. MIBG and somatostatin receptor analogs in children: Current con- cepts on diagnostic and therapeutic use. J Nucl Med 46 (Suppl) 2005;1:55s–61s.

8.Kilpatrick SE, Garvin AJ. Recent advances in the diagnosis of pediatric soft-tissue tumors. Med Pediatr Oncol 1999;32: 373-376.

PRIMARY IMMUNODEFICIENCY DISORDERS - WHEN TO SUSPECT AND HOW TO DIAGNOSE

*Revathi Raj

Abstract: Primary immune deficiency disorders are not as rare as thought and can affect about 1 in 10,000 live births. The diagnosis is often missed due to lack of awareness and can be made at any age starting from the newborn period to adulthood. Any child with recurrent infections, atypical organisms, unusual sites and refractory autoimmune disorder can have an underlying defect in their immune system. The introduction of flow cytometry based evaluation for these disorders has made rapid diagnosis a reality and has also given us good insight into the phenotype and genotype correlation. Awareness leads to early diagnosis and intervention with improved outcomes.

Keywords: Primary immunodeficiency, Recurrent infections, Flow cytometry, Atypical organisms, Autoimmunity.

*Consultant in Pediatric Hematology, Oncology and Bone Marrow Transplantation,

Apollo Speciality Hospital, Chennai.

email: revaraj@yahoo.com

Points to Remember

•Primary immune deficiency disorders can manifest at any age from the newborn period to adulthood and diagnosis is feasible only if there is adequate awareness.

•Any child with recurrent or unusual infections or refractory autoimmunity should be evaluated for a defect in the immune system.

•Flow cytometry based evaluation for T and B cell markers and serum immunoglobulins form a basic screening test for these children.

•Hematopoietic stem cell transplantation (HSCT) is the main curative option in many of the primary immune deficiency disorders.

References

1.Puck JM. Neonatal screening for severe combined immunodeficiency. Curr Opin Pediatr 2011;23:667-673.

2.de Vries E, Driessen G. Primary immunodeficiencies in children: a diagnostic challenge. Eur J Pediatr 2011; 170: 169–177.

3.Al-Herz W, Bousfiha A, Casanova JL, Chapel H, Conley ME, Rundles CC, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Front Immun 2011;2:54.

4.Subbarayan A, Colarusso G, Hughes SM, Gennery AR, Slatter M, Cant AJ, et al. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics 2011;127:810-816.

5.Slatter MA, Gennery AR. Clinical immunology review series: an approach to the patient with recurrent infections in childhood. Clin Exp Immunol 2008;152:389-396.

6.Wood P, Stanworth S, Burton J, Jones A, Peckham DG, Green T, et al. UK Primary Immunodeficiency Network. Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review. Clin Exp Immunol 2007;149:410-423.

7.Madkaikar M, Currimbhoy Z, Gupta M, Desai M, Rao M. Clinical profile of leukocyte adhesion deficiency. Indian Pediatr 2011;49:1-4.

CHIKUNGUNYA IN CHILDREN

*Pravakar Mishra **Rashmi Ranjan Das

Abstract: Chikungunya is a viral infection spread by the mosquito belonging to the Aedes species. The disease has been occurring in epidemic forms in our country over the past two decades. Unlike adults, the affected children have less of musculoskeletal involvement, but more of fever with skin rash and may also present with febrile seizures. Children also may have neurological manifestations, which are rare but severe, with sequelae. Perinatal chikungunya due to maternal infection can result in neonatal fever, rash, edema, neurologic problems and multiorgan failure. Treatment of chikungunya is symptomatic. Preventive strategies include control of mosquito breeding and personal protection against mosquito bites.

Keywords: Chikungunya, Children, Neurological, Mother-to-child transmission.

*Associate Professor, Department of Pediatrics, MKCG Medical College, Berhampur.

email: drpravakar@yahoo.co.in

**Assistant Professor, Department of Pediatrics, AIIMS, Bhubaneswar.

Points to Remember

•Chikungunya is a re emerging viral infection spread by Aedes mosquitoes.

•Like other mosquito-borne diseases, it is difficult to predict when an outbreak is going to occur in a particular location.

•Children present commonly with fever and rashes. Musculoskeletal manifestions are rare compared to adults.

•Mother-to-child transmission can occur with neonates presenting with fever, rash, edema and neurological problems.

•Management is entirely symptomatic.

•Mosquito breeding control and prevention of mosquito bites are the only currently available preventive strategies.

References

1.Burt FJ, Rolph MS, Rulli NE, Mahalingam S, Heise MT. Chikungunya: a re-emerging virus. Lancet 2012;379: 662- 671.

2.Kumar A, Best C, Benskin G. Epidemiology, Clinical and Laboratory Features and Course of Chikungunya among a Cohort of Children during the First Caribbean Epidemic. J Trop Pediatr 2016 Aug 10.pii: fmw051. [Epub ahead of print]

3.Powers AM, Logue CH. Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus. J Gen Virol 2007;88: 2363-2377.

4.Myers RM, Carey DE. Concurrent isolation from patient of two arboviruses, Chikungunya and dengue type 2. Science 1967;157: 1307-1308.

5.Padbidri VS, Gnaneswar TT. Epidemiological investigations of chikungunya epidemic at Barsi, Maharashtra state, India. J Hyg Epidemiol Microbiol Immunol 1979;23: 445-451.

6.Lahariya C, Pradhan SK. Emergence of chikungunya virus in Indian subcontinent after 32 years: A review. J Vector Borne Dis 2006;43: 151-160.

7.Petersen LR, Powers AM. Chikungunya: epidemiology.

F1000 Res. 2016 Jan 19;5. pii: F1000 Faculty Rev-82.

doi: 10.12688/f1000research.7171.1. eCollection 2016.

SUPPOSITORIES IN PEDIATRIC THERAPEUTICS

* Jeeson C Unni ** Ranjit Baby Joseph

Abstract: Generally, oral administration is the route of choice for medicating children. However, suppositories are considered as a practical alternative when oral administration is either impractical or impossible, when there is vomiting, convulsions, non-cooperation, unconsciousness and in perioperative period. This article reviews the mechanism of absorption of suppositories, various formulations available and the advantages and disadvantages of some of the medications.

Keywords: Suppositories, Formulation, Rectal drug delivery, Children

*Editor-in-Chief, IAP Drug Formulary, Senior Associate Consultant in Pediatrics,

**Pediatrician,

Aster Medcity, Kochi

email: jeeson1955@gmail.com

Points to Remember

•Suppositories are not superior to oral medications in terms of rapidity of onset of action.

•It should be considered only in conditions where there is practical difficulty in giving the oral medications or when there is specific indication.

•Many of the rectal formulations which are available elsewhere are not currently available in India.

References

1.Van Hoogdalem E, de Boer AG, Breimer DD. Pharmacokinetics of rectal drug administration, Part I. General considerations and clinical applications of centrally acting drugs. Clin Pharmacokinet 1991;21: 11-26.

2.Gross HM, Becker CH. A Study of Suppository Bases. J Pharm Sci 1953;42:90-95.

3.Polishchuk AY, Efremovich G. Application of Polymer systems. Multicomponent Transport in Polymer Systems for Controlled Release; 3:195.

4.Jannin V, Lemagnen G, Gueroult P, Larrouture D, Tuleu C. Rectal route in the 21st Century to treat children. Adv Drug Deliv Rev 2014;73: 34–49.

5.Joint formulary committee. British National Formulary for Children. BMJ group 2015; 69.

6.Scolnik D, Kozer E, Jacobson S, Diamond S, Young NL. Comparison of oral versus normal and high-dose rectal paracetamol in the treatment of febrile children. 2002;110(3):553-556.

7.Nabuls M, Tamim H, Sabra R, Mahfoud Z, Malaeb S, Fakih H, et al. Equal antipyretic effectiveness of oral and rectal paracetamol : a randomized controlled trial. BMC Pediatrics 2005;5:35.

8.Owczarzak V, Haddad J Jr. Comparison of oral versus rectal administration of paracetamol with codeine in postoperative pediatricadenotonsillectomy patients. Laryngoscope. 2006;116(8):1485-1488.

9.Knudsen FU. Plasma-diazepam in infants after rectal administration in solution and by suppository. Acta Pediatr Scand 1977;66(5):563-567.

10.Dhillon S, Ngwane E, Richens A. Rectal absorption of diazepam in epileptic children. Arch Dis Child 1982;57:264-267.

Indian Journal of Practical Pediatrics

11.Hirabayashi Y, Okumura A, Kondo T, Magota M, Kawabe S, Kando N,et al. Efficacy of a diazepam suppository at preventing febrile seizure recurrence during a single febrile illness. Brain Dev 2009 ;31:414-418.

12.Chiang LM, Wang HS, Shen HH, Deng ST, Tseng CH, Chen YI, et al. Rectal diazepam solution is as good as rectal administration of intravenous diazepam in the first- aid cessation of seizures in children with intractable epilepsy. Pediatr Neonatol 2011;52:30-33.

13.Godbole PP, Pinfield A, Stringer MD. Idiopathic megarectum in children. Eur J Pediatr Surg 2001;11: 48-51.

14.Burgers R, Bonanno E, Madarena E. The care of constipated children in primary care in different countries. ActaPaediatr 2012;101:677-680.

15.Portalatin M, Winstead N. Medical Management of Constipation. Clin Colon Rectal Surg. 2012;25:12–19

16.Heyman MB, Kierkus J, Spénard J. Efficacy and safety of mesalamine suppositories for treatment of ulcerative proctitis in children and adolescents. Inflamm Bowel Dis 2010;16:1931-1939.

17.Gionchetti P, Rizzello F, Venturi A. Comparison of oral with rectal mesalazine in the treatment of ulcerative proctitis. Dis Colon Rectum 1998;41:93-97.

18.Allgayer H, Kruis W, Eisenburg J, Paumgartner G. Comparative pharmacokinetics of sulphasalazine and sulphapyridine after rectal and oral administration to patients with ulcerative colitis.Eur J Clin Pharmacol 1984;26:275-277.

2016;18(3) : 244

19.Gomes MF, Faiz MA, Gyapong JO. Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial. Lancet 2009;373(9663): 557-566.

20.Gomes M, Ribeiro I, Warsame M, Karunajeewa H, Petzold M. Rectal artemisinins for malaria: a review of efficacy and safety from individual patient data in clinical studies. BMC Infect Dis 2008; 8:39.

21.Arvidsson J, Nilsson HL, Sandstedt P. Replacing carbamazepine slow-release tablets with carbamazepine suppositories: a pharmacokinetic and clinical study in children with epilepsy. J Child Neurol 1995;10:114-117.

22.Matsumoto Y, Watanabe Y, Yamamoto I. Difference in rectal absorption of morphine from hollow-type and conventional suppositories in rabbits. Biol Pharm Bull 1993; 16(2):150-153.

23.Lencz L. The importance of domperidone (Motilium) in controlling postoperative nausea and vomiting. Ther Hung 1990;38:106-109.

24.Amidona, Smitha DE. Determination of the Population Pharmacokinetic Parameters of Sustained-Release and Enteric-Coated Oral Formulations, and the Suppository Formulation of Diclofenac Sodium by Simultaneous Data Fitting Using NONMEM., Biopharm. Drug Dispos 1998;19:169–174.

CUTANEOUS ADVERSE DRUG

REACTIONS

*Madhu R

Abstract: Cutaneous adverse drug reactions (CADR) form a spectrum ranging from benign conditions to serious life-threatening reactions such as Steven Johnson syndrome, toxic epidermal necrolysis and drug hypersensitivity syndromes. In the latter conditions, skin manifestations do not occur in isolation and present as a systemic reaction. Various mechanisms, both immunological and non-immunological have been postulated to explain CADR. Antimicrobials, nonsteroidal anti-inflammatory drugs and anticonvulsants are the most common agents implicated in CADR. Exanthematous type which is the most common of CADR, often poses a diagnostic dilemma due to its close resemblance to viral exanthems. The most important step in the management is to withhold the offending agent and all the non-essential drugs. Early diagnosis and prompt treatment of severe cutaneous drug reactions pave the way to reduce the morbidity and improve the quality of life of these children.

Keywords: Cutaneous adverse drug reaction, Sulfonamides, Anticonvulsants, Steven Johnson syndrome, Toxic epidermal necrolysis.

*Senior Asst. Professor,

Department of Dermatology, (Mycology), Madras Medical College,

Chennai.

email: renmadhu08@gmail.com

Points to Remember

•Cutaneous adverse drug reactions are the most common adverse drug reactions seen in hospitalized children.

•Drugs with a tendency to produce reactive intermediates or toxins, low therapeutic indices and high levels of drug interactions are more prone to result in drug reactions.

•Dose, time and susceptibility (DoTS) classification provides a complete evaluation of the ADR and is ideal for pharmacovigilance studies.

•Detailed history regarding the drug and evolution of the eruption and astute clinical examination will help in correct diagnosis and appropriate management.

References

1.Dhar S, Banerjee R, Malakar R. Cutaneous drug reactions in children. Indian J Paediatr Dermatol 2014;15:5-11.

2.Aagaard L, Hansen EH. Cutaneous adverse drug reactions in children: a national register based study. Br J Dermatol 2013;168:pp434-437.

3.Pastrana LC, Ghannadan R, Rieder MJ, Dahlke E, Hayden M, Carleton B. Cutaneous adverse drug reactions in children: an analysis of reports from the Canadian pharmacogenomics network for drug safety (CPNDS). J Popul Ther Clin Pharmacol 2011;18:106-120.

4.Shear NH, Knowles SR. Cutaneous reactions to drugs. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS,

Leffel DJ, Wolff K, (Eds). Fitzpatrick’s dermatology in general medicine. 8th edn. New York: The McGraw-Hill companies 2012; pp449-457.

5.Ghosh S, Leelavathi D. Acharya, Padma GM Rao. Study and evaluation of the various cutaneous adverse reactions in Kasturba hospital, Manipal. Indian J Pharm Sci 2006; 68:212-215.

6.Nayak S, Acharjya B. Adverse cutaneous drug reactions. Indian J Dermatol 2008;53:2-8.

7.Kanneh AB. Adverse drug reactions in children Part I. Pediatric nursing 2004;16:32-35.

8.Ospina CC, Rojas CB. The DoTS classification is a useful way to classify adverse drug reactions: a preliminary study in hospitalized patients. Int J Pharm Pract 2010;18:230– 235.

Indian Journal of Practical Pediatrics

9.Revuz J, Allanore LV. Drug reactions. In: Bolognia JL, Jorizzo JL, Schaffer JV, (Eds). Dermatology vol 2. 3rdedn. Philadelphia: Elsevier Saunders 2012;pp335-356.

10.Ghosh K, Banerjee G, Ghosal A, Nandi J. Cutaneous Drug Hypersensitivity: Immunological and Genetic Perspective. Indian J Dermatol 2011;56:137-144.

11.Lansang P, Weistein M, Shear N. Drug reactions.

In: Schachner LA, Hansen RC, (Eds). Pediatric

dermatology, vol.2, 4th edn. Philadelphia: Mosby Elsevier 2011;pp1698-1711.

12.Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239-245.

13.Syed Ahmed Zaki. Adverse drug reaction and causality assessment scales. Lung India 2011;28:152-153.

14.Dilek N, Özkol HU, Akbaº A, Kýlýnç F, Dilek AR, Saral Y, et al. Cutaneous drug reactions in children: a multicentric study. Postep Dermatol Alergol 2014;31:368- 371.

15.Khoo BP, Giam YC. Drug Eruptions in Children:AReview of 111 Cases Seen in a Tertiary Skin Referral Centre. Singapore Med J 2000;41:525-529.

16.Jones MRA, Lee HY. Benign cutaneous adverse reactions to drugs. In: Griffiths CEM, Barker J, Bleiker T,

Chalmers R, Creamer D. Editors. Rook’s Textbook of dermatology. 9th edn. West Sussex: Wiley Blackwell, 2016p118. 1-118.17.

17.Sharma VK, Dhar S. Clinical pattern of cutaneous drug eruption among children and adolescents in north India. Pediatr Dermatol 1995;12:178-183.

18.Can C, Akkelle E, Bay B, Arýcan O, Yalcin O, Yazicioglu M. Generalized fixed drug eruption in a child dueto trimethoprim/sulfamethoxazole. Pediatr Allergy Immunol 2014;25:413–415.

19.Sarkar R, Kaur C, Kanwar AJ. Extensive fixed drug eruption to Nimesulide with cross-sensitivity to sulphonamides in a child. Pediatr Dermatol 2002;19:553- 554.

20.Heelan K, Shear NH. Cutaneous Drug Reactions in Children: An Update. Pediatr Drugs 2013;15:493-503.

21.Song JE, Sidbury R.An update on pediatric cutaneous drug eruptions. Clin Dermatol 2014; 32:516–523.

22.Pulido CF, Patos VG.Areview of causes of Steven-Johnson syndrome and toxic epidermal necrolysis in children.Arch Dis Child 2013;98:998–1003.

23.Steven AM, Johnson FC. A new eruptive fever associates with stomatitis and ophthalmia; report of two cases in children. Am J Dis Child 1922;24:526–533.

24.LyellA. Toxic epidermal necrolysis: an eruption resembling scalding of the skin. Br J Dermatol 1956;68:355-361.

2016;18(3) : 246

25.The hypersensitivity syndromes. In: Paller AS,

Mancini AJ (Eds). Hurwitz clinical pediatric dermatology. 4th edn. Philadelphia: Elsevier Saunders 2011; pp467-494.

26.Sethuraman G, Sharma VK, Pahwa P, Khetan P. Causative drugs and clinical outcome in Steven Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and SJS-TEN overlap in children. Indian J Dermatol 2012;57:199-200.

27.Koh MJ, Tay YK. Steven-Johnson syndrome and toxic epidermalnecrolysis in Asian children. J Am Acad Dermatol 2010;62:54-60.

28.Markovi MA, Medjo B, Jankulovi MG, Velickovic TC, Nikolic D, Nestorovic B. Steven-Johnson syndrome and toxic epidermal necrolysis in children. Pediatr Allergy Immunol 2013;24:645–649.

29.Sasidharanpillai S, Riyaz N, Khader A, Rajan U, Binitha MP, Sureshan DN. Severe cutaneous adverse drug reactions:Aclinic epidemiological study. Indian J Dermatol 2015;60:102.

30.Catt CJ, Hamilton GM, Fish J, Mireskandari, K, Ali A. Ocular Manifestations of Steven-Johnson Syndrome and Toxic Epidermal Necrolysis in Children. J Ophthalmol 2016;166:68-75.

31.Shokeen D. Cyclosporine in SJS/TEN management: a brief

review. Cutis 2016; 97: E17-18.

32.Singh GK, Chatterjee M, Verma R. Cyclosporine in Steven- Johnson syndrome and toxic epidermal necrolysis and retrospective comparison with systemic corticosteroid 2013;79:686-692.

INTESTINAL STRONGYLOIDIASIS IN AN IMMUNOCOMPETENT BOY

*Sumathi B **Nirmala D

***Bhaskar Raju B

****Sunil Kumar KS

Abstract: Strongyloides stercoralis is endemic in tropical and sub-tropical regions and is often reported in immunocompromised children. Creeping eruption due to dermal entry of larva, rather than the gastrointestinal route, is a common manifestation in chronic strongyloidiasis. Peripheral eosinophilia is often seen; however, its absence does not rule out the disease. Consecutive stool examinations for larva is diagnostic, but may be negative at times. Small bowel biopsy may help in diagnosis in children with chronic gastrointestinal symptoms. Treatment with ivermectin is rewarding. We report an immunocompetent boy presenting with chronic diarrhea, hypoproteinemia, anemia and cachexia due to intestinal strongyloidiasis, diagnosed by duodenal biopsy.

References

1.Olsen A, Van Lieshout L, Marti H, Polderman T, Polman K, Steinmann P, et al. Strongyloidiasis–The most neglected of the neglected tropical diseases? Trans R Soc Trop Med Hyg 2009;103(10):967-972.

2.Miller MA, Church LW, Salgado CD. Strongyloides Hyperinfection: A treatment Dilemma. Am J Med Sci 2008;36:358–361.

3.Siddiqui AA, Berk SL. Diagnosis of Strongyloides stercoralis Infection. Clin Infect Dis 2001;33(7):1041- 1047.

4.Chacín-Bonilla L Systemic strongyloidiasis. Review. Invest Clin 1991;32(3):131-145.

5.Marcos LA, Terashima A, Salmavides S, Alvarez H, Lindo F, Tello R, et al. Thiabendazole for the control of Strongyloides stercoralis infection in hyper-epidemic area in Peru Rev Gastroenterol Peru 2005;25:341–348.

6.Mirdha B. Human strongyloidiasis: often brushed under the carpet. Trop Gastroenterol 2009;30(1):1–4.

7.Iriemenam N, Sanyaolu A, Oyibo W, Fagbenro- Beyioku A. Strongyloides stercoralis and the immune response. Parasitol Int 2010;59(1):9–14.

TRACHEOMALACIA DUE TO VASCULAR ANOMALY IN A YOUNG CHILD

*Bhavik Langanecha *Sumant Prabhudesai **Bala Ramachandran

***Balakrishnan KR

Abstract: Tracheomalacia persisting beyond infancy is uncommon. We report a 3-year-old boy with persistent stridor who required endotracheal intubation and mechanical ventilation due to severe airway obstruction. He was found to have severe tracheomalacia. Imaging showed an anomalous innominate artery causing tracheal compression, which was relieved after aortopexy. Tracheomalacia is common in infancy, but its persistence through early childhood should prompt further investigation to rule out correctable secondary causes.

Keywords: Tracheomalacia, Anomalous innominate artery, Aortopexy

*Fellow - Pediatric Critical Care

**Consultant and Head,

Pediatric Critical Care and Emergency Medicine, Kanchi Kamakoti CHILDS Trust Hospital, Chennai.

***Consultant, Cardiovascular and Thoracic Surgery, Fortis Malar Hospitals, Chennai.

email: sumantprabhudesai2014@gmail.com

Points to Remember

•Persistence of tracheomalacia beyond infancy is uncommon.

•Such persistence warrants investigation for a correctable cause.

References

1.Wiatrak BJ. Congenital anomalies of the larynx and trachea. Otolaryngol Clin North Am 2000; 33: 91-110.

2.Sariaydin M, Findik S, Atici AG, Ozkaya S, Uluisik A. Asymptomatic double aortic arch. Int Med Case Rep J 2010; 3: 63–66.

3.Friedman E, Kennedy A, Neitzschman HR. Innominate Artery Compression of the Trachea: An Unusual Cause of Apnea in a 12-Year-Old Boy. South Med J 2003; 96(11): 1161-1164.

4.Mustard WT, Bayliss CE, Fearon B, Pelton D, Trusler GA. Tracheal compression by the innominate artery in children. Ann Thorac Surg 1969; 8:312-319.

5.Gross RE, Neuhauser EBD. Compression of the trachea by an anomalous innominate artery: An operation for its relief. Am J Dis Child 1948; 75: 570-574.

6.Torre M, Carlucci M, Speggiorin S, Elliott MJ. Aortopexy for the treatment of tracheomalacia in children: review of the literature. Ital J Pediatr 2012; 38: 62-70.

7.Sachdev MS, Joshi R, Kaul S, Kohli V. Innominate Artery Compression of Trachea. Indian J Pediatr 2007; 74 (8): 768- 769.

8.Strife JL, Baumel AS, Dunbar JS. Tracheal compression by the innominate artery in infancy and childhood. Radiology 1981; 139: 73-75.

9.Myer CM, Wiatrak BJ, Cotton RT. Innominate artery compression of the trachea: Current concepts. Laryngoscope 1989; 99: 1030-1034.

10.Minagawa T, Oizumi H, Emura T, Sadahiro M .Tracheal stenosis treated by division of the brachiocephalic artery: Report of a case. Surg Today 2010 Dec; 40(12):1152-1154.

11.Hawkins JA, Bailey WW, Clark SM. Innominate artery compression of the trachea: Treatment by reimplantation of the innominate artery. J Thorac Cardiovasc Surg 1992; 103: 678-682.