1. Approach to the child with immune based and/or allergic disease Khaled Saad, MD

2. Introduction Recurrent infections is a common reason for seeking medical advice in pediatrics. This may refer to infections that are: great in number long lasting Very severe Associated with unusual complications Or fail to resolve with standard therapy 3. Theses children can be grouped into 4 categories: 1. The normal child 2. The child with atopic disease 3. The child with another chronic condition 4. The child with immunodeficiency 4. The normal child 50% of children with recurrent infections The average child has (+/-) 4-8 respiratory infections per year The mean duration of viral respiratory symptoms is 8 days (however can extend beyond two weeks) Normal growth and development Respond quickly to treatment, with complete recovery Appear healthy between infections Physical examination and lab tests are normal 5. Child with atopic disease Account for 30% of children with recurrent infection Increased susceptibility to URTI Usually develop coughing and wheezing following respiratory infections (reactive airway disease/asthma) 6. Respond well to allergy or asthma medications Growth and development are usually normal Characteristic physical findings Elevated serum IgE 7. Child with chronic disease 10% of children with recurrent infection Cystic fibrosis, GERD, CHD, chronic aspiration, cerebral palsy Increased susceptibilty to infection: Inadequate clearance of secretions Increased pulmonary blood flow FB artificial cardiac valve, VP shunt, indwelling catheter 8. Child with immunodeficiency Account for 10% of children with recurrent infection PID usually affect B cells Secondary immune deficiency usually affects T cells (aging, malnutrition, drugs) 9. Types of immunity A Innate (natural) immunity responds to infection regardless of previous exposure to the agent Ex: PNL, phagocytic cells, complement system B Acquired (adaptive) immunity develops as a result of exposure to previous immunogens Ex: T lymphocytes, B lymphocytes, NK cells 10. Clinical features suggestive of a primary immunodeficiency: Family history of immunodeficiency Failure to thrive Need for IV antibiotics and or hospitalization to clear infection 4 or more ear infections with in one year 2 or more episodes of sepsis or meningitis in a life time 2 or more months of antibiotic treatment with little effect 11. Recurrent or resistant candidiasis Serious infections occuring at unusual sites (brain, liver abscess) Infection with opportunistic organisms Complications from live vaccines (rota virus, varicella) Non healing wounds Granulomas Lymphoma in infancy 12. Features suggestive of PID in neonates Hypocalcemia Congenital heart defects (conotruncal anomalies) Absence of thymic shadow in CXR Delayed umbilical cord detachment (>30 days) 13. History Birth history maternal illness, drug intake, length of gestation, birth weight neonatal problems, umbilical cord detachment Feeding history Growth and development Immunization history especially live vaccines (OPV, rota virus vaccines), vaccine failure Previous illnesses, school abscences Family history Consanguinity (autosomal recessive immunodeficiencies) 14. Infection history 1. Age of onset Birth to 6 months congenital neutropenias, leukocyte adhesion defects, severe combined immunodeficiency (SCID), and complete DiGeorge syndrome. 6 months to 2 years normal child, child with allergy. Persistent diarrhea, chronic cough, or failure to thrive suggests cystic fibrosis, or PID 15. 2 to 6 years children developing infection in this age group may also fit into any of the 4 categories. 2ry immunodeficiencies resulting from malignancy, nephrotic syndrome, or gastrointestinal problems start at this age 6 18 years it is unusual for recurrent infections to first present beyond the age of six 16. Infection history (contd) 2. Sites of infection: Upper respiratory tract Most common site, usually viral Chronic purulent nasal discharge and cough chronic siusitis Chronic or seasonal clear nasal discharge, congestion, itchy eyes, nocturnal cough allergic disease Recurrent oral thrush, stomatitis, gingivitis, t-cell and phagocytic cell disorder Recurrent pharyngitis, or tonsillitis usually not associated with immunodeficiency 17. Lower respiratory tract Recurrent pneumonia is rare in normal children or children with allergic disease Suggest chronic cardiopulmonary disease or immunodeficiency Recurrent pneumonia limited to a particular anatomic region local anatomical abnormality 18. Blood and brain Bacterial meningitis and sepsis suggest antibody deficiency or complement defect Chronic enteroviral encephalomyelitis occurs in patients with profound antibody deficiency and commonly follows OPV 19. Other Recurrent and or chronic GIT infections occur in patients with IgA deficiency Recurrent UTI is uncommon in immunodeficiency and suggests structural abnormality Abscesses of the skin, intestine, or LN suggest phagocytic or antibody deficiency 20. 3. Isolated organisms Recurrent sinopulmunary infections with encapsulated organisms B cell abnormalities Pneumocystis carnii is the hallmark of SCID and other T cell defects Enteroviral meningoencephalitis x-linked agammaglobulinemia Recurrent staph infections hyperimmunoglubulin E syndrome Severe candidiasis abnormal t cell immunity 21. Physical Examination General appearance, dysmorphic features Failure to thrive (growth charts) Discharging ears, perforated tympanic membrane suggest immunodeficiency Pallor without anemia, allergic shiners, conjunctivitis, transverse nasal crease, clear nasal discharge, suggest allergy 22. Mouth ulcers, gingivitis, oral thrush, poor dentition, suggest immunodeficiency Atopic dermatitis (eczema) suggest allergic disease. Immunodeficiencis associated with eczema: wiskott-aldrich, hyper IgE, SCID, omenn syndrome 23. Diminished or absent tonsils and cervical lymph nodes in the presence of recurrent respiratory infections suggest antibody deficiency Absence of lymphoid tissue suggest SCID or x linked agammaglobulinemia Adenopathy and HSM can be seen in IgA deficiency, common variable immunodeficiency, and HIV infection. 24. Clinical patterns of immunodeficiency Wiskott aldrich syndrome : petechiae, easy bleeding, eczema, chronic draining ears Ataxia telangiectasia: ataxia, telangiectasia, developmental delay Warts hypogammaglobulinemia infections myelokathexis (WHIM) syndrome : extensive warts or molluscum contagiosum 25. Hyper IgE syndrome: coarse features, chronic infected eczema, deep seated abscesses DiGeorge syndrome: short stature, CHD, developmental delay, low set ears, downturning eyes, micrognathia Chediak Higashi disease: 26. Laboratory Evaluation Initial tests (screening evaluation) should be done for all children with recurrent infections Abnormalities of these initial tests may suggest allergy, immunodeficiency or a chronic illness, and will need further investigations If screening tests are normal, the patients family can be reassured that a serious disorder has been excluded. 27. General screening tests Include: CBC with differential count Electrolytes, glucose, KFT, albumin Urine analysis ESR CRP CXR 28. CBC With special attention paid to the total absolute lymphocyte count: lymphopenia