Approach to a child with suspected immunodefeciency
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Immunodeficiency can be primary (genetic) or secondary (acquired) and results in increased susceptibility to infections. Primary immunodeficiencies can affect T cells, B cells, phagocytes, or the complement system. Secondary immunodeficiencies are caused by drugs, infections like HIV. Incidence is estimated at 1 in 10,000 people. Diagnosis involves assessing infection history and family history, immunological testing like immunoglobulin levels and antibody titers, and genetic testing if a specific mutation is known. Early diagnosis and treatment like antibiotics, immunoglobulin replacement or bone marrow transplant can be life-saving.
Approach to a child with suspected immunodefeciency
- 2. Immunodeficiency is a state in which the immune system’s ability to fight infectious disease is either compromised or is completely absent. 2 types:- I˚ Immunodeficiency 2˚ Immunodeficiency
- 3. Suspected cases are far more than actual , as most patients with recurrent infections do not have an identifiable immunodeficiency disorder. Exact incidence is not known but it is estimated to be 1:10000
- 4. PRIMARY IMMUNODEFECIENCY • TCELL DEFECT • B CELL DEFECT • COMPLEMENT DEFECT • PHAGOCYTIC DEFECT SECONDARY IMMUNODEFECIENC Y .DRUGS .INFECTIONS
- 5. Severe combined immunodeficiency Wiskott aldrich syndrome(Xp11) Ataxia telengectiasia(11q) Digeorge anomaly
- 6. XL agammaglobulinemia Common variable immunodeficiency Selective IgA deficiency AR agammaglobulinemia Hyper-IgM syndromes- XL Ig heavy-chain gene deletions- AR
- 7. C1q deficiency Factor I deficiency Factor H deficiency Factor D deficiency Properdin deficiency
- 8. Chronic granulomatous disease Leukocyte adhesion defect Chediac higashi syndrome Myeloperoxidase deficiency Cyclic neutropenia (elastase defect)
- 9. I˚ immunodeficiency diseases are not screened for at any time during life Most affected do not have abnormal physical features Extensive use of antibiotics may mask the classic presentation.
- 10. 1 or more systemic bacterial infections (sepsis, meningitis) 2 or more serious respiratory or documented bacterial infections (cellulitis, abscesses, draining otitis media, pneumonia, lymphadenitis) within 1 yr
- 11. Unusual sites (liver, brain abscess) Unusual pathogens (Pneumocystis jiroveci, Aspergillus, Serratia marcescens, Nocardia, Burkholderia cepacia) Common childhood pathogens but of unusual severity
- 12. • 4 or more new ear infections within 1 year. • 2 or more serious sinus infections within 1 year. • 2 or more months on antibiotics with little effect. • 2 or more pneumonias within 1 year. • Failure to gain weight or grow normally.
- 13. • Recurrent, deep skin or organ abscesses. • Persistent thrush in mouth or fungal infection on skin. • Two or more deep-seated infections including septicemia. • A family history of PID.
- 14. Depends on type of disordes ( T/B cell defect) Predisposition to infection by specific organism Family history
- 15. Whether patients have a history of risk factors for infection Symptoms and risk factors for secondary immunodeficiency disorders Family history is important
- 16. Onset before age 6 mo suggests a T-cell defect Onset between the age of 6 and 12 mo may suggest combined B- and T-cell defects or a B-cell defect Later than 12 mo usually suggests a B-cell defect or secondary immunodeficiency
- 17. Predominant T cell Early onset (2-6 mnths) Gram positive and neg bacteria, mycobacteria,CMV, EBV, and fungi – candida Lungs and GI tract
- 18. Predominant B cell Onset after 5-7 months of age Pneumococci,staph, strepto,enteroviruses,giar dia Sinopulmonary, GI infections
- 19. Phagocytic defect Early onset Staph, pseudomonas, candida, nocardia Skin abscess, LN suppuration,oral cavity infections
- 20. Compliment defect Onset at any age Pneumococci and neiserria Meningitis ,arthritis,sepsis
- 21. Patients may or may not appear chronically ill. Cervical lymph nodes and adenoid and tonsillar tissue Tympanic membranes may be scarred or perforated
- 22. CBC with manual differential Quantitative Ig measurements Antibody titers Skin testing for delayed hypersensitivity
- 23. Neutropenia-( ANC <1200) congenital or cyclic or may occur in aplastic anemia. Lymphopenia- T-cell disorder Leukocytosis that persists between infections may occur in leukocyte adhesion deficiency. Thrombocytopenia in male infants suggests Wiskott-Aldrich syndrome
- 24. Usually present Recurrent URTI Severe bacterial infections Not responding to treatment Often present Failure to thrive Recurrent pneumonia Diarrhoea and malabsorption Occasionaly seen LN pathy HS megaly Recurrent meningitis Chronic encephalitis
- 25. Infants 0-6 months Hypocalcemia, unusual facies and ears, heart disease DiGeorge anomaly Delayed umbilical cord detachment, leukocytosis, recurrent infections Leukocyte adhesion defect Persistent thrush, failure to thrive, pneumonia, diarrhea Severe combined immunodeficiency Bloody stools, draining ears, atopic eczema Wiskott-Aldrich syndrome Pneumocystis jiroveci pneumonia, neutropenia, recurrent infections X-linked hyper-IgM syndrome
- 26. 6 months to 5 years Severe progressive infectious mononucleosis X-linked lymphoproliferative syndroem Recurrent staphylococcal infections Hyper-IgE syndrome Persistent thrush, nail dystrophy, endocrinopathies Chronic mucocutaneous candidiasis
- 27. More than 5 years and adults Progressive dermatomyositis with chronic enterovirus encephalitis X-linked agammaglobulinemia Recurrent neisserial meningitis C6, C7, or C8 deficiency Sinopulmonary infections, neurologic deterioration, telangiectasia Ataxia-telangiectasia
- 29. Evaluated by measuring serum immunoglobulin levels Antibody titers to protein and polysaccharide antigens. Screening test for B-cell defects is the measurement of serum IgA. Selective IgA defeciency is most common varient
- 30. Low level of IgA & other Abs may be because of protein loosing conditions. Ab titers to specific Ag are obtained, before starting IVIG treatment Test for specific antibodies to diphtheria, tetanus, H. influenzae polyribose phosphate, and pneumococcal antigens.
- 31. If these titres are low then its confirmed 2 wk after Dtap or DT booster In a patients >2-3 years ability to respond to polysaccharide antigen can be tested by anti-pneumococcal antibodies measurement before and 3 wk after immunization with pneumococcal polysaccharide vaccine
- 32. Very high serum concentrations of 1 or more immunoglobulin classes suggest HIV infection, chronic granulomatous disease, chronic inflammation, or autoimmune lymphoproliferative syndrome (ALPS).
- 33. CD19 and CD20 should be innumerated by flow cytometry to distingwish between XLA and CVID Because children with hypogammaglobulinemia from XLA and CVID can have different clinical problems
- 34. Candida skin test:- - most cost-effective test of T-cell function Childrens >6 yrs:0.1 mL of a 1:1,000 dilution of a known potent Candida albicans extract, read at 24, 48 and 72 hrs if negative use 1:100 strengh positive, as defined by erythema and induration of ≥10 mm at 48 hr
- 35. Pediatric emergency that can be treated if diagnosed early Lymphopenic at birth TCR stimulated by mitogens like phytoagglutinin(PHA) or concanavalinvin A After incubation T cells are measured
- 36. Suspected if a patient has recurrent staphylococcal abscesses or gram-negative infections Screened by tests measuring the neutrophil respiratory burst after phorbol ester stimulation Flow cytometric assays of blood lymphocytes or neutrophils, using monoclonal antibodies to CD18 or CD11 (LAD1) or to CD15 (LAD2).
- 37. most effective screening test for complement defects is a CH50 assay The most common cause of an abnormal CH50 result, is a delay in or improper transport of the specimen to the laboratory.
- 38. Many primary immunodefeciency disorders can be diagnosed prenataly if specific mutation is known Selective sex determination can be done in case of X linked disorders
- 39. Depends on the primary immunodeficiency disorder Patients with an Ig or a complement deficiency have a good prognosis Other immunodeficient patients have a guarded prognosis If SCID is diagnosed before patients reach age 3 mo, transplantation of bone marrow life saving in 95%
- 40. High index of suspition Thorough history and complete physical examination is must Begin with screening tests and approperiate additional testing as required Teach patients how to avoid infections ,and do required preventive measures Early diagnosis and prompt treatment could be life saving
- 41. Nelsons textbook of pediatrics 19 th ed Diagnostic Approach to Primary Immunodeficiency Disorders; indian pediatrics,june 2013 Approach to the Patient With Suspected Immunodeficiency: Immunodeficiency Disorders: Merck Manual
Editor's Notes
- #9: Cdh- defective degranulation of neutrophils,LAD-B2 intigrins defect, cgd-defective generation of microbicidal o2 metabolite
- #22: Ln small in xla,scid othr t cell defects,,,,,,, cgd may have enlarged ln
- #24: (lymphocytes < 2000/μL at birth, < 4500/μL at age 9 mo, or < 1000/μL in older children or adults
- #29: Cd11, 18---LAD
- #34: Patients with XLA have a heightened susceptibility to persistent enteroviral infections CVID have more problems with autoimmune diseases and lymphoid hyperplasia
- #35: all primary T-cell defects are precluded, which obviates the need for more expensive in vitro tests such as lymphocyte phenotyping or assessments of responses to mitogens.
- #37: nitroblue tetrazolium (NBT) dye test,---- obsolete now
- #38: the serum dilution required to lyse 50% of antibodycoated RBCs is measured. This test (called CH50) detects complement component deficiencies in the classical complement pathway but does not indicate which component is abnormal. A similar test (AH50) can be done to detect complement deficiencies in the alternative pathway.
- #40: (eg, those with a phagocytic cell defect or combined immunodeficiencies, such as Wiskott-Aldrich syndrome or ataxiatelangiectasi