Approach to Immunodeficiency in children.pptx

Approach to immunodeficiency
Child with recurrent infections

1. APPROACH TO IMMUNODEFICIENCY DISORDERS DR JAMILA PG TRAINEE PAEDS 2

2. OBJECTIVES CLASSIFY THE IMMUNODEFICIENCY IDENTIFY THE WARNING SIGNS APPROACH TO A PATIENT WITH SUSPECTED PRIMARY IMMUNODEFICIENCY PROPER COUNSELLING

3. CLASSIFICATION Immunodeficiencies are broadly classified as Primary immunodeficiency Secondary immunodeficiency

4. CLASSIFICATION OF PRIMARY IMMUNODEFICIENCIES Antibody production defects Cellular or combined defects Phagocytic immune defects Complement defects

5. Strategies for treatment and management of pids disease supportive definitive CID/SCID IG replacement, antifungal and antibiotic prophylaxis, withhold all live vaccines. Aggressive management of established infections. BMT HSCT Gene therapy B cell disorder Ig replacement, antifungal and antibiotic prophylaxis, hearing and lung function assessment Gene therapy Innate disorder Antibiotic and antifungal prophylaxis, vaccinations, ig replacement at times needed. Cytokine replacement for CGD. BMT for CGD Gene therapy

6. KEY CONCEPTS SITE OF INFECTION POSSIBLE CAUSE UPPER RTI/ BLOOD OR CNS (MENINGES) ANTIBODY OR COMPLEMENTS DEFECTS LOWER RTI ANTIBODY OR COMPLEMENTS DEFECTS, T CELL DEFICIENCY,PHAGOCYTIC DEFECTS SKIN OR INTERNAL ORGANS PHAGOCYTIC DEFECTS

7. ANTIBODY PRODUCTION DEFECTS DISESASE COMMON NAME X LINKED AGAMMAGLOBINEMIA (BRUTON’S) AGAMMAGLOBINEMIA OR XLA COMMON VARIABLE IMMUNODEFICIENCY (CVID) LATE ONSET HYPO OR AGAMMAGLOBINEMIA(CVID) X LINKED OR AUTOSOMAL HYPER IG M SYNDROME HYPER Ig M SELECTIVE IG A DEFICIENCY Ig A DEFICIENCY

8. ANTIBODY PRODUCTION DEFECTS RECOGNITION: Recurrent Sino pulmonary infections Pneumonia Sinusitis documented by X-ray or Computerized tomography (C-T) scan Otitis media Meningitis and/or sepsis (blood stream infection) Gastrointestinal infections Cutaneous (skin) infection

9. ASSESSMENT: Complete blood count and manual differential Quantitative serum immunoglobulin (IgG, IgA, IgM and IgE ) levels Measurement of specific antibodies to vaccines Isohemagglutinins

10. MANAGEMENT, EXPECTATION, COMPLICATIONS AND LONG TERM MONITORING: Ig G antibody replacement (except for selective ig a deficiency and transient hypogammaglobinemia of infancy) Annual screening of ig g trough levels, xray or ct scans,spirometry,rfts and lfts , Annually or 6 monthly assessments of children with meningoencephalitis due to enterovirus.

11. Annual screening for hep a , b and c by pcr . Diagnostic screening for malignancies like LDH, ESR, ad uric acid.

12. Vaccinations: Household contacts should receive influenza vaccine yearly. All live vaccine are contraindicated in theses patients .

13. Commonly asked questions Will a patient outgrow disease? Any need for extra ig during infection or surgery? Can ig be given orally or via CV line? Can it be given during pregnancy? Is it important to keep a good record while infusing ig ? What are common reactions with ig g infusion? Lifestyle modifications needed?

14. CELLULAR OR COMBINED DEFECTS DISEASE COMMON NAME SEVERE COMBINED IMMUNODEFICEINCY BUBBLE BOY (SCID) DIGEORGE SYNDROME OR 22q11 DELETION THYMIC APLASIA ATAXIA TELANGIECTASIA AT WISCOTT ALDRICH SYNDROME WAS

15. Bulbar conjunctiva shows telangiectasia

16. RECOGNITION: Appear ill Have facial dysmorphia Fail to thrive » Weight is a more important determinant than length Have congenital heart disease Have skin change Have chronic intractable diarrhea Develop intractable viral infections due to RSV,CMV or adenovirus Have infections not accompanied by lymphadenopathy except in the Wiskott -Aldrich syndrome

17. Have adverse reactions after live vaccines such as Varivax , given to prevent chicken pox Have neurological findings such as ataxia or tetany of the newborn ( DiGeorge syndrome) Have X-linked immune dysregulation and polyendocrinopathy (IPEX), or chronic mucocutaneous candidiasis (CMC,APCED) Need to have a diagnosis of Human Immunodeficiency Virus (HIV) infection exclude

18. ASSESSMENT: WBC and platelet count T cell functional testing/ flow cytometry Genetic testing Quantitative ig measurement and antibody testing

19. MANAGEMENT, EXPECTATION AND LONGTERM COMPLICATIONS: Only irradiated, wbc depleted, cmv depleted blood products should be used. No live vaccine to be given. Household contact vaccinated yearly for influenza. Life threatening infections in SCID are PJP, candida, parainfluenza 3, CMV, RSV, adenovirus, and EBV.

20. Bonemarrow transplantation early in life for SCID. Ig replacement therapy in WAS. Thymic transplantation in Digeorge as susceptibility to other complications such as developmental delay, seizure, severe autoimmune disease or EBV induced lymphoma remains. AT (Ataxia Telangiectasia) patients and patients with SCID due to Artemis gene mutations should minimize their exposure to ionizing irradiation as highchance of chromosomal instability.

21. Counseling: Several of these disorder follow X linked pattern. Digeorge may follow autosomal dominance but maximum cases are sporadic.

22. Frequently asked questions: What kind of vaccine are safe?

23. PHAGOCYTIC CELL IMMUNE DEFECTS DISEASE COMMON NAME LEUKOCYTE ADHESION DEFECT LAD CHEDIAK HIGASHI SYNDROME CHS CHRONIC GRANULOMATOUS DISEASE CGD CYCLIC NEUTROPENIA KOSTMAN DISEASE NEUTROPENIA

24. RECOGNITION: Skin—abscesses (seen in CGD and the Hyper IgE syndrome) or cellulitis (seen in LAD) Lymph nodes—may be swollen and contain pus in CGD patients In LAD there may be delayed shedding of the umbilical cord or omphalitis and cellulitis but no abscesses. Osteomyelitis—(CGD). Hepatic Abscess—liver absesses may also be seen in CGD Lungs—Aspergillus (mold) lung disease is insidious and common in patients with CGD.

25. Gastrointestinal tract outlet and/or urinary tract obstruction resulting in abdominal or back pain is often seen in CGD, Mouth (gingivitis)—gum inflammation, mouth ulcers Unexplained fever without identifiable cause Malaise and fatigue Albinism may be seen in Chediak Higashi syndrome

26. ASSESSMENT: CBC (two time per week for 1 month in cyclic neutropenia) CD11/18 Respiratory burst assay.

27. MANAGEMENT, EXPECTATION AND LONGTERM COMPLICATIONS: Prophylactic antibiotics Prophylactic antifungals ( cgd ) G-CSF ( kostman syndrome) Patients with CGD have normal T cell and B cell function. Therefore, they are not susceptible to viral infections, can receive live virus (but not BCG) vaccines, and can attend school and visit public areas such as mall Bonemarrow transplantation in CGD.

28. Typically, hemogloblin , hematocrit, ESR (erythrocyte sedimentation rate) and/or CRP (C-reactive protein) and a chest X-ray should be followed regularly in CGD. Genetic counselling necessary specially in CGD.

29. Frequently asked questions: What places can my child visit or what activities can he/she participate? What vaccines are safe ?

30. COMPLEMENT DEFECTS DISEASE COMMON NAME C1 ESTERASE INHIBITOR DEFICIENCY HEREDITARY ANGIOEDEMA COMPLEMENT COMPONENT DEFICIENCY COMPLEMENT DEFICIENCY

31. RECOGNITION : C3 deficiency is very rare, but is characterized by recurrent serious bacterial infections, such as pneumonia or bacteremia, and development of MPGN. Systemic Neisseria infections in children and adolescents C5-7 deficiencies: Recurrent Central Nervous System (CNS) infections are more common in African Americans than Caucasians with complement component deficiencies. Genitourinary tract infections Cutaneous lupus and other autoimmunity with deficiencies of C1/C2/C4.

32. Hereditary Angioedema : Patients may experience recurrent episodes of abdominal pain, vomiting and laryngeal edema. The diagnosis is clinically and the repeated finding of qualitative or quantitative decrease of C1 inhibitor and reduced levels of C4.

33. ASSESSMENT: CH50 AH50

34. MANAGEMENT, EXPECTATION AND LONGTERM COMPLICATIONS: Prophylactic antibiotics Pnumococcal vaccine for prophylaxis. Complications include SLE, lupus like syndromes, and glomerulonephritis. Mannose binding lectin defect .

35. GENETIC COUNSELLING: All form of inheritance present. Angioedema more commonly with AD inheritance.

36. Frequently asked questions: Can my child attend public places? Can he be vaccinated?

37. TAKE HOME POINTS PIDs are more frequent then previously believed. Clinical presentation is variable , but most involve increased susceptibility to infection. PIDs should be suscepted at any age in patients with the warning signs.

38. Consultation with a clinical immunologist is required to confirm the diagnosis of PID and to establish an appropriate treatment plan. SCID is fatal unless the underlying defect is corrected therefore definitive therapy like HSCT should be initiated as early as possible. Ig replacemtn is the main stay of treatment for antibody deficiency disorder and importan supportive therapy for other forms of PID (SCID/CID).

39. THANKYOU FOR YOUR ATTENTION AND PATIENCE STAY SAFE ,STAY HEALTHY