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Immune Deficiency.

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Presentation on theme: "Immune Deficiency."— Presentation transcript:

1 Immune Deficiency

2 Immunoglobulin levels vs. age

3 Types of immunity Innate (natural) immunity  responds to infection regardless of previous exposure to the agent Ex: PNL, phagocytic cells, complement system Acquired (adaptive) immunity  develops as a result of exposure to previous immunogens Ex: T lymphocytes, B lymphocytes, NK cells

4 Immunologic defects (1) T cell (2) B cell (3) Macrophage
(4) Complement

5 Primary immunodeficiency
Inherited genetic defects in the immune cell development or function or inherited deficiency in a particular immune molecule Secondary immunodeficiency Loss of previously functional immunity due to infection, toxicity, radiation, splenectomy and malnutrition

6 When to suspect 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 Recurrent or resistant candidiasis Serious infections occuring at unusual sites (brain, liver abscess)

7 Infection with opportunistic organisms
Complications from live vaccines (rota virus, varicella) Non healing wounds Granulomas Lymphoma in infancy Features suggestive of PID in neonates Hypocalcemia Congenital heart defects (conotruncal anomalies) Absence of thymic shadow in CXR Delayed umbilical cord detachment (>30 days)

8 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)

9 Infection history 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 2 to 6 years – children developing infection in this age group may also fit into any of the 4 categories. Secondary immunodeficiencies resulting from malignancy, nephrotic syndrome, or gastrointestinal problems start at this age 6 to 18 years – it is unusual for recurrent infections to first present beyond the age of six

10 2. Sites of infection: Upper respiratory tract Most common site, usually viral Chronic purulent nasal discharge and cough  chronic siunsitis Chronic or seasonal clear nasal discharge, congestion, itchy eyes, nocturnal cough  allergic disease Recurrent oral thrush, stomatitis, gingivitis,  t-cell and phagocytic cell disorder 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

11 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 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

12 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

13 Organisms that suggests an immunodeficiency
disease Pneumocystis jiroveci HIV,SCID,HyperIgM,XLA Serratia marcescens Chronic granulomatous disease Aspergillus, nocardia Psedomonas sepsis XLA,ARA Mycobacteria/salmonella IFN-gamma,IL12 pathway

14 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 Mouth ulcers, gingivitis, oral thrush, poor dentition, suggest immunodeficiency Atopic dermatitis (eczema) suggest allergic disease.

15 Immunodeficiencis associated with eczema: wiskott-aldrich, hyper IgE, SCID,
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.

16 Characteristic features of primary immunodeficiency
Predominant T-cell defect Predominant B-cell defect Granulocyte defect Complement defect Age Early onset,2-6mo After maternal antibodies diminish,>5m Early onset Any age Sp pathogen involved Bact:mycobact Viruses:CMV,EBV,adeno Fungi:candida Bacteria: strep.staphylo,hemophilus Virus:entero Bact:staph,pseudo,klebsiella Neisseria,E-coli Affected organ FTT,protracted diarrhea, Recurrent sinupulmonary infections,GI infections,malabsorption Skin abscess,suppurative adenitis Meningitis, Recurrent sinupulmonary infections Special features GVH diseases,post vaccination,disseminated BCG Autoimmunity,lymphoma,post vaccination paralytic polio Prolonged attachment of umblical cord,poor wound healing Rheumatoid disotder:SLE, Vasculitis,glomerulonephritis

17 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 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: oculocutaneous albinism

18 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 patient’s family can be reassured that a serious disorder has been excluded.

19 General screening tests
Complete Blood Count With special attention paid to the total absolute lymphocyte count: lymphopenia <1500cells/uL in patients over 5 years or <2500 cells/uL in younger children Eisinophilia suggests allergy Thrombocytosis suggests chronic inflammation Electrolytes, glucose, KFT, albumin Urine analysis ESR, CRP, appropriate cultures should be done for evaluation of infection Chest X-ray should be done if the child has chronic cough or other features suggesting lung problems it should also be done in newborns presenting with recurrent infections for assessment of thymic size

20 Other initial investigations:
Immunoglobulin levels: Antibody defeciency is suggested by: IgG <200 mg/dL Total Ig (M + G + A) <400 mg/dL Complete absence of IgM or IgA An elevated IgE (>100mg/dL) suggests allergy, eczema, or chronic skin infections or may be found in hyper IgE syndrome, phagocytic disorders

21 Intermediate tests for immunodeficiency
These tests are indicated when the screening tests are abnormal or the clinical picture is highly suggestive for an immunodeficiency. Antibody titres The function of the antibody system is best assessed by checking antibody titres to previously administered vaccines (tetanus, diphtheria, and hemophilus influenza type b. Complement activity should be assessed in patients with recurrent sepsis of neisserial infection. A normal level of CH50 excludes nearly all hereditary complement deficiencies. Levels of individual complement componenets are measured of the CH50 is significantly reduced or zero.

22 Diagnostic tests Should be done when previous tests are abnormal or if there is a convincing history of immunodeficiency. Lymphocyte subset analysis: done by flow cytometry including CD3 (total T cells), CD4 (T helper), CD8 (cytotoxic), CD19 or CD20 (B cells) and CD16/56 (natural killer cells) is done when B or T cell defect is suspected. CD4 is the most valuable reflection of the cellular immune system CD19 (B cell) count <100 cells/uL suggests hereditary agammaglobulinemia A low CD16/56 count suggests a NK cell deficiency

23 Vaccine challenge Vaccine responsiveness is used to further assess the antibody system. A killed vaccine that has not been administered previously is given and titres are measured before and 6 weeks after vaccination. Other tests HIV Testing should be done in any patient suspected of a T cell deficiency Lymphoproliferative Assays these are in vitro assays used to further assess the cellular immune system

24 Management of the child with recurrent infection
Infections should be promptly recognized and treated with emperic antibiotic therapy until appropriate culture results are available Prophylactic antibiotics may be administered Live – virus vaccines and live BCG vaccines must not be administered to the child Only irradiated, leukocyte - poor, virus free should be used if blood transfusion is necessary IVIG should not be administered until there has been a thorough evaluation of the childs immune system. (expensive, side effects)

25 Initial immunologic testing of the child with recurrent infections
Complete blood count, differential, ESR Lymphocyte, neutrophils, platelets, Howell jolly bodies, ESR Screening tests for B-cell cefects IgA, if abnormal IgG, IgM measurement Isohemagglutinins Antibody titres to tetanus, diphtheria, H.influenzae Screening test for Tcell defect Absolute lymphocyte count Candida albicans intradermal test Screening test for phagocytic cell defect Absolute neutrophil count Respiratory burst assay Screening test for complement deficiency CH50

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