Primary Immunodeficiency How to Approach

by Supapat Bunyaratavej, M.D.

Table of contents
Who should be suspected to have primary immunodeficiency ? What type of immunodeficiency ? How to investigate ? How to management ?

Warning Sign of Primary Immunodeficiency Disorders

Warning Sign of Priamary Immunodeficiency Disorders

Warning Sign of Priamary Immunodeficiency Disorders

Warning Sign of Priamary Immunodeficiency Disorders

Warning Sign of Primary Immunodeficiency Disorders

Physical Examination Failure to thrive Absent lymph node or tonsils Skin lesion : Telangiectasia, Petechiae, Dermatomyositis or lupus like skin lesion Oral thrush > 1 y/o Ataxia

Table of contents
Who should be suspected to have primary immunodeficiency ? What type of immunodeficiency ? How to investigate ? How to management ?

Clinical Finding in the Major Subgroups of Primary Immunodeficiency Disorder

Disorder of humoral immunity Onset : After 6 mo., can present in adulthood Pattern of infection : Encapsulated bacteria e.g. pneumococci, Haemophilus influenzae Giardia lamblia, Cryptosporidium Other features : Recurrent infection of sinopulmonary system e.g. bronchiectasis, otitis media. Chronic GI problem include malaborption, autoimmunity, Postvaccination paralytic polio

Clinical Finding in the Major Subgroups of Primary Immunodeficiency Disorder

Disorder of T-cell or combined T-cell and B-cell Onset : Before 6 mo. Pattern of infection : Mycobacterium spp. CMV, EBV, varicella, Enterovirus Candida, PCP Other features : Failure to thrive, oral thrush, Graft versus host disease from maternal lymphocyte, excess diarrhea, Postvaccination disseminated bacille Calmette-Guerin infection or paralytic polio

Clinical Finding in the Major Subgroups of Primary Immunodeficiency Disorder

Disorder of phagocytic disorder Onset : Infancy or childhood Pattern of infection : Staphylococcus aureus, Pseudomonas spp. Serratia spp., Klebsiellla spp. FUNGUS : Candida, Aspergillus, Norcardia Other features : Granuloma formation e.g. granuloma enteritis, Poor wound healing, Abscess formation, Oral cavity or anorectal

Clinical Finding in the Major Subgroups of Primary Immunodeficiency Disorder

Disorder of complement disorder Onset : any age Pattern of infection : Neisseria meningitidis and gonorrhea Other features : Rheumatoid, Lupus like syndrome, scleroderma

Selected Primary Immunodeficiency Disorders

Disorder of humoral immunity Common variable immune deficiency (CVID) Selective IgA deficiency x-linked agammaglobulinemia

Selected Primary Immunodeficiency Disorders

Disorder of T-cell or combined B-cell and T-cell Severe combined immunodeficiency (SCID) DiGeorge syndrome Wiskott-Aldrich syndrome Ataxia-telangiectasia X-linked hyper IgM

Selected Primary Immunodeficiency Disorders

Disorder of phagocytic activity Chronic granulomatous disease (CGD)

Ataxia - Telangiectasia
This patient was diagnosed with ataxia telangiectasia when she presented at age 6 years. The family was concerned about the increased frequency of sinusitis during the past winter, and she was noted to have poor balance. Findings in her eyes had been explained as conjunctivitis since age 4 years

DiGeorges syndrome
affected children may have an upward bowing of their mouth, an underdeveloped chin, eyes that slant somewhat downward, low set ears and defective upper portions of their ear lobes. These facial characteristics vary greatly from child to child and may not be very prominent in many affected children

DiGeorges syndrome

Wiskott Aldrich syndrome

This 1-year-old boy was hospitalized because of respiratory syncytial virus bronchiolitis but was noted to have eczema and petechiae (note arrow). His history was significant for a subdural hematoma for which trauma was denied; at that time the platelet count was 212,000

Table of content
Who should be suspected to have primary immunodeficiency ? What type of immunodeficiency ? How to investigate ? How to management ?

Initial Screening Assays

CBC, PBS Serum immunoglobulin levels : IgM, IgG, IgA, IgD, IgE
Together with history and physical examination, these tests will identify more than 95% of patients with primary immunodeficiency

Other readily available assays

Quantification of blood mononuclear cell populations by immunofluorescence assays employing monoclonal antibody markers
T cell : CD3, CD4, CD8, TCR alpha beta , TCR gamma delta B cell : CD19, CD20, CD21, Ig Activation marker : HLA-DR, CD25, CD80 (B cell), CD154 (T cell) NK cells : CD16/CD56 Monocyte : CD15

Other readily available assays

T cell function evaluation
Delayed hypersensitivity skin test (PPD, Candida, Tetanus toxoid) Proliferative response to mitogen and allogeneic cells cytokine production

Other readily available assays

B cell function evaluation
Natural or commonly acquired antibodies : e.g. antibodies to common virus (influenza, rubella) and bacterial toxin (diptheria, tetanus) Response to immunization with protein (TT) and carbohydrate (pneumococcal vaccine, H. influenzae B vaccine) Quantitative IgG subclass determination

Other readily available assays

Complement
CH50(classic and alternative pathway) C3, C4 and other complement

Phagocyte function
Reduction of nitroblue tetrazolium Chemotaxis assays Bactericidal activity (Neutrophil oxidation burst)

Table of content
Who should be suspected to have primary immunodeficiency ? What type of immunodeficiency ? How to investigated ? How to management ?

Intravenous Immunoglobulin
IvIg is now standard treatment for most antibody deficiency
X-linked agammaglobulinemia CVID X-linked hyper IgM SCID Wiskott-Aldrich syndrome

Bone marrow transplantation

Can be curative in cellular immune deficiency
SCID Wiskott-Aldrich syndrome DiGeorge syndrome May be benefit in CGD

No role in immunodeficiency

Cautions of vaccines and blood products

Blood products should be come from CMV negative donors, and be filtrated to remove WBC and be irradiated to preveng GVHD Avoid live attenuated vaccine such as varicella, Polio, MMR Patients with IgA deficiency should be infomed about serious reaction of blood transfusion

Antibiotics prophylaxis and vaccination

Antibiotics Prophylaxis : may be useful Cotrimoxazole 5mg/k.g po bid reduced incidence of severe infection around 50% in CGD Immunization of encapsulated bacteria e.g. S. pneumoniae, Haemophilus influenzae type b in complement deficiency