Primary Immunodeficiency Flashcards
What are primary immunodeficiency diseases?
Conditions characterized by intrinsic deficits within the immune system and are caused by inherited or de novo genetic defects
What are three general symptoms of immunodeficiency?
Frequent, severe, unusual infections
Autoimmune disease
Immune dysregulation
When do phagocytic usually present?
Early in infancy, childhood
What is the infection pattern associated with phagocytic defects?
Catalase + bacteria (S. aureus)
Klebsiella, enteric flora
Mycobacteria including BCG
Fungi: Candida, Aspergillus, Paecilomyces
What is the workup for suspected neutrophil defects?
CBC with diff. (absolute neutrophil count)
Test ability of polymorphonuclear cells to generate an oxidative burst: Dihydrohodamine test (DHR), Nitroblue tetrazolium (NBT)
What are the clinical features of Chronic Granulomatous Disease?
Recurrent infections
Granulomas of skin, liver, lungs, viscera
GI/GU obstruction
X-linked or autosomal recessive
What is the diagnosis and treatment for chronic granulomatous disease?
Neutrophil oxidative burst assay by flow cytometry using DHR
Prophylactic antibiotics, Gamma interferon, Bone marrow transplantation
What are the clinical features of leukocyte adhesion deficiency type 1?
Infections affecting skin, respiratory tract, bowel and perirectal areas
Delayed wound healing, absence of pus
Severe periodontitis
Delayed separation of the umbilical cord
What is the diagnosis and treatment of LAD type 1?
Leukosytosis,
Absence of CH18 and CD11
Prophylactic antibiotics, bone marrow transplant
How are NK cell deficiencies characterized?
Severe, recurrent, or atypical infections with herpes virus
Can occur due to quantitative or functional NK cell deficiency
What is the infection pattern for complement deficiency?
Encapsulated organisms: Neisseria, pyogenic infection
Frequent autoimmune disease
What is the test for complement defects?
CH50
Generally 0 in complement deficiencies
What are the clinical features of complement component deficiency?
Recurrent pyogenic infection and CT disease
Late component deficiency - Neisseria infection
Deficiency of regulatory protein C1 esterase inhibitor is associated with angioedema
What is the infection pattern of antibody deficiency?
S. pneumonia, H. influenza, S. aureus, N. meningitidis etc.
Common respiratory and enteroviruses, rotavirus
Giardia, Cryptosporidium
What is the workup for antibody deficiencies?
Quantitative Igs
Vaccine titers - qualitative measure of antibodies
Lymphocyte subsets
What are the clinical features of X-linked Agammaglobulinemia?
Infancy/childhood with recurrent sinopulmonary pygoenic infections, 25% with neutropenia
What are the diagnostic criteria for XLA?
Absent B cells
~50% positive family history
Low IgG
B cells <2% of lymphocytes
What are the clinical features of common variable immunodeficiency?
Recurrent sinopulmonary infections
Autoimmune dieases
Possible malignancy
What are the diagnostic criteria and treatment for CVID?
Reduced IgG
Low IgA and low/normal IgM
Poor response to immunization
Treat: Replacement IG
What are the clinical features of Hyper IgM?
Recurrent sinopulmonary infections
Susceptible to opportunistic infections as well as liver disease due to CMV
What is the cause of Hyper IgM?
Mutations of CD40L - X-Linked
What are the diagnostic criteria for Hyper IgM?
Reduced total serum concentrations of IgG, IgA, and IgE
Norma/elevated IgM
Lack of antibody repsonse to protein
Normal total B cells, reduced memory B cells
What is the treatment for Hyper IgM?
Replacement IG
Prophylaxis for opportunistic infections
Hematopoietic cell transplantation (HCT)
What are the clinical features of selective IgA Deficiency?
Recurrent sinopulmonary
AI disease
Increased risk for GI disease
Allergic disease
What are the diagnostic criteria for selective IgA deficiency?
Reduced IgA
Normal IgM and IgG
Patient over 4
Normal antibody response
What is the workup for suspected T-cell/combined defects?
CBC with diff - low absolute lymphocyte count
Lymphocyte subset enumeration
Quantitative immunogloculins
T-cell proliferation
What are the clinical features of SCID?
Failure to thrive, chronic diarrhea, erythroderma or other skin eruption
What is the diagnostic criteria for SCID?
Lymphopenia in most
Diminished or absent T cells
Poor/absent in virto mitogen-induced T cell proliferation
What is DiGeorge Syndrome and the clinical features?
Underdevelopment of the thymus
Conotruncal cardiac anomalies, hypoplastic thymus, hypocalcemia
What is Wiskott-Aldrich Syndrome?
X-linked disease characterized by thrombocytopenia with small platelets, excema, cellular and humoral immunodeficiency
Caused by mutations in WASP protein
What is Ataxia-Telangiectasia?
Autosomal recessive chromosomal breakage syndrome characterized by progressive cerebellar neurodegeneration, ID, radiosensitivity, and increased cancer susceptibility
