immunodeficiency
immunodeficiency
primary immunodeficiencies
these are genetic conditions and there are over 100 known conditions
most present in childhood with abnormally frequent (recurrent) or unusual infections
transmission is often X-linked and thus males are affected more than females
overall incidence of symptomatic cases is 1/280
humoral (B-cell) immunodeficiencies
account for 50-60%
characterized by:
common variable immunodeficiency (CVID)
prevalence: 1 case per 50,000 population
low levels of IgG, IgA and perhaps IgM
lack of B lymphocytes or plasma cells that are capable of producing antibodies
variable inheritance, 5 distinct phenotypes
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usually diagnosed in young adults aged 20-40yrs, although peak of onset is in those aged 1-5 years and in those 16-20 years
20% develop autoimmune complications such as:
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pyoderma gangrenosum
enteropathy, malabsorption
alopecia universalis
alopecia areata
granulomas - necrotizing and non-necrotizing
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lymphoid interstitial pneumonia
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splenomegaly
Hyper-IgM syndromes
Selective antibody deficiency with normal immunoglobulins
Selective IgA deficiency
occurs in 1 in 400 to 1 in 18,500 depending upon ethnic population
it is a heterogeneous disorder and may be partial or total deficiency
it has a similar pathogenesis as CVID
variable genetics, but may also be acquired from infections or drugs although in these cases tends to be reversible
usually asymptomatic
may cause recurrent sinopulmonary infections, diarrhea, genito-urinary infections, allergies, autoimmune disorders (eg, celiac disease, inflammatory bowel disease, SLE, chronic active hepatitis)
as 10-44% have anti-IgA antibodies, rarely, severe allergic reactions to blood transfusions may occur as these contain IgA
occurs in ~2% of patients with celiac disease while celiac disease occurs in 10-30% of these patients
the condition may result in failed diagnosis of celiac disease as the high levels of certain IgA antibodies usually seen in celiac disease do not occur
not associated with increased risk of cancer
may progress to CVID
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Transient hypogammaglobulinemia of infancy
X-linked agammaglobulinemia (XLA) or Bruton agammaglobulinaemia
1 case per 250,000 population, only males are affected
most men live into their 40's
recurrent sinopulmonary and skin infections during infancy
transient neutropenia
lymphoid hypoplasia
persistent CNS infections resulting from live-attenuated oral polio vaccine, echoviruses, or coxsackieviruses
increased risk of infectious arthritis, bronchiectasis, and certain cancers
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cellular (T-cell) immunodeficiencies
5-10% of immunodeficiencies
predispose to infections by viruses, fungi, opportunistic and other pathogens
characterized by:
an incomplete reduction in T-cell number or activity
autoimmunity
inflammatory diseases
increased frequency or severity of infections
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elevated immunoglobulin E (IgE) production
DiGeorge syndrome (DGS)
autosomal
unusual facies with low-set ears, a congenital heart disorder (eg, aortic arch abnormalities), thymic hypoplasia or aplasia, hypoparathyroidism with hypocalcemic tetany, recurrent infections, developmental delay
chromosomal breakage syndromes (CBSs)
Wiskott-Aldrich Syndrome (WAS)
X-linked
typically, pyogenic and opportunistic infections, eczema, thrombocytopenia
possibly GI bleeding (eg, bloody diarrhea), recurrent respiratory infections, cancer (in 10% of patients > 10 yr), varicella-zoster virus infection, herpesvirus infection
chronic mucocutaneous candidiasis
persistent or recurrent candidal infections, onychomycosis
autosomal recessive autoimmune polyendocrinopathy–candidosis-ectodermal dystrophy (with hypoparathyroidism and adrenal insufficiency)
X-linked lymphoproliferative syndrome
asymptomatic until onset of
EBV infection, then fulminant or fatal infectious mononucleosis with liver failure, B-cell lymphomas, splenomegaly, aplastic anemia
ζ-Associated protein 70 (ZAP-70) deficiency
Omenn Syndrome
combined B-cell and T-cell immunodeficiencies
Severe Combined Immunodeficiency (SCID)
AR (50%) or X-linked (50%)
1 case per 50,000-75,000 births
most present before 3 months age with mean age at diagnosis of 6-7 months
without intervention, SCID usually results in severe infection and death in children by age 2 years
oral candidiasis, P. jirovecii pneumonia, diarrhea before 6 mo, failure to thrive, graft vs host disease, absent thymic shadow, lymphopenia, bone abnormalities (in ADA deficiency), exfoliative dermatitis as part of Omenn syndrome
CD70 deficiency
AR
reduced activity of pathogen-fighting T cells, poor activation of antibody-producing B cells and low production of antibodies
poor immune control over EBV
homozygous patients are predisposed to Hodgkin's lymphoma if also infected by EBV
1)
CD70 deficiency may also impair macrophage function and increase atheroclerosis
2)
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ataxia telangiectasia
AR
ataxia, telangiectasias, recurrent sinopulmonary infections, endocrine abnormalities (eg, gonadal dysgenesis, testicular atrophy, diabetes mellitus), increased risk of cancer
Cartilage-Hair Hypoplasia
Combined immunodeficiency with inadequate but not absent T-cell function and normal or elevated Igs
AR or X-linked
common and opportunistic infections, lymphopenia, lymphadenopathy, hepatosplenomegaly, skin lesions resembling those of Langerhans cell histiocytosis in some patients
Hyper-IgE syndrome
AD or AR
sinopulmonary infections; staphylococcal abscesses of skin, lungs, joints, and viscera; pulmonary pneumatoceles; pruritic dermatitis; coarse facial features; delayed shedding of baby teeth; osteopenia; recurrent fractures; tissue and blood eosinophilia
MHC antigen deficiencies
phagocytic cell immunodeficiencies
chronic granulomatous disease
X-linked or AR
granulomatous lesions in the lungs, liver, lymph nodes, and GI and GU tract (causing obstruction); lymphadenitis; hepatosplenomegaly; skin, lymph node, lung, liver, and perianal abscesses; osteomyelitis; pneumonia; staphylococcal, gram-negative, and aspergillus infections
leukocyte adhesion deficiency
types 1 and 2
AR
soft-tissue infections, periodontitis, poor wound healing, delayed umbilical cord detachment, leukocytosis, no formation of pus
developmental delay (type 2)
cyclic neutropenia
Chédiak-Higashi syndrome
AR
oculocutaneous albinism, recurrent infections, fever, jaundice, hepatosplenomegaly, lymphadenopathy, neurologic changes, pancytopenia, bleeding diathesis
Mendelian susceptibility to mycobacterial disease (MSMD)
complement immunodeficiencies
secondary immunodeficiencies
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drugs
radiation therapy
haematologic causes:
infections
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neonatal immaturity
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Down's syndrome
burns
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immunodeficiency.txt · Last modified: 2017/04/04 10:27 (external edit)