immunodeficiency

see also:

• immunology
• http://www.worldallergy.org/professional/allergic_diseases_center/suspected_immune_deficiency/
• the immunocompromised patient in the ED

• 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

• account for 50-60%
• characterized by:
  • low levels of serum immunoglobulins
  • recurrent bacterial infections

• 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
• recurrent bacterial infections eg. recurrent sinusitis, bronchiectasis, chronic giardiasis, etc
• 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:
  • rheumatoid arthritis
  • vitiligo
  • haemolytic anaemia
  • thrombocytopenia
  • neutropenia
  • pyoderma gangrenosum
  • enteropathy, malabsorption
  • alopecia universalis
  • alopecia areata
  • granulomas - necrotizing and non-necrotizing
    • eg. granulomatous interstitial lung disease
    • sarcoidosis-like syndrome
  • polyarteritis nodosa (PAN)
  • lymphoid interstitial pneumonia
• malignancies - esp. B-cell lymphoma and stomach cancer
• splenomegaly

• with AID or UNG deficiencies
  • autosomal recessive
  • similar to X-linked hyper-IgM syndrome but with lymphoid hyperplasia
• with CD40 deficiency
  • autosomal recessive
  • similar to X-linked hyper-IgM syndrome
  • lymphoid hypoplasia
  • neutropenia
• with CD40 ligand deficiency
  • X-linked
  • similar to X-linked agammaglobulinemia (eg, recurrent pyogenic bacterial sinopulmonary infections) but greater frequency of Pneumocystis jirovecii pneumonia, cryptosporidiosis, severe neutropenia, and lymphoid hypoplasia

• recurrent sinopulmonary infections
• sometimes atopic manifestations

• 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
• see also IgA deficiency

• usually asymptomatic
• sometimes recurrent sinopulmonary or GI infections, candidiasis, meningitis

• 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
• see http://emedicine.medscape.com/article/1050956-overview

• 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
  • lymphoproliferation and lymphoma
  • elevated immunoglobulin E (IgE) production

• 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

• 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

• persistent or recurrent candidal infections, onychomycosis
• autosomal recessive autoimmune polyendocrinopathy–candidosis-ectodermal dystrophy (with hypoparathyroidism and adrenal insufficiency)

• asymptomatic until onset of EBV infection, then fulminant or fatal infectious mononucleosis with liver failure, B-cell lymphomas, splenomegaly, aplastic anemia

• no CD8 cells

• account for 20%

• AR (50%) or X-linked (50%)
• 1 case per 50,000-75,000 births
  • 15% are due to adenosine deaminase (ADA) deficiency which is AR and occurs in 1:100,000 births, and these may present later in life
• 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

• 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⁾
• physiology of CD70 and its ligand, the CD27 receptor

• AR
• ataxia, telangiectasias, recurrent sinopulmonary infections, endocrine abnormalities (eg, gonadal dysgenesis, testicular atrophy, diabetes mellitus), increased risk of cancer

• AR
• short-limbed dwarfism, common and opportunistic infections

• AR or X-linked
• common and opportunistic infections, lymphopenia, lymphadenopathy, hepatosplenomegaly, skin lesions resembling those of Langerhans cell histiocytosis in some patients

• 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

• AR
• common and opportunistic infections

• account for 10-20%
• predispose to cutaneous staphylococcal and gram-negative infections in particular

• 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

• 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)

• AD
• pyogenic bacterial infections during recurrent episodes of neutropenia (eg, every 14 to 35 days)

• AR
• oculocutaneous albinism, recurrent infections, fever, jaundice, hepatosplenomegaly, lymphadenopathy, neurologic changes, pancytopenia, bleeding diathesis

• AD or AR
• susceptibility to tuberculosis (TB)

• account for up to 2% of primary cases
• are generally autosomal recessive except for:
  • deficiencies of C1 inhibitor (autosomal dominant)
  • deficiencies of properdin (X-linked)
• may cause:
  • recurrent bacterial infections due to defective opsonization
  • autoimmune disorders (eg, SLE, glomerulonephritis) due to defective clearance of antigen-antibody complexes

• diabetes mellitus
• drugs
  • immunosuppressants including corticosteroids
  • cytotoxic agents
• radiation therapy
• haematologic causes:
  • aplastic anaemia
  • lymphoma
  • leukaemia
  • multiple myeloma
  • sickle cell disease (SCD)
  • the patient who has had a splenectomy and congenital asplenia
• infections
  • viruses esp. HIV / AIDS, EBV / glandular fever / infectious mononucleosis, cytomegalovirus (CMV), measles, varicella-zoster virus (chickenpox/shingles)
  • bacteria esp. staph.
  • tuberculosis (TB)
• chronic illness or malnutrition (including alcohol abuse)
• neonatal immaturity
• chronic renal failure
• nephrotic syndrome
• rheumatoid arthritis
• systemic lupus erythematosus (SLE)
• sarcoidosis
• histiocytosis
• Down's syndrome
• burns
• neoplasia / cancer / tumours