Immunodeficiency in a child (incl. HIV) Flashcards
How are primary immunodeficiencies classified?
According to which component of the immune system is affected
- Neutrophil disorders
- B-cell disorders
- T-cell disorders
- Leukocyte function defects
- Complement disorders
Name a neutrophil disorder.
- Chronic granulomatous disease - lack of NADPH oxidase so less ability to produce ROS
Others:
- Chediak-Higashi syndrome - microtubule defect means less phagocytosis
- Leukocyte adhesion deficiency (under leukocyte adheson) - integrin CD18 and CD11b defect on surface means they cannot migrate to sites of infection/inflammation
Name a leukocyte function disorder.
Leukocyte adhesion deficiency (LAD) - integrin CD18 and CD11b defect on surface means they cannot migrate to sites of infection/inflammation
Name 3 examples of B-cell disorders.
- Common variable immunodeficiency (CVID)- risk of AI disease and B-cell defificency, causes Burton agammaglobulinaemia later
- Burton/X-linked agammaglobulinaemia - tyrosine kinase gene defect causing block in B cell development
- Selective IgA deficiency - maturation defect in B cells
- Hyper IgM syndrome - B cells produce IgM but do not switch to IgA or IgG
Name 3 examples of T cell disorders.
- DiGeorge syndrome - 22q11.2 delection causing failure to develop 3rd and 4th pharyngeal pouches
- Severe combined immunodeficiency (SCID) - most commonly a defect in the common gamma chain (x-linked) used in receptors for IL-. Fatal without treatment, affecting both humoral and cellular immunity.
- Ataxic telangiectasia - DNA repair defect
- Wiskott-Aldrich syndrome - WASP gene defect causing immunodeficiency, thrombocytopenia and eczema (X-linked)
- HIV infection
- Duncan disease (X-linked lymphoproliferative disease) - cannot generate normal response to EBV, succumb to infection or develop secondary lymphoma
Name a complement defect disorder.
- Early complement deficiency
- Terminal complement component deficiency
- Mannose-bidning lectin (MBL) deficiency
How do T cell defects classically present?
Severe and unusual fungal infections
Faltering growth
e.g. severe bronchiolitis, diarrhoea, oral thrysh, pneumocystic jirovecii (carinii) pneumonia (PCP), disseminated CMV infection
How do complement defects classically present?
- Recurrent bacterial infections
- SLE-like illness
- Recurrent meningococcal, pneumococcal and haemophilus influenzae infections with deficiency of complement components
How do B cell defects classically present?
In first 2 years of life (after birth because they passively get Ab from mother)
Severe bacterial infections especially ear, sinus, pulmonary, skin infections, recurrent diarrhoea, faltering growth,
Recurrent pnreumonias causing bronchiectasis and ear infections causing impaired hearing
How do neutrophil defect classically present?
- Recurrent bacterial infections and abscesses (skin, lymph nodes, lung, liver, spleen, bone)
- Poor wound healing
- Perianal disease and periodontal infections
- Invasive fungal infections e.g. aspergillosis
- Diarrhoea and faltering growth
- Granulomas from chronic inflammation
SCID
Heterogenous group of inherited disorders. Most commonly a defect in the common gamma chain (x-linked) used in receptors for IL-2. Fatal without treatment, affecting both humoral and cellular immunity.
DiGeorge syndrome
Abnormal development of the 5th branchial arch causing
The classical presentation is a triad of
- cardiac anomalies,
- absence of thymus,
- and hypocalcaemia (resulting from parathyroid hypoplasia).
- palatal and facial defects also occur
Ataxic telangiectasia
Autosomal recessive.
Features include
- cerebellar ataxia,
- telangiectasia (spider angiomas),
- recurrent chest infections
- and 10% risk of developing malignancy, lymphoma or leukaemia
Wiskott-Aldrich syndrome
X-linked recessive.
Features include
- recurrent bacterial infections,
- eczema,
- thrombocytopaenia.
- Low IgM levels
- Increased risk of autoimmune disorders
- and malignancy
Hyper IgM syndromes
- Infection/Pneumocystis pneumonia,
- hepatitis,
- diarrhoea
A newborn girl presents with cyanosis after an unremarkable pregnancy and delivery. A hyperoxia test suggests congenital heart disease, and an echocardiogram confirms tetralogy of Fallot. The infant subsequently has a seizure, and serum calcium is 5.8 mg/dL. Intact PTH level is low. T-cell enumeration by flow cytometry reveals a CD3+ cell count of 780 cells/mm^3. At age 4, she begins schooling but has difficulty performing up to the level of her peers. She has hypernasal speech that is sometimes difficult to understand. Nevertheless, she completes her schooling and is able to work productively. What condition is this?
DiGeorge syndrome
A 6-month-old boy is referred to an immunology centre for evaluation of recurrent viral pneumonias. Prior studies have documented parainfluenza type 3 and adenovirus by polymerase chain reaction of respiratory washings. Laboratory evaluations reveal lymphopenia (ALC of 1200 cells/mm³). A chest x-ray reveals an absent thymic shadow. Lymphocyte phenotyping by flow cytometry reveals severely reduced T cells, B cells, and NK cells (i.e., T-B-NK-). DeoxyATP levels in erythrocytes are markedly elevated, consistent with the diagnosis of adenosine deaminase deficiency. What condition is this?
SCID
A 2-year-old boy presents with patchy eczema affecting limbs, face, and trunk. He was delivered at term by forceps and noted to have a cephalhaematoma. Platelets at the time were below the normal range and were still low on re-testing. He has a history of recurrent ear infections and perforated eardrum for which he has received 4 courses of antibiotics in the past year. He has not had any other significant infections and is thriving. On examination he has moderate patchy eczema affecting limbs, face, and trunk with petechiae in areas of excoriation but is otherwise well. He is the first child of non-consanguineous parents, and one of his mother’s uncles died in infancy of bleeding. What is this condition?
Wiskott-Aldrich syndrome - triad of thormbocytopenia, eczema and recurrent infections
Which factors prevent HIV vertical transmission during birth and after?
Factors which reduce vertical transmission (from 25-30% to 2%)
- maternal antiretroviral therapy
- mode of delivery (caesarean section) with zodovudine infusion started before it
- neonatal antiretroviral therapy
- infant feeding (bottle feeding) - NOT breastfeeding
What investigations would you consider for immunodeficiency?
What management options exist for treating immunodeficiency?
- Antimicrobials e.g. antifungals
- Antibiotics e.g. for B cell disorders
- IVIG infusions - through Hickman or Portacath for central venous access
- Gene therapy
- Screens for end organ disease e.g. CT for bronchiectasis
- Bone marrow transplant e.g. for SCID
How do leukocyte function defects classically present?
- Delayed separation of umbilical cord
- Delayed wound healing
- Chronic skin ulcers
- Deep-seated infections
