Allergy & Immunology Flashcards
Cyclical neutropenia- genetics, features
AD (90% causes by mutation in ELANE elastase gene)
- Presents first few yrs with recurrent fever (every 21d), neutropenia, malaise +/- mouth ulcers (gingival hyperplasia = more significant disease)
- Monitor 2-3x/wk for 6-8wks to diagnose
Types of porphyria and features
Accumuation of intermediate in heme synthesis pathway
- erythropoetic- bone marrow
- hepatic pathway
Erythropoetic protoporphyria
-Most common in children
- Ferrochelatase deficiency, EPP elevated
- Photosensitivity within minutes of exposure
- Pain/erythema lasting days
-
Porphyria cutanea tarda
- Most common in adults
- Blistering/scarring of sun exposed
What vaccines should an egg allergic individual avoid?
Specialist consult prior to yellow fever and Q fever (potentially higher amounts of egg)
Influenza (traces) & MMR (no egg protein) safe
- If prev anaphylaxis to vaccine then avoid until specialist consult
Eczema, staph abscesses of lung, skin, joints. Very high IgE levels
Hyper IgE syndrome
Recurrent sinopulmonary infections, eczema, low IgG, IgA, IgM, B cells >1.
CVID
- MOstly AD, multiple genetic defects
- Hypogamm with phenotypically normal B-Cells
- Similar to XLA but less severe
- Equal sex distribution
- Normal tonsils +/- splenomegaly 25%
Infection with encapsulated bacteria, prone to lymphoproliferative disease/8% increased risk malignancy, no meningitis entero/hepatitis
Respiratory infections, chronic diarrhoea, type 3 (Ag/Ab complex) hypersensitivity reactions/transfusion reaction- low IgA
Selective IgA deficiency
<10mg/dL IGA
Assoc coeliac, allergic disease, autoimmunity, anti-IgA ABs 33%
Can be caused by drugs (CBZ/valproate, penacillamine, sulfasalazine, HCQ, NSAIDs), TORCH infections
Infections: Giardia common
Anaphylaxis to IgA products (need washed PRBC)
Rx: IVIG = RISK OF ANAPHYLAXIS
Hypersensitivity reactions
Thrombocytopenia, eczema
Wiskott Aldrich
- X-linked
- Thrombocytopenia with small platelets/decreased function
- Recurrent infection
- Eczema
- 5% go on to have lymphoreticular malignancies
Rx: splenectomy (fixes low plts), BMT curative
Recurrent sinopulmonary infections +/- meningitis, absent tonsils. Ig G,A,M low, B cells absent.
X-Linked Agammaglobulinemia
Xq22 – XLA gene = codes for B-cell protein tyrosine kinase (Bruton tyrosine kinase)
- Needed for B cell expansion/maturation
Well until 6-9mo when mat immunity wears off
- Recurrent pyogenic organisms (S.Pneumo, H.Influenza)
- Viral exacerbations with hepatitis/enterovirus (CNS echo/coxsackie virus/myositis)- other viruses tolerated
- Mycoplasma
- Fungal infections
Ix: lymphocyte subsets = B <1%, T cells elevated, IgG, IgA, IgM, IgE <95%, vaccine responses absent
Rx: lifelong IVIG, prophylactic ABx
What is XLP?
Rare, severe dysregulation of the immune system
Usually occurs in response to EBV
Risk of HLH, lymphoma
- Fulminant/fatal EBV 60%
- Lymphoma 30%
- B cell changes 20-30% ↓ IgG, ↑ IgA and ↑ IgM
Xq25, defect in SLAM associated protein (SAP) 🡪 signaling lymphocyte activation molecule in 60%
Rx: rituximab (anti-CD20) wipes out B cells can control primary infection / prevent infection pre BMT
- BMT if HLH, chemo if lymphoma
Poor prognosis
Child presents with these nail changes, oral aversion & rashes
Chronic mucocutaneous candidiasis
- Decreased responsiveness to candida
- IL17RA mutation (AR)
- Associated with APECED/APS1 (AIRE gene)/CARD9
- Limited to skin, rarely systemic
- Rx: systemic azoles
Symptoms/signs of neutrophil defects?
Recurrent deep tissue infections:
- Lymphadenitis
- Pneumonia
- OM
- Liver abscesses
Bugs (catalase +ve often):
- Staph Aureus
- Pseudomonas
- Klebsiella
- Aspergillus
- Burkholderia
- Nocardia
- Candida
Sx: FHx recurrent infection, gingivitis, chronic diarrhoea, HSM + lymphadenopathy
Causes of neutrophil defect?
Degranulation abnormalities:
1. Chediak Higashi (AR)- impaired chemotaxis/NK/platelet
- Recurrent pyogenic infections + HSM
2. Specific granule deficiency (AR)
- Impaired chemotaxis
- Abscesses
Adhesion abnormalities
- LAD1,2,3 (AR)
1. Decreased binding C3
2. Decreased adhesion to ELAM
3. Impaired platelet activation
- Recurrent infection without pus
- LAD3 = bleeding tendency
Disorders of cell motility
1. FMF - cyclical fever/arthritis,amyloidosis, IL1b
Depressed responses
1. IgG/C3/Properdin deficiency
2. Meds
3. Hyper IgE (AD) reccurrent sinopulmonary infections, eczema, eosinophilia
Decreased microbicidal activity
1. CGD
2. G6PD
3. MPO deficiency
4. RAC2 deficiency
5. Glutathione reductase deficiency
- Recurrrent pyogenic infections
Organisms/investigations for neutrophil defects?
Recurrent bacterial and fungal infections involving the skin and organs
Bacterial and fungal
Staphylococcus
Pseudomonas
Catalase positive bacteria
Candida
Aspergillus
Nocardia
Gingivitis
Screening test = Neutrophil count x 3 + neutrophil morphology
Neutrophil count and morphology +/- Ix neutropenia
NBT dye test for function (CGD) +/- dihydrohodamine 123 test
Chemotaxis assay (LAD) – Rebuck skin window test
Myeloperoxiase stain
Compate SCIG/IVIG pros/cons
IVIG
Pros: less frequent, rapid increase in IgG, no patient training
Cons: hospital based, requires IV, risk immediate reaction- 12-48h
SCIG
Pros: home based, used in patients with prev reaction IVIG, reduced hospital costs, more consistent IgG levels, faster infusion
Cons: more frequent administration, local SFx, parent training and treatment compliance
Teenage girl noted to have facial rash, joint pain and haematuria. C3 is low.
- what hypersensitivity type?
Type 3/Immune complex (IgG/M)
- Ag/Ab complexes deposited in tissues- complement activation & neutrophils- damage tissues
- SLE, polyarteritis nodosa, serum sickness, hypersensitivity pneumonitis
Teenage boy, the next day after taking his new watch off notices dermatitis in the underlying skin.
- what hypersensitivity type?
Type 4/Delayed/T-cell mediated
- Th1 cells release cytokines which activate macrophages/cytotoxic T cells
- Contact dermatitis, T1DM, MS
Role of EBV in autoimmune diseases?
EBV is a B cell tropic virus.
- Can activate B cells = increased cytokine production and co- stimulation -> differentiation of pathogenic T cells.
- Lives latent in memory B-cells
Rx: anti CD20 ocrelizumab
