HIV infection and secondary causes of immunodeficiency Flashcards
classification of immune deficiencies
far more common than primary immune deficiencies
malnutrition (most common around the world)
ID: HIV
environmental stress
age extremes: prematurity and old age
surgery and trauma splenectomy
immuno suppressive drgs
genetic and metabolic diseases
immune deficiencies exhibit diverse clinical features (4)
infections = severe, persistent, recurrent, unusual
autoimmune conditions (cytopaenias very common in 1o and 2o immune deficiencies) and allergic disease
persistent inflammation
cancer (viral associated EBV, HHV-8)
common causes of 2o immune deficiencies
malnutrition (common cause WW)
measles = immune defect lasts months to years, increased morbidity and mortalitty
TB = inflammatory immune re-constitution syndrome
HIV = residual immune dysfunction persists despite successful ART
SATS-CoV-2 infection = multi-factorial causes, virus, drugs, co-morbidities (renal disease and DM)
types of drugs that cause immune deficiency
small molecules
- glucocorticoids and mineralocorticoids
- cytotoxic agents: methotrexate, mycophenolate, cyclophosphamide and azathioprine
- calcineurin inhibitors: cyclosporine and tacrolimus
- antiepileptic drugs: phenytoin, carbamazepin, levetiracetam
- DMARD: sulphasalazine, leflunomide
JAK inhibitors
- tofacitinib, upadacitinib, ruxolitinib
note done biologics and cellular therapies causes of immune deficiency
biologics = anti-CD20, anti-TNF-a protein and receptor antagonists
cellular therapy = anti-CD19-/Tc therapy
- Antibody deficiency and bacterial/viral infections are observed with rituximab and other anti-CD20 agents
- Risk of infection increased with repeated courses and in patient in patients
haematological cancers as causes of 2o immune deficiency
B and plasma cell cancers (antibody deficiency syndromes are most common)
chemo, biological therapy, radiotherapy
Bc lymphoproliferative disorders
- Multiple myeloma
- CLL
- NHL
- monoclonal gammopathy of uncertain signficance
Good’s syndrome (thymoma and antibody deficiency)
- T and B cell (absent) defect
- CMV PJP and muco-cutaneuous candida
- Autoimmune disease (Pure red cell aplasia, Myasthenia gravis, Lichen planus)
evaluation of secondary immune deficiency: question to ask in history
FISH for an immunodeficiency
FBC
- Hb <10g/L
- neutrophil count
- lymphocyte count
- platelet count
Immunoglobulins (IgG/A/M/E)
Serum complement (C3,C4) = for serum complex disease, lupus
HIV test (18-80 years)
Strategy will pick up to 85% of all immune defects
front line ix for immune deficiency: chemistry
renal and liver profile
calcium and bone profile
total protein and albumin
urine protein/Cr ratio
serum
protein electorpohoresis
serum free light chains
front line ix for immune deficiency: serum Ig
- check lab issues age-releted reference intervals especially for children
- Ig profile helpful in diagnosis
- isolated IgG reduction = protein loosing enteropathy, prednisolone >10mg/day
- reduction IgG and IgM = monitor for B cell neoplasm, hx of exposure to rituximab
- reduction in IgG and IgA = primary antibody deficiency
front line ix for immune deficiency: electrophoresis
second line test to ix for immune deficiency: vaccinae antibodies
measure concentration of vaccine antibodies
- tetanus toxoid = protein antigen
- pneumovax vaccine = carbohydrate antigen (all 23 serotypes or to individual pneumococcal serotypes)
if vaccine antibody levels low = offer test immunisation with pneumovax II and tetanus to ix immune function
failure to respond to vaccination is part of diagnostic criteria for a nymber of 1o antibody deficiency syndromes and is a criteria for receipt of IgG replacement theerapy for 2o antibdoy defiicency syndromes
NOT DONE second line test to ix for immune deficiency:
mx of 2o immune deficiency
tx underlying cause
advise on measures to reduce exposure to infection
immunise against resp viruses and bacteria and offer vaccines to household contacts
education to tx bacterial infections promplty: may require high and longer therapies courses
prophylactic abx for confirmed recurrent bacterial infections
IgG replacement therapy for 2o antibody deficiency sundromes
HIV-1 virology
5 characteristic features of the immunology of HIV-1 infection
diagnosis of HIV-1 infection
baseline ix hiv
evaluation and mx of HIV-1 infection
cd4+ cell count and opportunistic infections
HIV-1 specific tests
standard ART in UK
- 2 NRTI and 1 NNRTI or 2NRTI and 1 Integrase inhibitor are standard first line anti-HIV-1 treatments in the UK
- Considerable efforts in last 5-10 years to combine different ART drugs in a single pill formulations to improve adherence to therapy
- Drug toxicity rather than virological failure is the main reason why HIV-1 patients change HIV therapy
- It is safer to continue to take ART rather than interrupt anti-HIV treatment course (SMART study)
monitoring individuals on ART
Check for compliance with drug therapy and for adverse side effects
Regular HIV-1 viral load
Monitor liver, renal, bone and lipid toxicity
CD4 T cell monitoring not needed for counts more than 350cells/ul
Assess cardiovascular and osteoporosis risk
