Secondary immune deficiencies and HIV-1 infection Flashcards
What are causes of secondary immune deficiencies?
Malnutrition
Infectious Diseases e.g. HIV
Environmental stress
Age Extremes: Prematurity and old age
Surgery and trauma splenectomy
Immunosuppressive drugs
Genetic and metabolic diseases
What are signs and symptoms of secondary immune deficiencies?
Infections: Severe, persistent, recurrent, unusual
Autoimmune conditions (cytopaenias) and allergic disease
Persistent inflammation
Cancer (viral associated EBV, HHV-8)
Which drugs can cause immune deficiencies?
Small molecules:
- Glucocorticoids and mineralocorticoids
- Cytotoxic agents: Methotrexate, mycophenolate, cyclophosphamide
- and azathioprine.
- Calcineurin inhibitors: Cyclosporine and tacrolimus
- Antiepileptic drugs (phenytoin, carbamazepine, levetiracetam)
- DMARD (sulphasalazine, leflunomide)
JAK inhibitors:
- Tofacitinib
- Upadacitinib
- Ruxolitinib
Which drug class can cause TB reoccurance?
Anti-TNF agents
Which cancers are common with secondary immune deficiencies?
B and plasma cell cancers can present with immune deficiency (antibody deficiency syndromes are most common).
Chemotherapy, biological agents, and radiotherapy can leads to loss of immune cells and immune deficiency.
Which specific B-cell lymphoproliferative disorders can arise from secondary immune deficiencies?
Multiple myeloma
Chronic lymphocytic leukaemia
Non Hodgkin’s lymphoma
Monoclonal gammopathy of uncertain significance
What is Good’s syndrome?
Thymoma and antibody deficiency
Combined T and B cell (absent) defect
CMV PJP and muco-cutaneous candida
Autoimmune disease (Pure red cell aplasia, Myasthenia gravis, Lichen planus)
What are appropriate investigations for secondary immune deficiencies?
Full Blood count
Hb < 10g/L
Neutrophil count
Lymphocyte count
Platelet count
Immunoglobulins (IgG, IgA, IgM, IgE )
Serum complement (C3, C4)
HIV test (18-80 years)
Strategy will pick up to 85% of all immune defects
What is serum protein electrophoresis?
SPE separation of serum proteins by charge
Detection of discrete bands: monoclonal identified by immunofixation with labelled IgG, IgA, IgM anti-sera
SPE can miss free light chain disease which is seen 20% multiple myeloma cases): hence measurement of free light chains is essential for work up of B cell LPD.
What are second line investigations for secondary immune deficiencies?
Measure concentration of vaccine antibodies:
- Tetanus toxoid: Protein antigen
- Pneumovax vaccine: Carbohydrate antigen ( all 23 serotypes or to individual pneumococcal serotypes)
What are third line investigations for secondary immune deficiencies?
Analysis of naïve and memory T and B cell subsets
Assessment of IgG subclasses
Determination of anti-cytokine and complement antibodies:
- Anti-Type 1 interferon antibodies (IFN-α and IFN-ω) in SARS-CoV-2 infection
- Anti Type 2 interferon antibodies (IFN-γ) in disseminated NTM infection
- Anti-GM-CSF antibodies disseminated in cryptococcal infection
- Anti-C1 inhibitor antibodies and acquired late onset angioedema ( B cell LPD and SLE)
Genetics (whole exome or whole genome sequencing in cases where it is difficult to work if you are dealing with primary or secondary immune defect
What is the management of secondary immune deficiencies?
Treat underlying cause
Advise on measures to reduce exposure to infection
Immunisation against respiratory viruses and bacteria and offer vaccines to household contacts
Education to treat bacterial infections promptly: May require higher and longer therapies courses (co-amoxiclav 625mg TDS for 10-14 days rather then 375mg for 5-7 days)
Prophylactic antibiotics for confirmed recurrent bacterial infection