diagnosis_management_immunodeficiencies_flashcards

Question 1

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Answer 1

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Question 2

What are the consequences of phagocyte deficiencies?

Answer 2

Recurrent deep bacterial infections, recurrent fungal infections.

Question 3

How are phagocyte deficiencies diagnosed?

Answer 3

NBT or DHR flow cytometry test. NBT is a dye that changes colour from yellow to blue, following interaction with hydrogen peroxide. DHR is oxidised to rhodamine, which is strongly fluorescent, following interaction with hydrogen peroxide.

Question 4

What is the treatment for phagocyte deficiencies?

Answer 4

Aggressive management of infection, Infection prophylaxis (Antibiotics – e.g., Septrin (co-trimoxazole) (oral/IV as needed), Anti-fungals – e.g., Itraconazole), Definitive therapy (Haematopoietic stem cell transplantation).

Question 5

What are the consequences of complement deficiencies?

Answer 5

Increased susceptibility to encapsulated bacterial infections.

Question 6

How are complement deficiencies diagnosed?

Answer 6

CH50 and AP50 tests.

Question 7

What is the treatment for complement deficiencies?

Answer 7

Vaccination, prophylactic antibiotics, high levels of suspicion + early treatment, screen family members.

Question 8

What are the consequences of T cell deficiency?

Answer 8

Viral infections (Cytomegalovirus), bacterial infections (Staphylococcus, Streptococcus), fungal infections (Pneumocystis, Cryptosporidium), toxins (Tetanus, Diphtheria).

Question 9

What are the consequences of antibody deficiency or CD4 T cell deficiency?

Answer 9

Some bacterial infections (esp. intracellular organisms (MTB, Salmonella)), some viral infections (Enterovirus), early malignancy.

Question 10

How is lymphocyte deficiency diagnosed?

Answer 10

1. WCC, 2. Lymphocyte subsets, 3. Serum immunoglobulins (if CD4 deficient as IgG is a surrogate marker for function) and protein electrophoresis, 4. Functional tests, 5. HIV.

Question 11

What is the management for T cell deficiencies?

Answer 11

Infection prophylaxis and treatment, Ig replacement, Haematopoietic stem cell transplantation, gene therapy (experimental), Thymic transplantation in DiGeorge syndrome (donor thymic tissue into quadriceps muscle – experimental).

Question 12

What is the management for B cell deficiencies?

Answer 12

Aggressive treatment of infection, Ig replacement every 3 weeks (pooled plasma containing diverse IgG), BMT, Immunisation in Selective IgA deficiency (not effective if no IgG).

Question 13

What are autoinflammatory diseases?

Answer 13

Innate immune response attacking your own body, in the absence of infection.

Question 14

What are autoimmune diseases?

Answer 14

Adaptive immune response attacking your own body, in the absence of infection.

Question 15

What are mixed innate/adaptive immune diseases?

Answer 15

Mutations in genes involved in pathways associated with both innate and adaptive immune function.

Question 16

What are monogenic auto-inflammatory diseases?

Answer 16

Mutations in a single gene involved in innate immune cell function.

Question 17

What are the main cytokines implicated in monogenic auto-inflammatory diseases?

Answer 17

TNF-alpha and IL-1.

Question 18

What is Familial Mediterranean Fever?

Answer 18

Autosomal recessive condition caused by mutation in MEFV gene, leading to increased IL-1 and TNF-alpha activation of neutrophils.

Question 19

What are the clinical presentations of Familial Mediterranean Fever?

Answer 19

Periodic fevers lasting 48-96 hours associated with abdominal pain (peritonitis), chest pain (pleurisy and pericarditis), arthritis, rash.

Question 20

What is the long term risk of Familial Mediterranean Fever?

Answer 20

Long term risk of AA amyloidosis.

Question 21

What is the treatment for Familial Mediterranean Fever?

Answer 21

Colchicine 500ug bd, Anakinra (Interleukin 1 receptor antagonist), Etanercept (TNF alpha inhibitor).

Question 22

What are polygenic auto-inflammatory diseases?

Answer 22

Mutations in multiple genes causing aberrant innate immune cell function.

Question 23

What is an example of a polygenic auto-inflammatory disease?

Answer 23

Crohn’s Disease – mutation in IBD1 gene on chromosome 16 identified as NOD2 (CARD-15).

Question 24

What are the causes of autoimmunity?

Answer 24

Failure of central tolerance (APS-1), failure of peripheral tolerance (IPEX), failure of lymphocyte apoptosis (ALPS), molecular self-mimicry, release of hidden intracellular antigens, modification of self/auto antigen.

Question 25

What is Autoimmune polyendocrine syndrome type 1 (APS1)?

Answer 25

Defect in autoimmune regulator gene (AIRE), leads to failure of central tolerance.

Question 26

What is Immune dysregulation, polyendocrinopathy, enteropathy (IPEX)?

Answer 26

Defect with T-reg cells, mutation in Foxp3 gene, leading to failure of peripheral tolerance.

Question 27

What is Autoimmune lymphoproliferative syndrome (ALPS)?

Answer 27

Fas L mutation / problems with Fas pathway, leading to failure of lymphocyte apoptosis.

Question 28

What is the clinical presentation of APS1?

Answer 28

Multiple auto-immune endocrine diseases: Hypothyroidism, Hypoparathyroidism, Addison’s, Diabetes, Vitiligo.

Question 29

What is the clinical presentation of IPEX?

Answer 29

The 3 Ds: Diabetes Mellitus, Diarrhoea and Dermatitis.

Question 30

What is the clinical presentation of ALPS?

Answer 30

High lymphocyte numbers with large spleen and lymph nodes, lymphoma, cytopenias.

Question 31

What are polygenic autoimmune diseases?

Answer 31

Mutations in multiple genes encoding proteins involved in adaptive immune cell function, HLA associations are common, auto-antibodies are found.

Question 32

What are examples of organ specific autoimmune diseases?

Answer 32

Autoimmune hepatitis, Autoimmune haemolytic anaemia, Autoimmune thrombocytopenic purpura, Bullous pemphigoid, Coeliac disease, Congenital heart block in infants of mothers with SLE, Dermatitis herpetiformis, Goodpasture’s syndrome, Graves’ disease, Hashimoto’s thyroiditis, Myasthenia gravis, Pernicious anaemia, Primary biliary cirrhosis, Type 1 diabetes mellitus.

Question 33

What are examples of multi-system autoimmune diseases?

Answer 33

Rheumatoid arthritis, SLE, Sjogren’s, Dermatomyositis, Polymyositis, CREST, Diffuse CREST, Granulomatosis with Polyangiitis (Wegener’s), Eosinophilic Granulomatosis with Polyangiitis (Churg Strauss), Microscopic Polyangiitis.

Question 34

What are HLA associations with autoimmune diseases?

Answer 34

PAIR (Psoriatic arthritis, Ankylosing spondylitis, IBD, Reactive arthritis) – HLA B27. Goodpasture’s syndrome – HLA DR15/DR2. Graves’ Disease – HLA- DR3. SLE – HLA-DR3. Type I diabetes – HLA DR3/DR4. Rheumatoid arthritis – HLA-DR4. Coeliac Disease – DQ2/DQ8.