Immunology

Question 1

B cells vs T cells

Answer 1

B cells make immunoglobulins and are responsible for immunity against extracellular bacteria.

T cells are responsible for immunity against intracellular bacteria, viruses and fungi

Question 2

Immunodeficiency disorders general

Answer 2

Congenital immunodeficiencies are rare and often present with chronic or recurrent infections (chronic thrush), unusual or opportunistic organisms, incomplete treatment response, or FTT

Question 3

B cell deficiencies

Answer 3

Most common (50%). Typically present after 6 months of age with recurrent sinopulmonary, GI, and urinary tract infections with encapsulated organisms (H flu, strep pneumo, neisseria meningitides). Treat with IVIG (except for IgA deficiencies)

1) Bruton’s - can be confused with transient hypogammaglobulinemia of infancy (THI) as both are characterized by increased susceptibility at 6mo of age when trasplacental maternal IgG is no longer active. Low B cells in Bruton’s
2) CVID - older males and females (15-35) and less severe
3) IgA

Question 4

T cell deficiencies

Answer 4

Tend to present earlier (1-3months) with opportunistic and low-grade fungal, viral and intracellular bacterial infections (mycobacteria).

Secondary B-cell dysfunction may also be seen

1) DiGeorge

Question 5

Phagocyte deficiencies

Answer 5

Characterized by mucous membrane infections, abscesses and poor wound healing

Infections with catalase positive organisms (S aureus), fungi, and gram negative enteric organisms are common

1) CGD
2) LAD
3) Chediak-Higashi
4) Job’s

Question 6

Complement deficiencies

Answer 6

Present in children with congenital asplenia or splenic dysfunction (sickle cell). Characterized by recurrent bacterial infections with encapsulated organisms.

1) C1 esterase deficiency (hereditary angioedema)
2) Terminal complement deficiency (C5-C9)

Question 7

Combined disorders

Answer 7

1) Ataxia Telangiectasia
2) SCID
3) Wiskott-Aldrich Syndrome

Question 8

Bruton’s Congenital Agammaglobulinemia

Answer 8

1) X linked recessive B cell deficiency found only in boys*
2) Symptoms begin after 6 months of age when maternal IgG is no longer active
3) Life threatening, characterized by encapsulated pseudomonas, strep pneumo, H flu infections after 6 months of age
4) Quantitative Ig levels. If low, conform with B and T cell subsets (B cells are absent, T is often high). Absent tonsils and other lymphoid tissue may provide a clue
5) Treat with ppx ABx and IVIG

Question 9

Common Variable Immunodeficiency

Answer 9

1) Usually a combined B and T cell defect. All Ig levels are low (in the 20s and 30s). Normal B cell numbers; low plasma cells. Symptoms usually later in life (15-35years)
2) Increased pyogenic upper and lower respiratory infections. Increased risk of lymphoma and autoimmune disease
3) Quantitative Ig levels. Confirm with B and T cell subsets.
4) Treat with IVIG

Question 10

IgA deficiency

Answer 10

1) Mild; most common immunodeficiency. Reduced IgA only
2) Usually ASx; patients may develop recurrent respiratory or GI infections (Giardia).
3) Anaphylactic transfusion rxn due to anti-IgA antibodies is a common presentation
4) Quantitative IgA levels; treat infections
5) DO NOT GIVE IVIG, as it can lead to production of anti-IgA antibodies

Question 11

Thymic aplasia (DiGeorge)

Answer 11

1) Presents with tetany (secondary to hypocalcemia) in first days of life. CATCH-22 (Cardiac abnormalities, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia, chromosome 22
2) Variable risk of infection. Greatly increased infections with viruses, fungi, and PCP. XR may show absent thymic shadow
3) Absolute lymphocyte count; mitogen stimulation response; delayed hypersensitivity skin testing
4) Treat with bone marrow transplant and IVIG for antibody deficiency. Give PCP ppx. Thymus transplant is an alternative

Question 12

Ataxia telangiectasia

Answer 12

1) Progressive cerebellar ataxia and oculocutaneous telangiectasias. Caused by DNA repair defect
2) Increased incidence of malignancies, including non-Hodgkin’s lymphoma, leukemia, and gastric carcinoma
3) No specific tx, may require IVIG depending on severity of Ig deficiency

Question 13

SCID

Answer 13

1) Severe lack of B and T cells due to defect in stem cell maturation and reduced adenosine deaminase. Referred to as “bubble boy disease” bc children are often confined to an isolated, sterile environment
2) Severe, frequent bacterial infections; chronic candidiasis; opportunistic organisms
3) Treat with bone marrow or stem cell transplant and IVIG for antibody deficiency. Requires PCP ppx

Question 14

Wiskott-Aldrich

Answer 14

1) X linked recessive only in boys. Symptoms usually present at birth. Patients have high IgE and IgA. Low IgM and low platelets.
2) Classic presentation involves bleeding, eczema, and recurrent otitis media. WIPE - Wiskott Infections Purpura Eczema
3) Increased risk of atopic disorders, lymphoma/leukemia and infection from strep pneumo, staph aureus, and HfluB (encapsulated organisms)
4) Treatment is supportive (IVIG and ABx). Patients rarely survive to adulthood. Patients with severe infections may be treated with bone marrow transplant

Question 15

CGD

Answer 15

1) X linked (two thirds) or autosomal recessive disease with deficient superoxide production by PMNs and macrophages
2) Anemia, lymphadenopathy, and hypergammaglobulinemia may be present
3) Chronic skin, LN, pulmonary, GI and urinary tract infections; osteomyelitis and hepatitis. Infecting organisms are catalase positive (Aureus, E Coli, Candida, Kleb, Pseudomonas, Aspergillus)
4) May have granulomas of the skin and GI/GU tracts
5) Absolute neutrophil count with neutrophil assays. The nitroblue tetrazolium test is diagnostic.
6) Treat with daily Bactrim; make judicious use ofABx during infections. IFN-gamma can reduce incidence of serious infection. Bone marrow transplant and gene therapy are new therapies

Question 16

Leukocyte Adhesion Deficiency

Answer 16

1) Defect in chemotaxis of leukocytes
2) Recurrent skin, mucosal, and pulmonary infection. May present as omphalitis in the newborn period with delayed separation of the umbilical cords*
3) No pus with minimal inflammation in wounds (due to chemotaxis defect). High WBCs in blood. Bone marrow transplant is curative.

Question 17

Chediak-Higashi

Answer 17

1) Auto recessive disorder that leads to defect in neutrophil chemotaxis/microtubule polymerization
2) The syndrome includes partial oculocutaneous albinism, peripheral neuropathy, and neutropenia
3) Increased incidence of overwhelming pyogenic infections with strep pyogenes, staph aureus, and pseudomonas
4) Look for giant granules in neutrophils
5) Bone marrow transplant is treatment of choice

Question 18

Job’s Syndrome

Answer 18

1) A defect in neutrophil chemotaxis. FATED - coarse Facies, Abscesses (staph aureus), Teeth (retained primary), hyper IgE, Derm (severe eczema)
2) Recurrent staph aureus infections and abscesses
3) Treat with penicillinase-resistant antibiotics and IVIG

Question 19

C1 esterase deficiency (hereditary angioedema)

Answer 19

1) Auto dominant* with recurrent episodes of angioedema lasting 2-72h and provoked by stress or trauma
2) Can lead to life threatening airway edema
3) Total hemolytic complement (CH50) to assess the quantity and function of complement. Purified C1 esterase and FFP can be used prior to surgery

Question 20

Terminal complement deficiency (C5-C9)

Answer 20

1) Inability to form MAC
2) Recurrent Neisseria infections, meningococcal or gonococcal. Rarely, lupus or glomerulonephritis.
3) Meningococcal vaccine and appropriate ABx

Question 21

Kawasaki Disease

Answer 21

Multisystemic acute vasculitis that primarily affects young children (80% are less than 5 years old), particularly those of Asian ancestry. Divided into acute, subacute and chronic phases.

Question 22

Acute phase of Kawasaki

Answer 22

Lasts 1-2w and presents with following symptoms (fever plus 4 or more of below stuff required for dx)

1) Fever. Usually above 104 for at least 5d
2) Bilateral, nonexudative painless conjunctivitis sparing the limbus
3) Polymorphous rash (mostly truncal)
4) Cervical LAD (often painful and unilateral, with at least 1 node above 1.5cm)
5) Diffuse mucous membrane erythema (strawberry tongue); dry, red, chapped lips
6) Erythema of the palms and soles; indurative edema of the hands and feet; late desquamation of the fingertips (in subacute phase)
7) Other manifestations include sterile pyuria, gallbladder hydrops, hepatitis, arthritis

Question 23

Subacute Kawasaki

Answer 23

Begins after abatement of fever and typically lasts an extra 2-3w.

Manifestations are thrombocytosis and high ESR.

Untreated kids may begin to develop coronary artery aneurysms (40%). All patients should be assessed by Echo at diagnosis

Question 24

Chronic Kawasaki

Answer 24

Begins when all clinical symptoms have disappeared; lasts until ESR returns to baseline. Untreated children are at risk of aneurysmal expansion and MI.

Question 25

Symptoms of Kawasaki shortcut

Answer 25

CRASH and BURN

Conjunctivitis
Rash
Adenopathy (unilateral)
Strawberry tongue
Hands and feet (red, swollen, flaky skin)

BURN (fever over 104 for 5 or more days)

Scarlet fever looks similar, but doesn’t have any lip or conjunctival involvement.

Question 26

Tx of Kawasaki

Answer 26

1) High dose ASA (for inflammation and fever) and IVIG (to prevent aneurysm)
2) Low dose ASA is then continued usually for 6w. Kids who develop coronary artery aneurysms may require chronic anticoagulation with ASA or other antiplatelet meds
3) Corticosteroids may be used in IVIG-refractory cases, but routine use is not recommended

Question 27

Juvenile Idiopathic Arthritis

Answer 27

An autoimmune disorder manifesting as arthritis with morning stiffness and gradual loss of motion that is present for at least 6w in patient under 16 years old. Formerly known as juvenile RA.

Question 28

Dx of JIA

Answer 28

1) Pauciarticular (oligoarthritis): most common; involves 4 or fewer joints (usually weight bearing); usually ANA positive and RF negative. Involves young females. Uveitis is common and requires slit-lamp exam for eval. No systemic symptoms
2) Polyarthritis: Involves 5 or more joints. Symmetric. RF positivity is rare and indicated severe disease; younger children may be ANA positive with milder disease. Systemic symptoms rare
3) Systemic-onset (Still’s Disease): May present with recurrent high fever (usually above 102.2), HSM, and a salmon-colored macular rash; usually RF and ANA neg

Question 29

Tx of JIA

Answer 29

1) NSAIDs and strengthening exercises

2) steroids (for carditis) and immunosuppressive meds (methotrexate, anti-TNF agents like etanercept) are second line