UWorld - Allergy and Immunology

Question 1

Contraindications and precautions to diphtheria/tetanus, containing vaccines

Answer 1

Contraindications
1) anaphylaxis to vaccine ingredients

Precautions

1) Moderate or severe acute illness with or without fever
2) Guillen Barre within 6w of tetanus toxoid-containing vaccine
3) Arthus type hypersensitivity reaction following diphtheria or tetanus toxoid containing vaccine

Question 2

Contra and precautions to pertussis containing vaccines

Answer 2

Contra

1) Anaphylaxis to ingredients
2) Progressive/unstable neuro disorder (uncontrolled epilepsy, infantile spasms)
3) Encephalopathy within a week of previous vaccine dose

Precautions

1) Moderate or severe acute illness with or without fever
2) Reactions to previous doses
(a) Seizure within 3d
(b) Temp above 40.5 (105) within 2d
(c) Hypotonic-hyporesponsive episode within 2d
(d) Inconsolable, persistent crying within 2d

Question 3

DTaP vaccine in kids

Answer 3

Children should receive 5 doses of inactivated diphtheria-tet-acellular pertussis from age 6w through 6y.

Contains acellular pertussis (replaced killed whole cell B.pertussis) antigens with diphtheria and tetanus toxoid.

Whole cell pertussis gives longer immunity but is associated with neuro disorders (encephalopathy and seizures)

Personal or family history of febrile seizures is NOT a contraindication to vaccine, ESP in setting of outbreak

You can give partial immunizations (not the combo) if contraindications for pertussis component are present.

Question 4

Hereditary angioedema

Answer 4

1) Rapid onset of
(a) Noninflammatory edema of the face, limbs and genitalia
(b) Laryngeal edema - can be life threatening
(c) Edema of the intestines resulting in colicky abdominal pain

2) No evidence of urticaria

A defect of C1 inhibitor deficiency, dysfunction or destruction can contribute to hereditary and acquired angioedema.

Defect in C1 inhibitor leads to elevated levels of the edema-producing factors C2b and bradykinin.

Most common cause of acquired isolated angioeema is due to ACEI use, which causes high bradykinin

**Hereditary form usually present in late childhood. Episodes usually follow an infection, dental procedure or trauma. C1q levels are NORMAL in hereditary angioedema and depressed in aquired form (presents later in life). C4 is depressed in all forms of angioedema

Question 5

Antibody-mediated hypersensitivty

Answer 5

Type II. Can be seen in immune hemolytic anemia and Rh hemolytic disease of the newborn

Involves specific reactions of IgG or IgM antibodies with cell bound antigens leading to complement activation and cell destruction.

Question 6

Type 1 hypersensitivity

Answer 6

Immediate. Involve IgE and result in mast cell and basophil degranulation with associated urticaria and pruritus

Question 7

Cell-mediated hypersensitivity

Answer 7

Type IV. Tuberculin skin test and allergic contact dermatitis.

In allergic contact dermatitis, the allergen causes dermal inflammation following direct contact with the skin after a latent period of 1-2d

Question 8

Low levels of C1q

Answer 8

seen in acquired angioedema, presenting in patients over 30. Hereditary angioedema has NORMAL C1q levels

Question 9

Immune complex-mediated hypersensitivity

Answer 9

Type III. Serum sickness. Antibodies form complexes with allergens that are present in tissues, leading to activation of the complement cascade wherever the immune complexes deposit.

Question 10

X-linked agammaglobulinemia (Brutons)

Answer 10

Clinical manifestation

1) Recurrent sinopulmonary and GI infections after age 6months
2) Absence of lymphoid tissue on exam (tonsils, lymph nodes)

Dx

1) Low immunoglobulins and B cells
2) Normal T cell concentration
3) No response to vaccines

Tx

1) Immunoglobulin replacement therapy
2) Ppx ABx if severe

XLA is caused by defect in tyrosine kinase that prevents the development of mature B cells. Low B cell concentrations lead to small or absent LNs on PE and low or absent Ig concentrations

Predisposed to infections with encapsulated organisms like Hflu and strep pneumo

Low IgA leads to increased risk of GI infection (Giardia)

Patients present after 6 months when protection from mom’s IgG begins to wane

Tx - IVIG monthly. Live vaccines are contraindicated. Other vaccines are not contraindicated but are incapable of generating a meaningful response

Question 11

Adenosine deaminase deficiency

Answer 11

One of several gene defects resulting in impaired T cell development and causing severe combined immunodeficiency (SCID).

Affected patients present with severe, recurrent viral, fungal (Candida) and bacterial infections and FTT

Question 12

Complement deficiencies - patients are higher risk of what?

Answer 12

Disseminated bacterial infections, particularly with encapsulated bacteria (strep pneumo, N mening). Giardia is NOT associated with complement deficiencies

Question 13

How does a doctor handle vaccine refusal?

Answer 13

Must respect parents’ wishes. Explain risks. Document in chart.

All states allow medical exemption (allergy to components). Some allow for exemption based on religious or personal beliefs. If child is not exempt, kid might not be allowed to go to school in some states. be aware of state laws.

Question 14

What childhood vaccine lowers cancer risk?

Answer 14

Hepatitis B. Decreases incidence of HCC, esp in regions with high levels of hepatitis B such as Asia and Africa.

Chronic Hep B infection secondary to vertical transmission from mom is a major cause of HCC in Africa and Asia. In USA, Hep B is most often contracted via contact with infected blood.

Question 15

SCID

Answer 15

LIFE THREATENING

Etiology

1) Gene defect leading to failure of T cell development
2) B cell dysfunction due to absent T cells (may see hypogammaglobulinemia)

Inheritance

1) X linked recessive
2) Autosomal recessive

Clinical features

1) Recurrent, severe viral, fungal or opportunistic (pneumocystis) infections
2) FTT
3) Chronic diarrhea

Tx - stem cell transplant

Absence of T cells causes severe defects in cellular immunity, increasing risk for infection with viruses, fungi and opportunistic pathogens (pneumocystis jirovecii). Loss of CD4 T cells also leads to B cell (humoral immunity) dysfunction, increasing the risk of sinopulmonary and GI bacterial infections. In addition to infections, chronic diarrhea and FTT in infancy as well as absence of Lymph tissue on exam are typical

Labs show lymphopenia and hypogammaglobulinemia. Stem cell transplant is only treatment. SCID is included in routine newborn screening in USA and is detected by absence of T cell receptor excision circles (circular DNA excreted by developing T cells in thymus) in dried blood

Question 16

Chronic granulomatous disease

Answer 16

Defect in NADPH oxidase in phagocytic cells, which leads to impaired killing of catalase-positive organisms (staph aureus, serratia marcescens, Burkholderia, Aspergillus, Nocardia). Other common infections are suppurative adenitis and osteomyelitis.

Affected patients have recurrent skin and soft tissue infections but normal lymphocyte and Ig concentrations

Most cases are X linked recessive.

Dx - Neutrophil function testing/oxidative burst testing (dihydrorhodamine 123 test, Nitroblue tetrazolium test). Confirmed by gene testing.

Tx - Patients with CGD should get ppx with TMP-SMX and Itraconazole. Severe phenotypes may benefit from Interferon-gamma injections

Typical infections:
Lungs - pneumonia, empyema
Skin/soft tissue - abscess, lymphadenitis

Question 17

CVID

Answer 17

Recurrent sinopulmonary or GI infections due to hypogammaglobulinemia. Unlike Bruton, CVID is less severe and presents at later age with normal T and B cell counts.

Question 18

Wiskott-Aldrich Syndrome

Answer 18

X linked recessive disease. presents in early infancy with eczema and bleeding (post circumcision, bleeding from umbilical stump) due to thrombocytopenia. T cell dysfunction and hypogammaglobulinemia worsen with age and presents as bacterial, viral and opportunistic infections

Question 19

Summary of some humoral immunodeficiency syndrome features (Hyper IgM, CVID, Job, Selective IgA Def, Bruton)

Answer 19

CD40 ligand deficiency (Hyper IgM Syndrome)

1) Normal B cell count
2) Low IgG
3) Low IgA
4) High IgM
5) Low IgE

CVID

1) Normal B cell count
2) Low IgG
3) Low IgA
4) Low IgM
5) Low IgE

Job (hyper IgE Syndrome)

1) Normal B cell count
2) Normal IgG
3) Normal IgA
4) Normal IgM
5) High IgE

Selective IgA deficiency

1) Normal B cell count
2) Normal IgG
3) Low IgA
4) Normal IgM
5) Normal IgE

Bruton

1) Low B cell count
2) Low IgG
3) Low IgA
4) Low IgM
5) Low IgE

Question 20

Transient hypogammaglobulinemia of infancy

Answer 20

Characterized by low IgG, variable IgM and normal IgA and B cell concentrations.

Affected patients present with increased sinopulmonary and GI infections that are usually mild rather than life threatening. Ig levels normalize by age 9-12 months

Question 21

DiGeorge

Answer 21

22q11. presents with classic triad of congenital heart disease, T cell deficiency, and hypocalcemia. Impaired T cell production leads to deficient cellular immunity (recurrent viral and fungal). B cell concentrations unaffected.

Question 22

Contraindications to rotavirus vaccine

Answer 22

1) Anaphylaxis to vaccine ingredients
2) History of intussusception
3) History of uncorrected congenital malformation of the GI tract (Meckel’s)
4) SCID

Live attenuated vaccine (like MMR and varicella). Small risk of intussusception.

Live vaccines not recommended during pregnancy BUT if someone lives with a pregnant person THEY can get the vaccine bc response is not such to make them contagious. So, living with a pregnant person is not a contraindication to vaccine.

Question 23

Rotavirus

Answer 23

Most common cause of gastroenteritis in infants and young children worldwide. Virus is highly contagious and transmitted fecal-oral through direct contact and through fomites.

Typical course consists of fever, vomit, and watery osmotic diarrhea. Affected kids often suffer from severe dehydration

Vaccine is best defense against rotavirus gastroenteritis and prevents most cases of infection. Vaccine series is typically administered at age 2-6months.

Question 24

CD40 ligand

Answer 24

Present on T cells and binds to CD40 expressed on B cells, which induces a change in B cell production of IgM to other immunoglobulins (class switching).

Absence of CD40 ligand prevents class switching, leading to high IgM levels and low levels of others.

CD40 ligand deficiency also inhibits plasma cell formation, which contributes to poor response to infection and immunization

Question 25

Features of Leukocyte Adhesion Deficiency

Answer 25

1) Recurrent skin and mucosal bacterial infections (omphalitis, periodontitis) - no pus (lack of neutrophils at inflammation site), poor wound healing
2) Delayed umbilical cord separation (more than 21d)
3) Marked peripheral leukocytosis with neutrophilia

LAD is caused by defective integrins on the leukocyte surface, which normally allow neutrophils to adhere to vascular endothelium, exit the vasculature and migrate to areas of infection or inflammation

Lack of neutrophil migration in LAD results in recurrent skin (cellulitis, abscess, omphalitis) and mucosal (periodontal) infections as well as poor wound healing. Exam shows inflammation with a notable lack of purulence.

Bx of infected tissue is devoid of neutrophils and culture often grows staph aureus or gram negative bacilli. Peripheral serum studies show marked leukocytosis and neutrophilia, particularly during episodes of infection.

Classically, first sign is delayed separation of umbilical cord (more than 3w)

Question 26

Standard peds immunizations

Answer 26

Inactivated (killed)

1) Polio
2) Hep A

Toxoid (inactivated toxin)

1) Diphtheria
2) Tetanus

Subunit/conjugate

1) Hep B
2) Pertussis
3) H flu B
4) Pneumococcal
5) Meningococcal
6) HPV
7) Influenza (injection)

Live

1) Rotavirus
2) Measles
3) Mumps
4) Rubella
5) Varicella
6) Influenza (intranasal)

Question 27

Immunizations in preterm infant

Answer 27

Give according to chronological age, not gestational age (as long as medically stable)

All stable preterm infants should get Hep B at birth (unless they weigh less than 2kg). Second dose of Hep B plus rotavirus, TDaP, H flu B, pneumococcal, inactivated polio at 2 months)

Summary: All vaccines should be administered according to chronologic rather than gestational age in preterm infants. The exception is that weight should be at least 2kg before first dose of Hep B vaccine.

Question 28

Chediak-Higashi Syndrome

Answer 28

Auto recessive disorder. Characterized by partial oculocutaneous albinism and recurrent cutaneous infections. Staph aureus and strep pyogenes are common.