Allergy & Immunology

Question 1

What is the antibody found in secretions?

Answer 1

IgA

It is usually a dimer (2 immunoglobulins). It is the main antibody in breast milk.

Question 2

An 18-year-old girl presents with:

• History of recurrent sinus and pulmonary infections
• History of sprue-like illness with diarrhea and steatorrhea
• IgG levels are low (< 200 mg/dL).
• IgA and IgM are also low (< 50 mg/dL).
• Hepatosplenomegaly is present, and biopsy shows noncaseating granulomas of the spleen and liver.
• Poor response to diphtheria/tetanus vaccines by immunoglobulin testing

What is the most likely diagnosis?

Answer 2

Common Variable Immunodeficiency (CVID)

Patients with CVID have recurrent sinopulmonary infections with encapsulated bacteria, a deficiency of at least 2 classes of immunoglobulins (IgG, IgA, or IgM), and poor immunoglobulin function as demonstrated by IgG titers to vaccines. The disorder most often presents in the teens and 20s and is very rare before 6 years of age.

Question 3

What is a good mnemonic for the most common food allergens?

Answer 3

WEMPS

The most common food allergies in children are:

• Wheat: IgE-mediated reaction (differentiates from celiac disease)
• Eggs: most common in atopic dermatitis
• Milk and soy
• Peanuts and tree nuts
• Seafood: crustacean shellfish and fish

Question 4

A child has skin-prick testing to various allergens. If the skin-prick test is negative, is that strong evidence against allergy to that item?

Answer 4

Yes

A negative skin-prick test to an item essentially means that the child is not allergic to that item. Positive skin-prick tests, however, are not specific and may or may not indicate true sensitivity to that item.

Question 5

Which T cells are the primary defense against exogenous antigens?

Answer 5

CD4+ T cells They can be activated only by antigens presented along with class II HLA antigens.

Question 6

A 6-year-old female has had 2 nightly episodes of wheezing and coughing requiring albuterol this month.

Is her asthma well controlled?

Answer 6

No

The criteria for asthma control are stricter for children under 12 years of age. So whereas a 12-year-old would be considered well controlled in this example, a 6-year-old (or anyone under 12) would not.

Question 7

A 2-month-old boy presents with these findings:

• Overwhelming sepsis
• Eczematous-like skin lesions
• Diarrhea
• Failure to thrive
• Absence of thymus shadow on CXR
• Lymphopenic for a 2-month-old

What is the most likely diagnosis?

Answer 7

Severe Combined Immunodeficiency (SCID)

SCID most commonly presents in the first few months of life with the described symptoms. On exams, look for the “absent thymus” on CXR. Additionally, these infants are lymphopenic for their ages.

Question 8

An infant is evaluated and found to have the following:

• Micrognathia
• Hypertelorism
• Shortened philtrum
• Low-set, dorsally rotated ears
• Interrupted aortic arch
• Tetralogy of Fallot
• Neonatal seizures

What chromosomal abnormality is likely?

Answer 8

22q11.2 Deletion Syndrome

(a.k.a. DiGeorge Syndrome)

Heterozygous interstitial deletions of chromosome 22q11.2 are responsible for DiGeorge syndrome. Other heart abnormalities can include transposition of the great vessels, double-outlet right ventricle, and ventricular septal defect. Subclinical hypoparathyroidism is common.

Question 9

A 10-year-old presents with:

• Asymmetric face
• Broad nose
• Prominent forehead
• Triangular jaw
• Eczema
• Scoliosis
• Hyperextensible joints
• Recurrent “cold abscesses” with Staphylococcus aureus and Streptococcus pneumoniae
• Eosinophilia

What is the most likely diagnosis?

Answer 9

Job Syndrome (Hyper-IgE Syndrome)

Hyper-IgE syndrome is a signal transducer and activator of transcription 3 (STAT3) deficiency that results in multiple system involvement. Patients also have postinfection pulmonary cysts (pneumatoceles) and 2 rows of teeth due to delayed dental exfoliation. Initially, they have elevated IgE levels (2,000–100,000 IU), but they may fall to normal levels later in life. An elevated IgE level is not needed to make the diagnosis.

Question 10

What is the body’s first line of defense against invading pathogens?

Answer 10

The Skin

This explains why patients with impaired skin barrier function, such as patients with severe burns, are susceptible to infection. Patients with atopic dermatitis also have altered skin barrier function; they are frequently colonized with Staphylococcus aureus and are prone to superinfection. The 2^nd line of defense against invading pathogens is the innate immune system, followed by the adaptive immune system.

Question 11

What is the first antibody produced in an infection?

Answer 11

IgM

IgM is secreted as a pentamer (5 immunoglobulins) and is the best antibody for complement activation. IgM is useful to confirm recent illness and can help distinguish acute vs. chronic infection. Look for IgM to be positive in acute infection.

Question 12

You diagnose a child with transient hypogammaglobulinemia of infancy.

What therapy do most children with this disorder require?

Answer 12

No Therapy

Most do not require any therapy, but you can consider IVIG in those with recurrent infections or markedly low IgG levels. Consider antibiotic prophylaxis for those with frequent respiratory and/or ear infections. Most have normal IgG levels by 3–4 years of age.

Question 13

What are the various antibody levels (IgA, IgG, IgM) in a child with Hyper-IgM syndrome?

Answer 13

IgA and IgG Low; IgM High or Normal

There are X-linked and autosomal recessive forms of hyper-IgM syndrome. The X-linked form is more common and has a poorer prognosis. These children are at high risk for malignancy by their 20s.

Question 14

An 8-month-old boy presents with:

• Recurrent otitis media
• 2 episodes of recurrent pneumonia that require hospitalization both due to Streptococcus pneumoniae
• Persistent giardiasis
• Lymph nodes and tonsils are absent

What is the most likely diagnosis?

Answer 14

X-Linked (Bruton) Agammaglobulinemia (XLA)

XLA presents strictly in males with recurrent bacterial infections in association with absent-to-low immunoglobulin levels. The disorder is due to a mutation in the BTK gene (at Xq22) that encodes for Bruton tyrosine kinase, which is necessary for B-cell development.

Question 15

A Caucasian child has early-onset systemic lupus erythematosus (SLE).

What immune deficiency should you look for?

Answer 15

C2 Deficiency

C2 deficiency is the most common complement deficiency in North American Caucasians and results in increased risk of early-onset SLE.

Question 16

A 2-week-old boy with eczema presents for circumcision. Circumcision is performed; the boy has profuse bleeding, and it is difficult to stop the bleeding. A CBC is done; he has thrombocytopenia, and, on peripheral smear, you note small platelets.

What is the most likely diagnosis?

Answer 16

Wiskott-Aldrich Syndrome

WAS is an X-linked disease with a classic triad:

• thrombocytopenia
• eczema
• susceptibility to encapsulated bacterial and opportunistic infections.

Classic clinical scenario: a boy with prolonged bleeding from the circumcision site.

Question 17

A 6-year-old presents with:

• Ataxia
• Oculocutaneous telangiectasia
• History of chronic sinus infections and several hospitalizations for pneumonia.

What is the most likely diagnosis?

Answer 17

Ataxia-Telangiectasia

It is an AR disorder with the ataxia occurring early in life, but the telangiectasia may not become noticeable until after 5 years of age. These children have elevated alpha1-fetoprotein.

Question 18

What type of hypersensitivity is seen in antibody-antigen mediated reactions?

Answer 18

Type III

Type 3 is an immune complex (antibody-antigen)–mediated hypersensitivity reaction. It is seen in immunoglobulin autoimmune diseases and in reaction to drugs.

Question 19

Patients with X-linked lymphoproliferative disease (Duncan syndrome) are susceptible to severe and fatal infections from what virus?

Answer 19

Epstein-Barr Virus (EBV)

EBV frequently causes fulminant hepatitis, B-cell lymphomas, agranulocytosis, aplastic anemia, or acquired hypogammaglobulinemia. This is because EBV triggers a polyclonal expansion of T and B cells. The most common causes of death are hepatic necrosis and/or bone marrow failure due to natural killer and cytotoxic T cells infiltrating these organs.

Question 20

Anaphylaxis to an allergen (foods such as peanuts or drugs such as penicillin) is mediated by which immunoglobulin?

Answer 20

IgE

IgE mediates the systemic reaction known as anaphylaxis. A similar reaction that is not IgE-mediated is called non-IgE-mediated anaphylaxis (formerly known as anaphylactoid). It is not possible to clinically distinguish between IgE- and non-IgE-mediated reactions. Non-IgE-mediated reactions are most commonly due to aspirin, NSAIDs, and radiographic contrast agents.

Question 21

A 3-year-old presents with:

• Small stature
• Telangiectasia
• CNS abnormalities
• Immunodeficiency
• Deficiency of DNA ligase I

What is the diagnosis?

Answer 21

Bloom Syndrome

Bloom syndrome is a chromosomal instability disorder like ataxia-telangiectasia. It is due to deficiency of DNA ligase I. Bloom syndrome also has a high association with leukemias.

Question 22

An infant has delayed umbilical cord separation.

What disorder should you consider in this child?

Answer 22

Leukocyte Adhesion Defect Type 1

LAD1 presents with delayed umbilical cord separation, omphalitis, and severe gingivitis. These patients have a baseline leukocytosis because they lack cluster of differentiation 18 (CD18), which is needed for the cells to leave the circulation and enter tissues to fight off infection. As a result, the leukocytes are stuck in the circulation and can’t get out to do their job.

Question 23

Previously sensitized T cells interact with an antigen, causing an inflammatory reaction that peaks in 24–72 hours.

Which type of hypersensitivity reaction is described here?

Answer 23

Type 4: Cell-Mediated Hypersensitivity

Type 4 or cell-mediated hypersensitivity reaction (a.k.a. delayed-type hypersensitivity) occurs due to exposure to a previously known antigen. TB skin testing is the common example of this.

Question 24

A 3-year-old boy presents with chronic and recurrent skin abscesses with Staphylococcus aureus, Serratia marcescens, Burkholderia cepacia, and Aspergillus. Now he has splenic abscesses as well with Serratia marcescens.

What is the most likely diagnosis?

Answer 24

Chronic Granulomatous Disease (CGD)

CGD is generally X-linked and presents as chronic and recurrent organ and skin abscesses, commonly caused by the listed bacteria. Nitroblue tetrazolium (NBT) reduction and more recently, dihydrorhodamine (DHR) oxidation are 2 methods to diagnose this. Patients cannot generate the superoxide “respiratory burst.”

Question 25

A 14-year-old girl presents with the following findings:

• Abdominal pain
• Lower extremity swelling without the presence of urticaria
• Her father has a similar condition

What is the most likely diagnosis?

Answer 25

Hereditary Angioedema (HAE)

HAE is an autosomal dominant complement disorder caused by a defect in C1 inhibitor enzyme (C1-INH) function with secondarily decreased C4 levels. Screen first by checking C4 levels; if C4 levels are low, then look for a decreased C1-INH functional assay. If the C1-INH level is also low, then it is HAE Type I. If the C1-INH level is normal, it is due to a nonfunctioning C1-INH enzyme, and the disorder is HAE Type II.

Question 26

A Caucasian child has early-onset systemic lupus erythematosus (SLE).

Which immune deficiency should you look for?

Answer 26

C2 Deficiency

C2 deficiency is the most common complement deficiency in North American Caucasians and results in increased risk of rheumatoid diseases—especially SLE. Consider it in patients with early-onset SLE.

Question 27

A 2-year-old child has had repeated episodes of wheezing during viral upper respiratory infections but neither parent has asthma. The child does not have eczema, allergic rhinitis, wheezing apart from colds, or eosinophilia.

How likely is it that this child will develop asthma by 6 years of age?

Answer 27

Unlikely

This child has a negative asthma predictive index (API), so it is unlikely that the child will develop asthma by 6 years of age (negative predictive value of 95%). The criteria for a positive API are as follows:

• Major criteria (1 of the following): 1 of the parents has asthma; the child has eczema, or
• Minor criteria (2 of the following): allergic rhinitis; wheezing unrelated to colds/URIs; eosinophilia

Question 28

Which T cells are “cytotoxic” and important in defense against viruses and neoplastic cells?

Answer 28

CD8+ T cells

CD8+ T cells are activated by neoplastic antigens and other antigens presented in association with Class I HLAs. They are cytotoxic and are important in the defense against intracellular organisms/antigens such as viruses and neoplastic cells.

Question 29

What is the distribution of surface lesions—extensor or flexural—in infants with atopic dermatitis?

Answer 29

Extensor

In infants, atopic dermatitis has a slightly different pattern of distribution, such as on the scalp, face, and extensor surfaces rather than flexor surfaces like it presents in older children.

Question 30

What mediates Type I hypersensitivity reactions?

Answer 30

IgE

IgE mediates the acute phase of immediate hypersensitivity reactions and occurs within 1 hour after exposure (typically within minutes). Mast cell degranulation is the cause of the symptoms.

Question 31

What antibody has the major role in allergic reactions?

Answer 31

IgE

IgE is the antibody with the lowest concentration in normal serum but has a major role in allergic conditions, including atopy, asthma, allergic rhinitis, and food allergies.

Question 32

You start a child on penicillin. He has never been on penicillin before; however, 8 days after being on the antibiotic, he develops the following:

• Fever
• Nausea/vomiting
• Skin rash with redness, itching, urticaria, and angioedema
• Joint pain of the knees and ankles
• Lymph node swelling
• Muscle aches
• Proteinuria

What is the most likely diagnosis?

Answer 32

Serum Sickness

Serum sickness does not require prior sensitization for a reaction to occur (unlike IgE-mediated hypersensitivity). Serum sickness is a Type 3 hypersensitivity reaction. It usually takes 6–12 days for the reaction to occur, but it can take up to 3 weeks. Treatment is to stop the offending agent.

Question 33

A 5-year-old presents with:

• Difficulty walking
• History of chronic sinus infections and several hospitalizations for pneumonia
• Elevated α1-fetoprotein

What is the most likely diagnosis?

Answer 33

Ataxia-Telangiectasia (AT)

AT is an autosomal recessive disorder with the ataxia occurring early in life, but the telangiectasia may not become noticeable until after 5 years of age. Note that these children have elevated α1-fetoprotein.

Question 34

A child is diagnosed with severe combined immunodeficiency (SCID).

Which vaccines should this child not receive?

Answer 34

Live Attenuated Virus Vaccines

Do not give a live attentuated virus vaccine (i.e., rotavirus, MMR, OPV, and varicella) to a child with SCID! Such vaccines can be fatal to these children.

Question 35

Children with spina bifida or congenital urogenital problems have an increased risk of having allergy to what common hospital substance?

Answer 35

Latex

Latex allergy is much more common in children with these problems because of their repeated exposure to latex from the many medical and surgical procedures they undergo. Latex allergy is due to sensitization to proteins—primarily hevein. Cross-reactivity can occur with papaya, kiwi, banana, potato, avocado, tomato, and chestnuts.

Question 36

Does breastfeeding for at least 4 months prevent or delay the occurrence of atopic dermatitis in early childhood?

Answer 36

Yes

Breastfeeding for at least 4 months prevents or delays the occurrence of atopic dermatitis, cow milk allergy, and wheezing in early childhood. Maternal dietary restrictions during pregnancy do not prevent the development of atopic disease.