Allergy/immunology

Question 1

You diagnose a child with transient hypogammaglobulinemia of infancy.

What therapy do most children with this disorder need?

Answer 1

Answer
No therapy
Explanation
Most of these children do not require any therapy, but you can consider IV immunoglobulin (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 2

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

What vaccines are contraindicated in this child?

Answer 2

Live attenuated virus vaccines are contraindicated in children with SCID.
Explanation
Do not give a live attenuated virus vaccine (i.e., rotavirus, MMR, OPV, and varicella) to a child with SCID. The child could contract the infection from the vaccine. The infection may be severe and potentially fatal since a child with SCID cannot mount an immune response to such an infection.

Question 3

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

Overwhelming sepsis
Eczematous skin lesions
Diarrhea
Failure to thrive
Absence of thymus shadow on chest x-ray (CXR)
Lymphopenic for his age
What is the most likely diagnosis?

Answer 3

Answer
Severe combined immunodeficiency (SCID)
Explanation
SCID most commonly presents in the first few months of life with the described symptoms. It is a medical emergency—untreated patients will die of infection. On exams, look for the “absent thymus” on CXR. Additionally, these infants are lymphopenic for their ages. Stem cell transplant can be curative.

All U.S. states now screen for SCID on newborn screening panels; however, patients who were born outside a U.S. hospital may not have been screened and may present in early infancy as described.

Question 4

Previously sensitized T cells interact with an antigen, causing an inflammatory reaction that peaks in 1–3 days.

Which type of hypersensitivity reaction is described here?

Answer 4

Type 4: cell-mediated hypersensitivity
Explanation
Type 4 hypersensitivity reaction (a.k.a. cell-mediated hypersensitivity reaction, delayed-type hypersensitivity) occurs due to exposure to a previously known antigen. The tuberculin skin testing is a common example of this.

Question 5

What is the body’s 1st line of defense against invading pathogens?

Answer 5

The skin
Explanation
The fact that the skin is the 1st line of defense against invading pathogens 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 2nd line of defense against invading pathogens is the innate immune system, followed by the adaptive immune system.

Question 6

What is the first antibody produced in response to an infection?

Answer 6

IgM
Explanation
IgM, the largest antibody, is the first to develop and first to respond to an infection. It is secreted as a pentamer and is found in blood and lymphatic tissue. It 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 7

An infant has delayed umbilical cord separation.

What disorder should you consider in this child?

Answer 7

Answer
Leukocyte adhesion defect Type 1 (LAD1)
Explanation
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) molecules, which are 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 cannot get out to do their job.

Question 8

Children with spina bifida or congenital urogenital problems have an increased risk of being allergic to which common hospital substance?

Answer 8

Latex
Explanation
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 9

A 10-year-old presents with:

Asymmetric face
Broad nose, prominent forehead, and triangular jaw
Eczema
Scoliosis
Hyperextensible joints
Recurrent “cold abscesses” with Staphylococcus aureus and Streptococcus pneumoniae
Eosinophilia
What is the most likely diagnosis?

Answer 9

Answer
Hyper-IgE syndrome (a.k.a. Job syndrome)
Explanation
Hyper-IgE syndrome (HIES) is typically caused by an autosomal dominant or sporadic mutation in signal transducer and activator of transcription 3 (STAT3). This mutation results in multiple system involvement. Patients have recurrent Staphylococcal infections of the skin and lung, chronic dermatitis, skeletal abnormalities, postinfectious pulmonary cysts (pneumatoceles), and retained primary teeth. Initially, they have elevated IgE levels (2,000 to > 50,000 IU/mL), but they may fall to normal levels later in life. An elevated IgE level is not needed to make the diagnosis.

Question 10

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

Answer 10

Answer
Epstein-Barr virus (EBV)
Explanation
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 11

Which antibody is found in secretions?

Answer 11

Answer
IgA
Explanation
Immunoglobulin A (IgA) is the antibody in mucous secretions and is usually a dimer (2 immunoglobulins joined together by a J-chain). It is the main antibody secreted in breast milk. It has 2 subclasses—IgA1 and IgA2.

Question 12

How do the IgA, IgG, and IgM antibody levels compare to normal in a child with hyper-IgM syndrome?

Answer 12

Answer
IgA and IgG low; IgM high or normal
Explanation
There are X-linked and autosomal recessive forms of hyper-IgM syndrome. The X-linked form is more common and has a poorer prognosis. Patients are prone to sinopulmonary infections, giardiasis, and opportunistic infections, including Pneumocystis jiroveci pneumonia. These children have increased risk of autoimmunity and are at high risk for malignancy by their 20s.

Question 13

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 13

Ataxia telangiectasia (AT)
Explanation
AT is an autosomal recessive disorder with the ataxia occurring early in life; telangiectasia may not become evident until after 5 years of age. Telangiectasia appears on bulbar conjunctivae and skin. Note that these children have elevated α1-fetoprotein. Immunodeficiency is variable and can affect both B and T cells. Patients are prone to sinopulmonary infections. They have an increased risk of cancers.

Question 14

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

Abdominal pain
Lower extremity swelling without the presence of urticaria
A similar condition to that of her father
What is the most likely diagnosis?

Answer 14

Hereditary angioedema (HAE)
Explanation
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 Type I HAE. If the C1-INH level is normal, it is due to a nonfunctioning C1-INH enzyme, and the disorder is Type II HAE.

Question 15

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

Answer 15

Extensor
Explanation
In infants, atopic dermatitis presents on the scalp, face, and extensor surfaces. In older children, atopic dermatitis tends to present on the flexor surfaces. Atopic dermatitis is the “itch that rashes.”

Question 16

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

Answer 16

Answer
CD8+ T cells
Explanation
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 17

In the last 4 weeks, a 6-year-old girl has had 2 episodes of wheezing and coughing at night, requiring albuterol treatment.
Is her asthma well controlled?

Answer 17

No
Explanation
The criteria for asthma control are strict for children < 12 years of age. Well-controlled asthma for this age range is defined as ≤ 2 episodes per week during the day and/or ≤ 1 episode per month during the night.

Question 18

An 18-year-old girl presents with:

History of recurrent sinus and pulmonary infections
History of spruelike illness with diarrhea and steatorrhea
Low IgG levels (< 200 mg/dL)
Low IgA and IgM (< 50 mg/dL)
Hepatosplenomegaly and biopsy showing noncaseating granulomas of the spleen and liver
Poor response to diphtheria/tetanus vaccines by immunoglobulin testing
What is the most likely diagnosis?

Answer 18

Common variable immunodeficiency (CVID)
Explanation
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. These patients are also prone to chronic lung disease and bronchiectasis as well as autoimmune disease. The disorder most often presents in the teens and 20s and is very rare before 6 years of age.

Question 19

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

Answer 19

Answer
WEMPS
Explanation
The most common food allergies in children are:
Wheat—IgE-mediated reaction (differentiates from celiac disease)
Eggs
Milk and soy
Peanuts and tree nuts
Seafood—crustacean shellfish and fish

Question 20

A 2-week-old boy with eczema presents for circumcision. Circumcision is performed, but the boy has profuse bleeding that is difficult to stop. CBC reveals thrombocytopenia. On peripheral smear, small platelets are found.

What is the most likely diagnosis?

Answer 20

Wiskott-Aldrich syndrome (WAS)
Explanation
WAS is an X-linked disease with a classic triad: thrombocytopenia, eczema, and susceptibility to encapsulated bacterial and opportunistic infections. The classic clinical scenario is a boy with prolonged bleeding from the circumcision site.

Question 21

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 both absent
What is the most likely diagnosis?

Answer 21

Answer
X-linked agammaglobulinemia (XLA; a.k.a. Bruton agammaglobulinemia)
Explanation
XLA is an X-linked disorder that is also called Bruton agammaglobulinemia. XLA presents after 6 months of age (when maternal immunity wanes) with recurrent bacterial sinopulmonary 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 22

What can prevent or delay the occurrence of atopic dermatitis in early childhood?

Answer 22

Answer
Breastfeeding for at least 4 months
Explanation
Breastfeeding for at least 4 months may decrease the risk of atopic dermatitis, cow’s milk allergy, and wheezing in early childhood. Maternal dietary restrictions during pregnancy do not prevent the development of atopic disease.

Question 23

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

Answer 23

Answer
IgE
Explanation
IgE mediates the systemic reaction known as anaphylaxis. This occurs within minutes to an hour after exposure to the trigger allergen. A similar reaction that is not IgE mediated is called nonimmunologic or non-IgE-mediated anaphylaxis (formerly known as anaphylactoid). This is much less common. 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 24

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

Answer 24

Yes
Explanation
The negative predictive value (NPV) of skin-prick testing is very high. Positive skin-prick tests, however, are not specific and may or may not indicate true sensitivity to that item.

Question 25

A 3-year-old presents with:

Small stature
Telangiectasia
CNS abnormalities
Immunodeficiency
Deficiency of DNA ligase I
What is the diagnosis?

Answer 25

Answer
Bloom syndrome
Explanation
Bloom syndrome is a chromosomal instability disorder like ataxia telangiectasia. Patients do not have ataxia. It is due to deficiency of DNA ligase I. Bloom syndrome also has a high association with leukemias.

Question 26

A White child in Colorado has early-onset systemic lupus erythematosus (SLE).

Which immunodeficiency should you look for?

Answer 26

C2 deficiency
Explanation
C2 deficiency is the most common complement deficiency, especially in the White population, and results in increased risk of rheumatoid diseases—especially SLE. Consider it in patients with early-onset SLE and recurrent sinopulmonary and ear infections. The initial screening test for this would be a total hemolytic complement assay (CH50); results would be 0 because all factors (C1–C9) need to be present for this test to be normal.

Question 27

Which type of reaction occurs when immune complexes that have not been cleared by the innate immune system accumulate, causing an inflammatory response?

Answer 27

Answer
Type 3: Immune complex hypersensitivity
Explanation
Type 3 hypersensitivity occurs when immune complexes (ICs) that have not been cleared by the innate immune system accumulate, causing an inflammatory response. Immune complexes form when antibodies combine with an antigen (self or foreign). The immune complexes can then precipitate and activate complement with subsequent small vessel inflammation and necrosis. Significant precipitation occurs when there is slight excess of antigen in relation to antibodies. When the antibody response begins, there is initially a large excess of antigens compared to antibodies. The ICs that are formed are small, soluble, and quickly cleared. Within 1–2 weeks, as increasingly more antibodies are produced, a point is reached when there is only slight antigen excess, and the ICs interlace and become bigger and less soluble. These precipitate in the small vessels and activate complement, which starts a cascade that causes the release of more cytokines and the gathering of more inflammatory cells. This process ultimately results in necrosis of the small vessels.

Question 28

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 28

Serum sickness–like reaction (SSLR)
Explanation
SSLRs do not require prior sensitization for a reaction to occur (unlike IgE-mediated hypersensitivity). SSLRs are usually caused by antibiotics and are common in children. Classic serum sickness is caused by heterologous serum proteins such as anti-thymocyte globulin, monoclonal antibodies, Hymenoptera stings, and antiserum. SSLRs start 6–12 days after initial exposure to the medication, but it can take up to 3 weeks. Treatment is to stop the offending agent and provide supportive care. A short course of steroids may be helpful in severe cases.

Question 29

A 2-year-old child has had repeated episodes of wheezing during viral upper respiratory infections (URIs), 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 29

Unlikely
Explanation
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 ≥ 1 major criterion or ≥ 2 minor criteria:
Major criteria: One of the parents has asthma. The child has eczema.
Minor criteria: The child has allergic rhinitis, wheezing unrelated to colds/URIs, eosinophilia

Question 30

What mediates Type 1 hypersensitivity reactions?

Answer 30

Immunoglobulin E (IgE)
Explanation
IgE mediates the acute phase of immediate hypersensitivity reactions. Mast cell degranulation causes release of histamine and other mediators. Histamine is responsible for many acute symptoms. The most common type of allergic reaction is IgE-mediated Type 1 hypersensitivity reaction. Examples include anaphylactic reactions to foods (e.g., peanuts, tree nuts), insect and Hymenoptera (e.g., bees, wasps) stings, drugs (e.g., penicillin, chemotherapeutics), and latex. Other types of IgE-mediated reactions include hives/urticaria, allergic rhinitis, and allergic asthma

Question 31

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 31

Chronic granulomatous disease (CGD)
Explanation
CGD can be X-linked (most cases) or autosomal recessive and presents as chronic and recurrent organ and skin abscesses, commonly caused by the listed bacteria. Patients cannot generate the superoxide “respiratory burst,” which is important for bacterial killing. Dihydrorhodamine (DHR) oxidation by flow cytometry is the diagnostic test of choice.

Question 32

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 32

Answer
22q11.2 deletion syndrome (a.k.a. DiGeorge syndrome)
Explanation
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. Immunodeficiency is variable and is related to thymic hypoplasia or absence. Patients can present with neonatal seizures due to hypocalcemia and tetany.

Question 33

Which antibody has the major role in allergic reactions?

Answer 33

IgE
Explanation
IgE is the antibody with the lowest concentration in normal serum but has a major role in Type 1 hypersensitivity and allergic diseases, including atopy, asthma, allergic rhinitis, and food allergies. It is also involved in immunity against parasites.