Recurrent infections evaluation — MCQs

10 questions

A 7-month-old Caucasian male presents with recurrent sinusitis and pharyngitis. The parents say that the child has had these symptoms multiple times in the past couple of months and a throat swab sample reveals the presence of Streptococcus pneumoniae. Upon workup for immunodeficiency it is noted that serum levels of immunoglobulins are extremely low but T-cell levels are normal. Which of the following molecules is present on the cells that this patient lacks?

A 3-month-old boy presents to his pediatrician with persistent diarrhea, oral candidiasis, and signs and symptoms of respiratory syncytial virus (RSV) pneumonia. He is very lean with weight in the 10th percentile. His blood pressure is 105/64 mm Hg and heart rate is 84/min. He is being evaluated for an immunodeficiency. Laboratory results for HIV are negative by polymerase chain reaction (PCR). Which of the following is the most likely cause of this child’s presentation?

A father brings his 3-year-old son to the pediatrician because he is concerned about his health. He states that throughout his son's life he has had recurrent infections despite proper treatment and hygiene. Upon reviewing the patient's chart, the pediatrician notices that the child has been infected multiple times with S. aureus, Aspergillus, and E. coli. Which of the following would confirm the most likely cause of this patient's symptoms?

You are seeing a 4-year-old boy in clinic who is presenting with concern for a primary immune deficiency. He has an unremarkable birth history, but since the age of 6 months he has had recurrent otitis media, bacterial pneumonia, as well as two episodes of sinusitis, and four episodes of conjunctivitis. He has a maternal uncle who died from sepsis secondary to H. influenza pneumonia. If you drew blood work for diagnostic testing, which of the following would you expect to find?

A 3-year-old boy is brought to the emergency department because of persistent fever and cough. Three days ago, he was diagnosed with pneumonia and acute otitis media. He was started on ampicillin-sulbactam and clarithromycin, but his symptoms did not improve. The mother reports that her son has been hospitalized 3 times due to pneumonia. He was first diagnosed with pneumonia at the age of 10 months. She also reports several episodes of bilateral otitis media and recurrent respiratory tract infections. His immunizations are up-to-date. He is at the 50th percentile for height and 20th percentile for weight. He appears fatigued. His temperature is 38°C (100.4°F). Pneumatic otoscopy shows purulent otorrhea bilaterally. Pulmonary examination shows decreased breath sounds over both lung fields. The palatine tonsils and adenoids are hypoplastic. Which of the following is the most likely underlying cause of this patient's condition?

An 8-year-old boy presents to his pediatrician accompanied by his father with a complaint of chronic cough. For the past 2 months he has been coughing up yellow, foul-smelling sputum. He has been treated at a local urgent care center for multiple episodes of otitis media, sinusitis, and bronchitis since 2 years of age. His family history is unremarkable. At the pediatrician's office, his temperature is 99.2°F (37.3°C), blood pressure is 110/84 mmHg, pulse is 95/min, and respirations are 20/min. Inspection shows a young boy who coughs occasionally during examination. Pulmonary exam demonstrates diffuse wheezing and crackles bilaterally. Mild clubbing is present on the fingers. The father has brought an electrocardiogram (ECG) from the patient’s last urgent care visit that shows pronounced right axis deviation. Which of the following is the most likely etiology of this patient’s condition?

A 22-month-old girl is brought to the emergency department with a 24-hour history of fever, irritability, and poor feeding. The patient never experienced such an episode in the past. She met the normal developmental milestones, and her vaccination history is up-to-date. She takes no medications, currently. Her temperature is 38.9°C (102.0°F). An abdominal examination reveals general tenderness without organomegaly. The remainder of the physical examination shows no abnormalities. Laboratory studies show the following results: Urine Blood 1+ WBC 10–15/hpf Bacteria Many Nitrite Positive Urine culture from a midstream collection reveals 100,000 CFU/mL of Escherichia coli. Which of the following interventions is the most appropriate next step in evaluation?

A 10-year-old boy is brought to the pediatric clinic because of persistent sinus infections. For the past 5 years, he has had multiple sinus and upper respiratory infections. He has also had recurrent diarrhea throughout childhood. His temperature is 37.0°C (98.6°F), the heart rate is 90/min, the respirations are 16/min, and the blood pressure is 125/75 mm Hg. Laboratory studies show abnormally low levels of one immunoglobulin isotype but normal levels of others. Which of the following is the most likely diagnosis?

A 2-year-old boy is brought to the physician by his mother for evaluation of recurrent infections and easy bruising. He has been hospitalized 3 times for severe skin and respiratory infections, which responded to treatment with antibiotics. Examination shows sparse silvery hair. The skin is hypopigmented and there are diffuse petechiae. Laboratory studies show a hemoglobin concentration of 8 g/dL, leukocyte count of 3000/mm3, and platelet count of 45,000/mm3. A peripheral blood smear shows giant cytoplasmic granules in granulocytes and platelets. Which of the following is the most likely underlying cause of this patient's symptoms?

Q10

A 3-year-old boy is brought to the physician for the evaluation of recurrent skin lesions. The episodes of lesions started at the age of 3 months. He has also had several episodes of respiratory tract infections, enlarged lymph nodes, and recurrent fevers since birth. The boy attends daycare. The patient's immunizations are up-to-date. He is at the 5th percentile for length and 10th percentile for weight. He appears ill. Temperature is 38°C (100.4°F). Examination shows several raised, erythematous lesions of different sizes over the face, neck, groin, and extremities; some are purulent. Bilateral cervical and axillary lymphadenopathy are present. What is the most likely underlying mechanism of this patient's symptoms?

Recurrent infections evaluation US Medical PG Practice Questions and MCQs

Question 1: A 7-month-old Caucasian male presents with recurrent sinusitis and pharyngitis. The parents say that the child has had these symptoms multiple times in the past couple of months and a throat swab sample reveals the presence of Streptococcus pneumoniae. Upon workup for immunodeficiency it is noted that serum levels of immunoglobulins are extremely low but T-cell levels are normal. Which of the following molecules is present on the cells that this patient lacks?

A. CD8
B. CD3
C. CD4
D. NKG2D
E. CD19 (Correct Answer)

Explanation: ***CD19*** - The patient's symptoms of **recurrent bacterial infections** (sinusitis, pharyngitis with *Streptococcus pneumoniae*) and **extremely low serum immunoglobulin levels** despite normal T-cell levels are highly indicative of **X-linked agammaglobulinemia (XLA)**. - XLA is characterized by the absence of **mature B cells**, which are responsible for antibody production. **CD19** is a pan B-cell marker, universally expressed on B cells from their earliest stages in the bone marrow (pro-B cells) through to mature circulating B cells, identifying the cell population that is lacking in this patient. *CD8* - **CD8** is a co-receptor expressed on **cytotoxic T cells**, involved in recognizing antigens presented by MHC class I molecules. - The patient's T-cell levels are reported as **normal**, indicating that both CD4+ and CD8+ T-cell populations are likely present. *CD3* - **CD3** is a complex of proteins expressed on the surface of all **T lymphocytes** (both helper and cytotoxic T cells) as part of the T-cell receptor (TCR) complex. - Since the patient has **normal T-cell levels**, cells expressing CD3 are present and functional. *CD4* - **CD4** is a co-receptor primarily expressed on **helper T cells**, which recognize antigens presented by MHC class II molecules. - Similar to CD8 and CD3, **normal T-cell levels** suggest that CD4+ T cells are present in this patient. *NKG2D* - **NKG2D** is an activating receptor expressed primarily on **NK cells** (natural killer cells), as well as on subsets of CD8+ T cells and gamma-delta T cells. - While NK cells play a role in innate immunity, their absence or dysfunction would not directly explain the specific deficiency of **immunoglobulins** and recurrent bacterial infections seen here, which points to a B-cell defect.

Question 2: A 3-month-old boy presents to his pediatrician with persistent diarrhea, oral candidiasis, and signs and symptoms of respiratory syncytial virus (RSV) pneumonia. He is very lean with weight in the 10th percentile. His blood pressure is 105/64 mm Hg and heart rate is 84/min. He is being evaluated for an immunodeficiency. Laboratory results for HIV are negative by polymerase chain reaction (PCR). Which of the following is the most likely cause of this child’s presentation?

A. Grossly reduced levels of B cells
B. An X-linked inheritance of HLA genes
C. Selective IgA deficiency
D. Defective T cell function (Correct Answer)
E. Defective isotype switching

Explanation: ***Defective T cell function*** - The presentation with recurrent infections (oral candidiasis, RSV pneumonia), persistent diarrhea, and **failure to thrive (lean, 10th percentile weight)** in a young infant, despite negative HIV PCR, strongly suggests a **severe combined immunodeficiency (SCID)**. - **T-cell dysfunction is the hallmark of SCID**, leading to a broad susceptibility to opportunistic pathogens and impaired immune responses. *Grossly reduced levels of B cells* - While some immunodeficiencies involve B-cell defects (e.g., **X-linked agammaglobulinemia**), the primary clinical picture here (severe viral and fungal infections, failure to thrive) points more strongly to a profound T-cell defect affecting both humoral and cellular immunity. - Reduced B cells alone would primarily result in recurrent bacterial infections rather than the observed opportunistic infections. *An X-linked inheritance of HLA genes* - **HLA genes (Major Histocompatibility Complex)** are located on **chromosome 6**, not the X chromosome, and are crucial for antigen presentation, not typically associated with X-linked inheritance patterns. - Defects in HLA (e.g., bare lymphocyte syndrome) can impair T-cell function but are not solely X-linked and would still fall under the umbrella of defective T-cell function. *Selective IgA deficiency* - Patients with selective IgA deficiency are often **asymptomatic** or experience **recurrent sinopulmonary and gastrointestinal infections** but typically do not present with severe opportunistic infections like RSV pneumonia and persistent candidiasis with failure to thrive. - **T-cell function is preserved** in selective IgA deficiency, making the severe presentation less likely. *Defective isotype switching* - This primarily affects the ability of B cells to produce different classes of antibodies **(IgG, IgA, IgE)**, often due to defects in T follicular helper cells or B cell intrinsic defects. - While it can lead to recurrent infections, particularly bacterial, it does not typically cause the severe, opportunistic infections and failure to thrive seen with primary T-cell defects like SCID.

Question 3: A father brings his 3-year-old son to the pediatrician because he is concerned about his health. He states that throughout his son's life he has had recurrent infections despite proper treatment and hygiene. Upon reviewing the patient's chart, the pediatrician notices that the child has been infected multiple times with S. aureus, Aspergillus, and E. coli. Which of the following would confirm the most likely cause of this patient's symptoms?

A. Increased IgM, Decreased IgG, IgA, and IgE
B. Negative nitroblue-tetrazolium test (Correct Answer)
C. Positive nitroblue-tetrazolium test
D. Normal dihydrorhodamine (DHR) flow cytometry test
E. Increased IgE and IgA, Decreased IgM

Explanation: ***Negative nitroblue-tetrazolium test*** - A **negative nitroblue-tetrazolium (NBT) test** indicates an inability of phagocytes to produce a respiratory burst, which is characteristic of **Chronic Granulomatous Disease (CGD)**. - CGD patients suffer from recurrent infections with catalase-positive organisms such as *Staphylococcus aureus*, *Aspergillus*, and *E. coli*, consistent with the patient's history. *Increased IgM, Decreased IgG, IgA, and IgE* - This pattern of immunoglobulin levels is characteristic of **X-linked hyper-IgM syndrome**, where there is a defect in CD40L on T cells. - While it also causes recurrent infections, the typical pathogens differ from those stated in the question, often including *Pneumocystis jirovecii*. *Positive nitroblue-tetrazolium test* - A **positive NBT test** indicates that phagocytes are capable of producing a respiratory burst and forming superoxide, thus ruling out CGD. - This result would be expected in a healthy individual or someone with an immunodeficiency not affecting the phagocytic oxidative burst. *Normal dihydrorhodamine (DHR) flow cytometry test* - A **normal DHR flow cytometry test** indicates that neutrophils can produce reactive oxygen species (ROS) effectively, meaning the respiratory burst is intact. - This result would rule out CGD, as CGD patients have an abnormal (decreased) DHR test. *Increased IgE and IgA, Decreased IgM* - This specific pattern of immunoglobulin abnormalities is not typically associated with a single, well-defined primary immunodeficiency that would present with the described infections. - **Hyper-IgE syndrome (Job's syndrome)**, for example, features very high IgE levels but usually a normal IgM.

Question 4: You are seeing a 4-year-old boy in clinic who is presenting with concern for a primary immune deficiency. He has an unremarkable birth history, but since the age of 6 months he has had recurrent otitis media, bacterial pneumonia, as well as two episodes of sinusitis, and four episodes of conjunctivitis. He has a maternal uncle who died from sepsis secondary to H. influenza pneumonia. If you drew blood work for diagnostic testing, which of the following would you expect to find?

A. Abnormally low number of T cells
B. Abnormally high number of B cells
C. Elevated immunoglobulin levels
D. Abnormally low number of B cells (Correct Answer)
E. Abnormally high number of T cells

Explanation: ***Abnormally low number of B cells*** - The recurrent bacterial infections (otitis media, pneumonia, sinusitis, conjunctivitis) and the family history of death from *H. influenza* pneumonia suggest a **primary B-cell immunodeficiency**, such as **X-linked agammaglobulinemia (XLA)**. - In XLA, there is a block in B-cell development, leading to a profound absence of mature B cells and immunoglobulins. *Abnormally low number of T cells* - This would point towards a **T-cell immunodeficiency** or a **combined immunodeficiency**, typically presenting with opportunistic infections, viral, or fungal infections, rather than predominantly bacterial infections. - Examples include **Severe Combined Immunodeficiency (SCID)**, which often presents earlier and more severely. *Abnormally high number of B cells* - This is not characteristic of a primary immunodeficiency with recurrent bacterial infections; rather, it might be seen in certain autoimmune conditions or lymphoproliferative disorders. - **High B cell counts** generally imply a functioning humoral immune system, which contradicts the infectious history. *Elevated immunoglobulin levels* - This finding would generally indicate a **functioning humoral immune response**, possibly due to chronic infection or an inflammatory process, but not a primary B-cell immunodeficiency causing recurrent bacterial infections. - In conditions like **Common Variable Immunodeficiency (CVID)**, some immunoglobulin levels might be normal, but often key classes (like IgG, IgA, or IgM) are low. *Abnormally high number of T cells* - This finding is generally not associated with the pattern of recurrent bacterial infections described, which strongly points to a **humoral (antibody) deficiency**. - **Elevated T cells** could be seen in some autoimmune conditions or certain viral infections, but not typically in a primary immunodeficiency characterized by recurrent bacterial infections.

Question 5: A 3-year-old boy is brought to the emergency department because of persistent fever and cough. Three days ago, he was diagnosed with pneumonia and acute otitis media. He was started on ampicillin-sulbactam and clarithromycin, but his symptoms did not improve. The mother reports that her son has been hospitalized 3 times due to pneumonia. He was first diagnosed with pneumonia at the age of 10 months. She also reports several episodes of bilateral otitis media and recurrent respiratory tract infections. His immunizations are up-to-date. He is at the 50th percentile for height and 20th percentile for weight. He appears fatigued. His temperature is 38°C (100.4°F). Pneumatic otoscopy shows purulent otorrhea bilaterally. Pulmonary examination shows decreased breath sounds over both lung fields. The palatine tonsils and adenoids are hypoplastic. Which of the following is the most likely underlying cause of this patient's condition?

A. Tyrosine kinase gene mutation (Correct Answer)
B. Defect in the ATM gene
C. Defective NADPH oxidase
D. Defective IL-2R gamma chain
E. WAS gene mutation

Explanation: ***Tyrosine kinase gene mutation*** - This patient has **X-linked agammaglobulinemia (XLA)**, caused by a mutation in the **Bruton's tyrosine kinase (BTK)** gene, which is essential for B-cell development and maturation. - **Classic features present**: Recurrent **bacterial infections** (pneumonia, otitis media) starting around **6-12 months** when maternal IgG wanes, and **absent or hypoplastic tonsils and adenoids** (hallmark finding due to lack of B-cells in lymphoid tissue). - Patients have normal T-cell function, so they can initially tolerate live vaccines and do not typically have severe viral or opportunistic infections seen in combined immunodeficiencies. - Treatment involves lifelong **immunoglobulin replacement therapy** and prophylactic antibiotics. *Defective IL-2R gamma chain* - This causes **X-linked Severe Combined Immunodeficiency (SCID)**, which presents much earlier (typically **2-4 months**) with severe viral, fungal, and opportunistic infections (e.g., PCP pneumonia, CMV). - SCID patients have both **T-cell and B-cell deficiencies**, leading to failure to thrive and life-threatening infections in early infancy. - **Live vaccines are contraindicated** in SCID; the fact that this child's immunizations are up-to-date makes SCID less likely. - The later onset (10 months) and predominantly bacterial infection pattern do not fit SCID. *Defective NADPH oxidase* - This defect causes **Chronic Granulomatous Disease (CGD)**, characterized by recurrent infections with **catalase-positive organisms** (Staphylococcus aureus, Aspergillus, Burkholderia). - Patients develop **abscesses and granulomas** in lymph nodes, liver, lungs, and skin. - Lymphoid tissue is **normal**, not hypoplastic, and immunoglobulin levels are typically normal. *Defect in the ATM gene* - A defect in the **ataxia-telangiectasia mutated (ATM)** gene causes **Ataxia-Telangiectasia**, with the triad of **progressive cerebellar ataxia** (usually by age 2), **oculocutaneous telangiectasias**, and immunodeficiency (mainly IgA deficiency). - This patient lacks neurological symptoms and telangiectasias, making this diagnosis unlikely. *WAS gene mutation* - **Wiskott-Aldrich syndrome** presents with the classic triad of **thrombocytopenia** (petechiae, bleeding), **eczema**, and recurrent infections. - The absence of bleeding manifestations and skin findings makes this diagnosis unlikely.

Question 6: An 8-year-old boy presents to his pediatrician accompanied by his father with a complaint of chronic cough. For the past 2 months he has been coughing up yellow, foul-smelling sputum. He has been treated at a local urgent care center for multiple episodes of otitis media, sinusitis, and bronchitis since 2 years of age. His family history is unremarkable. At the pediatrician's office, his temperature is 99.2°F (37.3°C), blood pressure is 110/84 mmHg, pulse is 95/min, and respirations are 20/min. Inspection shows a young boy who coughs occasionally during examination. Pulmonary exam demonstrates diffuse wheezing and crackles bilaterally. Mild clubbing is present on the fingers. The father has brought an electrocardiogram (ECG) from the patient’s last urgent care visit that shows pronounced right axis deviation. Which of the following is the most likely etiology of this patient’s condition?

A. Failure of neural crest cell migration
B. Maldevelopment of pharyngeal pouches
C. Transient bronchoconstriction
D. Defective maturation of B-lymphocytes
E. Decreased motility of cilia (Correct Answer)

Explanation: ***Decreased motility of cilia*** - The recurrent respiratory infections (**otitis media, sinusitis, bronchitis**), chronic productive cough with **foul-smelling sputum**, and **bronchiectasis** (implied by chronic cough, wheezing, crackles) are highly suggestive of **primary ciliary dyskinesia (PCD)**. - **Clubbing** and **right axis deviation** (suggesting right ventricular hypertrophy from pulmonary hypertension) are complications of chronic lung disease such as severe bronchiectasis, which is characteristic of PCD. *Failure of neural crest cell migration* - This is associated with conditions like **DiGeorge syndrome** or **Hirschsprung disease**, which present with different clinical features (e.g., cardiac defects, hypocalcemia, intestinal obstruction). - It does not directly explain the recurrent respiratory tract infections and bronchiectasis seen in this patient. *Maldevelopment of pharyngeal pouches* - Similar to neural crest cell defects, issues with pharyngeal pouch development (e.g., **DiGeorge syndrome**) affect the immune system and cardiac structures. - While it can lead to recurrent infections, it typically involves **T-cell deficiencies** and specific cardiac anomalies, rather than chronic suppurative respiratory disease and bronchiectasis as the primary presentation. *Transient bronchoconstriction* - This describes conditions like **asthma**, which causes reversible airway narrowing and wheezing. - However, asthma does not explain the chronic **foul-smelling sputum**, **clubbing**, persistent recurrent infections like otitis media and sinusitis, or the development of bronchiectasis. *Defective maturation of B-lymphocytes* - This leads to **immunodeficiencies** primarily affecting **antibody production**, such as **X-linked agammaglobulinemia**. - While patients would experience recurrent bacterial infections, the specific pattern of chronic sinusitis, otitis, and bronchiectasis with **foul-smelling sputum** (suggesting chronic bacterial colonization and impaired clearance) points more towards a structural or ciliary defect than a purely humoral immune deficiency.

Question 7: A 22-month-old girl is brought to the emergency department with a 24-hour history of fever, irritability, and poor feeding. The patient never experienced such an episode in the past. She met the normal developmental milestones, and her vaccination history is up-to-date. She takes no medications, currently. Her temperature is 38.9°C (102.0°F). An abdominal examination reveals general tenderness without organomegaly. The remainder of the physical examination shows no abnormalities. Laboratory studies show the following results: Urine Blood 1+ WBC 10–15/hpf Bacteria Many Nitrite Positive Urine culture from a midstream collection reveals 100,000 CFU/mL of Escherichia coli. Which of the following interventions is the most appropriate next step in evaluation?

A. No further testing
B. Voiding cystourethrography
C. Renal and bladder ultrasonography (Correct Answer)
D. Intravenous pyelography
E. Dimercaptosuccinic acid renal scan

Explanation: ***Renal and bladder ultrasonography*** - For a febrile infant or young child (2 to 24 months) with a first **culture-proven urinary tract infection (UTI)**, renal and bladder ultrasonography is the recommended imaging study. - This imaging is crucial to evaluate for **anatomic abnormalities** of the kidneys and urinary tract that could predispose to recurrent infections or renal damage. - Current AAP guidelines recommend ultrasound as the **initial imaging modality** to assess for conditions like vesicoureteral reflux (VUR), hydronephrosis, or obstructive uropathy. *No further testing* - This option is incorrect because a **febrile UTI** in a young child warrants imaging to rule out **underlying genitourinary abnormalities** that could predispose to recurrent infections or renal damage. - Skipping further evaluation could miss conditions like **vesicoureteral reflux (VUR)** or obstructive uropathy. *Voiding cystourethrography* - **Voiding cystourethrography (VCUG)** was historically recommended for all young children after a first UTI but is now reserved for specific situations, such as **abnormal renal/bladder ultrasound findings** or recurrent UTIs. - VCUG involves radiation exposure and catheterization, making it less favorable as a first-line imaging study. *Intravenous pyelography* - **Intravenous pyelography (IVP)** involves intravenous contrast and radiation, making it an **invasive and high-radiation study** that has largely been replaced by ultrasound and CT for evaluating the urinary tract. - It is not recommended as the initial imaging of choice for a child with a first UTI due to its **risks and availability of safer alternatives**. *Dimercaptosuccinic acid renal scan* - A **dimercaptosuccinic acid (DMSA) renal scan** is primarily used to detect **renal scarring** and assesses differential renal function. - While it can be useful in identifying long-term consequences of UTIs, it is not the primary imaging study for initial evaluation of **ureteral or bladder abnormalities** in a first febrile UTI.

Question 8: A 10-year-old boy is brought to the pediatric clinic because of persistent sinus infections. For the past 5 years, he has had multiple sinus and upper respiratory infections. He has also had recurrent diarrhea throughout childhood. His temperature is 37.0°C (98.6°F), the heart rate is 90/min, the respirations are 16/min, and the blood pressure is 125/75 mm Hg. Laboratory studies show abnormally low levels of one immunoglobulin isotype but normal levels of others. Which of the following is the most likely diagnosis?

A. Chediak-Higashi syndrome
B. Selective IgA deficiency (Correct Answer)
C. Common variable immunodeficiency
D. Drug-induced IgA deficiency
E. Transient hypogammaglobulinemia of infancy

Explanation: ***Selective IgA deficiency*** - This condition is characterized by **abnormally low levels of IgA** with normal levels of other immunoglobulins, leading to recurrent **respiratory and gastrointestinal infections**. - The patient's history of persistent sinus infections, upper respiratory infections, and recurrent diarrhea is highly consistent with the mucosal immune defects seen in IgA deficiency. *Chediak-Higashi syndrome* - This syndrome is a rare autosomal recessive disorder characterized by **partial oculocutaneous albinism**, recurrent pyogenic infections, and neurological abnormalities due to defective lysosomal trafficking. - While it involves recurrent infections, the clinical picture does not include the characteristic features like albinism, nor does it typically present as an isolated IgA deficiency. *Common variable immunodeficiency* - This involves **low levels of IgG and IgA**, and sometimes IgM, leading to recurrent infections, particularly bacterial infections of the respiratory and gastrointestinal tracts. - The patient's lab results specifically mention abnormally low levels of **one immunoglobulin isotype** (IgA), which differentiates it from CVID where multiple isotypes are low. *Drug-induced IgA deficiency* - While certain medications can cause IgA deficiency, the patient's symptoms have been persistent for 5 years, suggesting a **hereditary or primary immunodeficiency** rather than a transient drug-induced effect without a clear history of causative drug use. - Common drugs causing IgA deficiency include phenytoin or D-penicillamine, which are not mentioned in the patient's history. *Transient hypogammaglobulinemia of infancy* - This condition typically resolves by **2-3 years of age** as the infant's immune system matures and starts producing its own antibodies. - The patient is 10 years old, and his symptoms have persisted for 5 years, making this diagnosis unlikely due to the persistent nature of the deficiency at this age.

Question 9: A 2-year-old boy is brought to the physician by his mother for evaluation of recurrent infections and easy bruising. He has been hospitalized 3 times for severe skin and respiratory infections, which responded to treatment with antibiotics. Examination shows sparse silvery hair. The skin is hypopigmented and there are diffuse petechiae. Laboratory studies show a hemoglobin concentration of 8 g/dL, leukocyte count of 3000/mm3, and platelet count of 45,000/mm3. A peripheral blood smear shows giant cytoplasmic granules in granulocytes and platelets. Which of the following is the most likely underlying cause of this patient's symptoms?

A. Defective tyrosine kinase gene
B. WAS gene mutation
C. Defective NADPH oxidase
D. Defective lysosomal trafficking regulator gene (Correct Answer)
E. Defective CD40 ligand

Explanation: ***Defective lysosomal trafficking regulator gene*** - This clinical presentation including **recurrent infections**, **easy bruising (thrombocytopenia)**, **sparse silvery hair**, **hypopigmented skin**, and **giant cytoplasmic granules in granulocytes and platelets** is characteristic of **Chediak-Higashi syndrome**. - **Chediak-Higashi syndrome** is an **autosomal recessive disorder** caused by a mutation in the **LYST (lysosomal trafficking regulator)** gene, leading to defective lysosomal function and formation of giant granules. *Defective tyrosine kinase gene* - A defective tyrosine kinase gene (such as **BTK**) is associated with **X-linked agammaglobulinemia (Bruton's agammaglobulinemia)**, which features recurrent bacterial infections due to absent B cells and immunoglobulins. - It does not typically present with **oculocutaneous albinism**, **bleeding diathesis**, or **giant granules** in white blood cells. *WAS gene mutation* - A **WAS gene mutation** causes **Wiskott-Aldrich syndrome**, an **X-linked recessive disorder** characterized by the triad of **thrombocytopenia with small platelets**, **eczema**, and **recurrent infections**. - While it involves recurrent infections and easy bruising, it does not include **silvery hair**, **hypopigmentation**, or **giant cytoplasmic granules**. *Defective NADPH oxidase* - A defective **NADPH oxidase** causes **Chronic Granulomatous Disease (CGD)**, characterized by **recurrent severe bacterial and fungal infections** due to impaired phagocyte oxidative burst. - CGD is not associated with **silvery hair**, **hypopigmentation**, **thrombocytopenia**, or the presence of **giant cytoplasmic granules**. *Defective CD40 ligand* - A defective **CD40 ligand** on T cells causes **Hyper-IgM syndrome**, an **X-linked immunodeficiency** characterized by normal or elevated IgM levels but low levels of IgG, IgA, and IgE, leading to recurrent infections. - It does not present with **silvery hair**, **hypopigmentation**, or the characteristic **hematologic abnormalities** seen in this patient.

Question 10: A 3-year-old boy is brought to the physician for the evaluation of recurrent skin lesions. The episodes of lesions started at the age of 3 months. He has also had several episodes of respiratory tract infections, enlarged lymph nodes, and recurrent fevers since birth. The boy attends daycare. The patient's immunizations are up-to-date. He is at the 5th percentile for length and 10th percentile for weight. He appears ill. Temperature is 38°C (100.4°F). Examination shows several raised, erythematous lesions of different sizes over the face, neck, groin, and extremities; some are purulent. Bilateral cervical and axillary lymphadenopathy are present. What is the most likely underlying mechanism of this patient's symptoms?

A. Defective cytoplasmic tyrosine kinase
B. NADPH oxidase deficiency (Correct Answer)
C. Impaired signaling to actin cytoskeleton reorganization
D. Defective neutrophil chemotaxis
E. Impaired repair of double-strand DNA breaks

Explanation: ***NADPH oxidase deficiency*** - The recurrent skin abscesses (purulent lesions), respiratory tract infections, lymphadenopathy, and fevers point to chronic granulomatous disease (CGD), which is caused by a deficiency in **NADPH oxidase**. - **NADPH oxidase** is essential for the production of reactive oxygen species (ROS) in phagocytes, which are critical for killing catalase-positive bacteria and fungi. *Defective cytoplasmic tyrosine kinase* - This mechanism is associated with **X-linked agammaglobulinemia (Bruton's agammaglobulinemia)**, which primarily causes recurrent bacterial infections due to a lack of B cells and antibodies. - While recurrent infections occur, the typical presentation involves encapsulated bacteria and lacks the widespread purulent skin lesions and lymphadenopathy seen in CGD. *Impaired signaling to actin cytoskeleton reorganization* - This defect is characteristic of **Wiskott-Aldrich syndrome**, leading to thrombocytopenia, eczema, and recurrent infections, particularly by encapsulated bacteria. - The clinical picture of recurrent widespread skin abscesses and granuloma formation is not typical for Wiskott-Aldrich syndrome. *Defective neutrophil chemotaxis* - This can be seen in conditions like **leukocyte adhesion deficiency (LAD)** or **Chédiak-Higashi syndrome**. - LAD presents with recurrent bacterial infections, impaired wound healing, and delayed umbilical cord separation, while Chédiak-Higashi involves partial oculocutaneous albinism and recurrent pyogenic infections, distinct from this patient's symptoms. *Impaired repair of double-strand DNA breaks* - This defect is associated with conditions like **ataxia-telangiectasia**, which involves cerebellar ataxia, telangiectasias, and immunodeficiency (T-cell and IgA deficiency). - The patient's symptoms of recurrent purulent skin lesions and infections are not characteristic of the DNA repair defects seen in ataxia-telangiectasia.

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