Diseases of the Immune System

Question 1

1. A graduate student in an immunology lab is
   studying a certain cell that plays a role in adaptive
   immunity. Of the following, which cell type might
   the student be studying?
   A. Macrophage
   B. Neutrophil
   C. Eosinophil
   D. Natural killer cell
   E. Lymphocyte

Answer 1

1. Correct: Lymphocyte (E)
   The lymphocyte is a cell type found in adaptive
   (also referred to as specific, or acquired) immunity
   (E), whereas the other cell types listed play a role in
   innate (also referred to as native or natural) immunity
   (A-D).

Question 2

2. A graduate student has developed a protein that
   binds to CD3 and blocks its interaction with TCR,
   which is composed of γ and δ subunits. Of the following,
   which organ is the student studying?
   A. Brain
   B. Heart
   C. Intestine
   D. Liver
   E. Kidney

Answer 2

2. Correct: Intestine (C)
   The TCR (T-cell receptor) binds to the MHC (major
   histocompatibility complex) on antigen-presenting
   cells, with CD4 in helper T cells and CD8 in cytotoxic
   T cells participating. TCR is normally composed of an
   α and a β subunit, however, T cells with a TCR composed of a γ and δ subunit are found associated with mucosal surfaces (C). For (A-B, D-E), see previous
   information.

Question 3

3. A 32-year-old male with a known severe peanut
   allergy is inadvertently exposed to peanuts by
   eating a homemade cookie. Within minutes of exposure
   he develops a widespread rash and difficulty
   breathing, which resolve with a self-administered
   epinephrine injection. Which of the following statements
   is most characteristic regarding this type of
   allergic reaction?
   A. The immediate reaction is triggered by IgM
   bound to antigen.
   B. The immediate allergic reaction is triggered by
   activation of eosinophils.
   C. This type of allergic reaction is caused by
   excessive a TH2 response.
   D. Prostaglandins do not play a role in this type of
   reaction.
   E. Previous exposure to the antigen is not required
   for this type of reaction.

Answer 3

3. Correct: This type of allergic reaction is
   caused by excessive TH2 response (C)
   This patient is experiencing an anaphylactic reaction,
   a classic type I (immediate) hypersensitivity reaction.
   Type I hypersensitivity reactions are triggered by crosslinking of membrane-bound IgE on mast cells (A, B). Previous antigen exposure is required for the production of this antigen-specific IgE (E). This previous exposure results in TH2 cells secreting IL-4 and IL-5, which promotes B-cell class switching to produce the IgE (C). These reactions follow a characteristic pattern of initial reaction (caused by mast cell activation and release of mediators, including prostaglandins) followed 2 to 24 hours later by a late-phase reaction mostly due to activation of eosinophils (D).

Question 4

4. A 42-year-old woman presents to her primary
   care physician complaining of itching and watery
   eyes, runny nose, and frequent sneezing. She denies
   fever or cough. She experiences similar symptoms
   every year in the spring. Which of the following is
   responsible for her symptoms?
   A. Binding of antigen to IgE on mast cell surfaces
   B. Recognition of antigen associated with MHC-1
   C. Binding of polysaccharide to membrane-bound
   lectin receptors
   D. Destruction of cells coated with IgM
   E. Inflammation due to deposition of antigenantibody
   complex

Answer 4

4. Correct: Binding of antigen to IgE on mast cell
   surfaces (A)
   This woman is presenting with classical symptoms
   of seasonal allergies, a type 1 hypersensitivity reaction
   caused by crosslinking of IgE on previously sensitized mast cells (A). Recognition of antigen presented on MHC1 activates CD8+ T-cells, which plays an important role in defense against viruses and intracellular pathogens but no role in seasonal allergies (B). Recognition of microbial polysaccharides by lectin receptors activates leukocytes in response to extracellular pathogens (C). (D, E) describe the
   mechanism of Type 2 and Type 3 hypersensitivity
   reactions respectively.

Question 5

5. A blood type O+ infant is delivered to a multiparous
   blood type O- mother without prenatal care.
   The infant is born with severe anemia, jaundice, and
   severe edema. What is the underlying mechanism of
   this disease?
   A. Crosslinking of IgE on mast cell surfaces
   B. IgG binding to cell surfaces
   C. Deposition of antigen antibody complexes in the
   fetal tissue
   D. T-cell mediated cytotoxicity
   E. Antibody mediated activation of apoptosis

Answer 5

5. Correct: IgG binding to cell surfaces (B)
   Autoimmune hemolytic disease of the newborn is a
   type 2 hypersensitivity reaction. In this condition a
   previously sensitized woman develops IgG antibodies
   against Rh+ antigens on fetal red cells. These antibodies
   cross the placenta and lead to lysis of fetal red
   cells (B). For (A, C-E), see previous information.

Question 6

6. A 32-year-old man hiking in Guatemala is bitten
   by a rattlesnake. He is treated with equine antivenin.
   He recovers; however, 2 weeks afterward, he
   develops rash, fever, and polyarthralgia. Laboratory
   evaluation reveals a leukocyte count of 3200/μL, a
   hemoglobin concentration of 16.0 g/dL, a platelet
   count of 95,000/μL, and a serum creatinine of 1.8 mg/
   dL. What is the most likely diagnosis?
   A. Chikungunya fever
   B. Lyme disease
   C. Serum sickness
   D. Malaria
   E. Autoimmune hemolytic anemia

Answer 6

6. Correct: Serum sickness (C)
   This patient is suffering from serum sickness, a type 3 (immune complex mediated) hypersensitivity reaction. The history of recent treatment with equine antivenin makes serum sickness much more likely than the other options (C). Although Lyme disease, malaria, and Chikungunya fever are present in Central America, again the history suggests another diagnosis (A-B, D). The normal hemoglobin concentration makes a hemolytic anemia unlikely (E).

Question 7

7. A 32-year-old female immigrant is hired for a
   food service job at the local cafeteria. As part of her
   pre-hire physical examination she is given a purified
   protein derivative (PPD) skin test. She returns to
   the occupational health clinic 48 hours later with a
   denuded 22 mm bulla and induration and erythema
   involving the majority of the volar surface of her right
   arm. A wound culture is performed; however, there
   is no growth at 48 hours. A biopsy of the skin lesion
   would most likely show which of the following?
   A. Neutrophil predominant infiltrate
   B. Perivascular accumulation of lymphocytes and
   mononuclear cells
   C. Granulomatous inflammation
   D. Immune complex deposition in the soft tissue
   E. Abundant eosinophils

Answer 7

7. Correct: Perivascular accumulation of lymphocytes and mononuclear cells (B)
   This is a markedly positive PPD test in a patient who
   probably has latent or active tuberculosis. This type of
   reaction is a CD4+ T-cell-mediated delayed type hypersensitivity (Type IV hypersensitivity) reaction. Expected findings include dermal edema and perivascular (“cuffing”) accumulation of macrophages and lymphocytes (B). Granulomatous inflammation would be unlikely in the skin but would likely be seen in the lungs and hilar lymph nodes (C). Bacterial infection such as cellulitis would cause a neutrophilic infiltrate, but her wound culture was negative (A). Eosinophils would be expected in a drug reaction or parasitic infection (E). The mechanism of this type of hypersensitivity reaction does not involve immune complex deposition (D).

Question 8

8. A 10 year-old girl is stung by a bee while with
   her family at a school picnic. About 10 minutes
   later, she becomes nauseated and vomits twice,
   and shortly thereafter her parents notice that her
   face begins to swell and she begins to wheeze. Her
   parents rush her to the hospital, where treatment
   is administered. Which of the following statements
   best describes her condition?
   A. The reaction is mediated by preformed IgG
   antibodies.
   B. She is having a type II hypersensitivity reaction.
   C. The main cellular mediator is macrophages.
   D. The most likely cause of her symptoms is foreign
   body ingestion.
   E. A similar reaction can occur in people given
   penicillin.

Answer 8

8. Correct: A similar reaction can occur in
   people given penicillin (E)
   The girl is having a type I hypersensitivity anaphylactic
   reaction (B). After a first exposure to an antigen (A), these patients have a heightened TH2 response that leads to the development of mast cells with IgE that is specific for the antigen. These reactions occur as a result of the binding of antigen to IgE on the surface of mast cells in a previously sensitized individual; however, up to half of all fatal insect sting reactions occur in persons with no prior history of insect stings. Amongst medications, penicillins, aspirin, and nonsteroidal anti-inflammatory drugs are most commonly associated with anaphylaxis. Subsequent exposure to the antigen will cause a release of mediators from the mast cell (C),
   leading to vasodilation and increased vascular permeability, which can clinically cause swelling of the airway. Given her history, foreign body ingestion is not likely, and would be associated with stridor, and not the precipitating bee sting (D). In addition to bee stings, other allergens known to cause a type I hypersensitivity reaction
   are peanuts and penicillin (E)

Question 9

9. A 10 year-old girl is stung by a bee while with
   her family at a school picnic. About 10 minutes
   later, she becomes nauseated and vomits twice,
   and shortly thereafter her parents notice that her
   face begins to swell and she begins to wheeze. Her
   parents rush her to the hospital, where treatment
   is administered.Given the previous clinical scenario, of the following,
   what is the diagnosis?
   A. A type I hypersensitivity reaction
   B. A type II hypersensitivity reaction
   C. A type IIIa hypersensitivity reaction
   D. A type IIIb hypersensitivity reaction
   E. A type IV hypersensitivity reaction

Answer 9

9. Correct: A type I hypersensitivity reaction (A)
   See explanation for question #8. The patient is
   experiencing a type-I hypersensitivity anaphylactic
   reaction (A). These reactions occur as a result of the
   binding of antigen to IgE on the surface of mast cells
   in a previously sensitized individual. Type III hypersensitivity reactions are not usually subdivided into
   types a and b (C, D). The reaction is neither type II (B) or type IV (E).

Question 10

10. A 23-year-old male is hit by a bullet during a
    drive-by shooting at a local store. He is rushed to the
    emergency room and is determined to have a hemothorax.
    A chest tube is placed and intravenous fluids and
    blood are given. Immediately after the transfusion, he
    develops a temperature of 100.3°F and chills. Shortly
    thereafter, he develops a blood pressure of 80/50 mm
    Hg. Of the following, which is most likely occurring?
    A. A type I hypersensitivity reaction
    B. A type II hypersensitivity reaction
    C. A type IIIa hypersensitivity reaction
    D. A type IIIb hypersensitivity reaction
    E. A type IV hypersensitivity reaction

Answer 10

10. Correct: A type II hypersensitivity reaction (B)
    Given that the patient just received blood and
    immediately afterward developed fever and chills,
    an immediate transfusion reaction, caused by IgM
    reacting against AB blood antigens, is the most likely
    cause. This is a type II hypersensitivity reaction (B).
    The IgM antibodies against the A or B antigen are
    naturally occurring and do not require previous sensitization to the antigen. Intravascular hemolysis will
    occur, causing free hemoglobin to be identified in the
    blood. This type of transfusion reaction can be fatal.
    For (A, C-E), see previous information.

Question 11

11. A 23-year-old male is hit by a bullet during a
    drive-by shooting at a local store. He is rushed to the
    emergency room and is determined to have a hemothorax.
    A chest tube is placed and intravenous fluids and
    blood are given. Immediately after the transfusion, he
    develops a temperature of 100.3°F and chills. Shortly
    thereafter, he develops a blood pressure of 80/50 mm
    Hg. Given the previous clinical scenario, of the following,
    which antibody type is responsible for his
    reaction?
    A. IgA
    B. IgD
    C. IgE
    D. IgG
    E. IgM

Answer 11

11. Correct: IgM (E)
    See explanation for Question #10.
    Given that the patient just received blood and
    immediately afterward developed fever and chills,
    an immediate transfusion reaction, caused by IgM
    reacting against AB blood antigens, is the most likely
    cause. This is a type II hypersensitivity reaction (B).
    The IgM antibodies against the A or B antigen are
    naturally occurring and do not require previous sensitization to the antigen. Intravascular hemolysis will
    occur, causing free hemoglobin to be identified in the blood. This type of transfusion reaction can be fatal. For (A, C-E), see previous information.

Question 12

12. A 47-year-old male with a history of Zollinger-
    Ellinson’s syndrome presents to the emergency
    room vomiting bright red blood. He has twice before
    presented to the emergency room vomiting blood.
    On arrival, a complete blood cell count is performed,
    revealing a hemoglobin of 5.6 g/dL. A decision to
    transfuse is made, and he receives 4 units of blood.
    His blood type is O–. His bleeding is brought under
    control and he is admitted to the hospital. He is
    scheduled for surgery the next day. Prior to surgery,
    a complete blood cell count reveals a hemoglobin of
    6.2 g/dL. Of the following, which best explains his
    low hemoglobin prior to surgery?
    A. Bleeding from a second ulcer
    B. Insufficient number of units of blood transfused
    C. An immediate hemolytic transfusion reaction
    D. A delayed hemolytic transfusion reaction
    E. Laboratory error

Answer 12

12. Correct: A delayed hemolytic transfusion
    reaction (D)
    Given the fact that the patient has twice before been
    seen in the emergency room for vomiting blood, he
    has most likely been transfused. This exposure has
    caused him to develop antibodies against a blood
    group antigen that is not A or B (e.g., D, Kell, Duffy,
    Kidd). When he was exposed to the blood group
    antigen this time, he had already formed IgG against
    the antigen, which bound to the antigen and led to
    extravascular hemolysis, a delayed transfusion reaction
    (D). Because the blood he was given elicited this
    response, much of it was removed from circulation,
    and his hemoglobin did not rise much. For (A-C, E),
    see previous information.

Question 13

13. A 47-year-old male with a history of Zollinger-
    Ellinson’s syndrome presents to the emergency
    room vomiting bright red blood. He has twice before
    presented to the emergency room vomiting blood.
    On arrival, a complete blood cell count is performed,
    revealing a hemoglobin of 5.6 g/dL. A decision to
    transfuse is made, and he receives 4 units of blood.
    His blood type is O–. His bleeding is brought under
    control and he is admitted to the hospital. He is
    scheduled for surgery the next day. Prior to surgery,
    a complete blood cell count reveals a hemoglobin of
    6.2 g/dL. Given the previous clinical scenario, of the following,
    which antibody type is responsible for the
    reaction?
    A. IgA
    B. IgD
    C. IgE
    D. IgG
    E. IgM

Answer 13

13. Correct: IgG (D)
    See explanation for question #12.
    Given the fact that the patient has twice before been
    seen in the emergency room for vomiting blood, he
    has most likely been transfused. This exposure has
    caused him to develop antibodies against a blood
    group antigen that is not A or B (e.g., D, Kell, Duffy,
    Kidd). When he was exposed to the blood group
    antigen this time, he had already formed IgG against
    the antigen, which bound to the antigen and led to
    extravascular hemolysis, a delayed transfusion reaction
    (D). Because the blood he was given elicited this
    response, much of it was removed from circulation,
    and his hemoglobin did not rise much. For (A-C, E),
    see previous information.

Question 14

14. A 26-year-old Hispanic female presents to her
    primary care physician complaining of 2 months of
    fatigue. She has persistent arthralgias of the distal
    and proximal interphalangeal joints of both hands
    and reports that when the weather turns cold her
    hands frequently change colors. Her physical examination
    is normal and there is no tenderness or deformity
    of the joints of the hands. A complete blood
    count is normal and her antinuclear antibody titer
    is elevated at 1:90. Which of the following additional
    tests would confirm the diagnosis of lupus
    erythematosus?
    A. Positive SS-A
    B. Positive SS-B
    C. Positive anti-cyclic citrullinated peptide
    (CCP-IgG)
    D. Positive rheumatoid factor
    E. Positive anti-Smith

Answer 14

14. Correct: Positive anti-Smith (E)
    Anti-Smith (E) is most specific for systemic lupus.
    Anti-CCP IgG is most specific for rheumatoid arthritis
    (C). SS-A, SS-B, and rheumatoid factor are typically
    associated with other rheumatologic illnesses but can be seen in patients with lupus, particularly in overlap syndromes, but are not specific for lupus (A, B, D).

Question 15

15. A 36-year-old African-American with stage
    2 hypertension is started on hydralazine for better
    blood pressure control. Four months after starting
    the medications, he develops recurring low-grade
    fevers and pains in the joints of both hands. Examination
    of both hands is normal; however, there is a
    slight erythematous dermatitis over both cheeks.
    Of the following, which test is most likely to be
    abnormal?
    A. Anti-Smith antibody
    B. Anti–double-stranded DNA antibody
    C. Serum uric acid level
    D. Antinuclear antibody (ANA)
    E. Low serum complement levels

Answer 15

15. Correct: Antinuclear antibody (ANA) (D)
    This patient has classic hydralazine-induced lupus.
    Antinuclear antibodies are positive in the majority
    of patients with drug-induced lupus; however, anti-
    Smith and anti-dsDNA antibodies are rare in hydralazine- induced lupus (D, A, B). An elevated serum
    uric acid level would suggest gout, which can be provoked in patients treated with hydrochlorothiazide
    but has not been described as a side effect of hydralazine treatment, and the symmetrical involvement
    of multiple joints in both hands would be unusual for
    gout (C). Low serum complement levels can be seen
    in idiopathic systemic lupus but are rare in drug induced
    lupus (E).

Question 16

16. A 55-year-old white female with stable hypertension
    presents to her primary care physician
    complaining of fatigue and joint pain. The symptoms
    started 6 months ago. She reports pain in the
    metacarpophalangeal (MCP) joints, the proximal
    interphalangeal (PIP) joints, and both wrists, with
    the pain worse in the morning, associated with stiffness,
    and improving somewhat throughout the day.
    On examination there is tenderness and mild swelling
    of the MCP joints, the PIP joints, and the wrists,
    but there is no tenderness or deformity of the distal
    interphalangeal (DIP) joints. What is the most likely
    diagnosis?
    A. Osteoarthritis
    B. Rheumatoid arthritis
    C. Lyme disease
    D. Systemic lupus
    E. Gout

Answer 16

16. Correct: Rheumatoid arthritis (B)
    This patient has rheumatoid arthritis (RA) (B). Rheumatoid
    arthritis, in contrast to osteoarthritis, typically
    spares the distal interphalangeal joints (A). RA
    is usually polyarticular and symmetric as opposed
    to gout, which is typically monoarticular and most
    often affects the metatarsophalangeal joint of the
    foot (E). Including Lyme disease in the differential
    diagnosis would be appropriate, but Lyme disease
    is much less common than RA and there is no evidence
    to suggest she is at risk for Lyme disease (C).
    Similarly, including systemic lupus in the differential
    diagnosis would be appropriate; however, the clinical
    history is much more suggestive of RA than lupus
    (D).

Question 17

17. Given the patient’s most likely diagnosis of Rheumatoid arthritis, of
    the following tests, which, if positive, would confirm
    the diagnosis?
    A. Rheumatoid factor (RF)
    B. Anti-cyclic citrulinated peptide (CCP IgG)
    C. Borrellia titers
    D. Anti–double-stranded DNA (dsDNA)
    E. Serum uric acid levels

Answer 17

17. Correct: Anti–cyclic citrulinated peptide
    (CCP IgG) (B)
    The most likely diagnosis is rheumatoid arthritis (RA). Of the answers above, only anti-CCP IgG is specific to RA (B). For (A, C-E), see previous information.

Question 18

18. A 45-year-old female immigrant presents
    with progressive shortness of breath and fatigue that
    have developed over the past 3 weeks. She also has
    sores on both legs. She has a long-standing history of
    joint pain but has not received medical attention for
    this problem. Her temperature is 98.6°F (37°C), pulse
    78 bpm, blood pressure 132/64 mm Hg, respirations
    20/min, and oxygen saturation 92% on room air. On
    examination she has deep cutaneous ulcers around
    the lateral malleoli of both ankles. Her heart sounds
    are normal, and there are faint crackles in both lung
    bases. The abdomen is not tender and the spleen is
    enlarged. A plain chest radiograph shows bibasilar
    ground glass opacities. The phalanges demonstrate
    flexion of the proximal and hyperextension of the
    distal interphalangeal joints and ulnar deviation.
    There are several nontender, moveable nodules on
    the extensor surface of the elbow. What is the most
    likely diagnosis?
    A. HLA-B27-positive spondyloarthropathy
    B. ANCA positive vasculitis
    C. Psoriatic arthritis
    D. Felty’s syndrome
    E. Systemic lupus erythematosus

Answer 18

18. Correct: Felty’s syndrome (D)
    Physical examination findings include boutonnière
    deformity and ulnar deviation of the fingers as well
    as rheumatoid nodules, all of which are highly suggestive
    of rheumatoid arthritis (RA). The remainder of the extra-articular findings (interstitial lung disease, splenomegaly, and vasculitis) are characteristic of Felty’s syndrome, a complication of long standing or poorly controlled RA (D). For (A-C, E), see previous information.

Question 19

19. Of the following,
what is a risk factor for developing Felty's syndrome?
A. Multiparity
B. Male sex
C. Breast feeding
D. Haplotype HLA-B27
E. Cigarette smoking

Answer 19

19. Correct: Cigarette smoking (E)
    Cigarette smoking is strongly associated with the
    development of rheumatoid arthritis (E). Multiparity
    and breast-feeding both decrease the risk (A, C). The
    HLA-B27 haplotype is associated with several autoimmune diseases including ankylosing spondylitis,
    Reiter’s syndrome (reactive arthritis), and inflammatory
    bowel disease but is present in patients with RA no more frequently than in the general population (D). Male sex is not a risk factor (B).

Question 20

20. A 40-year-old woman with long-standing
    lupus erythematosus presents complaining of chest
    pain. She reports that the pain started 8 hours prior
    to her arrival, is sharp, is worse with deep breaths
    and cough, and is improved by sitting up and leaning
    forward. Her temperature is 100.3°F (37.9°C),
    pulse 108/min, BP 120/75 mm Hg, respirations 20/
    min, and oxygen saturation 98% on room air. She
    looks uncomfortable. On examination her lungs are
    clear, and her heart rate is regular with no murmurs.
    A chest radiograph is normal. Her 12-lead ECG shows
    diffuse ST elevation in all leads. What is the most
    likely diagnosis?
    A. Acute myocardial infarction
    B. Pulmonary embolism
    C. Aortic dissection
    D. Pericarditis
    E. Libman-Sacks endocarditis

Answer 20

20. Correct: Pericarditis (D)
    Examination: Pleuritic chest pain with diffuse ST
    elevation on ECG is typical of pericarditis, a common
    complication of systemic lupus (D). The presence of
    ST elevation in every lead makes acute myocardial
    infarction and pulmonary embolism unlikely (A, B). Patients with systemic lupus do have a 50-fold increased risk for myocardial infarction compared with the general population. Libman-Sacks endocarditis is a classic manifestation of lupus rarely seen in the modern era of disease-modifying therapy and would present as valve vegetations on echocardiogram but would not cause chest pain or ECG abnormalities (E). An aortic dissection will often produce a wide mediastinum on chest X-ray (C).

Question 21

21. A 40-year-old woman is evaluated for eye discomfort.
    She reports a foreign body sensation in both
    eyes for the past 3 weeks. Fluorescein examination
    reveals bilateral corneal ulcers. She has mild cervical
    lymphadenopathy and bilateral parotid enlargement
    on examination. Her rheumatoid factor is positive at
    75 units/mL. What is the most likely diagnosis?
    A. Sjögren’s syndrome
    B. Rheumatoid arthritis
    C. Systemic sclerosis
    D. Polymyositis
    E. Systemic lupus erythematosus

Answer 21

21. Correct: Sjögren’s syndrome (A)
    Corneal ulcers from keratoconjunctivitis sicca are
    a common complication of Sjögren’s syndrome (A).
    Lymphadenopathy and parotid enlargement are also
    common in this disease. Rheumatoid factor is positive
    in 75% of patients, and antinuclear antibodies (ANA)
    are positive in 50 to 80% of patients with Sjögren’s
    syndrome. Up to 90% of patients are positive for SS-A
    (Ro) or SS-B (La). For (B-E), see previous information.

Question 22

22. A 75-year-old male presents complaining of
    stiffness. He reports a 4-week history of stiffness and
    pain in both shoulders causing difficulty swinging a
    golf club. He also has neck stiffness and pain and significant
    fatigue. The stiffness in his shoulders is worse
    in the mornings and lasts for at least an hour. The small
    joints of his hands are not affected. He has lost 10 lbs.
    over the past month and reports frequent low-grade
    fevers. On examination his temperature is 98.8°F
    (37.1°C), pulse 85/min, and blood pressure 135/85
    mm Hg. There is moderate tenderness of the shoulder
    girdle with decreased range of motion with active
    abduction. The remainder of his musculoskeletal
    examination is normal. Complete blood count shows a
    normal leukocyte count and a normochromic normocytic
    anemia. His rheumatoid factor is negative. His
    erythrocyte sedimentation rate (ESR) is 109 mm/hr,
    and his C-reactive protein is 2.3 mg/dL. Of the following,
    which complication is this patient at risk for?
    A. Erosive arthritis
    B. Blindness
    C. Interstitial lung disease
    D. Renal failure
    E. Pericarditis

Answer 22

22. Correct: Blindness (B)
    This patient has polymyalgia rheumatica and is at
    high risk for giant cell (temporal) arteritis, a condition,
    which if untreated, commonly causes vision loss and blindness (B). Seronegative rheumatoid arthritis is possible; however, the lack of small joint involvement makes this unlikely. Erosive arthritis and interstitial lung disease are complications of rheumatoid arthritis (A, C). Renal failure and pericarditis are complications of systemic lupus (D, E).

Question 23

23. A 38-year-old woman presents to her primary
    care physician complaining of joint pain and fatigue. She
    reports progressive difficulty over the past two months
    in grasping objects. Exposure to cold temperatures frequently
    causes paresthesias and pallor in the fingers, followed
    by cyanosis, then erythema with rewarming. On
    examination her vital signs are normal. The heart and
    lung sounds are normal. There is puffy edema of the fingers
    with several ulcers of the fingertips and thickening of
    the skin of both hands. Antinuclear antibody (ANA) is positive.
    Of the following, what is the most likely diagnosis?
    A. Rheumatoid arthritis
    B. Systemic lupus erythematosus
    C. Polymyositis
    D. Subacute endocarditis
    E. Systemic sclerosis

Answer 23

23. Correct: Systemic sclerosis (E)
    The skin changes, digital ischemic ulcerations, and
    presence of Raynaud phenomenon are highly suggestive
    of systemic sclerosis (E). Up to 95% of patients with systemic sclerosis have positive ANA titers. None of the other choices would be expected to produce the skin changes described in the question, and thus they are unlikely in the absence of an overlap syndrome with other rheumatologic disease (A-D).

Question 24

24. A 55-year-old woman presents with painless
    enlargement of the parotid glands, which began
    6 months earlier. On examination, ocular dryness
    and cervical lymphadenopathy are present. Biopsy
    of the parotid gland is likely to show which of the
    following?
    A. Lymphocytic and plasma cell infiltrate with
    ductal epithelial hyperplasia
    B. Well-demarcated tumor consisting of a mixture
    of epithelial and myoepithelial cells dispersed
    within loose myxoid tissue
    C. Inflammation with neutrophil predominance
    and necrosis of salivary ducts
    D. Coagulative necrosis of acini with squamous
    metaplasia of ducts
    E. Sheets of small B-cells with infiltration and
    distortion of epithelial structures and scattered
    centroblast-like cells

Answer 24

24. Correct: Lymphocytic and plasma cell
    infiltrate with ductal epithelial hyperplasia (A)
    Characteristic pathologic findings in Sjögren’s syndrome include periductal and perivascular infiltration of lymphocytes. As the disease progresses, extensive lymphocytic infiltration can lead to formation of lymphoid follicles with germinal centers. With time, hyperplasia of the ductal epithelia can progress to atrophy of the acini, fibrosis, and hyalinization (A). (B) describes pleomorphic adenoma of the parotid gland, not Sjögren’s syndrome. Acute inflammatory infiltrate (C) or coagulative necrosis
    (D) would not be expected. (E) describes lymphoma,
    which is a complication that can develop in patients
    with Sjögren’s syndrome; however, it would not be
    expected.

Question 25

25. A 34-year-old female is brought to the emergency
    room by EMS after a seizure during dinner.
    Her past medical history includes arthritis, which
    has developed in the last few years. On a recent visit
    to her family physician for complaints of fatigue, she
    was found to have a serum leukocyte count of 3.3 ×
    109/L and a urine dipstick positive for protein, but
    negative for leukocyte esterase and glucose. Of the
    following, which is the most likely mechanism for
    the protein in her urine?
    A. An undiagnosed neoplasm
    B. A urinary tract infection
    C. Antibodies directed against the basement
    membrane
    D. Deposition of antigen-antibody complexes in the
    glomeruli
    E. Accumulation of advanced glycosylation endproducts
    in the glomerulus

Answer 25

25. Correct: Deposition of antigen-antibody
    complexes in the glomeruli (D)
    Of the choices, the most likely diagnosis is systemic
    lupus erythematosus, as it can cause fatigue, arthritis,
    leukopenia, and seizures, whereas none of the
    other conditions would cause all of these signs and
    symptoms. The mechanism of glomerular injury in
    systemic lupus is deposition of immune complexes
    in the glomerulus (D). For (A-C, E), see previous
    information.

Question 26

26. A 34-year-old female is evaluated by her family
    physician for moderate proteinuria, found incidentally
    on a urinalysis performed to evaluate for a
    urinary tract infection. A comprehensive metabolic
    panel shows a serum creatinine of 1.6 mg/dL. A kidney
    biopsy is performed, revealing an increase in
    the mesangial matrix. Of the following, which serologic
    test would be most helpful in confirming her
    diagnosis?
    A. Anti-dsDNA antibodies
    B. Anti-SSB antibodies
    C. Anti-SSA antibodies
    D. Anti-centromere antibodies
    E. Anti-scl70 antibodies

Answer 26

26. Correct: Anti-dsDNA antibodies (A)
    The presence of proteinuria associated with mesangial
    proliferation identified on kidney biopsy in a young female patient would most often be associated with underlying systemic lupus. Of the antibodies listed, anti-dsDNA antibodies are most specific to systemic lupus and are present in 40 to 60% of cases (A). Anti-SSA and anti-SSB antibodies are common in systemic lupus, but nonspecific (B, C). Anti-centromere and anti-SCL 70 antibodies are suggestive of systemic sclerosis (D, E).

Question 27

27. A 56-year-old female presents to her family
    physician. She complains that over the past year she
    has noticed that her mouth has been much drier, and
    that she has been using more eyedrops than previously.
    She has also noticed decreased mobility of the
    joints in her fingers, a situation which is worse in the
    morning but improves toward the evening. Of the
    following, what is the most likely diagnosis?
    A. Osteoarthritis
    B. Psoriatic arthritis
    C. Lyme disease
    D. Sjögren’s syndrome
    E. Osteomyelitis

Answer 27

27. Correct: Sjögren’s syndrome (D)
    Dry mouth and dry eyes (keratoconjunctivitis sicca)
    are the hallmark symptoms of Sjögren’s disease, an
    autoimmune disease characterized by lymphocytic
    infiltration and destruction of the salivary and lacrimal
    glands (D). With osteoarthritis, the pain usually worsens during the day (A). While psoriasis and Lyme disease can cause arthritis, they are not usually associated with the dry eyes and mouth (B, C). The clinical scenario is not consistent with osteomyelitis (E).

Question 28

28. A 56-year-old female presents to her family
    physician. She complains that over the past year she
    has noticed that her mouth has been much drier, and
    that she has been using more eyedrops than previously.
    She has also noticed decreased mobility of the
    joints in her fingers, a situation which is worse in the
    morning but improves toward the evening. Given the previous clinical scenario, of the following, what is serologic testing most likely to reveal?
    A. Anti-dsDNA
    B. Anti-Smith
    C. Anti-histone
    D. Anti-SSA
    E. Anti-centromere

Answer 28

28. Correct: Anti-SSA (D)
    This patient is suffering from Sjögren’s syndrome (SS),
    characterized by autoimmune destruction of the salivary
    and/or lacrimal glands. 25% or more of patients with Sjögren’s syndrome will experience extra glandular
    symptoms such as arthritis. Of the antibodies listed in the question, only anti-SSA, present in 70% of patients with Sjögren’s syndrome, would be expected (D). For (A-C, E), see previous information.

Question 29

29. A 56-year-old female presents to her family
    physician. She complains that over the past year she
    has noticed that her mouth has been much drier, and
    that she has been using more eyedrops than previously.
    She has also noticed decreased mobility of the
    joints in her fingers, a situation which is worse in the
    morning but improves toward the evening. Given the previous clinical scenario, of the following,
    histologic examination of her submandibular
    gland would most likely reveal?
    A. Granulomas
    B. Neutrophilic infiltrate
    C. Eosinophilic infiltrate
    D. Lymphocytic infiltrate
    E. Fibrosis and extensive calcification

Answer 29

29. Correct: Lymphocytic infiltrate (D)
    This patient’s clinical presentation is consistent with
    Sjögren’s syndrome. Of the answer choices, the most
    classic histologic finding in a biopsy of a submandibular
    gland in a patient with Sjögren’s syndrome is lymphocytic infiltrate (D). For (A-C, E), see previous information.

Question 30

30. A 52-year-old female presents to her internist
    with neck swelling. On examination there is marked
    enlargement of the submandibular gland bilaterally.
    The mucous membranes of the oropharynx are dry,
    and a small corneal ulceration is present on the right.
    Given her most likely diagnosis, which of the following
    complications is she most at risk for?
    A. MALToma
    B. Thymoma
    C. Follicular lymphoma
    D. Mantle cell lymphoma
    E. Hodgkin’s lymphoma

Answer 30

30. Correct: MALToma (A)
    This patient presents with physical examination
    findings consistent with Sjögren’s syndrome.
    Patients with Sjögren’s syndrome are at risk for
    development of lymphoma, which occurs in up to
    10% of patient. The majority of Sjögren-associated
    lymphomas are non-Hodgkin’s lymphomas, with
    MALToma being the most common (A). For (B-E), see
    previous information.

Question 31

31. A 38-year-old female presents to the emergency
    room. She has recently been feeling weak
    and fatigued, unable to work out at the gym as she
    normally has in the past. Her trip to the emergency
    room is because she developed double vision today.
    Physical examination reveals ptosis. A CT scan of
    her body reveals a mass in the upper portion of the
    mediastinum. Of the following, what is the most
    likely diagnosis?
    A. Multiple sclerosis
    B. Amyotrophic lateral sclerosis
    C. Early onset Parkinson’s disease
    D. Myasthenia gravis
    E. Systemic lupus erythematosus

Answer 31

31. Correct: Myasthenia gravis (D)
    Myasthenia gravis is due to autoantibodies that block
    the postsynaptic acetylcholine receptors, causing
    muscle weakness. Ptosis and diplopia are common
    symptoms and occur due to weakness of extraocular
    muscles (D). The degree of weakness fluctuates,
    and can become severe very quickly. About one-fifth
    of patients with myasthenia gravis have a thymoma,
    which is the mediastinal mass identified on the
    CT scan. About 50% of thymomas occur in patients
    with myasthenia gravis. Thymectomy is beneficial to
    these patients. Although the other conditions could
    be considered in the differential diagnosis, none are
    associated with a mediastinal mass (A-C, E)

Question 32

32. A 38-year-old female presents to the emergency
    room. She has recently been feeling weak
    and fatigued, unable to work out at the gym as she
    normally has in the past. Her trip to the emergency
    room is because she developed double vision today.
    Physical examination reveals ptosis. A CT scan of
    her body reveals a mass in the upper portion of the
    mediastinum. Given the previous clinical scenario, of the following,
    what is the most likely mechanism for her
    symptoms?
    A. Antibodies against the acetylcholine receptor
    B. Immune-mediated destruction of
    oligodendroglial cells
    C. Elevated T3 hormone concentrations
    D. Ischemic injury of the precentral gyrus
    bilaterally
    E. A mass at the optic chiasma

Answer 32

32. Correct: Antibodies against the acetylcholine
    receptor (A)
    See the explanation for question #18. The mechanism
    by which myasthenia gravis causes disease is blockage of postsynaptic acetylcholine receptors. The other choices (B-E) do not apply.

Question 33

33. A 73-year-old man with stable hypertension
    presents to his primary care physician complaining
    of bruising around the eyes, which occurred
    after blowing up balloons for his granddaughter’s
    birthday party. He reports no pain and has no other
    complaints. On examination there are bilateral periorbital
    purpurae but no other facial trauma. Scalloping
    of the borders of the tongue caused by the
    patient’s teeth is noted. The lungs are clear, and heart
    sounds are normal; however, the point of maximal
    impulse is laterally displaced. Moderate hepatomegaly
    is noted. What is the most likely diagnosis?
    A. T-cell lymphoma
    B. Thrombotic thrombocytopenic purpura
    C. Leukoclastic vasculitis
    D. AL amyloidosis
    E. Idiopathic thrombocytopenic purpura

Answer 33

33. Correct: AL amyloidosis (D)
    The patient has two characteristic signs of AL amyloidosis:
    scalloping of the tongue by the teeth due to enlargement of the tongue (macroglossia) and periorbital purpura from trivial injury or Valsalva maneuver (raccoon sign). The displacement of the point of maximal impulse, consistent with cardiac hypertrophy, and the hepatomegaly are also frequently seen in AL amyloidosis (D). There is no history of laboratory findings to suggest any of the other diagnoses (A-C, E).

Question 34

34. An 18-month-old boy is hospitalized with
    lobar pneumonia. He has had three ear infections in
    the past four months. At ages 12 and 14 months he
    was treated for Staphylococcus aureus cellulitis and
    abscess. He is fair-skinned with silvery-white hair
    and blue eyes. Angular cheilosis and oral ulcers are
    present on examination. A complete blood count is
    remarkable for a leukocyte count of 3.7 × 109/L and
    a hemoglobin of 8.9 mg/dL. His bleeding time is prolonged.
    Bone marrow biopsy shows giant azurophilic
    granules in the myeloid cells. What is the underlying
    defect?
    A. Fusosyl transferase deficiency
    B. Phagocyte NADPH oxidase deficiency
    C. Myeloperoxidase deficiency
    D. Impaired phagosome-lysosome fusion
    E. Mutation in the γ-chain subunit of cytokine
    receptors

Answer 34

34. Correct: Impaired phagosome-lysosome
    fusion (D)
    This patient suffers from Chediak-Higashi syndrome.
    The hallmark of Chediak-Higashi syndrome is impaired phagosome-lysosome fusion, which produces
    characteristic giant azurophilic granules in neutrophils, eosinophils, and other granulocytes (D). The underlying cause is mutations in LYST, a lysosomal membrane trafficking protein. Fucosyl transferase deficiency causes absence of Sialyl-Lewis X and impaired leukocyte adhesion and rolling (leukocyte adhesion deficiency 2) (A). The patient’s physical appearance and the presence of giant granules are inconsistent with either chronic granulomatous disease (caused by phagocyte oxidase deficiency) or myeloperoxidase deficiency (B, C). Mutation in the γ-chain subunit of cytokine receptors is the underlying defect in X-linked SCID (E).

Question 35

35. A 16-month-old male is admitted with fever
    and difficulty breathing. He has a history of recurrent
    Staphylococcus aureus skin abscesses and is
    being treated for pulmonary Aspergillosis. On arrival
    his temperature is 100.8°F (38.2°C), pulse 118/min,
    and blood pressure 90/55 mmHg. His weight is
    below the 10th percentile for age. On examination
    he has ronchi in both lung fields. There are multiple
    skin lesions of the face and neck. A plain chest radiograph
    reveals a small pulmonary abscess in the right
    middle lobe and left lower lobe pneumonia as well as
    hilar adenopathy. His leukocyte count is 14.2 x 109/L.
    Culture of the tracheal aspirate grows out Burkholderia
    cepacia. Biopsy of one of the skin lesions shows
    aggregates of epithelioid macrophages surrounded
    by lymphocytes. What additional test results would
    be expected in this patient?
    A. Low gammaglobulin levels
    B. Abnormal sweat chloride test
    C. Very low IgA levels
    D. Abnormal nitroblue tetrazolium test
    E. Positive antinuclear antibodies (ANA)

Answer 35

35. Correct: Abnormal nitroblue tetrazolium
    test (D)
    This patient suffers from chronic granulomatous
    disease. The nitroblue tetrazolium test will show
    absence of superoxide activity (D). Cystic fibrosis is
    high on the differential diagnosis, but this patient
    has recurrent extrapulmonary infections and cutaneous
    granulomatous disease, neither of which
    would be expected in cystic fibrosis. His sweat chloride
    test therefore would be normal (B). The primary
    defect in chronic granulomatous disease is with the
    phagocyte; thus immunoglobulin levels are normal
    or increased (due to persistent and recurrent infection)
    (A, C). (E) is incorrect, as this patient has signs
    and symptoms of immunodeficiency rather that
    autoimmunity.

Question 36

36. A 16-month-old male is admitted with fever
    and difficulty breathing. He has a history of recurrent
    Staphylococcus aureus skin abscesses and is
    being treated for pulmonary Aspergillosis. On arrival
    his temperature is 100.8°F (38.2°C), pulse 118/min,
    and blood pressure 90/55 mmHg. His weight is
    below the 10th percentile for age. On examination
    he has ronchi in both lung fields. There are multiple
    skin lesions of the face and neck. A plain chest radiograph
    reveals a small pulmonary abscess in the right
    middle lobe and left lower lobe pneumonia as well as
    hilar adenopathy. His leukocyte count is 14.2 x 109/L.
    Culture of the tracheal aspirate grows out Burkholderia
    cepacia. Biopsy of one of the skin lesions shows
    aggregates of epithelioid macrophages surrounded
    by lymphocytes. Given the previous clinical scenario, what is
    the primary defect causing the recurrent infections?
    A. Fusosyl transferase deficiency
    B. Phagocyte NADPH oxidase deficiency
    C. Myeloperoxidase deficiency
    D. Impaired phagosome-lysosome fusion
    E. Mutation in the γ-chain subunit of cytokine
    receptors

Answer 36

36. Correct: Phagocyte NADPH oxidase
    deficiency (B)
    The primary defect in chronic granulomatous disease
    is deficiency of phagocyte NADPH oxidase, which
    can be inherited in either an autosomal recessive or
    an X-linked pattern (B). The resultant impairment
    in superoxide production renders the phagocyte
    impaired in microbial killing. The clinical picture is
    that of a much more severe illness than is usually
    seen with myeloperoxidase deficiency (C), which is
    asymptomatic in 95% of patients and when symptomatic
    generally causes recurrent Candida infections.
    For (A, D-E), see previous information.

Question 37

37. A 12-year-old girl presents with swelling of
    the face and lips. The symptoms started gradually 4
    hours ago and were preceded by fatigue, nausea, and
    flu-like symptoms. She has had 3 prior episodes with
    similar symptoms. Her vital signs are normal. On
    examination she has diffuse edema of the face and
    lips. Lungs are clear, without stridor or wheezing,
    and examination of the skin is normal. Her C1-INH
    activity is undetectable. Which of the following
    additional historical or examination findings would
    be consistent with her illness?
    A. Recurrent urticaria
    B. Recurrent abdominal pain
    C. Elevated serum tryptase
    D. Wheezing
    E. Resolution of symptoms with epinephrine and
    glucocorticoids

Answer 37

37. Correct: Recurrent abdominal pain (B)
    In addition to angioedema, recurrent, often severe
    abdominal pain and skin edema are common
    manifestations of hereditary angioedema (HA) (B).
    Wheezing, stridor, urticaria, and elevated serum
    tryptase levels are manifestations of anaphylaxis
    (Type I hypersensitivity reaction) and are not seen in
    attacks of hereditary angioedema (A, C-D). Likewise,
    anaphylaxis is usually responsive to epinephrine and
    glucocorticoids, whereas these agents have no effect
    on attacks of HA (E).

Question 38

38. A 21-year-old male presents to the college
    health clinic complaining of malaise, fatigue, and
    sore throat. He denies cough or shortness of breath.
    The symptoms started abruptly 2 weeks ago and are
    accompanied by low-grade fever, arthralgia, diarrhea,
    and a 10 lb. weight loss. His vaccinations are up
    to date. Temperature is 100.3°F (37.9°C), heart rate
    is 98/min, and blood pressure is 123/89 mm Hg. On
    examination there is cervical and axillary lymphadenopathy,
    pharyngeal erythema without exudates or
    tonsillar enlargement, and a diffuse maculopapular
    rash on the face, thorax, and extremities. His heart
    and lung sounds are normal. A rapid strep test,
    monospot test, CMV and Lyme titers, and antinuclear
    antibodies are negative. What test should be ordered
    next?
    A. Anti CCP-IgG
    B. Anti-Smith
    C. Anti-dsDNA
    D. Peripheral blood smear
    E. HIV antibodies and viral load

Answer 38

38. Correct: HIV antibodies and viral load (E)
    This patient is suffering from acute retroviral syndrome.
    The main differential diagnosis is pharyngitis
    from Group A Streptococcus and infectious mononucleosis (D), which have been excluded. With a negative ANA, acute HIV infection (E) should be excluded
    prior to further workup for autoimmune disease
    (A-C). A Lyme titer (not given as an option in this
    question) would also be appropriate.

Question 39

39. A 55-year-old man with long-standing HIV
    disease, recently nonadherent to his antiretroviral
    therapy, presents complaining of persistent cough. He
    denies any recent travel or hospitalization. His temperature
    is 100.4°F (38.0°C), pulse is 106/min, blood
    pressure is 120/76 mm Hg, and room air oxygen saturation
    is 93%. On examination he has crackles over the
    right lower lung field, and a plain chest radiograph
    shows consolidation of the right lower lobe. Of the following,
    what is the most likely causative agent?
    A. Pneumocystis jirovecii
    B. Histoplasma capsulatum
    C. Streptococcus pneumoniae
    D. Cryptococcus neoformans
    E. Mycobacterium tuberculosis

Answer 39

39. Correct: Streptococcus pneumoniae (C)
    This patient has community-acquired lobar pneumonia
    (C). Despite the emphasis placed on the many
    opportunistic pathogens that HIV-positive patients
    are at risk for, the most common causes of community-
    acquired pneumonia are the same pathogens
    prevalent in the general population (C). For (A-B,
    D-E), previous information.

Question 40

40. A 38-year-old homeless HIV-positive man presents
    with cough and shortness of breath. His temperature
    is 101.0°F (38.3°C), pulse is 110/min, blood pressure
    is 106/60 mm Hg, and room air oxygen saturation is 88%.
    On examination he is cachectic. He has white pharyngeal
    exudates. He is tachycardic without murmur. There
    are fine crackles in both lung fields. His breathing is
    labored. A plain chest radiograph shows diffuse bilateral
    interstitial infiltrates. Lactate dehydrogenase level is 530
    IU, and the CD 4 count is 173 cells/μL. Of the following,
    what is the most likely causative agent?
    A. Pneumocystis jirovecii
    B. Histoplasma capsulatum
    C. Streptococcus pneumoniae
    D. Cryptococcus neoformans
    E. Mycobacterium avium complex

Answer 40

40. Correct: Pneumocystis jirovecii (A)
    The presence of fever, hypoxia, and bilateral diffuse
    infiltrates with elevated serum LDH is consistent
    with pneumonia due to Pneumocystis jirovecii (A).
    Pneumococcal pneumonia would not be expected
    to produce bilateral interstitial infiltrates (C).
    All of the other agents listed should be in the
    differential; however, infection with Histoplasma
    and Cryptococcus are less common in patients with
    CD4 count > 100 cells/μL (B, D), and Mycobacterium
    avium complex infections are unusual in patients
    with CD 4 count > 50 cells/μL (E).

Question 41

41. A 45-year-old man with known HIV and no
    prior HAART treatment presents with a rash. His
    temperature is 99.8°F (37.6°C), pulse is 89/min, and
    blood pressure is 132/88 mm Hg. Examination of
    his oropharynx reveals white exudates on the palate
    and several purple nodular lesions of the gingival
    mucosa. His lungs are clear, and no murmurs
    are present. He has several nontender, nonulcerated
    raised purple lesions on both arms and the anterior
    chest wall. Biopsy of one of the skin lesions shows
    whorls of spindle-shaped cells with leukocytic infiltrate
    and neovascularization. Which of the following
    is true regarding this skin disease?
    A. It is rapidly progressive and fatal if untreated.
    B. It is caused by a fastidious gram-negative bacillus.
    C. It is uncommon in heterosexual men with HIV.
    D. Antibiotic prophylaxis can prevent this disease.
    E. Extracutaneous manifestations of this illness are
    rare.

Answer 41

41. Correct: It is uncommon in heterosexual
    men with HIV (C)
    This patient’s clinical presentation and biopsy findings
    are consistent with Kaposi sarcoma. Infection
    with human herpes virus-8 (HHV-8), a sexually
    transmitted infection, is required to develop this disease.
    HHV-8 seropositivity is much more common in
    men who have sex with men than in women or heterosexual men (C). The primary differential diagnosis
    of Kaposi sarcoma (KS) is bacillary angiomatosis,
    caused by Bartonella; however, there is no mention
    of bacterial organisms on the biopsy (B). Antibiotic
    prophylaxis cannot prevent development of KS, and
    extraintestinal manifestations are common (D, E).
    Most cases of KS have an indolent course (A).

Question 42

42. A 6-year-old boy is brought to his pediatrician
    with a cough, which started 3 weeks earlier.
    He has a history of recurrent Staphylococcus aureus
    skin infections. His temperature is 101.4°F, pulse is
    110/min, blood pressure is 88/54 mm Hg, oxygen
    saturation is 89% on room air. On examination he has
    bilateral crackles. A plain chest radiograph shows
    bilateral reticulonodular infiltrates. Sputum silver
    stain reveals Pneumocystis jirovecii. He has a younger
    brother who was also diagnosed with Pneumocystis
    pneumonia. HIV testing is negative; however, serum
    levels of IgA, IgG, and IgE are low and serum IgM
    levels are elevated. His condition is a result of which
    underlying defect?
    A. Defective development of the third and fourth
    pharyngeal pouches
    B. Defective CD 40 ligand
    C. Mutation in the cytokine receptor common
    γ-chain
    D. Adenosine deaminase deficiency
    E. Mutation in Jak3

Answer 42

42. Correct: Defective CD 40 ligand (B)
    This patient suffers from hyper-IgM syndrome,
    which, given the presence of a similar illness in his
    brother, is likely the X-linked form, resulting from a
    defect in CD40 ligand (B). The autosomal recessive
    form is due to a defect in CD40 itself. Defective development of the third and fourth pharyngeal pouches
    causes DiGeorge’s syndrome (A). Adenosine deaminase
    deficiency and mutations in the cytokine receptor
    common γ-chain and Jak3 cause severe combined
    immunodeficiency (SCID) (C-E). A child with SCID
    would not be expected to survive to age 6 years
    without a stem cell transplant.

Question 43

43. A 7-month-old boy is brought to his pediatrician
    for a cough, which started 1 week ago. He has
    also been experiencing diarrhea for the past 3 weeks.
    His temperature is 99.2°F (37.3°C), pulse is 112/min,
    blood pressure is 88/48 mm Hg, and room air saturation
    is 88%. His weight is less than the 10th percentile
    for age. He is nondysmorphic. There are white
    plaques on the tongue and oropharynx. No murmur
    is heard. Bilateral crackles are present on auscultation.
    Complete blood count shows normal hemoglobin
    and platelet counts. Serum chemistry is normal.
    The leukocyte count is 5400 cells/μL, 88% granulocytes
    and 12% lymphocytes. A plain chest radiograph
    shows ground-glass infiltrates, and a bronchoalveolar
    lavage was positive for Pneumocystis jirovecii. The
    cytomegalovirus DNA PCR is positive, and HIV viral
    load is negative. Serum levels of IgG, IgM, IgA, and
    IgE are low, and flow cytometry reveals an extremely
    low T-cell count with a relatively normal B-cell count.
    Of the following, what is the most likely diagnosis?
    A. X-linked agammaglobulinemia
    B. Transient hypogammaglobulinemia of the
    newborn
    C. DiGeorge’s syndrome
    D. Common variable immunodeficiency
    E. Severe combined immunodeficiency

Answer 43

43. Correct: Severe combined
    immunodeficiency (E)
    This patient presents with combined defects of both
    humoral and cellular immunity, consistent with
    severe combined immunodeficiency (SCID) (E). The
    presence of relatively normal levels of B-lymphocytes
    makes X-linked agammaglobulinemia less likely (A).
    DiGeorge is important in the differential diagnosis
    of SCID; however, in the absence of cardiac defect
    or hypocalcemia there is no indication of DiGeorge’s
    syndrome (C). Neither transient hypogammaglobulinemia
    nor common variable immunodeficiency (CVID) would be expected to produce such severe disease in a 7-month-old, and CVID typically presents with recurrent infections later in childhood or in early adolescence (B, D).

Question 44

44. A 6-month-old boy is brought to his pediatrician
    for pneumonia. He was treated 2 weeks ago for
    severe otitis media. On examination, his tonsils and
    adenoids are absent. Heart sounds are normal, and
    there are crackles in the left lower lung field. Serum
    levels of IgG, IgA, and IgM are low, and B-lymphocytes
    are undetectable. What is the underlying defect
    responsible for this patient’s recurrent infections?
    A. Impaired B-cell maturation
    B. Impaired cytokine receptor signaling
    C. Failure of development of the third and fourth
    pharyngeal pouches
    D. Disruption of the CD40-CD40 ligand interaction
    E. Complement deficiency

Answer 44

44. Correct: Impaired B-cell maturation (A)
    This patient has X-linked agammaglobulinemia. The
    underlying defect is a mutation in a tyrosine kinase
    that blocks signal transduction by the pre-B cell
    receptor required for B-cell maturation (A). For (B-E),
    see previous information.

Question 45

45. A 33-year-old man is evaluated for recurrent
    sinusitis. He has had episodes of bacterial sinusitis
    occurring at least four times a year for the past 3
    years. Complete blood count is normal, as is a total
    hemolytic complement panel (CH50). Serum IgG,
    IgM, and IgE levels are normal; however, serum IgA
    levels are undetectable. Which of the following complications
    is this patient at least risk for?
    A. Transfusion reaction
    B. Pneumonia
    C. Parasitic gastrointestinal infection
    D. Crohn’s disease
    E. Lymphoid malignancy

Answer 45

45. Correct: Lymphoid malignancy (E)
    This patient has selective IgA deficiency, which when
    symptomatic, causes recurrent sinopulmonary infection.
    This condition is associated with increased risk
    for transfusion reactions, pneumonia, Giardia lamblia
    intestinal infections, and, rarely, with Crohn’s disease (A-D). Unlike common variable immunodeficiency, selective IgA deficiency has not been associated with an increased risk of malignancy (E).

Question 46

46. A 32-year-old HIV-positive man presents with
    fever, headache, and neck stiffness. His temperature
    is 101.1°F (38.4°C), pulse is 102/min, and blood pressure
    is 102/58 mm Hg. On examination he appears
    malnourished. There is oral candidiasis on exam. His
    heart and lungs are normal to auscultation. Multiple
    umbilicated papular lesions are noted on the skin.
    Neurologic examination reveals lethargy and meningismus,
    but no focal deficits. A CT of the head is preformed
    and is unremarkable. The opening pressure
    on lumbar puncture is slightly elevated at 28 cm H2O
    and fluid analysis reveals a CSF leukocyte count of 38
    cells/μL with a mononuclear predominance, as well
    as elevated protein and low CSF glucose. What is the
    most likely causative organism of this man’s illness?
    A. Toxoplasma gondii
    B. Mycobacterium tuberculosis
    C. Streptococcus pneumoniae
    D. Cryptococcus neoformans
    E. Molluscum contagiosum

Answer 46

46. Correct: Cryptococcus neoformans (D)
    Cryptococcus is the most common cause of central
    nervous system (CNS) infection in patients with
    AIDS. In this case, the presence of umbilical papules
    (molluscum-like rash) is classic for disseminated cryptococcal infection (D). The normal brain imaging,
    the absence of radiologic signs, and the presence
    of meningeal signs make Toxoplasma less likely (A).
    The historical and clinical findings in tuberculous
    meningitis are frequently very similar; however, the
    molluscum-like rash is a clue to making the right
    diagnosis (B). Streptococcus is excluded based on the
    CNS fluid analysis (C), and Molluscum does not infect
    the CNS (E).

Question 47

47. A 57-year-old female immigrant with HIV/
    AIDS and CD4 count of 53 cells/μL presents with a
    headache, fever, and confusion. A CT of the head performed
    on arrival shows multiple enhancing lesions
    of the frontal and parietal lobe. Which of the following
    prophylactic treatments could have prevented
    this complication?
    A. Trimethoprim-sulfamethoxazole
    B. Itraconazole
    C. Fluconazole
    D. Azithromycin
    E. Acyclovir

Answer 47

47. Correct: Trimethoprim-Sulfamethoxazole (A)
    This patient has central nervous system toxoplasmosis
    with characteristic signs, symptoms, and imaging
    findings. In addition to preventing Pneumocystis
    infection, trimethoprim-sulfamethoxazole is indicated
    for the prevention of toxoplasmosis in AIDS (A).
    For (B-E), see previous information.

Question 48

48. An 8-month-old male is brought to his pediatrician
    for cough and fever. Past medical history is
    significant for 3 episodes of otitis media since age 6
    months. His brother died at age 11 months of pneumonia.
    His temperature is 102.4°F (39.1°C), pulse is
    120/min, and blood pressure is 88/48 mm Hg. The
    auscultation of the heart is normal. There are crackles
    in both lung fields. He has a petechial rash on both
    lower extremities and a scaly erythematous dermatitis
    of the extensor surfaces of the arms and legs. His
    platelet count is 19,000/μL. His serum IgG and IgA
    levels are normal; however, his IgM levels are very
    low. What is the underlying cause of this patient’s
    illness?
    A. Shiga toxin
    B. IgG anti-glycoprotein IIb/IIIa complex
    C. Abnormal linking of membrane receptors to
    cytoskeletal elements
    D. Deposition of misfolded fibrillar proteins
    E. Mutated cytokine receptor

Answer 48

48. Correct: Abnormal linking of membrane
    receptors to cytoskeletal elements (C)
    This patient has Wiskott-Aldrich syndrome, characterized
    by recurrent infections, eczema, and thrombocytopenia. Usually inherited in an X-linked recessive pattern, Wiskott-Aldrich syndrome is caused by mutations in Wiskott-Aldrich syndrome protein (WASP), thought to be involved in linking membrane receptors to cytoskeletal elements (C). For (A-B, D-E), see previous information.

Question 49

49. A 33-year-old man develops severe pharyngitis
    for which he seeks evaluation by his primary care provider. A rapid strep test is negative. He has marked splenomegaly on exam and is noted to be febrile. His monospot test is positive. He dies 3 days later. His brother died at age 18 of Epstein-Barr virus. What is the underlying defect causing this man’s disease?
    A. Mutation in the gene encoding WASP protein
    B. Defect in the receptor for the B-cell activating
    cytokine
    C. Loss of function mutation in CD40
    D. Mutation in the gene for SLAM-associated
    protein
    E. Adenosine deaminase deficiency

Answer 49

49. Correct: Mutation in the gene for SLAMassociated
    protein (D)
    The history of fatal Epstein-Barr virus (EBV) infections
    in male siblings is most consistent with X-linked lymphoproliferative disorder, caused in most cases by mutations in the gene coding for SLAM-associated protein (SAP) (D). Patients with this disorder have impaired NK cell function and are susceptible to fulminant infection with EBV. For (A-C, E), see previous information.