Review Test

1.A 3-year-old Caucasian girl is brought to your office with a 3-week history of bruising, left elbow pain, and fever. Her white blood cell (WBC) count is 25,000 cells/mm3. You refer her to a pediatric oncologist who performs a bone marrow aspirate, which confirms your suspicion that she has acute lymphocytic leukemia (ALL). Immunophenotyping reveals that the leukemic cells have pre–B-cell phenotype and are common acute lymphocytic leukemia antigen (CALLA) negative. In addition, the leukemic cells demonstrate hyperploidy (>53 chromosomes). Which of the following characteristics predict an unfavorable prognosis in this patient?

A.Leukemic cells that are CALLA-negative

B.WBC count at diagnosis <50,000 cells/mm3

C.Female sex

D.Leukemic cells that demonstrate hyperploidy

E.Age of 3 years

2.A 10-year-old girl has started induction chemotherapy for acute lymphocytic leukemia (ALL). Which of the following statements regarding the treatment of childhood ALL and its complications is correct?

A.Remission is induced in 25% of patients.

B.Fever associated with neutropenia is an anticipated complication of treatment and may be managed with acetaminophen alone.

C.Intrathecal methotrexate is used only for children with an unfavorable prognosis at the time of diagnosis.

D.Intracranial radiation is generally safe and free from side effects in children older than 1 year.

E.Tumor lysis syndrome may include hyperkalemia, hyperphosphatemia, and hyperuricemia.

3.A 4-year-old boy has fever of unknown origin, enlargement of the spleen and liver, and gingival hypertrophy. A complete blood count shows leukemic myeloblasts. Which of the following statements regarding this patient’s diagnosis is correct?

A.Further examination would likely reveal generalized lymphadenopathy and testicular swelling.

B.A blood smear may demonstrate Auer rods within his leukemic blasts.

C.Evaluation of the chromosomes would reveal the Philadelphia chromosome.

D.Bone marrow transplant is usually not necessary for treatment, given the high cure rate with standard chemotherapy.

E.If this boy had Down syndrome, his leukemia would be very difficult to treat and would likely be fatal.

4.A 15-year-old boy has a 3-month history of fever and weight loss. Physical examination reveals posterior cervical and supraclavicular lymphadenopathy. You refer the patient to a pediatric general surgeon, who performs a lymph node biopsy. The diagnosis is Hodgkin disease. Which of the following statements regarding this diagnosis is correct?

A.The cancer would be classified as stage IA.

B.Airway obstruction is a common complication of this type of cancer.

C.Associated infertility is rare.

D.Prognosis is poor.

E.The biopsy likely shows Reed–Sternberg cells.

5.A 6-year-old girl has a 1-month history of vomiting in the early morning on awakening, occipital headache, and an unsteady gait. Physical examination is normal with the exception of

547

a noticeable wide-based gait with ataxia. Although you were unable to view her optic discs to determine whether papilledema is present, you suspect that she may have a brain tumor. Which of the following statements regarding her probable diagnosis and her evaluation is correct?

A.She most likely has a high-grade astrocytoma.

B.She likely has a medulloblastoma in the infratentorial region.

C.A head computed tomography (CT) is the best imaging modality for diagnosis.

D.Combination chemotherapy and radiation therapy are the principal treatments for suspected brain tumor.

E.The cerebrospinal fluid tumor markers homovanillic acid and vanillylmandelic acid will be absent on evaluation.

6.A 15-year-old boy has a routine health maintenance examination. A firm, painless right testicular mass is found. Which of the following statements regarding a testicular tumor in this boy is correct?

A.The tumor is most likely benign.

B.Teratoma is the most common type of testicular tumor.

C.Metastasis most commonly occurs to bone.

D.A history of unilateral cryptorchid testes has put this patient at higher than usual risk for a testicular tumor.

E.Chemotherapy and radiation therapy are the most appropriate initial treatments.

7.A 7-year-old boy with a history of biliary atresia managed with a Kasai portojejunostomy performed at 5 weeks of age now presents with a 10-pound weight loss during a 4-month period. His parents state that his appetite has been very poor. Physical examination shows a mass in the right upper quadrant of the abdomen. You suspect hepatocellular carcinoma given his prior history of biliary atresia. Which of the following statements regarding this type of cancer in childhood is correct?

A.The malignancy is also associated with chronic active hepatitis B infection.

B.Careful examination of the conjunctiva would likely reveal evidence of jaundice.

C.A liver transplant is recommended because of the poor prognosis associated with this malignancy.

D.Urine catecholamines are elevated.

E.Human chorionic gonadotropin is elevated and diagnostic.

The response items for statements 8–11 are the same. You will be required to select one answer for each statement in the following set.

A.Acute myelogenous leukemia

B.Retinoblastoma

C.Burkitt lymphoma

D.Wilms tumor

E.Neuroblastoma

F.Brain tumor

G.Acoustic neuroma

For each patient with a genetic syndrome or infection, select the associated malignancy.

1.A 7-year-old African boy with a history of Epstein–Barr virus infection.

2.A 2-year-old girl with Down syndrome.

3.A 6-year-old boy with Beckwith–Wiedemann syndrome.

4.A 10-year-old boy with neurofibromatosis type 2.

548

The response items for statements 12–16 are the same. You will be required to select one answer for each statement in the following set.

A.Osteogenic sarcoma

B.Ewing sarcoma

C.Rhabdomyosarcoma

D.Langerhans cell histiocytosis

E.Yolk sac tumor

F.Teratoma

G.Non-Hodgkin lymphoma

For each patient, select the most likely diagnosis.

1.A 4-year-old boy with a painless, growing, soft tissue mass within the orbit, with accompanying proptosis and eyelid swelling.

2.A 14-year-old boy with a painful, growing, soft tissue mass at the distal femur. Radiography reveals periosteal elevation with a “sunburst” appearance.

3.A 5-month-old girl with a soft tissue mass in the lower portion of the back near the coccyx.

4.A 5-year-old boy with a painful, growing mass behind the right ear with chronic right ear discharge.

5.A 16-year-old girl with a painful, growing, soft tissue mass involving the right pelvis. Radiography reveals periosteal elevation with an “onionskin” appearance.

549

Answers and Explanations

1.The answer is A [Table 14-2]. Factors at the time of diagnosis that predict a favorable prognosis include female sex, age between 1 and 9 years, Caucasian race, white blood cell (WBC) count <50,000 cells/mm3, hyperploidy of leukemic cells, absence of chromosomal translocation, and lack of involvement of the central nervous system, liver, spleen, and other organs. However, a common acute lymphocytic leukemia antigen (CALLA) negative immunophenotype is an unfavorable prognostic indicator, whereas CALLA-positive is a favorable prognostic indicator.

2.The answer is E [II.A.6.f]. Many complications may result from therapy for leukemia. Tumor lysis syndrome occurs when cells break apart spontaneously or after chemotherapy and release uric acid, potassium, and phosphate into the circulation. Therefore, hyperuricemia, hyperkalemia, and hyperphosphatemia may be seen. Induction chemotherapy induces remission in approximately 95% of patients. Fever associated with neutropenia is a feared complication that mandates immediate therapy with intravenous antibiotics because of the higher than usual risk of serious bacterial infection in immunosuppressed patients. Intrathecal methotrexate is administered to all patients, regardless of prognosis, during induction as prophylaxis against central nervous system involvement, and to all patients during the consolidation phase of chemotherapy. Intracranial radiation is associated with many longterm complications and should generally be avoided, if possible, in children younger than

5 years.

3.The answer is B [II.B.5–7]. This patient’s clinical presentation and the finding of leukemic myeloblasts are consistent with the diagnosis of acute myelogenous leukemia (AML). Auer rods found within the leukemic blast cells are consistent with the diagnosis of AML. AML is generally more difficult to treat than acute lymphocytic leukemia (ALL), and remission occurs with aggressive chemotherapy in only approximately 50% of patients. Bone marrow transplant is one of the mainstays of therapy in AML. Patients with AML may present with fever, hepatosplenomegaly, bruising, bone pain, and gingival hypertrophy, but testicular involvement and lymphadenopathy are not common clinical features. The Philadelphia chromosome is found in adult-type chronic myelogenous leukemia, rather than in AML. AML associated with Down syndrome is highly treatable.

4.The answer is E [III.A.2–4 and Table 14-3]. Patients with Hodgkin disease most commonly present with painless lymphadenopathy, generally in the cervical or supraclavicular regions. Systemic features, such as weight loss, night sweats, and fever, may also be present. Diagnosis is proven on the basis of the finding of Reed–Sternberg cells on lymph node biopsy. From the involvement of two lymph node regions on the same side of the diaphragm and systemic features in this patient, his cancer would be classified as stage IIB, rather than stage IA (in which only one lymph node region is involved and there would be no systemic manifestations such as fever and weight loss). Airway obstruction caused by involvement of anterior mediastinal nodes is more common in non-Hodgkin lymphoma. Impaired fertility is common in Hodgkin disease. Prognosis for stage II disease is excellent.

5.The answer is B [IV.B–D]. The clinical presentation is consistent with a brain tumor. Between 1 and 12 years of age, infratentorial brain tumors are most common. In addition, the ataxia suggests an infratentorial tumor. Medulloblastoma, a primitive neuroectodermal tumor, is the most common infratentorial tumor and would therefore be the most likely tumor in this patient. Astrocytoma is the second most common infratentorial tumor, and brainstem glioma is the third most common infratentorial tumor. Although astrocytomas are possible tumors in the infratentorial region, they tend to be low-grade, rather than high-grade, tumors. Magnetic resonance imaging is the preferred diagnostic imaging study because of the likely cerebellar

550

location of the medulloblastoma. The principal treatment is surgical resection, if it is possible. The tumor markers, homovanillic acid and vanillylmandelic acid, which are secreted by medulloblastomas, are detectable in the cerebrospinal fluid.

6.The answer is D [X.B.2]. Cryptorchid testes (testes that fail to descend into the scrotum) are at much higher than usual risk for malignancy. Two-thirds of testicular tumors in childhood are malignant and one-third are benign. Teratomas account for approximately 15% of testicular tumors. In contrast, yolk sac tumors account for 60% of testicular tumors and are the most common testicular tumor. Management of testicular tumors is based on the tumor type, size, and presence of metastases that may involve the retroperitoneal lymph nodes, liver, or lung. Metastasis to bone is more unusual. Treatment of yolk sac tumors involves radical orchiectomy and retroperitoneal lymph node dissection, if necessary.

7.The answer is A [VIII.A.2]. Hepatocellular carcinoma is associated with chronic active hepatitis B infection, biliary atresia, α1-antitrypsin deficiency, and glycogen storage disease type I. Typical presentation includes a right upper quadrant abdominal mass, weight loss, and anorexia; however, jaundice is generally absent. Liver transplant is not curative because of the high rate of metastatic disease. Diagnosis is based on findings on abdominal imaging and elevation of the serum marker α-fetoprotein. Urine catecholamines are not present, and human chorionic gonadotropin is not elevated.

8.The answers are C, A, D, and G, respectively [Table 14-1, II.B.2, I.B.2.b, and I.B.3]. Genetic syndromes and infections may predispose to childhood cancers. Epstein–Barr virus infection may predispose to both Hodgkin disease and non-Hodgkin lymphoma, including Burkitt lymphoma, which is endemic in Africa. Down syndrome may predispose to both acute myelogenous leukemia and acute lymphocytic leukemia. Beckwith–Wiedemann syndrome may predispose to Wilms tumor, rhabdomyosarcoma, and hepatoblastoma. Neurofibromatosis type 2 may predispose to acoustic neuroma, whereas neurofibromatosis type 1 may predispose to brain tumors and lymphoma.

9.The answers are C, A, F, D, and B, respectively [VI.C.1.a, Table 14-4, XI.C.1.d, and X.B.1.a]. Rhabdomyosarcoma is the most common soft tissue sarcoma and typically presents as a painless soft tissue mass. The head and neck are involved 40% of the time, and if the orbit is involved, the patient may present with proptosis, eyelid swelling, or cranial nerve palsies. Both osteogenic sarcoma and Ewing sarcoma present as painful soft tissue masses. Osteogenic sarcoma generally involves the metaphysis of tubular long bones, especially the distal femur and proximal tibia. Ewing sarcoma more commonly involves flat bones and the diaphysis of tubular bones. The axial skeleton, including the pelvis, is most commonly involved. Radiographic appearances of both osteogenic sarcoma and Ewing sarcoma reveal periosteal elevation; however, osteogenic sarcoma has a more typical “sunburst” appearance (question 13), whereas Ewing sarcoma has a more typical “onionskin” appearance (question 16). Langerhans cell histiocytosis often presents as bony lesions. If the mastoid bone is involved, a child may present with a mass behind the ear and chronic ear drainage. Sacrococcygeal teratoma, the most common teratoma in infancy, occurs as a soft tissue mass in the area of the coccyx. The majority (75%) of these teratomas occur in females.

551

C H A P T E R 1 5

552

Allergy and Immunology

Rajashri Shuba, Iyengar

553

I.Anaphylaxis

A.Definition. Anaphylaxis is a potentially life-threatening, acute systemic IgE-mediated reaction (type 1 hypersensitivity). Antigen binding to IgE on the surface of primed mast cells and basophils results in the release of potent mediators that affect vascular tone and bronchial reactivity.

B.Etiology. Anaphylaxis is a systemic reaction that occurs most commonly to drugs, insect venom, foods, latex, and biologic agents.

C.Clinical features. Anaphylaxis involves two or more organ systems, and some cutaneous and mucosal involvement is present 90% of the time.

1.Pruritus, flushing, urticaria, and angioedema

2.Dyspnea and wheezing

3.Nausea, vomiting, diarrhea, and crampy abdominal pain

4.Cardiovascular symptoms, ranging from mild hypotension to shock

D.Diagnosis is on the basis of the presence of clinical signs and symptoms, which occur within 30–90 minutes after exposure to the offending agent.

E.Management

1.Epinephrine is the principal treatment for acute respiratory and cardiovascular complications.

2.Systemic antihistamines, corticosteroids, and β-adrenergic agonists are also used to treat the signs and symptoms of anaphylaxis.

554

II.Allergic Rhinitis

A.Definition. Allergic rhinitis is an IgE-mediated inflammatory response in the nasal mucosa to inhaled antigens.

B.Epidemiology. Allergic rhinitis affects 10–20% of children. It is one of the most common allergic conditions of childhood (Figure 15-1).

C.Etiology. Allergic rhinitis may be seasonal or perennial.

1.Seasonal rhinitis occurs in specific seasons in response to tree, grass, or weed pollens

(e.g., tree pollen in the spring, grass pollen in the summer, ragweed pollen in the fall).

2.Perennial rhinitis occurs across seasons in response to indoor allergens, most commonly dust mites, molds and animal dander. Molds and dust mites are associated with high-

humidity indoor environments.

D.Pathophysiology

1.Sensitization to airborne allergens induces IgE formation.

2.Allergen-specific IgE binds to receptors on mast cells and basophils in the nasal mucosa.

3.Subsequent exposure (known as “priming”) produces an IgE-mediated inflammatory response, which occurs within minutes. Primed mast cells degranulate and release histamine, leukotrienes, kinins, and prostaglandins.

E.Clinical features

1.Signs and symptoms include sneezing, nasal congestion, rhinorrhea, nasal itching, and pale nasal mucosa.

a.Allergic shiners are dark circles under the eyes caused by venous congestion.

b.Dennie lines are creases under the eyes as a result of chronic edema.

c.Allergic salute occurs when the patient uses the palm of the hand to elevate the tip of the nose to relieve itching. This can lead to a transverse crease or line noted between the upper two-thirds and lower one-third of the nasal bridge.

2.Allergic rhinitis is commonly associated with asthma, chronic sinusitis, otitis media with effusion, and nasal polyps.

F.Diagnosis. The diagnosis of allergic rhinitis is on the basis of clinical signs and symptoms.

1.Medical history may include multiple episodes of otitis media, sinusitis, atopic dermatitis (eczema), and food or drug allergies.

2.Laboratory evaluation

a.Total IgE concentration may be elevated.

b.Allergen skin testing (prick or intradermal testing)

1.Skin tests using purified allergens are the preferred method to diagnose and identify causes of allergic rhinitis. Radioallergosorbent (RAST) tests can identify serum IgE antibodies to specific allergens but are not as sensitive as skin testing.

2.To avoid false-negative results, patients must discontinue antihistamines 4– 7 days before skin testing.

c.Nasal smear for cytology may be helpful in differentiating allergic rhinitis from other disorders.

1.More than 10% eosinophils suggests allergic rhinitis.

2.A preponderance of polymorphic leukocytes suggests an infectious cause.

G.Management

1.Allergen avoidance is the first step in the management of allergic rhinitis.

a.Avoidance measures

1.The child’s bedroom should be free of allergens to the extent possible.

2.Remove pets or keep them outdoors.

555

3.Dust mite control measures include the use of zippered allergen-proof mattress and pillow covers and the removal of carpets and stuffed animals from the bedroom.

4.Reduce humidity to less than 50% to inhibit growth of dust mites and mold.

5.Avoid open windows during pollen season.

b.IgE antibody production may decrease with time in the absence of continual antigen exposure.

2.Pharmacotherapy

a.Intranasal steroids are the most effective class of drugs for controlling rhinitis symptoms. Side effects include local irritation, which may be minimized by careful technique of administration. Systemic absorption is minimal. The hypothalamic– pituitary–adrenal axis is not measurably affected at recommended doses.

b.Antihistamines

1.First-generation antihistamines (over-the-counter products [e.g., diphenhydramine]) are often first-line therapy; however, they may cause sedation and impair academic performance.

2.Second-generation antihistamines (e.g., cetirizine, fexofenadine, loratadine) are safer and better tolerated than first-generation agents but no more effective.

3.Intranasal antihistamines may be effective.

c.Intranasal cromolyn sodium prevents mast cell degranulation and can be helpful.

d.Decongestants (e.g., pseudoephedrine) cause vasoconstriction and relieve nasal congestion. Because side effects include insomnia, nervousness, and rebound rhinitis, decongestants should be used judiciously and only for short periods of time (<48–72 hours).

e.Leukotriene receptor antagonists are emerging as effective therapy.

3.Immunotherapy is effective for allergic rhinitis, allergic asthma, and insect venom allergy.

a.The principle of immunotherapy is that repeated injections of allergens at escalating doses with time lead to better tolerance of the allergen by the patient.

b.Indications

1.Other therapies are ineffective in controlling symptoms.

2.Environmental controls have been tried and failed, or exposure is unavoidable.

4.Patient education should include written instructions to enhance compliance.

556

FIGURE 15-1 Allergic conditions of childhood.

557

III.Atopic Dermatitis

A.Definition. Atopic dermatitis is a chronic inflammatory dermatitis (also known as eczema) characterized by dry skin and lichenification (i.e., thickening of the skin). The skin is overly sensitive to many stimuli that produce pruritus, which leads to scratching, which causes many of the skin manifestations.

B.Epidemiology

1.Atopic dermatitis affects 5–8% of children.

2.Atopic dermatitis typically begins in early infancy, and 85% of patients have signs and symptoms before 5 years of age.

3.Atopic dermatitis is often worse in winter (i.e., dry, cold weather) or with extremes of temperature.

4.Family history commonly reveals family members with atopic dermatitis, asthma, or other allergic diseases.

C.Clinical features

1.Pruritus is universal.

2.Skin manifestations may be acute or chronic (Table 15-1).

a.Acute changes include erythema, weeping and crusting, and secondary bacterial (Staphylococcus aureus) or viral (herpes simplex virus) infection.

b.Chronic changes include lichenification, dry scaly skin, and pigmentary changes

(most commonly, hyperpigmentation; less commonly, hypopigmentation).

3.Clinical presentation varies with age.

a.Infantile form. Truncal and facial areas, along with the scalp, are involved.

Extensor surfaces are more involved than flexural surfaces.

b.Early childhood. Flexural surfaces are more severely involved, and lichenification, the hallmark of chronic itching, is seen.

c.Late childhood. Disease may be more localized, or there may be a tendency toward remission.

D.Diagnosis

1.Three of four major criteria should be present:

a.Pruritus

b.Personal or family history of atopy

c.Typical morphology and distribution

d.Relapsing or chronic dermatitis

2.Minor criteria, such as xerosis (i.e., abnormal dryness), pruritus with sweating, wool intolerance, dermatographism (stroking of the skin with a dull instrument that produces a pale wheal with a red flare), or skin infections are also helpful in making the diagnosis.

E.Management

1.Known triggers, which may include wool, foods (especially eggs, milk, and peanuts), excessive heat or cold, and harsh chemicals or soaps, should be avoided.

2.Lowto medium-potency topical corticosteroids are indicated as needed on affected areas. Systemic corticosteroids are used in severe cases.

3.Antihistamines may be used at bedtime to decrease the itch–scratch cycle.

4.Baths should be in tepid water. After bathing, the patient should blot the skin dry with absorbent towels, and skin lubricants should be applied.

Table 15-1

Acute Versus Chronic Manifestations of Atopic Dermatitis

558

559