Case Files Pediatrics, (LANGE Case Files) 4th Ed.

CASE 57

A previously healthy 3-year-old boy presents with sudden onset of rash. His mother says he had been playing when she noticed small red spots and a large purple area on his skin. He has had no fever, upper respiratory tract infection (URI) symptoms, weight loss, bone pain, or diarrhea, and he is not taking medications. Three weeks previously, he had a mild illness that self-resolved after 48 hours. He is playful on examination, but he has multiple petechiae and purpuric lesions on his upper and lower extremities and on his trunk. He has neither adenopathy nor splenomegaly. His white blood cell (WBC) count is 8500/mm3, hemoglobin level is 14 mg/dL, and his platelet count is 20,000/mm3.

Image What is the most likely diagnosis?

Image What is the next step in management?

ANSWERS TO CASE 57: Immune Thrombocytopenic Purpura

Summary: A healthy 3-year-old develops thrombocytopenia, petechiae, and purpuric lesions. He is well-appearing but recently had a febrile illness. His WBC count and hemoglobin levels are normal.

• Most likely diagnosis: Immune thrombocytopenic purpura (ITP).

• Next step in management: Evaluation of his peripheral blood smear.

ANALYSIS

Objectives

1. Know the most common causes of childhood thrombocytopenia.

2. Understand the natural history of ITP.

Considerations

This 3-year-old has purpuric lesions and petechiae resulting from thrombocytopenia. He lacks the systemic signs of illness expected with disseminated intravascular coagulation or hemolytic-uremic syndrome (HUS). Because his hemoglobin level and WBC count are normal, bone marrow infiltration is less likely the cause of his thrombocytopenia. A peripheral blood smear is examined to identify immature WBCs and red cell morphology. Children with ITP have normal peripheral blood smears without evidence of leukemic or microangiopathic processes. This child has a platelet count of 20,000/mm3 and lacks evidence of active bleeding; the next step is close observation.

APPROACH TO:

Thrombocytopenia

DEFINITIONS

HEMOLYTIC-UREMIC SYNDROME (HUS): A syndrome of nephropathy, thrombocytopenia, and microangiopathic hemolytic anemia. It is associated with Escherichia coli 0157:H7, Shigella, and Salmonella. A prodrome of bloody diarrhea is common.

HENOCH-SCHÖNLEIN PURPURA (HSP): A syndrome of small-vessel vasculitis in young children. The syndrome may have dermatologic (petechial/purpuric rash), renal (nephritis), gastrointestinal (abdominal pain, gastrointestinal bleeding, intussception), and joint involvement (arthritis).

IMMUNE THROMBOCYTOPENIC PURPURA (ITP): A condition of increased platelet destruction by circulating antiplatelet antibodies, most frequently antiglycoprotein IIb/IIIa.

CLINICAL APPROACH

Acute ITP is the most common cause of thrombocytopenia in a well child usually aged 2 to 10 years. The evidence suggests an immunologic etiology triggered by a preceding viral illness, but the specific pathophysiologic mechanism is unknown. Acute ITP occurs with an equal gender distribution. Young children usually present with acute onset of petechiae and purpura and a history of a viral illness 1 to 4 weeks previously. Bleeding from the gingivae and other mucous membranes may occur. Examination findings include petechiae and purpura, especially in trauma areas. If significant lymphadenopathy or organomegaly is found, other causes for thrombocytopenia are considered.

Laboratory findings include thrombocytopenia, which can be severe (<20,000/mm3), but the platelet size is normal or increased. The WBC count and hemoglobin level are normal (unless excessive bleeding has occurred). Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are normal. The peripheral blood smear may reveal eosinophilia or atypical lymphocytes; immature WBCs and abnormal red cell morphology are absent. Generally, bone marrow aspiration is unnecessary. If the peripheral blood smear is concerning, the WBC count is abnormal, or adenopathy or organomegaly is present, bone marrow evaluation aids in proper diagnosis, demonstrating an increased number of megakaryocytes in ITP. Within a month of presentation, more than half of untreated children have complete resolution of their thrombocytopenia and up to another 30% have resolution by 6 months. Persistence beyond 6 months is considered chronic ITP.

The most serious ITP complication, intracranial hemorrhage, occurs in less than 1% of affected children. Patients with severe thrombocytopenia (<20,000/mm3), extensive mucosal bleeding, severe complications (eg, massive gastrointestinal bleeds), or without a protective environment may require medical intervention. Treatment to decrease platelet destruction includes intravenous immunoglobulinfor 1 to 2 days, intravenous anti-D therapy,or a 2- to 3-week course of systemic corticosteroids. Platelet transfusion is reserved for life-threatening bleeding. Splenectomy may be considered in children with serious complications not responding to other therapies. After splenectomy, pneumococcal vaccine and penicillin prophylaxis are required because of risk for sepsis.

From 10% to 20% of ITP patients have chronic thrombocytopenia lasting for more than 6 months, occurring more commonly in older children and in females; it may be part of other autoimmune disease or may occur with infection such as human immunodeficiency virus (HIV) or Epstein-Barr virus (EBV). The ITP treatment options listed above are available for chronic ITP patients; the goal remains prevention of serious thrombocytopenia complications.

Many pharmacologic agents may cause immune-mediated thrombocytopenia, including penicillins, trimethoprim-sulfamethoxazole, digoxin, quinine, quini-dine, cimetidine, benzodiazepine, and heparin. The measles, mumps, and rubella (MMR) vaccine is associated with thrombocytopenia and is used cautiously in ITP patients.

COMPREHENSION QUESTIONS

57.1 A 2-year-old girl has a rash. She was well until 2 weeks prior when she had fever and URI symptoms that resolved without treatment. On examination, she has petechiae on her upper and lower extremities and trunk. Her platelet count is 25,000/mm3. Her WBC count is 9000/mm3 and hemoglobin level is 11 mg/dL. Which of the following is the best next step in management?

A. Obtain a review of the peripheral blood smear.

B. Administer intravenous immunoglobulin.

C. Send a blood culture and begin empiric antimicrobial therapy.

D. Order a platelet transfusion.

E. Arrange for bone marrow biopsy.

57.2 A 14-year-old adolescent female has a rash on her arms and legs. She was diagnosed with a urinary tract infection 4 days ago, which is being treated with trimethoprim-sulfamethoxazole. She denies fever, vomiting, diarrhea, headache, and dysuria. On examination she has multiple upper- and lower-extremity petechiae. Her WBC count is 7000/mm3and hemoglobin level is 13 mg/dL; her platelet count is 35,000/mm3. Which of the following is the best next step in management?

A. Send blood for antinuclear antibody (ANA).

B. Send a repeat urinalysis.

C. Discontinue the trimethoprim-sulfamethoxazole.

D. Obtain HIV testing.

E. Administer intravenous immunoglobulin.

57.3 A 7-year-old boy has a rash on his lower extremities and pain in his right knee. He has had a low-grade fever and abdominal pain, and he has felt tired. He is nontoxic appearing, but he has palpable petechiae on his lower extremities and buttocks. His right knee is mildly edematous and he can bear weight on his right leg, but complains of pain. His prothrombin time (PT), partial thromboplastin time (PTT), and platelet counts are normal. Which of the following is the best next step in management?

A. Begin a course of systemic corticosteroids.

B. Begin empiric antimicrobial therapy for sepsis.

C. Obtain a urinalysis and provide supportive care.

D. Perform aspiration of the synovial fluid in his right knee.

E. Administer intravenous immunoglobulin.

57.4 A 3-year-old boy has pallor, lethargy, and decreased urine output. He was well until the preceding week, when he had fever, vomiting, and bloody diarrhea (now resolved). On examination, he is lethargic and has hepatosplenomegaly and scattered petechiae. Urinalysis reveals hematuria and proteinuria. Which of the following statements about his condition is accurate?

A. A complete blood (cell) count (CBC) is likely to reveal thrombocytosis.

B. Initial therapy includes systemic corticosteroids.

C. Empiric antimicrobial therapy for sepsis should be initiated.

D. An emergent oncology consultation for probable leukemia should be arranged.

E. Peripheral blood smear is likely to reveal helmet cells and burr cells.

ANSWERS

57.1 A. This child has the classic ITP features of isolated thrombocytopenia in a well-appearing child. An examination and peripheral blood smear are necessary. If no lymphadenopathy or organomegaly is found and the peripheral blood smear is normal, initial management includes close observation and a protective environment.

57.2 C. The thrombocytopenia may be the result of the trimethoprim-sulfamethoxazole; the medicine is discontinued and her platelet count is monitored. If thrombocytopenia continues, she may have ITP and is followed for chronic ITP. Chronic ITP occurs in older children (female predominance); it may be seen with autoimmune disease such as systemic lupus erythematosus or with chronic infections including HIV.

57.3 C. This child has signs and symptoms of HSP, a vasculitis of the small vessels with renal, gastrointestinal, joint, and dermatologic involvement. Initial therapy consists of hydration and pain control. With renal involvement, urinalysis reveals red blood cells (RBCs), WBCs, casts, or protein. Gastrointestinal complications include hemorrhage, obstruction, and intussusception(see Case 49, Question 49.4 for more discussion about intussusception); abdominal pain requires careful evaluation.

57.4 E. This child has features of HUS, which frequently follows a bout of gastroenteritis; it has been associated with E coli 0157:H7, Shigella, and Salmonella. Patients have pallor, lethargy, and decreased urine output; some have hepatosplenomegaly, petechiae, and edema. Laboratory findings include hemolytic anemia and thrombocytopenia; peripheral blood smear demonstrates helmet cells, burr cells, and fragmented RBCs. Acute renal failure is manifested by hematuria, proteinuria, and an elevated serum creatinine level. Management is supportive with careful monitoring of renal and hematologic parameters; dialysis may be required.


CLINICAL PEARLS

Image Idiopathic thrombocytopenic purpura is the most common cause of acute thrombocytopenia in a well young child.

Image Approximately 70% to 80% of children with idiopathic thrombocytopenic purpura have spontaneous resolution within 6 months.

Image Hemolytic-uremic syndrome consists of nephropathy, thrombocytopenia, and microangiopathic hemolytic anemia; it is associated with E coli 0157:H7 and Shigella.


REFERENCES

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Davis ID, Avner ED. Hemolytic-uremic syndrome. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: WB Saunders; 2007:2181-2182.

Devarajan P. Hemolytic uremic syndrome (HUS). In: Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA eds. Rudolph’s Pediatrics. 22nd ed. New York, NY: McGraw-Hill; 2011:1727-1729.

Devarajan P. Henoch-Schönlein purpura (HSP) nephritis. In: Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA eds. Rudolph’s Pediatrics. 22nd ed. New York, NY: McGraw-Hill; 2011:1720-1721.

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Van Why SK, Avner ED. Hemolytic-uremic syndrome. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: WB Saunders; 2011:1791-1794.