PEDIATRIC PUZZLER

GEORGE K. SIBERRY, MD, MPH, SECTION EDITOR

Abrupt hearing loss in a preschooler:
Behind the "white noise"

By Carolyn Boylan, MD, PhD

The story of a 4-year-old girl who has been referred to your hospital's emergency department from another hospital began several days before you met her this morning, when her parents noted that this previously healthy child was having difficulty hearing. Now, in your ED, they explain that, although they are accustomed to the occasional episode of "selective hearing" by their four children when engrossed in play or television, this is, without question, more pronounced and more persistent. The girl does not respond unless spoken to very loudly and in her line of vision, and even her brothers noticed that they had to repeat themselves when talking and playing with her. This is not, they insist, the typical behavior of their bright, precocious daughter, who normally has the run of the house and of her three older brothers! Your interest is piqued, and you move to obtain additional history.

The patient is the product of an uncomplicated, full-term pregnancy and has no significant medical history. Her mother, an emergency room nurse at a nearby hospital, recalls that the child passed the state's mandatory hearing screen performed on all newborns before discharge. Her pediatrician also performed a screening hearing exam two months ago at the 4-year-old well-child visit; she passed without difficulty. The girl has never been hospitalized, has been growing and developing normally, and has received all recommended immunizations for her age, including the conjugate pneumococcal vaccine. There is no family history of deafness and her three brothers are healthy. The only medications she is taking are gentamicin ophthalmic drops, prescribed by her pediatrician over the telephone for a report of pink eye, and a pediatric formulation of acetaminophen for a low-grade fever the day before. The prescription for the antibiotic was filled two days ago, and her eyes are already much improved.

This is an active child by nature, her parents relate, although, they acknowledge, she has seemed more tired than usual over the past several weeks. She has, however, been attending prekindergarten class, with its busy schedule of activities, daily, they are quick to add. She has been eating well, they confirm, and has not had any significant weight loss.

Yesterday evening, when the girl spiked a fever of 101° F, her mother confesses to having been almost relieved—thinking that her daughter's difficulty hearing might be explained by something as simple as an ear infection. With that possibility in mind, she checked the schedule at the hospital where she worked and was happy to see that the ED physician on call this morning was one whom she trusted. So off mother and daughter went for what Mother expected to be a quick examination and uncomplicated diagnosis. But she and the ED physician were shocked by what was found: Not otitis media but bilateral hemotympanum was impairing the child's hearing! Working in a busy ED, both had seen this condition before—in trauma patients who had sustained a head injury and basilar skull fracture. But this child had no history of trauma, just typical bumps and bruises of childhood.

Upon a moment's reflection, however, the girl's mother considered that maybe her daughter had been bruising more easily after minor falls and injuries over the past few weeks. On closer inspection of the skin, the ED physician noted multiple bruises on the shins and several purpuric lesions on the legs and thighs. Realizing that the ED visit wasn't as straightforward as initially hoped, the physician outlined his concerns to the mother. They agreed that the child might need subspecialty care, and he referred her to your emergency room.

Proceeding, with a raised voice

On physical examination, you encounter a very pleasant child of stated age who is in no apparent distress. She is sitting comfortably in her father's lap and cooperates with the exam. Sure enough, however, she does not seem to hear your questions unless she is spoken to in a loud voice. Vital signs are generally reassuring: axillary temperature, 36.9° C; heart rate, 129/min; respirations, 24/min; blood pressure, 79/43 mm Hg; and oxygen saturation, 100%.

The head is normocephalic and atraumatic. Pupils are equal, round, and reactive to light; conjunctiva, somewhat pale. Cranial nerves appear intact. Mucous membranes are moist, without lesions. Both tympanic membranes appear intact but are a startling shade of purple. The neck is supple without lymphadenopathy.

The chest is clear and the cardiovascular exam is notable for tachycardia without murmur. Peripheral pulses are strong and equal bilaterally. Her abdomen is soft, nondistended, and nontender. You hear bowel sounds and do not appreciate either hepatomegaly or splenomegaly. There are no palpable clavicular, axillary, epitrochlear, inguinal, or popliteal lymph nodes. Scattered about her shins are bruises; you note a few purpura on her lateral and anterior thighs. There are no petechiae or rashes. Given her natural olive skin tone, you find it difficult to determine whether she is in fact pale.

Quickly, you review the findings of the history and physical exam in your mind: fever, tachycardia, fatigue, bilateral hemotympanum, easy bruising, purpura. What are you to make of the hemotympanum? You're aware of this condition only in the setting of head trauma; her parents insist that she hasn't sustained any. A quick search of the medical literature confirms that most cases of hemotympanum are caused by head trauma but also alerts you that the condition can be seen—rarely—as a result of spontaneous hemorrhage into the temporal bone during hemoptysis associated with advanced tuberculosis¹ and in patients with systemic bleeding abnormalities.

You consider the differential diagnosis of bleeding and bruising: sepsis, coagulopathy, thrombocytopenia, vasculitis, Henoch-Schönlein purpura, serum sickness, local trauma, leukemia, and aplastic anemia.^2,3 Her history of easy bruising and purpura could easily be caused by thrombocytopenia, but her systemic symptoms lead you to worry more about malignancy. Pale conjunctiva and tachycardia suggest anemia, which only adds to your growing concern.

With such suddenness does the sky change

You place an intravenous line and order lab tests, including a complete blood count with differential, electrolytes, a chemistry panel, and clotting assays. Your heart sinks when the results arrive. The white blood cell count is normal (12.7 x 10³/µL) but the differential is very abnormal: 29% neutrophils, 45% lymphocytes, 1% atypical lymphocytes, 5% monocytes, 2% promyelocytes, 2% metamyelocytes, 3% myelocytes, 2% unidentified cells, and 11% blasts. The hematocrit is very low at 21.4%; mean corpuscular volume is 94 (normal, 86). The platelet level is exceedingly low (14 x 10³/µL). Electrolyte levels are normal, but the lactate dehydrogenase level is high (384 IU/L; normal, 122 to 220 IU/L) and the uric acid level is slightly low (1.8 mg/dL; (normal, 2.0 to 5.5 mg/dL).

The prothrombin time is prolonged at 13.7 seconds (normal, 10.8 to 13.0 seconds), with a ratio of 1.2; so is the activated partial thromboplastin time at 43.0 seconds (normal, 23.4 to 33.5 seconds), with a ratio of 1.5. The International Normalized Ratio (INR) is 1.3. A chest radiograph is unremarkable.

Given the presence of blasts and unidentified cells as well as the profound anemia and thrombocytopenia, your concern about malignancy in this young girl is, unfortunately, appropriate.

With those test results in hand, you quickly call your colleagues in pediatric oncology to arrange for an examination and a review of the lab work. They inspect the peripheral blood smear and confirm the diagnosis: leukemia. After a long discussion with the parents, the oncologist arranges to admit the child to his service and to plan for a bone marrow biopsy and central venous line placement the next day.

You follow your patient's progress while she is an inpatient and read the results of the bone marrow biopsy when they become available in the electronic patient record two days later. The finding is acute myeloid leukemia (AML). She then undergoes chemotherapy and an allogeneic bone marrow transplant. On her last clinic visit, she is reportedly doing very well and is in full remission without any evidence of active disease.

Leukemia, the most common childhood cancer, affects about one of every 2,500 children under 15 years old in the United States each year. It can be classified as acute or chronic, based on the maturity of the proliferating malignant cell type.⁴ Acute leukemia is the result of the proliferation of immature or blastic cells; chronic leukemia is the result of the proliferation of mature or differentiated cells. Congenital leukemia is much less common and develops during the first month of life. Most childhood leukemias are acute and lymphoblastic in nature; in fact, acute lymphoblastic leukemia (ALL) accounts for approximately 80% of acute leukemias of children and adolescents and AML accounts for the remaining 15% to 20% of cases.^4,5 ALL and AML are further subdivided based on the morphologic analysis of leukemic cells in the marrow.

Although the presentation of acute leukemia can be highly variable, children with the disease generally have a several-week history of some combination of pallor, easy bruising, lethargy, anorexia, malaise, fever, bone pain, arthralgias, abdominal pain, and bleeding. In some, the presentation is acute, with significant bleeding or severe infection; others may be essentially asymptomatic.

Physical examination often reveals pallor, petechiae, ecchymosis, lymphadenopathy, and hepatosplenomegaly. Both ALL and AML are characterized by varying degrees of anemia, thrombocytopenia, and abnormalities of the WBC count. Marrow biopsy is essential for definitive diagnosis. Treatment—comprising chemotherapy and bone marrow transplantation—is tailored to the subtype of disease and individual prognostic variables.

Despite significant advances in diagnosing and treating childhood cancers, leukemia remains, overall, the leading cause of death from disease in children and adolescents.⁶ The treatment of AML has been less successful than the treatment of ALL: Although the 10-year survival rate of children with ALL is reported at greater than 80%, fewer than 50% of children with AML will be cured.^5,6

For a mother who began the day puzzled but optimistic, much news followed that she herself would have been glad not to hear.

REFERENCES

1. Pulec JL, DeGuine C: Hemotympanum from trauma. ENT: Ear, Nose & Throat J 2001;80:486

2. Cohen BA: Pediatric Dermatology, ed 2. St. Louis, Mo.: Mosby, Inc., 1999, pp 163–170

3. Davis HW, Carrasco MM: Child abuse and neglect, in Zitelli BJ and Davis HW (eds): Atlas of Pediatric Physical Diagnosis, ed 3. St. Louis, Mo.: Mosby, Inc., 1997, pp 149–150

4, Pui C-H, Crist WM: Leukemia, in Rudolf AM, Hoffman JI, Rudolf, CD (eds): Rudolf's Pediatrics, ed 20. Stamford, Conn. Appleton & Lange, 1996, pp 1269–1279

5. Arceci RJ: Progress and controversies in the treatment of pediatric acute myelogenous leukemia. Curr Opin Hematol 2002;9:353

6. Reaman GH: Pediatric oncology: Current views and outcomes. Pediatr Clin North Am 2002;49:1305

DR. BOYLAN is a first-year fellow in the division of neonatology at The Johns Hopkins University School of Medicine, Baltimore, Md.

DR. SIBERRY is an assistant professor of pediatrics in the divisions of general pediatric and adolescent medicine and pediatric infectious diseases at The Johns Hopkins Hospital.