Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 13-5

Two-and-a Half-Year-Old Boy

STEPHEN LUDWIG

BRANDON C. KU

HISTORY OF PRESENT ILLNESS

Patient is a 2.5-year-old white male who presented to the emergency department with a 4-day history of fever and 2 days prior awoke with his head twisted to the left and an estimated 3 cm swollen lymph node in the right cervical region. He was brought to his primary physician who prescribed amoxicillin-clavulanate for suspected bacterial lymphadenitis. On the day prior to admission, his fevers continued. Two days prior to these symptoms he was at a friend’s house where he was exposed to several cats, but there was no cat-scratch noted. During the past 2 days the parents noticed increased irritability, fevers, chills, and night sweats. The child also had decreased oral intake during the past 3 days. There was no diarrhea or emesis. There was no joint swelling.

MEDICAL HISTORY

Patient was a full-term infant of spontaneous vaginal delivery with no complications. The medical history is notable for beta-thalassemia minor diagnosed at 9 months of age on a screening complete blood count. He had no prior hospital admissions. There were no known allergies, and immunizations are up-to-date. The amoxicillin-clavulanate was the patient’s only medication. The family history is notable for beta-thalassemia in the mother, juvenile polyps in the father, and systemic lupus erythematosus in the paternal grandmother. The boy lives with his parents and a healthy 5-month-old sister.

PHYSICAL EXAMINATION

T 40.0°C; HR 153 bpm; RR 26 min; BP 135/77; Weight 12.2 kg (10th percentile)

On general examination, the patient was irritable. His tympanic membranes were mildly erythematous but had normal movement with insufflation. He had mild bulbar and palpebral conjunctival injection. His lips were dry and cracked (Figure 13-9A). His pharynx was erythematous but without exudate. There was a 1.5 × 3 cm right cervical lymph node; it was not tender. His lungs were clear to auscultation and there was no murmur. He had mild right upper quadrant tenderness and his liver edge was palpable 1.5 cm below the right costal margin. The spleen was not palpable. His hands looked swollen (Figure 13-9B).

DIAGNOSTIC STUDIES

WBCs, 14 900/mm3 (11 basophils, 75 segmented neutrophils, 9 lymphocytes, 5 monocytes); hemoglobin, 8.8 g/dL—MCV 57.2; RDW 16.2; platelets, 410 000/mm3; ESR, 65; total bilirubin, 0.9; albumin, 3.4; AP, 282; ALT, 205; AST, 136; ALT, 205; GGT, 176; amylase, <30 lipase, 63.

A chest radiograph revealed normal heart size. There are no areas of consolidation.

Viral PCR panel on nasopharyngeal aspirates: negative for respiratory syncytial virus, adenovirus, influenza A/B, parainfluenza virus 1, 2, and 3, and human metapneumovirus.

Image

FIGURE 13-9. Photographs of the patient’s: A. Lips. B. Hands.

Blood culture negative. Urinalysis, negative nitrite, moderate leukocytes; 0-2 RBCs; 15-20 WBCs.

COURSE OF ILLNESS

During the next 1-2 days he developed more prominent conjunctival injection and an erythematous rask on his trunk and extremities; the rash consisted of 0.5-2 cm nonconvalescent maculopapular lesions. No lesions were apparent on his hands or feet. There were no oral lesions but one examiner noted strawberry tongue.

DISCUSSION CASE 13-5

DIFFERENTIAL DIAGNOSIS

This child was evaluated for a number of causes of acute lymph node enlargement including group A beta-hemolytic Streptococcus, mononucleosis, cat-scratch disease, hepatitis, cytomegalovirus, adenovirus, and other infectious causes. All of those infections are in the differential diagnosis. The adenopathy was not progressive to a suppurative state but was more subacute in its course. Other considerations would be tuberculosis and atypical mycobacterium.

DIAGNOSIS

The boy’s lips were red, dry, and cracked (Figure 13-9A). He had palmar erythema and his fingers were (Figure 13-9B) swollen and “sausage-like.” The final constellation of symptoms and clinical course best fit the diagnosis of Kawasaki disease. The findings of decreased shortening fraction on echocardiograph also supported the diagnosis. The child was treated with intravenous immune globulin (IVIG) and aspirin. His fevers resolved within 16 hours of starting the IVIG infusion.

INCIDENCE AND EPIDEMIOLOGY OF KAWASAKI DISEASE

The peak incidence is in early childhood. The median age for Kawasaki disease is 2 years; more than 80% of children are under 4 years of age. It is extremely rare beyond 8 years of age. Children of Japanese and Korean descent are at highest risk, and even for children of Asian descent living in the United States. The incidence in Japan and Korea is 50-100/100 000 in less than 5 year olds. In the United States, the incidence by ethnic background is 5/100 000 in Asians, 1.5/100 000 in African Americans, and less than 1/100 000 in Europeans and Hispanics. Kawasaki disease is more prevalent in the winter and spring.

CLINICAL PRESENTATION

The criterion for the diagnosis is to identify the common clinical presentations. This includes fever higher than 38.2°C for more than 5 days, and four of the five clinical criteria: (1) nonpurulent conjunctivus, (2) polymorphous rash, (3) mucous membrane changes, particularly cracked red lips and strawberry tongue, (4) enlarged lymph node that measures greater than 1.5-2 cm (a single enlarged lymph node as opposed to multiple enlarged lymph nodes), and (5) extremity changes usually swelling of the hands and feet. Despite this set of clinical criteria there are many other potential manifestations including cardiac disease, vasculitis symptoms, aseptic meningitis, hydrops of the gall bladder, hepatic dysfunction, urethritis, uveitis, and arthritis/arthralgia. Young children with this disease are often extremely irritable, and the irritability and fever often abruptly resolve with treatment. Children less than 1 year of age often do not meet all the diagnostic criteria and are often considered to have “atypical” or “incomplete” Kawasaki disease. Many authors have described the clinical manifestations in terms of three phases: acute, subacute, and convalescent.

DIAGNOSTIC APPROACH

The diagnosis is not based on any single laboratory test but on a confluence of the clinical findings. Beyond documentation of the findings there may be suggestive laboratory evidence.

Complete blood count. The WBC count may be normal but more than 50% of affected children have a WBC count more than 15 000/mm3. A normocytic anemia is often present. Thrombocytosis is virtually always present after the first week of fever.

Inflammatory markers. Most patients have an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). While these test abnormalities are nonspecific, a normal ESR or CRP makes the diagnosis of Kawasaki disease unlikely.

Hepatic function tests. The alanine aminotransferase and aspartate aminotransferase values are mildly elevated. There may also be elevations in the gamma glutamyl transferase and bilirubin. Approximately half the patients with Kawasaki disease have at least one abnormality in the tests of hepatic “function.”

Lumbar puncture. A lumbar puncture is not routinely required but may be performed to diagnose or exclude bacterial meningitis in an irritable child. Among those undergoing lumbar puncture, cerebrospinal fluid white blood cell count is elevated in 25%-50%; the CSF pleocytosis is mild and lymphocytes predominate.

Urinalysis and urine culture. Urethritis leads to sterile pyuria from a clean catch sample; bladder catheterization may not reliably permit detection of pyuria attributable to urethritis.

Slit lamp examination. Uveitis is present in up to 85% of children with Kawasaki disease. While the absence of uveitis does not exclude the possibility of Kawasaki disease, the presence of uveitis makes other conditions in the differential diagnosis, particularly systemic juvenile idiopathic arthritis, unlikely.

Electrocardiogram (ECG). An ECG may demonstrate arrhythmia, ischemia, or low voltage.

Echocardiogram. An echocardiogram should never be performed to “rule out” Kawasaki disease as abnormalities typically develop after 10 or more days of symptoms. An echocardiogram is important to document the presence or absence of findings such as coronary artery ectasia or aneurysms, pericardial effusions, valvular abnormalities, and diminished ventricular function that may warrant additional treatment or monitoring.

TREATMENT

Initial treatment is IVIG, 2 g/kg infused over 12 h. Often aspirin is prescribed for its antiplatelet adherence effects. The role of corticosteroids remains controversial. A randomized, placebo-controlled trial found no difference in clinical outcomes between children treated with IVIG and 30 mg/kg methyl-prednisolone (administered as a single dose) and those treated with IVIG alone. Patients will also require supportive care depending on their symptom complex. Regular follow-up care with a pediatric cardiologist is indicated.

SUGGESTED READINGS

1. Shulman ST, Inocencio J, Hirsh R. Kawasaki’s disease. Pediatr Clin North Amer. 1995;42:1205-1222.

2. Newburger JW, Takahashi M, Beiser AS, et al. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med. 1991;324:1633-1639.

3. Mori M, Imagawa T, Yasui K, et al. Predictors of coronary artery lesions after intravenous [gamma]-globulin treatment in Kawasaki disease. J Pediatr. 2000;137:177-180.

4. Shinohara T, Tanihira Y. A patient with Kawasaki disease showing severe tricuspid regurgitation and left ventricular dysfunction in the acute phase. Pediatr Cardiol. 2003;24:60-63.

5. Kanegaye JT, Van Cott E, Tremoulet AH, et al. Lymph node first presentation of Kawasaki disease compared with bacterial cervical adenitis and typical Kawasaki disease. J Pediatr. 2013 [epub ahead of print].

6. Dominquez SR, Anderson MS. Advances in the treatment of Kawasaki disease. Curr Opin Pediatr. 2013; 25:103-109.

7. Newburger JW, Sleeper LA, McCrindle BW, et al. and the Pediatric Heart Network Investigators. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med. 2007;356: 663-675.