The clinical features of Kawasaki disease are protean. Prompt diagnosis is important because treatment with intravenous immunoglobulin can prevent serious vascular complications. In the absence of a specific test, the diagnosis is made by the presence of five of the following six criteria:1
* fever, generally >40°C, lasting >5 days,
* bilateral conjunctivitis,
* acute cervical lymphadenopathy, frequently unilateral,
* oropharyngeal erythema (lips, tongue, buccal, and pharyngeal mucosa),
* dermatitis of the palms and soles with induration and desquamation, and
* dermatitis of the trunk (polymorphic maculopapular rash).
Although it usually occurs in infancy, Kawasaki disease can affect older children. This article presents a 10-year-old girl with an atypical and misleading presentation of which clinicians should be aware.
A previously healthy 10-year-old girl was referred to the ophthalmology clinic with a 4-day history of swelling and redness around the left eye. The general practitioner had made a diagnosis of preseptal cellulitis and had started treatment with oral erythromycin, but the inflammation continued to spread.
On examination, redness and swelling of die lids of die left eye, mild conjunctival injection, and a single enlarged left preauricular lymph node were noted. The patient was afebrile. Visual acuity, the globe white, pupils, and eye movements were all normal. Systemic and ear-nose-throat examinations were normal.
Laboratory values revealed neutrophil leukocytosis (1 1.1 × 10p 9/L), a normal platelet count (271×10p 9/L), and a raised C-reactive protein (22 mg/L). The findings seemed consistent with the diagnosis of preseptal cellulitis, so the patient was admitted for intravenous antibiotics, and cefotaxime (100 mg/kg/day) and flucloxacillin (100 mg/kg/day) were administered.
Over die next 3 days, die patient developed a high swinging fever ranging from 36°C-40°C, the periorbital inflammation spread further, and the tonsils and pharynx became inflamed. Visual acuity, eye movements, and pupils remained normal. Blood cultures and conjunctival swabs taken on admission were sterile. Computed tomography of the orbits and sinuses showed no sinus pathology, but there were inflammatory changes around the left orbit extending close to the globe laterally, compatible with a diagnosis of orbital cellulitis.
The antibiotic regimen was changed to intravenous benzylpenicillin (100 mg/kg/day), ofloxacin (100 mg twice daily), vancomycin (in a dose guided by blood levels), and metronidazole (22.5 mg/kg/day), but die patient's condition worsened and die erythema spread down die left cheek to die jawline and across the bridge of the nose to involve rhe right eyelid (Figure 1). There was bilateral conjunctivitis and limitation of abduction of die left eye. The lips were swollen, dry, and cracked, and die patient had difficulty swallowing solid food because of oropharyngeal inflammation. There was now left submandibular and cervical lymphadenopathy in addition to the preauricular node. The patient was pyrexial and tachycardie (100-120 beats per minute). Her hands were edematous with palmar erythema, and a multiform macular rash developed on her thighs and back (Figure 2). Further laboratory values showed a persisting neutrophil leukocytosis (9.46×10p 9/L), a normal platelet count (192×10p 9/L), and an increased erythrocyte sedimentation rate (85 mm/hour) and C- reactive protein (274 mg/L).
Figure 1 : Erythematous rash and edema affecting the left side of the face, bridge of the nose, and periorbital regions.
Figure 2: Multiform macular rash with target lesions on the back.
Kawasaki disease was considered die probable diagnosis despite the patient's age because of the lack of evidence of an infectious etiology and die presence of five of the six diagnostic criteria for Kawasaki disease, ie, die high swinging fever of 5 days' duration, bilateral conjunctivitis, cervical lymphadenopathy, mucous membrane involvement, and macular rash. She therefore was treated with intravenous gamma globulin (2 g/kg in a single infusion) and aspirin (75 mg/kg/day). The patient responded rapidly; her fever and tachycardia resolved within 48 hours, and her facial inflammation, swelling of the hands, and rash progressively resolved. Her erythrocyte sedimentation rate and Creactive protein also fell rapidly. Echocardiography was normal, showing no coronary artery lesions, but there was a thrombocytosis in the second week of the illness, peaking at 480× 10p 9/L.
The patient was discharged from the hospital 10 days after admission, taking a low dose of aspirin (5 mg/kg/day) only. She was completely recovered 3 months later, with no abnormality on follow-up echocardiography.
Kawasaki disease, or mucocutaneous lymph node syndrome, is an acute vasculitic disorder affecting small- and medium-sized vessels. The incidence has been reported to range from 6.5-33.3 cases per 1 00,000 children per year, with die highest rates seen in Japanese and Asian populations.2 Forty percent of cases occur in children <2 years old and 95% in children <5 years old, with die peak incidence occurring between 12 and 18 mondis. Boys are affected more often than girls, with a ratio of 1 .5: 1 . The cause of the disease is not known, but seasonal peaks in winter and spring, and die occurrence of epidemics suggest an infectious agent.
The cardinal features include fever, erythema of the conjunctivae and mucous membranes, a maculopapular rash with subsequent desquamation, and lymphadenopadiy affecting the anterior cervical chains. Odier symptoms and signs that may be present include a mild anterior uveitis, intense erydiema of perineal skin, irritability, diarrhea, pneumonia, arthralgia, arthritis, tympanitis, meatitis, aseptic meningitis, hydrops of the gallbladder, and sterile pyuria.
The differential diagnosis includes infections Streptococcus, Staphylococcus, Hemophilus, herpes virus, enterovirus, measles, and arbovirus), drug allergy, hypersensitivity reactions (Stevens-Johnson syndrome and erythema multiforme), and other vasculitides (systemic lupus erythematous and polyarteritis nodosa).
Three stages of the illness have been defined:
* acute febrile stage (days 1-14), characterized by fever, rash, anorexia, irritability, aseptic meningitis, and diarrhea,
* subacute stage (days 10-25) during which there is a thrombocytosis, with die concomitant risk of myocardial infarction secondary to coronary artery thrombosis, and
* chronic stage (days 45-60) during which there is resolution of the rash and lymphadenopathy.
Coronary artery aneurysms develop in 15%-20% of cases during this period. If left unrecognized and untreated, mortality is up to 30% from aneurysm rupture, myocardial infarction, or cardiac failure.
Intravenous immunoglobulin in a single dose of 2 g/kg has been shown to speed resolution and reduce mortality.3 Salicylates also are used in therapeutic doses (30-100 mg/kg of aspirin per day) during the period of thrombocytosis to reduce the risk of coronary artery thrombosis. Systemic corticosteroids should be avoided, as these may increase the incidence of aneurysms.4
Patients should be observed closely for evidence of carditis, and echocardiography should be performed to detect coronary aneurysms. Low-dose aspirin (2-3 mg/kg/day) should be given for 1 or 2 years after an episode and possibly for life. Coronary artery bypass grafting or cardiac transplantation rarely may be required for the treatment of aneurysms or cardiac failure.
The prognosis of Kawasaki disease is generally good, but sudden death from cardiac involvement has been reported in approximately 0.04%- 1% of cases.3 Resolution is hastened and mortality reduced by treatment with intravenous immunoglobulin and aspirin, and by screening for coronary artery aneurysms.6-7
Our patient was atypical both in her age and presenting features, which initially seemed typical of a preseptal cellulitis progressing to orbital cellulitis. However, there was no evidence for an infectious etiology. Blood and conjunctival cultures were sterile, there was no response to therapeutic doses of broad-spectrum antibiotics, and streptococcal and virus serology was negative. Stevens-Johnson syndrome and erythema multiforme also were less likely diagnoses because there was no mucosal or corneal ulceration, and no bullous skin eruption.
There has been only one previous report of Kawasaki disease presenting in this manner. This case was a 3-year-old girl who presented with swelling, tenderness, and redness of the left orbital region, as well as the classic clinical findings of Kawasaki disease.8
The diagnosis of Kawasaki disease should be considered in cases of apparent preseptal or orbital cellulitis, especially as this condition is much less common since universal immunization against Hemophilus influenzae. Other clues include a lack of response to antibiotics, an inappropriate degree of lymphadenopathy, and the other clinical features of Kawasaki disease. It is important to establish the correct diagnosis to prevent the serious complications of the disease, which may cause late cardiac death.
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3. Newburger JW, Takahashi M, Beiser AS, et al. A single intravenous infusion of gamma globulin as compared with four infusions in die treatment of acute Kawasaki syndrome. N Engl J Med 1991;324:1633-1639.
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6. Annotations. Kawasaki disease: recent advances. Arch Dis Child. 1991;66:1369-1374.
7. Dhillon R, Newton L, Rudd PT, Hall SM. Management of Kawasaki disease in the British Isles. Arch Dis Child. 1993;69:631-638.
8. Demirsoy S, Gucuyener K, Olgunturk R, Oguz D, Or M. A case of Kawasaki syndrome associated with preseptal cellulitis in orbita. Turk J Pediatr. 1988;30:55-59.