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Endgames Case Report

Persistent fever and rash in a young child

BMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d5196 (Published 19 September 2011) Cite this as: BMJ 2011;343:d5196
  1. Peter J Gill, medical student12,
  2. David Burgner, paediatric infectious diseases physician3,
  3. Anthony Harnden, university lecturer in general practice2
  1. 1Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
  2. 2Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  3. 3Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Australia
  1. Correspondence to: Peter J Gill peter.gill{at}phc.ox.ac.uk

A 22 month old white Australian boy presented to his general practitioner with irritability, red eyes, and a two day history of high fever (highest at 41°C) that did not respond to paracetamol and ibuprofen. He had no history of cough, coryza, or rash. His medical history was unremarkable and immunisations were up to date. On examination, he had bilateral non-exudative conjunctival injection and was diagnosed with a non-specific febrile illness with associated conjunctivitis. His family then took him on a planned family holiday to Thailand where his conjunctivitis improved, but the fevers continued unabated. In addition to the fevers, his parents noted a mild nappy rash. On day 8 of the illness, his parents took him to a local clinic after a couple of episodes of diarrhoea. He was diagnosed with gastroenteritis. Later that day he became more unwell with increasing irritability and a progressive rash so his parents took him to hospital. He was dehydrated and lethargic and physical examination showed cervical lymphadenopathy, fissured lips, and an injected pharynx. His hands and feet were oedematous and his legs were covered in a pink maculopapular rash. Blood tests showed leucocytosis and increased acute phase reactants, but other haematological markers were normal. A chest radiograph was normal. He was admitted with presumed bacterial sepsis and started on broad spectrum intravenous antibiotics. However, after two days of antibiotics, his symptoms did not improve.

Questions

  • 1 What is the most likely diagnosis in this case?

  • 2 How is this condition diagnosed and what further investigations are needed for a definitive diagnosis?

  • 3 What is the treatment for this condition?

  • 4 What are the cardiovascular complications of this condition?

Answers

1 What is the most likely diagnosis in this case?

Short answer

Kawasaki disease.

Long answer

The most likely diagnosis is Kawasaki disease. Differential diagnoses to be considered in a child with a history of persistent fever and rash include viral infections (particularly measles, Epstein-Barr virus, adenovirus, enterovirus, parvovirus, and influenza), bacterial infections (including group A streptococcal infection, staphylococcal scalded skin syndrome, and toxic shock syndrome), drug hypersensitivity reactions, and systemic onset juvenile idiopathic arthritis.

Kawasaki disease is the leading cause of acquired heart disease in childhood in the developed world and is the second most common cause of vasculitis in childhood, primarily affecting medium sized arteries.1 2 In most populations, about 85% of cases of Kawasaki disease are reported in children under 5 years old,3 and it is rarely seen in patients under 6 months or older than 8 years.4 5 The annual incidence of the disease in children younger than 5 years varies notably by ethnicity, from 8 per 100 000 in British children of non-Chinese origin to 218 per 100 000 in Japan.6 7 8 The cause of Kawasaki disease is still unknown.6 9 10 11 12

2 How is this condition diagnosed and what further investigations are needed for a definitive diagnosis?

Short answer

There is no definitive diagnostic test for Kawasaki disease. Kawasaki disease can be diagnosed when a child has been febrile for five or more days together with four or more of these findings:

  • Polymorphous exanthema

  • Bilateral non-exudative conjunctival injection

  • Changes in the lips and oral cavity

  • Changes in the extremities

  • Cervical lymphadenopathy.

Long answer

Children with Kawasaki disease are febrile and extremely irritable. The signs and symptoms typically develop over the first 10 days of illness before gradually resolving spontaneously.3 The diagnosis is usually made in children who have been febrile for five or more days and have four or more of the following criteria, without another known disease process to explain the illness:13

  • Polymorphous exanthema

  • Bilateral non-exudative conjunctival injection

  • Changes in the mucous membranes of the upper respiratory tract

  • Changes in the extremities

  • Cervical lymphadenopathy.

The nature of the rash in Kawasaki disease is variable, ranging from pink maculopapular lesions (fig 1), sharply demarcated red lesions, to a more generalised redness. The rash often begins in the nappy area and spreads to the rest of the torso, extremities, and face.14 Conjunctival injection is not associated with purulent discharge and usually spares the limbus. Oropharyngeal changes include bright red dry lips (“the lipstick sign”), a strawberry tongue, and pharyngeal erythema without exudates. The child’s hands and feet may be swollen, erythematous, and painful to touch or on weight bearing, and the child usually refuses to walk or crawl. In older children, desquamation of fingers and toes, which occurs two to three weeks after fever onset (fig 2), may be the only peripheral feature. Cervical lymphadenopathy is more common in older children and consists of a solitary lymph node (≥1.5 cm), which is often non-fluctuant, firm, and mildly tender.14

However, 15-20% of children have fever and three or fewer criteria, which is classified as incomplete Kawasaki disease.13 A diagnostic algorithm to assist the management of incomplete Kawasaki disease has been formulated by the American Heart Association.13

Some laboratory investigations are usually abnormal during the first seven to 10 days and can support the diagnosis of Kawasaki disease, although in isolation they lack adequate sensitivity and specificity:14

  • Haematology: leucocytosis, anaemia, thrombocytosis

  • Urine: sterile pyuria

  • Blood chemistry: raised acute phase reactants; low serum sodium, protein, and albumin; raised liver enzymes; abnormal lipid profile

  • Cerebrospinal fluid: pleocytosis

  • Electrocardiography: tachycardia, reduced QRS voltages, flattened T waves, prolonged rate corrected QT intervals, cardiac conduction abnormalities15 16

  • Echocardiography: coronary artery dilation, reduced left ventricular function, mitral regurgitation, or pericardial effusion.

Other clinical features can include notable irritability, reinflammation of a recent BCG scar, arthritis or arthralgia, pneumonitis, anterior uveitis, and gastroenteritis.3

3 What is the treatment for this condition?

Short answer

The treatment is intravenous immunoglobulin (2 g/kg body weight as a single infusion) and aspirin.

Long answer

The appropriate treatment for Kawasaki disease is a single dose of 2 g/kg intravenous immunoglobulin infused over 10-12 hours. A single intravenous immunoglobulin infusion is more effective than multiple smaller infusions given over several days.13 17 18 Aspirin is often initially given at an “anti-inflammatory” dose (30-80 mg/kg/day in divided doses), together with intravenous immunoglobulin, although there is no good evidence to support this practice.18 Some clinicians start a lower “antiplatelet” dose of aspirin (3-5 mg/kg/day) from the initial diagnosis. In about 85% of cases, the fever abates within 36 hours of intravenous immunoglobulin; a further dose of intravenous immunoglobulin is usually given if there is lack of response to the initial dose.

All patients with Kawasaki disease and persisting inflammation (fever or raised acute phase reactants) should be treated even if the diagnosis is delayed. The risk of cardiovascular complications at seven weeks reduces from 15-25% to less than 5% if intravenous immunoglobulin treatment is given before day 10.19 If the patient was started on a higher dose of aspirin, this should be reduced to a lower dose once the patient has been afebrile for more than 48 hours and continued for at least six weeks until the echocardiogram is repeated. If the echocardiogram is normal, aspirin is usually stopped. After intravenous immunoglobulin, administration of live virus vaccine (for example, MMR) should be deferred for nine months because of reduced immunogenicity.3

4 What are the cardiovascular complications of this condition?

Short answer

Coronary artery aneurysms are the most important cardiovascular complication.

Long answer

Although all arteries can be affected in Kawasaki disease, coronary arteries are most commonly damaged. Coronary artery dilation can occur in more than a quarter of all patients but is usually transient.20 Giant coronary aneurysms (internal diameter >8 mm) (fig 3) have the worst prognosis.13 21 Rarely these aneurysms can thrombose acutely or rupture; more commonly, aneurysms persist, resolve, or heal with scarring, resulting in coronary artery stenosis.13 21 Treatment of Kawasaki disease reduces coronary artery damage.13 The case fatality rate of Kawasaki disease in Japan is 0.08% while in-hospital mortality in the United States is 0.17%.13

Echocardiography is a sensitive and reliable method to detect coronary artery abnormalities.22 23 The American Heart Association consensus guidelines state that the initial echocardiogram should be done as soon as the diagnosis is suspected, and then at two weeks, and at six to eight weeks after disease onset, although in many non-US centres the repeat test at two weeks is not performed.24 Patients with no coronary artery aneurysms detected during the acute and subacute phases are clinically asymptomatic at least 10 years later.25 However, about 20% of patients who develop coronary artery aneurysms during the acute disease will develop coronary artery stenosis.3

Patient outcome

After receiving the appropriate diagnosis of Kawasaki disease, the patient responded well to treatment and had an uncomplicated recovery. He did not develop any coronary artery lesions and is doing well.

Notes

Cite this as: BMJ 2011;343:d5196

Footnotes

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

  • Peer review and provenance: Commissioned and externally peer reviewed.

  • Patient consent obtained.

References

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