Mycoplasma pneumoniae and Kawasaki Disease

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A 12-year-old African American girl was transferred to our facility for urgent echocardiography secondary to concerns of her having Kawasaki disease. Her illness began with productive cough and nasal congestion followed by high fever, which continued for 6 days. Her parents also noticed swollen palms and soles, an itchy rash mainly on her lower extremities, injected conjunctiva, and a strawberry-appearing tongue. Her past medical history was significant for numerous occurrences of otitis media. At the referring hospital, she was being treated with ibuprofen and diphenhydramine for fever and rash.

On admission to our facility, clinical findings included bilateral nonexudative conjunctivitis, nasal congestion, cracked lips with strawberry tongue (A), and erythematous maculopapular rash on the lower extremities (B). Left submandibular lymph nodes were palpable at 2 cm. Crackles were heard in the left lower lung. The rest of the examination findings were normal.

The results of echocardiography did not show any aneurysms, but the left main coronary artery was mildly dilated (3.6 mm on day 6 of illness). The white blood cell count was 8,200/µL, with neutrophil predominance. Hemoglobin was 12.2 g/dL, and the platelet count was 269 × 10³/µL. Erythrocyte sedimentation rate was 18 mm/h, C-reactive protein level was 67.3 mg/L, total bilirubin was 1.2 mg/dL with direct 0.4 mg/dL, alkaline phosphatase was 263 U/L, aspartate aminotransferase was 218 U/L, alanine aminotransferase was 187 U/L, total protein was 4.9 g/dL, albumin 2.6 g/dL, and antistreptolysin O titer was 26. Results of a coagulation profile, serum electrolytes, blood urea nitrogen, serum creatinine, and urinalysis were within normal limits. A monospot test, rapid streptococcus A with throat culture, cytomegalovirus serology, and polymerase chain reaction test results for influenza A and B, respiratory syncytial virus, human metapneumovirus, and parainfluenza virus were negative.

With suggestive clinical features and laboratory reports and an equivocal echocardiography result, infectious disease and cardiology consultants decided to treat the patient for presumptive diagnosis of Kawasaki disease. She was given intravenous immunoglobulin G and was started on aspirin. Because of persistent significant cough and a chest radiograph demonstrating central peribronchial thickening and an interstitial pattern, a diagnosis of atypical pneumonia was entertained.

The final diagnosis was made when Mycoplasma pneumoniae serology was reported positive for immunoglobulin M at 2.15 U/L (reference interval: 0.76 U/L or less, negative; 0.77 to 0.95 U/L, equivocal; and 0.96 U/L or greater, positive) and immunoglobulin G at 1.36 U/L (reference interval: 0.09 U/L or less, negative; 0.10 to 0.32 U/L, equivocal; and 0.33 U/L or greater, positive). She was treated with azithromycin for 5 days, and her symptoms resolved completely in that time.

The association between M pneumoniae and Kawasaki disease was first reported in 1996.¹ To the best of our knowledge only 3 cases have been reported in the English literature,^1-3 although some recent reports have appeared in the French,^4,5 Italian,⁶ and Chinese⁷ literatures. These reported cases featured either no cardiac involvement,¹ or documented lesions ranged from mild dilatation of coronary arteries³ to aneurysm in the left main coronary artery.² Other clinical manifestations such as strawberry tongue were present in only about half of these cases. The age of the patients ranged from early childhood to early adolescence. In the latter age group, Kawasaki disease is reported less frequently. Moreover, cardiac manifestations are known to occur with M pneumoniae infection.⁸ Ethnic differences are presumed to account for variable extrapulmonary manifestations of M pneumoniae infection. The strength of association between these two disease processes seems tenuous, but is probably more common than has been reported. The mechanism recently proposed for this association is indirect-type immune modulation such as autoimmunity playing a role by way of cross-reaction between human cells and bacterial cell components.⁸ It is speculated that some antigens overlap in M pneumoniae infections and Kawasaki disease.

M pneumoniae infection may present as typical or incomplete Kawasaki-like illness, with or without pneumonia; thus it is worth ordering M pneumoniae serology in patients with Kawasaki disease, since it may reveal this hitherto unrecognized association while possibly providing clues to the unresolved etiopathogenesis of Kawasaki disease. 

REFERENCES:

1. Leen C, Ling S. Mycoplasma infection and Kawasaki disease [letter]. Arch Dis Child. 1996;75(3):266-267.

2. Wang JN, Wang SM, Liu CC, Wu JM. Mycoplasma pneumoniae infection associated with Kawasaki disease. Acta Paediatr. 2001;90(5):594-595.

3. Narita M, Yamada S, Nakayama T, Sawada H, Nakajima M, Sageshima S. Two cases of lymphadenopathy with liver dysfunction due to Mycoplasma pneumoniae infection with mycoplasmal bacteraemia without pneumonia. J Infect. 2001;42(2):154-156.

4. Chemli J, Hassayoun S, Ketata S, et al. Kawasaki disease and Mycoplasma pneumoniae infection [in French]. Med Mal Infect. 2010;40(12):717-719.

5. Merlin E, Al Fatuhi H, Crost P. Kawasaki syndrome and Mycoplasma pneumoniae infection [in French]. Arch Pediatr. 2004;11(8):972-973.

6. Vitale EA, La Torre F, Calcagno G, et al. Mycoplasma pneumoniae: a possible trigger of Kawasaki disease or a mere coincidental association? Report of first four Italian cases. Minerva Pediatr. 2010;62(6):605-607.

7. Zhang YF, Zhao ZQ. Clinical analysis of 12 cases of Kawasaki disease complicated by Mycoplasma pneumoniae pneumonia [in Chinese]. Zhongguo Dang Dai Er Ke Za Zhi. 2007;9(6):603-604.

8. Narita M. Pathogenesis of extrapulmonary manifestations of Mycoplasma pneumoniae infection with special reference to pneumonia. J Infect Chemother. 2010;16(3):162-169.