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Pleural effusion as an atypical presentation of Kawasaki disease: a case report and review of the literature

  • Elif Arslanoglu Aydin
  • Selcan Demir
  • Orkun Aydin
  • Yelda Bilginer
  • Seza OzenEmail author
Open Access
Case report

Abstract

Background

Kawasaki disease is an acute, febrile vasculitis of childhood that affects medium-sized arteries, predominantly the coronary arteries. It is a multisystem disease; therefore, it may present with non-cardiac findings of disease.

Case presentation

Here, we report the case of 7-year-old Turkish girl who presented with symptoms of fever, chest pain, and vomiting, who was diagnosed as having Kawasaki disease. We also present a literature review on pulmonary involvement due to Kawasaki disease.

Conclusion

Pediatricians should consider the diagnosis of Kawasaki disease in the presence of pneumonia and pleural effusion that is nonresponsive to antibiotic therapy. This will prevent delay in diagnosis and the adverse consequences of the disease.

Keywords

Kawasaki disease Pleural effusion Pulmonary involvement 

Abbreviations

AP

Anteroposterior

CAI

Coronary artery involvement

CRP

C-reactive protein

ESR

Erythrocyte sedimentation rate

IVIG

Intravenous immunoglobulin

KD

Kawasaki disease

SAM

Sulbactam ampicillin

TTE

Transthoracic echocardiography

Background

Kawasaki disease (KD) is one of the most common vasculitis disorders of childhood [1]. Although it is a multisystem disease that mainly affects the coronary arteries, it can, rarely, present with unusual system involvement of the pulmonary system, gastrointestinal tract, central nervous system, and genitourinary system [1]. Here, we report the case of a patient with KD who presented with an unusual form of pleural effusion. We also present a literature review on the subject.

Case presentation

A 7-year-old Turkish girl presented to a local hospital with fever, chest pain, and vomiting. At hospital admission, she was febrile with a respiratory rate of 50 per minute. On physical examination, auscultation of her lungs revealed diminished breath sounds of the lower lobe of her left lung. An anteroposterior (AP) chest X-ray and chest ultrasonography showed a left lower lobar consolidation with minimal pleural effusion. She was hospitalized and sulbactam ampicillin (SAM), ceftriaxone, and clarithromycin were initiated. On the third day, her condition worsened with increasing pleural effusion (Fig. 1). Thoracentesis was performed. SAM and ceftriaxone treatments were discontinued and meropenem and vancomycin were started. A chest tube was inserted and 130 mL of pus was drained. Light’s criteria were positive for an exudative pleural effusion; a pleural fluid culture was sterile. After 4 days, the chest tube was removed. High fever persisted for 15 days despite broad spectrum antibiotics, and acute-phase reactants remained high; therefore, she was referred to our hospital for further evaluation.
Fig. 1

Chest X-ray of the patient showing left lower lobar consolidation with pleural effusion

She had a fever with a temperature of 38.1 °C, her respiratory rate was 48/minute, heart rate was 125/minute, blood pressure was 90/65 mm Hg, and oxygen saturation was 95%. A physical examination revealed non-purulent conjunctivitis in both eyes, perianal peeling, and periungual desquamation on her hand, fingers, and toes. All other findings in the physical examination were unremarkable. She had unilateral cervical lymphadenopathy and a rash on her extremities while in the other hospital. Her past medical history was unremarkable, as was her family history. Immunizations were up-to-date for her age.

On admission to our hospital, the laboratory findings were as follows: hemoglobin 10.2 g/dL, white blood cells 14,000/μL, and platelets 736,000/μL. C-reactive protein (CRP) was 4.26 mg/dL (normal, 0–0.8 mg/dL), the erythrocyte sedimentation rate (ESR) was 42 mm/hour (normal, 0–20 mm/hour), and the albumin, creatinine, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, blood urea nitrogen, calcium, sodium, chloride, and potassium levels were normal. Urine analysis was normal.

A chest X-ray was normal. Perivascular brightness and echogenicity of her right coronary artery was noted on transthoracic echocardiography (TTE). She was diagnosed as having KD based on the presence of fever, bilateral non-purulent conjunctivitis, cervical adenopathy, perianal peeling, periungual desquamation, elevated acute-phase reactants (ESR, CRP), thrombocytosis, and coronary artery involvement (CAI). Intravenous immunoglobulin (IVIG) (2 g/kg, infusion in 12 hours) and acetylsalicylic acid (60 mg/kg per day) were initiated. The fever resolved after IVIG infusion. At a 3-month follow-up visit, the acute-phase reactants and a TTE were normal. One year after the diagnosis, a TTE was normal and she was perfectly healthy.

Discussion and conclusion

The most important complication of KD is CAI, which leads to enlargement, aneurysm, ischemic heart disease, and sudden death [1]. The clinical course of KD is highly variable. There are no pathognomonic clinical or laboratory findings to help diagnose KD. The diagnosis of KD in this case was made using the criteria of the American Heart Association [1]. In the presence of at least 5 days of fever, if there are at least four of the five principal criteria (cervical adenopathy, bilateral non-purulent conjunctivitis, oropharyngeal mucosal changes, polymorphous rash, erythema of the palms or soles, and edema of the hands or feet) the patient is diagnosed as having KD [1].

KD may present with uncommon symptoms such as pneumonia, pleural effusion, diarrhea, vomiting, sterile pyuria, gallbladder hydrops, acute cholestatic hepatitis, arthritis, and aseptic meningitis [2, 3, 4, 5, 6, 7]. Pulmonary system involvement of KD is very rare; KD can present as pneumonia, pulmonary nodules, bronchopneumonia, hydropneumothorax, and pleural effusion [6, 8, 9]. Singh et al. showed that 1.3% of patients had pulmonary involvement and pleural effusion was seen in 54.5% of these patients [6]. Ugi et al. reported the case of an adult patient who presented with pulmonary involvement, specifically bilateral massive pleural effusions [10]. Occasionally, pleural effusion may be associated with bacterial agents such as Mycoplasma pneumoniae and Streptococcus [11, 12]. Pulmonary symptoms are mostly initially treated with antibiotics. However, if fever and accompanying signs ensue, the diagnosis of KD should be considered. Patients with pulmonary involvement may be more likely to have CAI due to delays in diagnosing KD and administration of IVIG [12, 13, 14, 15, 16, 17].

We performed a review of the literature using PubMed and the search terms: Kawasaki disease AND pulmonary involvement; OR Kawasaki disease AND pulmonary presentation; OR Kawasaki disease AND pleural effusion. The searches were limited to the English language and pediatric patients. Case series and single case reports involving pediatric patients with KD with pulmonary involvement were included. Inconsistencies were resolved through discussion with the author SO, who also reviewed the literature. The authors EAA and OA searched the literature and manually screened titles and abstracts for relevance. Inconsistencies were resolved through discussion with the author SO.

Figure 2 lists the schematic analyses of the systematic literature review. At first, 25 related articles were found, but nine articles were excluded because of duplication, non-English language, and adult age, which left 16 articles [6, 8, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]. The characteristics of these patients are summarized in Tables 12, and 3. Finally, 20 patients with pleural effusions due to KD were identified [6, 11, 12, 13, 14, 15, 16, 17, 18, 20, 24]. Of the 20 reviewed patients, TTE results were available in nine patients and seven had CAI [6, 12, 13, 14, 15, 16, 17, 24]. Eleven patients presented with respiratory symptoms such as cough, dyspnea, and tachypnea [6, 12, 13, 14, 15, 20]. Only four patients [14, 17, 18, 24] had complete KD, 10 patients [6, 13, 15, 16, 20] had incomplete KD, and six patients’ [11, 12] presentations were not available. Although a definite infectious agent could be shown for two patients [18, 24], all of the patients received antibiotics except one [14]. Two patients [6, 17] received a second dose of IVIG, and five patients received a second dose of IVIG and corticosteroid treatment for KD [13, 14, 15, 16, 18].
Fig. 2

Study flowchart

Table 1

Clinical symptoms and laboratory parameters of patients who had pulmonary involvement associated with Kawasaki disease

Authors, year, reference number

Rash

Oral changes

Extremity changes

Red eyes

Adenitis

Other clinical symptoms

Hb (g/dL)

WBC (/mm3)

Plt (/mm3)

CRP (mg/dL)

ESR (mm/hour)

Singh et al., 2018, [6]

5a

1 a

8a

1 a

0 a

Perianal desquamation, 3 a;

irritability, 1 a

NA

25,009b

886,545b

14.05c

53.75 d

Alhammadi and Hendaus, 2013, [12]

NA

NA

NA

NA

NA

NA

NA

24,000

600,000

10

65

Lee et al., 2011, [11]

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

NA

Lee et al., 2010, [14]

Yes

Yes

Yes

Yes

Yes

Perianal desquamation

NA

5500

178,000

2.8

21

Falcini et al., 2009, [15]

No

No

No

Yes

No

Irritability

9.5

21,800

710,000

27.8

99

Elizabeth et al., 2007, [16]

No

Yes

Yes

No

Yes

Irritability

10.2

12,800

550,000

7.7

86

Yavuz et al., 2007, [17]

Yes

Yes

Yes

Yes

No

Non-pigmented keratic precipitates in both of the patient’s eyes, sterile pyuria

10.4

32,800

734,000

21.8

90

Sittiwangkul and Pongprot, 2004, [13]

Yes

No

Yes

Yes

No

Irritability

NA

21,200

231,000

4.77

66

de Magalhães et al., 2012, [21]

Yes

Yes

Yes

Yes

No

Induration at the BCG site, perianal desquamation

6.5

25,000

905,000

34

120

Hamada et al., 2005, [18]

Yes

Yes

Yes

No

Yes

Hepatomegaly

NA

17,800

NA

13.9

NA

D'Souza et al., 2006, [20]

No

No

Yes

No

Yes

Sterile pyuria

9.8

56,800

690,000

NA

138

de Maddi et al., 2009, [22]

 Case 1

No

Yes

No

Yes

Yes

No

8.7

11,200

561,000

10.4

70

 Case 2

No

No

No

No

No

No

9

26,960

142,000

40.8

107

 Case 3

Yes

Yes

No

Yes

No

Irritability, sterile pyuria

11

18,500

1,087,000

2.95

50

Freeman et al., 2003, [23]

 Case 1

Yes

Yes

No

Yes

No

Irritability

NA

NA

1,120,000

NA

NA

 Case 2

No

Yes

No

Yes

Yes

Torticollis

NA

NA

1,102,000

NA

114

 Case 3

Yes

No

No

No

Yes

Anorexia

NA

NA

450,000

10.5

NA

Kobayashi et al., 2006, [24]

 Case 1

Yes

Yes

No

Yes

Yes

 

9.6

13,000

321,000

12.6

102

 Case 2

Yes

Yes

Yes

Yes

No

Induration at the BCG site

11.6

18,800

314,000

7.6

NA

Vaidya et al., 2017, [8]

Yes

Yes

Yes

No

No

 

8.9

15,600

567,000

5.6

40

Akagi et al., 2017, [19]

 Case 1

Yes

Yes

Yes

No

No

 

NA

NA

NA

4.26

NA

 Case 2

Yes

Yes

No

No

No

 

NA

NA

NA

4.32

NA

aNumber of the patients who had the symptom

b,c,dValues are expressed as mean for 11, 8, and 10 patients, respectively

BCG Bacille Calmette–Guérin, CRP C-reactive protein, ESR erythrocyte sedimentation rate, Hb hemoglobin, NA not available, Plt platelet, WBC white blood cell

Table 2

Demographic parameters and clinical presentations of patients who had pulmonary involvement associated with Kawasaki disease

Authors, year, reference number

Patients (n)

Sex

Age at onset of disease (months)

Initial symptoms

Fever duration (days)

Chest X-ray findings

Singh et al., 2018, [6]

11

F, 6 a;

M, 5 a

30 b

Fever, cough, tachypnea

14.1 b

Consolidation,11 a; pleural effusion,6 a;

empyema, 3 a; pneumothorax, 2 a

Alhammadi and Hendaus, 2013, [12]

1

F

36

Fever, cough, sore throat

18

Consolidation, pleural effusion

Lee et al., 2011, [11]

54

NA

NA

NA

NA

Reticulonodular,17 a; opacification, 34 a; consolidation, 12 a; pleural effusion, 5 a

diffuse interstitial, 5 a; atelectasis, 2 a;

Lee et al., 2010, [14]

1

M

22

Fever, cough, rhinorrhea

6

Infiltration, pleural effusion

Falcini et al., 2009, [15]

1

F

30

Fever, cough,

12

Pleural effusion

Elizabeth et al., 2007, [16]

1

F

36

Fever, gum bleeding

21

Pleural effusion

Yavuz et al., 2007, [17]

1

M

11

Fever, pharyngeal erythema, dyspnea

> 5

Pleural effusion

Sittiwangkul and Pongprot, 2004, [13]

1

F

11

Fever, jaundice, diarrhea, dyspnea

15

Pleural effusion

de Magalhães et al., 2012, [21]

1

F

3

Fever

10

Infiltration

Hamada et al., 2005, [18]

1

F

60

Fever, abdominal pain, knee joint pain

15

Pleural effusion

D'Souza et al., 2006, [20]

1

M

5

Fever, diarrhea, dyspnea

7

Pleural effusion

 Case 1

1

M

8

Fever, sore throat

8

Consolidation

 Case 2

1

F

11

Febrile seizure, sore throat, cough

14

Consolidation

 Case 3

1

F

23

Fever, cough

10

Consolidation

Freeman et al., 2003, [23]

 Case 1

1

M

4

Fever, cough, rash

21

NA

 Case 2

1

M

6

Fever

60

Normal;

thorax CT, pulmonary nodule

 Case 3

1

NA

5

Fever cough, rash

4

Infiltration, multiple pulmonary nodules

Kobayashi et al., 2006, [24]

 Case 1

1

F

24

Fever, cracked lips, rash

5

Infiltration, pleural effusion

 Case 2

1

F

24

Fever, cough, nasal discharge

4

Atelectasis

Vaidya et al., 2017, [8]

1

F

3

Fever, rash, dyspnea

32

Hydropneumothorax, consolidation, pneumatoceles

Akagi et al., 2017, [19]

 Case 1

1

F

4

Fever, erythema of the lips, rash

NA

NA;

thorax MRI, bilateral multiple

pulmonary nodules

 Case 2

1

F

5

Fever, erythema of the lips, rash

9

Infiltration;

thorax CT, bilateral pulmonary nodules

aNumber of the patients who had noted findings

bValues are expressed as mean for 11 patients

CT computed tomography, F female, M male, MRI magnetic resonance imaging, NA not available

Table 3

Treatment, coronary artery involvement, follow-up, and outcomes of patients who had pulmonary involvement associated with Kawasaki disease

Authors, year, reference number

Infectious agent

Antibiotic treatment

CAI

Treatment

Follow-up and outcome

Singh et al., 2018, [6]

2 a

11 a

3 a

2 a, Second dose of IVIG

9 a Normal, 2 a NA

Alhammadi and Hendaus, 2013, [12]

No

Yes

Yes

IVIG

Normal

Lee et al., 2011, [11]

NA

NA

NA

NA

NA

Lee et al., 2010, [14]

No

No

Yes

Second dose of IVIG and corticosteroid

Normal

Falcini et al., 2009, [15]

No

Yes

Yes

Second dose of IVIG and corticosteroid

Normal

Elizabeth et al., 2007, [16]

No

Yes

Yes

Second dose of IVIG and corticosteroid

Normal

Yavuz et al., 2007, [17]

No

Yes

Yes

Second dose of IVIG

Normal

Sittiwangkul and Pongprot, 2004, [13]

No

Yes

Yes

Second dose of IVIG and corticosteroid

Aneurysm persisted in 2 years

de Magalhães et al., 2012, [21]

No

Yes

Yes

Second dose of IVIG, corticosteroid, MTX, and ETN

Aneurysm decrease but persisted

Hamada et al., 2005, [18]

No

Yes

No

Second dose of IVIG and corticosteroid

Normal

D'Souza et al., 2006, [20]

No

Yes

No

IVIG

Normal

de Maddi et al., 2009, [22]

     

 Case 1

No

Yes

No

IVIG

Normal

 Case 2

No

Yes

No

Not given IVIG

Normal

 Case 3

No

Yes

No

IVIG

Normal

Freeman et al., 2003, [23]

 Case 1

No

Yes

Yes

IVIG

Death

 Case 2

NA

Yes

Yes

IVIG

Normal

 Case 3

No

Yes

Yes

IVIG

Normal

Kobayashi et al., 2006, [24]

 Case 1

Yes

Yes

NA

IVIG

Normal

 Case 2

Yes

Yes

NA

IVIG

Normal

Vaidya et al., 2017, [8]

No

Yes

Yes

IVIG

NA

Akagi et al., 2017, [19]

 Case 1

No

No

Yes

IVIG

Normal

 Case 2

No

Yes

Yes

IVIG

Normal

aNumber of the patients

CAI coronary artery involvement, ETN etanercept, IVIG intravenous immunoglobulin, MTX methotrexate, NA not available

In this case, our patient initially had an exudative, noninfectious pleural effusion and no response to antibiotics. CAI was also noticed and IVIG was administered on the 15th day of fever. After IVIG treatment, our patient’s clinical and laboratory findings improved dramatically, and the fever and acute-phase reactants returned to normal. It remains unclear as to whether the KD was triggered by the infection of the pleural space or if the pulmonary finding was a feature of the inflammation of KD.

KD can affect various systems as well as the coronary arteries, and may present with an unusual clinical picture. The diagnosis of KD with atypical presentations may be difficult for pediatricians. Early diagnosis and treatment can prevent complications.

Notes

Acknowledgements

Not applicable.

Authors’ contributions

EAA, OA, and SD drafted the initial manuscript. EAA and OA retrieved the pertinent literature. SD, YB, and SO contributed to the patient management. SO critically reviewed the manuscript. All authors have read and approved the final submitted manuscript.

Funding

No funding.

Ethics approval and consent to participate

No ethical committee approval is required for this case report.

Consent for publication

Written informed consent was obtained from the patient’s legal guardian(s) for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  • Elif Arslanoglu Aydin
    • 1
  • Selcan Demir
    • 2
  • Orkun Aydin
    • 3
  • Yelda Bilginer
    • 2
  • Seza Ozen
    • 2
    Email author
  1. 1.Department of PediatricsHacettepe University Faculty of MedicineAnkaraTurkey
  2. 2.Department of Pediatric RheumatologyHacettepe University Faculty of MedicineAnkaraTurkey
  3. 3.Department of Pediatric EmergencyHacettepe University Faculty of MedicineAnkaraTurkey

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