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Min-Chung Shen, et al.

J Med Sci 2011;31(3):117-120


http://jms.ndmctsgh.edu.tw/3103117.pdf
Copyright 2011 JMS

Mycoplasma Pneumoniae-associated Bronchiolitis Obliterans


Organizing Pneumonia
Min-Chung Shen1, Fu-Chang Ko4*, Junn-Liang Chang2, and Huan-Chu Lo3
1

Department of Internal Medicine; 2Department of Pathology; 3Department of Radiology;


4
Intensive Care Unit, Taoyuan Armed Forces General Hospital,
Taoyuan, Taiwan, Republic of China.

A 52-year-old man presented with fever, non-productive cough and progressive dyspnea for 10 days. Chest X-ray showed
pneumonia and serological test for Mycoplasma pneumoniae was positive. His symptoms exacerbated in spite of antibiotics treatment. Follow-up chest X-ray and CT scan of the lungs showed bilateral air space opacifications. For further evaluation, video-assisted thoracoscopic biopsy was performed and bronchiolitis obliterans organizing pneumonia (BOOP) was
diagnosed. Steroid was administered; clinical and radiographic findings then revealed marked and rapid improvements.
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia. If clinical symptoms deteriorated after
appropriate treatment, BOOP must be considered. The key therapy of BOOP is steroid and early diagnosis is very important to avoid irreversible damage to lungs.
Key words: mycoplasma pneumoniae, bronchiolitis obliterans organizing pneumonia

INTRODUCTION
Bronchiolitis obliterans organizing pneumonia
(BOOP) is a clinicopathological entity that occurs in a
wide variety of pulmonary injuries. It is a nonspecific response, which is histologically characterized by intraluminal fibrosis involving the small conducting airways,
alveolar ducts and peribronchial alveolar space.1-3 This
rare disorder is either idiopathic or associated with various illnesses, including infections.1
Here, we describe an interesting case of Mycoplasma
pneumoniae infection and BOOP. The pneumonia was
revealed by radiographic findings and Mycoplasma pneumoniae infection was proven serologically. The failure of
antibiotics therapy and progressive symptoms indicated
a need for further diagnostic evaluation. The patient accordingly underwent a video-assisted thoracoscopic lung
biopsy, and BOOP was then diagnosed. We suggest that
BOOP should be included in the differential diagnosis for

Received: July 2, 2010; Revised: December 8, 2010;


Accepted: February 10, 2011
*
Corresponding author: Fu-Chang Ko, Intensive Care
Unit, Department of Internal Medicine, Taoyuan Armed
Forces General Hospital, No.168, Chong Shin Road,
Lungtan, Taoyuan County 32551, Taiwan, Republic of
China. Tel: +886-3-4803363; Fax: +886-3-4803363;
E-mail: airfly100@ms47.url.com

patients with Mycoplasma pneumoniae infection who do


not respond to antibiotic therapy.

CASE REPORT
A 52-year-old man was admitted to our hospital with
a 10-day history of intermittent fever, nonproductive
cough, and progressive dyspnea. Except a history of
smoking (34 pack years), there was no other significant
medical history. At the time of admission, his vital signs
were as follows: temperature, 38 oC; blood pressure,
117/61 mmHg; pulse rate, 119/min; and respiratory rate,
36/min. On auscultation, crackles were heard over both
lungs, and a grade 3/6 early diastolic murmur was heard
over the left lower sternal border. The patients arterial
blood gas analysis revealed the following: pH, 7.45;
PaO2, 70 mmHg; PaCO2, 35 mmHg; and O2 saturation,
99.4%. The results of other laboratory tests revealed
white blood cell counts of 1.8109/L (neutrophils, 84%;
lymphocytes, 8%; monocytes, 2%; and eosinophils, 0%)
and C-reactive protein of 1.05 mg/dl. Chest radiography
showed bilateral patchy infiltrates in both lungs along
with cardiomegaly (Fig. 1A). Empirical intravenous antibiotics (ceftriaxone, 2.0 gm every 24 h; and ciprofloxacin, 400 mg every 12 h) were administered; however,
by day 2, the patients respiratory status deteriorated,
and he required intubation with mechanical ventilation.
A follow-up chest radiography showed mixed air space
and diffuse reticular opacification (Fig. 1B). Serologi117

Mycoplasma pneumoniae and bronchiolitis obliterans organizing pneumonia

Fig. 1 (A) Chest radiograph shows bilateral patchy infiltration in both lung fields and
cardiac enlargement. (B) Another chest radiograph 2 days later, shows diffuse
consolidation, which is worse than before. (C) Chest computed tomography
demonstrates diffuse bilateral air space opacifications, ground-glass appearance with air-bronchograms, interlobular septal thickening and peribronchial
thickening. (D) Chest radiograph shows marked improvement as compared with
previous study, but still reveals mild residual infiltration of both lower lobes and
cardiomegaly.

cal test for Legionella was negative. An enzyme-linked


immunosorbent assay test (ELISA) for Mycoplasma
pneumoniae IgM was positive, indicating a recent infection. Echocardiography demonstrated severe aortic valve
regurgitation, dilated left ventricle, normal wall motion,
and a left ventricle ejection fraction of 66%. The coexistence of Mycoplasma pneumoniae and chronic aortic
regurgitation-associated acute pulmonary edema were
diagnosed. The patient was treated with intravenous furosemide, intravenous nitroglycerin, and oral enalapril.
After 3 days, chest radiography continued to show bilateral patchy infiltrates in both lungs. Blood cultures, and
acid-fast staining of three sputum samples were negative.
We also checked Epstein-Barr virus IgM, cytomegalovirus IgM, human immunodeficiency virus 1 IgG and IgM,
influenza virus type A IgM, influenza virus type B IgM,
and serum cryptococcus antigen; but their results were
all negative. Antinuclear antibodies and rheumatoid factor were also negative. Complement levels, IgG, IgA and
IgM were within normal limits. Cultures of three sputum
samples on Lowenstein-Jensen medium were negative.
A computed tomography (CT) scan showed diffuse
bilateral air space opacifications and ground-glass appearance with air-bronchograms (Fig. 1C). A videoassisted thoracoscopic biopsy was therefore performed.
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Histological analysis of a biopsy specimen showed scattered fibroblastic plugs (Massonss bodies) of spindle
mesenchymal cells filling air spaces and obstructing
terminal bronchioles (Fig. 2). We therefore diagnosed
the patient with BOOP on 10th day of admission and discontinued the intravenous ceftriaxone and ciprofloxacin.
Systemic corticosteroid (methylprednisolone, 40 mg
intravenously every 12 h) was administered, and marked
clinical and radiological improvements were noted in 2
weeks. The steroid dosage was gradually reduced during
out-patient follow-up and tapered off after 6 months. At 6
months, follow-up of chest radiography showed marked
improvement of the pulmonary lesion (Fig. 1D).

DISCUSSION
We report a patient who developed increasing dyspnea and acute respiratory failure related to Mycoplasma
pneumoniae, with no improvement of clinical symptoms
and radiographic findings despite antibiotic treatment.
BOOP was documented by video-assisted thoracoscopic
lung biopsy and the subsequent course under corticoster-

Min-Chung Shen, et al.

Fig. 2 Hematoxylin and eosin stain, 200 X. The sections


show scattered fibroblastic plugs (Massonss bodies) of spindle mesenchymal cells filling air spaces
and obstructing terminal bronchioles. There are
fibrin deposition and chronic inflammation in the
surrounding parenchyma. These plugs have a typical elongated to serpinginous shape and are formed
by spindle to stellate fibroblasts embedded in a palestaining matrix, and clusters of foamy-macrophages,
a few scattered neutrophil, and thickening of the
alveolar septa.

oid therapy was satisfactory.


Clinically, the cause of BOOP cannot be determined.
It can be idiopathic, which is also termed cryptogenic
organizing pneumonia (COP), or it can accompany
several disorders, including connective tissue diseases;
drug- or radiation-induced injury; infections from bacteria, viruses, and parasites; toxic fumes inhalation; and
a variety of other systemic illnesses. BOOP associated
with autoimmune disorders, such as systemic lupus erythematous, rheumatoid arthritis, Sjogrens syndrome,
dermatomyositis, and inflammation bowel disease, has
been described.1,4-6 However, our patient showed no other
symptoms or signs of an underlying autoimmune disorder apart from the above mentioned autoantibodies. We
therefore attribute their occurrence to the Mycoplasma
pneumoniae infection as a consequence of a host immune
response to the infection. To the best of our knowledge,
this is the first documented case of Mycoplasma pneumoniae-associated BOOP in Taiwan.
The pathogenesis of BOOP involves damage of the
bronchiolar epithelial cells and recruitment of T lymphocytes and neutrophils to the site of injury; many inflammatory cytokines and chemokines are secreted, perpetuating the inflammatory response and leading to fibroblast

formation with obliteration of the airways.7 Infection was


a common cause of BOOP. Bacterial infection associated with organizing pneumonia happens mostly in nonresolving pneumonia. The inflammatory response still
progresses despite appropriate antibiotic treatment, and
therefore further organizes fibrous tissue plugs within the
alveoli and the airways.
Although multiple bilateral alveolar patchy opacities
are the most characteristic radiographic manifestations
of cryptogenic or secondary organizing pneumonia4,5,9,
focal opacities, nodules, cavities and unilateral opacities
have been reported.8,9 Clearly, chest radiography is the
first imaging technique performed in the examination
of patients with pneumonia or with pulmonary edema.
The most common radiographic findings of Mycoplasma
pneumoniae include unilateral or bilateral areas of airspace consolidation or ground-glass opacities. However,
the findings are variable and can include reticular or nodular opacities. Associated features include bronchial wall
thickening and, occasionally, small pleural effusions.10,11
The major radiographic findings of pulmonary edema
are combination of septal thickening and ground-glass
opacity, but septal thickening or ground-glass opacity
can predominate in individual cases.12 Crazy paving and
consolidation may also be seen. The radiographic findings of BOOP can mimic Mycoplasma pneumoniae and
pulmonary edema . Therefore, it is difficult to establish
the diagnosis by chest radiography or CT scan. The diagnosis of BOOP has usually been made by open lung
biopsy, especially if the clinical and radiographic features
are uncertain.
To further understand Mycoplasma pneumoniae associated with BOOP, we reviewed four cases in the literature and summarized their clinical features in Table
1, including respiratory symptoms, CxR, chest CT, time
to diagnosis, treatment and outcome. Dyspnea and fever
were major clinical manifestations. The radiologic patterns were diverse. Lung biopsy was performed because
of empiric antibiotic therapy failure. The reported patients improved rapidly both clinically and radiologically
within a few days after steroid treatment commenced;
except patient 3, who ameliorated rapidly after minocycline treatment. No relapses occurred when the dose was
tapered.
In conclusion, BOOP can follow pneumonia when
symptoms and radiographic changes persisted in spite of
treatment. Clinicians must be aware of this possibility
when patients have complicated Mycoplasma pneumoniae. Early diagnosis of BOOP is very important for its
dramatic response to steroid therapy.
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Mycoplasma pneumoniae and bronchiolitis obliterans organizing pneumonia

Table 1 Summary of reported cases of BOOP associated


with Mycoplasma pneumoniae infection in the
literature.13,14,15
Characteristics

Age (yr)/Sex

Patient number
1

57/F

39/M

Cough,
Respiratory
Cough,
symptoms dyspnea fever, dyspnea
fever
tachypnea

71/F

52/M

fever, malaise

Cough,
dyspnea,
fever,
tachypnea

Patchy and
A fine
nodular non-segmental
with
interstitial
pattern mixed alveolar
and interstitial
pattern

Mixed air
space and
diffuse
reticular
opacification

CxR

Bilateral,
migratory
patchy
infiltrates

Chest CT

Bilateral
airspace
consolidation

Diffuse
bilateral air space
opacifications
and
ground-glass
appearance
with air
bronchograms

Time to
diagnosis

1 month

3 days

10 days

Treatment

Steroid

Steroid

Minocycline

Steroid

Outcome

Recovered

Recovered

Recovered

Recovered

Key: , our patient; F, female; M, male; -, absent;

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