(Chest. 2001;120:674-678.)
© 2001
American College of Chest Physicians
TB or Not TB*
Cavitary Bronchiolitis Obliterans Organizing Pneumonia Mimicking Pulmonary Tuberculosis
Israel Heller, MD;
Simon Biner, MD;
Aharon Isakov, MD;
Yulia Kornitzky, MD;
Itzhak Shapira, MD;
Silvia Marmor, MD and
Marcel Topilsky, MD, FCCP
*
From the Department of Internal Medicine H and Pathology, Sourasky Tel Aviv Medical Center, and Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Correspondence to: Israel Heller MD, Department of Internal Medicine H, Sourasky Tel Aviv Medical Center, 6 Weizman St, Tel Aviv 64239, Israel; e-mail: iheller{at}tasmc.health.gov.il
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Abstract
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Two patients with subacute symptoms and signs compatible with
pulmonary tuberculosis (TB) had right upper lobe cavitary infiltrates
shown on chest radiography. In both patients, purified protein
derivative and microbiologic testing excluded TB, and tissue
examination yielded typical histologic changes of bronchiolitis
obliterans organizing pneumonia (BOOP). Glucocorticoid therapy led to
clinical and radiologic resolution. Though probably rare in this
situation, BOOP should be considered in the differential diagnosis of
patients presenting with clinical and radiologic features of pulmonary
TB.
Key Words: bronchiolitis obliterans organizing pneumonia • radiography, thoracic • tuberculosis, pulmonary
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Introduction
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Patients
with bronchiolitis obliterans organizing pneumonia (BOOP) present with
clinical and radiologic manifestations that are not specific to this
entity. Depending on the clinicoradiologic presentation, a number of
other diseases may have to be considered in the differential diagnosis
of BOOP. Tuberculosis (TB), however, is not usually included in this
differential diagnosis. We describe two patients who presented with
clinical and radiologic features suggestive of pulmonary TB but turned
out to have BOOP instead.
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Case Reports
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Case 1
A 66-year-old man was hospitalized with a 2-month history of
productive cough, anorexia, and weight loss. One month prior to
hospital admission, fever, night sweating, and malaise ensued. He had a
history of mild chronic obstructive lung disease and benign prostatic
hypertrophy. On hospital admission, the patient looked ill with a
temperature of 39°C and a regular pulse rate of 110 beats/min. BP was
140/85 mm Hg, and respiratory rate was 18 breaths/min. Tubular
breathing and rales were heard in the upper region of the right lung.
The physical examination was otherwise normal.
A chest radiograph (Fig 1
, top) showed a massive right upper lobe alveolar infiltrate
with multicavitary lesions. CT of the chest (Fig 1
, bottom)
performed at the same time showed a "Swiss cheese" alveolar
infiltrate with multiple cavities in the posterior segment of the right
upper lobe.
The erythrocyte sedimentation rate (ESR) was 14 mm/h. With the
exception of mild normocytic anemia (hemoglobin, 11.7 g/dL) and a
thrombocyte count of 585,000/µL, all routine laboratory test results,
including a CBC count, liver and kidney function tests, serum proteins,
and urinalysis, were normal. Blood, sputum, and urine culture findings
were negative.
Sputum examination results for microorganisms including acid-fast
bacilli were repeatedly negative. Results of purified protein
derivative skin test and polymerase chain reaction of the sputum for
Mycobacterium tuberculosis were negative. Serologic test
results for Mycoplasma, Legionella, cytomegalovirus, Candida,
Aspergillus, and Nocardia were negative. Antinuclear antibodies and
antineutrophil cytoplasmic antibodies (ANCAs) were not found.
Bronchoscopy revealed diffuse inflammatory bronchial changes. No
bacteria, acid-fast bacilli, or fungi were seen in the bronchial
secretions, and culture findings for TB organisms were negative.
Treatment with IV cefuroxime and erythromycin did not improve the
patient’s condition. Transbronchial biopsy (Fig 2
) showed myxoid fibroblastic tissue and intrabronchiolar aggregates of
mononuclear cells invading alveolar spaces. These findings were
considered to be consistent with BOOP.
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Figure 2.. Transbronchial biopsy from patient 1 shows
ramifying masses of myxomatous connective tissue extending from
bronchioles along alveolar ducts into alveoli. Mild inflammation of the
alveolar wall is present (hematoxylin-eosin, original x 200).
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Treatment with prednisone was started at a dosage of 60 mg/d. Rapid
lysis of the fever resulted. Within a few days, the other symptoms
regressed as well. The patient was discharged receiving prednisone, 60
mg/d with slow tapering, and was followed up in the outpatient clinic.
Six months later, he was asymptomatic, and a chest radiograph (Fig 3
) showed only moderately severe hyperinflation and minimal residual
infiltrate in the right apex.
Case 2
Ten weeks after the hospital admission of Case 1, a 76-year-old
man was admitted to the hospital for progressive dyspnea, pleuritic
pain, and malaise of 1-month duration. Cough, fever, and increased
sweating were denied. Medical history consisted of peptic disease,
diaphragmatic hernia, heavy smoking, and stable ischemic heart disease.
On hospital admission, the patient was cachectic, with no fever,
pallor, or cyanosis. Respiratory rate was 30 breaths/min, BP was 150/65
mm Hg, and the pulse rate was 88 beats/min. Rales were heard in the
right apical region of the lungs, the examination findings being
otherwise unremarkable. The ESR was 70 mm/h, a leukocyte count showed
13,200 cells/µL, and the serum albumin level was 3.0 g/dL. Findings
of all other routine laboratory tests were normal.
A chest radiograph (Fig 4
, top) showed severe hyperinflation, and alveolar and
interstitial infiltration involving mainly the right upper lobe, with
multiple cavities. CT of the chest (Fig 4
, bottom)
demonstrated severe bullous emphysema with massive alveolar
infiltration and multiple cavities. Treatment with IV cefuroxime and
erythromycin was started.
Results of sputum examinations, including Ziehl-Nielsen preparations,
were negative, as were a skin tuberculin test and cultures of the
blood, sputum, and urine. As in the first case, serology findings for
infectious etiologies were negative. The result of testing for
antinuclear antibodies was weakly positive, and cytoplasmic ANCA
findings were positive, at a low titer of 1:20.
Copious purulent secretions were seen on bronchoscopy, which
microscopically showed few Gram-negative and Gram-positive bacteria and
no acid-fast bacilli or fungi. Culture of these secretions grew
Pseudomonas aeruginosa but was negative for mycobacteria.
When the result of the sputum culture became available, treatment with
cefuroxime was switched to ciprofloxacin. There was no clinical
response to antibiotic therapy.
A transbronchial biopsy (Fig 5
) was diagnostic of BOOP, showing findings similar to those described in
the first case. Treatment with antibiotics was discontinued, and
prednisone, 60 mg/d, was started. This led to rapid clinical
improvement, and the patient was discharged 4 days after initiation of
treatment without fever or dyspnea. One month later, he was readmitted
to the hospital with epigastric distress. His respiratory symptoms had
disappeared and, other than his abdominal complaint, he was well. A
chest radiograph (Fig 6
) showed mild-to-moderate improvement of the right upper lobe findings
seen at the time of the previous hospital admission. Famotidine, 40 mg
bid, was administered with good clinical response, and the patient was
again discharged. Two weeks later, despite medical advice to the
contrary, the patient discontinued prednisone and was unavailable for
follow-up.
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Figure 5.. Transbronchial biopsy from Case 2 shows organizing
pneumonia, again with mild inflammation of the alveolar wall, and
patchy rounded masses of characteristic myxomatous connective tissue
(hematoxylin-eosin, original x 200).
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Discussion
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The main differential diagnosis of cavitary lung infiltrates
includes pyogenic abscess from a variety of bacterial organisms,
pulmonary TB, fungal infection, and parasitic disease of the lungs.
In addition to these infectious sources, pulmonary cavities have been
well documented in patients with primary or secondary malignancies,
collagen disease, Wegener granulomatosis, and less frequently other
vasculitides. Rarely, lymphoma, sarcoidosis, and cysts may also present
in this fashion.1
Our two patients presented with cavitary infiltrates that were confined
to the right upper lobe. This radiologic pattern, especially when
accompanied by compatible clinical manifestations as in these patients,
suggests TB rather than most of the other diagnostic contenders listed
above. Pulmonary TB was therefore the working diagnosis in both
patients at hospital admission. Testing results for TB were negative,
however, and tissue biopsy demonstrated BOOP.
The clinical manifestations of BOOP2
can account for all
of the complaints our two patients presented with. Cough, dyspnea,
fever, night sweating, and weight loss are all common in this entity,
being observed in 
50% of the cases at presentation. Pleuritic pain
occurs in one of four patients with BOOP. An ESR > 60 mm/h is seen in
40% of patients, and leukocytosis in seen in 50% of the patients at
presentation. Thrombocytosis, which we observed in our first patient,
has been described in 20% of cases.
In addition to its cryptogenic variant, BOOP may be associated with
conditions such as pulmonary infection or tumor, collagen disease,
hematologic malignancy, vasculitis, hypersensitivity
reactions, and other rare diseases.3
No evidence for
any of these was found in our first patient, who therefore
qualifies for a diagnosis of cryptogenic BOOP.
Two points need clarification with regard to the second case. First,
other than the pulmonary infiltrates, no additional cardinal features
of Wegener granulomatosis were present and findings characteristic of
this disorder were not seen on biopsy. Thus, the low titer of classic
pattern ANCA in this case was considered a false-positive finding.
Secondly, the patient’s clinical presentation, as well as his response
to steroids after adequate antibiotic therapy had failed,
do not suggest Pseudomonas pneumonia, and a MEDLINE search identified
only one description4
of BOOP associated with this
organism. We therefore believed that the positive culture result could
be yet another incidental finding, but a remote possibility remains
that in this case BOOP developed from a Pseudomonas pneumonia.
BOOP may present with a variety of radiologic patterns, including
multiple patchy alveolar infiltrates, diffuse interstitial infiltrates,
solitary opacities that may sometimes resemble tumors,2
and rarely other patterns.5
Although cavitary infiltrates
are not usually included in textbook descriptions of the disease, BOOP
presenting with cavitating infiltrates has indeed been described,
albeit rather rarely. Two of the 42 cases of cryptogenic BOOP in the
series published by Epler et al5
in 1985 appear to
represent the earliest mention of a cavitary radiologic pattern in this
disorder. Several additional cases6
7
8
9
10
demonstrate that
this pattern occurs in the cryptogenic form of BOOP, as well as in BOOP
associated with disorders such as essential mixed
cryoglobulinemia11
and lymphoma.12
In view of these cases, Cordier13
in a recent editorial
stressed that BOOP must be included in the differential diagnosis of
cavitary lung disease. However, only one of the patients described to
date presented with upper lobe cavitation,14
and, to our
knowledge, there are no descriptions of BOOP actually mimicking TB in
both its clinical and radiologic aspects. Our two patients presented
with subacute symptoms and radiologic findings characteristic of
pulmonary TB. When this strong first impression could not be
corroborated by laboratory test results, the diagnosis of BOOP by
tissue examination was surprising. In our view, this course
of events proves that BOOP not only presents sometimes with cavitary
disease but may also resemble, both clinically and radiologically,
typical pulmonary TB, a possibility not emphasized in the literature.
Whether this is a very rare occurrence or, as might be suggested by the
short interval in which these two cases presented, a more common
phenomenon, remains to be seen.
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Footnotes
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Abbreviations: ANCA = antineutrophil cytoplasmic
antibody; BOOP = bronchiolitis obliterans organizing pneumonia; ESR =
erythrocyte sedimentation rate; TB = tuberculosis
Received for publication March 10, 2000.
Accepted for publication February 20, 2001.
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References
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Swartz, MN (1998) Approach to the patient with pulmonary infections. Fishman, AP eds. Pulmonary diseases and disorders ,1915-1916 McGraw-Hill New York, NY.
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Lohr, RH, Boland, BJ, Douglas, WW, et al (1997) Organizing pneumonia: features and prognosis of cryptogenic, secondary and focal variants. Arch Intern Med 157,1323-1329[Abstract]
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Miller, RF, Pugsley, WB, Griffiths, MH (1995) Open lung biopsy for investigation of acute respiratory episodes in patients with HIV infection and AIDS. Genitourin Med 71,280-285[ISI][Medline]
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Epler, RG, Colby, TV, McLoud, TC, et al (1985) Bronchiolitis obliterans organizing pneumonia. N Engl J Med 312,152-158[Abstract]
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Froudarakis, M, Bouros, D, Loire, R, et al (1995) BOOP presenting with hemoptysis and multiple cavitary nodules. Eur Respir J 8,1972-1974[Abstract]
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Cordier, JF, Loire, R, Brune, J (1989) Idiopathic bronchiolitis obliterans organizing pneumonia: definition of characteristic clinical profiles in a series of 16 patients. Chest 96,999-1004[Abstract/Free Full Text]
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Zackrison, LH, Katz, P (1993) Bronchiolitis obliterans organizing pneumonia associated with essential mixed cryoglobulinemia. Arthritis Rheum 36,1627-1630[ISI][Medline]
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Safadi, R, Berkman, N, Haviv, YS, et al (1997) Primary non-Hodgkin’s lymphoma of the lung presenting as bronchiolitis obliterans organizing pneumonia. Leuk Lymphoma 28,209-213[ISI][Medline]
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Cordier, JF (1995) Cavitary bronchiolitis obliterans organising pneumonia [editorial]. Eur Respir J 8,1822-1823[Medline]
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Alegre-Martin, J, Fernandez de Sevilla, T, Garcia, F, et al (1991) Three cases of idiopathic bronchiolitis obliterans with organising pneumonia. Eur Respir J 4,902-904[Abstract]
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Abstract
Introduction
