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Bronchocentric granulomatosis and adult respiratory distress syndrome
Br.
J. Dis.
Chest
(1982)
74, 184
BRONCHOCENTRIC GRANULOMATOSIS AND ADULT RESPIRATORY DISTRESS SYNDROME ALAN Barlow
Hospital
for
S. RROOKER AND OM P. SHARMA
Respiratory Los
Diseases and University Angeles, California, USA
of Southern
California,
Summary \Ve describe a case of bronchocentric granulomatosis in a young woman with several diffuse interstitial unusual features. She developed spontaneous pneumothoraces, infiltrates and the adult respiratory distress syndrome during the course of her illness. A pathological diagnosis was not made until treatment with corticosteroids had led to a marked improvement in the patient’s condition and an open lung biopsy was performed.
Bronchocentric granulomatosis is a recent addition to a long and rapidly growing list of pulmonary hypersensitivity reactions (Liebow 1973). The diagnosis is based upon the recognition of palisading granulomatous reaction under and replacing the bronchial epithelium in small and medium-sized airways. Angiitis may occur but is not a prominent feature. The disease has a favourable outcome. We recently treated a young woman with bronchocentric granulomatosis who developed spontaneous pneumothoraces, acute respiratory failure and the adult respirttory tract symptoms.
Case Report A 27-year old woman was admitted to hospital with a three-day history of coryza, malaise, headache, non-productive cough and a fever of 38.9 C. Two weeks before admission she was given sulphamethoxazolc and doxycycline for a urinary tract infection. Otherwise, her past medical history was unremarkable. There was no history of atopy in the family. Examination revealed a temperature of 37.8’ C and bilateral lower zone riles. A chest radiograph revealed a normal size heart and rcticulonodular infiltrates, which were most prominent in the right lower lung field (Fig. 1). The haemoglobin level was 13.3 g/dl. The white blood cell count was 8600/mms with 90:; neutrophils, 9:,\ lymphocytes and 1”” monocytcs. She was given penicillin, doxycycline and supplemental oxygen, but three days later developed severe respiratory distress and collapsed. A chest radiograph revealed bilateral pneumothoraces but because of an inability to maintain the Paoz and of a rising Pacos, assisted ventilation was begun. The penicillin and doxycycline were discontinued and ampicillin and gentamicin started. A sputum culture grew Escherichia coli.
A. S. Booker
and Om P. Sharma
On the seventh hospital day a transbronchial biopsy specimen was obtained which revealed hyaline membrane formation. Hydrocortisone was begun. On the nineteenth hospital day she was transferred to the University of Southern California-Los Angeles County Medical Center. Blood pressure was then 124/80 mmHg; pulse rate 88/minute; temperature 37.6 C; and respiratory rate 18/minute. There were no rashes or lymphadenopathy. Auscultation of the lungs revealed decreased breath sounds on the left and scattered rLles and rhonchi bilaterally. A chest radiograph showed bilateral alveolar and interstitial infiltrates, subcutaneous emphysema and a left pneumothorax.
Fig. 1. Chest
radiograph
on
admission
shows
bilateral
reticulonodular
infiltrates
most
prominent
in the bases The white cell count was 18 20O/mms with 82y0 segmented neutrophils, 4:; band forms, 8”,, lymphocytes, lyO monocytes and 20,d eosinophils. The platelets were normal and tests for rheumatoid factor, cold agglutinins and antinuclear antibodies were negative. The serological tests for toxoplasmosis and Legionnaire’s disease were coccidioidomycosis, histoplasmosis, psittacosis, non-diagnostic. Arterial blood gases on intermittent mandatory ventilation with an Fios=0.6 and 5 cm HsO of PEEP revealed a pH of 7.49, a Paos of 56 mmHg (7.45 kPa) and a Paces of erythromycin and hydrocortisone. A repeat 34 mmHg (4.65 kPa). She was given tetracycline, transbronchial lung biopsy showed a few alveoli with non-specific inflammatory reaction. Over the next 12 days her condition improved and she was weaned from mechanical ventilation. The hydrocortisone dosage was reduced and with decreasing doses the eosinophil count in the was performed. peripheral blood was noted to rise to 1 SOO/mm 3. An open lung biopsy
Bronchocentr%- Granulomatosis and Adult Respiratolry Distress Syndrome
191
icroscopic examination of the resected lung tissue re\,ealed granulomata in areas of ela stic e, as demonstrated by special stains, and it was felt that this elastic tissue was representat tive vnchioles which had been destroyed by this necrotizing granulomatous process (Figs 2, 3). :ulture the lung biopsy tissue did not grow any bacteria, acid-fast bacilli or fungi.
Fig.
with
17. Lung luminal
biopsv. occlusion
Fig. .?. Lung biopsy. damag:ed multi-laminated
There is cxuherant (arrows). X 400
Destruction elastic
of the lamcllae
granulomatous
hronchiolar (arrows).
replacement
wall is evidenced x 400
of
the
bronchiolar
by giant
cell
muc
reaction
osa
with
192
A. S. Brooker and Om P. Skarma DISCUSSION
Katzenstein et al. (1975) d escribed 23 cases of bronchocentric granulomatosis, the histological features of which were similar to that of our patient. Numerous necrotic granulomata, bronchocentric in nature, were seen along with some bronchioles which could only be discerned through the use of elastic stains. We have failed to find reports of another case with a fulminant course characterized by profound hypoxaemia, decreased lung compliance and interstitial hyaline membrane formation. At no time in the early stages was our patient shocked or hypotensive and there was no good evidence of severe pulmonary infection. Most of Katzenstein’s patients exhibited a radiographic pattern of lobar or sublobar consolidation, atelectasis or patchy pneumonic infiltration, but a few had mass-like lesions, nodular and linear densities. Three-quarters had unilateral radiographic findings but, in contrast to our patient, there were no cases of diffuse interstitial or alveolar infiltration. Our patient differed from those of Katzenstein et al. in several other ways. Pneumothorax was not seen in their patients, nor has it been reported since. Only two of their non-asthmatic patients developed mild eosinophilia but our patient, who had no prior history of atopy or asthma, developed eosinophilia up to 1500/mms. The clinical course of our patient was markedly different from the generally benign course noted in others. Finally, multiple transbronchial biopsies failed to reveal the nature of the disease and it was not until an open lung biopsy was performed, much later in the course, that the diagnosis was made. This, once again, demonstrates the need for aggressive biopsy procedures in the face of progressive, diffuse lung disease of unknown aetiology. The aetiology of bronchocentric granulomatosis remains obscure, but the finding of fungal organisms in the lungs of asthmatics with this disease (Hanson et al. 1977) invites speculation that it may be a type of allergic reaction to these fungi. This association is not clearly seen in the non-asthmatic patient, however, and in our patient no fungal elements were seen in the resected lung tissue. Our patient had received sulphonamides before admission and sulphonamides have been reported to cause a vasculitis of the granulomatous type (Rosenow 1972) but these granulomata are angiocentric rather than bronchocentric. Sulphonamides have also been reported to produce pulmonary infiltration with eosinophilia but bronchocentric granulomata are not seen in this disorder either and it seems unlikely that the sulphonamide was an aetiological agent in our patient’s illness. In summary, we have described a patient with bronchocentric granulomatosis in whom the disease pursued an unusual and fulminant course. We suggest that bronchocentric granulomatosis be added to the burgeoning list of disorders which may on occasion be associated with the adult respiratory distress syndrome.
ACKNOWLEDGEMENTS
The authors wish to acknowledge the assistance of Dr John Gmelich and Dr Shanti Sahgal in the interpretation of pathological material. Thanks are due to Mr Andy Gero for the photography. This work was supported by a grant from the Tuberculosis and Respiratory Disease Association of California.
Bronchocentric Granulomatosis and Adult Respiratory Distress Syndrome
193
REFEREKCES LIEBOW, A. A. (1973) The J. Burns Amberson lecture-pulmonary angiitis and granulomatosis. Am. Rev. resp. Dis. 108, 1. KATZENSTEIN, A. L., LIEBOW, A. A. & FRIEDMAN, I’. J. (1975) B ronchocentric granulomatosis, mucoid impaction, and hypersensitivity reactions to fungi. Am. Rea. resp. Dis. 111, 497. HANSON, G., FLOD, X., WELLS, I. COVEY, H. & GALANT, S. (1977) B ronchocentric granulomatosis : A complication of allergic bronchopulmonary aspergillosis. J. Allergy din. Immunol. 59, 83. ROSENOW, E. C. III (1972) The spectrum of drug induced pulmonary disease. Ann. intern. Med. 77, 977.
17
J. Dis.
Chest
(1982)
74, 184
BRONCHOCENTRIC GRANULOMATOSIS AND ADULT RESPIRATORY DISTRESS SYNDROME ALAN Barlow
Hospital
for
S. RROOKER AND OM P. SHARMA
Respiratory Los
Diseases and University Angeles, California, USA
of Southern
California,
Summary \Ve describe a case of bronchocentric granulomatosis in a young woman with several diffuse interstitial unusual features. She developed spontaneous pneumothoraces, infiltrates and the adult respiratory distress syndrome during the course of her illness. A pathological diagnosis was not made until treatment with corticosteroids had led to a marked improvement in the patient’s condition and an open lung biopsy was performed.
Bronchocentric granulomatosis is a recent addition to a long and rapidly growing list of pulmonary hypersensitivity reactions (Liebow 1973). The diagnosis is based upon the recognition of palisading granulomatous reaction under and replacing the bronchial epithelium in small and medium-sized airways. Angiitis may occur but is not a prominent feature. The disease has a favourable outcome. We recently treated a young woman with bronchocentric granulomatosis who developed spontaneous pneumothoraces, acute respiratory failure and the adult respirttory tract symptoms.
Case Report A 27-year old woman was admitted to hospital with a three-day history of coryza, malaise, headache, non-productive cough and a fever of 38.9 C. Two weeks before admission she was given sulphamethoxazolc and doxycycline for a urinary tract infection. Otherwise, her past medical history was unremarkable. There was no history of atopy in the family. Examination revealed a temperature of 37.8’ C and bilateral lower zone riles. A chest radiograph revealed a normal size heart and rcticulonodular infiltrates, which were most prominent in the right lower lung field (Fig. 1). The haemoglobin level was 13.3 g/dl. The white blood cell count was 8600/mms with 90:; neutrophils, 9:,\ lymphocytes and 1”” monocytcs. She was given penicillin, doxycycline and supplemental oxygen, but three days later developed severe respiratory distress and collapsed. A chest radiograph revealed bilateral pneumothoraces but because of an inability to maintain the Paoz and of a rising Pacos, assisted ventilation was begun. The penicillin and doxycycline were discontinued and ampicillin and gentamicin started. A sputum culture grew Escherichia coli.
A. S. Booker
and Om P. Sharma
On the seventh hospital day a transbronchial biopsy specimen was obtained which revealed hyaline membrane formation. Hydrocortisone was begun. On the nineteenth hospital day she was transferred to the University of Southern California-Los Angeles County Medical Center. Blood pressure was then 124/80 mmHg; pulse rate 88/minute; temperature 37.6 C; and respiratory rate 18/minute. There were no rashes or lymphadenopathy. Auscultation of the lungs revealed decreased breath sounds on the left and scattered rLles and rhonchi bilaterally. A chest radiograph showed bilateral alveolar and interstitial infiltrates, subcutaneous emphysema and a left pneumothorax.
Fig. 1. Chest
radiograph
on
admission
shows
bilateral
reticulonodular
infiltrates
most
prominent
in the bases The white cell count was 18 20O/mms with 82y0 segmented neutrophils, 4:; band forms, 8”,, lymphocytes, lyO monocytes and 20,d eosinophils. The platelets were normal and tests for rheumatoid factor, cold agglutinins and antinuclear antibodies were negative. The serological tests for toxoplasmosis and Legionnaire’s disease were coccidioidomycosis, histoplasmosis, psittacosis, non-diagnostic. Arterial blood gases on intermittent mandatory ventilation with an Fios=0.6 and 5 cm HsO of PEEP revealed a pH of 7.49, a Paos of 56 mmHg (7.45 kPa) and a Paces of erythromycin and hydrocortisone. A repeat 34 mmHg (4.65 kPa). She was given tetracycline, transbronchial lung biopsy showed a few alveoli with non-specific inflammatory reaction. Over the next 12 days her condition improved and she was weaned from mechanical ventilation. The hydrocortisone dosage was reduced and with decreasing doses the eosinophil count in the was performed. peripheral blood was noted to rise to 1 SOO/mm 3. An open lung biopsy
Bronchocentr%- Granulomatosis and Adult Respiratolry Distress Syndrome
191
icroscopic examination of the resected lung tissue re\,ealed granulomata in areas of ela stic e, as demonstrated by special stains, and it was felt that this elastic tissue was representat tive vnchioles which had been destroyed by this necrotizing granulomatous process (Figs 2, 3). :ulture the lung biopsy tissue did not grow any bacteria, acid-fast bacilli or fungi.
Fig.
with
17. Lung luminal
biopsv. occlusion
Fig. .?. Lung biopsy. damag:ed multi-laminated
There is cxuherant (arrows). X 400
Destruction elastic
of the lamcllae
granulomatous
hronchiolar (arrows).
replacement
wall is evidenced x 400
of
the
bronchiolar
by giant
cell
muc
reaction
osa
with
192
A. S. Brooker and Om P. Skarma DISCUSSION
Katzenstein et al. (1975) d escribed 23 cases of bronchocentric granulomatosis, the histological features of which were similar to that of our patient. Numerous necrotic granulomata, bronchocentric in nature, were seen along with some bronchioles which could only be discerned through the use of elastic stains. We have failed to find reports of another case with a fulminant course characterized by profound hypoxaemia, decreased lung compliance and interstitial hyaline membrane formation. At no time in the early stages was our patient shocked or hypotensive and there was no good evidence of severe pulmonary infection. Most of Katzenstein’s patients exhibited a radiographic pattern of lobar or sublobar consolidation, atelectasis or patchy pneumonic infiltration, but a few had mass-like lesions, nodular and linear densities. Three-quarters had unilateral radiographic findings but, in contrast to our patient, there were no cases of diffuse interstitial or alveolar infiltration. Our patient differed from those of Katzenstein et al. in several other ways. Pneumothorax was not seen in their patients, nor has it been reported since. Only two of their non-asthmatic patients developed mild eosinophilia but our patient, who had no prior history of atopy or asthma, developed eosinophilia up to 1500/mms. The clinical course of our patient was markedly different from the generally benign course noted in others. Finally, multiple transbronchial biopsies failed to reveal the nature of the disease and it was not until an open lung biopsy was performed, much later in the course, that the diagnosis was made. This, once again, demonstrates the need for aggressive biopsy procedures in the face of progressive, diffuse lung disease of unknown aetiology. The aetiology of bronchocentric granulomatosis remains obscure, but the finding of fungal organisms in the lungs of asthmatics with this disease (Hanson et al. 1977) invites speculation that it may be a type of allergic reaction to these fungi. This association is not clearly seen in the non-asthmatic patient, however, and in our patient no fungal elements were seen in the resected lung tissue. Our patient had received sulphonamides before admission and sulphonamides have been reported to cause a vasculitis of the granulomatous type (Rosenow 1972) but these granulomata are angiocentric rather than bronchocentric. Sulphonamides have also been reported to produce pulmonary infiltration with eosinophilia but bronchocentric granulomata are not seen in this disorder either and it seems unlikely that the sulphonamide was an aetiological agent in our patient’s illness. In summary, we have described a patient with bronchocentric granulomatosis in whom the disease pursued an unusual and fulminant course. We suggest that bronchocentric granulomatosis be added to the burgeoning list of disorders which may on occasion be associated with the adult respiratory distress syndrome.
ACKNOWLEDGEMENTS
The authors wish to acknowledge the assistance of Dr John Gmelich and Dr Shanti Sahgal in the interpretation of pathological material. Thanks are due to Mr Andy Gero for the photography. This work was supported by a grant from the Tuberculosis and Respiratory Disease Association of California.
Bronchocentric Granulomatosis and Adult Respiratory Distress Syndrome
193
REFEREKCES LIEBOW, A. A. (1973) The J. Burns Amberson lecture-pulmonary angiitis and granulomatosis. Am. Rev. resp. Dis. 108, 1. KATZENSTEIN, A. L., LIEBOW, A. A. & FRIEDMAN, I’. J. (1975) B ronchocentric granulomatosis, mucoid impaction, and hypersensitivity reactions to fungi. Am. Rea. resp. Dis. 111, 497. HANSON, G., FLOD, X., WELLS, I. COVEY, H. & GALANT, S. (1977) B ronchocentric granulomatosis : A complication of allergic bronchopulmonary aspergillosis. J. Allergy din. Immunol. 59, 83. ROSENOW, E. C. III (1972) The spectrum of drug induced pulmonary disease. Ann. intern. Med. 77, 977.
17