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case records of the massachusetts general hospital

Founded by Richard C. Cabot Nancy Lee Harris, m.d., Editor Jo-Anne O. Shepard, m.d., Associate Editor Sally H. Ebeling, Assistant Editor

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Case 9-2005: A 67-Year-Old Man with Acute Respiratory Failure

David M. Systrom, M.D., and Conrad Wittram, M.B., Ch.B.

presentation of case
From the Departments of Pulmonary and Critical Care (D.M.S.) and Radiology (C.W.), Massachusetts General Hospital; and the Departments of Medicine (D.M.S.) and Radiology (C.W.), Harvard Medical School. N Engl J Med 2005;352:1238-46.
Copyright 2005 Massachusetts Medical Society.

A 67-year-old man was transferred to this hospital with acute respiratory failure. Four days before admission, the patient had visited his primary care physician because of a three-month history of chest congestion and cough productive of sputum that was initially clear but then became more opaque. His chest felt tight when he breathed deeply, and deep inspirations triggered the cough. During the week before the physician visit, he had had slight nasal congestion, poor appetite, and decreased energy, but no fever, chills, nocturnal sweats, or postnasal drip. His physician obtained a chest radiograph, which showed increased markings at the base of the right lung; a computed tomographic (CT) scan of the chest was recommended. A combination inhaler consisting of salmeterol and fluticasone was prescribed. Over the next 24 hours, severe pleuritic chest pain developed, with productive cough and severe shortness of breath. The patient went to the emergency department of another hospital. On examination there, he was alert and afebrile, with a respiratory rate of 24 breaths per minute and somewhat labored breathing. Pulse oximetry showed an oxygen saturation of 86 percent while he was breathing ambient air. Bilateral rales were heard on examination of the lungs although chest pain prevented deep inspiration but no wheezing. The remainder of the physical examination was unremarkable. A chest radiograph showed opacifications that now involved the left lower lobe, in addition to those previously seen in the right middle and lower lobes. His white-cell count was 17,800 per cubic millimeter, with 74 percent neutrophils and 7 percent band forms; the hematocrit was 32.9 percent. The levels of serum electrolytes and cardiac enzymes and the results of tests of liver and renal function were all within normal ranges. He was admitted to the intensive care unit. Two chest radiographs over the next 24 hours showed progressive worsening of the opacifications to include both upper lobes. The patients respiratory rate increased, his dyspnea worsened, and his oxygen saturation dropped to 76 percent while he was breathing 100 percent oxygen with the use of a face mask; the trachea was intubated, and he was placed on ventilator support. Treatment with levofloxacin was begun, but as his condition deteriorated the antibiotic agents were changed to ceftriaxone and azithromycin, and he received two doses each of tetracycline and erythromycin. A spu-

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case records of the massachusetts general hospital

tum culture grew normal flora, and two blood cultures showed no growth. He was transferred to the intensive care unit at this institution. The patient had a history of gastroesophageal reflux disease and chronic back pain, for which he took esomeprazole and rofecoxib. He had had an appendectomy, bilateral inguinal hernia repairs, a transurethral resection of the prostate, and removal of benign colon polyps. He was married with two children. He was a retired engineer who had worked in a metal machine shop. He had no known toxic exposures, although he recalled a coworker becoming very ill from an undefined respiratory illness in the 1970s. He had never smoked and rarely drank alcohol. He had not traveled outside the United States nor had he been in contact with anyone who had traveled recently. He swam regularly to help with his back pain. He had recently rewired his daughters attic, but had not been exposed to excessive dust or mold. He had no pets and did not hunt. His wife reported that several weeks before the onset of this illness, he had been exposed to bird droppings when he was changing an outdoor bird feeder and a gust of wind blew the droppings into his face. The temperature was 36.7C, the blood pressure 113/54 mm Hg, and the pulse 79 beats per minute. The oxygen saturation was 97 percent with the fraction of inspired oxygen at 0.5. On physical examination, he was a well-developed man, who was intubated and sedated. The results of an examination of the head, eyes, ears, nose, and throat were unremarkable. Auscultation of the lungs disclosed diminished breath sounds throughout both lungs with bronchial breath sounds at the bases. An examination of the heart, abdomen, and extremities disclosed no abnormalities. The white-cell count was 13,900 per cubic millimeter; the hematocrit was 26.1 percent. A chest radiograph obtained with portable equipment showed bilateral air-space consolidation, more on the left than the right, and a probable left pleural effusion. An electrocardiogram showed no abnormalities. Bronchoscopy and bronchoalveolar lavage were performed. Thin secretions were noted and the sputum was not grossly purulent. The lavage fluid contained 367 white cells per cubic millimeter, with 53 percent neutrophils, 21 percent lymphocytes, 4 percent monocytes, and 1 percent eosinophils. Doxycycline and levofloxacin were administered. On the second and third hospital days, chest radiographs showed no change. The patient remained

afebrile. Cultures of blood and urine and nasal and rectal secretions were negative for bacteria, including pneumocystis and legionella; chlamydia and mycoplasma were not detected by polymerase chain reaction. There were no antigens of adenovirus or influenza, parainfluenza, or respiratory syncytial virus. The results of fungal and mycobacterial cultures were pending. Serologic-test results are shown in Table 1. On the third day, the oxygen-saturation percentages improved, and the trachea was extubated; the oxygen saturation was 99 percent while the patient was breathing 40 percent oxygen by face mask. On the fourth day, he was transferred to the general medical service. On the fifth hospital day, a chest radiograph showed slight improvement in the bilateral air-space opacifications, particularly in the left upper lobe. His condition continued to improve, and he was discharged on the sixth hospital day. Three days after discharge, fever up to 38.9C, increased shortness of breath, and cough developed after the patient had been sitting in his hot tub. He was readmitted to the other hospital, where his symptoms rapidly abated, and he was discharged af-

Table 1. Results of Serologic Tests. Test Varicella antibody Serum cryptococcal antigen Histoplasma capsulatum urine antigen Chlamydia psittaci antibody Q fever antibody Aspergillus fumigatus 3 antibody A. fumigatus 6 antibody Thermoactinomyces sacchari antibody T. candidus T. vulgaris antibody Streptococcus viridans antibody Micropolyspora faeni antibody Pigeon serum antibody Enzyme-linked immunoassay for human immunodeficiency virus Cold agglutinins Blastomycosis complement-fixation (CF) test Coccidioidomycosis CF test Histoplasmosis CF test: yeast antigen Histoplasmosis CF test: histoplasmin antigen Result Positive IgG Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Nonreactive at 1:16 titer Negative Negative Positive 1:16 titer Negative

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ter several days. One month later, he was seen at a follow-up appointment at the infectious disease clinic of this hospital. He reported that he routinely treated the hot tub with bromine. He had had no further recurrence of respiratory symptoms and had resumed his exercise regimen. CT scanning of the chest showed diffuse ground-glass opacifications with a few secondary pulmonary lobules that had been spared and that may have represented a minor degree of air trapping. On high-resolution CT, centrilobular nodules were seen, which predominantly affected the upper lobes diffusely and the middle, lingular, and lower lobes more peripherally. No mediastinal lymphadenopathy or pleural disease was present. The results of a diagnostic test were reported.

differential diagnosis
Dr. David M. Systrom: May we review the chest radiographs, please? Dr. Conrad Wittram: The first chest radiograph shows that the patient is intubated and has a nasogastric tube. There is bilateral diffuse ground-glass opacification with consolidation affecting the left upper and right lower lobes. The left hemidiaphragm is obscured, indicating collapse of the left lower lobe, and a small amount of left-sided pleural fluid is present (Fig. 1A). A radiograph obtained on the fifth hospital day shows clearing of the opacity in the left upper lobe. There are linear opacities within the right lower lobe suggesting subsegmental atelectasis. The left lower lobe has partially reexpanded; there appears to be some consolidation within the middle lobe laterally, and there are small bilateral pleural effusions (Fig. 1B). The high-resolution CT scan performed one month later shows centrilobular ground-glass opacities within the upper lobes, some of which form a rosette pattern (Fig. 2). Some secondary pulmonary lobules have been spared. Dr. Systrom: This previously healthy mans respiratory illness developed first in a subacute phase, followed by a fulminant phase. Important clinical and laboratory clues to the differential diagnosis include the rapid and apparently spontaneous resolution of hypoxemic respiratory failure, certain environmental exposures, and the results of bronchoalveolar lavage. The high-resolution CT scan of the

Figure 1. Chest Radiographs Obtained on the First and Fifth Hospital Days. On the first hospital day, the patient is intubated and there is a nasogastric tube (Panel A). There is bilateral diffuse ground-glass opacification with consolidation affecting the left upper and right lower lobes. The left hemidiaphragm is obscured, indicating collapse of the left lower lobe. There is a small amount of left-sided pleural fluid. On the fifth hospital day, there is improvement of the diffuse ground-glass opacification and the left upper lobe consolidation (Panel B). A new patch of ground-glass opacification is present in the right upper lobe. A small region of ground-glass opacification persists. Subsegmental atelectasis affects both lower lobes, worse on the left. The left lower lobe collapse appears to have improved. Opacification of the middle lobe appears marginally worse laterally, which may be related to consolidation or atelectasis. There are small bilateral pleural effusions.

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case records of the massachusetts general hospital

pulmonary edema

Figure 2. High-Resolution CT Scan Obtained One Month after Admission. There are centrilobular ground-glass opacities, some of which have a rosette pattern (arrows). A few secondary pulmonary lobules appear to have been spared.

Noncardiogenic pulmonary edema due to acute inhalational injury deserves mention, given some of this patients reported exposures. At the time of his second hospitalization, he described the use of a hot tub that had been disinfected with bromine, raising the specter of inhalational injury. In 1997, Burns and Linden2 reported two cases of acute pneumonitis attributed to exposure to bromine and hydrobromic acid in a hot tub. Although I believe the hot-tub exposure may be important in this case, I shall dismiss acute inhalational injury, because the subsequent high-resolution CT image either should have been completely clear or should have shown nonspecific changes suggesting fibrosis; diffuse centrilobular nodules would not have been expected.3
pulmonary hemorrhage

chest that was obtained later and showed diffusely distributed pulmonary nodules was also helpful. Diffuse pulmonary nodules fall into four categories.1 Nodules along pleural surfaces or abutting the interlobular septa are designated perilymphatic. Ground-glass attenuation nodules along the arterial branch of the secondary lobule are designated centrilobular and usually reflect disorders of the accompanying bronchiole. Nodules that are due to bronchiolar impaction and associated airspace disease occur often in infection and are termed tree-in-bud or small airways disease associated. Well-defined nodules that do not fit any of the above patterns are termed random and are seen in hematogenous metastases. An important clinical feature of this case was rapidly reversible hypoxemic respiratory failure. On day 1 in the other hospital, the patient appeared to meet the criteria for the acute respiratory distress syndrome (ARDS), with bilateral air-space disease on chest radiography, a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen that was less than 200, and no clearcut cardiogenic cause. The causes of rapidly reversible ARDS include pulmonary edema, pulmonary hemorrhage, acute eosinophilic pneumonia, atypical infection, and diffuse parenchymal lung disease with an accelerated phase.

The reported drop in hematocrit in the absence of obvious gastrointestinal-tract blood loss could suggest diffuse alveolar hemorrhage, even in the absence of hemoptysis. Diffuse alveolar hemorrhage can occur in disorders of hemostasis and when pulmonary capillaries are disrupted by inflammation. Examples include angiotrophic infections, such as aspergillus, and vasculitis; the latter may be associated with centrilobular nodules.4 This patient, however, had no known bleeding diathesis and, to our knowledge, he was immunocompetent. There were no reported extrapulmonary stigmata of vasculitis, such as petechiae or purpura, an active urine sediment, or abnormal neurologic findings. The bronchoalveolar-lavage fluid was not reported to be bloody. For these reasons and because the highresolution CT scan did not show patchy groundglass opacities or consolidation typical of diffuse alveolar hemorrhage, I will dismiss pulmonary hemorrhage as a unifying diagnosis.
acute eosinophilic pneumonia

The differential diagnosis of ARDS that has no apparent precipitant should always include acute eosinophilic pneumonia. Accepted diagnostic criteria include an acute febrile illness of short duration, acute lung injury (or ARDS), and eosinophilia in specimens obtained from bronchoalveolar lavage (>25 percent) or in lung tissue, in the absence of known causes (e.g., drugs). Like this patient, many

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One type of viral pneumonia deserves special mention because of the timing of this case. An outbreak of pneumonia due to a coronavirus variant, or what came to be known as the severe acute respiratory syndrome (SARS), was peaking as this patient became ill in 2003. Although severe cases of SARS were described in the Far East and Canada, only three patients in the United States required mechanical ventilation.6 In Massachusetts, of eight suspected cases, none was confirmed. This patient atypical infection had no travel or contacts with other sick people, inAt the time of this patients initial presentation cluding those who had visited areas of endemic to the other hospital, he had a peripheral leukocy- disease. I will dismiss the diagnosis of SARS betosis with a leftward shift and a chest radiograph cause of the poor epidemiologic fit. that showed changes that suggested communityacquired pneumonia. These findings and scanty atypical bacterial pneumonia sputum production led his treating physicians to Is it possible that this patients clinical and radioconsider an atypical community-acquired pneumo- graphic course can be explained by incomplete antinia, which in its narrowest definition is reserved for biotic treatment of atypical community-acquired conditions due to mycoplasma, legionella, and chla- bacterial pneumonia? Atypical bacteria cause pneumydia. A more inclusive definition of atypical pneu- monia in more than a third of outpatient cases.7 Negative cultures from sputum and bronchoalveomonia is shown in Table 2. lar-lavage specimens, and negative results on a polyviral pneumonia merase-chain-reaction assay for mycoplasma and The patient had nasal congestion and nonspecific chlamydia8,9 argue against this diagnosis. The paconstitutional symptoms over the course of the tients exposure to bird droppings several weeks beweek preceding the initial admission, which sug- fore the onset of acute illness might suggest psittagested a viral infection. Viral bronchiolitis causes cosis. Polymerase chain reaction is less sensitive centrilobular nodules, but usually with at least for Chlamydia psittaci than for C. pneumoniae, and some acinar involvement and a tree-in-bud pattern therefore a negative test does not rule out this entity. as visualized by high-resolution CT. Moreover, the Psittacosis, however, occurs only rarely in wild tests for antigens were negative and rapid resolu- birds, and spontaneous recovery would not be extion of hypoxemic respiratory failure in viral bron- pected.10 chiolitis would be unusual.
acute fungal pneumonia
Table 2. Some Atypical Community-Acquired Pneumonias. Viral Varicella Respiratory syncytial virus Influenza A, B Parainfluenza Adenovirus Severe acute respiratory syndrome Bacterial Mycoplasma pneumoniae Legionella species Chlamydia pneumoniae C. psittaci Fungal Histoplasma capsulatum

patients with acute eosinophilic pneumonia have progressive respiratory failure, and spontaneous improvement (without glucocorticoids) has been reported.5 Although acute eosinophilic pneumonia is a logical diagnosis, I will dismiss it because the high-resolution CT scan failed to show the typical random pattern of ground-glass opacities, and because the examination of the bronchoalveolarlavage specimen showed only 1 percent eosinophils.

Primary histoplasma pneumonia can occur in an immunocompetent host, especially after exposure to a high inoculum of bird or bat droppings in an enclosed space. The usual symptoms are high-grade fever, headache, nonproductive cough, chills, and pleuritic chest pain days to weeks after exposure, and most patients recover spontaneously after two to three weeks. Massachusetts, however, is not an area where histoplasma is endemic. In addition, it was assumed that the patients daughters attic was well ventilated and we know that he cleaned the bird feeder outdoors. Serologic testing was negative for fungi, as was the test for the Histoplasma capsulatum urine antigen and the bronchoalveolarlavage fungal stain. His recovery from ARDS without treatment with corticosteroid agents or anti-

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fungal agents was almost certainly too quick if his illness had been fulminant H. capsulatum pneumonia. Similar arguments can be made against the probability of the illness having been either blastomycosis or coccidioidomycosis.
diffuse parenchymal lung disease

I now turn to the genre of disease that I believe best accounts for this patients presentation: diffuse parenchymal lung disease with an accelerated phase. Some examples, including the newly classified idiopathic interstitial pneumonias,11 are shown in Table 3. The patients medication list did not suggest a drug-induced lung disease, nor were there extrapulmonary stigmata of an undiagnosed connectivetissue disease. Silicoproteinosis can be manifested as recurrent pneumonia after intense inhalation of crystalline silica, and a high-resolution CT of the chest can show centrilobular nodules.12 I will dismiss this pneumoconiosis because the patients history does not report a return to the metal shop and because there was no sign of the typical groundglass opacities and consolidation on high-resolution CT.
idiopathic interstitial pneumonias

The several types of idiopathic interstitial pneumonias11 share many features of this case, and all of them are capable of mounting an accelerated phase. Acute interstitial pneumonia, formerly known as the HammanRich syndrome, does have a fulminant course, but spontaneous recovery with-

Table 3. Diffuse Parenchymal Lung Diseases. Known causes Drugs Connective-tissue disease Pneumoconioses Idiopathic interstitial pneumonias Acute interstitial pneumonitis Respiratory bronchiolitis interstitial lung disease or desquamative interstitial pneumonitis Usual interstitial pneumonia Nonspecific interstitial pneumonitis Lymphocytic interstitial pneumonitis Cryptogenic organizing pneumonia Granulomatous diseases Sarcoidosis Langerhans-cell histiocytosis Hypersensitivity pneumonia

in days does not occur. Respiratory bronchiolitis interstitial lung disease is associated with centrilobular ground-glass opacities and patchy areas of hyperinflation, a pattern, revealed by high-resolution CT, that is identical to the pattern in this case. This patient never smoked, however, which would make both respiratory bronchiolitis interstitial lung disease and the closely related desquamative interstitial pneumonia extremely improbable conditions for him to have. Usual interstitial pneumonia is increasingly diagnosed by findings on high-resolution CT images of bibasilar honeycombing (which suggests fibrosis) and upper-lung irregular lines.13 Nonspecific interstitial pneumonia is similar to usual interstitial pneumonia, although with less fibrosis and a better prognosis. The findings on high-resolution CT in this case suggested neither. Lymphocytic interstitial pneumonitis is a benign polyclonal proliferation of mature B cells that can diffusely involve the lung, yielding a pattern on high-resolution CT scanning similar to the pattern in this case14 and the finding of lymphocytosis in the bronchoalveolarlavage fluid. Lymphocytic interstitial pneumonitis, however, usually occurs in the presence of connective-tissue disease or an immunodeficiency condition; furthermore, spontaneous resolution would not be expected in association with this type of pneumonia. Finally, bronchiolitis obliterans organizing pneumonia, either idiopathic cryptogenic organizing pneumonia or as a nonspecific reaction of the lung to insults such as infection and connective-tissue disease, can be recurrent, as in this case, although spontaneous resolution would be unusual. In summary, although the idiopathic interstitial pneumonias share some of the clinical and radiographic features of this case, none offers a reasonable unifying diagnosis.
granulomatous lung disease

Pulmonary sarcoidosis is one of the great masqueraders in pulmonary disease. Signs and symptoms that are associated with it include hilar and mediastinal lymphadenopathy, upper-lobe interstitial changes, fibrosis, and less commonly, pulmonary parenchymal nodules or a fulminant vasculitis. The high-resolution CT findings usually include perilymphatic nodules rather than centrilobular nodules, however, and the vasculitis does not resolve spontaneously. Langerhans-cell histiocytosis is a

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diffuse parenchymal lung disease with a propensity for the upper lobes of smokers and former smokers. An accelerated phase is extremely unusual, and the expected cystic lesions that would appear on high-resolution CT scans were not found in this case.
hypersensitivity pneumonitis

The spontaneous resolution of ARDS over a threeday hospitalization and then the recurrence after an environmental exposure strongly suggest hypersensitivity pneumonitis. Hypersensitivity pneumonitis is a granulomatous immunologic response of a sensitized host to inhaled biologic aerosols. The disease is more common in nonsmokers and includes constitutional symptoms, cough, and dyspnea that appear four to six hours after exposure. The physical examination reveals rales and, rarely, wheezing. Symptoms subside over hours to days upon removal of the affected person from exposure. The hallmark of acute and subacute hypersensitivity pneumonitis is recurrence with reexposure, although with chronic exposure to the antigens, the pattern of waxing and waning symptoms may be lost. On radiographic examination, acute hypersensitivity pneumonitis may be observed as a fleeting, micronodular, interstitial pattern in the lower and middle lung zones, whereas the subacute and chronic forms involve the middle to upper lung zones. The findings on the high-resolution CT scan of the patients chest are characteristic of this condition: diffuse centrilobular micronodules with ground-glass attenuation and focal air trapping with only mild fibrotic changes or no changes. After acute exposure, the complete resolution of the findings on high-resolution CT may take weeks. Laboratory findings may include a precipitating IgG antigen, but a positive test may merely reflect exposure, and negative results of a standard antigen panel (as was obtained in this case) may be meaningless. The finding obtained by bronchoalveolar lavage of lymphocytosis of greater than 30 percent is characteristic; flow cytometry may show an inversion of the normal ratio of CD4+ to CD8+ T cells (which helps distinguish hypersensitivity pneumonitis from sarcoidosis). Typical pathological findings include poorly formed, noncaseating granulomas and mononuclear-cell inflammation in a peribronchial distribution. Thus, hypersensitivity pneumonitis accounts for nearly all of the clinical, laboratory, and radio-

graphic features of this case. Although the culprit antigen was not defined, the patients relapse after soaking in his hot tub strongly suggests the entity, hot-tub lung. Hot-tub lung15-21 is thought to be a hypersensitive response to aerosolized Mycobacterium avium complex, a frequent contaminant of standing water. Chlorine is not used in hot tubs because it bubbles off (in most forms). Bromine is used because of its lower vapor pressure, but it is highly reactive and most likely helps form the antigens with M. avium intracellulare that lead to hot-tub lung. In cases of hot-tub lung, M. avium complex is sometimes cultured from lung secretions, which may lead to controversy about infection versus hypersensitivity as the pathogenesis. Currently, most reports favor a hypersensitivity pathway, because the high-resolution CT image does not typically show the treein-bud appearance characteristic of infection, and hot-tub lung resolves quickly without antimicrobial therapy. Thus, hypersensitivity pneumonitis due to infection with M. avium complex seems an extremely probable diagnosis in this immunocompetent patient who had never smoked and who had a subacute course of the condition followed by a fulminant phase, spontaneous remission, and recurrent symptoms with repeated exposure to his hot tub; lymphocytosis in the bronchoalveolar-lavage fluid; and centrilobular nodules on CT scanning. Since the hypersensitivity panel was negative and a lung biopsy was not done, how could a specific diagnosis have been made? My guess is that M. avium complex was cultured, either from the patients bronchoalveolar-lavage fluid or from a sample of his hot-tub water. Dr. Nancy Lee Harris (Pathology): Dr. Thorner, you saw this patient both during and after the hospitalization; would you give us your clinical impressions and then tell us about the diagnostic test result that was received? Dr. Anna R. Thorner (Infectious Disease): When we saw the patient initially at this hospital, we thought that an infection, particularly one of the atypical causes of pneumonia, was possible, although the rapid resolution was unusual. When we saw him in follow-up one month after his acute illness, he reported the recurrence of his symptoms after exposure to the hot tub, and by that time, we had the results of a mycobacterial culture that had been obtained from the bronchoalveolar lavage.

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clinical diagnosis
Hypersensitivity pneumonitis due to M. avium complex infection (hot-tub lung).

dr. david m. systroms diagnosis

Hypersensitivity pneumonitis due to M. avium complex infection (hot-tub lung).

pathological discussion

Dr. Thorner: The mycobacterial culture yielded growth three weeks after it had been obtained, and a nucleic acid hybridization probe identified the isolate as M. aviumintracellulare complex. The patients pulmonary symptoms had resolved, and there were no signs of recurrence. We counseled him to avoid hot tubs, to which he agreed; he had already drained his hot tub. We obtained another sample of sputum anatomical diagnosis for an acid-fast bacilli smear and for a mycobacterial culture, both of which were negative. A chest CT Hypersensitivity pneumonitis due to M. avium scan two months after the acute illness showed complex infection (hot-tub lung). clearing of the parenchymal abnormalities.
references
1. Gruden JF, Webb WR, Naidich DP, McGuinness G. Multinodular disease: anatomic localization at thin-section CT multireader evaluation of a simple algorithm. Radiology 1999;210:711-20. 2. Burns MJ, Linden CH. Another hot tub hazard: toxicity secondary to bromine and hydrobromic acid exposure. Chest 1997; 111:816-9. 3. Nobauer-Huhmann IM, Eibenberger K, Schaefer-Prokop C, et al. Changes in lung parenchyma after acute respiratory distress syndrome (ARDS): assessment with highresolution computed tomography. Eur Radiol 2001;11:2436-43. 4. Choi YH, Im JG, Han BK, Kim JH, Lee KY, Myoung NH. Thoracic manifestation of Churg-Strauss syndrome: radiologic and clinical findings. Chest 2000;117:117-24. 5. Philit F, Etienne-Mastroianni B, Parrot A, Guerin C, Robert D, Cordier JF. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med 2002; 166:1235-9. 6. Update: outbreak of severe acute respiratory syndrome worldwide, 2003. MMWR Morb Mortal Wkly Rep 2003;52: 269-72. 7. Marrie TJ, Peeling RW, Fine MJ, Singer DE, Coley CM, Kapoor WN. Ambulatory

Dr. Harris: Dr. Mark, would you comment on the pathological findings in hot-tub lung? Dr. Eugene J. Mark (Pathology): The characteristic pathological feature of hypersensitivity pneumonitis is the presence of poorly formed bronchiolocentric granulomas. However, in a case of hot-tub lung seen at this hospital and reported previously in the Case Records,22 a lung biopsy showed bronchiolocentric granulomas that were more distinct than would be typical for hypersensitivity pneumonia, and acid-fast bacilli were found within some giant cells. M. aviumintracellulare was cultured from the lung and from the water from the hot tub. The earlier patient was treated with both corticosteroid therapy and antibiotic therapy for mycobacterial infection, and the patient recovered. In that case, it was not clear, therefore, whether the clinical symptoms were manifestations of hypersensitivity, infection, or both.

patients with community-acquired pneumonia: the frequency of atypical agents and clinical course. Am J Med 1996;101:508-15. 8. Blackmore TK, Reznikov M, Gordon DL. Clinical utility of the polymerase chain reaction to diagnose Mycoplasma pneumoniae infection. Pathology 1995;27:17781. 9. Miyashita N, Saito A, Kohno S, et al. Multiplex PCR for the simultaneous detection of Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila in community-acquired pneumonia. Respir Med 2004;98:542-50. 10. Verweij PE, Meis JF, Eijk R, Melchers WJ, Galama JM. Severe human psittacosis requiring artificial ventilation: case report and review. Clin Infect Dis 1995;20:440-2. 11. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias: this joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 2002;165:277-304. [Erratum, Am J Respir Crit Care Med 2002;166:426.] 12. Marchiori E, Ferreira A, Muller NL. Sili-

coproteinosis: high-resolution CT and histologic findings. J Thorac Imaging 2001;16: 127-9. 13. Hunninghake GW, Lynch DA, Galvin JR, et al. Radiologic findings are strongly associated with a pathologic diagnosis of usual interstitial pneumonia. Chest 2003; 124:1215-23. 14. Johkoh T, Muller NL, Pickford HA, et al. Lymphocytic interstitial pneumonia: thinsection CT findings in 22 patients. Radiology 1999;212:567-72. 15. Embil J, Warren P, Yakrus M, et al. Pulmonary illness associated with exposure to Mycobacterium-avium complex in hot tub water: hypersensitivity pneumonitis or infection? Chest 1997;111:813-6. 16. Kahana LM, Kay JM, Yakrus MA, Waserman S. Mycobacterium avium complex infection in an immunocompetent young adult related to hot tub exposure. Chest 1997;111:242-5. 17. Rickman OB, Ryu JH, Fidler ME, Kalra S. Hypersensitivity pneumonitis associated with Mycobacterium avium complex and hot tub use. Mayo Clin Proc 2002;77:12337. 18. Aksamit TR. Hot tub lung: infection, inflammation, or both? Semin Respir Infect 2003;18:33-9.

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19. Pham RV, Vydareny KH, Gal AA. High-

resolution computed tomography appearance of pulmonary Mycobacterium avium complex infection after exposure to hot tub: case of hot-tub lung. J Thorac Imaging 2003;18:48-52. 20. Khoor A, Leslie KO, Tazelaar HD, Helm-

ers RA, Colby TV. Diffuse pulmonary disease caused by nontuberculous mycobacteria in immunocompetent people (hot tub lung). Am J Clin Pathol 2001;115:755-62. 21. Cappelluti E, Fraire AE, Schaefer OP. A case of hot tub lung due to Mycobacterium avium complex in an immunocompe-

tent host. Arch Intern Med 2003;163:8458. 22. Case Records of the Massachusetts General Hospital (Case 27-2000). N Engl J Med 2000;343:642-9.
Copyright 2005 Massachusetts Medical Society.

slide sets for the case records available in digital format Any reader of the Journal who uses the Case Records of the Massachusetts General Hospital as a teaching exercise or reference material is eligible to receive digital images, with identifying legends, of pertinent radiographic, neurologic, and cardiac studies, gross specimens, and photomicrographs. The images on the CD for each case are in both PowerPoint and 300 dpi jpg format. For some cases, additional images that have not been selected for publication will be included on the CD. These images, which illustrate the current cases in the Journal, are mailed from the Department of Pathology to correspond to the week of publication and may be retained by the subscriber. Each year approximately 250 images from 40 cases are sent to each subscriber. The cost of the subscription is $450 per year. Application forms for the current subscription year, which began in January, may be obtained from the Lantern Slides Service, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114 (telephone 617-726-2974) or Pathphotoslides@partners.org. Images from individual cases may be obtained at a cost of $35 per case.

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