A case of flomoxef-induced pneumonitis]

We report a case of flomoxef-induced pneumonitis. A 22-year-old man was treated with flomoxef following liver biopsy. A few days later he developed a high fever and severe dyspnea, and his chest X-ray film revealed diffuse reticulo-nodular shadows in both lung fields. We suspected interstitial pneumonitis due to flomoxef, and pulse therapy with methylprednisolone was started. He showed rapid recovery of symptoms and marked regression of pulmonary infiltration in his chest X-ray. Lymphocyte stimulation test was positive to flomoxef, which was compatible with the diagnosis of drug-induced pneumonitis. To our knowledge, there has been no previous case of pulmonary hypersensitivity to flomoxef reported in Japan.     

A case of acetaminophen-induced pneumonitis]

A 20-year-old woman took 1.2 g of acetaminophen for toothache. She subsequently developed a dry cough, pyrexia, and dyspnea. Chest X-ray revealed diffuse reticulo-nodular shadows in both lung fields. Broncho-alveolar lavage examination showed a marked increase in the total cell number and an increase in the percentage of eosinophils, neutrophils, and lymphocytes. Because drug-induced pneumonitis was suspected, all drugs were stopped and she was administered methylprednisolone. Consequently her symptoms resolved, and pulmonary function and chest X-ray findings improved remarkably. The lymphocyte stimulation test was positive for Norshin and its acetaminophen element. Based on these findings, the diagnosis of acetaminophen-induced pneumonitis was made. Acetaminophen intoxication is well-known, but to our knowledge this is the first reported case of acetaminophen-induced allergic pneumonitis in Japan.     

A case of hepatitis and pneumonitis caused by Bofutsusyo-san herbal medicine]

We report a case of drug-induced pneumonitis and hepatitis associated with the herbal medication Bofutsusyo-san. A 41-year-old woman was admitted to our hospital with pneumonitis and hepatitis. She complained of fever and dyspnea. Fine crackles were heard on chest auscultation and a chest X-ray film revealed diffuse reticulo-nodular shadow in both lung fields. Cessation of the medication improved the patient' s clinical and X-ray findings. Bronchoalveolar lavage showed an increase of the lymphocytes and a diminished CD4/CD8 ratio. A drug-induced lymphocyte stimulation test was positive. Challenge tests for Bofutsusyo-san were positive. A diagnosis of drug-induced pneumonitis and hepatitis was made. Our findings suggested an association with Ou-gon.     

A case of sho-seiryu-to-induced pneumonia with a marked increase in peripheral eosinophils]

A 25-year-old woman presented with a high temperature, cough and dyspnea three days after taking sho-seiryu-to, a Chinese herbal preparation, for a cough and throat pain. A chest X-ray film and computed tomography (CT) scan revealed diffuse infiltrative shadows in both the middle and lower lung fields. Arterial blood gas analysis showed hypoxemia (PaO2 43Torr under room air). The white cell count was 40,800/mm3, with eosinophilic cells accounting for 56.5% of the cells. The patient was treated with methylprednisolone under a diagnosis of drug-induced pneumonia and the administration of sho-seiryu-to was discontinued. Immediately after the prednisolone administration, her chest X-ray film findings, clinical symptoms and laboratory data markedly improved. A lymphocyte stimulation test for sho-seiryu-to using peripheral lymphocytes was positive. In 29 cases of herbal medicine-induced pneumonia reported in Japanese medical literature over a 10-year period, sho-saiko-to has been the predominant cause of drug-induced pneumonia. This is the second case of sho-seiryu-to-induced pneumonia.     

A case of chronic hypersensitivity pneumonitis induced by shiitake mushroom spores]

A 73-year-old woman was admitted to our hospital with a low-grade fever, dry cough and dyspnea on exertion as the chief complaints. She had been a professional shiitake mushroom grower for 50 years. Three years before visiting our hospital, she had been suspected of having hypersensitivity pneumonitis as a result of chest X-ray examination, bronchoalveolar lavage and transbronchial lung biopsy performed at another clinic. No antigens were identified at that time, but prednisolone was administered. On admission to our hospital, chest radiography and chest computed tomography revealed an interstitial shadow with subpleural honey-combing in both lower lung fields. After steroid pulse therapy, dyspnea on exertion and hypoxia improved moderately. Because of recurrence of the dyspnea, however, she was admitted on four separate occasions. On the second admission, an increase in lymphocytes was found by bronchoalveolar lavage, and septal lymphocytic infiltration accompanying fibrosis was demonstrated by transbronchial lung biopsy. On the fourth admission, a detailed immunological examination and an environmental survey were performed. The environmental provocation test yielded clinical symptoms similar to those experienced at the mushroom farm. Furthermore, tests of precipitation and lymphocyte proliferation in response to shiitake mushroom extracts were positive. Finally a diagnosis of chronic hypersensitivity pneumonitis induced by shiitake mushrooms was confirmed.     

A case of pigeon breeder's disease

A 73-year-old woman developed dry cough and exertional dyspnea. She had been breeding pigeons for thirty years. Her serum showed positive precipitin reaction against pigeon serum. Furthermore the lymphocyte stimulation test against pigeon serum was positive. An X-ray film of the chest showed diffuse ground glass infiltrate, fine nodular shadows and reticular shadows. Histopathology revealed diffuse interstitial infiltration with mononuclear cells and occasional giant cell formation as well as granuloma formation in the bronchiole. The symptoms subsided after admission. From these results, this case was diagnosed as pigeon breeder's disease. She had the subacute form probably because of her old age and smoking. It could be that exacerbation of pneumonitis was caused by cessation of smoking in an attempt to alleviate the symptoms. This is the fifth case reported in Japan.     

A case of hypersensitivity pneumonitis caused by a humidifier]

A 58-year-old woman was admitted complaining of dry cough and exertional dyspnea. Physical findings, chest X-ray films, chest CT scan and respiratory function tests were suggestive of interstitial pneumonia. Transbronchial lung biopsy showed specific findings of hypersensitivity pneumonitis. As a result of positive provocation test using her home humidifier, a diagnosis of humidifier lung was made. Many microorganisms including Flavobacterium meningosepticum were cultured from the water left in the humidifier for one week. As both complement fixation test and precipitation test were positive to humidifier water and to extract of Flavobacterium meningosepticum, the humidifier and Flavobacterium meningosepticum were suggested to be causative in this case.     

A case of steroid-resistant acute hypersensitivity pneumonitis successfully treated with an immunosuppressive drug]

A 28-year-old man complaining of cough and fever was hospitalized because of bilateral diffuse granular lung shadows. Hypersensitivity pneumonitis was diagnosed based on bronchoalveolar lavage fluid (BALF) and transbronchial lung biopsy (TBLB). Since antigen avoidance alone was not effective, steroid pulse therapy was started, and his symptoms and chest X-ray findings improved. After discharge, he moved to another residence. A few weeks later, fever and dyspnea recurred, then he was hospitalized on the suspicion of acute exacerbation of hypersensitivity pneumonitis. Steroid therapy resulted in no improvement on this occasion. Lung biopsy under video-assisted thoracoscopy was performed, and acute hypersensitivity pneumonitis was diagnosed pathologically. Although steroid therapy was continued, hypoxia still remained and a KL-6 level markedly increased. Combined therapy with steroid and cyclosporin A was started, and his symptoms, physical findings, laboratory data, and chest X-ray findings gradually improved. There has been no report in which cyclosporin A was used for acute hypersensitivity pneumonitis but this case indicates that cyclosporin A is efficacious for its treatment.     

A case of pneumonitis due to serrapeptase

A case of pneumonitis due to Serrapeptase was described. A 69-year-old man was treated with Serrapeptase for 16 days because of common cold, then fever, nonproductive cough and dyspnea developed and chest X-ray revealed diffuse fine granular shadows in bilateral lung fields. Once the administration of Serrapeptase was halted, symptoms, chest X-ray abnormalities and laboratory data improved markedly. The fraction of lymphocytes increased in bronchoalveolar lavage fluid and OKT4/T8 decreased. Microscopic examination of transbronchial lung biopsy showed interstitial pneumonia. Both leukocyte migration inhibition test and sensitized hemagglutination test were positive for Serrapeptase. Based on these findings, we diagnosed this case as Serrapeptase-induced pneumonitis.     

A case of Kartagener's syndrome]

This case describes a 57-year-old woman in whom situs inversus had been noted at her birth. She had bronchial asthma and bilateral sinusitis during her childhood. She married and experienced childbirth. In December 2003, she was admitted to our Division complaining of wheezing, expectoration and dyspnea on effort. Bronciectasis was visualized on chest X-ray and CT. Electron microscopic examination of the nasal cavity epithelium and bronchial epithelial cilia revealed a deficit of bilateral dynein arms. These findings, helped establish a diagnosis of Kartagener's syndrome, which is characterized by primary ciliary dyskinesia. The restrictive and obstructive pulmonary dysfunction with increase of residual volume in the lung function tests and diffuse centrilobular small nodules with hyperinflation on chest CT were consistent with the findings of diffuse panbronchilitis (DPB) and suggested extended obliterative peripheral airway disease. Clarithromycin which is highly effective for DPB failed to prevent the aggravation of airway infection, arousing the concern about the progression into chronic respiratory failure.     

Case of chronic pigeon breeder's disease accompanied by pulmonary cysts]

We treated a case of chronic pigeon breeder's disease with pulmonary cysts. The patient was a 49-year-old woman whose husband had started to breed pigeons 23 years earlier. She was given a diagnosis of hypersensitivity pneumonitis due to pigeons 1 year previously, but since her husband refused to stop keeping the birds, she could not stay out of contact with them. A chest CT scan showed bilateral multiple pulmonary cysts and a diffuse groundglass appearance. The transbronchial lung biopsy (TBLB) specimens showed bronchioloalveolitis characterized by infiltration of lymphocytes and plasma cells into the walls of the bronchioles and the surrounding alveolar walls. Tests for antibodies to extracts of both pigeon droppings and budgerigar droppings were positive. After admission to our hospital and avoidance of contact with birds, the groundglass changes, dyspnea, and hypoxemia ameliorated. Multiple pulmonary cysts in a non-smoker is a rare manifestation of chronic pigeon breeder's disease.     

Two cases of hypersensitivity pneumonitis due to contamination of an ultrasonic humidifier

Two cases of hypersensitivity pneumonitis due to contamination of ultrasonic-humidifier were reported. The first case, a 64-year-old man, developed fever and dyspnea on exertion in January 1986. He was hospitalized for 18 days and received antibiotics for presumptive bacterial pneumonia. Half a day after discharge, those symptoms recurred. On readmission, fine crackles were heard at the left lung base, and chest X-ray film showed ground glass shadows all over the lung fields. Bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed on the next day after readmission. TBLB specimen revealed lymphocyte alveolitis, granulomatous tissue and infiltration of polymorphonuclear neutrophils (PMN) in alveoli. Differential cell count of the BAL fluid showed not only lymphocytosis (38.2%) but also increased PMNs (44.2%). In the second BAL performed 18 days later, the value of PMNs demonstrated a dramatic decrease. Environmental challenge tests revealed that his hypersensitivity pneumonitis was caused by an ultrasonic humidifier in his bed room. Immunological examinations showed positive Arthus type skin reaction and serum precipitin against Aspergillus fumigatus. Inhalation challenge with A. fumigatus produced cough and dyspnea with a decrease of 10 Torr in PaO2. These data suggest that A. fumigatus may be the causative antigen in this case. The second case, a 64-year-old man who had used ultrasonic humidifier in his living room, was admitted for 8 weeks with an illness characterized by cough, low fever and general malaise on 22 January 1987. Examination revealed fine crackles on both lung bases. Chest X-ray film demonstrated diffuse nodular shadows. The TBLB specimen showed lymphocytic alveolitis and bronchiolitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of interstitial pneumonitis associated with polymyositis complicated by renal cell carcinoma]

A 55-year-old woman was referred to the department of urology in our hospital with left renal tumor, discovered during examinations at another hospital for fever and dyspnea on exertion. Because surgery was difficult due to severe hypoxemia, pulmonary function impairment (restrictive) and bilateral diffuse interstitial shadows on chest X-ray film, the patient was referred to our department. Interstitial pneumonitis was found on transbronchial lung biopsy, and serum GOT, LDH and CPK values were elevated. These symptoms and abnormalities of laboratory data were improved by administration of prednisolone 60 mg/day, and left nephrectomy was performed without any complications. Pathological examination of the surgical specimen showed clear cell carcinoma (Grawitz). Steroid therapy was tapered off and her clinical course was good. Six months after surgery, the patient developed a recurrence of fever, which was not responsive to antibiotics. Polymyositis was diagnosed on the basis of elevated serum GOT, LDH and CPK, electromyogram and muscle biopsy findings and positive anti-Jo-1 antibody. Polymyositis/dermatomyositis is sometimes associated with interstitial pneumonitis or malignant neoplasms, but rarely with both simultaneously. Moreover, renal cell carcinoma is very rare among the malignant neoplasms associated with polymyositis/dermatomyositis, and we therefore report this unusual case.     

An autopsy case of pulmonary metastasis of cholangiocellular carcinoma associated with marked fibrotic change of the lungs]

An autopsy case of pulmonary metastasis of cholangiocellular carcinoma is presented. A 44-year-old woman was admitted to our hospital because of dyspnea, general fatigue and a sense of abdominal fullness on February 5, 1990. In November 1986, at an other hospital, she had been diagnosed as having diffuse metastatic lung tumor and multiple bone metastases, by transbronchial lung biopsy and other examinations. During the clinical course, she was not received chest irradiation and chemotherapy which induced fibrotic change of lungs. Chest X-ray film on December 21, 1986 showed diffuse nodular shadows in both lung fields. Chest X-ray film on February 4, 1990 showed diffuse reticular shadows with marked shrinkage of lung fields. She died two months after admission. The primary site of the carcinoma was not determined clinically, but was revealed by autopsy to be cholangiocellular carcinoma of the liver, with generalized metastasis. Microscopic findings of the autopsied lung showed markedly increased connective tissue around bronchi and blood vessels, in areas where microtubular adenocarcinoma was scattered. This is a very rare case of pulmonary metastasis of cholangiocellular carcinoma, associated with marked fibrotic change of the lungs during about 3.5 years. To our knowledge, this is the first reported case.     

A case of hypersensitivity pneumonitis caused by Gyrodontium versicolor]

A 36-year-old woman was admitted to our hospital because of fever, dry cough, dyspnea on exertion and body weight loss in August 2000. Chest radiography and CT scanning showed diffuse ground glass opacity and small centrilobular nodules in the middle and lower lung fields of both lungs. Serum antibody against Trichosporon cutaneum was positive; and summer-type hypersensitivity pneumonitis was therefore initially diagnosed. Treatment with methylprednisolone and prednisolone decreased the symptoms, but the dyspnea reappeared when the patient was at home. Inspection of her house revealed the presence of fungi under the floor. After these were removed, her symptoms disappeared completely. The lymphocytic stimulation test of the peripheral blood was positive for the fungi, and it was therefore suggested that they were the cause of her hypersensitivity pneumonitis. The fungi were identified as Gyrodontium versicolor. This is the first report of hypersensitivity pneumonitis caused by Gyrodontium versicolor.     

A case of combined hypersensitivity pneumonitis and bronchial asthma due to isocyanate (MDI)]

A 29-year-old man was admitted to our hospital complaining of cough, wheezing, dyspnea, and fever one month after handling paint spray containing isocyanate (MDI). Chest HRCT findings showed diffuse ground-glass attenuation in both lung fields. A pulmonary function test revealed restrictive impairment, and the reversibility test was positive. His symptoms, HRCT findings, and pulmonary dysfunction were improved only after the cessation of isocyanate administration. BALF showed lymphocytosis, and the pathological findings of the TBLB specimen revealed cellular alveolitis, but no Masson bodies or epitheloid cell granuloma. As a result of environmental provocation, fever, hypoxia, and reduced peak expiratory flow developed, and the environmental provocation test was positive. The specific antibodies against MDI and TDI were positive in both serum and BALF, and the lymphocyte stimulation test against MDI was positive in peripheral blood. Combined hypersensitivity pneumonitis and bronchial asthma due to isocyanate were therefore diagnosed. Pulmonary dysfunctions due to isocyanate are known to include bronchitis, bronchial asthma, and hypersensitivity pneumonitis. However, case reports of combined hypersensitivity pneumonitis and bronchial asthma due to isocyanate are rare.     

Induction of interstitial pneumonitis during interferon treatment for chronic hepatitis C

A 48-year-old woman developed interstitial pneumonitis while receiving interferon treatment for chronic hepatitis C. Laboratory studies prior to treatment showed elevated serum alanine aminotransferase levels, but chest X-rays and physical examination revealed no abnormalities suggestive of interstitial pneumonitis. At the 9th week of interferon treatment (total dose, 380MU of recombinant interferon-α, without other medications), the patient began to complain of cough and exertional dyspnea. A chest X-ray film revealed diffuse reticulo-nodular shadows in bilateral lung fields, suggesting a diagnosis of interstitial pneumonitis. A marked increase in lymphocyte count was observed in bronchoalveolar lavage fluid and a diagnosis of interstitial pneumonitis was made as a result of transbronchial lung biopsy. Her clinical symptoms and abnormal lung shadows were reversible, improving within a month of the discontinuation of interferon, and disappearing promptly after exogenous corticosteroid was instituted. This may be the first case of drug-induced interstitial pneumonitis occurring during the course of treatment with interferon alone. We should be aware of the possibility of interstitial pneumonitis developing during treatment of chronic hepatitis C with interferon.     

Hypersensitivity pneumonitis due to mushroom (Pholiota nameko) spores

Hypersensitivity pneumonitis due to the inhalation of spores from the edible mushroom Pholiota nameko was demonstrated. A 52-year-old mushroom worker noticed cough, exertional dyspnea, and high fever several hours after work in the mushroom-cultivating room. His examination revealed bilateral basilar crepitations, fine granular shadows in both lung fields of chest x-ray film, and slight decrease in diffusion capacity. Precipitin and macrophage migration inhibition factor were found against the mushroom spore extract and not other contaminants and molds. Histologic finding by transbronchial lung biopsy showed granulomatous alveolitis. Manifest increase of lymphocytes was found in his bronchoalveolar lavage fluid. Provocative inhalation test with the extract revealed similar symptoms and signs in his workplace eight hours after inhalation. It seems to be the first case of hypersensitivity pneumonitis to the Pholiota nameko mushroom spores.     

A case of hypersensitivity pneumonitis due to isocyanate (TDI)

A 46-year-old man who had worked in a paint processing plast for over 29 years was admitted to our hospital with complaints of nocturnal dyspnea and dry cough. A chest X-ray film showed diffuse granular shadows in bilateral lungs. Pulmonary function tests revealed reduction of diffusing capacity and restrictive impairments. Hypersensitivity pneumonitis (HP) due to isocyanates was speculated from his occupational history and clinical course. Positive skin tests against TDI-HSA and MDI-HSA, precipitating antibody against TDI-HSA, and negative lymphocyte stimulating tests of peripheral blood and bronchoalveolar lavage fluid were also noticed. Environmental provocation test was positive. Histological findings of transbronchial lung biopsy specimens showed diffuse alveolitis and Masson body, but no granulomas. According to these results, the patient was diagnosed as HP due to TDI. Type III allergy of Gell-Coombs seems to participate in this case. The granulomatous lesion is seen less frequently in isocyanate-related HP than in HP induced by organic dusts, which suggests the difference in immunological and histological reactions between both types of HP.     

Extrinsic allergic alveolitis with eosinophil infiltration induced by 1,1,1,2-tetrafluoroethane (HFC-134a): a case report

A 22-year-old woman was admitted with symptoms of dyspnea and fever with pulmonary infiltrates noted on her chest X-ray study. She developed these symptoms in the workplace; her job included the removal of body hair using a diode-laser with 1,1,1,2-tetrafluoroethane (HFC134a, an alternative to chlorofluorocarbon) as a coolant. A chest X-ray examination revealed ground-glass opacities in the lower lung fields, and a chest computed tomographic study showed diffuse centrilobular opacities. An examination of the bronchoalveolar lavage fluid revealed increased lymphocytes with a slight increase in the number of eosinophils. An examination of the transbronchial biopsy specimens revealed eosinophil infiltration. A peripheral blood eosinophilia was also seen. The patient's symptoms, chest X-ray findings, and arterial blood gas analysis all returned to normal within a week. A challenge test of 1,1,1,2-tetrafluoroethane (HFC134a) inhalation was performed, which resulted in an elevation of body temperature, the development of a cough, and laboratory data indicating increased inflammation. We then determined the patient's diagnosis to be extrinsic allergic alveolitis with eosinophil infiltration, caused by HFC134a.