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.     

Significance of lymphocytosis in bronchoalveolar lavage in suspected ocular sarcoidosis.

Ocular sarcoidosis is frequent in Japan, but in many cases the condition remains undiagnosed in patients with suspected ocular sarcoidosis. Bronchoalveolar lavage (BAL) was performed in order to study the clinical implications of lymphocytosis of BAL fluid in such patients with characteristic ocular manifestations. The subjects included in this study were 39 patients with suspected ocular sarcoidosis. The patients were divided into four types based on high-resolution computed tomography (HRCT) findings; no lung involvement (HRCT-0), bilateral hilar lymphadenopathy (BHL) without lung involvement (HRCT-I), lung involvement and BHL (HRCT-II), and lung involvement and no BHL (HRCT-III). Transbronchial lung biopsy (TBLB) and BAL were conducted after examining serum angiotensin-converting enzyme and serum lysozyme values, skin test for purified protein derivative chest radiograph, HRCT, and gallium scintigram. Twenty patients were histologically diagnosed as having sarcoidosis, and 19 patients remained undiagnosed. Granuloma was identified by TBLB in 19 of 20 patients in type HRCT-II but in only one of 19 patients in types HRCT-0 and HRCT-I (p<0.0001). Lymphocytosis in BAL (>15%) was identified in all patients who showed lung field involvement (type HRCT-II) and in 16 of 19 patients without lung field involvement (types HRCT-0 and HRCT-I). There were 10 patients whose only relevant findings were lymphocytosis in BAL. Among these 10 patients, an increased CD4+/CD8+ ratio (>3.5) in BAL was seen in 60%. The authors conclude that high-resolution computed tomography results yield the same degree of diagnostic accuracy as transbronchial lung biopsy in ocular sarcoidosis suspects. However, bronchoalveolar lavage revealed significant lymphocytosis in patients with negative high-resolution computed tomography results. It should be kept in mind that a diagnostic group of patients with sarcoidosis who manifest ocular involvement and lymphocytosis in bronchoalveolar lavage exists.     

A case of angioimmunoblastic T-cell lymphoma with interstitial shadow which disappeared after injection of hydrocortisone]

A case of angioimmunoblastic T-cell lymphoma (AITL) was reported. A 56-year-old woman was admitted because of high fever and systemic lymphademopathy. Her chest X-ray on admission showed mediastinal and bilateral hilar lymphademopathy (BHL) and interstitial shadows in both lower lung fields. Chest CT scan revealed thickening of interlobular septum and bronchovascular bundles. There was a remarkable elevation in serum soluble interleukin-2 receptor. A biopsy of cervical lymph nodes for histopathological examination revealed AITL. After intravenous injection of 200mg of hydrocortisone for 7 days, the interstitial shadows and BHL disappeared. It was suspected that interstitial shadow was caused by pulmonary infiltration of AITL.     

Identification of propionibacterium acnes in a case with stage III pulmonary sarcoidosis involving hepatosplenic disease]

A 35-year-old woman was admitted to our hospital because of an abnormal chest radiograph. Chest X-ray on admission showed multiple small nodular shadows in both lung fields but no bilateral hilar lymphadenopathy (BHL). Moreover, abdominal CT showed some nodules in the liver and spleen, and serum ACE was slightly increased to 23.3U/L (normal range: 8.3-21.4U/L). Transbronchial lung biopsy and liver biopsy resulted in a diagnosis of stage III pulmonary sarcoidosis with hepatosplenic disease. Histopathological findings demonstrated non-caseating epithelioid cell granulomas with giant cells in both specimens. Interestingly, propionibacterium acnes (P. acnes), the possible pathogen of sarcoidosis, was detected in giant cells in the lung and epitheliod cell granuloma of liver tissue. This case was of interest considering P. acnes might have been the causative pathogen.     

Sarcoidosis with primary acute cavitation exacerbated by bronchial asthma]

A 22-year-old woman complaining of blurred vision visited our hospital in March 1995 and was given a diagnosis of uveitis. Chest X-ray and computed tomographic (CT) films demonstrated bilateral hilar lymphadenopathy (BHL), diffuse granular shadows in both lung fields, and a cavity with a thin, smooth wall in the right upper lung field. Because histopathologic findings from transbronchial lung biopsy specimens of the lung and cavity tissues disclosed sarcoid granuloma, the diagnosis was sarcoidosis with primary cavitation, which is very rare for this disease. Although BHL disappeared without medication, in November the patient experienced dyspnea due to attacks of bronchial asthma that had been in remission for a long period. Treatment with inhalation of becromethazone propionate markedly alleviated her symptoms. In May 1998, follow-up chest CT films demonstrated that the cavity had disappeared. This case suggested that sarcoidosis leads to a deterioration of asthma control, a conclusion supported by previous reports.     

Acute-onset sarcoidosis with erythema nodosum and polyarthralgia (Löfgren's syndrome) in Japan: a case report and a review of the literature

L?fgren's syndrome is an acute form of sarcoidosis that is characterized by erythema nodosum (EN), bilateral hilar lymphadenopathy (BHL), and polyarthralgia or polyarthritis. This syndrome is common among white people, but is considered rare among Japanese people. We present the case of a 26-year-old Japanese woman with L?fgren's syndrome. The patient complained of polyarthritis and EN of the lower extremities that lasted for 3 months. A chest radiograph revealed BHL and nodular shadows. The angiotensin-converting enzyme (ACE) level was within the normal range. Transbronchial lung biopsy revealed a noncaseating granuloma with giant cells. Six Japanese cases of L?fgren's syndrome have been reported previously. Five of the seven Japanese patients with L?fgren's syndrome had normal ACE levels; all of them exhibited BHL. L?fgren's syndrome should be considered as a possibility when examining a patient with EN and articular symptoms, even if the patient is Japanese.     

A case of sarcoidosis with primary acute pulmonary cavitation]

A 23-year-old man was admitted to our hospital on June 24, 1991, because of worsening chest X-ray findings of sarcoidosis. In August 1990, he was referred to our outpatient office, because of BHL and nodular lesions on chest X-ray film performed at his company 4 months earlier. At that time, serum ACE was elevated to 34.0 IU/l, and Ga scintigraphy showed abnormal uptake in bilateral lacrimal and salivary glands, mediastinal and hilar lymph nodes, and in the lung fields. TBLB specimen showed noncaseating epithelioid granuloma with giant cells and negative stains for acid-fast bacilli. Although it was planned to follow this patient without medication, he did not return to our outpatient department. In June 1991, because of worsening of lesions in the lung at annual checkup at his company, he was referred and admitted for steroid therapy. Chest X-ray film on admission showed BHL, multiple nodular lesions in both lung fields, and bullous change in the left upper lobe. Chest CT on admission showed three cavitating lesions within preexisting nodules. PPD skin test was negative, and sputum smears and cultures were repeatedly negative for pyogenic bacteria and acid-fast bacilli. Therapy was initiated with prednisolone 30 mg daily. Four months later, there was marked resolution of BHL and nodular lesions, and the cavitating lesions were no longer visible on chest X-ray film. From the clinical and radiological observations, it is concluded that the cavitating lesions in the present case were primary acute pulmonary cavitation in sarcoidosis, distinct from infection, bullae, or cystic bronchiectasis which are seen in the chronic and fibrotic stages of sarcoidosis.     

IgG4-related airway involvement which developed in a patient receiving corticosteroid therapy for autoimmune pancreatitis

A 66-year-old man was diagnosed with autoimmune pancreatitis in February 2009 and started 40 mg of oral prednisolone followed by a maintenance dose of 5 mg daily. The patient developed a cough in October 2010 and visited our division. He had a high serum concentration of immunoglobulin (Ig) G4 and his chest computed tomography showed airway stenosis without bilateral hilar lymphadenopathy (BHL). The bronchial biopsy specimens revealed lymphoplasmacytic infiltrations with IgG4-positive/IgG-positive plasma cells of more than 50%. Thus, we diagnosed the airway lesion with IgG4-related airway involvement. This is the first report of a patient with IgG4-related airway involvement without BHL.     

Humidifier lung: possible contribution of endotoxin-induced lung injury

A 56-year-old man was admitted with cough, fever, myalgia, and arthralgia. Chest computed tomography demonstrated bilateral diffuse ground-glass opacities predominantly in the upper lungs. Subpleural non-segmental consolidation was observed in the late phase. Hypersensitivity pneumonitis was suspected, and an environmental provocation test with the incidental use of a home ultrasonic humidifier was positive. Unlike typical hypersensitivity pneumonitis, serum KL-6 levels were normal. Although several microorganisms were isolated from the humidifier water, there was no evidence for immune sensitization. We detected high amounts of endotoxin in the humidifier water, which may have contributed to the lung injury of this patient.     

A case of pleural sarcoidosis in which vats lung biopsy, obtained pleural and pulmonary lesions]

Here we report a case that was diagnosed as sarcoidosis but required differential diagnosis from pneumoconiosis. A 51-year-old asymptomatic man, who showed signs of bilateral hilar lymphadenopathy (BHL) on a chest X-ray taken during a medical check, was given a diagnosis of sarcoidosis, based on the results of mediastinoscopic mediastinal lymph node biopsy. Because of the presence of large and small nodular lesions adjacent to the pleura extending from the bilateral upper lobes into the lung field, and continuous bead-like, small nodular lesions in the right interlobar pleura, pleural sarcoidosis was suspected and thoracoscopy was performed. Macroscopically, multiple grayish-white nodules with distinct margins, up to 1cm in diameter surrounded by a proliferation of capillaries were found in the pleura, particularly in the upper lobes. Lesions were also scattered over the interlobar pleura and diaphragmatic surface. Histopathologically, several non-caseous epithelioid cell granulomas and silicotic nodule-like lesions of hyaline degeneration were found; therefore, pneumoconiosis, or more specifically chronic berylliosis, was suspected. Despite these symptoms, the patient did not have a history of exposure, and the results of the lymphocyte stimulation test using beryllium were negative in blood and bronchoalveolar lavage fluid. The patient was given a diagnosis of pleural sarcoidosis and has been observed without treatment.     

Hypersensitivity pneumonitis caused by a factory humidifier. A case report]

A 64-year-old man was hospitalized for productive cough and dyspnea. Both chest radiographs and CT scans showed areas of ground-glass opacity in the middle and lower lung fields on both sides. The BAL and TBLB findings were compatible with hypersensitivity pneumonitis. The serum was negative for antibodies against Trichosporon species, and the result of a lymphocyte stimulating test for administered drugs including a Chinese medicine was also negative. A humidifier was suspected as the cause because it had been used for more than 10 years in the factory where the patient had been working. An inhalation test using the humidifier fluid successfully provoked dyspnea, fever and fine crackle, and laboratory tests demonstrated hypoxemia, reduction in vital capacity and the elevation of CRP. Agar gel diffusion using the patient's serum showed a precipitating line against Cephalosporium acremonium, but this line did not fuse with any precipitating line formed between the humidifier fluid and the serum, indicating that no Cephalosporium was Present in the humidifier fluid. Since a high level of beta-D glucan was detected in the humidifier fluid, an unidentified fungus was suspected to be the antigen.     

Clinical significance of gallium-67 scintigraphy in assessing pulmonary lesions of sarcoidosis and idiopathic pulmonary fibrosis]

To evaluate whether one can predict the course and prognosis of interstitial lung diseases from lung gallium-67 (67Ga) uptake, we studied 31 subjects with sarcoidosis and 28 with idiopathic pulmonary fibrosis (IPF) retrospectively. We quantified the lung 67Ga uptake using posterior scans by Line's method, and calculated a visual index (VI). The normal range of 67Ga uptake was defined as less than 65 VI values, obtained from the 95 percent confidence interval of the control subjects. All subjects with stage I sarcoidosis, having only bilateral hilar lymphadenopathy (BHL) on chest X-ray, revealed normal lung 67Ga uptake. Fifty percent of patients with stage II sarcoidosis, with both BHL and pulmonary involvement on chest X-ray, showed increased lung 67Ga uptake. The patients with increased lung 67Ga uptake showed decreased percent vital capacity and increased alveolar-arterial oxygen tension difference, but none of them showed clinical deterioration during the follow-up period of more than 6 months. Fifty-four percent of subjects with IPF showed increased lung 67Ga uptake. But there was no difference between the subgroups with normal and increased lung 67Ga uptake with respect to the severity of dyspnea, percent vital capacity, arterial oxygen tension, or alveolar-arterial oxygen tension difference. There was also no difference between the two subgroups of IPF in the cumulative percent survival after either the onset of symptoms or the 67Ga scintigram. We conclude that lung 67Ga uptake was not able to predict the clinical course or the prognosis of patients with sarcoidosis and IPF.     

A case of polyarteritis nodosa with bilateral hilar lymphadenopathy]

A 55-year-old male was admitted with non productive cough and fever which had continued for 6 weeks. The patient had symptoms of peripheral neuralgia. Chest X-ray revealed bilateral hilar lymphadenopathy (BHL) and reticular shadows in both lung fields. Other laboratory abnormalities included hematuria, RBC cast, high BUN, leukocytosis and thrombocytosis. Destruction of the internal membrane of arterioles was observed in a livedo reticularis on the right lower extremity. Renal angiography showed irregularity in the diameter, discontinuation and narrowing of peripheral arteries of both kidneys. These findings suggested the existence of "angiitis". These data were compatible with the diagnosis of polyarteritis nodosa (PN). Prednisolone (60 mg/day) administration resulted in the improvement of his symptoms and laboratory findings. A case of PN with lymph node swelling has been reported, however PN with BHL has not yet been reported. This is the first report of PN with BHL.     

A case of pulmonary sarcoidosis with calcification in the lung

A 35 year-old male farmer presented with complaints of productive cough and sputum. The chest X-ray films showed reticulonodular shadows bilaterally in the upper and middle lung fields, segmental infiltration in the right lung, and no BHL. Tuberculin reaction was negative. Serum angiotensin converting enzyme level was 26.5 IU/ml. Precipitating antibodies for Thermophilic actinomycetes and M.f. were negative. BAL showed moderate lymphocytosis (24.3%), and CD 4/8 was 1.67. A biopsy specimen of right scalene lymph node showed epithelioid cell granulomas and TBLB epithelioid cell granulomas and spot-like calcification. Pulmonary sarcoidosis with calcification in the lung is very rare.     

Propionibacterium acnes-associated Sarcoidosis Possibly Initially Triggered by Interferon-alpha Therapy

A 46-year-old woman with uveitis was referred to our respiratory diseases department in July 2018. Her medical history included transient bilateral hilar mediastinal lymphadenopathy (BHL) and multiple pulmonary nodules in May 2013 during pegylated interferon-alpha and ribavirin treatment for chronic hepatitis C infection. Five years post-treatment, chest X-ray revealed BHL and nodular recurrence. A biopsy of the subcutaneous buttock nodules revealed scattered non-caseating epithelioid granulomas with positive PAB immunohistochemical staining. This seem to be the first report of Propionibacterium acnes-associated sarcoidosis possibly initially triggered by interferon-alpha therapy. Understanding the mechanisms underlying interferon-triggered P. acnes-associated sarcoidosis may clarify the sarcoidosis immunopathogenesis.     

A case of miliary tuberculosis complicated by acute respiratory failure after bronchofiberscopy]

A 79-year-old man presented with persistent nonproductive cough and high fever. The chest radiograph showed bilateral miliary shadows. We performed bronchoalveolar lavage and transbronchial lung biopsy to assist diagnosis. Severe dyspnea developed after the bronchofiberscopy, when the chest radiograph revealed bilateral ground-glass shadows and the oxygen saturation in the room air fell to 60%. It was suspected that the patient had acute respiratory distress syndrome, so that methylprednisolone was given intravenously at a dose of 250 mg daily for 3 days, which resulted in a reduction in ground glass shadows and an improvement in oxygen saturation. We diagnosed miliary tuberculosis because the transbronchial lung biopsy specimen showed caseous granuloma and the PCR test for Mycobacterium tuberculosis in the bronchoalveolar lavage fluid was positive. The patient was cured with antituberculosis chemotherapy.     

Extrinsic allergic alveolitis induced by the yeast Debaryomyces hansenii.

A 65-yr-old female developed cough, fever and dyspnoea following repeated exposure to a home ultrasonic humidifier. High-resolution computed tomography showed ground-glass opacity in both lung fields. Arterial blood gas analysis gave an oxygen tension of 8.38 kPa (63 Torr). Pulmonary function testing revealed restrictive ventilatory impairment with a reduction in the diffusing capacity. The diagnosis of extrinsic allergic alveolitis (EAA) was confirmed by radiographic findings, pathological evidence of alveolitis and reproductive development by a provocation test to the humidifier water. The yeast Debaryomyces Hansenii was the only microorganism cultured from the water of the humidifier. The double diffusion precipitating test and lymphocyte proliferative response was positive for an extract of D. Hansenii, providing evidence to incriminate this fungus. This is the first described case of EAA caused by D. Hansenii.     

A case of primary pulmonary cavitation with thin smooth walls in sarcoidosis]

A 27-year-old female was admitted to our hospital after a regular medical check revealed BHL and cavitation in the right upper lung field on a chest radiograph. Ga scintigraphy showed abnormal uptake bilaterally in the mediastinal and hilar lymph nodes. We strongly suspected lung sarcoidosis, then performed TBLB and BAL. BAL fluid disclosed a high proportion of lymphocytes with a marked elevation of the CD4/CD8 ratio, compatible with sarcoidosis. A TBLB specimen revealed non-caseating epithelioid cell granuloma compatible with a diagnosis of lung sarcoidosis. From the clinical and radiological observations, it was concluded that the cavitation in the present case was primary pulmonary cavitation in sarcoidosis, as distinct from infection, malignancy, bulla or cystic bronchiectasis. Chest radiographs taken a half year after diagnosis showed reduction of the cavitary lesion and disappearance of BHL.     

Sarcoidosis with acute recurrent polyarthritis and hypercalcemia

A 45-year-old woman had bleary eyes and recurrent episodes of fever and arthritis in the knees and ankles. The patient had anterior uveitis, negative findings of the tuberculin test, and an increased serum lysozyme level, but bilateral hilar lymphadenopathy (BHL) was absent. During the course of her disease, the serum calcium and angiotensin-converting enzyme levels gradually increased to above the normal level, and the patient was clinically diagnosed as having sarcoidosis. The clinical features of arthritis were typical of those of L?fgrens syndrome although BHL and erythema nodosum were absent. The patient was successfully treated with 15 mg/day of prednisolone.     

Variation in immunoglobulin levels and circulating immune complexes in sarcoidosis. Correlation with extent of disease and duration of symptoms

Sixty-three patients with clinically definite sarcoidosis confirmed histologically and/or by a positive Kveim test were studied according to the clinical and radiographic extent and known duration of their disease and symptoms. Immunoglobulin levels were not raised among patients with bilateral hilar lymphadenopathy (BHL) alone, but IgG and IgA were raised among patients with pulmonary sarcoidosis, most markedly among patients with long-standing active disease. Serum IgM was found elevated in extrathoracic sarcoidosis. West Indian males had the highest levels of IgG. The presence of circulating immune complexes reacting with conglutinin was strongly associated with a recent symptomatic onset of sarcoidosis; they were more prevalent in patients with BHL and erythema nodosum. In contrast, polyethylene glycol precipitable immunoglobulins were associated with long-standing active disease and with neurologic involvement.