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.     

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.     

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.     

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.     

A case of elderly onset sarcoidosis

Although sarcoidosis is generally considered a disease of young and middle aged adults, there have been a certain number of cases among elderly. However it is unknown whether sarcoidosis in the elderly is recurrence of prior disease or initial onset at old ages. We present a 77-year-old woman with sarcoidosis the onset of which was considered to be in the last 6 months prior to the initial diagnosis. The patient was admitted to our hospital for further evaluation of bilateral hilar and mediastinal lymphadenopathy (BHL) and uveitis. BHL was not present in a chest radiograph taken 6 months prior to the admission. A clinical diagnosis of sarcoidosis was made by elevated serum angiotensin converting enzyme (ACE) and lysozyme (24.9 IU/L and 18.2 micrograms/ml, respectively), negative tuberculin skin test, concomitant presence of uveitis, and a high proportion of lymphocytes (33.2%) in bronchoalveolar lavage fluid with an elevated CD4/CD8 ratio (24.5). This is a noteworthy case of sarcoidosis in which we could confirm elderly onset of the disease.     

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.     

Clinical study on soluble interleukin-2 receptor in patients with sarcoidosis]

Levels of soluble IL-2 receptor in sera of 18 patients with sarcoidosis were measured by a sandwich ELISA method established by the authors and were found to be significantly higher than those in sera of normal subjects. Levels of soluble IL-2 receptor in sera of sarcoidosis cases of bilateral hilar lymphadenopathy (BHL) were significantly higher than those in sera of sarcoidosis cases without BHL. In patients with sarcoidosis, levels of soluble IL-2 receptor did not differ in relation to the presence or absence of ocular lesions, or in relation to positive or negative response to protein purified derivative of tuberculosis (PPD).     

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.     

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.     

Metastatic renal cell carcinoma simulating sarcoidosis. Analysis of 12 patients with bilateral hilar lymphadenopathy

Case summaries of four patients with bilateral hilar lymphadenopathy (BHL) caused by metastatic renal cell carcinoma are presented, and these and eight similar cases from the literature are analyzed. In nine patients, sarcoidosis was the provisional clinical diagnosis, but four of these patients had a past history of renal cell carcinoma. In the remaining five patients, a distinction from sarcoidosis could not be made by history, physical examination, and chest roentgenogram. This underscores the need for tissue confirmation in the diagnosis of sarcoidosis and alerts the physician to consider metastatic renal cell carcinoma in the differential diagnosis of BHL.     

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.     

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.     

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 pneumothorax and pleural effusion after improvement of pulmonary impairment]

A 23-year-old man was admitted to our hospital for a complete medical evaluation of abnormal pulmonary shadows found on a chest radiograph during his annual check-up. Chest radiography and chest CT showed a diffuse spread of micronodules in both lung fields and mediastinal lymphadenopathy. A transbronchial lung biopsy demonstrated evidence of noncaseating epithelioid cell granuloma with multinucleated giant cells, and a diagnosis of sarcoidosis was made. The pulmonary shadows improved without therapy. Twenty months later, the patient was readmitted to the hospital because of chest pain and dyspnea. Pneumothorax appeared on the right in a chest radiograph, but subsided after drainage therapy, and two weeks later, a right side pleural effusion was seen. We determined that the pleura was involved in the sarcoidosis, and the patient was treated with oral prednisolone 20 mg daily. The pleural effusion gradually subsided. This is the first reported case in Japan of pulmonary sarcoidosis with pneumothorax and pleural effusion after improvement of pulmonary impairment.     

Diagnosis and parameters for the evaluation of disease activity and prognosis in patients with pulmonary sarcoidosis

We evaluated the usefulness of serum ACE, BALF lymphocyte%, CD4+/CD8+ ratio when diagnosing pulmonary parenchymal lesion in patients with sarcoidosis. The results showed the substantial usefulness but lesser specificity. Furthermore, we evaluated the values of the above three parameters in terms of the judgment of the disease activity and the reliability for foreseeing the prognosis in BHL sarcoidosis. Elevated serum ACH had a good relationship with the disease activity in both nonsmoker and smoker cases. BALF lymphocyte % also had in smoker cases. But none of three parameters showed a significant relationship with the prognosis in BHL sarcoidosis.     

Sarcoidosis acutely involving the musculoskeletal system

A 69-year-old man complained of knee pain, subsequent polyarthralgia, and pains of the muscles of the pelvic girdle and thighs. At the same time, erythema of the face and hands appeared. Biopsy of the skin and muscle revealed non-caseating granuloma of epithelioid cells. The level of serum angiotensin-converting enzyme was normal, but that of lysozyme was elevated. Chest X-ray and CT did not show bilateral hilar lymphadenopathy (BHL) but revealed infiltrative ground glass appearance-like shadows of both lungs, and a Ga scintigram disclosed accumulation in the right hilar region, but not in the muscles. These complaints were quickly ameliorated by the administration of prednisolone. The present patient represented a rare case of acute musculoskeletal system involvement in sarcoidosis not typical of L?fgren's syndrome.     

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.     

Acute-onset sarcoidosis with polyarthralgia and hilar lymphadenopathy

A 33-year-old man was admitted to our hospital because of fever and arthralgia. Radiographic findings revealed bilateral hilar lymphadenopathy (BHL) and enlargement of lymph nodes of the mediastinum. Tissue from a mediastinum lymph node showed noncaseating granulomas. An acute form of sarcoidosis, Lofgren’s syndrome, was diagnosed. Prednisolone was administered. Because this syndrome is rare in Japan, histopathological examination was necessary to diagnose and treat this patient.     

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.     

Granulomatous pneumonitis following bone marrow transplantation

We describe the rare occurrence of a granulomatous pneumonitis seen in a patient following allogeneic bone marrow transplantation. Interestingly sarcoidosis was diagnosed in the marrow donor less than a year after donating his bone marrow.