Sarcoidosis in a patient with autoimmune hemolytic anemia

A 65-year-old woman was admitted to our hospital because of severe anemia. A skin biopsy was done in January 1994 and sarcoidosis was diagnosed. Diffuse reticular shadows were seen in both lung fields on a chest X-ray film and mediastinal lymph node swelling was seen on a chest CT scan. She was followed as an outpatient and was not treated. She suddenly experienced vertigo and general fatigue in March 1995. Laboratory findings on admission were as follows: Hb 6.2 g/dl, MCV 115.9 fl, Ret 198%, LDH 732 IU/L, I-Bil 1.9 mg/dl, and Coombs' test was positive. Autoimmune hemolytic anemia was diagnosed, and she was treated with prednisolone (1 mg/kg). As of the time of this writing, she has no relapse of hemolytic anemia though prednisolone was discontinued 6 months ago.     

Moyamoya disease associated with pulmonary sarcoidosis--case report

A 61-year-old female presented with a unique case of moyamoya disease associated with pulmonary sarcoidosis. She was admitted for sudden onset of left temporalgia with episode of numbness on face, tongue, and upper extremity on the right side. The next morning, she had symptoms of Gerstmann syndrome and her ability to speak was disturbed. Her medical history included radical resection of lung cancer on the right side. She had no symptoms of pulmonary sarcoidosis. Neuroimaging showed an infarction in the left occipital lobe. Angiography showed occlusions of the bilateral internal carotid arteries at the supraclinoid portions. Subsequently, a left superficial temporal artery-middle cerebral artery anastomosis with encephalo-myo-synangiosis was performed. Ninety-three days after admission, she suddenly developed dyspnea which resulted in death 3 hours later. Autopsy findings showed typical epithelioid granulomas of sarcoid type in the lymph nodes of the peribronchus, lung, and liver. Thrombotic emboli were found in the bilateral pulmonary arteries, and marked fibrous intimal thickening in the bilateral internal carotid arteries. Immunological reaction with inflammatory events may cause pathological changes in patients with moyamoya disease or sarcoidosis. The co-incidence in this case suggests that some common inflammatory events may be involved in the pathogenesis of these diseases.     

Human herpesvirus 8 variants in sarcoid tissues

BACKGROUND: The cause of sarcoidosis is unknown, although mycobacteria have been implicated. We examined sarcoid tissues for human herpesvirus 8 (HHV-8) in addition to mycobacterial genomic sequences. METHODS: Biopsy samples from 17 patients with sarcoidosis were studied (eight transbronchial, 27 lymph node, two skin, and two oral mucosa). We used tissues (n = 137) from 96 patients without sarcoidosis as negative controls. A nested PCR was applied to amplify a segment of open reading frame (ORF) 26 of the HHV-8 genome, and a heminested PCR was to amplify a segment of ORF 25 of HHV-8 and of the 16 S rRNA gene of mycobacteria. Differences in base sequences of the amplified fragments were resolved with single-strand conformation polymorphism and dideoxy sequencing. FINDINGS: HHV-8 ORF 26 DNA was detected in significantly higher proportions of sarcoid than of non-sarcoid tissue samples from lung (8/8 vs 0/54; p < 0.0001), lymph nodes (26/27 vs 6/29; p < 0.0001), skin (2/2 vs 0/17; p = 0.006), and oral tissues (2/2 vs 1/13; p = 0.029). 31 (82%) of the 38 ORF 26 DNA-positive sarcoid specimens were also positive for ORF 25 DNA. For mycobacteria-like 16 S rRNA DNA, the proportion positive was significantly higher in sarcoid than non-sarcoid tissues for lymph node samples (11/27 vs 2/29; p = 0.003) but not for other tissues (lung 3/8 vs 22/54; skin 2/2 vs 15/17; and oral tissues 1/2 vs 0/13). Overall, the prevalence of HHV-8 ORF 26 sequences was higher in sarcoid tissues than in non-sarcoid tissues (p < 0.0001). When patients whose tissues were included in a masked phase of the study were treated as units of analysis, eight of eight sarcoidosis patients were positive for HHV-8 ORF 26 DNA, compared with three of 56 control patients (p < 0.0001); for mycobacteria-like sequences, three of eight sarcoidosis patients were positive, compared with four of 56 controls (p = 0.0464). The HHV-8 ORF 26 sequences, ten of which were unique, could be segregated into four groups according to peptide motifs. In seven of nine patients from whom biopsy samples were taken from various sites, different sequences were recovered. The mycobacterial sequences amplified from sarcoid tissues were also varied, but none was homologous to those of known species. INTERPRETATION: Variant HHV-8 DNA sequences are found in a wide range of sarcoid but not non-sarcoid tissues. Mycobacteria-like 16 S rRNA sequences are more frequently present in sarcoid lymph nodes and not in other tissue types, but do not indicate infection by a particular mycobacterial species.     

Extraocular muscle involvement in sarcoidosis

BACKGROUND: Sarcoidosis is a granulomatous inflammatory disease that may have a variety of ocular and orbital manifestations. The most common ocular manifestation is uveitis, and the most common orbital manifestation is dacryoadenitis. Extraocular muscle involvement in sarcoidosis has rarely been reported. The authors report a case of sarcoidosis involving the extraocular muscles of a 15-year-old boy with bilateral, painful, external ophthalmoplegia and enlargement of all extraocular muscles on computed tomography (CT) scan. RESULTS: Lateral rectus muscle biopsy and transbronchial lung biopsy showed noncaseating granulomas characteristic of sarcoidosis. Cultures and serologic studies excluded fungal and mycobacterial diseases. Treatment with oral corticosteroids improved symptoms and signs. CONCLUSIONS: The authors report the first case of sarcoidosis in a patient with symptomatic extraocular muscle involvement, and only the third case in which extraocular muscle involvement has been shown histologically.     

Interstitial lung disease more than 40 years after a 5 year occupational exposure to talc

A 62 yr old woman was initially diagnosed with sarcoidosis until a thoracoscopic biopsy revealed the presence of numerous birefringent particles in fibrotic areas of the centrilobular lung zones. These particles were examined by electron microscopy and X-ray spectrometry and characterized as impure talc. Further inquiry into her occupational history revealed that she had worked from the age of 14-18 yrs in a factory making rubber hoses, where she had had an intense exposure to talc. There was no evidence of silicosis or asbestosis, and other significant causes of interstitial lung disease were excluded. This case emphasizes the importance of a thorough occupational history, which may reveal a remote and forgotten exposure to a significant cause of interstitial lung disease. Although this presentation of talcosis is unusual, this case suggests that even a relatively short, but presumably intense exposure to talc more than 40 yrs previously may be a cause of progressive lung fibrosis.     

Failure to detect the presence of Chlamydia pneumoniae in sarcoid pathology specimens

The pathogenesis of sarcoidosis is not yet known. On the basis of seroepidemiological data, an association between Chlamydia pneumoniae infection and sarcoidosis has been suggested, but so far no study has addressed the direct detection of this agent in the affected tissues. The aim of the present study was to detect C. pneumoniae deoxyribonucleic acid (DNA) within sarcoid tissue specimens by means of a two-step polymerase chain reaction. Lung biopsy specimens of 33 patients with histologically confirmed pulmonary sarcoidosis and 21 control lung biopsies or pathology specimens of patients with pulmonary carcinoma or emphysema were retrospectively analysed. A nested polymerase chain reaction was applied using two sets of primers designed to detect a fragment of the 16 strand ribosomal ribonucleic acid (rRNA) gene of C. pneumoniae. The results of the study failed to demonstrate the presence of C. pneumoniae in biopsy specimens of sarcoid tissue and in the control lung biopsies or pathology specimens. Our results, therefore, tend to rule out the possibility of a direct involvement of Chlamydia pneumoniae in the pathogenesis of sarcoidosis.     

Central alveolar hypoventilation in neurosarcoidosis

Although the lung is almost always involved in sarcoidosis and respiratory failure is not uncommonly caused by intrinsic lung disease, chronic alveolar hypoventilation on the basis of neurosarcoidosis has not been previously described. This report describes the case of a 42-year-old woman with sarcoidosis and documented involvement of the lungs, muscle, peripheral nerves, and skin. She presented with ventilatory failure and a vital capacity of 700mL and required hospitalization for intubation and mechanical ventilation. After failing ventilator weaning attempts and requiring continuous ventilatory assistance, she was extubated to continuous use of noninvasive intermittent positive pressure ventilation (IPPV). She eventually weaned to nocturnal-only use of noninvasive IPPV. However, her PaCO2 remained elevated during daytime hours despite the fact that her vital capacity had returned to 3,600mL. She was not obese, and her oxyhemoglobin saturation (SaO2) was normal on room air. Subsequent attempts to discontinue nocturnal nasal IPPV resulted in marked nocturnal decreases in SaO2 and return of symptoms. This case illustrates successful noninvasive management of an apparently unique occurrence of central alveolar hypoventilation caused by neurosarcoidosis.     

Three resected cases of pulmonary cryptococcosis

Case 1 was a 53-year-old female who had a small nodule in the right S3 segment on chest CT. As she was not diagnosed by transbronchial lung biopsy (TBLB), open thoracotomy was performed. Case 2 was a 65-year-old female who had a nodule with pleural indentation in the right S6 segment. As this nodule showed difficulty to differentiate from small lung carcinoma, thoracoscopic surgery was performed. Case 3 was a 63-year-old female who had multiple lesions with cavity in the left S4 and S5 segments, which was preoperatively diagnosed by TBLB. She was performed thoracoscopic partial resection of the lingular segment because of poor response to antimycotic agents. All cases received preventive antimycotic agents for one or two months after the operation. There was no recurrence or postoperative meningitis. Thoracoscopic surgery is the effective procedure for the diagnosis and treatment of the localized pulmonary cryptococcosis.     

Concussion history in elite male and female soccer players

BACKGROUND/AIMS: Recent studies in primary biliary cirrhosis have reported the detection of serum antibodies against Mycobacterium gordonae and of mycobacterial DNA in liver sections. The aim of this study was to investigate whether mycobacterial DNA is present in liver biopsy material in primary biliary cirrhosis. METHODS: Archival liver biopsy specimens from 11 patients with primary biliary cirrhosis (10 female, mean age 52 years) and 11 patients with autoimmune hepatitis (10 female, mean age 53 years) were identified. Positive control tissue comprised five archival lymph node specimens from patients with tuberculous lymphadenopathy, three of which had stained positive on ZN staining, and also a liver biopsy specimen from a patient with tuberculous hepatitis (ZN positive). Fixed sections were deparaffinised and DNA was extracted by mechanical disruption with glass beads. DNA was purified by use of diatoms and lysis in guanidinium thiocyanate in a technique previously validated for archival DNA. Primers were directed to amplify a partial 16S ribosomal RNA gene yielding the species-specific character for mycobacteria, and also to amplify the constitutively-expressed human gene GAPDH. RESULTS: The polymerase chain reaction was shown to be capable of detecting 1 fg of M. gordonae DNA in 'spiked' samples, equivalent to 1-5 bacterial cells. No mycobacterial DNA was detected in liver biopsy samples from either the primary biliary cirrhosis or autoimmune hepatitis groups. Of the tuberculous control sections, mycobacterial DNA was detected in four of five lymph nodes and the liver biopsy specimen. GAPDH amplification was detected in all tested samples from liver disease and tuberculous control samples. CONCLUSION: These data do not support a role for mycobacteria in the aetiology of primary biliary cirrhosis.     

Oxidative stress response and characterization of the oxyR-ahpC and furA-katG loci in Mycobacterium marinum

Oxidative stress response in pathogenic mycobacteria is believed to be of significance for host-pathogen interactions at various stages of infection. It also plays a role in determining the intrinsic susceptibility to isoniazid in mycobacterial species. In this work, we characterized the oxyR-ahpC and furA-katG loci in the nontuberculous pathogen Mycobacterium marinum. In contrast to Mycobacterium smegmatis and like Mycobacterium tuberculosis and Mycobacterium leprae, M. marinum was shown to possess a closely linked and divergently oriented equivalents of the regulator of peroxide stress response oxyR and its subordinate gene ahpC, encoding a homolog of alkyl hydroperoxide reductase. Purified mycobacterial OxyR was found to bind to the oxyR-ahpC promoter region from M. marinum and additional mycobacterial species. Mobility shift DNA binding analyses using OxyR binding sites from several mycobacteria and a panel of in vitro-generated mutants validated the proposed consensus mycobacterial recognition sequence. M. marinum AhpC levels detected by immunoblotting, were increased upon treatment with H2O2, in keeping with the presence of a functional OxyR and its binding site within the promoter region of ahpC. In contrast, OxyR did not bind to the sequences upstream of the katG structural gene, and katG expression did not follow the pattern seen with ahpC. Instead, a new open reading frame encoding a homolog of the ferric uptake regulator Fur was identified immediately upstream of katG in M. marinum. The furA-katG linkage and arrangement are ubiquitous in mycobacteria, suggesting the presence of additional regulators of oxidative stress response and potentially explaining the observed differences in ahpC and katG expression. Collectively, these findings broaden our understanding of oxidative stress response in mycobacteria. They also suggest that M. marinum will be useful as a model system for studying the role of oxidative stress response in mycobacterial physiology, intracellular survival, and other host-pathogen interactions associated with mycobacterial diseases.     

Dermatomyositis complicated by sarcoidosis

We encountered a patient with dermatomyositis complicated by sarcoidosis. A 57-year-old woman was admitted to our hospital because of fever dry cough, and myalgias. There were reticular shadows on her chest X-ray film. Although the typical skin rash and myositis suggested the diagnosis of dermatomyositis biopsy specimens from a salivary gland, muscle, and lung revealed noncaseating granulomas as well. Uveitis was also noted. These findings suggested the coexistence of sarcoidosis with dermatomyositis. Examination of the lung-biopsy specimens showed interstitial pneumonia compatible with dermatomyositis, except for the granuloma. The typical rash of dermatomyositis and pathological findings of the lung specimen were inconsistent with sarcoidosis. Therefore we concluded that this patient had both dermatomyositis and sarcoidosis. This case sheds new light on the importance of pathological examinations.     

A case of lymphocytic interstitial pneumonia

A 56-year-old female was admitted on November 1995 to our hospital because of the abnormal shadow on her chest X-ray. Although the chest X ray film revealed diffuse reticulonodular shadows in the bilateral lung fields and right hilar lymphadenopathy, she had not any complaints. Furthermore, mediastinal lymphadenopathy and polyclonal hypergammaglobulinemia were noted. For a further examination, transcutaneous thoracoscopic lung biopsy was performed on August 1996. The lung specimens showed a interstitial infiltration of small lymphocytes exclusively around bronchioles. And the diagnosis of lymphocytic interstitial pneumonia (LIP) was made. She had been suffered from bronchial asthma for 27 years. This is the first report of LIP accompanied with bronchial asthma. Its relationship between LIP and bronchial asthma remains unclear. In the 2 years of follow-up, she remained asymptomatic with unchanged chest radiogram. And her pulmonary function was preserved for the 2 years. But lymphocytic interstitial pneumonia may induce malignant lymphoproliferative disease potentially, we should carefully follow up.     

The case for a heroin substitution treatment trial in Canada

A patient with malaise, uveitis and a nodular infiltrate in the left lower lobe of the lung is described. An open lung biopsy established the diagnosis of necrotizing sarcoid granulomatosis. The differential diagnosis of necrotizing sarcoid granulomatosis with sarcoidosis and angiocentric granulomatosis (Wegener's disease) is extensively discussed. Our case illustrates that NSG and sarcoidosis could be pathogenetically related.     

Sarcoidosis manifesting as uveitis and menometrorrhagia

PURPOSE: To report a rare systemic manifestation of sarcoidosis identified in a 47-year-old white woman while she was undergoing evaluation for bilateral recurrent uveitis. METHODS: The patient underwent clinical and laboratory evaluation for bilateral recurrent uveitis including serologic and radiologic testing, a gallium scan, and an endometrial biopsy. RESULTS: Although the serologic tests and chest x-ray were normal, the gallium scan was consistent with sarcoidosis, and the endometrial biopsy provided a tissue diagnosis. CONCLUSION: Sarcoidosis involving the female reproductive tract is rare. A thorough review of systems is crucial in the evaluation of any patient with recurrent uveitis.     

Primary lung cancer associated with diffuse granulomatous lesions in the pulmonary parenchyma

A 60-year-old man was admitted to our hospital for productive cough. Chest roentgenography and CT scan disclosed a left hilar tumor invading the mediastinum, with mediastinal lymphadenopathy and diffuse micronodular shadows in both lung fields. A biopsied sample of the tumor revealed squamous cell carcinoma, while noncaseating epithelioid cell granulomas were observed in the samples obtained by transbronchial lung biopsy. The granulomas in the pulmonary parenchyma were determined to be sarcoid reactions secondary to lung cancer, since there was no evidence of sarcoidosis. Combination chemotherapy was effective for the tumor, and the granulomas disappeared after completion of the chemotherapy. These findings suggest the presence of a relationship between sarcoid reactions and lung cancer in this case.     

Intense muscle uptake of gallium-67 in a patient with sarcoidosis

Sarcoidosis has been associated with muscle involvement. In general, this involvement remains asymptomatic. The following case report demonstrates a patient with a 4-mo history of sarcoidosis who reported severe fatigue and slight muscular complaints at a regular checkup. Gallium scintigraphy indicated unexpected and unusually extensive muscular localizations of the disease. The latter findings were confirmed by examination of biopsy specimens. The importance of gallium scintigraphy lies in the possibility of wholebody screening for inflammation localizations, particularly when physical, laboratory, lung function and radiographic examinations fail to provide convincing evidence of active sarcoidosis. Furthermore, it can be helpful in the follow-up of the effect of supportive treatment.     

Diagnostic accuracy of Alzheimer''s disease: a neuropathological study

We report a 83 year-old woman with dementia. She was apparently well until December of 1993 when she was 81-year-old. At that time, she was operated or her cataract. Her post operative course was uneventful, however, shortly after her operation, she had an onset of memory loss and abnormal behavior. She showed a fluctuating course in her mental disturbance. In 1995, her dementia worsened with nocturnal agitation. She was admitted to our service on June 12, 1995. She was alert and her blood pressure was 140/100 mmHg. She showed recent memory loss and disorientation to time. Motor wise, she was unable to stand unsupported. Her gait with support showed small steps and a wide base. She was bradykinetic and ataxic in her finger-to-nose and heel-to-knee test, however, no rigidity or tremor was noted. Her MRI showed T2-high signal lesions in both medial thalamic areas, in the right occipital lobe, and in the bilateral cerebral white matters as well as in the basal ganglia. She was discharged for out-patient follow up on July 3, 1995. Four days after the discharge, she showed declining responses to stimuli and she developed dyspnea on July 14, 1995. She was admitted again on the same day. Her body temperature was 38.5 degrees C and moist rales were heard in the left lung field. She appeared drowsy and no verbal response was obtained; no apparent motor palsy was noted. Blood count showed leukocytosis (14,300/ml). Blood gas analysis under 61 of oxygen inhalation through a mask was as follows: pH 7.460, PCO2 39.6 mmHg, PO2 67 mmHg, and HCO3-28.5 mEq/l. Two days after admission, she developed a convulsion in her left arm and she became unconscious. Her EEG showed periodically recurring lateralized epileptic discharges on the right fronto-central areas. Her subsequent course was complicated by status epilepticus and respiratory distress. She died on July 26, 1995. She was discussed in a neurological CPC. The chief discussant arrived at a conclusion that she suffered from multi-infarct dementia. Bilateral thalamic infarctions were considered to have played a significant role in her dementia. Post-mortem examination revealed subcortical leukoencephalopathy of Binswanger's type and cerebral infarctions in the thalamic and basal ganglia regions and in the right occipital lobe. In addition, she showed isolated angitis of the central nervous system involving mainly in the small arteries located in the superficial areas of the brain and the spinal cord. This patient was interesting in that despite relatively mild leukoaraiosis in MRI, post-mortem examination revealed profound pathologic changes in the subcortical white matters. In addition, she showed the isolated angitis of the CNS. The cause and the clinical correlates of her angitis were unclear.     

A case of sarcoid reaction associated with papillary thyroid carcinoma

Sarcoid reaction, a granulomatous lesion similar to those seen in sarcoidosis, has been reported to be associated with various disorders. Here we describe a 54-year-old woman, who was diagnosed with sarcoid reaction associated with papillary carcinoma of the thyroid. Her history included total thyroidectomy with radical neck dissection for a papillary carcinoma of the thyroid. She was found to have a right subclavian mass. Dissection of the mass was performed for the diagnosis of metastatic papillary carcinoma to the lymph node, but the pathological examination showed granuloma without caseation as well as metastasis to the lymph node. Polymerase chain reaction (PCR) of the specimen excluded a possibility of Mycobacterium infection. There was no supporting evidence for systemic sarcoidosis in this patient; the patient showed no skin, eye, or lung lesions, or bilateral hilar lymphadenopathy, and she did not show increase in serum gamma-globulin or in plasma angiotensin-converting enzyme (ACE) levels, or increased CD4/CD8 ratio of lymphocytes obtained from bronchoalveolar lavage. These findings suggest that the present case had sarcoid reaction associated with papillary carcinoma. Although sarcoid reaction has been reported to be associated with various malignancies, only five cases, to our knowledge, are reported in the literature, which were associated with papillary carcinoma.     

Cost-minimization analysis of intravenous adenosine and dipyridamole in thallous chloride TI 201 SPECT myocardial perfusion imaging

This paper deals with two patients with acetaminophen-induced pneumonitis. A 64-year-old woman suffered from mastitis while being treated by corticosteroid therapy for phemphigoid. She was administered antibiotics and acetaminophen. However, her fever continued and she subsequently developed dyspnea and interstitial pneumonia. The other patient, a 70-year-old woman, was treated with corticosteroid for lower motor neuron disease. Anti-GM1-IgM antibodies were positive in her serum. She developed wet cough and mild fever. During treatment with antibiotics and acetaminophen, her illness was complicated by dyspnea and interstital pneumonia. As a result of histological findings of transbronchial lung biopsy specimens showing interstitial infiltration of mononuclear cells, as well as clinical courses in which cessation of acetaminophen directly lead to the improvement of interstitial pneumonia, both patients were diagnosed to have acetaminophen-induced pneumonitis. The peumonitis responded well to steroid therapy. In vitro culture of peripheral lymphocytes showed stimulated proliferation by acetaminophen in both patients. These findings suggest that allergic mechanism was involved in the pathogenesis of the pneumonitis. Underlying immunological disorders may have enhanced the occurrence. Although acetaminophen is one of the most popular drugs because of a very low incidence of side effects, this drug should be applied carefully, especially with patients who have such immunological disorders.     

Lung transplantation for pulmonary sarcoidosis

Patients with end-stage sarcoidosis have now undergone lung transplantation successfully with good short-term and intermediate-term results. Lung transplantation for sarcoidosis requires several considerations unique to this disease. Selection of pulmonary sarcoidosis patients for transplantation requires that medical therapy has been exhausted. This may involve the use of corticosteriods and alternative medications. Causes of pulmonary dysfunction other than pulmonary sarcoidosis, such as bronchiectasis and myocardial sarcoidosis, must be excluded before candidates are considered for transplantation. The extent and severity of extrapulmonary disease must also be assessed and may preclude lung transplantation. The presence of mycetomas is considered a relative contra-indication by some transplant centres and an absolute contra-indication by others. Relatively few patients with pulmonary sarcoidosis have undergone transplantation and, therefore, there are few data on outcome. Sarcoidosis frequently recurs in the allograft, but rarely causes symptoms or pulmonary dysfunction. More severe acute rejection episodes may occur in sarcoidosis transplant recipients, although at present there is no evidence of an increased risk of obliterative bronchiolitis or increased mortality.