Biomedical subjects
Publications and source records attributed to D Valeyre.
A case of sarcoidosis with iterative spontaneous increase and decrease of thoracic lymphadenopathy is described. No condition such as infectious disease, particular environmental exposure or medication could explain this unusual course of thoracic sarcoidosis.
The "syndrome of inappropriate calcitriol secretion" may be observed in diseases with disseminated granulomas. The main examples are sarcoidosis and tuberculosis, but it can also be observed in fungal infections, in granulomas due to foreign bodies and in lymphomas. The syndrome is due to autonomous production of 1 alpha hydroxylase by granulomas. The insuing synthesis of calcitriol escapes normal regulation by serum calcium and phosphate levels. The syndrome includes hypercalcemia, hypercalciuria, high 1,25(OH)2D3 serum levels and reduced PTH secretion. It can supervene in anephric or hypoparathyroid patients. The notion that calcitriol may be secreted extrarenally is new. It could have important bearings on several issues in nephrology, immunology and oncology.
To examine the possibility that mast cells have a central role in the pathogenesis of hypersensitivity pneumonitis, 20 patients with this disease were studied with the aim of seeking evidence for mast cell degranulation. The number of mast cells recovered by bronchoalveolar lavage from patients with hypersensitivity pneumonitis was more than 1,000 times greater than those recovered from normal individuals. Furthermore, discontinuation of antigen exposure resulted in an increase in the number of mast cells observed, consistent with the possibility that antigen exposure had induced mast cell degranulation. Cessation of antigen exposure also resulted in a rapid decrease in the number of neutrophils and eosinophils recovered by lavage, followed by an increase in the number of T8+ T lymphocytes present. In each case the time course of the changes was consistent with the possibility that mast cell degranulation had been important in regulating the number of the immune and inflammatory cells present in the lung. Histamine was present in lavage fluid supernatant from patients with hypersensitivity pneumonitis. The amount of histamine present was, however, closely correlated with the number of mast cells present and not with the interval since last antigen exposure. Delay in separating cells from lavage fluid supernatant resulted in an increase in histamine content. These results suggest that the free histamine in lavage fluid resulted from the degranulation of mast cells induced by the lavage procedure as histamine released in vivo has a short half life. We suggest that hypersensitivity pneumonitis results from a "late phase reaction" initiated by antigen induced mast cell degranulation.
The pulmonary manifestations of varicella are observed more frequently in adults than in children. They make present according to 3 modes: acute, subacute or chronic. The authors report 2 cases of chronic pulmonary manifestations in the form of diffuse, partially calcified micronodular lesions of both lung fields observed in the course of varicella in adults.
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Cigarette smoking produces marked alterations in the lung parenchyma and in the population of immune and inflammatory cells present in the lower respiratory tract. These cigarette-induced changes appear to influence the incidence of two different interstitial lung diseases, histiocytosis X and sarcoidosis. Smoking is a strong risk factor for the development of pulmonary histiocytosis X, since the incidence of smoking is very high among patients with histiocytosis X: 90% of the patients with histiocytosis X were smokers; 46% of the controls were smokers (p less than .001). In contrast, smoking appears to reduce the incidence of sarcoidosis: 31% of the patients with sarcoidosis were smokers (p less than .05 compared to controls). In an effort to understand how cigarette smoking influences the incidence of these two disorders, we compared the numbers and types of immune and inflammatory cells recovered by bronchoalveolar lavage from nonsmoking and smoking controls and patients with histiocytosis X and sarcoidosis. Although nonsmoking patients with histiocytosis X did not have a significant increase in the number of alveolar macrophages recovered by lavage (p greater than .2 compared to normals), smoking patients had an increase in the number of alveolar macrophages similar to that observed in the control population. In contrast, the number of macrophages recovered from patients with sarcoidosis who smoked was considerably less than that observed in normal smokers (p less than .05 comparing patients with sarcoidosis and controls who smoked 1-20 cigarettes/day). This difference in the intensity of the cigarette-induced macrophage alveolitis observed in the two patient groups may be important in explaining the opposite effects of cigarette smoking on the incidence of histiocytosis X and sarcoidosis.
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Two cases of lymphoid interstitial pneumonia, diagnosed according to Liebow's criteria, are reported. In both cases an extra-thoracic lymphoma developed 3 and 6 years respectively after the interstitial pneumonia was diagnosed. Simultaneously, the radiological images of the lungs became more pronounced. Only a few similar cases have been published. This raises the question of whether lymphoid interstitial pneumonia and lymphomas are distinct entities, especially since the histological and immunopathological discriminating criteria seem to be discussed.
A Tl 201 scan was performed on one young patient who met all of the criteria for the diagnosis sarcoidosis. A resting scan before treatment showed marked defects which were not resolved on the redistribution scan, thus leading to the diagnosis of cardiac sarcoidosis, which was also suspected from clinical signs. After dipyridamole infusion (0.142 mg/kg per minute over 4 min), his 201Tl scan was quite normal. Haemodynamic investigation showed a low coronary sinus blood flow with a low lactate extraction: these abnormalities were fully reversed by i.v. dipyridamole infusion. Afterwards, the patient was given oral dipyridamole (450 mg/day) over 4 weeks; at the end of this treatment, his resting 201Tl scan was quite normal. These results suggest that myocardial perfusion abnormalities in sarcoidosis may be reversible after pharmacological vasodilation. Thus, in order to assess cardiac sarcoidosis, a resting myocardial scan should be performed before a scan after dipyridamole infusion. These results may have clinical, pathophysiological and therapeutic implications with regard to cardiac sarcoidosis.
Twenty-two families, the ethnic origins of which were Caucasian (16) or mixed Caribbean (6), each with two or three members suffering from sarcoidosis, were studied. The frequency of familial sarcoidosis when all races are considered is 2.4 p. 100 but it is higher in people born in the Caribbean. Clinically, this form is no different from non-familial cases but there is a tendency, especially in homozygotic twins, for the dates of revelation of the disease to be very close to each other, and for the clinical and radiological features and the evolution to be the same. A higher frequency of pairs of the same sex with equal numbers of parent-sibling and sibling-sibling pairs were observed. There was no predominance of mother-sibling with respect to father-sibling pairs. The HLA system study was too fragmented to draw any conclusion about the mode of transmission of familial sarcoidosis.
Sarcoidosis is frequently attended by hypercalciuria and sometimes by hypercalcaemia. The type of hypercalciuria and its relationships with disease extension and activity have rarely been investigated. In order to clarify these issues we undertook an investigation by a calcium absorption test in 39 patients with untreated thoracic sarcoidosis, and tried to establish correlations with vitamin D3 metabolism and some features of the disease. We found three types of responses. Group I (n = 12) with a normal test had normal 1,25-(OH)2D3 and rare extrathoracic localisations. Group II (n = 14) with absorptive hypercalciuria had higher serum calcium; 1,25-(OH)2D3 (p less than 0.001) and the free 1,25-(OH)2D3 index (p less than 0.05) were raised. Sarcoidosis was more often inflammatory, developing and disseminated. Group III (n = 13) had resorptive hypercalciuria, and hypercalcaemia was frequent. 1,25-(OH)2D3 (p less than 0.01) and the free 1,25-(OH)2D3 index (p less than 0.05) were raised but to the same degree as in Group II. Sarcoidosis was more disseminated and developing than in Groups I and II. In the 39 patients, iPTH and nephrogenous cAMP were low. Post-calcium load urinary calcium/creatinine (Ca/Cr) and 1,25-(OH)2D3 were correlated (p less than 0.05). Extrathoracic extension was associated with higher fasting urinary Ca/Cr (p less than 0.001), and development with higher post-load urinary Ca/Cr (p less than 0.001). Thus, absorptive hypercalciuria is related to the development of sarcoidosis and can be explained by high free 1,25-(OH)2D3, while resorptive hypercalciuria seems to be linked with disease extension. In such a case, the mechanism of osteolysis is not solely accounted for by high 1,25(OH)2 vitamin D3 serum levels, and we postulate that some other factor is at work, related to the extent of the granulomatous process.
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In order to investigate the initial course of pulmonary sarcoidosis, the following investigations were carried out in 14 nonsmoking patients with Logfren 's syndrome 3 to 12 wk after the onset of erythema nodosum (EN): bronchoalveolar lavage (BAL) (cellular and protein components), serum assays of lgG and of the activity of angiotensin-converting enzyme (SACE), and pulmonary function tests. These results were related to the disease duration, estimated by the time lapse separating the onset of EN from the investigations. All patients but one showed a large increase in the percentage of lymphocytes (%-L) in BAL fluid (more than 30%). Although each patient was evaluated only once, and thus this work was not an actual longitudinal study, a linear relationship between lymphocyte count per milliliter of recovered fluid during BAL (L-count) and disease duration was found during the first 8 wk (r = 0.78, p less than 0.01), suggesting a fast-developing alveolitis. The delayed rise in SACE level may indicate a secondary activation of macrophages; SACE and L-count were well related, either up to 8 wk (SACE versus L-count: r = 0.84, p less than 0.01) or up to 12 wk (SACE versus L-count: r = 0.61, p less than 0.01). Serum lgG levels were found to follow the L-count (serum lgG versus L-count: r = 0.79, p less than 0.01) and appeared to be a reliable index of disease activity. Respiratory function showed a univocal pattern, with a marked decrease in all of the patients in carbon monoxide diffusing capacity (DLCO), contrasting with normal lung volumes.(ABSTRACT TRUNCATED AT 250 WORDS)
This study discusses mediastinal and pulmonary involvement in sarcoidosis. The main points of discussion are the clinical consequences of the histopathological changes of the disease, especially the alveolitis, the initial lesion preceding granuloma formation and, new methods of investigation such as measurement of the angiotensin converting enzyme, Gallium 67 scintigraphy and bronchoalveolar lavage. Assessment of the activity of the disease and the indications of steroid therapy are analysed with respect to these informations.
Lymphocyte counts in the peripheral blood were performed in 123 patients with thoracic sarcoidosis and in 33 healthy subjects. A significant decrease in the number of lymphocytes as compared to controls was observed, at least in patients of Caucasian origin. This lymphopenia was more pronounced when the disease was of more than 10 years' duration, was accompanied by extrathoracic manifestations and belonged to radiological groups II or III. The only parameter of pathological activity with which it correlated was serum angiotensin converting enzyme activity. Patients from the french Caribbean had scattered lymphocyte counts which precluded any firms conclusion.
This paper discusses the problems of cardiac sarcoidosis in patients with respiratory diseases. Emphasis is placed on the difficulty of diagnosing minimal and atypical lesions, the value of thallium scintigraphy and therapeutic problems.