Sarcoidosis and cancer revisited: a long-term follow-up study of 555 Danish sarcoidosis patients.

For more than 20 yrs it has been debated whether the systemic disease sarcoidosis predisposes to malignant neoplasms. The aim of this study was to examine the occurrence of cancer in Danish sarcoidosis patients observed for 9-30 yrs. The clinical data of 555 consecutive sarcoidosis patients were linked with the nationwide Danish Cancer Registry in a database, comparing the results with the expected incidence in the Danish population, adjusted for sex, age and calendar time. The sarcoidosis patients were diagnosed in two areas during the periods of 1960-1971 and 1970-1981, respectively, and followed until December 31, 1991. No excess of cancer was observed in sarcoidosis patients. A total number of 48 patients were observed with cancer (20 males and 28 females). Cancer occurred 1-29 yrs after sarcoidosis diagnosis (median 14 yrs) The observed versus expected (O/E) ratio was 1.16 (95% confidence interval (CI) 0.75-1.79) in males and 1.28 (95% CI 0.88-1.86) in females. No increased occurrence of lung cancer or malignant lymphoma (O/E ratios 0.23, 95% CI 0.00-1.25 and 1.25, 95% CI 0.02-6.95, respectively) was found. Neither age at diagnosis of sarcoidosis nor clinical sarcoidosis features were indicators of later occurrence of malignancy. The study could not confirm previous reports of an increased occurrence of malignant neoplasms in Danish sarcoidosis patients.

[Significant extrapulmonary manifestations of sarcoidosis]. / Betydende ekstrapulmonale manifestationer af sarkoidose.

Sarcoidosis is a granulomatous multisystem disorder of unknown genesis. Although the course is most often benign and self-limiting, serious or life-threatening extrapulmonary manifestations may occur when heart, central nervous system, kidney or the haemopoietic system are involved. In these cases, corticosteroid treatment is necessary to suppress the inflammation, prevent fibrosis in vital organs, and improve the general condition.

[Pulmonary sarcoidosis]. / Pulmonal sarkoidose.

Sarcoidosis is a systemic granulomatous disorder of unknown genesis with an average annual incidence of 10/100,000 population in Denmark. The clinical picture and prognosis are dominated by the pulmonary changes in the majority of cases. The patho-anatomical picture consists of a T-lymphocyte-dominated interstitial inflammation with non-caseating epithelioid granulomas followed by fibrosis in varying degrees. The different types and courses of pulmonary disease are reviewed. Clinical examination, chest radiography, pulmonary function tests (especially the carbon dioxide diffusion capacity) and S-angiotensin-converting enzyme (S-ACE) are the most important measures of disease activity. The value of systemic corticosteroids is critically evaluated; most patients in this country can be observed without treatment because the spontaneous resolution rate is high. It is recommended that steroids should be administrated primarily in symptomatic and progressive parenchymal lung disease, or when critical or disabling extrathoracic sarcoidosis is present. If the pulmonary parenchymal infiltrates do not disappear within approximately 18 months, a course of prednisolone for at least one year should be considered to prevent disabling or even lethal pulmonary fibrosis.

Acute neurogenic pulmonary oedema following generalized tonic clonic seizure. A case report and a review of the literature.

A case of acute neurogenic pulmonary oedema following a generalized tonic clonic seizure is presented. The condition is rare and the exact pathophysiology is unknown. Pulmonary oedema is a serious complication of epileptic seizures, however, and the importance of awareness of this condition and its treatment is emphasized by a high mortality rate in older epileptics and by the demonstration of pulmonary oedema in recent series of young epileptics who died suddenly.

Angiotensin-converting enzyme and coronary haemodynamics in coronary artery disease.

Coronary sinus pacing was performed in 12 patients with and 12 patients without significant coronary artery disease as verified by angiography in order to elucidate a possible link between cardiac exchange of angiotensin-converting enzyme and the coronary circulation. The coronary sinus and arterial blood enzyme activity remained unchanged and were similar in the two groups, both at rest and during pacing, and the activity was not related to pacing-induced changes in oxygen consumption or coronary vascular resistance. Therefore it does not seem that global cardiac formation or depletion of angiotensin-converting enzyme is of regulatory importance in the coronary vascular bed in patients with and without coronary artery disease under these circumstances.

Angiotensin-converting enzyme activity in sarcoidosis and other disorders.

A review is given on S-angiotensin-converting enzyme (SACE) and its clinical value, based upon 327 sarcoidosis patients and 1,274 patients with various disorders. SACE was elevated in 55% of the sarcoidosis patients, although with a higher frequency in those with active disease. Erythema nodosum was associated with normal initial SACE, subsequently rising, and sarcoid hypercalcaemia was consistently followed by elevated SACE. In non-sarcoid patients, elevated SACE was observed in only 10 cases. The sensitivity and specificity were 0.55 and 0.99, respectively, and the positive and negative predictive values were 0.95 and 0.90, respectively. Elevated SACE pointed strongly towards the presence of sarcoidosis, although reservations must be made in patients with liver disorders, diabetes mellitus, hyperthyroidism, asbestosis or silicosis which are rather common disorders also associated with elevated SACE. Normal SACE does not exclude sarcoidosis.

Serum angiotensin-converting enzyme in sarcoidosis and psoriasis.

Untreated pulmonary sarcoidosis is associated with an increased level of serum angiotensin-converting enzyme (SACE), which is regarded as a valuable method of diagnosing sarcoidosis and measuring the activity of the disease. The level of SACE in cutaneous sarcoidosis or other skin diseases has not been clearly established. We therefore examined SACE in 31 patients with systemic sarcoidosis, including cutaneous manifestations, and 12 patients with isolated cutaneous sarcoidosis. Also, 23 patients with psoriasis were studied. The level of SACE was generally elevated only in patients with untreated systemic sarcoidosis, whereas it was normal in cutaneous sarcoidosis and psoriasis. If the level of SACE is elevated in "isolated" cutaneous sarcoidosis, systemic disease must be strongly suspected.

Studies of peripheral blood monocytes in pulmonary sarcoidosis.

In 14 patients with pulmonary sarcoidosis and 14 matched controls we studied peripheral blood lymphocyte and monocyte counts, distribution of T and B lymphocytes, the functional helper:suppressor T cell balance, the antibody-dependent cell-mediated cytotoxicity of monocytes (monocyte ADCC), and the capacity of peripheral monocytes to generate angiotensin converting enzyme (ACE) in culture. Apart from lymphopenia in sarcoidosis patients we found a normal lymphocyte subset distribution and no evidence of increased suppressor T cell activity, using a PWM driven proliferative assay. The patients exhibited a normal monocyte count, but the proportion of monocytes was increased in sarcoidosis. Patients with active sarcoidosis had a significantly increased monocyte ADCC which was positively correlated with raised serum ACE. Peripheral monocytes had a measurable, but low ACE activity, which was modestly higher in active sarcoidosis than in controls. We could not reproduce earlier reported results on a glucocorticoid induced ACE synthesis from cultured human monocytes.

Angiotensin-converting enzyme: an indicator of bleomycin-induced pulmonary toxicity in humans?

In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or radiological evidence of pulmonary damage. While the static and dynamic lung function parameters were unchanged, carbon monoxide diffusion capacity (DLCO) decreased significantly (P less than 0.01) during a total of 126 days of pulsed regimen, indicating damage to the alveolar-endothelial membrane. S-ACE was unchanged within each treatment course but increased significantly (P less than 0.05) from the initial value to the last treatment course. Two months after cessation of treatment S-ACE returned to pretreatment values. Although the changes were modest they might mirror treatment-associated endothelial damage.

Repeated measurements of serum immunoglobulin-free light chains in early sarcoidosis.

Serum immunoglobulin free light chains (LC) are frequently increased in chronic active sarcoidosis but rarely in disease of less than 2 years duration. LC were re-measured in 19 sarcoidosis patients who were previously examined during early disease. At first examination LC were elevated in only 4 patients; all of them had achieved normal values at second LC measurement, at an average of 28 months later, in parallel with remission or inactive sarcoidosis in most cases. Elevated LC appeared eventually in 2 patients with clinical evidence of active sarcoidosis, but not in other patients with a similar clinical course. The frequent elevation of LC in chronic active sarcoidosis is, in most cases, dependent on a year-long stimulation of the immune system, longer than has been present in this series.

Angiotensin-converting enzyme activity in renal disorders: influence of disease pattern, hemodialysis and transplantation.

Serum angiotensin-converting enzyme activity (s-ACE) was measured spectrophotometrically in a variety of renal disorders. In 111 renal patients not on dialysis, s-ACE was slightly lower (22.9 +/- 5.9 U/ml; mean +/- SD) than in 116 controls 24.4 +/- 6.2 U/ml). In 52 patients on chronic hemodialysis s-ACE was 24.1 +/- 4.7 U/ml; serial analyses done before initiation of chronic dialysis showed a significant increase in s-ACE levels towards normal values. In 38 renal allograft recipients s-ACE was relatively low (22.0 +/- 5.0 U/ml); a significant decrease in s-ACE was observed in patients followed from the time of transplantation (24.6 +/- 6.4 U/ml) to two weeks after transplantation (20.2 +/- 4.5 U/ml). S-ACE was also depressed (17.4 +/- 2.6 U/ml) in 12 patients with acute renal failure, and it increased in parallel with normalization of renal function. S-ACE was normal (24.4 +/- 5.7 U/ml) in 14 patients with essential hypertension. Elevated s-ACE (above mean of controls + 2 SD) was observed in only one patient of the total series. We could not confirm previous reports on elevated s-ACE in dialysis patients, but several factors invalidate a direct comparison between series. Thus, the deviations in s-ACE in renal disorders seem to be discrete: depressed levels in acute renal failure and a relative depression in undialyzed patients with chronic renal disorders. The low activity after transplantation may be secondary to the immunosuppressive treatment.