Hot issues from the fifth WASOG meeting Essen Germany, September 17-19 1997. World Association for Sarcoidosis and Other Granulomatous Disorders.
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Germany↗
Biomedical subjects
G Rizzato
Publications and source records attributed to G Rizzato.
[Detection of mycobacterium tuberculosis DNA using nested polymerase chain reaction in lymph nodes with sarcoidosis, fixed in formalin and embedded in paraffin].
An involvement of mycobacteria in the pathogenesis of sarcoidosis has often been hypothesized, but not confirmed reproducibly. In this study we applied a nested Polymerase Chain Reaction (PCR) to the insertion sequence IS6110 for detection of Mycobacterium tuberculosis (MT) DNA in formalin-fixed and paraffin-embedded tissues from patients with sarcoidosis, with tuberculosis and atypical mycobacteriosis confirmed by culture, and from negative control samples. MT-DNA could be detected in 2/30 samples of sarcoidosis, in 10/10 tuberculoses, in 0/5 atypical mycobacterioses and in 0/10 negative controls. Nested PCR confirmed its high sensitivity and specificity in detecting MT-DNA on archival histopathological specimens. From our results we conclude that in the granulomatous lesions of sarcoidosis MT-DNA is only sporadically demonstrable and probably it doesn't play a role in the pathogenesis of this disease.
DNA, Bacterial↗
Uveitis as a presenting feature of chronic sarcoidosis.
Uveitis is often a manifestation of sarcoidosis. Less well-recognized, however, is the development of uveitis several years before the diagnosis of systemic sarcoidosis. The possibility that presentation of uveitis is a marker for the chronicity of sarcoidosis has never been investigated. The aim of this work was to evaluate, in a Caucasian population, the epidemiology of uveitis as the primary manifestation of sarcoidosis with long-term follow-up, and the relationship of uveitis to the chronicity of sarcoidosis. The records of 1,156 Caucasian patients with histologically proven sarcoidosis, first seen in the period 1976-1992, were reviewed. In patients in whom uveitis was the primary feature of sarcoidosis, the following parameters were identified: systemic manifestations; time interval between the diagnosis of uveitis and sarcoidosis; therapy; the evolution of chest radiographic image over time; chronicity; the relationship between sarcoidosis and uveitis; and, finally, status in October 1994. In nine patients, uveitis was the reason for seeking medical treatment, resulting in the discovery of systemic sarcoidosis, which was then found to be chronic in 7 out of 9 cases. In an additional eight patients, uveitis preceded the diagnosis of systemic sarcoidosis by 1-11 yrs, and yet most subjects had systemic manifestations that went unrecognized during this time period, with chest radiograph at the time of diagnosis suggesting a long-standing chronic disease. Thus, uveitis appeared to be the primary manifestation of sarcoidosis in 17 of the 1,156 patients studied (1.5%). In conclusion, any uveitis of unknown origin may be due to sarcoidosis, although its systemic manifestations may not occur for up to 11 yrs. Uveitis patients need a very long-term follow-up, including periodic diagnostic tests for systemic sarcoidosis. Furthermore, when uveitis precedes the systemic symptoms and diagnosis of sarcoidosis by more than one year, it may be regarded as a marker of the chronicity of sarcoidosis.
Adult↗
An iceberg from Hokkaido and Scandinavia.
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Biopsy↗
Nephrolithiasis as a presenting feature of chronic sarcoidosis: a prospective study.
BACKGROUND AND AIM OF THE WORK: The presentation of sarcoidosis with renal stones has never been evaluated in a prospective study. DESIGN: We have studied 110 consecutive patients with histologically proven sarcoidosis, first seen in the years 1993-1994 in the Milan Sarcoid Clinic. Those who had renal stones preceding or suggesting the diagnosis of sarcoidosis, and those who had evidence of renal calculi at presentation, were studied up to 31 December 1995 with serial evaluation of calcaemia, calciuria and serum 1,25 (OH)2D3 and are the basis of this report. RESULTS: Four patients had had calculi a long time ago and probably unrelated to their sarcoidosis. Three patients had a previous history of recurrent colic with calculi. In one further patient the occurrence of calculi suggested the diagnosis. In three other patients pyuria or microscopic haematuria at the presentation of pulmonary sarcoidosis led to the diagnosis of asymptomatic calculi. All the above seven patients had features of chronic disease and required long term corticosteroid therapy. Four of them required lithotripsy or pyelotomy before starting steroid therapy. Another had further calculi during the follow-up, and an episode of hydronephrosis requiring lithotripsy, due to poor compliance to corticosteroid therapy. Another patient had a single stone during follow-up in spite of proper therapy. In all the others prednisone was useful to control the disease. Summing up the results of a previous similar but retrospective study from our clinic, we can describe the full spectrum of nephrolithiasis at presentation of sarcoidosis, as it appears from the examination of 729 consecutive patients seen over 17 years (1978-1994), with a further follow-up of at least one year (see Conclusions). CONCLUSIONS: 1. Renal stones may be the presentation of sarcoidosis in 3.6% of cases, but the etiology may go unrecognized for many years in most of them. 2. There are asymptomatic renal stones at presentation in a further 2.7%: pyuria or microscopic haematuria may suggest such an occurrence. 3. Renal calculi appear to be a marker of chronicity, with long term corticosteroid therapy required in most cases. 4. A diagnosis of sarcoidosis should always be considered when patients present with renal calculi of unknown origin.
Adult↗
Nephrolithiasis as a presenting feature of chronic sarcoidosis.
BACKGROUND: Renal calculi have been reported to occur in about 10% of patients with chronic sarcoidosis, but nephrolithiasis as a presentation of this disease has not been studied. METHODS: The charts of 618 patients with histologically proven sarcoidosis, seen in the period October 1978-1992, were reviewed in order to identify nephrolithiasis at presentation. RESULTS: Seventeen patients had renal calculi which preceded other manifestations of sarcoidosis. In six the occurrence of calculi suggested the diagnosis. Another eight patients had a previous history of recurrent colic with calculi. The time intervals between the first calculus and the appearance of other manifestations of sarcoidosis ranged from one to 25 years, but it was over four years in only two cases and all had at least one calculus in the year before the diagnosis was made. In the other three patients appearance of the calculus was distant in time and was probably unrelated to their sarcoidosis. In most cases the sarcoidosis was chronic and needed long term treatment with corticosteroids. Four patients had further calculi during follow up (one month to 16 years) due to an improper withdrawal of treatment decided by the patient in two cases, and to the reduction in the corticosteroid dose in the other two. CONCLUSIONS: Calculi were the presenting feature of sarcoidosis in six (1%) patients, and were the first manifestation of the disease in a total of 14 (2.2%). This frequency is over 20 times the likely incidence of calculi in the general population. Renal calculi may therefore be a rare primary manifestation of sarcoidosis. In such cases the disease is likely to be chronic and to require long term corticosteroid therapy. Sarcoidosis should always be suspected in cases of nephrolithiasis of unknown origin.
Adrenal Cortex Hormones↗
Efficacy of a three day course of azithromycin in moderately severe community-acquired pneumonia.
This study was designed to evaluate the efficacy of a 3 day course of azithromycin in low to moderately severe community-acquired pneumonia. Forty patients with low to moderately severe community-acquired pneumonia (29 males, 11 females, mean age 46 +/- 17 yrs; 20 pretreated with betalactams for 2-10 days with no results before admission to hospital; 18 with evidence of co-morbidity) were enrolled in an open, randomized study with azithromycin, 500 mg q.d. oral therapy for 3 days, versus clarithromycin, 250 mg b.i.d. oral therapy for 10 +/- 2 days. The aetiology of pneumonia was identified in 18 patients by serology (nine Mycoplasma pneumoniae, four Chlamydia pneumoniae, five Legionella pneumophila; one patient with chlamydial infection also had Klebsiella pneumoniae bacteraemia). A presumptive aetiological diagnosis was obtained with sputum culture in three other patients (one Haemophilus influenzae, two Haemophilus parainfluenzae), all strains were sole isolates with 10(8) Colony forming units (CFU), and with Gram stain in one patient with Streptococcus pneumoniae. All patients in the azithromycin group (one after a second 3 day course), and all but two (of those available for evaluation) of the clarithromycin group were cured. Defervescence occurred after 2.6 +/- 1.6 days, and chest roentgenogram cleared after 8.9 +/- 3.3 days, with no difference between the two groups. Tolerance was good, and there were no withdrawals from therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The differential diagnosis of hard metal lung disease.
Hard metal lung disease is usually easy to diagnose, on the basis of occupational history, chest X-ray appearance of interstitial lung disease and, if necessary, by bronchoalveolar lavage (BAL). However, other interstitial lung diseases may affect patients with an occupational history of exposure to cobalt. In hard metal disease, the hylar lymphnodes may enlarge due to high draining of hard metals from the lung tissue via lymphatic vessels. Also, the presence of Giant Cells (even if Langhan's type) in the BAL fluid of sarcoid patients may be high. We present four patients with a history of exposure to hard metals and whose chest X-rays suggest sarcoidosis, stage II; in each, a pulmonary biopsy was necessary to confirm the diagnosis. Final diagnosis was sarcoidosis in one (showing typical granulomata in the lung tissue), and hard metal disease in three: two of these had foreign body-type granulomata in the lung tissue. Neutron activation analysis (NAA) study was carried out on these four patients using specimens of BAL fluid, blood, urine, toenails, pubic hair and sperm. In the light of available data, the concentration of elements may not be useful in differentiating between sarcoidosis and hard metal pneumoconiosis. However, NAA on BAL fluid or other specimens may be helpful in confirming the presence of the offending agent in suspected cases when the occupational history is not clear.
Adult↗
Gastrointestinal presentation of Churg Strauss syndrome.
Gastrointestinal involvement is frequent in patients with Churg Strauss Syndrome: clinical symptoms (abdominal pain, diarrhea or bleeding) range from 44 to 89%, pathologic involvement of the bowel from 33 to 92%, and gastrointestinal death (bleeding or perforation), described in 8% of cases, is the fourth leading cause of death after heart, CNS and renal failure. In spite of this wide-spread digestive involvement, gastrointestinal presentation has never been described. We present a 56 year old man with Churg Strauss Syndrome, where eosinophilia, diarrhea and gastrointestinal bleeding appeared three years before asthma. This is probably the first description of gastrointestinal presentation of Churg Strauss Syndrome.
Abdominal Pain↗
Sarcoid extrapulmonary features. Shift of the bioptic approach from the mediastinoscopy to the pleuroscopy.
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Biopsy↗
Reversibility of exogenous corticosteroid-induced bone loss.
Osteoporosis is not usually considered to be reversible, as it is a consequence of the ageing process. However, an improvement of bone mineral density after successful surgery in Cushing's syndrome has been shown in several reports. The question of reversibility of exogenous corticosteroid-induced osteoporosis is, as yet, unanswered, possibly because of the difficulty in discontinuing steroids after long-term use. We describe six patients, all under 45 yrs of age, with chronic long-standing sarcoidosis, in whom long-term prednisone therapy resulted in 15 +/- 7% bone loss, as evaluated by quantitative computed tomography. This side-effect appeared fully reversible after prednisone withdrawal. This report of the reversibility of exogenous corticosteroid-induced bone loss needs confirmation in elderly people, where the capacity for recovery of bone mass could be reduced. Such potential for recovery may have implications for the pattern of use of corticosteroids.
Adult↗
Treatment with low dose metformin in patients with peripheral vascular disease.
Low dose metformin (500 mg b.i.d.) was tested in 11 patients with symptomatic peripheral vascular disease (PVD) in an open design. At -1, 0, 1, 4, 7 months the major lipid and lipoprotein parameters, arterial function, and fibrinolytic activity were monitored. Arterial function changes were similar to those found with a high dose (850 mg t.i.d.) metformin but plasma lipids did not change to an appreciable extent. Post-ischaemic blood flow, by plethysmography, rose 30%; the exercise capacity, evaluated by treadmill test, also increased significantly by 105.7% for relative and 53.3% for absolute claudication. Total fibrinolytic activity did not change during the treatment but the antigens of two of the major components of the fibrinolytic system, i.e. t-PA and PAI-1, were significantly reduced at the end of the study. This study gave results quite consistent with those obtained with higher metformin doses, associated with a potentially higher risk of lactic acidosis.
Aged↗
Bronchopulmonary lavage (BAL). A window of the lungs.
Bronchopulmonary lavage (BAL) has provided a fresh dimension for the investigation of pulmonary and multisystem disorders. BAL fluid may be analysed for cells and chemical mediators in the diagnosis and also serially for the management of several granulomatous disorders including sarcoidosis, extrinsic allergic alveolitis, chronic beryllium disease, talc granulomatosis, tuberculosis, Langerhans' histiocytosis-x and Crohn's disease. It may also provide information in fibrosing alveolitis, collagen vascular disease, occupational and drug-induced lung disease, acquired immune deficiency syndrome, bronchial asthma, neoplasia, transplantation, pulmonary alveolar proteinosis and eosinophilic lung disease. This survey analyses the value of BAL and how it has provided a new window for the chest physician.
Bronchoalveolar Lavage Fluid↗
Multi-element follow up in biological specimens of hard metal pneumoconiosis.
The movement of Co and the other components of the hard metal in the body fluids, their solubility, their links to the cells and proteins of the body, and their clearance are largely unknown. The first aim of this work is to evaluate whether Neutron Activation Analysis (NAA), a new analytical technique based on the radiochemical separation of samples irradiated in a Nuclear Reactor, may be suitable for studying the movement of elements in tissues or body fluids of workers over time. We have investigated seven hard metal workers, all employed in the grinding process, with NAA studies (single study in two, follow-up in five) of 29 elements on lung tissue, BAL fluid, blood, urine, pubic hair, toenails and sperm. In three, the diagnosis of hard metal pneumoconiosis was easy; in the other four, due to evident bilateral hilar lymphadenopathy, it was difficult to distinguish between pneumoconiosis and sarcoidosis stage II, and the final diagnosis, after pulmonary biopsy, was hard metal pneumoconiosis in three, and sarcoidosis in one. In spite of high potential, NAA gives a number of unexpected results, with apparent controversies and no clear relationship in the evolution of levels of Co, W and Ta: there is no simple explanation for such apparent inconsistencies at present, so that the study of the movement of elements in body fluid sometimes appears disappointing with this technique. Other observations were noted from the data available: 1) the concentration of elements (Co, Ta, W) in lung tissue is far higher than in BAL fluid, but the factor is so variable that BAL fluid cannot be taken as representative of the concentration of elements in lung tissue. 2) High concentrations in tissues or body fluids are indicative for exposure, but not for disease. In the light of available data, there are no levels above which development of disease is inevitable. 3) When the problem is to distinguish between sarcoidosis and pneumoconiosis in exposed subjects, the concentration of elements is of no value, and the pulmonary biopsy is still necessary. However a NAA study may be helpful to confirm the presence of the offending agent, and to avoid pulmonary biopsy in cases where the occupational history is unclear.
Adult↗
Prevention of corticosteroid-induced osteoporosis with salmon calcitonin in sarcoid patients.
The aim of this study was to evaluate the usefulness of salmon calcitonin (sCT) in preventing corticosteroid-induced osteoporosis. Three groups of patients with sarcoidosis requiring long-term steroid therapy were followed for 2 years with yearly evaluations of vertebral cancellous mineral content (VCMC) by quantitative computed tomography. The first group (n = 18) was treated with intramuscular (i.m.) sCT for the 2-year study period; the second (n = 11) with i.m. sCT for the first 4 months and then with sCT nasal spray for 20 months; the third (n = 35) received no sCT. We observed a large mineral loss in the third group but a very slight drop of VCMC in the two groups receiving sCT. SCT nasal spray was better tolerated and as effective as i.m. injections. The action of sCT appeared extremely useful, especially in the first year of steroid therapy when corticosteroid-induced mineral loss was maximal. We conclude that sCT nasal spray is a good tool for preventing corticosteroid-induced osteoporosis.
Administration, Intranasal↗
Long-term therapy with deflazacort in chronic sarcoidosis.
PURPOSE: To evaluate the long-term action of deflazacort (DF), a new calcium-sparing and bone-saving corticosteroid, in chronic sarcoidosis patients needing prolonged therapy. PATIENTS AND METHODS: 40 patients with chronic histologically proved sarcoidosis requiring long-term corticosteroid therapy were treated with DF and followed for a mean period of 958 +/- 515 days (range 382-2, 068). The indication for giving corticosteroid therapy was pulmonary impairment in most (36), but also other events including hypercalcemia (2), kidney stones (5, 2 with recurrent colic), uveitis (2), lupus pernio (3), suspected heart impairment (5), hypersplenism (1), and other causes. Follow-up examination included serial ACE, chest x-ray, 67Ga lung scan, pulmonary function data, serum and urinary calcium levels. Eleven patients (UT group) were not receiving glucocorticoids when first seen at our clinic; 29 patients (PT group) were on therapy with glucocorticoids (27 wity prednisone, 2 with DF) for 870 +/- 1,128 days (range 27-4,310) RESULTS: In the PT group, DF maintained the good results previously obtained with prednisone; in this group, chest x-ray film showed improvement in 16 patients, 67Ga lung scan was better in 13, while worsening chest x-ray film findings in 1 and 67Ga lung scan in 2 was seen coincident with DF tapering. Respiratory function data showed a mild nonsignificant improvement. SACE decreased significantly from 114.6 +/- 38.7 to 91.5 +/- 37.9 nM/ml/min (p less than .05). In the UT group the results were better, as expected in a population where the action of corticosteroids did not influence the first observation. FVC increased significantly from 76.3 +/- 13.0 to 89.9 +/- 19.5 percent predicted (p less than .01); the 67Ga lung scan and chest x-ray film findings improved in all but 1 patient, and ACE dropped significantly (p less than .01) from 131.8 +/- 46.3 to 83.7 +/- 25.0. In both groups the side effects were mild, and only 2 patients discontinued the treatment, 1 for gastric ulcer, and the other for amenorrhea plus a 14 kg weight gain. CURRENT STATUS: One patient died of cancer, 9 discontinued treatment (5 because therapy was no longer necessary, 2 for the above described side effects, 2 for non-drug-related reasons), 4 dropped out and were last seen when taking DF 22.5, 18, 12 and 6 mg daily respectively. Twenty-six are continuing the drug on a long-term basis at the current mean daily dose of 12.1 +/- 7.3 mg (range 3-30). In a number of these, an attempt to discontinue DF resulted in a sarcoid relapse, and DF was restarted. CONCLUSION: DF is a good and safe approach to the long-term corticosteroid therapy of sarcoidosis.
Adult↗
Bone loss in untreated longstanding sarcoidosis.
The introduction of new techniques for the study of Bone Mineral Content (BMC) has not yet been extensively applied to sarcoidosis. Using Quantitative Computed Tomography (QCT) in a long-term prednisone-treated sarcoid population we have shown in 1988 [1] that Bone Mineral Loss is more frequent than elsewhere reported with other techniques on patients with different diseases. It was not clear if this difference was due to the sarcoidosis itself or to the better sensitivity of QCT compared to former techniques [2]. Thus we have now studied QCT in a group of 36 untreated patients with active, histologically proven sarcoidosis, chronic in most cases, to clarify the action of sarcoidosis itself over the BMC. For each patient Vertebral Cancellous Mineral Content (VCMC) has been expressed in terms of Z score (i.e. the number of Standard Deviations (SD) above or below the normal value) in order to overcome the differences due to age and sex. In the whole group, mean value of Z score was -0.41 +/- 0.30 (P > 0.05 vs. 190 normals). Nevertheless VCMC was below the normal range in 13 out of 36 patients; in five of them, all with longstanding sarcoidosis for at least 2 years, VCMC was more than two SD below the normal; four out of 36 had a VCMC lower than 110 mg/cm3 K2HPO4 eq, that is considered the threshold level under which the risk of fracture begins (but three of them were postmenopausal females).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Is sarcoidosis a borreliosis?
Recently some Authors have suggested that sarcoidosis may be a borreliosis. Thus in the period April to June 1991 we studied serum samples of 12 sarcoid patients (pts) by ELISA in order to identify antibodies to Borrelia burgdorferi (Bb). None had positive results. We conclude that great caution is to be used in advancing the hypothesis of an etiologic role of Bb in sarcoidosis.
Adult↗