Hydrocephalic neurosarcoidosis diagnosed by cutaneous lesions.
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Biomedical subjects
Publications and source records attributed to Juan Mañá.
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OBJECTIVE: To determine whether Mycobacterium tuberculosis ribosomal RNA (rRNA) is present in fresh tissue specimens from patients with sarcoidosis. DESIGN: A prospective study. SETTING: A university-based hospital. Patients Thirty-five patients diagnosed as having sarcoidosis at the University Hospital of Bellvitge, Barcelona, Spain, were included in the study. Fresh tissue samples with granulomatous inflammation were prospectively collected between 1997 and 2001 from all patients. For each sample tested, approximately 1 negative control was included. MAIN OUTCOME MEASURES: Mycobacterium tuberculosis rRNA was detected using an isothermal enzymatic amplification system of target rRNA of M tuberculosis complex via DNA intermediates. Smears for acid-fast staining and mycobacteriological cultures were also obtained. RESULTS: A total of 78 biopsy specimens (57 skin, 10 lymph node, 3 lacrimal gland, 2 spleen, 2 lung, 2 muscle, 1 bone, and 1 nerve) collected from 74 patients (35 patients with sarcoidosis and 39 control patients) were included in the study. Stains for acid-fast bacilli and mycobacterial cultures were negative for organisms in all cases. Mycobacterium tuberculosis rRNA was not detected in the specimens from any patients with sarcoidosis or in those from control patients whose cultures were negative for organisms. Ribosomal RNA was detected in 6 tissue specimens from patients with cultures that were positive for M tuberculosis and that were processed in parallel to the samples included in the study. CONCLUSIONS: Although previous studies have reported that mycobacterial antigens may play a role in granuloma formation in some patients with sarcoidosis, our results suggest that M tuberculosis cannot be considered to be the etiologic agent of the disease.
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We describe the clinical characteristics, the patterns of association, and the role of antiviral therapies in patients with sarcoidosis associated with chronic hepatitis C virus (HCV) infection. Sixty-eight patients were included in the current study, 56 cases identified in the literature search plus 12 unpublished cases from our department. In 50 HCV patients, sarcoidosis appeared after starting antiviral therapy. Antiviral therapy associated with triggered sarcoidosis consisted of alpha-interferon monotherapy in 20 cases and combined therapy with alpha-interferon and ribavirin in 30. Sarcoidosis appeared during the first 6 months after starting therapy in 66% of patients. The clinical picture of sarcoidosis included predominantly pulmonary disease in 38 (76%) patients and cutaneous sarcoidosis in 30 (60%). Antiviral therapy was discontinued in 60% of patients and continued or adjusted in 14%, while sarcoidosis appeared after completed therapy in the remaining cases. Specific therapy for sarcoidosis was started in only 21 patients, mainly with oral corticosteroids. The outcome of patients was detailed in 46 cases: remission or improvement was observed in 38/46 (83%) patients, stabilization of sarcoidosis in 5/46 (11%), and reactivation of sarcoidosis after an initial improvement in 3/46 (6%). Finally, 18 treatment-naive HCV patients presented sarcoidosis, with 14/18 (87%) patients presenting with pulmonary involvement and 8/18 (44%) with cutaneous involvement. In summary, sarcoidosis may be observed in HCV patients in 2 different situations: triggered by antiviral therapy (in 75% of cases) and unrelated to treatment. Sarcoidosis during antiviral therapy may present mainly as cutaneous or pulmonary disease, with a benign, uncomplicated evolution in more than 85% of cases. However, more complicated cases are observed, especially in HCV patients with preexisting sarcoidosis and/or with previous antiviral treatment. Clinicians should be aware of the possibility that sarcoidosis may initially manifest or be reactivated during or shortly after treatment with antiviral therapy in patients with chronic HCV infection.
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BACKGROUND: In recent years we have systematically explored the skin whenever sarcoidosis was suggested and we have observed with increasing frequency the presence of granulomatous cutaneous lesions of sarcoidosis involving the knees. OBJECTIVE: We sought to evaluate the specific cutaneous lesions of sarcoidosis involving the knees. METHODS: A total of 18 patients with biopsy-proven specific cutaneous sarcoidosis predominantly involving the knees were included in the study. Biopsy specimens were evaluated under polarized light. RESULTS: Of these cases, 4 corresponded to scar-sarcoidosis, 1 to plaque-type sarcoidosis, and 13 were an admixture of papules and minute scars frequently associated with erythema nodosum (papular sarcoidosis of the knees). Foreign particles were observed in 10 of 13 patients with papular sarcoidosis. CONCLUSION: Papular sarcoidosis of the knees can be considered a frequent form of cutaneous sarcoidosis, mainly observed in acute forms of the disease, and frequently associated with erythema nodosum.
In sarcoid granulomas, apoptotic events are reduced, which explains their characteristic long-lasting inflammation. We have described that interferon-gamma (IFN-gamma) inhibits apoptosis in macrophages through the expression of p21(Waf1). Here, we explore the molecular mechanisms involved in the inhibition of apoptosis in sarcoid granulomas. We analyzed skin biopsies from 19 sarcoidosis patients and 16 controls. Total RNA was subjected to semiquantitative reverse transcriptase-polymerase chain reaction analysis. There was no difference found in the expression of proapoptotic (Bax and Bcl-X(s)) or antiapoptotic (Bcl-2 and Bcl-X(L)) genes nor in the expression of the tumor suppressor gene p53. Furthermore, the expression of IFN-gamma and the cdk inhibitors p21(Waf1) and p27(Kip1) were analyzed. IFN-gamma was detected in 37% of the sarcoidosis patients, and controls were negative (P<0.02). In addition, a higher proportion of patients expressing p21(Waf1) (58%) versus controls (12%) was found (P<0.005). There was a significant correlation between the expression of IFN-gamma and p21(Waf1) (r=0.69) and between p21(Waf1) and fibronectin (r=0.65). Finally, using immunohistochemistry, high p21(Waf1) reactivity was observed inside the granuloma. We conclude that the high levels of p21(Waf1) in sarcoidosis may explain the absence of apoptosis in the granuloma and the persistence of inflammation.
BACKGROUND AND AIM: Recurrence of sarcoidosis following complete remission and after a prolonged time of inactivity is considered a very unusual clinical event. The aim of this study was to investigate the clinical characteristics of a series of patients diagnosed as having recurrent sarcoidosis. METHODS: Recurrent sarcoidosis was defined as reappearance of the disease following complete spontaneous clinical, radiographic and other markers of activity resolution or following resolution after corticosteroid treatment and maintained for at least during 3 years without therapy. The clinical records of patients diagnosed as having episodes of recurrent sarcoidosis during a period of 28 years at the university hospital of Bellvitge in Barcelona, Spain, were reviewed. RESULTS: Seventeen patients suffering from 24 recurrences were identified. All but one patient were women. The mean follow-up time was 143 +/- 80 months (range: 52 to 282 months). Two patients had 3 recurrences, 3 had 2 and 12 had 1. The disease-free interval without treatment between the time when the disease became inactive after the initial presentation until the first recurrence varied from 10 months to more than 17 years, and the time of inactive disease without therapy between recurrences fluctuated from 23 months to more than 12 years. All the cases but one at onset and 17 at recurrence presented as Löfgren syndrome. At the time of the last control, 14 patients showed complete remission of the disease, one of them under corticosteroid therapy, 2 still had activity because of a recent recurrence, and 1 developed into chronic sarcoidosis. CONCLUSIONS: Acute sarcoidosis, and particularly Löfgren's syndrome, may recur many years after complete remission and, in general, still has a good outcome. In consequence, a long-term follow-up is recommended even in patients with inactive disease. This clinical observation strongly suggests that a re-exposure to or reinfection by an extrinsic antigen triggers the new flare-ups of the disease.
BACKGROUND: We have previously reported that the decrease in high-density lipoprotein (HDL)-cholesterol that is observed in patients with untreated sarcoidosis is limited to those with active disease. AIM: To determine the effect of corticosteroids, used in the treatment of active sarcoidosis, on the reported lipoprotein metabolism abnormalities. METHODS: We studied 62 patients with biopsy-proven sarcoidosis, all of them with active disease. Sarcoidosis activity was evaluated by means of clinical, chest X-ray, gallium-67 scan, serum angiotensin-converting enzyme (peptidyl-dipeptidase A) values, and pulmonary function tests. A total of 40 patients were not treated with prednisone and 22 patients were treated with prednisone. The mean daily prednisone dosage in the treated patients with sarcoidosis was 20 mg and the mean duration of prednisone therapy was 6 months. Analysis of lipoprotein metabolism included: serum cholesterol, low-density lipoprotein (LDL)-cholesterol, HDL-cholesterol, HDL(2)-cholesterol, HDL(3)-cholesterol, apolipoprotein (apo) A-I, apo B, and triglyceride concentrations. RESULTS: When patients with active sarcoidosis not treated with prednisone were compared to those treated with prednisone, the former had significantly lower HDL-cholesterol (1.17+/-0.36 vs. 1.42+/-0.42 mmol/l; P=0.01) and HDL(2)-cholesterol (0.37+/-0.18 vs. 0.53+/-0.25 mmol/l; P=0.009) levels. Multiple regression analysis demonstrated that the HDL-cholesterol (P=0.004), HDL(2)-cholesterol (P=0.002), HDL(3)-cholesterol (P=0.02), and apo A-I (P=0.02) levels were the variables independently and significantly associated with steroid therapy. CONCLUSIONS: Corticosteroid therapy, used in the treatment of active sarcoidosis, increased HDL-cholesterol levels to those seen in inactive disease. These changes are manifestations of reducing disease activity.
A 29-year-old man presented with diplopia and decreased strength in the left arm. A magnetic resonance image (MRI) showed an extensive hypothalamic and pituitary gland mass, and hormonal studies showed partial hypopituitarism and mild hyperprolactinemia without diabetes insipidus. Biopsies of the hypothalamic lesion and of a mediastinal lymph node demonstrated noncaseating granulomas, and a Kveim-Siltzbach test was positive. He was successfully treated with a regimen of high-dose intravenous methylprednisolone pulse therapy for eight weeks along with a low dose of oral corticosteroids which was maintained indefinitely. An MRI obtained immediately after pulse therapy revealed a substantial reduction in the hypothalamic-pituitary mass, which was maintained in an MRI performed 3 years later. However, hormonal deficits persisted and indefinite hormonal substitutive therapy was required.
MRI has become of great importance in the study of several aspects of sarcoidosis. The main development has taken place in the assessment of neurosarcoidosis, but MRI may be also useful in the evaluation of sarcoidosis of the bone, muscle, heart, and intrathoracic. Nuclear imaging in sarcoidosis acquired a great expansion with the introduction of (67)gallium scanning as a marker of activity. Although its current use has decreased, it is still very helpful in particular situations of the disease. Other more recently introduced nuclear imaging techniques may have a role in the evaluation of cardiac sarcoidosis and in the assessment of the extension of the disease.
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