Sarcoidosis and multiple sclerosis: systemic toxicity associated with the use of interferon-beta therapy.

Sarcoidosis is a multi-systemic inflammatory disease of unknown origin characterized by the presence of noncaseating epitheloid cell granulomas in multiple organs. Diagnosis is made on the basis of a compatible clinical-radiological scenario and the histological demonstration of the typical granulomas in the affected tissues. Interferons are immuno-modulators that have been used in a wide range of diseases, including hepatitis C virus infection, multiple sclerosis, and multiple myeloma and other types of tumours, including leukemia, lymphomas, Kaposi's sarcoma, and melanoma. Interferon-alpha-induced sarcoidosis has been reported repeatedly and there are two reports in the literature of cases of pulmonary sarcoidosis treated with interferon-1b therapy: one for advanced renal cell carcinoma and the other for multiple myeloma. A 35-year-old man on chronic immune-modulant Interferon-1b-based therapy for multiple sclerosis presented to the Neurology Unit with mild dyspnoea, dry cough, and transient pain to right upper abdomen. Lungs, spleen, liver, and almost all lymphnode stations of abdomen and mediastinum were clearly involved on ultrasound examination, chest X-ray, and computed tomography. A transbronchial biopsy showed non-caseating granuloma on histopathologic evaluation of the lungs. To the best of our knowledge, this is the first report of a chronic multisystemic sarcoidosis that was associated with interferon-beta treatment.

Omalizumab: when the non-responder is a late-responder.

UNLABELLED: Omalizumab is an anti-IgE monoclonal antibody available since 2006 for the treatment of GINA step 4 asthma. We studied a 41-year old male who has been suffering from severe steroid-resistant asthma with severe co-morbidity and treated with Omalizumab. He was found to be non-responder to the treatment until the 48th week, starting from which we began to see a distinct improvement in the symptoms and all the correlated parameters, in addition to remission of the co-existent allergy to milk. CONCLUSIONS: we wish to point out the late response to Omalizumab, which occurred way beyond the times envisaged in literature. It seems possible that some patients are late responders to the drug.

Relapsing bronchiolitis obliterans organising pneumonia and chronic sarcoidosis in an atopic asthmatic patient.

Asthma is thought to be a Th2 disease while sarcoidosis is considered a Th1 granulomatous disorder. Organising pneumonia is a histologic pattern of lung injury. When it has no recognisable cause it is defined as cryptogenic organising pneumonia. We herein report the case of a patient with recurrent and steroid sensitive organising pneumonia associated with chronic sarcoidosis in an atopic, moderate persistent asthmatic patient. Each disease has been documented with transbronchial biopsies and recurrence of organising pneumonia was suggested by clinical features and by follow up HRCT which shows distinctive signs even in associated disease. Steroids are the mainstay of therapy for these disorders and especially for the consolidated processes typical of organising pneumonia but prognostic indices for relapse and progression are lacking.

Haemorrhagic pericardial effusion in an asbestos worker.

BACKGROUND: Occupational exposure to asbestos may cause pleural and lung disorders and, less frequently, diseases of the peritoneum and pericardium. An exceedingly small number of cases of benign pericardial effusion have been described so far in the medical literature. OBJECTIVES: To report a rare case of haemorrhagic pericardial effusion caused by occupational asbestos exposure in a patient with pre-existent aortic regurgitation, bilateral pleural plaques and no signs of interstitial lung involvement due to asbestosis. METHODS: A thorough clinical and instrumental evaluation (laboratory tests, tuberculin skin test, chest X-rays, transthoracic and transesophageal echocardiography, contrast coronary and aortic angiography, a histological examination of pericardial and pleural surgical specimens) was performed to examine all the known causes of pericardial effusion. RESULTS: The tests performed did not demonstrate any specific cause of pericardial effusion. Surgical assessment three months later, during an aortic valve replacement, showed no signs of aortic dissection or intraparietal hematoma. A nine-year follow up did not reveal any reoccurrence of pericardial effusion. CONCLUSIONS: Asbestos related pericardial effusion is rarely described in the medical literature but must be considered in patients with previous occupational asbestos exposure. There are no specific clinical or pathological aspects indicative of this etiology and the diagnosis remains one of exclusion. A thorough occupational history should be obtained in patients with pericardial effusion of unknown etiology.

[Round atelectasis of the lung: clinicopathological study of 6 cases and review of the literature]. / Atelettasia rotonda del polmone: studio clinicopatologico di 6 casi e revisione della letteratura.

OBJECTIVE: To report about 6 new patients with round atelectasis of the lung, 1 of them professionally exposed to asbestos and another to silicates. RESULTS: The patients, 5 males and 1 female, presented with a peripheral, rounded pulmonary opacity, simulating a neoplasm. The examination of the surgical specimen revealed a pleuritis, with multiple pleural folding: the underlying lung parenchima was compressed, but otherwise unremarkable. CONCLUSIONS: Round atelectasis is relatively unusual for the pathologist. However, the correct diagnosis is potentially important, because the lesion can be the sign of a significant asbestos exposure.

[Bartter's syndrome: two case reports in childhood] / Síndrome de Bartter: relato de dois casos em crianças.

OBJECTIVE: To report a syndrome that is uncommon in childhood and call pediatriciansattention to the tubular diseases - just like Bartters syndrome - in differential diagnosis of failure to thrive and other diseases that can be usually found in children.METHODS: Two patients are presented. The first, a 3 years and 2 months old boy who was submitted for investigation of a failure to thrive detected when he was 9 months old. The second patient, a 3 months old girl, was admitted to the Intensive Care Unit due to severe electrolyte disturbances. She was supposed to have a pyloric hypertrophic stenosis.RESULTS: Both patients had failure to thrive, hypocloremic alkalosis, hypokalemia, and hypercalciuria. The first had a positive obstetric history for polihydramnios that is frequently found in the neonatal form of this syndrome. Treatment was done by blood potassium correction, together with indometacin and spironolactone administration. These drugs where well tolerated by the patients who have improved their growth rhythm only a short time after electrolytic disturbances had been corrected.CONCLUSIONS: The Bartter's syndrome is a tubular disease that is unusual in childhood. It must be considered as a possible cause of failure to thrive. The neonatal form is rare and can produce severe hydro-electrolytic disturbances, increasing the difficulties for diagnosis. The treatment is well tolerated, even by small children, and must begin early to reduce the troubles to thrive.

Evaluation of a western blot serum test for the diagnosis of Mycobacterium tuberculosis infection.

This study was designed to evaluate the possibility of monitoring Mycobacterium tuberculosis infection using a serological assay. A discriminant score comprising antigen fractions of 38, 28, 24 and 19 kDa, identified in western blots using the Mycobacterium bovis bacille Calmette-Guérin (BCG) A60 antigen complex was established in a sample of 57 purified protein derivative (PPD)-negative and 47 PPD-positive individuals. It was then tested in a group of 140 subjects undergoing BCG vaccination as a model of tuberculosis complex infection and in a group of human immunodeficiency virus (HIV)-infected individuals as a model of cell-mediated immunodeficiency-related risk of tuberculosis. The discriminant score identified 57 out of 57 (100%) PPD-positives and none (0%) of the 47 PPD-negatives. In the BCG vaccinated subjects, 1.4% tested positive before vaccination and 90% after vaccination. In the HIV-positive subjects, 90% of the PPD-positive and 5% of the PPD-negative subjects had a positive score. This study suggests that the western blot discriminant score is an accurate test to survey M. tuberculosis infection in serum samples.

The immunological events leading to the "in vitro" response to PPD.

In normal individuals the 5/9 monoclonal antibody (5/9 MAb) recognizes a T-cell fraction that includes all T lymphocytes with inducer activities. Here, circulating 5/9+ and 5/9- T lymphocytes were isolated from tuberculim skin-positive subjects and the proliferative response induced by PPD was investigated. The results show that the total PPD-induced lymphocyte DNA synthesis is confined to the 5/9+ T cell fraction. PPD was unable to induce a direct or indirect (through the 5/9+ cells) proliferation of T8+ cells. Whether 5/9 antigen, expressed on the PPD responsive T-cell subset, is involved in PPD-induced cell proliferation, was also analyzed. No significant effect was observed adding 5/9 MAb, whereas complete inhibition of antigen-induced blastogenesis was observed upon addition of a MAb (D1.12) directed to common determinants of Ia antigens. The supernatant fluids of 5/9+ and 5/9- cells stimulated with PPD were studied for the presence of IL-2 and IFN-gamma. Production of both these lymphokines was detected in the 5/9+ T-cell supernatants, whereas neither IL-2 or IFN-gamma were found in supernatants of 5/9- cells. In addition, preliminary experiments suggested that only the supernatants of PPD-stimulated 5/9+ T cells were able to activate a macrophage cell line, inducing a remarkable release of hydrogen peroxide. These results indicate that the lymphocyte responsiveness to PPD is confined in a small T cell fraction, expressing the 5/9 antigen; only these T cells are able to release soluble factors (i.e., IL-2 and IFN-gamma); those or other soluble factor(s) produced in PPD-stimulated cultures seem able to activate the macrophages.

[Anergic miliary tuberculosis, with principally splenic localization simulating hemolymphopathy. Report of 4 cases]. / Tubercolosi miliare anergica a principale localizzazione splenica simulante una emolinfopatia. Descrizione di 4 casi.

Four cases of disseminated tuberculosis with prevailing spleen involvement and lack of tuberculin reactivity are described. The atypical clinical picture justified, at the beginning of the disease, the suspect of a lymphoreticular disorder (malignant lymphoma in 3 cases) or of a pulmonary hemosiderosis (in 1 case). The splenectomy and the following anti-tubercular chemotherapy were fully successful in all 4 patients and the skin reactivity was restored. The Authors discuss the pathogenesis of the observed features and the differential diagnosis of the cases of tuberculosis with only extrapulmonary involvement. These cases represent today about 1/6 of the patients with postprimary tuberculosis.