Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis.

BACKGROUND: Pulmonary hypertension (PH) is a rare complication of sarcoidosis, although it is not uncommon in advanced disease. METHODS: A retrospective series of 22 sarcoidosis patients (16 men) of mean (SD) age 46 (13) years with PH was divided into two groups depending on the absence (stage 0: n = 2, stage II: n = 4, stage III: n = 1) or presence (n = 15) of radiographic pulmonary fibrosis at the time of PH diagnosis. RESULTS: In both groups PH was moderate to severe and there was no response to acute vasodilator challenge. In non-fibrotic cases no other cause of PH was found, suggesting a specific sarcoidosis vasculopathy, although no histological specimens were available. In cases with fibrosis there was no correlation between haemodynamics and lung volumes or arterial oxygen tensions, suggesting other mechanisms for PH in addition to pulmonary destruction and hypoxaemia. These included extrinsic arterial compression by lymphadenopathies in three cases and histologically proven pulmonary veno-occlusive disease in the five patients who underwent lung transplantation. Ten patients received high doses of oral prednisone for PH (stage 0: n = 1, stage II: n = 4 and stage IV: n = 5); three patients without pulmonary fibrosis experienced a sustained haemodynamic response. Survival of the overall population was poor (59% at 5 years). Mortality was associated with NYHA functional class IV but not with haemodynamic parameters or with lung function. CONCLUSION: Two very different phenotypes of sarcoidosis combined with PH are observed depending on the presence or absence of pulmonary fibrosis. PH is a severe complication of sarcoidosis.

[Atypical forms of sarcoidosis]. / Formes atypiques de sarcoïdose.

Many atypical forms of sarcoidosis have been described. mediastinum-lung involvement, observed in 90% of the cases, may cause atypical manifestations: hemoptysis, chest pain, predominant pleural or proximal bronchial involvement. Diffuse "unpolished glass" images or air cavities may be observed on the chest x-ray. A rigorous diagnostic work-up is necessary for these atypical forms. Pathological confirmation is mandatory: non-caseous tuberculoid granuloma. A very wide range of extra-thoracic localizations have been described with variable clinical manifestations. In cases with no mediastinum-lung involvement, pathology data must be confronted with the notion of multiple organ dissemination to reach diagnosis.

[Inflammatory pseudotumors of the lung with severe course]. / Pseudo-tumeurs inflammatoires pulmonaires d'évolution sévère.

Pulmonary inflammatory pseudotumors are usually unique lesions of unknown etiology with good prognosis. We report two severe cases with mediastinal invasion, local recurrence, extrathoracic locations, one of them with a fatal evolution. Certain microscopic features, which were present in our cases (increased cellularity, nuclear pleomorphism, mitotic activity, focal necrosis, bizarre giant cells, vascular invasion), may have prognostic relevance in determining an aggressive behavior of these tumors. Surgical resection is the recommended treatment, and incomplete resection, as in our cases, seems to be a risk factor for developing recurrent inflammatory pseudotumor. Immunosuppressive therapy was ineffective as well as radiotherapy in one of our cases. Only high doses of corticosteroids seemed to slow the evolution of the disease.

[Retinal vascularization in sarcoidosis]. / Vascularite rétinienne au cours de la sarcoïdose.

OBJECTIVES: To describe the characteristics of retinal vasculitis related to sarcoidosis, and to study the radio-clinical findings of sarcoidosis in case of retinal vasculitis. METHODS: We performed a retrospective study on 33 cases of retinal vasculitis associated with sarcoidosis. Our patients had a complete ophthalmological examination and a systematic fluorescein angiography was performed. Recorded data included clinical, biological and radiological evaluation of sarcoidosis. RESULTS: Retinal vasculitis were and remained asymptomatic in almost a third of the patients (n = 10). In 11 patients (33%) a decreased visual acuity of more than 3 lines was observed. Periphlebitis was observed in all cases, and 75.7% were of non ischemic forms. Thirty patients out of 33 (90.9%) were treated with systemic steroids in whom 17 were treated for ophthalmological reasons. The presence of anterior or posterior uveitis, more than one attack of vasculitis, and significant hyalitis were statistically associated with visual acuity decrease. Ninety percent of patients regained their initial visual acuity, only three patients at the end of the medical follow-up remained with a visual acuity below or equal to 2/10. Thirty one patients (91%) presented with mediastinal and pulmonary signs concordant with sarcoidosis on chest x-rays. Extrapulmonary localisations were common in case of retinal vasculitis (91% of patients). CONCLUSION: Retinal vasculitis associated with sarcoidosis are often asymptomatic. In most cases, there are bilateral, non ischaemic periphlebitis. They seem to have a relatively better prognosis than in other etiologies of vasculitis and they are part of an evolutive multisystemic sarcoidosis. Most of the time treatment with systemic steroids was indicated for ophthalmological or extra ophthalmological reasons.

Is high-resolution computed tomography a reliable tool to predict the histopathological activity of pulmonary Langerhans cell histiocytosis?

High-resolution computed tomography (HRCT) has proved to be very useful in the diagnosis and follow-up of pulmonary Langerhans cell histiocytosis (PLCH), but the precise relationships between nodules and thin-wall cysts observed by HRCT, and granulomatous or cystic lesions present in lung tissue, remain to be established. The aim of this study was to compare quantitative data obtained by HRCT and those obtained by histopathological examination of corresponding lung tissue specimens in patients with biopsy-proven PLCH. The results demonstrated that the extent of nodular abnormalities was strongly correlated with the density of florid granulomatous lesions in lung tissue. A strong correlation was also found between the extent of cystic abnormalities and the density of cavitary lesions, but the latter included both still inflammatory cavitary granulomas and cicatricial fibrous cysts. Interestingly, small isolated florid granulomas were found in lung tissue from most patients with a predominant cystic CT scan pattern. Taken together, these results demonstrate that HRCT has to be considered with caution to evaluate the histopathological activity of PLCH. Patients presenting with predominant HRCT cystic abnormalities should benefit from a long-term follow-up. Because these patients are susceptible to developing severe respiratory insufficiency, they should also be considered for treatment as soon as an effective therapy for LCH is available.

Sarcoidosis with pulmonary fibrosis: CT patterns and correlation with pulmonary function.

OBJECTIVE: The purpose of our study was to identify CT patterns of pulmonary fibrosis in patients with sarcoidosis and to correlate these patterns with pulmonary function tests. MATERIALS AND METHODS: We conducted a retrospective review of CT scans of 80 patients with proven sarcoidosis and evidence of fibrotic changes on chest radiographs. RESULTS: Three main CT patterns were identified: bronchial distortion (n = 38, 47%), mainly central; honeycombing (n = 23, 29%), mainly peripheral; and linear (n = 19, 24%), mainly diffuse. In most cases, a pattern was clearly identified as shown by the good agreement between observers (kappa = 0.87). Nodules were significantly associated with the linear (87%) and distorted (71%) patterns, but not with the honeycomb pattern (35%). The honeycomb pattern was most often associated with restriction and decreased lung diffusing capacity for carbon monoxide. Patients with bronchial distortion had lower expiratory airflow rates. The linear pattern was generally associated with the least functional impairment. CONCLUSION: CT may be a useful tool for defining subgroups of patients with fibrotic pulmonary sarcoidosis. CT reveals three main patterns that may reflect different distributions of fibrotic lesions in the lung with different functional pulmonary impairments. The persistence of active pulmonary lesions suggested by the presence of nodular lesions was often associated with linear and distorted patterns.

Airway obstruction in bronchial sarcoidosis: outcome with treatment.

STUDY OBJECTIVE: Airway obstruction (AO) in sarcoidosis is reported to be associated with respiratory symptoms, increased morbidity, and an increased mortality risk. Because AO in sarcoidosis may result from several causes, the therapeutic benefit of corticosteroids is difficult to determine. The aim of this study was to evaluate the therapeutic response of AO attributable to sarcoid granulomas in the bronchial wall. PATIENTS: We selected 11 patients who had sarcoidosis with AO (defined as FEV(1)/vital capacity [VC] < 70%) associated with sarcoid granulomas on an endobronchial biopsy. Exclusion criteria were history of asthma, smoker or ex-smoker, stage 4 disease, evidence of extrinsic compression by enlarged lymph nodes, and localized endobronchial stenosis seen during fiberoptic bronchoscopy. INTERVENTIONS: We compared the results of pulmonary function tests and clinical, radiologic, and biological findings at baseline with those obtained at the time of the last pulmonary function tests available, between the sixth and 12th months of treatment. Eight patients took oral corticosteroids (20 to 60 mg/d initially), one received IV methylprednisolone pulses, another took oral hydroxychloroquine, and the last one received IM methotrexate. MEASUREMENTS AND RESULTS: With treatment, FEV(1) and FEV(1)/VC significantly improved in eight patients (72%), normalized in four patients, and was unchanged in the remaining three patients. The mean FEV(1) increased from 60.8 +/- 10.8% to 76 +/- 13.7% of the predicted value (p < 0.02). VC did not change significantly. FEV(1)/VC increased from 76.1 +/- 6.4% to 87.6 +/- 10.7% of the predicted value (p < 0.01). Dyspnea on exertion and other clinical findings were attenuated in 10 patients; the chest radiograph improved in 9 patients, and normalized in 5 patients. The mean serum angiotensin-converting enzyme level decreased from 112 +/- 48 to 58 +/- 40 IU/mL (p < 0.05), and normalized in four patients. CONCLUSION: The present study indicates that AO caused by sarcoid granulomas in the bronchial wall can be either partially or completely reversed by treatment with a concomitant attenuation of pulmonary symptoms.

Familial extensive idiopathic bilateral pleural fibrosis.

The authors report three sisters with bilateral isolated apical pleural fibrosis of unknown origin, which did not respond to empirical antituberculosis therapy and oral corticosteroids. The disease evolved in an unrelenting fashion producing pleural fibrosis at the lung bases and leading to the death of two sisters and to lung transplantation in the other one. There was no history of other familial disease or consanguinity. The particular features of these cases and the differences from other reports of apparently cryptogenic pleural fibrosis are outlined.

[Late relapse of sarcoidosis. Report of 3 cases]. / Rechutes tardives de sarcoïdose. A propos de 3 cas.

We report patients who were treated with corticosteroids for sarcoïdosis and developed recurrent disease after 9 and 28 years of remission. The clinical latency, the type III radiographic aspect different from the initial presentation and the spontaneous course with periods of partial or total remission are characteristic of these late relapses. Clinicians should be aware of this uncommon clinical course and monitor cured cases for prolonged periods.

[Cardiogenic shock presenting a cardiac sarcoidosis. Apropos of a case]. / Choc cardiogénique révélant une sarcoïdose cardiaque. A propos d'un cas.

The authors report a case of cardiac sarcoidosis in a 38 year old patient presenting initially with cardiogenic shock. The diagnosis was made by myocardial biopsy. The patient underwent cardiac transplantation for terminal, refractory cardiac failure but postoperative complications led to the death of the patient a few weeks later. This rare observation should be noted because the causal disease may benefit from specific therapy.

Relapsing nodular lesions in the course of adult pulmonary Langerhans cell histiocytosis.

In most patients with pulmonary Langerhans cell histiocytosis (LCH), clinical and radiological abnormalities initially either stabilize or regress, often without treatment. Little information is available, however, concerning the subsequent evolution of disease in patients who initially follow a benign course. We describe four patients with biopsy-confirmed pulmonary LCH whose initial course was characterized by regression of parenchymal nodular lesions, but who subsequently developed one or more episodes of active disease 7 mo to 7.5 yr after their initial presentation. In each case, the subsequent episodes of active disease were characterized by the reappearance or marked increase in nodular radiographic abnormalities, whose presence was confirmed by high-resolution computed tomography (HRCT). Thus, initial regression of nodular lesions in pulmonary LCH does not preclude the reappearance of one or more episodes of active disease, and may have important consequences on the long-term prognosis of these patients.

[Chronic pseudo-hypertrophic myopathy in sarcoidosis. Apropos of 3 cases]. / Myopathie chronique pseudo-hypertrophique au cours de la sarcoïdose. A propos de 3 cas.

We report three cases of pseudohypertrophic chronic myopathy in patients with sarcoidosis. The patients were aged 41-50 years and were of African or mixed ethnic origin. All three patients had multiorgan sarcoidosis recently diagnosed by the presence of hiliary and/or mediastinal node enlargement with or without reticulomicronodulation in the lung fields. Hypertrophy of the proximal portion of the limbs dominated the clinical presentation. In 2 cases, the myopathy was preceded by myalgia and in 2 cases associated with muscle nodules. The muscle enzymes were elevated in 2 cases. The importance of tuberculoid granulomas and the discretion of the myopathy characterised the histological findings in all 3 cases. Cortisone therapy was given early and long-term treatment led to favorable course in 2 cases, probably due to the importance of the granulomatous muscle mass. In the third case, peripheral neuropathy developed.

[Pulmonary sarcoid-like granulomatosis associated with Hodgkin's disease and complicated by bleomycin-induced pulmonary nodules]. / Granulomatose pulmonaire sarcoid-like associée à une maladie de Hodgkin et compliquée de nodules pulmonaires induits par la bléomycine.

We report the case of a man in whom multiple lung macronodules developed after chemotherapy containing bleomycin for Hodgkin's disease, which was itself shortly preceded by a pulmonary sarcoid-like granulomatosis. Biopsy of the nodules showed fibrotic and granulomatous lesions. The etiological diagnosis is discussed.

Pulmonary Langerhans cell histiocytosis: evolution of lesions on CT scans.

PURPOSE: To document the evolution of pulmonary lesions of Langerhans cell histiocytosis (LCH) with sequential computed tomography (CT). MATERIALS AND METHODS: Initial and final CT scans of 21 patients with LCH and CT evidence of pulmonary disease were compared retrospectively. Histologic confirmation of pulmonary involvement was available in 11 patients. RESULTS: On initial CT images, a nodular pattern (n = 14) was seen more frequently than a cystic pattern (n = 7). On final CT images, a cystic pattern (n = 14) was seen more often than a nodular one (n = 6). There was complete resolution of parenchymal abnormality in one case. Nodular opacities, thick-walled cysts, and ground-glass opacities underwent regression. Thin-walled cysts, linear opacities, and emphysematous lesions remained unchanged or progressed. CONCLUSION: Pulmonary CT allows good assessment of the evolution of LCH lesions. Nodular lesions probably represent active disease and often undergo regression or transform into cysts.

Erdheim-Chester disease with prominent pulmonary involvement associated with eosinophilic granuloma of mandibular bone.

We report a patient with eosinophilic granuloma localized to the left mandible who was subsequently shown to have Erdheim-Chester disease involving the lower extremities, omentum and lung. The diagnosis of eosinophilic granuloma was based on the presence of typical CD1a+ Langerhans' cell granulomas in a biopsy of mandible. The diagnosis of Erdheim-Chester disease was established on the basis of the pattern of radioisotopic uptake by long bones, seen on a technetium bone scan, and the presence of characteristic histopathological features in biopsies of lung and peritoneum. The pathological findings in lung were compatible with the abnormalities observed by tomodensitometry, but strikingly different from those seen in Langerhans' cell granulomatosis. The differences in the histological features of pulmonary involvement seen in the two diseases, and the possible relationship between Langerhans' cell granulomatosis and Erdheim-Chester disease, are discussed.

[Visceral larva migrans in adults with severe pulmonary manifestations]. / Larva migrans viscérale de l'adulte avec manifestations pulmonaires sévères.

BACKGROUND: Toxocariosis, the most frequent cause of visceral larva migrans, is usually a disease of children due to ingestion of eggs from the roundworm of dogs (Toxocara canis). Clinical expression varies from an symptomatic state to fuminant disorders; hepatomegaly with fever is frequent. Severe symptoms (rarely in adults) may occur. CASE REPORT: A 42-year-old male with no past medical history complained of sudden onset pulmonary disorders. Laboratory findings included eosinophilia on blood tests, a severe respiratory obstructive syndrome and positive serum tests for Toxocara canis. All clinical and biological abnormalities regressed in a few weeks. DISCUSSION: Diagnosis of visceral larva migrans is exceptional in adults and can only be proven by positive serological tests. Correct treatment remains under debate.

[Diagnostic approach of chronic diffuse infiltrative diseases of the lung in non-immunosuppressed patients]. / Approche diagnostique des maladies infiltratives diffuses chroniques du poumon du sujet non immunodéprimé.

Diagnosis in non-immunosuppressed subjects with chronic diffuse infiltrative lung disease is a progressive process. Because of the large number of diseases involved, the relative frequency of certain causes (for example sarcoidosis, primary pulmonary fibrosis, carcinomatous lymphangitis) is of prime importance. Generally, history taking and physical examination are essential to guide exploratory examinations required for diagnosis. Standard radiography often gives the first indication of chronic diffuse infiltrative lung disease, but the recent development of high-resolution computed tomography which provides a better visualization of the predominant elementary aspects and their anatomic distribution has been a major step forward. Bronchoalveolar lavage is also highly contributive and although certain diagnosis may not be achieved, the type of cells involved in the development of alveolitis can be identified. Pathology examination of a surgical biopsy specimen is sometimes required for certain diagnosis. Videothoracoscopy is generally used and should be guided by CT scan data to optimize the probability of sampling in areas of "active" inflammation. Indications for videothoracoscopy must be made on an individual basis according to the team's experience with this type of pathology.