Mechanisms of Exercise Limitation and Prevalence of Pulmonary Hypertension in Pulmonary Langerhans Cell Histiocytosis.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) determines reduced exercise capacity. The speculated mechanisms of exercise impairment in PLCH are ventilatory and cardiocirculatory limitations, including pulmonary hypertension (PH). RESEARCH QUESTION: What are the mechanisms of exercise limitation, the exercise capacity, and the prevalence of dynamic hyperinflation (DH) and PH in PLCH? STUDY DESIGN AND METHODS: In a cross-sectional study, patients with PLCH underwent an incremental treadmill cardiopulmonary exercise test with an evaluation of DH, pulmonary function tests, and transthoracic echocardiography. Those patients with lung diffusing capacity for carbon monoxide (Dlco) < 40% predicted and/or transthoracic echocardiogram with tricuspid regurgitation velocity > 2.5 m/s and/or with indirect PH signs underwent right heart catheterization. RESULTS: Thirty-five patients were included (68% women; mean age, 47 ± 11 years). Ventilatory and cardiocirculatory limitations, impairment suggestive of PH, and impaired gas exchange occurred in 88%, 67%, 29%, and 88% of patients, respectively. The limitation was multifactorial in 71%, exercise capacity was reduced in 71%, and DH occurred in 68% of patients. FEV1 and Dlco were 64 ± 22% predicted and 56 ± 21% predicted. Reduction in Dlco, an obstructive pattern, and air trapping occurred in 80%, 77%, and 37% of patients. FEV1 and Dlco were good predictors of exercise capacity. The prevalence of PH was 41%, predominantly with a precapillary pattern, and mean pulmonary artery pressure correlated best with FEV1 and tricuspid regurgitation velocity. INTERPRETATION: PH is frequent and exercise impairment is common and multifactorial in PLCH. The most prevalent mechanisms are ventilatory, cardiocirculatory, and suggestive of PH limitations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02665546; URL: www.clinicaltrials.gov.

Use of sirolimus in the treatment of lymphangioleiomyomatosis: favorable responses in patients with different extrapulmonary manifestations.

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day). METHODS: We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus. RESULTS: After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma. CONCLUSIONS: Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

Use of sirolimus in the treatment of lymphangioleiomyomatosis: favorable responses in patients with different extrapulmonary manifestations / Uso de sirolimo no tratamento de linfangioleiomiomatose: resposta favorável em pacientes com diferentes manifestações extrapulmonares

OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day). METHODS: We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus. RESULTS: After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma. CONCLUSIONS: Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols. .

OBJETIVO: A linfangioleiomiomatose (LAM) é uma doença rara que é atualmente considerada uma neoplasia de baixo grau com potencial metastático e evolução variável. Os inibidores de mammalian target of rapamycin (mTOR), como o sirolimo e o everolimo, recentemente se tornaram uma opção para o tratamento de pacientes com LAM, especialmente daqueles com manifestações extrapulmonares. O objetivo deste estudo foi descrever quatro casos de pacientes com LAM no Brasil que apresentaram melhora, especialmente das manifestações extrapulmonares, após tratamento com sirolimo (em doses de 1-4 mg/dia). MÉTODOS: Descrevemos quatro casos de pacientes com LAM e diferentes manifestações extrapulmonares tratados com sirolimo. RESULTADOS: Após o tratamento com sirolimo por 12 meses, um paciente apresentou resolução do quilotórax de difícil manejo, um paciente teve redução significativa do volume do angiomiolipoma renal, e uma paciente apresentou regressão importante de linfangioleiomiomas retroperitoneais e linfonodomegalias abdominais. Após tratamento com sirolimo por 6 meses, um paciente apresentou redução significativa de volumoso linfangioleiomioma retroperitoneal. CONCLUSÕES: Nossos achados confirmam que os inibidores de mTOR são benéficos para pacientes com LAM, especialmente para aqueles com manifestações extrapulmonares, tais como angiomiolipomas renais, linfangioleiomiomas e derrames de origem quilosa. Entretanto, alguns pontos, tais como a dose ideal, a duração do tratamento e os efeitos adversos em longo prazo, ainda precisam ser esclarecidos para que os inibidores de mTOR possam ser incorporados na abordagem da LAM. .

Paget's disease of bone: analysis of 134 cases from an island in Southern Brazil: another cluster of Paget's disease of bone in South America.

Paget's disease of bone (PDB) exhibits a marked geographic variation. In Brazil, the prevalence of PDB is unknown and only a few clinical data are available. The aim is to determine clinical, laboratory, imaging and response to treatment data in a large PDB case series in the city of Florianopolis, Brazil. We have performed a retrospective study based on charts reviews of all patients with PDB followed at the University Hospital of the Federal University of Santa Catarina and at five different private rheumatology outpatient offices in Florianopolis, between 1995 and 2009. One hundred and thirty-four patients with PDB were identified. Mean age at diagnosis was 63.2 ± 10.5 years, 67.2% were women, and 91.1% were Caucasian. Positive family history was reported in only 8.2%. Polyostotic disease was found in 75.0% of the cases, bone pain in 77.9%, and bone deformities in 15.9%. Higher levels of AP were significantly associated with polyostotic disease and skull involvement. Pelvic bones were the most frequently affected (53.7%). Complications included deafness in 8.2%, bone fractures in 3.0%, hydrocephalus in 2.2%, and cauda equina syndrome in 0.7% of the cases. Treatment with zoledronic acid achieved the best response with only 2.9% failing to respond adequately. According to literature data, PDB in South America seems to be characterized by an overall low prevalence, but with localized clusters with higher prevalence. The authors have described a cluster of PDB in Florianopolis, in Southern Brazil. Further properly designed studies are necessary to clarify the PDB epidemiology in South America.

Síndrome de Pancoast - perdendo o melhor momento de diagnosticar / Pancoast Syndrome - losing the best time to diagnose

Os autores descrevem um caso de Síndrome de Pancoastcom desfecho desfavorável por atraso no diagnóstico.Enfatiza-se a necessidade de alto índice de suspeiçãopara esta síndrome, a fim de oportunizar a sua detecçãoprecoce e, consequentemente, a possibilidade de tratamentocurativo ou maior sobrevida.

The authors describe a case of Pancoast Syndrome withunfavorable outcome because of delay on diagnosing.It?s emphasized the need of high suspicion index to thesyndrome, in order to nurture it?s early detection and,consequently, the possibility of curative treatment or increasedsurvival.