Imatinib is Partially Effective for the Treatment of Pulmonary Capillary Hemangiomatosis

Adachi, Shiro; Hirashiki, Akihiro; Kondo, Takahisa; Nakaguro, Masato; Ogawa, Aiko; Miyaji, Kohei; Matsubara, Hiromi; Yokoi, Toyoharu; Murohara, Toyoaki

doi:10.2169/internalmedicine.53.1157

Cited by 13 publications

(7 citation statements)

References 15 publications

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“…There are 4 case reports regarding the efficacy of imatinib in PVOD/PCH. Three reports suggested the efficacy of imatinib in 1 patient with PVOD [13] and 2 patients with PCH [11,14]. A single report described a patient with PVOD who was refractory to imatinib [15].…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of long-term imatinib therapy for patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis

Ogawa

Miyaji

Matsubara

2017

Respiratory Medicine

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Section: Discussionmentioning

confidence: 99%

“…Baseline characteristics were also compared between imatinib group and non-imatinib group. Three of the included patients (1 in the imatinib group and 2 in the non-imatinib group) were presented previously elsewhere [4,11].…”

Section: Data Collectionmentioning

confidence: 99%

Efficacy and safety of long-term imatinib therapy for patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis

Ogawa

Miyaji

Matsubara

2017

Respiratory Medicine

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“…While case reports have described improvement with doxycycline, interferon alfa, and imatinib in some patients, consistent benefit has not been demonstrated. [23][24][25][26] Additionally, treatment of PAH in these patients is challenging since initiation of prostacyclin therapy can result in pulmonary edema. 27 Two of our 3 patients tolerated phosphodiesterase inhibitors without the development of pulmonary edema and experienced mild symptomatic improvement.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Capillary Hemangiomatosis: The Role of Invasive Cardiopulmonary Exercise Testing

et al. 2015

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Pulmonary capillary hemangiomatosis (PCH) is a rare form of pulmonary arterial hypertension (PAH) characterized by pulmonary capillary proliferation and pseudoinvasion of collagenous septal structures. PCH is often accompanied by veno-occlusive changes and pulmonary hypertensive arterial remodeling. The clinical and pathological diagnosis of PCH can be subtle and easily missed. Most reported cases of PCH have been associated with resting PAH. We report the cases of 3 patients who initially presented with exertional dyspnea with normal to mildly elevated resting pulmonary arterial pressures and marked intrapulmonary shunting. In all 3 patients, invasive cardiopulmonary exercise testing was suggestive of pulmonary vascular disease. Owing to abnormalities on invasive exercise testing, lung biopsies were performed; these were diagnostic of PCH, and the patients were referred for lung transplantation. We describe unique features of these 3 cases-including novel pathological findings and the presence of intrapulmonary shunting in all 3 patients-and we discuss the role of cardiopulmonary exercise testing in the evaluation of PCH.

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“… 76 Imatinib, a platelet growth factor receptor antagonist, showed efficacy in PCH treatment. 77 , 78 Doxycycline, a matrix metalloproteinase and angiogenesis inhibitor, could be a treatment option for the PCH patients who have elevated levels of matrix metalloproteinase and capillary proliferation. 79 Interferons are cytokines secreted by host cells in response to stimuli.…”

Section: Correlate Pch Case Pathogenesis With Diagnosis and Treatmentioning

confidence: 99%

Pulmonary capillary hemangiomatosis: a focus on the EIF2AK4 mutation in onset and pathogenesis

Ma¹,

Bao²

2015

TACG

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Pulmonary capillary hemangiomatosis (PCH) is a pulmonary vascular disease that mainly affects small capillaries in the lung, and is often misdiagnosed as pulmonary arterial hypertension or pulmonary veno-occlusive disease due to similarities in their clinical presentations, prognosis, and management. In patients who are symptomatic, there is a high mortality rate with median survival of 3 years after diagnosis. Both idiopathic and familial PCH cases are being reported, indicating there is genetic component in disease etiology. Mutations in the eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4) gene were identified in familial and idiopathic PCH cases, suggesting EIF2AK4 is a genetic risk factor for PCH. EIF2AK4 mutations were identified in 100% (6/6) of autosomal recessively inherited familial PCH and 20% (2/10) of sporadic PCH cases. EIF2AK4 is a member of serine/threonine kinases. It downregulates protein synthesis in response to a variety of cellular stress such as hypoxia, viral infection, and amino acid deprivation. Bone morphogenetic protein receptor 2 (BMPR2) is a major genetic risk factor in pulmonary arterial hypertension and EIF2AK4 potentially connects with BMPR2 to cause PCH. L-Arginine is substrate of nitric oxide synthase, and L-arginine is depleted during the production of nitric oxide, which may activate EIF2AK4 to inhibit protein synthesis and negatively regulate vasculogenesis. Mammalian target of rapamycin and EIF2α kinase are two major pathways for translational regulation. Mutant EIF2AK4 could promote proliferation of small pulmonary arteries by crosstalk with mammalian targets of the rapamycin signaling pathway. EIF2AK4 may regulate angiogenesis by modulating the immune system in PCH pathogenesis. The mechanisms of abnormal capillary angiogenesis are suggested to be similar to that of tumor vascularization. Specific therapies were developed according to pathogenesis and are proved to be effective in reported cases. Targeting the EIF2AK4 pathway may provide a novel therapy for PCH.

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Imatinib is Partially Effective for the Treatment of Pulmonary Capillary Hemangiomatosis

Cited by 13 publications

References 15 publications

Efficacy and safety of long-term imatinib therapy for patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis

Efficacy and safety of long-term imatinib therapy for patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis

Pulmonary Capillary Hemangiomatosis: The Role of Invasive Cardiopulmonary Exercise Testing

Pulmonary capillary hemangiomatosis: a focus on the EIF2AK4 mutation in onset and pathogenesis

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