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Dasatinib-induced pulmonary arterial hypertension complicated with scleroderma: a case report.

ABSTRACT: Background:Although the BCR-ABL tyrosine kinase inhibitor dasatinib is a potent treatment for chronic myeloid leukaemia, it is associated with the risk of dasatinib-induced pulmonary arterial hypertension (DASA-PAH), for which predisposing factors have yet to be elucidated. However, animal studies have shown that dasatinib exacerbates pulmonary hypertension (PH) in rodent models of PH but not in controls, providing support for a two-hit theory of DASA-PAH pathophysiology. Case summary:A 63-year-old man with worsening dyspnoea was diagnosed with severe DASA-PAH and concomitant scleroderma. He was successfully treated with discontinuation of dasatinib and administration of pulmonary vasodilators. Discussion:Our case suggests that scleroderma may be a predisposing factor for the development of DASA-PAH, providing new insight into its pathophysiology.

SUBMITTER: Toya T

PROVIDER: S-EPMC6439368 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Dasatinib-induced pulmonary arterial hypertension complicated with scleroderma: a case report.

Toya Takumi T Nagatomo Yuji Y Kagami Kazuki K Adachi Takeshi T

European heart journal. Case reports 20190315 1

<h4>Background</h4>Although the BCR-ABL tyrosine kinase inhibitor dasatinib is a potent treatment for chronic myeloid leukaemia, it is associated with the risk of dasatinib-induced pulmonary arterial hypertension (DASA-PAH), for which predisposing factors have yet to be elucidated. However, animal studies have shown that dasatinib exacerbates pulmonary hypertension (PH) in rodent models of PH but not in controls, providing support for a two-hit theory of DASA-PAH pathophysiology.<h4>Case summary ...[more]

PMID: 31020267

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Project description:BackgroundScleroderma-associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very dismal response to therapy and poor survival. We assessed the effects of up-front combination PAH therapy in patients with SSc-PAH.MethodsIn this prospective, multicenter, open-label trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg daily for 36 weeks. Functional, hemodynamic, and imaging (cardiac magnetic resonance imaging and echocardiography) assessments at baseline and 36 weeks included changes in right ventricular (RV) mass and pulmonary vascular resistance as co-primary endpoints and stroke volume/pulmonary pulse pressure ratio, tricuspid annular plane systolic excursion, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide as secondary endpoints.ResultsAt 36 weeks, we found that treatment had resulted in significant reductions in median (interquartile range [IQR]) RV mass (28.0 g [IQR, 20.6-32.9] vs. 32.5 g [IQR, 23.2-41.4]; P < 0.05) and median pulmonary vascular resistance (3.1 Wood units [IQR, 2.0-5.7] vs. 6.9 Wood units [IQR, 4.0-12.9]; P < 0.0001) and in improvements in median stroke volume/pulmonary pulse pressure ratio (2.6 ml/mm Hg [IQR, 1.8-3.5] vs. 1.4 ml/mm Hg [IQR 8.9-2.4]; P < 0.0001) and mean ( ± SD) tricuspid annular plane systolic excursion (2.2 ± 0.12 cm vs. 1.65 ± 0.11 cm; P < 0.0001), 6-minute walk distance (395 ± 99 m vs. 343 ± 131 m; P = 0.001), and serum N-terminal pro-brain natriuretic peptide (647 ± 1,127 pg/ml vs. 1,578 ± 2,647 pg/ml; P < 0.05).ConclusionsUp-front combination therapy with ambrisentan and tadalafil significantly improved hemodynamics, RV structure and function, and functional status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for this patient population. In addition, we identified novel hemodynamic and imaging biomarkers that could have potential value in future clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT01042158).

Project description:Introduction/objectivesScleroderma is a rare complication in taxanes therapy. Although individual cases of taxanes-induced scleroderma have been reported, the clinical manifestation and treatment outcomes were reviewed and summarized rarely. This study reported a patient who developed diffuse scleroderma and possible scleroderma renal crisis after paclitaxel therapy for ureter cancer.MethodA PubMed literature review on published cases of taxanes-induced scleroderma up until April 2022 was included for analysis.ResultsThe search identified 27 patients with adequate information for analysis. Of the 28 patients, including the one presented here, 22 were female. Peripheral edema was the most common symptom in all but one patient, and often accompanied by erythema in 11. Symptoms usually occurred in half of the patients within the 4th course of treatment. Skin lesions gradually progressed to skin fibrosis, and extended proximally. Internal organ involvements were uncommon. Antinuclear antibody tests were positive occasionally, but anti-Scl70 and anti-centromere usually were negative. Taxanes therapy was discontinued, continued and unavailable in 21, 3, and 4 patients, respectively. Corticosteroids for skin lesions with or without immunosuppressive drugs were given to 15 patients. Of 25 patients with available skin outcomes, 19 improved. There was no significant skin improvement between those who did or did not receive skin treatment (62.5% vs. 75.0%, p = 0.37). Skin usually improved after discontinuing taxanes.ConclusionTaxanes-induced scleroderma is different from idiopathic scleroderma. Physicians should be aware of this condition in order to provide early diagnosis and apply appropriate management in order to avoid serious complications from severe skin sclerosis. Key Points • Scleroderma is a rare but unique and serious complication of taxanes therapy • Skin manifestations and distribution are similar to idiopathic scleroderma, but vascular phenomenon, internal organ involvement and scleroderma-associated auto-antibodies are presented rarely. Skin improvement usually occurs shortly after discontinuing taxanes • The role of immunosuppressive therapy in treating taxanes-induced scleroderma is not clear.

Dataset Information

Dasatinib-induced pulmonary arterial hypertension complicated with scleroderma: a case report.

Publications

Dasatinib-induced pulmonary arterial hypertension complicated with scleroderma: a case report.

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