A rare case of drug-induced hypersensitivity syndrome by pirfenidone for idiopathic pulmonary fibrosis

Suda, K; Chiang, Binluen; Okada, Hirofumi; Mato, Naoko; Maekawa, Takeo; Komine, Mayumi; Murata, Satoru; Ohtsuki, Mamitaro

doi:10.1016/j.alit.2018.02.010

Cited by 3 publications

(1 citation statement)

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“…Based on our experimental data, we speculate that Th2-predominant eosinophilic inflammation and endothelial barrier disturbance may be triggers for unfavourable pirfenidone effects in patients. The clinical relevance of our findings is highlighted by case reports describing increased wheezing and cough, eosinophilic pneumonia, and increased numbers of lymphocytes and eosinophils after the administration of pirfenidone in IPF patients [51,52,53]. Assessment of IL-4 levels, eosinophilia and soluble VE-cadherin as a possible surrogate marker for endothelial barrier dysfunction, might therefore be useful tools to distinguish pirfenidone responders from patients at risk of disease exacerbation.…”

Section: Discussionmentioning

confidence: 54%

Pirfenidone exacerbates Th2-driven vasculopathy in a mouse model of systemic sclerosis-associated interstitial lung disease

et al. 2022

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Systemic sclerosis (SSc) is an autoimmune disease characterised by severe vasculopathy and fibrosis of various organs including the lung. Targeted treatment options for SSc-associated interstitial lung disease (SSc-ILD) are scarce. Here we assessed the effects of pirfenidone in a mouse model of SSc-ILD.Pulmonary function, inflammation and collagen deposition in response to pirfenidone were assessed in Fra-2-overexpressing (Fra-2 TG) and bleomycin-treated mice. In Fra-2 TG mice, lung transcriptome was analysed after pirfenidone treatment. In vitro, pirfenidone effects on human eosinophil and endothelial cell function were analysed using flow cytometry-based assays and electric cell-substrate impedance measurements, respectively.Pirfenidone treatment attenuated pulmonary remodelling in the bleomycin-model, but aggravated pulmonary inflammation, fibrosis, and vascular remodelling in Fra-2 TG mice. Pirfenidone increased interleukin (IL)-4 levels and eosinophil numbers in lung tissue of Fra-2 TG mice without directly affecting eosinophil activation and migration in vitro. A pronounced immune response with high levels of cytokines/chemokines and disturbed endothelial integrity with low VE-cadherin levels were observed in pirfenidone-treated Fra-2 TG mice. In contrast, eosinophil, IL-4 and VE-cadherin levels were unchanged in bleomycin-treated mice and not influenced by pirfenidone. In vitro, pirfenidone exacerbated the IL-4 induced reduction of endothelial barrier resistance leading to higher leukocyte transmigration.This study shows that anti-fibrotic properties of pirfenidone may be overruled by unwanted interactions with pre-injured endothelium in a setting of high Th2 inflammation in a model of SSc-ILD. Careful ILD patient phenotyping may be required to exploit benefits of pirfenidone while avoiding therapy failure and additional lung damage in some patients.

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Section: Discussionmentioning

confidence: 54%