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Severe Inflammatory Ophthalmopathy in a Euthyroid Patient during Nivolumab Treatment.

ABSTRACT: Introduction:Nivolumab is a promising treatment in patients with advanced malignancies. Among immune-related adverse events, autoimmune thyroid disorders are frequently reported. Patient:A 61-year-old male patient had no history of familial or personal thyroid disease. In 2012, this patient, a heavy smoker, presented with non-small-cell lung cancer that was treated with radiotherapy and chemotherapy. In 2015, the cancer progressed with cervical compressive symptoms, and the patient was treated with nivolumab. Results:After 3 infusions, bilateral eyelid ptosis and bilateral conjunctival redness with chemosis were observed. Ophthalmologic examination revealed severe proptosis with complete ophthalmoplegia but with normal vision, color test, and optic disk. Thyroid function tests were normal (TSH = 0.65 mU/L, free T4 = 15.4 pmol/L) without anti-thyroperoxidase or anti-TSH receptor antibodies. CT scan of the orbits confirmed marked bilateral proptosis with expansion of the orbital adipose tissue without significant thickening of extraocular muscles. T2-weighted MRI showed inflammation of orbital adipose tissue. Nivolumab treatment was withdrawn, and the patient received weekly intravenous high-dose methylprednisolone (1 g for 2 weeks, 500 mg for 4 weeks, and 250 mg for 5 weeks). After the first 3 cycles, significant improvement of left chemosis was observed whereas bilateral ptosis and ophthalmoplegia were unchanged. The patient was euthyroid without thyroid autoimmunity 1 week prior to his death due to massive hemoptysis. Conclusion:We report severe inflammatory ophthalmopathy in a euthyroid patient with non-small-cell lung cancer during nivolumab therapy. The occurrence of such ophthalmic adverse events is likely to increase during nivolumab therapy in patients with advanced malignancies.

SUBMITTER: Campredon P

PROVIDER: S-EPMC5869363 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Severe Inflammatory Ophthalmopathy in a Euthyroid Patient during Nivolumab Treatment.

Campredon Pauline P Imbert Philippe P Mouly Céline C Grunenwald Solange S Mazières Julien J Caron Philippe P

European thyroid journal 20180104 2

<h4>Introduction</h4>Nivolumab is a promising treatment in patients with advanced malignancies. Among immune-related adverse events, autoimmune thyroid disorders are frequently reported.<h4>Patient</h4>A 61-year-old male patient had no history of familial or personal thyroid disease. In 2012, this patient, a heavy smoker, presented with non-small-cell lung cancer that was treated with radiotherapy and chemotherapy. In 2015, the cancer progressed with cervical compressive symptoms, and the patien ...[more]

PMID: 29594059

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Project description:Graves' ophthalmopathy (GO) is a common orbital disease that threatens visual function and appearance. Orbital fibroblasts (OFs) are considered key target and effector cells in GO. In addition, hyaluronan (HA) production, inflammation, and orbital fibrosis are intimately linked to the pathogenesis of GO. In this study, we explored the therapeutic effects of dihydroartemisinin (DHA), an antimalarial drug, on GO-derived, primary OFs. CCK8 and EdU assays were applied to evaluate the antiproliferative effect of DHA on OFs. Wound healing assays were conducted to assess OF migration capacity, while qRT-PCR, western blotting, ELISA, and immunofluorescence were used to determine the expression of fibrosis-related and pro-inflammatory markers in these cells. Moreover, RNA sequencing was conducted to identify differentially expressed genes (DEGs) in DHA-treated OFs, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs was performed to explore potential mechanisms mediating the antifibrotic effect of DHA on GO-derived OFs. Results showed that DHA dose-dependently inhibited OF proliferation and downregulated, at the mRNA and protein levels, TGF-β1-induced expression of fibrosis markers, including alpha smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF). Furthermore, DHA inhibited TGF-β1 induced phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3), which suggested that DHA exerted antifibrotic effects via suppression of the ERK and STAT3 signaling pathways. In addition, DHA suppressed the expression of pro-inflammatory cytokines and chemokines, including IL-6, IL-8, CXCL-1, MCP-1, and ICAM-1, and attenuated HA production induced by IL-1β in GO-derived OFs. In conclusion, our study provides first-time evidence that DHA may significantly alleviate pathogenic manifestations of GO by inhibiting proliferation, fibrosis- and inflammation-related gene expression, and HA production in OFs. These data suggest that DHA may be a promising candidate drug for treatment of GO.

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Severe Inflammatory Ophthalmopathy in a Euthyroid Patient during Nivolumab Treatment.

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Severe Inflammatory Ophthalmopathy in a Euthyroid Patient during Nivolumab Treatment.

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