C40-03 A Lichenoid Reaction With Anti-TNF Therapy for Sarcoidosis

Abstract A 55-year-old African American female presented with fever, cough, and dyspnea. Chest CT demonstrated peribronchovascular ground glass opacities, mild upper lobe bronchiectasis, and mediastinal/hilar lymphadenopathy. She did not improve with antibiotic therapy. Extensive connective tissue disease work-up was negative. Transbronchial biopsies revealed non-necrotizing granulomas with negative AFB and fungal stains. There was no evidence of malignancy, and she was diagnosed with pulmonary sarcoidosis. Her symptoms remained refractory to prednisone, methotrexate, and mycophenolate, so therapy was escalated to infliximab. After her third infusion, she developed several hyperpigmented plaques on her arms, legs, abdomen, and back that worsened with additional infliximab infusions (Fig. 1). Histopathology demonstrated lichenoid tissue reaction, not consistent with cutaneous sarcoidosis and infliximab was discontinued. Lesions were treated with topical tacrolimus and griseofulvin. Sarcoidosis is a multisystem inflammatory disease characterized by the formation of non-caseating granulomas and the exclusion of other differentials. Management utilizes immunosuppressive agents to target tumor necrosis factor-alpha (TNF-a) and interferon- gamma (IFN-y), the pro-inflammatory cytokines that recruit CD4+ T helper 1 cells, epithelioid cells, and multinucleated giant cells needed to form granulomas. Paradoxical lichenoid reactions have been linked to a variety of medications, including TNF-a inhibitors. However, few lichenoid reactions have been reported in patients on therapy for sarcoidosis. One theory suggests that anti-TNF therapy causes overexpression of INF-y, which enables inflammation. IFNs can be classified as type 1 (IFN-a and IFN-b) and type 2 (IFN-y). TNF-a is known to suppress the activity of dendritic cells and the production of type 1 IFNs. Therefore, it has been proposed that an interruption to this balance may lead to the immune-mediated disease processes mentioned above. Another theory is that genetic susceptibility places certain individuals at greater risk for hypersensitivity reactions. One such example is the IL-23R polymorphism which has been identified in individuals with known Crohn disease and spondylarthritis who developed psoriasis-like lesions. IFN-y activity may be enhanced by IL-12 and IL-18. Thus, genetic polymorphisms for these cytokines have been proposed to play a role in lichenoid skin eruptions. This case demonstrates that infliximab can induce rare, paradoxical lichenoid skin reactions in patients with sarcoidosis. Our patient’s cutaneous adverse event improved after cessation of infliximab, highlighting the importance of vigilance for immune-mediated toxicities and the need for individualized management in refractory sarcoidosis. Clinicians should be aware that TNF-α inhibitors may trigger unexpected inflammatory skin eruptions, and discontinuation may be necessary when severe reactions occur. This abstract is funded by: none