Introduction: Sarcoidosis is often approached as a predominantly pulmonary disease, yet clinically important progression may occur despite stable thoracic imaging. Although Lofgren syndrome is generally considered a favorable acute presentation, not all patients follow a benign or self-limited course. This case highlights the need to reassess disease activity when extrapulmonary manifestations evolve and to escalate therapy promptly when organ-threatening involvement develops.

Clinical Case Description: 57-year-old man with clinically diagnosed sarcoidosis initially recognized in 2018 as Lofgren syndrome, based on migratory arthralgias, erythema nodosum, and bilateral hilar adenopathy, with pulmonary, cutaneous, and joint involvement. Despite treatment with prednisone, methotrexate, hydroxychloroquine, inhaled corticosteroids, leflunomide, and later adalimumab, he had persistent symptoms and recurrent flares. Notably, CT chest remained stable, potentially underestimating ongoing systemic disease activity. In late 2023, while receiving methotrexate, hydroxychloroquine, and adalimumab, he developed worsening skin lesions, progressive visual symptoms, and left eye vision loss. MRI demonstrated bilateral active optic neuritis, left worse than right, establishing new neuro-ophthalmic sarcoidosis and progression to multisystem, organ-threatening disease. High-dose prednisone led to early visual improvement, but given the severity of ocular/CNS involvement and inadequate response to prior therapy, adalimumab was discontinued and treatment was escalated to infliximab. Infliximab was favored over rituximab because of stronger supporting evidence in severe sarcoidosis, particularly neuro-ophthalmic disease, and because lack of response to adalimumab does not exclude benefit from infliximab. He remains on infliximab, methotrexate, and hydroxychloroquine, is off prednisone, and has had stabilization of vision without major further progression.

Conclusions: Stable pulmonary imaging does not exclude active or worsening sarcoidosis. An initially classic Lofgren syndrome presentation may evolve into refractory multisystem disease with sight-threatening neuro-ophthalmic involvement. Early recognition of extrapulmonary progression and escalation to infliximab may be critical to preserving organ function and preventing irreversible visual loss. Rituximab remains a reasonable later-line option if infliximab is ineffective or cannot be continued.