Systemic Drug-Induced Lupus Erythematous Related to Golimumab: Report of a Rare Case and Review of the Literature

Introduction: Drug-induced lupus erythematous (DILE) is a lupus-like syndrome associated with continuous drug exposure and resolves with drug discontinuation. DILE has been reported with anti-TNF agents, with most cases in infliximab, adalimumab, and etanercept use. Its pathogenesis is poorly understood. While the induction of autoantibodies in anti-TNF treated patients is common, DILE is rare, with an estimated incidence of 0.5-1% and a mean onset of 40.6 weeks. DILE is divided into systemic (SDILE), subacute cutaneous (DISCLE) and chronic cutaneous. DISCLE is the most common, characterized by a milder photosensitive rash than idiopathic SCLE. SDILE resembles a mild form of idiopathic SLE, with arthralgias, myalgias and fever. SDILE related to anti-TNF drugs has distinct characteristics, including higher incidence in women, and is more likely to have cutaneous involvement and positive anti-dsDNA Ab. We present a case of SDILE related to golimumab in an ulcerative colitis (UC) patient. To date, no cases of golimumab-induced SDILE have been reported. Case Description/Methods: A 25-year-old woman with a 10-year history of UC and inflammatory arthritis, well-controlled with golimumab 100 mg/month for 46 months, presented with 3 weeks of severe arthralgias, painless subcutaneous nodules over her hands, oral ulcers, and fatigue. Blood count and metabolic panel were normal. Serological studies showed positive antinuclear Ab (homogenous, titer >1:2650), elevated anti-histone Ab at 3.3 U (strong positive), and positive anti-dsDNA Ab (titer 1:80). CRP, anti-Ro, anti-La, anti-RNP, anti-Smith antibodies, C3 and C4 levels were normal. Our patient was diagnosed with DILE related to golimumab and commenced on prednisone 10 mg/daily. Golimumab was discontinued. The patient was switched to 45 mg upadacitinib for management of UC and inflammatory arthritis. One month after starting treatment, the patient's arthralgias resolved. Discussion: To our knowledge, this is the first reported case of SDILE associated with golimumab. Prior cases have discussed DISCLE and the exacerbation of SCLE due to golimumab (Table 1). This case illustrates the importance of early recognition and investigation of SDILE in patients using anti-TNF agents, particularly as autoantibody positivity may be interpreted as normal in these patients, symptoms are milder than idiopathic SLE and may present without rash or mimic other conditions. Discontinuation of the offending drug leads to resolution, and systemic steroids can be considered in severe cases. Table 1. - Cases of Golimumab-induced lupus-like syndromes reported in the literature Case Author and Year Type of DILE Patient gender and age Time to onset of symptoms follow drug initiation Presenting symptoms Positive antibodies Treatment Outcome Wilkerson et al. (2012) Exacerbation of SCLE Female, 66 0.5 months scaly, annular, erythematous plaques photo distributed on the arms, legs, and upper trunk. -ANA (pattern and titer not reported)-anti-histone-anti-Ro-anti-La -Withdrawal of golimumab-Photoprotection-Topical desonide lotion-Hydroxychloroquine 200mg twice daily-Oral prednisone 40 mg/daily-Methotrexate (12.5mg/wk.) Resolution of cutaneous lesions after addition of methotrexate. Unspecified length of time to resolution. Brunnaso et al. (2013) DISCLE Female, 52 16 months persistent erythematous violaceous macules, papules, and diffuse erythema on the upper trunk, back and upper extremities, which worsened on exposure to the sun. -ANA (nucleolar pattern, titer >1:640) -Withdrawal of golimumab-Photoprotection-Topical mometasone furoate Resolution of cutaneous lesions 7 weeks following the withdrawal of golimumab. Blasco-Morente et al. (2016) DISCLE Female, 47 5 months erythematous plaques and papules the face, scalp, chest, and hands -ANA (homogenous pattern, >1:320) -Withdrawal of golimumab Resolution of cutaneous lesions 2 months following withdrawal of golimumab. Al Izzi et al. (2017) DISCLE Female, 63 2 months annular erythematous scaly psoriasiform eruption on the chest, upper back, and arms -Not reported -Not reported Not reported Gianarakis et al. (2023) SDILE Female, 25 46 months severe arthralgias; painless subcutaneous nodules over the bilateral hands, oral ulcers, and fatigue. -ANA (homogenous pattern, titer >1:2650)-anti-histone-anti-dsDNA (titer 1:80) -Withdrawal of golimumab-Oral prednisone 10mg/daily-Upadacitinib, loading dose 45mg oral daily Resolution of systemic symptoms 3 months following withdrawal of golimumab, 1 month following oral prednisone 10 mg/daily and 3 weeks after initiating upadacitinib.