Nocardiosis in Lupus Patient Associated with Benlysta Therapy, Case Report Suggests

A patient treated with Benlysta (belimumab), an FDA-approved treatment for active systemic lupus erythematosus (SLE), developed central nervous system nocardiosis, according to a recent case report.

The report, “A Case Of Central Nervous System Nocardiosis In A Patient With Lupus Treated With Belimumab,” was published in the European Journal of Rheumatology.

Benlysta is a human monoclonal antibody that blocks a stimulator molecule from binding to B-lymphocytes (a type of immune system cell), preventing their survival and improving autoimmune inflammatory reactions.

Nocardiosis is an opportunistic infection that immunosuppressed patients often acquire, affecting the lungs, skin, or central nervous system (CNS). According to the study’s authors, this was the first case reported of CNS nocardiosis in an SLE patient treated with Benlysta.

The patient was a 41-year-old woman with a history of SLE and lupus nephritis who didn’t respond appropriately to other immunosuppressive agents. She arrived at the clinic with several symptoms, including persistent diffuse rash, arthralgia, fatigue, abnormal blood analyses and proteinuria (high levels of protein in the urine). At the time, she was receiving daily treatment with mycophenolate mofetil (3,000 mg), hydroxychloroquine (400 mg), prednisone (10 mg) and isoniazid to treat her latent tuberculosis.

Two months after her visit to the clinic, the patient started a standard regimen of Benlysta — an infusion of 10 mg per kg of body weight every two weeks for the first three doses, and then monthly infusions in addition to her other immunosuppressive drugs. After the fourth drug infusion, the patient showed a marked improvement in her joint pain and blood analyses.

But after seven infusions of Benlysta, the patient started complaining of a headache on both sides of her head at least three or four times a week. The pain was relieved by sleep but worsened with prolonged sitting.

Doctors found no neurological cause for the headache. However, a brain magnetic resonance imaging (MRI) and CT scan detected and confirmed a hemangioma, a non-cancerous growth in the brain.

Her doctors then analyzed samples of the patient’s cerebrospinal fluid (CSF) and performed fungal cultures to check whether the lesion resulted from an infection. Results indicated that the patient was infected with the Nocardia bacteria.

Both Benlysta and mycophenolate mofetil were immediately discontinued, and the patient was hospitalized to receive intravenous meropenem and trimethoprim-sulfamethoxazole (TMP-SMX), as recommended by an infectious disease specialist for the treatment of CNS nocardiosis. But the TMP-SMX therapy was also discontinued due to induced dermatitis (skin inflammation).

Meropenem treatment was continued for three months, combined with a minocycline for one month. A new MRI after the treatment showed no change compared to the first one, and repeated analysis of the CSF revealed no organisms.

Six months after this treatment, the patient was restarted on hydroxychloroquine (400 mg daily) and mycophenolate mofetil (2,000 mg daily) for her SLE symptoms. The headaches disappeared and the patient was reported to be doing well with her active exercise routine.

“As the patient was on mycophenolate and belimumab [Benlysta], one can argue whether this infection was because of belimumab or mycophenolate or a combination of both,” the researchers wrote. “We will argue that belimumab or the combination because of the timing of symptom onset and the diagnosis of nocardiosis in relationship to belimumab exposure.

“According to safety data from the extension study, the cumulative rate of severe infections in patients who received mycophenolate with belimumab over four years was 1.5-fold greater than that in patients who received immunosuppressants other than mycophenolate with belimumab (9.4 vs. 6.3/100 patient-years),” they added.

“Although headache is a common side effect of belimumab [Benlysta], CNS infections, such as nocardiosis, should be considered in the differential diagnosis of patients with SLE presenting with a new onset of unremitting headache even if other systemic signs remain unremarkable,” the team concluded. “When the clinical suspicion is high, head CT or brain MRI should be considered in addition to lumbar puncture for CSF analysis.”