Adalimumab is a recombinant human monoclonal antibody directed against tumor necrosis factor alpha (TNF-α) which significantly improves symptoms, limits joint damage progression, and leads to disability in patients with rheumatoid arthritis (RA).1

Among the known secondary effects related with adalimumab, skin reactions, reactivation of tuberculosis, congestive heart failure, lupus like syndromes, cytopenias, and worsening or onset of demyelinating neurologic diseases are found,2 as well as rhinitis, headache, upper respiratory tract infections,3 joint pain, nausea, diarrhea, and other more serious infections needing hospitalization and tumors.4 Neurologic diseases associated to this treatment are Guillain–Barrè (SGB)5–7 syndrome, Miller–Fisher (SMF)6 syndrome, optic neuritis,8 hypertrophic pachimeningitis,9 meningitis due to Lysteria monocytogenes10 and demyelinating encephalomyelitis.11 However, infections have also been described which may constitute the causal agent of the process due to molecular mimicry induced immune mediated damage, and the resulting neurologic affection, as in the case of Mycoplasma pneumoniae.12

We present the case of a 31-year-old male diagnosed with seropositive RA 5 years prior and had a negative Mantoux test. He was treated with sulphasalazine and leflunomide. Treatment was optimized with methotrexate 25mg/week, deflazacort 12.5mg/day and, because of the poor response, adalimumab was added at a dose of 40mg every 2 weeks. After the second dose of adalimumab, the patient presented vomiting, diarrhea and fever, and was diagnosed as having acute gastroenteritis. After 72h without improvement, treatment with ciprofloxacin was initiated. The patient then presented lower back pain, a reduction in muscle strength of the lower limbs 4/5 distal and 4+/5 proximal, arheflexia, difficulty for standing and walking and pain on cervical movement with neck rigidity and no other meningeal signs.

Lumbar puncture obtained 850leukocytes/mm3 (91% neutrophils), glucose 39mg/dl (glucose: 144mg/dl), proteins 155mg/dl, no microorganisms on Gram stain and no acid-fast bacilli on Ziehl–Nielsen stain. Laboratory studies showed an ESR of 51mm, a CRP 5.2mg/l. The serologic study included HSV 1 and 2, VZV, CMV, EBV, HBV, HCV, HIV, Coxiella burnetti, M. pneumoniae, Parvovirus B19, Salmonella, Shigella, Proteus OX19, Borrelia burgdorferi, Brucella abortus, Rickettsia typhi and R. conorii, Treponema pallidum, and all of them resulted in negative. Anti-ganglioside GQ1b antibodies were not studied. No pathologic findings were seen on cranial, cervical, dorsal, and lumbar magnetic resonance. An electromyogram manifested a mixed sensitive-motor demyelinating polyneuropathy with affection of upper and lower limbs and signs of acute denervation, with a loss in axonal volume of the common left perineal nerves, which showed no latency, and both posterior tibialis nerves, with latencies of 5.15ms on the left side and 6.55ms on the right. The F wave of the left tibialis nerve was slightly lengthened (56.25ms).

In the diagnosis of meningeal syndrome (possibly bacterial meningitis due to an unknown germ versus decapitated) and GBS, adalimumab was suspended and intravenous treatment with ceftriaxone, vancomycin, and ampicillin for the suspected meningitis, and immunoglobulin and hidrocortisone for GBS resulted with a good clinical progression.

When administering a TNF-α antagonist, the drug may reach the nervous system through the roots and nerve terminals, where the blood brain barrier is insufficient or absent, and neutralizes it in the peripheral nervous system. Low levels of TNF-α may increase or prolong specific T cell responses to myelin and increase the risk of development of an immune mediated neuropathy by altering the intrinsic balance of TNF-α and its receptors in the peripheral nervous system.13

We present the case of a patient with a meningeal syndrome, probably related to bacterial meningitis due to an unknown germ, and GBS diagnosed based on clinical progression and the patients history. Other diagnoses, such as vasculitic neuropathy, diffuse polyneuropathy or germ-associated polyradiculoneuritis were ruled out by the symmetrical clinical presentation, electromyographic results and negative serology.

We propose three possibilities as an explanation for our case. First, cell induced immunosuppression due to adalimumab may facilitate both infectious processes (gastrointestinal infection and the resulting GBS, and the possible infectious meningitis). Second, both the diarrhea and the GBS may be adverse events from adalimumab, and the possible meningitis due to immunosuppression, decapitated due to antibiotics administered for diarrhea. Third, an infectious agent may be the cause of all of the symptoms due to immune mediated, induced damage due to molecular mimicry. Even then, we assume that this clinical picture is caused by the treatment with adalimumab due to the temporal association between the injection of the drug and the onset of symptoms.

There are case reports of patients with RA who develop demyelinating diseases such as MFS,6 optic neuritis,8,14 demyelinating encephalomyelitis11 or mononeuritis multiplex15 ranging in time from 1 month to 1 year after the onset of treatment with adalimumab, or GBS5 and chronic inflammatory demyelinating polyneuropathy16 between 2 weeks and 1 year after treatment onset with etanercept or infliximab, but none of them have shown two simultaneous manifestations.

Our patient could be the first case of demyelination of the peripheral nervous system described and infection of the central nervous system simultaneously. However, it is impossible to know if these clinical events are due to an associated opportunistic infection associated to cellular immunosuppression induced by adalimumab or a drug associated adverse event.