Tacrolimus-Associated Guillain-Barre Syndrome.

To the Editor: Guillain–Barr e syndrome (GBS) is one of the common causes of acute polyneuropathy in adults affecting approximately 1, 00,000 people every year worldwide. It mainly affects peripheral nerves and is characterized by asymmetrical ascending paralysis; however, areflexia and loss of proprioception can also be present.1 It is most commonly demyelinating, but there are other variants such as motor or sensorimotor axonal neuropathies. Its most severe complication is acute respiratory failure, which has a mortality rate of 15%–30%. 2 Most of the cases are usually preceded by any immune stimulation or infection that triggers an aberrant autoimmune response damaging peripheral nerves with their spinal roots. Commonly associated infections are respiratory or gastrointestinal infection such as cytomegalovirus (CMV), Campylobacter jejuni, etc.3 It has also been associated with neurotoxicity caused by calcineurin inhibitors. We describe a case of acute GBS in a postrenal transplantation patient associated with tacrolimus. A 48-year-old man underwent a renal transplant surgery for end-stage renal disease secondary to IgA nephropathy. He received a live-related donor renal transplant, ABO compatible (one haplomatch) from his mother. The induction therapy given at the time of transplantation consisted of methylprednisolone 500 mg; no monoclonal or polyclonal antibody was used. His immediate post-transplant immunosuppressive regimen consisted of tacrolimus (maintaining a trough level between 8 and 10 ng/L) and mycophenolate mofetil (1.5 gm/d). He had uneventful posttransplant recovery. He received prophylactic oral cotrimoxazole, oral fluconazole for local application, and oral valganciclovir for CMV prophylaxis. On the 15th day post-transplant, the index patient developed sudden onset, bilateral symmetrical lowerlimb weakness with inability to walk. Gradually, his weakness progressed to bilateral upper limbs within 2–3 days. He did not reveal any history of respiratory distress or dysphagia. He also denied any history of fever, diarrhea, and recent vaccination. Clinical examination was suggestive of bilateral flaccid lowerand upper-limb weakness (grade 3 power in all muscle groups) and loss of patella and ankle reflexes bilaterally. Vibration and position senses were normal. Plantar reflexes were flexor, and there was no involvement of cranial nerves. No abnormality was detected in extraocular movements, facial sensations, and corneal reflexes. Palatal movements and gag reflex were also normal. On investigations, he had normal graft function. His tacrolimus level was 17.5 ng/mL. Nerve conduction velocity tests revealed a motor conduction block with demyelination and a mixed motor and sensory axonal-type polyneuropathy. Differential diagnosis for this condition includes infections, most likely virus-associated AIDP, vasculitis neuropathies, drugrelated neuropathies, and metabolic neuropathy etc. The patient’s screening for infections including virology and immunology for EBV, CMV, auto-antibodies (antinuclear, antineutrophil cytoplasmic and antismooth muscle antibodies) was all negative. Serology for HIV, HTLV-1, Lyme, CMV, hepatitis B, and hepatitis C was negative. Antibodies to monosialotetrahexosylganglioside (anti-GM1) were not performed. Cerebrospinal fluid analysis showed elevated protein without pleocytosis. Cerebrospinal fluid analysis for culture sensitivity, India ink, TORCH, and adenosine deaminase returned negative. Magnetic resonance imaging for the cervical spine with screening of the whole spine was performed, which did not reveal any abnormality. Metabolic parameters such as serum TSH, levels of vitamin B12, B6, folic acid, zinc, and lead were also turned out to be negative. Because no other cause could be identified other than CNI therapy, tacrolimus was immediately discontinued and replaced with cyclosporine. Plasma exchange with replacement solution as human albumin was performed. The patient started recovering after 5 sessions of plasma exchange. Partial neurological recovery was noted after 2 months. Tacrolimus is a potent and essential immunosuppressive agent for a post-transplant patient, and various studies have proved its association with a reduced incidence of rejection. In the literature, very few cases of postrenal transplant GBS have been described.4 Most of the published cases are attributed to infectious etiologies such as with CMV or C. jejuni, or use of ciclosporin A.5 In our patient, tacrolimus was the probable etiology considering temporal association with time and American Journal of Therapeutics 0, 1–2 (2020)