Etanercept/methotrexate

Abstract

Brachial plexus neuropathy induced by diffuse large B-cell lymphoma: case report A 74-year-old woman developed brachial plexus neuropathy induced by diffuse large B-cell lymphoma during treatment with etanercept and methotrexate for rheumatoid arthritis. The woman started receiving oral methotrexate 8–16mg per week at the age of 70 years, 2 months following the onset of seropositive rheumatoid arthritis with high disease activity. Three months later, SC injections of etanercept 25–50mg per week were added. Thereafter, the arthritis improved, and after 1 year of methotrexate initiation, her disease remained in remission. After 2 years of methotrexate initiation, the dose of initiation was maintained at 10mg per week. However, 4 years and 1 month following the onset of rheumatoid arthritis (i.e., at the age of 74 years), she reported dysaesthesia, as well as movement difficulty in her left fourth and fifth fingers. After 3 months, her grip strength became 0kg, and after another 2 months, she developed difficulty in left elbow flexion and extension. Of note, her arthritis remained in remission during this time. After another 2 months, she was hospitalised due to severe muscle weakness of her left upper limb. Physical examination was notable for soft elasticity of the left axillary lymph node. Neurological findings revealed the following: clear consciousness, absence of cranial nerve abnormalities, fourth grade of manual muscle testing (MMT) of her left deltoid muscle, with zero to one grade of MMT for the other muscles of her left upper limb, 0kg on tests of her left grip strength, absence of muscle weakness in her other limbs, absence of reflex abnormalities in any of her four limbs, absence of positivity for pathological reflex, hypoalgesia, sense of vibration, left limb dysaesthesia, ataxia, bladder or rectal disturbance, gait abnormality and amyotrophy of muscles. Blood tests were notable for the following: HbA1c 5.2%, CRP 0.053 mg/dL, sIL-2R 420 U/mL, RF 91.9 U/mL, MMP-3 31.9 ng/mL, anti-cyclic citrullinated peptide antibody 317 U/ mL, M peak at γglobulin region for serum protein fraction, Epstein-Barr Virus (EBV) IgG anti-VCA antibody forty times for ten times as upper limit of normal and IgG anti-EBV-nuclear antigen antibody positive. The results of cerebrospinal fluid analyses were normal. Acute and chronic denervation findings of her first dorsal interosseous muscle and biceps brachii muscle, as well as chronic denervation findings of the deltoid muscle on her left side were observed in the cervical spinal cord region. No abnormal findings were seen in other regions during electromyography. Nerve conduction studies revealed the following: amplitudes of evoked distal and proximal compound muscle action potential (CMAP), motor nerve conduction velocity (MCV), and distal motor latency (DML) at the left median nerve were 60μV, 30μV, 29 m/s, and 2.6 ms, respectively. The amplitudes of evoked distal and proximal CMAP, MCV, and DML at the left ulnar nerve were 630μV, 460μV, 47 m/s, and 3.5ms, respectively. Diffuse white matter hyperintensity lesions were seen on fluid-attenuated inversion recovery MRI. Nerve hypertrophy and contrast effects were noted at her left brachial plexus (indicating brachial plexus neuropathy), as well as on the more distal peripheral nerves on T1 fat saturation contrast MRI. CT scan identified hypertrophy at her left axillary lymph node. Attenuated images were observed at the same node during fluorine-18 fluorodeoxyglucose positron emission tomography CT (FDG-PET CT). A biopsy sample was obtained from the left axillary lymph node. Thereafter, the woman started receiving immune globulin for the brachial plexus neuropathy, with little improvement. Histological diagnosis of the biopsy showed diffuse large B-cell lymphoma. Lymph follicles were not observed inside the capsula fibrosa of the the left axillary lymph node. The cells with chromatin condensation appeared larger than endothelial cells and were Ki-67 positive, CD20-positive, CD5 negative and EBER in-situ hybridisation negative. Methotrexate-associated lymphoproliferative disorder (LPD; diffuse large B-cell lymphoma) was diagnosed (after a total dose of 2732mg). Hence, methotrexate was discontinued. Etanercept was also discontinued due to the possibility of etanercept-associated LPD (after a total dose of 9200mg). Eighteen days following the last dose of methotrexate, she became able to move her left finger. After 9 days, left elbow flexion, as well as forward flexion of her left limb 135 degrees became possible. After 1 month, fine finger movement became possible. The dysaesthesia gradually disappeared. Two months following the last dose of methotrexate, the weakness in her left upper limb considerably diminished. Three months after the last administration of methotrexate, nerve hypertrophy and contrast effects disappeared at her left brachial plexus and the more distal peripheral nerves on T1 fat saturation contrast. Based on these observations, the diagnosis of brachial plexus neuropathy induced by methotrexate-associated LPD was established. She did not experience a clinical relapse over 6 months.