D-penicillamine induced myasthenia gravis in rheumatoid arthritis: An unpredictable common occurrence?

Abstract

Five patients out of 71 with rheumatoid arthritis (RA), who received D-penicillamine, developed myasthenia gravis (MG) within a two-year period. They all responded promptly to discontinuation of the drug and pyridostigmine administration. None of the patients had anti-Ro(SSA) antibodies or features of Sjögren's syndrome, whereas three of the five had the HLA-DR1 phenotype. The relatively high frequency of MG observed in our population, along with its unpredictability and potentially serious sequelae, necessitates its inclusion in the list of side effects of D-penicillamine routinely discussed with the patient, prior to initiation of the treatment. Full alertness of both the patient and the physician to even minor initial myasthenic symptoms, that dictate immediate discontinuation of the drug, is of obvious importance.

Myasthenia gravis associated with etanercept therapy

“…These are predominately autoimmune peripheral nerve disorders such as chronic inflammatory demyelinating polyneuropathy, Guillain‐Barré syndrome, and mononeuritis 4, 17, 36, 40. Drug‐induced MG is a well‐described occurrence in patients with RA treated with penicillamine, but it has not been reported previously with etanercept therapy 1, 9, 11, 28. Although etanercept has been shown to be beneficial in MG, 3 of the 11 patients studied by Rowin et al37 did not complete the study because of worsened symptoms.…”

Update on Ocular Myasthenia Gravis

“…Historically, D-penicillamine (used in the treatment of rheumatoid arthritis) was known to induce AChR Ab-positive MG in up to 7% of treated patients. 34,35 In contemporary practice, MG is now increasingly being recognized as a complication of immune checkpoint inhibitors (ICPis). These medications are being increasingly used to upregulate the immune system to target a variety of malignancies.…”

Pathomechanisms and Clinical Implications of Myasthenic Syndromes Exacerbated and Induced by Medical Treatments

“…When studying the effects of different calcium channel blockers on transmitter release at the neuromuscular junction, it was found that P-type calcium channel blockers inhibited nerve-evoked action potentials and subsequent synaptic transmission, while transmitter release remained unaffected by selective L-type and N-type channel blocking agents (Protti et al, 1996). These findings underscore that P-type channels Vincent et al, 1978;Aldrich et al, 1979;Albers et al, 1981;Kuncl et al, 1986;Drosos et al, 1993;Andonopoulos et al, 1994;Adelman et al, 1995;Penn et al, 1998 Chloroquine Anti-malarial drug that prevents biocrystallization of heme Parmar et al, 2002;Cartwright et al, 2004;Purvin et al, 2006;Oh et al, 2008;Khalid et al, 2016 Ach, Acetylcholine; AChR, Acetylcholine receptor; COVID-19, coronavirus disease 2019; CTLA4, cytotoxic T-lymphocyte-associated protein 4; EMG, Electromyography; GVHD, Graft-versus-host disease; HSCT, Hematopoietic stem cell transplantation; HMG-CoA reductase, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase; IFN, Interferon; MG, Myasthenia gravis; PD-1, Programmed cell death protein 1; PD-L1, Programmed cell death 1 ligand 1; Th2, T helper type 2.…”