THYMECTOMY IN COEXISTENT MYASTHENIA GRAVIS AND SYSTEMIC LUPUS ERYTHEMATOSUS: A CASE REPORT

The coexistence of multiple autoimmune diseases in an individual patient has become relatively common. Due to shared environmental, genetic, and immunological factors in the pathogenesis of autoimmune diseases, patients with one autoimmune condition are susceptible to developing additional autoimmune conditions^[1]. Approximately 13% to 22% of MG patients, and 33%–45% of patients with SLE, are affected by additional autoimmune disorders. There have been few reports regarding the coexistence of MG and SLE in the same patient^[9]. A study of 132 MG patients by Bekircan-Kurt et al. found that SLE was present in 3.78% of patients^[10]. In another study of 1,300 SLE patients, MG was prevalent in 1.3%^[11]. The nature of the relationship between these two conditions remains unclear, as either could precede, or follow the development of the other^[7]. Several mechanisms have been proposed explaining this association, including loss of central tolerance following thymectomy, molecular mimicry due to structural similarities between the immunogenic region of the AChR and U1 small nuclear ribonucleoprotein, functional defects involving T regulatory cells in the thymus, effects of chloroquine over the NMJ, the dysregulated expression of Fas (CD95) in both SLE and MG, and the role of chemokine CXCL13 in the pathogenesis of both SLE and MG^[10,11]. Furthermore, the implications this relationship has towards treatment, in particular thymectomy, remains unclear.

The role and effects of thymectomy in patients with coexisting MG and SLE remain controversial. In MG, thymectomy is beneficial as anti-AchR autoantibody production is sourced in the thymus^[3]. In SLE, there are additional concerns that thymectomy could lead to a loss of central tolerance and result in an excessive generation of autoantibodies, which may exacerbate or even induce SLE^[6]. Previous studies have observed hypergammaglobulinemia, B lymphocyte hyperreactivity, and mild T cell lymphopenia in MG patients following thymectomy, and there have been several reports of the emergence of SLE following thymectomy in MG patients^[7,8].

However, while previous reports suggest that in most cases, MG preceded SLE, in which this relationship is attributable to antecedent thymectomy, there are multiple mechanisms in which both conditions may be linked. In our patient, the diagnosis of SLE preceded the onset of myasthenic symptoms by approximately 2 years, suggesting an alternative mechanism, such as a shared pathogenic mechanism (molecular mimicry, non-thymomatous functional thymic defect, chemokine dysregulation), as a more likely cause of this association. Furthermore, aberrant T lymphocyte profiles and signaling has been implicated in the pathogenesis of both MG and SLE^[12,13] As the thymus serves as the site of T lymphocyte differentiation, pathological changes could lead to abnormal activation of autoreactive CD4+ T lymphocytes, which, following interaction with B lymphocytes, leads to autoantibody production, subsequent immune complex formation, and organ damage. Under normal conditions, regulatory T lymphocytes can halt the autoimmune process by inhibiting CD4+ T lymphocyte activity. Thus, dysfunction or deficiency of regulatory CD4+ CD25+ T lymphocytes could predispose to MG and SLE^[12,14,15]. In such situations, thymectomy may be safe to perform, and may even be beneficial in cases in which thymic abnormalities underlie both conditions.

Thymectomy was performed in our patient due to inadequate response to multiple trials of conventional treatment, namely acetylcholinesterase inhibitor, steroid, and IVIg administration. The response towards thymectomy in our patient were observed to be safe and beneficial (modified Osserman class IV pre-and class II post-thymectomy), with marked improvement in the symptomatic control of diplopia and motor strength that was maintained on periodic evaluations 6 months after the procedure without the deterioration or flare of SLE symptoms. However, it is important to note in our patient, thymectomy is likely not the sole reason for improvement. The patient has undergone both IVIg and TPE, in which clinical improvement takes effect at approximately 1 to 7 days, and time to maximal effect is 1 to 3 weeks. Furthermore, the patient was also given azathioprine and mycophenolate mofetil.^[16] These agents, in addition to IVIg and TPE, could also have contributed to symptomatic improvement.

Thymectomy is safe and may even be beneficial in MG patients with coexistent SLE. Other reports report the emergence of SLE post-thymectomy in MG patients, saying that thymectomy and resultant loss of central tolerance is to blame. But in our patient, SLE preceded MG, thus suggesting a shared pathomechanism, and thymectomy was shown to be safe and may even be beneficial. We conclude that thymectomy is safe in SLE, and that SLE and fear of relapse should not contraindicate the procedure when it is needed.