MG treatment includes oral acetylcholinesterase inhibitors such as pyridostigmine bromide and immunosuppressive drugs. Moreover, patients with MG exacerbation or crisis are treated with intubation or noninvasive ventilation, IVIg, and plasma exchange. We decided to administer IVIg in this case when the patient exhibited head drop and dyspnea as signs of MG crisis. Previously, stroke, myocardial infarction, and other thrombotic complications have been reported as rare but severe side effects of IVIg, due to the associated increase in blood viscosity [5, 6]. In this case, we considered the patient’s chest pain and dyspnea to be acute ischemic heart disease or pulmonary embolism in response to IVIg. We could not perform enhanced computed tomography of the chest and abdomen to exclude pulmonary embolism, pneumothorax and aortic dissection. However, the improvement seen with the injection of glyceryl trinitrate would suggest coronary artery spasm rather than stenosis or obstruction.
Previous reports have suggested that there is a deficiency of nitric oxide (NO) activity in the endothelial cells of the coronary arteries with CSA [7]. Moreover, the spastic arteries are sensitive to nitroglycerin, a vasodilator, and to the effect of acetylcholine, a parasympathetic neurotransmitter, which can induce vasospasm by constricting the vascular smooth muscle when the endothelium is damaged [7,8,9,10,11]. Other reports showed that atherosclerotic lesions detected by intravascular ultrasound may be sites of focal vasospasm, even in the absence of significant angiographically confirmed coronary disease [12]. The patient had diabetes mellitus, so there may have been undetected atherosclerotic lesions at the site of the spasm.
A case of CSA induced by acetylcholinesterase inhibitor (ambenonium chloride) had been reported in an MG patient 3 weeks after dosing [13]. The patient in this report had taken pyridostigmine bromide, an acetylcholinesterase inhibitor, for 25 days, with her last dose several hours before CSA symptoms were noted. IVIg therapy in severe MG and MG crisis shows rapid effect, so there is no speculation, we hypothesized that the CSA might be induced by IVIg rather than the acetylcholinesterase inhibitor.
As shown in previous studies, IVIg has multiple modes of action, which include activation of bacterial phagocytosis, Fc receptors blockade, complement downregulation, suppression of cytokine activity modulation of dendritic cells, and T and B cell activation and differentiation [14]. In addition, IVIg may induce the production of vasoconstrictive cytokines, arterial vasospasm, and disrupt atherosclerotic plaques leading to thrombotic events [15, 16]. IVIg therapy causes an increase in serum viscosity; therefore, the risk for thromboembolic events such as myocardial infarction, pulmonary embolism, and stroke, especially in patients with risk factors for cerebral vascular disease as in our case, must be considered. Further study is required to confirm the relationship between IVIg and CSA. Practitioners should be aware of the potential risk of CSA, and we recommend caution when administering IVIg to treat MG patients, particularly in elderly patients with vascular risk factors and several comorbidities.