Cholinesterase inhibitors inhibit the breakdown of acetylcholine (Ach) at the neuromuscular junction, thus increasing the availability of Ach to bind AChR. Pyridostigmine bromide is the most widely used compound, average doses are 30–90 mg every 4 h. A sustained release form (180 mg) of the drug is available and prescribed at bedtime to improve weakness in the morning.

MG exacerbations can be rapidly improved by short-term immunomodulating strategies, namely plasma exchange (PLEX) or high-dose intravenous immunoglobulins (IVIG).

More recently, semiselective techniques have been introduced in clinical practice. They use filters able to remove mainly IgG from the patient’s plasma without the need for any replacement fluid. Different adsorbents are available. Filters with Protein A and anti-human IgG are particularly efficient in removing massively circulating IgG and hence pathogenic autoantibodies [9].

Cholinesterase inhibitors rarely induce stable and sustained improvement.

The majority of patients need long-term maintenance of low-dose corticosteroid to avoid relapses, thus increasing the incidence of side effects. In this regard, immunosuppressive drugs have been introduced as steroid-sparing agents [1].

Azathioprine (AZA), a purine antimetabolite, remains the drug of choice, with a safe profile regarding side effects and tolerability. The onset of benefit can be very slow and take up to 12 months. Treatment is usually started at 50 mg daily and increased by 50 mg every week up to the required dose (2–3 mg/bw/day). A randomized study provided Class I evidence regarding its steroid-sparing effect [11]. Measurement of Thiopurine Methyltransferase (TPMT) activity or checking for TPMT genotype [12] status can be considered to better address the issue of potentially severe side effects.

Alternative immunosuppressive drugs include micophenolate mophetil (MMF), methotrexate (MTX), cyclosporine A (CYA), cyclophosphamide (CYP), and tacrolimus.

The absolute indication to thymectomy is the presence of thymoma. Randomized controlled studies on the effect of surgery in MG without thymoma are not available. A metanalysis of the literature on this topic concluded that thymectomy should be considered as a treatment option for patients with non-thymomatous MG to increase the probability of remission or improvement as stated after ad hoc metanalysis [13]. Thymectomy should not be performed as an emergency procedure; patients with severe forms of the disease must be stabilized with PLEX/IVIG and adequate immunosuppression before surgery. There is general agreement that non-thymomatous MG patients with generalized MG and disease onset before the age of 50 years may benefit from thymectomy. The issue of thymectomy in patients with anti-MuSK MG is still controversial.

Myasthenic crisis is a severe and potentially life-threatening exacerbation of the clinical picture leading to respiratory insufficiency requiring admission to the intensive care unit (ICU) for assisted ventilation. The expert opinion is that PLEX or IVIG should be performed soon and associated with high-dose corticosteroid therapy (or the ongoing dose increased).

Some drugs are contraindicated or must be used with great caution in patients with MG, particularly a restricted group of antibiotics. A list of contraindicated drugs is reported in Table 37.2.