eMedicine Specialties > Obstetrics and Gynecology > Medical Problems in Pregnancy
Myasthenia Gravis and Pregnancy: Treatment & Medication
Updated: Dec 13, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- Many medications can adversely affect patients with myasthenia gravis (MG). The following drugs must be avoided:
- Narcotics
- Tranquilizers
- Barbiturates
- Inhalation anesthetics (ie, halothane, trichloroethylene, ether)
- Magnesium and lithium salts
- Penicillamine
- Beta-adrenergic agents
- Quinidine
- Aminoglycoside antibiotics
- Colistin
- Neomycin
- Tetracycline drugs
- Lincomycin
- Polymyxin
- Quinacrine
- Chloroquine
- MG is associated with many other autoimmune disorders. Patients must be checked for the following conditions:
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Pemphigus
- Hashimoto thyroiditis
- Scleroderma
- Dermatitis herpetiformis
- Autoimmune hemolytic anemia
- Polymyositis
- Sarcoidosis
- Thymic abnormalities are also associated with MG. As many as 50-60% of patients have lymphofollicular hyperplasia, and 10-20% have a thymoma.
- Therapy should be individualized, and each patient must be followed closely by a neurologist and an obstetrician/gynecologist during pregnancy. Although medical therapy is effective, the patient's condition may worsen. Crisis can occur as a result of a worsening disease processes, reduced effects of anticholinesterase drugs, or overdose of anticholinesterase medication. Management of myasthenic crisis requires careful monitoring. Arterial blood gas values must be monitored in patients with increasing weakness.
- Plasmapheresis is an expensive procedure used in patients in myasthenic crisis. Together with steroids, plasmapheresis is a very effective treatment. It consists of 3-6 exchanges of 2-3 L over 1-2 weeks. It is safe during pregnancy and has even saved patients during fulminant crises. As the etiology of preterm delivery is unknown, plasmapheresis is (or may be) associated with preterm delivery. Other complications can occur from hypovolemic reactions or allergies. Large hormone shifts may cause preterm delivery. Patients undergoing plasmapheresis should be monitored.
- Intravenous immunoglobulin is also useful in patients in myasthenic crisis. It is thought to interfere with anti-AChR antibodies. It is infused at 0.4 g/kg/d for 5 consecutive days. Improvement is noticeable in 3-21 days and lasts as long as 3 months.
- Monitoring patients for infection is important, especially those on steroids. Serial ultrasonography, nonstress tests, and biophysical profiles should be used for kids at risk as per the usual obstetrical management protocol.
- Many patients develop depression or comorbid depressive episodes. Bupropion (Wellbutrin XL) has been studied extensively and may be a good addition for these patients.
Surgical Care
- Surgery is very stressful; therefore, delivery via cesarean delivery is reserved only for necessary cases. Also, the hazards of anesthesia must be kept in mind because patients are sensitive to sedatives and narcotics. Not depressing respiration is important. In 1978, Rolbin and colleagues reported on their evaluation of the safety of anesthesia for MG patients.4 They concluded that regional anesthesia is good for abdominal delivery. They stated that epidural anesthesia could be used to decrease the requirements of systemic medications and provide anesthesia for outlet forceps. Amide-type local anesthetics are thought to be safe when large doses of drugs are needed. The group recommended general endotracheal anesthesia for cesarean delivery in patients with respiratory problems. Depolarizing anesthetics must always be avoided.
- Thymectomy is recommended for most young patients. It improves the disease course and can improve remission. Thymectomy is thought to remove an antigen source and reduce an anti-AChR antibody source. A thymoma, which is a potentially invasive tumor that must be removed, is found in few cases. In 1999, Batocchi et al reported that 4 of 44 patients had thymomas.3 To avoid any postoperative problems, thymectomy is performed when the disease is in control. Plasmapheresis can be used for disease control. In 1986, Ip et al used thymectomy as a treatment for myasthenic crisis during pregnancy.5 The patient improved, and although she had to receive large doses of pyridostigmine, she delivered her baby at 39 weeks' gestation.
Activity
Rest is very important to restore muscle strength, especially during pregnancy.
Medication
Combination drug therapy is reported to be safer and more effective than monotherapy. Pharmaceutical treatment for myasthenia gravis (MG) is very effective.
Anticholinesterase muscle stimulants
Preferred treatment for MG and reportedly are safe in pregnancy. Increase the amount of acetylcholine available to bind to receptors. Neostigmine was the first drug used for MG.
Neostigmine (Prostigmin)
Longer-acting cholinesterase inhibitor that can be used when edrophonium is ineffective. Inhibits destruction of acetylcholine by acetylcholinesterase, which facilitates transmission of impulses across myoneural junctions.
Although it has a short duration, activity is more pronounced.
Because of changed renal excretion rates and changed absorption of drugs, patients who are pregnant receive increased doses in increments of 5-10 mg. IM injection may eliminate these problems.
Adult
15 mg/dose PO q2-3h; not to exceed 375 mg/d
Pediatric
Not established
Atropine antagonizes muscarinic effects; effects of neuromuscular agents are increased
Documented hypersensitivity; GI or GU obstruction
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in epilepsy, asthma, bradycardia, hyperthyroidism, cardiac arrhythmia, or peptic ulcer; anticholinesterase insensitivity can develop for brief or prolonged periods
Pyridostigmine (Regonol, Mestinon)
Acts in smooth muscle, CNS, and secretory glands. Blocks action of acetylcholine at parasympathetic sites and facilitates transmission of impulses across myoneural junctions.
Longer-acting medication that may last throughout night. Edrophonium test can be used with caution to find therapeutic doses.
Because of changed renal excretion rates and changed absorption of drugs, pregnant patients receive increased doses in increments of 15-30 mg. IM injection may eliminate these problems.
Adult
30 mg PO tid/qid; not to exceed 120 mg q4h
Pediatric
Not established
Increases effects of depolarizing neuromuscular blockers; increases toxicity of edrophonium
Documented hypersensitivity; GI or GU obstruction
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in bronchial asthma and persons receiving cardiac glycosides; overdose may cause cholinergic crisis, which may be fatal; have IV atropine readily available for treatment of cholinergic reactions; adverse muscarinic effects include flatulence, diarrhea, vomiting, abdominal cramps, and salivation
Corticosteroids
Immunosuppressants useful in treatment of MG. Deoxycorticosteroids (DOCs) for severely ill patients. Work by decreasing antibody synthesis and inhibiting CD4+ T-cell proliferation. Johns' regimen is the accepted regimen for steroid use in MG. Prednisone is fairly safe during pregnancy. Patients who wish to become pregnant are recommended to get pregnant while in steroid-induced remission. Cleft lip and palate in newborns of patients on steroids were noted in a few instances. High-dose corticosteroids can lead to premature rupture of membranes. Weight gain and cushingoid appearance are common complications.
Prednisone (Deltasone, Orasone, Meticorten, Sterapred)
Immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production.
Steroids cannot be discontinued because relapse will follow.
Adult
60-80 mg/d PO until improvement is observed; taper over 2 wk as symptoms resolve
Pediatric
Not established
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, MG, growth suppression, and infections may occur with glucocorticoid use
Antimetabolites
Azathioprine is used when response to corticosteroids is not adequate or when corticosteroid dosage must be decreased. Also, this drug added if symptoms are not controlled satisfactorily with acetylcholinesterase. It is converted to the metabolite mercaptopurine and inhibits T-cell reactivity. Azathioprine is found to reduce serum anti-AChR antibody titers. Cyclosporine is a strong immunosuppressant and inhibits T-cell activation. It is restricted to patients who do not respond well to other medications.
Azathioprine (Imuran)
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and protein. May decrease proliferation of immune cells, which results in lower autoimmune activity.
Adult
50 mg/d PO initially; may increase qwk to 3 mg/kg/d PO; eventually decrease to 1 mg/kg/d PO
Pediatric
Not established
Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity; low levels of serum TPMT
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level prior to therapy and follow liver, renal, and hematologic function; pancreatitis is rare; monitor CBC count and LFT results qwk for first month; can be used during pregnancy but with caution
Cyclosporine (Neoral, Sandimmune)
Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease for a variety of organs.
For children and adults, base dosing on ideal body weight.
Adult
3 mg/kg/d PO initially; may increase to 5 mg/kg/d PO bid
Pediatric
Not established
Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis because may increase risk of cancer
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adverse effects include renal toxicity and hypertension, which are reversible with cessation of drug; evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzymes; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO
Immunoglobulins
Useful in myasthenic crisis. Neutralize circulating myelin antibodies through antiidiotypic antibodies. Down-regulate proinflammatory cytokines (including INF-gamma), block Fc receptors on macrophages, suppress inducer T and B cells and augment suppressor T cells, block complement cascade, and promote remyelination.
Immune globulin, intravenous (Gamimune, Gammagard, Sandoglobulin, Gammar-P)
Thought to interfere with anti-AChR antibodies. Improvement noticeable in 3-21 d and lasts as long as 3 mo.
Adult
0.4 g/kg/d IV over 5 d
Pediatric
Not established
Increases toxicity of live virus vaccine (MMR); do not administer within 3 mo of vaccine
Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-5 d postinfusion to 30 d); increases risk of renal tubular necrosis in elderly patients and those with diabetes, volume depletion, or preexisting kidney disease; laboratory test result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia
More on Myasthenia Gravis and Pregnancy |
| Overview: Myasthenia Gravis and Pregnancy |
| Differential Diagnoses & Workup: Myasthenia Gravis and Pregnancy |
 Treatment & Medication: Myasthenia Gravis and Pregnancy |
| Follow-up: Myasthenia Gravis and Pregnancy |
| References |
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Further Reading
Keywords
MG, autoimmune neuromuscular disease, human acetylcholine receptors, AChRs, pregnancy complications, pregnancy comorbidity, autoimmune neuromuscular disease, rheumatoid arthritis, systemic lupus erythematosus, SLE, pemphigus, Hashimoto thyroiditis, Hashimoto's thyroiditis, thymic abnormality, scleroderma, dermatitis herpetiformis, autoimmune hemolytic anemia, polymyositis, sarcoidosis, MG and pregnancy
