A 64 y/o Woman with Dyspnea Pamela Ryan MD February 14, 2007

January 30, 2006 CC: “I’m short of breath.” 64 y/o woman with increased dyspnea on exertion over the past 2 weeks. Notes a “heaviness in my chest”, also described it as a band of pressure across her chest and upper abdomen. Denies PND, orthopnea. No personal hx of CAD or pulmonary disease.

64 y/o woman with dyspnea Past Medical History –Htn –Obesity –Rosacea –h/o lower extremity cellulitis –s/p hysterectomy

64 y/o woman with dyspnea ROS: significant for an increase in lower extremity edema, recent episodes of urinary incontinence, occasional visual changes, reports her “eyelids feel heavy”, and generalized fatigue. The patient also notes she has not been taking her bp medication.

64 y/o woman with dyspnea Meds: –HCTZ 25 mg po qd (had not taken for the past few weeks) –Minocycline Social Hx –Widow –Lifetime non smoker; rare ETOH –Lives on a dairy farm.

Exam BP: 214/116 Pulse:98 Temp 98.1 RR 14 O2 Sat on room air is 97% HEENT: No papilledema. ?Slight right eyelid droop. EOMI PERRLA CV: RRR nl S1 S2. S4 also present. Lungs: Clear Abd: Soft, nontender Ext: 1+ pitting edema bilaterally.

64 y/o woman with dyspnea EKG: NSR, rate 86. Poor R wave progression—unchanged compared to 2003 EKG. Troponin ordered. CXR: within normal limits.

64 y/o woman with dyspnea Hypertensive urgency Concern for CAD. Pt was given O2, nitro SL and ASA, and transferred to UW Cardiology.

Inpatient Evaluation/Treatment Ruled out for MI. Begun on metoprolol, captopril, and lasix. Echo: Mildly dilated left atrium, normal RV size and systolic function, LV: Distal posterolateral wall is thin and hypokinetic relative to other segments. Normal chamber size. Global systolic function is at the lower limits of normal.

Inpatient Eval/Treatment Dobutamine stress: 71% of predicted heart rate, test stopped secondary to anxiety. No evidence of wall motion abnormalities. No ischemia. Discharged to home 02/01/06

Inpatient evaluation/Treatment Assessment: DOE was secondary to hypertensive urgency. Discharged on ASA, toprol XL, lisinopril, HCTZ and a statin. Rec: wt loss, low sodium, low cholesterol diet.

F/U visits 02/09/06 Pt reports “some improvement” in dyspnea. F/U on bp. Discussed PFT’s—pt would like to wait. Increased metoprolol. 2/20/06 Pt reporting increased fatigue and dyspnea. Decreased metoprolol dose (from 100 mg to 50 mg) and ordered PFTs. 2/27/06 Drug rash. Dyspnea and fatigue continue. Ordered dopplers of LE and D-dimer. (both negative) PFT’s to be performed later that day.

2/27 Pulmonary Function Tests Moderate reduction in FEV1 and FVC; significant improvement in FEV1 following albuterol administration. Testing consistent with a combined restrictive and obstructive ventilatory defect.

Restrictive Lung Disease Intrinsic lung diseases, which cause inflammation or scarring of the lung tissue (interstitial lung disease) or fill the airspaces with exudate or debris (acute pneumonitis). (DLCO generally reduced) Extrinsic disorders, such as disorders of the chest wall or the pleura, which mechanically compress the lungs or limit their expansion. Neuromuscular disorders, which decrease the ability of the respiratory muscles to inflate and deflate the lungs.

03/06/06 Patient reports she feels tired. Eyes are “droopy”. New onset of intermittent double vision over the past week. Dyspnea is worse. No cough. No wheezing. Feels anxious. Occasional chest tightness. Exam: BP 146/86 Pulse 60 O2 Sat 94% – Bilateral ptosis noted. EOMI PERRLA –Rest of neuro exam normal

Summary at this point Increased DOE, hypertension, restrictive/obstructive component on PFT’s, bilateral ptosis, unrevealing cardiac workup. Discussed obtaining spiral CT, optho evaluation and EMG. Ordered anti-acetylcholine receptor antibody.

64 y/o woman with dyspnea EMG results: “Electrodiagnostic Findings indicate a postsynaptic neuromuscular transmission defect consistent with myasthenia gravis.” Anti-acetylcholine receptor antibody level still pending. Patient was begun on pyridostigmine 30 mg qid.

Objectives Discussion of Myasthenia Gravis –Epidemiology –Clinical Presentation –Diagnosis –Associated Conditions –Treatment

Myasthenia Gravis Most common disorder of neuromuscular transmission. Hallmark of the disorder is a fluctuating degree of weakness involving the respiratory, ocular, limb and bulbar muscles. Weakness is the result of antibodies to the acetylcholine receptor in the postsynaptic membrane of the NM junction.

Epidemiology Annual incidence is new cases per million people. Occurs at any age, but tends to have a bimodal distribution—early peak in second and third decades (> women) and late peak in sixth to eighth decade (>men)

Clinical Fluctuating weakness and fatigue in specific muscle groups. More than 50% present with ptosis and/or diplopia. 15% present with bulbar sxs (dysarthria, dysphagia, and fatigable chewing) Extraocular muscles often involved.

Myasthenia Gravis Two clinical forms: –Ocular: limited to the eyelids and extraocular muscles. –Generalized: may affect ocular muscles, but also bulbar, limb and respiratory muscles.

Clinical Course Early on, symptoms are often transient. Maximal extent of disease is typically seen by 3 years of onset of sxs.

Drugs which can exacerbate MG All beta blockers Fluoroquinolones Aminoglycosides OCPs Narcotics Phenytoin and Gabapentin

Diagnosis Clinical diagnosis, supported by electrophysiological studies as well as autoantibodies. Tensilon Test Serologic Testing—autoantibodies against the acetylcholine receptor. Present in 85% of patients with generalized disease. These are highly specific. If the AChR antibodies are negative, an assay for MuSK(muscle specific receptor tyrosine kinase) antibodies should be performed.

Diagnosis Electrophysiologic studies: –Repetitive nerve stimulation (sens. 75%) –Single fiber electromyography (sens-95%) –Positive 90-95% of the time on ocular MG –Positive >95% of the time in generalized MG

Associated conditions Autoimmune disorders –Autoimmune thyroid disease, RA, SLE Thymic tumors (thymic hyperplasia, primary thymoma) –Imaging of the mediastinum should be considered part of the evaluation in any patient with MG.

Treatment Symptomatic Immunomodulating treatments (steroids and other immunosuppressive drugs) Rapid immunomodulating treatments (plasma exchange and IVIG) Surgical (thymectomy)

Treatment Acetylcholinesterase inhibitors— pyridostigmine Commonly used immunomodulating drugs in MG are prednisone, azathioprine, cyclosporine, and mycophenolate. Plasmapheresis and IVIG are rapid acting, but have a short duration of action— typically reserved for myasthenic crisis, as a bridge to initiation of other therapies

My patient Treated with pyridostigmine 30 mg qid and had a remarkable improvement in her symptoms. Discussed treatment with steroids, but patient was hesitant due to long term consequences of steroid therapy. CT scan of chest was normal (no thymoma) One year later she continues to do well on the pyridostigmine alone.