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 10-20 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.