A 64 y/o Woman with Dyspnea

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

2. 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.

3. 64 y/o woman with dyspnea • Past Medical History • Htn • Obesity • Rosacea • h/o lower extremity cellulitis • s/p hysterectomy

4. 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.

5. 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.

6. 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.

7. 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.

8. 64 y/o woman with dyspnea • Hypertensive urgency • Concern for CAD. • Pt was given O2, nitro SL and ASA, and transferred to UW Cardiology.

9. 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.

10. 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

11. 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.

12. 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.

13. 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.

14. 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.

15. 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

16. 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.

17. 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.

18. Objectives Discussion of Myasthenia Gravis • Epidemiology • Clinical Presentation • Diagnosis • Associated Conditions • Treatment

19. 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.

20. 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)

21. 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.

22. 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.

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

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

25. 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.

26. 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

27. 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.

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

29. 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

30. 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.