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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
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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.