Dyspnea resulting from Fibromyalgia

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Dyspnea resulting from Fibromyalgia by J. Weiss, Chest (Journal for

Doctors)

Two patients with chronic, severe, episodic dyspnea underwent prolonged,

extensive, and invasive evaluations without a diagnosis being made. Both

were subsequently diagnosed with fibromyalgia, and therapy directed at this

condition resulted in resolution of their symptoms. Fibromyalgia is rarely

included in the differential diagnosis of dyspnea, and timely diagnosis and

treatment may be delayed. However, this condition must be considered

because it can only be established by seeking the appropriate history and

physical findings.

Key words: dyspnea; fibromyalgia; pleuritic chest pain

Fibromyalgia is a syndrome of unknown origin characterized by chronic

muscle pain, fatigue, and sleep disturbance. Two patients are reported with

chronic, episodic dyspnea who were referred to our clinic after extensive and

invasive evaluations had yielded no diagnosis. Both patients had clinical

manifestations of fibromyalgia, and their symptoms of dyspnea resolved with

treatment directed at this condition. Fibromyalgia generally is not included in

textbook or primary reference lists of the differential diagnoses of dyspnea.

Similarly, dyspnea is not commonly recognized as a clinical manifestation of

fibromyalgia. An increased awareness of this association is needed.

CASE REPORTS

CASE 1

A 67-year-old white woman was referred to the University of Washington

School of Medicine for evaluation of unexplained episodic dyspnea. She was

a lifelong nonsmoker. In January 1995, she noted the onset of exertional

dyspnea. A cardiac stress test was performed and did not disclose

abnormalities. In February 1995, she had an acute exacerbation of her

dyspnea accompanied by chest wall pain that resulted in her being

hospitalized. Serial cardiac enzyme values and ECGs showed no suggestion

of cardiac ischemia or infarction and subsequent cardiac catheterization

showed no atherosclerotic disease. Chest radiographs, ventilation and

perfusion lung scans, a serum protein C level, CBC, and serum electrolyte

levels were within normal limits. Pulmonary function testing performed after

discharge showed no obstruction or restriction and her diffusion capacity was

normal. In September 1995, she again was hospitalized for acute dyspnea

and chest pain; at that time, a myocardial infarction was again excluded.

Another ventilation-perfusion lung scan was interpreted as very low

probability for pulmonary emboli; a lower extremity duplex ultrasound

evaluation showed no evidence of deep venous thrombosis; and an

echocardiogram demonstrated mild concentric left ventricular hypertrophy

with normal contractility, mild aortic sclerosis, and a trace of mitral

regurgitation. Thyroid-stimulating hormone level was within normal limits. A

cardiopulmonary exercise test revealed no evidence of ventilatory or cardiac

limitation. The patient attained a minute ventilation value of 36% of maximum

voluntary ventilation and an oxygen consumption of 73% predicted maximal

oxygen consumption. Dead space was normal, and the patient reached 82%

of predicted maximal heart rate with a normal BP response and no ischemic

or strain changes noted on ECG. The patient stopped the test due to fatigue,

and the results were interpreted as consistent with " deconditioning. " It must be

noted, however, that her severely limiting dyspnea and chest wall discomfort

were not reproduced during this evaluation. A spiral CT scan of the chest

demonstrated a 1-cm filling defect in the pulmonary artery of the upper lobe of

the right lung; this defect was thought to represent a pulmonary embolus.

Accordingly, anticoagulation therapy was administered, but she experienced

no improvement in her episodic dyspnea. Pulmonary angiography

demonstrated a tiny filling defect in a small branch vessel going to the right

apex that was believed to represent an old or chronic embolus.

During her initial visit to the clinic, the patient suffered another episode of

acute dyspnea and chest pain which was precipitated by reclining in the

supine position. During this episode, her respiratory rate remained at 16

breaths per minute, and auscultation revealed no evidence of crackles,

wheezes, or upper airway stridor. Pulse oximetry showed arterial saturations

of 99 to 100% and an ECG demonstrated normal sinus rhythm at 70 beats per

minute with no evidence of ischemia. Subsequent physical examination

revealed evidence of trigger point tenderness in her fight shoulder as well as

parasternal discomfort on palpation. Palpation of either of these areas

increased her symptoms of dyspnea. In response to specific questioning, the

patient described chronic fight shoulder pain, chronic tennis elbow,

temperomandibular jaw pain, a sleep disturbance characterized by early

morning fatigue despite a good night's sleep, and a tidal volume that was

unconsciously self-limited in an attempt to prevent the chest wall pain. A

presumptive diagnosis of fibromyalgia was made, and the patient was treated

with amitriptyline hydrochloride (25 mg given orally at bedtime). She also

started a structured exercise program. After several weeks on this regimen,

her muscular pain, sleep disturbance, and dyspnea had markedly improved.

CASE 2

A 52-year-old white woman was referred to the University of Washington

School of Medicine for consideration of lung transplantation for pulmonary

hypertension. She had been in good health without dyspnea until 2 years

prior when she became acutely dyspneic while attending a wedding on Mt.

Hood (elevation, 6,000 feet). She did not see a physician at that time. One

month later, she had a recurrent episode of dyspnea accompanied by chest

pain while playing bingo. Emergency department evaluation revealed a

normal ECG and arterial blood gas value determinations included a pH of

7.43, a [Pco.sub.2] of 43 mm Hg, and a [Po.sub.2] of 73 mm Hg while she was

breathing air. The patient was referred to a pulmonologist for further

evaluation. The evaluation included a chest radiograph, pulmonary function

tests, a methacholine challenge test, and thyroid function tests, and all of the

values were within normal ranges. A cardiopulmonary exercise test revealed

no exercise limitation; however, the test did not reproduce the patient's

symptoms of dyspnea and chest pain. She reached 88% of predicted

maximum oxygen consumption (16.6 mL/min/kg) and a minute ventilation of

58% of her measured maximum voluntary ventilation. Her alveolar-arterial

oxygen gradient increased from 13 mm Hg at rest to 34 mm Hg during

exercise (ear lobe sampling) and her dead space fell from 39% at rest to 27%

at maximal exercise. The cardiac response was notable for her attaining 82%

predicted maximal heart rate but demonstrating nonspecific ST changes in

the inferior and lateral leads which resolved early in recovery. The patient

stopped the test secondary to leg and back pain. Urinary catecholamine and

5-hydroxyindoleacetic acid levels and CT scan of the abdomen were

obtained to exclude a pheochromocytoma or carcinoid tumor. The patient

also had a normal lower extremity duplex ultrasound evaluation and

ventilation and perfusion scans that were interpreted as being of low

probability for acute or chronic pulmonary emboli.

Her episodes of dyspnea became more frequent and more severe over the

following year; this forced her to quit working. Fiberoptic bronchoscopy was

performed to exclude an endobronchial carcinoid tumor. A repeat

cardiopulmonary exercise evaluation demonstrated a mild limitation in

maximal oxygen consumption (75% of predicted), however maximum minute

ventilation was 64% of her maximum voluntary ventilation indicating

adequate breathing reserve. Cardiac response and dead space were similar

to those in her previous examination. The patient also did not experience

dyspnea or chest discomfort during this evaluation and stopped the test due

to a pain in her side. Therapy was started with atenolol and chlorthalidone as

well as verapamil for presumptive diastolic dysfunction, and transient

improvement was noted. After several weeks, however, her dyspnea

reappeared and progressively worsened in frequency and severity of

episodes. An exercise thallium evaluation showed no evidence of ischemia or

of ventricular dysfunction; however, an increased [P.sub.2] that was not noted

before was detected with cardiac auscultation. Serologic evaluation was

positive for the lupus anticoagulant. Serum antinuclear antibody, rheumatoid

factor, carcinoembryonic antigen, and anticardiolipin antibody, however, were

negative and her erythrocyte sedimentation rate was 12 mm/h. A subsequent

pulmonary function test revealed a decreased diffusing capacity (53% of

predicted). A pulmonary angiogram demonstrated possible irregular changes

in third, fourth, and fifth generation vessels that were thought to be possibly

consistent with vascular obliteration or vasculitis.

A diagnosis of pulmonary hypertension secondary to lupus anticoagulant

syndrome was made, and treatment with warfarin (Coumadin) was started.

Echocardiography demonstrated an estimated peak pulmonary artery

pressure of 25 to 30 mm Hg. The patient subsequently developed sternal

chondritis and a malar rash. Another serologic evaluation demonstrated a

positive antinuclear antibody titer (1:80). Rheumatoid factor, extractable

nuclear antigens, and subsequent measurements of the lupus anticoagulant,

however, were negative twice. Biopsy of the malar rash revealed rosacea.

The patient was treated with diltiazem hydrochloride and prednisone (40 mg

qd); her symptoms markedly improved. Catheterization of the right side of the

heart demonstrated pulmonary artery pressure of 44/16 mm Hg, right atrial

pressure of 12 mm Hg, pulmonary capillary wedge pressure of 12 mm Hg,

and a cardiac output of 3.5 L/min. Thoracoscopic lung biopsy revealed only

moderate centrilobular emphysema and mild respiratory bronchiolitis; these

were consistent with the patient's history of tobacco use. No evidence of

vasculitic, fibrotic, granulomatous, or thromboembolic disease was noted, and

there was no evidence of anatomic changes suggestive of pulmonary

hypertension.

Over the next several months, the patient continued to experience episodic

dyspnea and parasternal chest pain. In response to direct questioning in the

clinic, she also described early morning stiffness, fatigue, and left elbow

pain.

No sleep disturbance was described. Trigger point tenderness was found

over her left epicondyle, her parasternal region, and bilaterally over her

latissumus dorsi. A presumptive diagnosis of fibromyalgia was made, and the

patient began therapy with amitriptyline (25 mg given orally at bedtime) and a

strnetured exercise program. Over the next several weeks, she noted a

marked improvement in her muscular pains and in her dyspnea. The

amitriptyline dose was raised to 75 mg given orally at bedtime with essentially

complete relief of her symptoms, and the patient has subsequently returned to

work.

DISCUSSION

Fibromyalgia is characterized by chronic fatigue, stiffness, and widespread

pain, usually localized to characteristic locations such as the shoulder, elbow,

and temperomandibular joint. The pain is muscular in origin and usually can

be elicited through palpation of one or more trigger points. Other areas

affected include the paravertebral muscles of the cervical and thoraeolumbar

spine, the intereostals, and the abdominal muscles. Xiphoid and costosternal

pain also are common. Wise and colleagues identified fibromyalgia as the

cause of chest wall pain in 5 of 100 individuals evaluated for chest pain of

noncardiac origin. Fibromyalgia is most commonly seen in middle-aged

women and often may be difficult to diagnose because there are no specific

laboratory or radiologic abnormalities, and the diagnosis can only be made

by history and physical examination. The American College of Rheumatology

criteria for fibromyalgia include widespread pain in combination with

tenderness at specific point sites regardless of accompanying symptoms or

radiographic or laboratory abnormalities. Histopathologic evaluations of

muscle tissue from fibromyalgia patients have demonstrated decreased

adenosine triphosphate and phosphocreatine levels as well as muscle fiber

and mitochondrial changes compatible with chronic muscle hypoxemia

although more recent studies have demonstrated these to be nonspecific for

fibromyalgia.[6] Fibromyalgia has been described in association with a variety

of other disorders including systemic lupus erythematosus, polymyositis,

osteoarthritis, and hypothyroidism.

The syndrome also commonly involves sleep disturbances although none are

specific for fibromyalgia. Patients frequently report waking with fatigue and

muscle stiffness despite sleeping well through the night. Disordered sleep

has been postulated as a cause of fibromyalgia with deterioration of non-

rapid eye movement sleep occurring in response to environmental or

endogenous stress, sleep deprivation leading to an enhanced perception of

pain, and the pain leading to further stress, resulting in a self-maintained

neuropsyehiatric disturbance.

Up to 20% of patients with fibromyalgia have been reported to have comorbid

psychiatric disorders, particularly major depression. There is, however, no

consensus on the cause of fibromyalgia, and controversy remains as to

whether fibromyalgia is primarily a psychological or a pathophysiologic

disorder. Therapeutic options are limited and have been directed toward

treating accompanying medical or psychiatric disorders or toward providing

restorative sleep. Alleviation of symptoms has been described in some

patients following a structured exercise program or use of tricyclic

antidepressants or cyclobenzaprine hydrochloride, although there are few

randomized controlled trials.

Chronic dyspnea has been associated with fibromyalgia. Caidahl and

colleagues studied 87 consecutive women, aged 25 to 65 years, referred to a

rehabilitation clinic for management of fibromyalgia. Using the World Health

Organization self-rating scale of perceived dyspnea, 73 (84%) reported

dyspnea and 10 of these were of stage 3 (ie, having to stop for breath when

walking at own pace on level ground), or stage 4 (ie, shortness of breath

when washing or dressing). Resting dyspnea did not correlate with age,

obesity, smoking, heart rate, hypertension, [FEV.sub.1], [FEV.sub.1]/FVC ratio,

or electromyographic evidence of myopathy although both maximum

inspiratory and maximum expiratory pressures at rest were significantly lower

than those of a reference control group. Ventilatory drive studies in a subset

of

patients demonstrated no abnormality in the response to hypercapneic

stimulation.

The two patients described here had long medical histories of episodic

dyspnea associated with chest wall pain that were unexplained despite

extensive and invasive workups. The episodic nature of these patients'

complaints very likely explains why cardiopulmonary exercise testing,

performed twice in one patient, was unable to reproduce the patients'

symptoms. A more focused examination seeking evidence of fibromyalgia

uncovered classic symptoms including sternal, elbow, rib cage, and shoulder

pain with trigger points. Sleep disturbance was also found in one patient. One

patient had several other confounding issues including pulmonary

hypertension and a transiently positive serum lupus anticoagulant, however,

fibromyalgia can coexist with a variety of autoimmune syndromes. Both

patients responded well to therapy directed at fibromyalgia with a marked

decrease in the frequency and severity of their chest wall pain and dyspnea.

Detailed psychologic evaluation was not performed for either patient.

Chronic severe episodic dyspnea may result from fibromyalgia. In the two

patients described in this report, chest wall discomfort appeared to be the

etiologic factor causing dyspnea. This diagnosis can only be made by

searching for characteristic historical features and physical findings of

fibromyalgia. Fibromyalgia should be considered prior to extensive, invasive,

and costly testing for other causes of dyspnea.