Sleep apnea in male patients with the fibromyalgia syndrome

Sleep Apnea in Male Patients With the Fibromyalgia Syndrome KIMBERLY P. MAY, M.D., STERLING G. WEST, M.D., MICHAEL R. BAKER, M.D., DAVID W. EVERETT, R.P.s.G.T., Aurora, Colorado

PURPOBE Fibromyalgia is a common pain syndromethatisoften associated with sleep disturbanThe most chamcteristic pattern noted on formal sleep study is a-wave intrusion on 6wave sleep. Tbis nonrestorative sleep pattern may be e&ogenous, or caused by any of a number of sleep disturbancea. Our goal was to determine the frequency of sleep apnea and its relationship to a nonrestorative sleep pattern in our patients with fibromyalgia syndrome. PATIEiNTSANDMElMODe~ newfibromyalgia patients seen in the Rheumatology Clinic at FitiArmy Medical Center were screened using history and physhl examination for suspicion of sleep apnea When this condition was suspected, the patients underwent formal polysomnqphy to delineate any sleep disturbance. RESUL’J’SZ Four of 92 women, and 13 of 25 men with the new diagnoh of fibromyalgia syndrome underwent polysomnography. Of the women, 22% (2 of 92) had significant sleep apnea at formal eval+io~ both were obese and oWructive findhga In contra@ 44% (11 of 26) of the men had significant sleep apne% CONCLUSIONSZ&ep apnea is not a significant cause of fibromyalgia symptoms in females. In male patie& with fibromyalgh, sleep apnea was observed in a large percentage. Fibromyalgia may be a marker for occult sleep apnea in male&

From the Department of Rheumatology (KPM. SGW, MRB) and the Pulmonary Sleap Laboratory @WE). Fitzsimons Army Medical Center, Aurora, Colorado. The opinions and assertions herein are the opinionsof the authors, and are not to be construed as official or reflecting the views of the Department of the Army, the Department of the Air Force, or the Department of Defense. Requests for reprints should be addressed to Kimberly P. May, M.D., Department of Medicine, Rheumatology Division,FitzsimonsArmy Medical Center, Aurora, Colorado 80045~5001. Manuscript submitted May 12, 1992, and accepted in revised form October 26,1992.

F

ibromyalgia syndrome (FS) is a common musculoskeletal pain syndrome characterized by complaints of widespread discomfort of longer than 3 months’ duration, and palpable tenderness at 11 or more of 18 specific sites [l]. It is associated with sleep disturbances in 60% to 90% of patients [2-51. The most characteristic sleep abnormality is a nonrestorative sleep pattern, where rapid (Ywaves intrude on the slower 6 waves of deep sleep, reducing the time spent in that restorative phase of sleep [6]. Many factors may cause a-6 intrusion, including bruxism, nocturnal myoclonus, nocturia, arthritic pain, and sleep apnea (SA) [7,8]. The contribution of each of these to a nonrestorative sleep pattern in FS is unknown. Because SA may be a reversible cause of nonrestorative sleep, we sought to define its frequency in our patients with FS.

PATIENTS AND METHODS We prospectively studied 117 consecutive patients with a new diagnosis of FS, in the absence of other rheumatic conditions, made in the Rheumatology Clinic at Fitzsimons Army Medical Center in the 3-year period between March 1989 and February 1992. These patients are described in Table I, and comprised 92 women and 25 men, of whom 85% were white. The mean age of women with FS at evaluation was 44.2 years (range: 21 to 72), with an average duration of symptoms prior to diagnosis of 4.5 years (range: 0.3 to 20). The men with FS had a mean age of 42.1 years (range: 28 to 67), and duration of symptoms of 4.6 years (range: 0.5 to 23). The criteria used for the diagnosis of FS were those proposed by Wolfe et al [l]. These criteria included: (1) widespread aching of more than 3 months’ duration in combination with (2) local tenderness at greater than 11 of 18 specified sites (bilateral occiput, lower cervical spine, second costochondral junction, trapezius, supraspinous, lateral epicondyle, buttock, greater trochanter, and the medial knee). We sought to exclude other chronic pain states and diseases, and therefore also required: (1) absence of traumatic, neurologic, endocrine, muscular, infectious, or other rheumatic conditions, (2) normal Westergren erythrocyte sedimentation rate, creatine phosphokinase, and thyroid-stimulating hormone, and negative rheumatoid factor and antinuclear antibodies, (3) normal radiographs of affected areas, with age-related May 1993

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SLEEP APNEA IN FIBROMYALGIA / MAY ET AL

TABLE I Characteristicsof Patients With FibromyalgiaSyndrome(n = 117) Characteristic Total no. Ethnic origin White Black Hispanic Asian Mean age (range) Years of symptoms (range) Body weight > 120% predicted

Men

Women 92/l 17 (79%) 78192 9/92 3/92 2/92 44.2 4.5 24/92

(84.7%) (9.8%) (3.3%) (2.2%) (21-72) (0.3-20) (26%)

25/117

(21%)

22125 (88%) II25 (4%) 2125 (8%) 42.1;8-67) 4.6 (0.5-23) 5/25 (20%) I

TABLE II Characteristicsof Patients With FibromyalgiaSyndromeAssociated With Sleep Apnea (n = 13) Characteristic Sleep apnea symptoms Restless sleep Daytime somnolence Morning fatigue Morning headache Snoring CII;XI breathing abnormality Polysomnography results Obstructive Central Mixed (central and obstructive) Mean AHI (range)* u-6 Intrusion+

Men

Women 2/92 2/2 l/2 20;;

(2.2%) (100%) (50%) ;;U$’

2/2 Clo”O%, 2/2 (100%) 2/2 (100%) 2/2 (100%) z 12 (6-18) 2/2 (100%)

1 l/25 (44%) 4/11 (36%) 5/l 1 (45%) 6111 (55%) l/11 (9%) 9/l 1 (82%) 8/l 1 (73%) 3111 (27%)

RESULTS

5/l 1 (45%) 2/11 (18%) 4/l 1 (36%) 18 (5.1-46) 6/11 (55%)

!pnea-hypnpneaindexin eventsper hour. 1-sIntrusionwas definedas the spontanwus occurrenceof (I waves in h-wavesleep,as detected

Isleep electroencephalogram. Ofthe six malepatients,one hadobstructiveapnea,two hadcentral men,and three had mixedapnea.

changes permitted, and (4) nontender control points (forehead, bilateral volar forearms, thumbnails, and anterior thigh muscles) on examination. All patients were asked a series of questions to ascertain the presence or absence of symptoms and signs commonly associated with SA [9]. The history included inquiry about restless sleep, daytime somnolence, morning fatigue and headaches, snoring, and breathing abnormalities (reported by a bedmate). The examination included assessment of height and weight, with greater than 120% of ideal body weight (predicted by standard tables based on height and gender) considered a risk factor. If a breathing abnormality in sleep was observed, or if four of the remaining six signs or symptoms were present, SA was suspected, and formal polysomnography was performed. Standard nocturnal polysomnography included an assessment of oxyhemoglobin saturation, electroencephalogram (10-20 lead placement system), electrooculogram, bilateral anterior and submental electromyogram, electrocardiogram for rhythm 599

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analysis, inductive plethysmography, and nasal and oral airflow. Apneas and hypopneas were identified and the number of these events per hour (apneahypopnea index) was calculated. SA was present if the apnea-hypopnea index was greater than five events per hour with duration of apneas at least 10 seconds [lo]. Apnea was further classified as obstructive, central, or mixed based on observation by the same experienced sleep technologist who was unaware of the clinical presentation of the patient. Sleep architecture was evaluated by observation of the electroencephalogram via a standard central lead (&/AZ) and an occipital lead (Os/Ai). (Y Waves were defined as those seen in awake but drowsy individuals, with a frequency of 7 to 11 cycles per second [ll]. 6 Waves are the slow waves of deep sleep, with a frequency less than 2 cycles per second, and amplitude greater than 75 PV [ll]. a-6 Intrusion was defined as the spontaneous occurrence of (Ywaves in d-wave sleep.

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Seventeen of the 117 patients with FS had signs or symptoms of SA. These patients included 4 females and 13 males. In response to questions about SA-related symptoms, the most common complaints included restless sleep, daytime somnolence, morning fatigue, and snoring. Morning headache was reported by only one patient. In 11 of the 17 patients, an observer reported sleep-related breathing abnormalities (snorting, loud snoring, apnea, restlessness). Table II illustrates the characteristics of the 13 patients with SA by polysomnography. Two of the four women with symptoms were markedly obese (both were greater than 200% ideal body weight), and found to have obstructive SA on polysomnography. Both of these patients had (~-6 intrusion associated with apneic episodes. The other two had normal sleep studies. Thus, 2 of 92 (2.2%) female patients with FS had SA. Eleven of 13 male FS patients with SA symptoms had significant SA on formal study. Five of the 11 had obstructive SA, and 2 of these patients were obese. Of the other six, two had central SA, and four had mixed SA (with components of both obstructive and central apnea). (~-6Intrusion was seen in 6 of the 11 patients, but was not specifically associated with any type of apnea (1 had obstructive SA, 2 central, and 3 had a mixed apnea pattern). An additional patient had frequent awakenings due to sleep terrors since being stationed in Vietnam in 1967. The 13th patient was normal. Thus, 11 of 25, or 44% of our male patients with FS manifested significant SA. All patients with significant SA have been treat-

SLEEP APNEA IN FlBRUMYALfM / MAY ET AL

ed with surgical, mechanical, or medical therapies. Both of the women were advised to lose weight, and treated with nasal continuous positive airway pressure. Both had resolution of SA and ar-6 intrusion with these interventions, one with reduction in FS symptoms. In the males, therapy was varied. For the five with obstructive SA, two were treated with nasal continuous positive airway pressure, with resolution of SA, one had resolution of SA with position change; and two were referred to otorhinolaryngology for surgical therapy. The first three noted improved FS symptoms, while the surgical patients were lost to follow-up. The two patients with central SA were treated with oxygen, and both have had continued symptoms of SA and FS. Of the four with mixed SA, two had improvement of SA and a-6 intrusion with nasal continuous positive airway pressure and oxygen. Both had decreased FS symptoms. One of the other two patients with mixed apnea has been difficult to treat, with no change in symptoms, and the last has been lost to follow-up. Thus, of the 13 patients, 1 of the 2 females and 5 of the 11 males had improvement with appropriate therapy. One female and three males had no improvement in symptoms, and three were lost to follow-up.

Representative Case A 51-year-old man reported gradual onset of diffuse aches and pains over 4 years, with 2 years of more intense symptoms in the shoulders and low back after a fall. Evaluation at the time of the fall revealed no physical examination or radiographic abnormality. His history was also remarkable for greater than 10 years of loud snoring with morning headaches, and prominent diffuse morning stiffness. He was receiving hydrochlorothiazide for hypertension, and denied alcohol or tobacco use. The patient was 1.78 m tall and weighed 98 kg (134% of predicted ideal body weight). He had multiple paired tender points and negative control points consistent with fibromyalgia. Plain radiographs of the cervical and lumbosacral spine, knees, feet, and hands were unremarkable. Laboratory examination revealed normal complete blood count and chemistries, a Westergren erythrocyte sedimentation rate of 4 mm/h, creatine phosphokinase of 62 mg/dL (normal: 20 to 220 mg/dL), normal thyroid-stimulating hormone, and negative rheumatoid factor and antinuclear antibodies. He was referred to the pulmonary sleep laboratory and underwent a sleep study confirming the presence of SA. He had cyclic central apneas with oxyhemoglobin desaturations into the low 80s. Snoring was also prominent, with decreased tidal volumes. On subsequent polysomnography 6

months later, nasal continuous positive airway pressure abolished the obstructive findings, and oxygen improved the central apneas. He also noted an improvement in his FS symptoms.

COMMENTS FS is found most commonly in females, who comprise 80% to 90% of all patients with the syndrome [2-51. Conversely, 95% of all SA patients are males [ll]. It is estimated that sleep-related breathing disorders are present in about 1% of the adult male population [lo]. Additionally, two thirds of all persons with SA may be obese [lo]. In this study, 44% of males with FS had significant SA, the same was noted in only 2.2% of females. This implies that SA may be causally related to FS in males. Both of the females, and 3 of the 11 males in our study were obese. SA has been previously associated with FS [8,12]. In the Hamm [12] study, 44 FS patients, of whom 89% were female, underwent repeated sleep studies [12]. Forty-three percent had a-6 intrusion, and 25% were reported to have SA or hypopnea. Unfortunately, the degree of SA was not quantitated, and the patient characteristics were not further described. Molony et al [8] identified a male FS patient with 13 years of musculoakeletal complaints, daytime somnolence, and frequent nocturnal awakenings. Sleep study revealed severe mixed apnea. They then evaluated 11 male patients with SA for FS, and 3 of 11 met the criteria. In the second phase of the study, seven women with FS underwent sleep study; none had SA. They concluded that SA was excluded as an occult cause of FS in women, and believed that the 3 of 11 male patients with SA meeting the diagnostic criteria for FS were not different from the expected prevalence in their clinic. This seemingly high incidence of FS in male patients with SA lends support to our findings. Lack of association was recently noted in a study where 30 SA patients (27 men and 3 women) were evaluated for fibromyalgia [13]. Only 1 of 30 patients (3%) had FS, and these authors concluded that SA alone was not sufficient to produce FS. The small sample size in the study, and relative scarcity of males with FS in the general population may account for their results. Certainly this study suggests that not all SA patients will develop FS. Other polysomnographic investigations of FS patients have not revealed a significant prevalence of SA [6,14], but did not evaluate male patients specifically. Our data would support the theory that SA is not a significant cause of FS in females. Our two female patients were older and markedly obese, and could be expected to be at risk for SA for these reasons [9]. May 1993

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However, in our male patients with FS, significant SA was observed in 44%. This suggests that SA is a frequent cause of FS in males. Our findings have three major implications. First, FS is uncommon in males, and may be part of a symptom complex for occult SA rather than an idiopathic disease entity. Second, the high prevalence of SA found in our males with FS suggests that male FS patients should be aggressively screened by history and physical examination for SA. Formal polysomnography should be performed if indicated. Third, FS is notoriously difficult to treat [l&17]. This may reflect the failure to recognize and treat underlying SA (especially in males), which may be the cause of a nonrestorative pattern of sleep causing FS. Identification and treatment of SA as the cause of nonrestorative sleep may provide an avenue to successful therapy.

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