Rheumatoid (Ankylosing) Spondylitis

Rheumatoid (Ankylosing) Spondylitis From the Rackham Arthritis Research Unit and the Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan

WILLIAM M. MIKKELSEN, M.D., A.A.C.l'. Assistant Professor, Department of Internal Medicine, and Associate Physician, Rackham Arthritis Research Unit

IVAN F. DUFF, M.D., F.A.C.l'. Professor of Internal Medicine, In Charge, Rackharn Arthritis Research Unit

RHlWMA'l'OID SPONDYLI'l'IS is a systemic illness of unknown etiology afflicting young males predominantly and producing symptoms of pain and stiffness as a result of inflammatory involvement of the sacroiliac, intervertebral and costovertebral joints. As a result of paraspinal calcification and ossification and ankylosis of the spinal joints, complete rigidity of the spine and thorax may be produced. The hips, shoulders and peripheral joints are frequently involved. Certain complications, including impaired pulmonary function, aortic insufficiency, iritis and amyloidosis, occur with significant frequency.

TERMINOLOG Y

The gross pathology of advanced rheumatoid spondylitis was first described by Bernard Connor in 1691 in a report of a skeleton with bony ankylosis of the ribs and vertebrae. Connor's contribution has recently been reprinted together with a brief biographical sketch. l In spite of this and other early descriptions of the gross pathology of the advanced disease, it was not until the dose of the nineteenth century that the reports of Striimpe1l 37 and Marie 22 began to permit elinical recognition of the disease and differentiation from degenerative joint disease of the spine. There are a number of synonyms and eponyms for the disease, ineluding Marie-Striimpell disease, spondylitis rhizomelique, ankylosing spondylitis, pelvo-spondylitis ossificans and rheumatoid spondylitis. The

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American Rheumatism Association in its classification 19 of rheumatic diseases adopted the last term, reflecting the prevalent opinion in this country that the disease is a spinal variant of rheumatoid arthritis. The ::;trongest support for this view is the high incidence in patients with ::;pondyliti::; of peripheral joint di::;ease which is virtually indistinguishable clinically and histopathologically from rheumatoid arthritis. The British view that the diseases are separate entities is supported by several ob::;ervations, among them the striking difference in sex incidence in the t\\O conditions, the unique calcification of the paravertebral soft tissues illspondy litis and the greater frequency of iritis, absenee of ::;ubcutancolls nodules and negative test for "rheumatoid factor" in that disorricJ'. Hille(~ this question cannot be resolved on the basis of present cvidence, the descriptive term ankylosing spondylitis has some advantage. PREVALENCE, SEX AND AGE DISTRIBUTION, GENETIC STUDIES, ETIOLOGY

Adequate information regarding prevalence and incidence ill the general population is not available. The most satisfactory data arc tho::;c of West,40 who found a prevalence of 1 in 2000 among the population "at risk" of Bristol, England. Among 1974 patients from ten reported series, 85 per cent were males. 3D Onset of the disease is characteristically in late adolescence or early adult life and is uncommon after age 40. The tendency for multiple cases to occur within the same family is somewhat more pronounced than is the case with rheumatoid arthriti::;. Rheumatoid spondylitis has been reported 26 in nine sets of monozygotic twins, with involvement of both twins in six instances. Hersh and associates20 found the frequency of rheumatoid spondylitis among 257 relatives of 50 propositi with the disease to be thirty times greater than among 2525 relatives of 406 control patients. It has been pointed out that heredity may play an important etiologic role, one investigation suggesting an autosomal dominant factor with about 70 per cent penetrance in the male and about 10 per cent penetrance in the female. A recent reportl8 suggests penetrance may be greatly increased in both sexes in those families in which a female, especially the mother, is affected. Several investigators have reported a high frequency of chronic genitourinary infection in patients with rheumatoid spondylitis. 30 • 24 Romanus30 in particular has stressed this relationship, suggesting that dissemination of infection via the vertebral venous system, which communicates with the venus plexus about the prostate, seminal vesicles and rectum, might be of etiologic importance. Of interest in this regard is the recognized progression of some patients with the urethritis, conjunctivitis and arthritis of Reiter's disease into rheumatoid spondylitis. Inflammatory disease of the gastrointestinal tract has also been suggested as an

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etiologic factor.36 In two recent studies 1o , 42 the prevalence of rheumatoid spondylitis in patients with ulcerative colitis was approximately five cent. Like rheumatoid arthritis, rheumatoid spondylitis seems to be associated with psoriasis more frequently than would be expected on the basis of chance. In one recent reportll four of 100 spondylitics had psoriasis. Although physical trauma, emotional disturbances and infectious processes occasionally appear related to the onset or exacerbations of the disease their pathogenetic role remains obscure and the etiology remains unknown.

PATHOLOGY Very little information has been gathered about the late, and virtually none ahout the early, pathologie changes in rheumatoid spondylit.is. The most satisfactory descriptions of the histopathology of the dis('a~n are those of Collins5 and Cruikshank. 7, 8 The changes which have been observed in the diarthrodial joints of j he spine and extremities are essentially similar to those described in rheumatoid arthritis, namely proliferation of the synovial cells producing villous hyperplasia, hyperemia, edema and infiltration with inflammatory cells (chiefly lymphocytes and plasma cells) which are occasionally arranged in large follicles. Cartilage surfaces are overgrown by vascular granulation tissue (pannus) which leads to the eventual destruction of cartilage and then to fibrous, and finally bony, ankylosis. Inflammatory foci are often present in the subchondral bone. Cruickshank 8 believes that the process differs from rheumatoid arthritis in that the end stage is bony rather than fibrous ankylosis. Cartilaginous joints, notably the manubriosternal joint and the symphysis pubis, are frequently involved. Cruickshank 8 has described the earliest stage as a subacute osteitis adjacent to the joint. Granulation tissue is produced which eventually replaces cartilage and subchondral bone and becomes ossified to produce a true synostosis. The characteristic "ligamentous calcification" is believed in most instances to occur in the outer fibers of the annulus fibrosus rather than in the ligaments proper. 7 This calcification and later ossification produces, in its early stages, the typical longitudinally oriented "syndesmophytes" as seen radiologically and, in later stages, bridges the gap between adjacent vertebral bodies producing the "bamboo spine" appearance so characteristic of the late disease. The bony bridges often develop marrow spaces continuous with those of the vertebral bodies. The intervertebral disks themselves are generally not involved and the vertebral bodies are usually normal except for bone atrophy. Erosive and destructive bone lesions can occur, however, and cervical spine subluxations, particularly at the atlanto-axial joint, have been reported. Classic rheumatoid nodules occur with extreme rarity, if at all, in

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rheumatoid spondylitis and rheumatoid granulomas have not been described in visceral organs in this disease. 8 Amyloidosis is an occasional complication in patients with severe, long-standing disease. DIAGNOSIS

Clinical Features

A number of excellent reviews of the clinical manifestations of rheumatoid spondylitis have appeared, only a few of which can be cited here.27, 4,2, 13,31,41,3 ONSET. The disease most often has an insidious onset with symptoms of aching, pain and stiffness in the low back. In some instances discomfort is localized to the buttocks or hips. The symptoms are generally mild in severity and intermittent rather than persistent. Like the ~ymptoms of rheumatoid arthritis they tend to be greatest on arising or after periodR of inactivity during the day and to be relieved by phy~i­ cal activity. Not uncommonly, patients complain of nocturnal pain which may awaken them after four to six hours of sleep. When severe, if often forces them to get out of bed and occasionally to spend the remainder of the night pacing the floor or sitting in a chair. The pain of spondylitis is characteristically aggravated by coughing or sneezing, straining at the stool or sudden or jarring movements of the spine. The combined inactivity and jarring of automobile riding may be particularly troublesome. The early symptoms rarely occur in the dorsal or cervical region. In approximately 10 per cent27 the onset is marked by sciatic pain which tends to alternate from side to side and to be associated with normal neurologic findings. The possibility of rheumatoid spondylitis flhould be considered in every young male who complains of sciatic pain. In approximately 25 per cent of cases onset occurs in the peripheral joints.27 The lower extremities are more often affected. Involvement tends to oceur in the larger joints, to be asymmetric, to involve multiple rather than Ringle joints, and, in approximately half of the caRes, to clear without residual abnormality. Occasionally pain in the heels may herald the onset of the disease. It has been stated 9 that symptoms or x-ray evidence of calcaneal periostitis or spurs in a young male should be suspected of being due to rheumatoid Rpondylitis. In rare instances iritis or uveitis may occur before the Rpondylitis. SUBSEQUEN'l' SYMPTOMS. Although the disease may remain confined to the sacroiliac joints it tends to be progressive and may affect the entire spine. With progreRsive involvement of the lumbar, dorsal and cervical spine the localization of symptoms shifts correspondingly. The course is usually characterized by exacerbations and partial or complete

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remissions. Prominent symptoms continue to be aching, pain and stiffness. Chest pain may result from involvement of the costovertebral or costotransverse joints. The manubriosternal joint, which is generally spared in rheumatoid arthritis, is rather frequently involved in spondylitis. Radicular pain is not uncommon in the dorsolumbar regions, \\ here it may be confused with pain of visceral origin, but does not usually occur in the cervical region. As the disease progresses, restriction of motion, \\ hi ch is at first produced by muscle spasm and therefore reversible, becomes more marked and is present even in periods of comfort. In many instances the patient assumes a stoop-shouldered stance with forward projection of the head and neck. As cervical motion is lost it may be necessary for him to shift his feet in order to look to the side. When ankylosis or fixation as a result of paravertebral ossification occurs, symptoms from that area frequently subside although pain may recur at any time. Peripheral Joints. The peripheral joints are affected at some time in the course of the disease in up to 5027 to 67 2 per cent of cases. The older literature stresses involvement of the so-called "root joints," the hips and shoulders. Arthritis of the hip occurred in 28 per cent of 1035 cases reported from the Mayo Clinic; it is frequently the cause of much pain and disability. Shoulder involvement is less frequent, however, and was found in only 7 per cent in the same series. In some instances "shoulder" pain may be due to disease in the acromioclavicular or sternoclavicular joints. In the extremities, involvement tends to be more frequent in the larger joints, particularly the knees, and to decrease in frequency in the smaller, more peripheral joints. Several studies 27 , 2 have revealed the interesting fact that in only about half of those with peripheral disease is involvement associated with permanent objective joint change. Symptoms are those of rheumatoid arthritis. Systemic Symptoms. These are usually present during periods of disease activity, although milder than in rheumatoid arthritis. They include anorexia, weight loss, malaise, ease of fatigue, and low-grade fever. OTHER CLINICAL MANIFESTATIONS. Pulmonary. It is well recognized that pulmonary function in rheumatoid spondylitis may be impaired as a result of involvement of the costovertebral joints, aggravated in some cases by marked dorsal kyphosis. In one recent study,39 significant reduction in vital capacity, increase in residual volume and functional residual capacity was found. Pulmonary function, which resembled obstructive pulmonary empyema in these respects, differed from findings in that condition in that ventilation-perfusion relationships, intrapulmonary gas mixing, one-second vital capacity and flow resistance were normal. Recent reports41, 39 have indicated that pulmonary insufficiency and chronic or recurrent pulmonary infections are not characteristic complications of the disease,

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Ocular. Iritis may occur before other manifestations of the disease are apparent. Recurrent iritis, especially in young men, should raise the suspicion of spondylitis. It is stated15 to occur in up to 30 to 50 per cent of cases. When severe, inflammatory eye disease may be complicated by cataract formation and blindness. Cardiac. It is now accepted that there is a form of cardiac disease peculiar to rheumatoid spondylitis. Aortic insufficiency, which is the outstanding clinical characteristic of this condition, was present in 24 of 51917 and in 7 of 26438 patients. Among 100 patients being evaluated for surgical correction of aortic insufficiency, rheumatoid spondylitis was present in five. 32 Among the associated cardiac findings which have been described are conduction defects, cardiac enlargement, pericarditis and anginal pain. Most patients have presented no evidence of previous rheumatic fever or syphilis. The histopathologic findings have resembled those of syphilis in some respects but have been unlike those of the carditis of rheumatic fever or rheumatoid arthritis. The prevalence of aortic insufficiency seems to increase with the duration and severity of the spondylitis. Physical Findings The physical findings in rheumatoid spondylitis vary widely depending upon the degree of disease activity and extent of its progression. The results of the physical examination are of value in confirming the diagnosis and in following the course of the disease and should be carefully recorded. As in all cases, evaluation of the musculoskeletal system should be only a part of the complete physical examination. In the patient with early disease there is generally tenderness on percussion over the involved sacroiliac joints. In addition, tenderness may be present over the ischial tuberosities, symphysis pubis and pelvic prominences. Spasm, rigidity and tenderness are usually present in the paravertebral muscles. As a result, the normal lumbar lordotic curvature is flattened and the range of motion in the dorsolumbar spine decreased (Fig. 1). Restriction of motion can sometimes be best determined with the patient in a quadruped position. Lateral and rotatory as well as forward and backward motion should be evaluated. As the disease progresses up the spine, tenderness is usually present over the spinous processes in the area affected. The lumbar lordosis is obliterated and the range of motion, which was previously normal except during periods of pain and muscle spasm, becomes permanently reduced as a result of the pathologic changes in the intervertebral joints and paraspinal tissues. Decreased chest expansion, sometimes overemphasized as an early finding in spondylitis, results from involvement of the dorsal spine and costovertebral joints. As a result, breathing may be largely abdominal in type. Increased dorsal kyphosis and cervical hyperextension may lead to significant loss of height. Loss of motion in

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Fig. 1. Patient with early rheumatoid spondylitis demonstrating limitation of flexion in lumbar and lower dorsal spine.

the cervical region is at first temporary, as in lower segments, but with progression of the pathologic changes becomes permanent and, in advanced cases, complete. It should again be emphasized that complete ankylosis is by no means an inevitable development of the disease. The systematic and serial recording of certain physical measurements are of great value in the long-term management of patients with spondylitis. Among those used commonly are: (1) estimation (in terms of percentage of normal or degrees from normal position) of range of forward, backward, lateral and rotatory motion in the dorsolumbar and cervical regions; (2) distance from finger tips to floor on maximal forward flexion with the knees held in extension; (3) horizontal distance from occiput to wall, with the patient standing as firmly against the wall as possible; (4) chest expansion (difference between maximal inspiration and expiration) measured at the xiphoid; and (5) the patient's height. The localization of peripheral joint involvement has been discussed. Objective joint changes, when present, cannot be distinguished from those of rheumatoid arthritis. Subcutaneous nodules are extremely rare, even in those patients with advanced peripheral disease.

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Laboratory Studies

Unfortunately, there is no diagnostic laboratory test for rheumatoid spondylitis. Routine examination of the blood is commonly normal, although mild hypochromic anemia may be observed. The blood proteins may be abnormal, showing a decrease in albumin and elevation of fibrinogen and the alpha-2 and gamma globulins. These deviations are usually mild in degree, similar to the findings in other disorders and therefore of little diagnostic significance. Examination of the cerebrospinal fluid may show moderate elevation of protein concentration, although the cell count, colloidal gold curve and sugar concentration are generally normal. If peripheral joints are involved, the synovial fluid findinl!:s are indistinguishable from those of rheumatoid arthritis, namely an increase in total leukocyte count with a predominance of polymorphonuclear cells, impairment of mucin clot formation and decrease in relative viscosity. During periods of disease activity the erythrocyte sedimentation rate, C-reactive protein test and other "acute phase phenomena" are often, but not always, abnormal. Several investigators have reported normal sedimentation rates in approximately 20 per cent of patients. 13 , 19, 27 It is, therefore, apparent that a normal sedimentation rate is not strong evidence against the diagnosis of rheumatoid spondylitis, nor does it necessarily correlate well with fluctuations in disease activity. Radiology

Although the diagnosis of early rheumatoid spondylitis can often be strongly suspected on clinical grounds, confirmation usually depends upon demonstration of characteristic radiologic features. These occur first in the sacroiliac joints12 where demineralization produces a blurring of the joint margins and apparent widening of the joint space. Bony erosions produce an irregular, scalloped joint margin. Subchondral sclerosis appears on both sides of the joint, although it is sometimes earlier or more pronounced on the iliac side causing confusion with osteitis condensans ilii (Fig. 2). New bone formation eventually produces areas of bony ankylosis which increase in extent as the disease progresses. It is axiomatic that both sacroiliac joints are involved, although in early cases changes may sometimes be observed in one while the other remains normal. Infectious disease cannot be excluded so long as the roentgen findings are unilateral. Patients may occasionally be seen sufficiently early in the course of their disease that the sacroiliac joints will appear normal; the diagnosis in such cases should be regarded as presumptive until the characteristic radiologic features appear. Although radiologists differ in their preference, we have found the sacroiliac joints to be best delineated on stereoscopic frontal oblique views (taken with patient

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Fig. 2. Sacroiliac joints in rheumatoid spondylitis demonstrating irregularity of the articular surfaces. Subchondral sclerosis is more apparent on the iliac side of the joint.

supine, and the central beam aimed at the midsacrum at an angle of 20 degrees toward the head). Radiologic changes in the intervertebral (apophyseal) joints are an essential part of the disease but difficult to demonstrate even with special projections. Of greater diagnostic importance is demonstration of the characteristic paravertebral ossification, the evolution of which has been well documented by Romanus and Y den in their classic monograph. 31 Laterally, this usually appears first in the vicinity of the dorsolumbar junction as a hazy streak of calcification standing out several millimeters from the margin of the vertebral body and extending upward or downward (Fig. 3). Calcification and ossification continue until adjacent vertebrae are united by bony bridges which, when fully developed, have an inner and outer cortex and a middle spongiosa in continuity with that of the vertebral body. These bony lesions, termed syndesmophytes by Forestier,14 differ from the osteophytes of degenerative disease of the spine in that the latter are broad based, oriented in a horizontal rather than vertical plane and have distinct borders even in their early stages. The importance of early destructive lesions in the production of paravertebral calcification is clearly seen anteriorly where the earliest change is a loss of definition of the vertebral corners. ·Bone resorption planes aW3,y the upper and lower thirds of the vertebral margin, sparing the middle third, thus destroying the usual anterior concavity and producing Hsquare vertebrae."31 The bone adjacent to the areas of destruction is

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Fig. 4

Fig. 3. Anterposterior view of dorsolumbar junction showing syndesmophytes in several stages of formation. Fig. 4. Lateral view of lumbar spine showing calcification "in" the anterior ligament and demineralization of the vertebral bodies.

often sclerotic, appearing in x-ray films as the so-called "shining corners."31 The reparative process results in calcification and ossification identical with that which occurs laterally (Fig. 4). Roentgenologic evidence of periostitis over the ischial tuberosities is frequently present in advanced cases. Although the vertebral bodies are usually normal except for demineralization, destructive lesions are occasionally observed. In the cervical spine erosive lesions may be responsible for subluxations,21 which have also been described in association with rheumatoid arthritis. 23 Changes in the hips and peripheral joints cannot be distinguished from those of rheumatoid arthritis. TREATMENT

In most cases of rheumatoid spondylitis the intelligent application of selected modes of available therapy will achieve worthwhile results. The primary goals of treatment are relief of pain, maintenance and improvement of function and prevention or minimization of spinal deformity. The basic program of management is much like that for rheumatoid arthritis with emphasis on analgesia, regulated rest, physical therapy and measures to improve general health. 25 . 28 Also of importance is education of the patient regarding the nature and possible course of his disease. It is vital that he understand that, although cures do not exist,

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Fig. 5. A 46 year old patient with rheumatoid spondylitis showing marked improvement in flexion deformity of the spine and hips as a result of intensive medical and physical therapy, including cervical traction at night, for a 2-month period. A, Before, B, after treatment. (Reproduced, by permission, from Calabro, J. J.: A Therapeutic Approach to Rheumatoid Spondylitis. GP 22: 88, 1960.)

much can be accomplished by faithful adherence to simple measures which are readily available. A more complete degree of patient cooper.ation can be secured if it is possible to demonstrate that pain can be relieved and function improved (Fig. 5). For this reason, whenever possible, the patient with active spondylitis should be hospitalized for indoctrination in this basic program. Following discharge from the hospital, arrangements must be made for adequate follow-up. General Measures

As a baseline of reference for future evaluation of disease progression and response to therapy, every patient should have a complete physical examination with a careful record made of symptomatology and objective abnormalities of the neck, back and peripheral joints. At this time the patient's general health should be carefully evaluated and any necessary corrective measures taken. In some instances evidence of significant weight loss and impairment of nutrition will be present. Although there is no evidence that the nutritional requirements in spondylitis differ in any way from those of the optimal diet, or that

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dietary manipulation will alter the course of the disease, the patient should be provided with a diet which is liberal in calories, protein and vitamin content. Focal infections, if present, should be eradicated although such general measures will rarely have any specific effect 011 the spondylitis. The presence of hypochromic anemia should prompt a search for evidence of gastrointestinal bleeding. The anemia associated with spondylitis is usually mild and seldom calls for any measures other thana trial of oral administration of ferrous sulfate. Coexisting ulcerative colitis or regional ileitis, and complications such as iritis, congestive failure or amyloid disease, are treated when present by accepted medical and surgical measures. Rest

Regulation of rest and physical activity constitutes an important part of the basic program. In the active inflammatory phase of the disease bed rest should be increased to at least nine to ten hours at night, with an additional rest in mid-day. A firm mattress, with bed boards if necessary, is required to maintain the spine in optimal position and to minimizeJlexion Qi,the hips. Elevation of the bed on blocks and placement of In/!~asily gra~p'ed overhead bar may make it easier for the patient to getl in and out of' bed. To minimize flexion of the cervical spine, either no pillow or the smallest possible pillow should be used under the head; it may be helpful to place a thin pillow or folded towel between the shoulder blades when the patient is resting on his back. The patient must learn to discontinue physical activity at the onset of fatigue and before the point is reached at which it interfercs with rest or aggravates symptoms. Household tasks such as ironing or cleaning, sitting for long periods at a desk or movie, bending over an assembly line and prolonged automobile riding are common examples of activities in which fatigue and discomfort may be alleviated by frequent "breaks" or rest periods. Activities involving a great deal of bending, heavy lifting and prolonged standing should be limited so far as possible. Caution should be advised with respect to strenuous physical activities, especially competitive or contact sports, although less active sports such as swimming may safely be encouraged except during periods of severe disease activity. Trauma docs not appear to play an important role in the progression of the disease and the spondylitic generally can be expected to perform successfully in most occupational and recreational situations. Analgesics

In large degree the success of the entire therapeutic regimen depends upon the ability of the physician to provide relief of pain, thereby facilitating rest and an effective physical therapy program. For this purpose ehief reliance is placed Oil the salicylate,., which possess the

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virtues of safety and economy and are generally effective. Acetylsalicylic acid (aspirin) is most commonly employed. The patient should be impressed with the desirability of taking what may seem to him large doses on a regular basis. Unless reassured of the safety of such dosages he may subsequently modify them downward in deference to the common ::mperstition that aspirin "hurts the heart." Immediately upon awakening the patient should take 1 gram (three 5-grain tablets) of aspirin to make early ambulation and dressing easier. If necessary, this or a slightly smaller dose is repeated at breakfast. Additional doses of 1 gram are taken with lunch, the evening meal and at bedtime. It is often helpful to leave an aspirin supply at the bedisde so that the patient who is awakened by pain and stiffness during the night can take an additional dose at that time. The total dose administered by this plan averages 4 to 6 grams in 24 hours. The appearance of tinnitus calls for reduction in dosage. Gastritis can usually be avoided by taking all doses of aspirin with meals, milk or an antacid. The patient with gastritis or peptic ulcer presents a therapeutic challenge which can usually be met by institution of a medical ulcer regimen and perhaps reduction in dosage, in addition to the above precautions. Most buffered aspirin preparations do not eontain amounts of antacids which are adequate in this situation. Sodium salieylate does not appear to possess any appreciable advantage and enteric-eoated preparations in our experience generally result in lowered salicylate blood levels. The more expensive combinations of aspirin with adrenocortical steroids, tranquilizers, salts of para-aminobenzoic acid and other agents offer no therapeutic advantages and their use should not be encouraged. Analgesic agents with addicting properties should not be employed. In some cases salicylates can be advantageously supplemented with non-narcotic analgesics such as dextro-propoxyphene (Darvon) or ethOheptazine (Zaetirin). In the individual who fails to obtain adequate relief with full doses of salicylates, phenylbutazone (Butazolidin) frequently effects very satisfactory relief of pain and stiffness. The initial dose is 100 mg. three or four times daily; after four or five days this is reduced to 100 mg. twiee daily. After symptomatic control is achieved many patients can be maintained on 100 mg. daily or every other day. Supplementary doses of salicylates are employed. As with the salicylates, combinations of this agent with antacids, corticosteroids, etc. arc not recommended. In view of its toxic potentialities it should be stated that: (1) its use is contraindicated in the presence of edema, cardiac failure or severe liver or renal disease; it should be used with great caution, or not at all, in patients with a history of drug allergy, blood dyscrasia, hypertension or peptic ulcer ;(2) if an effect definitely superior to that of aspirin is not achieved within a week the drug should be discontinued; (3) the maximal daily dose should not exceed 400 mg.; if therapy is continued the smallest

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effective dose should be employed; (4) while receiving the drug the patient must be kept under observation and determination of white blood cell count, hemoglobin concentration and estimation of platelets made at four to six week intervals; and (5) the patient must be cautioned to stop the drug and inform the physician immediately should pruritus, skin rash, sore throat, stomatitis or abnormal bruising or bleeding develop. The effect of phenylhutazone is entirely symptomatic and there is no evidence that it alters the disease course. A metaholite of phenylbutazone, oxyphenhutazone (Tandearil), possessing similar but not definitely superior effects, has recently been introduced. Since much of the discomfort of spondylitis results from muscular spasm an effective "muscle relaxant" would be a welcome addition to the therapeutic program. Although none of the multitude of agents available for this purpose has been demonstrated to be uniformly effective, therapeutic trial is sometimes followed by apparent benefit. At present, the element of muscle spasm is most effectively managed by the judicious combination of analgesic agents and selected measures of physical therapy.

Physical Therapy Employment of the various modalities of physical therapy is, in n sense, the essence of the therapeutic program since it is largely responsible for what can be achieved in avoidance of deformity and maintenance of function. Ideally, the program must be adjusted to the special problems which each patient presents. This is best accomplished, whenever possible, by consultation with a physician with special training and experience in this field. Detailed and repeated demonstration of the exercise program by a trained physical therapist is desirable. The patient should be provided with printed or written instructions regarding the home program. 28 This should be reviewed with the patient at frequent intervals and altered in the light of changes in his condition. HEAT AND MASSAGE. The most effective management of acute pain nnd muscle spasm is achieved by administration of analgesic agents together with the application of moist heat (Hubbard tank, hot tub bath or hot packs) followed by gentle massage and range of motion exercises. In less acute situations dry heat utilizing a luminous baker or infrared lamp is very helpful. POSTURAL TRAINING AND REMEDIAL EXERCISES. The eventual posture displayed by the spondylitic is largely the result of what has occurred during the periods of disease activity. Postural training and remedial exercises should therefore be instituted as soon as possible. They are designed to obtain and maintain the best possible position of the spinal column, strengthen the paraspinal muscles, increase breathing capacity and relieve symptoms. These goals should be stressed to the patient along with the necessity of making these exercises a permanent part of

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his daily routine. The patient must be trained to maintain a high degree of "posture consciousness" at all times. The following exercises are ordinarily performed once or twice daily at times when the patient is not rushed and preferably after an ample dose of aspirin and application of heat to the back. 1. Deep breathing exercises. (a) Lie on back; clasp hands behind the head; pull elbows to the bed while breathing-in deeply; hold breath in for a count of ten; exhale and relax; repeat 10 to 20 times. (b) With a rolled towel under the back between the shoulder blades inhale slowly, raising the arms up and over the head; exhale and lower the arms to the sides; repeat 10 to 20 times. 2. Spinal extension exercises. (a) Lying on the abdomen, stretch arms out at shoulder level, raise head, chest, shoulders and arms off the bed as far as possible; relax; repeat 10 to 20 times. (b) Stand facing the corner of a room, place one hand on each wall at shoulder level, bend elbows slightly and pull abdomen in, slowly go forward to force the chest toward the corner; return to original position; repeat 10 to 20 times. 3. Spinal stretching exercise. Suspend the body by grasping an overhead bar with hands a shoulder width apart. With elbows extended, remain as relaxed as possible for a count of 10. Rest and repeat five to ten times. Repetition of certain of these exercises (especially 2b) during breaks between physical activities during the day may help to counteract the fatigue and discomfort associated with a constant position. Other special exercises for hips, shoulders and peripheral joints are prescribed on the basis of the individual patient's needs.

Other Forms of Therapy It is our impression that judicious use of the previously described measures will provide reasonably satisfactory results in the majority of cases. Consideration of other forms of therapy is reserved for those few patients who fail to be satisfactorily benefited. X-RAY THERAPY. Carefully documented experience has indicated that the satisfactory relief of symptoms is achieved by therapeutic doses of x-rays in the majority of selected patients with active rheumatoid spondylitis. 34 In some patients "remissions" associated with one or more courses of therapy have been of impressive duration. There is evidence, however, that in spite of symptomatic benefit, radiographic progression of the disease is not necessarily interrupted. 29 More disturbing, however, have been reports 6, 16, 33 of an increased incidence of leukemia in spondylitics who have received x-ray irradiation therapeutically. At the present time the conservative view would be that ionizing irradiation has little place in the treatment of nonmalignant or nonfatal diseases, and therefore should be reserved as a last resort for those few patients who are resistan( to all other forms of therapy. ADRENOCORTICAL STEROIDS. In our experience adrenocortical ste-

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roids are rarely required in the management of patients with spondylitis. Complications of steroid therapy are similar to those occurring in patients with rheumatoid arthritis and the same conservative principles must govern their use. If corticosteroids are employed, both patient and physician should accept the point of view that their use should be temporary and the minimal effective dose must be employed. Steroid therapy should be added to, not substituted for, the conservative program of management. At intervals the situation should be carefully evaluated and, if reasonable objectives or relief have not been obtained, the steroid is cautiously withdrawn. ORTHOPEDIC SURGERY. In carefully selected cases the orthopedic surgeon may have much to offer. Reconstructive surgical procedures on the hip may provide especially gratifying results. In recent years osteotomy has been employed, sometimes with dramatic results, to correct advanced flexion deformities in the dorsolumbar and even the low cervical spine. In special circumstances other procedures including the use of bivalved body casts, back supports or cervical traction may be indicated. REHABILITATION OF THE SPONDYLITIC

Much remains to be done in the field of rehabilitation of the patient with rheumatic disease, including spondylitis, for whom the conservative measures outlined are inadequate. In the individual patient, the associated problems are often complex and may appear insurmountable. The immediate problem may be identification of such individuals and establishment of contact with available facilities. This is best done by the informed and conscientious physician. Our medical schools must assume responsibility, however, by emphasizing to every medical student the present day capabilities of rehabilitation. Whenever possible, the potentialities of rehabilitation are best explored in institutions which provide the ancillary services which are indispensable to this task. These include the internist with special training in the field of rheumatology, the orthopedic surgeon, the physiatrist, trained physical and occupational therapists, the social worker, and in some instances, a representative of the state Office of Vocational Rehabilitation. Unfortunately, at present this ideal approach is available only in a few rehabilitation and teaching hospitals. REFERENCES 1. Blumuerg, B. D.: Bernanl Connor's Description of Pathology of Ankylosing

Spondylitis. Arthritis & Rheum. 1: 553, 1\)58. 2. Blumberg, B. and Ragan, C.: Natural History of Rheumatoid Spondylitis. Medicine 35: 1, 1956. 3. Boland, E. W.: In Arthritis, .T. L. Hollander, cd.: Philadelphia, Lea & Febiger, 1960.

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4. Buckley, C. W.: In Copeman, W. S. C., ed.: Textbook of the Rheumatic Diseases. Edinburgh & London, E. & S. Livingstone, 1955. 5. Collins, D. H.: Pathology of Articular and Spinal Diseases. London, Edward Arnold & Co., 1949. 6. Court-Brown, W. M. and Doll, R.: Leukemia and Aplastic Anaemia in Patients Irradiated for Ankylosing Spondylitis. Privy Council, Medical Research Council Special Report Series, No. 25, London, Her Majesty's Stationery Office, 1957. 7. Cruickshank, B.: Histopathology of Diarthrodial Joints in Ankylosing Spondylitis. Ann. Rheumat. Dis. 10: 393, 1951. 8. Cruickshank, B.: Pathology of Ankylosing Spondylitis. Bull. Rheum. Dis. 10: 211, 1960. 9. Davis, J. B. and Blair, H. C.: Spurs of Calcaneus in Striimpell-Marie Disease. J. Bone & Joint Surg. 32A: 838, H150. lO. Fernandez-Herlihy, L.: Articular Manifestations of Chronic Ulcerative Colitis. New England J. M. 261: 259,1959. 11. Fletcher, E. and Rose, F. C.: Psoriasis Hpondylitica. Lancet 1: 695, H155. 12. Forestier, J.: Importance of Sacro-iliac Changes in Early Diagnosis of Ankylosing Spondylarthritis. Radiology 33: 389, H139. 13. Forestier, J., Jacqueline, F. and Rotes-Querol, J.: Ankylosing Spondylitis. Trans. by A. U. Desjardins. Springfield, Charles C Thomas, 1956. 14. Forestier, J. and Robert, P.: Osteophytes et syndesmophytes. Gaz. med. France (suppl. Radiol.) 1934, p. 192. 15. Godtfredsen, E.: Mesenchymal Aspects in Ophthalmology. In Connective Tissue in Health and Disease, G. Asboe-IIansen, ed. Copenhagen, E. Munksgaard, 1954. Hi. Graham, D. C.: Leukemia Following X-ray Therapy for Ankylosing Spondylitis. A.M.A. Arch. Int. Med. 105: 51, 1960. 17. Graham, D. C. and Smythe, H. A.: The Carditis and Aortitis of Ankylosing Spondylitis. Bull. Rheumat. Dis. 9: 171, 1958. 18. Graham, W. and Uchida, I. A.: Heredity in Ankylosing Spondylitis. Ann. Rheumat. Dis. 16: 334, 11l57. Ill. Hench, P. S. and others: Ninth Rheumatism Review. Ann. Int. Med. 28: 66,1948. 20. Hersh, A. H. and others: Heredity in Ankylosing Spondylitis: A Study of Fifty Families. Am. J. Human Genetics 2: 391, 1950. 21. Kornblum, D., Clayton, M. L. and Nash, H. H.: Nontraumatic Cervical Dislocations in Rheumatoid Spondylitis. J.A.M.A. 14.'1: 4:11, 1952. 22. Marie, P.: Hur la spondylose rhizomelique. Rev. med. 18: 285, 1898. 23. Martel, W. and Page, J. W.: Cervical Vertebral Erosions and Subluxations in Rheumatoid Arthritis and Ankylosing Spondylitis. Arthritis & Rheum. 3: 546,1960. 24. Mason, R. M., Murray, It. H., Oates, ,}. K., and Young, A. C.: Prostatitis and Ankylosing Hpondylitis. Brit. M. J. 1: 748, H158. 25. Medical and Scientific Committee, Arthritis and Rheumatism Foundation: Home Care in Rheumatoid Arthritis, 10 Columbus Circh~, New York Ill. 26. Moesmann, G.: Hereditary and Exogenous Etiologic Factors in Ankylosing Spondylitis. Acta rheum. scandinav. 6: 144, 1960. 27. Polley, H. F.: Diagnosis and Treatment of Rheumatoid Spondylitis. M. CLIN. NOR'l'H AMERICA 39: 501l, 1955. 28. Rae, J. W. Jr. and Bender, L. F.: Treatment of Patients with Hhcumatoid Arthritis by Physical Means. J.A.M.A. 160: 611, 1956. 29. Hobinson, W. D. and Lampe, I.: Long-Range Evaluation of Radiotherapy in Rheumatoid Spondylitis. Ann. Rheumat. Dis. 7: 245, 1948. :{O. Romanus, R.: Pelvo-spondylitis Ossifieans in Male (Ankylosing Bpondylitis), and Genito-urinary Infection. Aetiological Signifi(~ance of Latter and Nature of the Disease Based on Study of 117 Male Patients. Aeta med. scandinav. 145: suppl. 280, 1953. 31. Homanus, R. and Y den, S.: Pelvo-sponclylitis Ossificans, Hheumatoid or Ankylosing Spondylitis, A ROl'ntgenological and Clinical Guide to Its Early Diagnosis

1324 32. 33. 34. 35. 36. 37.

a8. ::I!l.

40. 41. 42.

W ILLIAM

M. MIKKELSEN,

I V AN F.

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(Especially Anterior Spondylitis). Trans. by J. Whitehollse. Coppnhagen, Mllnksgaard, and Chicago, Year Book Publishers, 1955. Schilder, D. P., Harvey, W. P. and Hufnagel, C. A.: Rheumatoid Spondylitis and Aortic Insufficiency. New England J. M. 255: 11, 1956. Silberberg, D. H., Frohman, L. A. and Duff, I. F.: Incidence of Leukemia and Related Diseases in Patients with Rheumatoid (Ankylosing) Spondylitis Treated with X-ray Therapy. Arthritis & Rheum. 3: 64, 1960. Smyth, C. J., Freyberg, R. H. and Lampe, I.: Roentgen Therapy for Rheumatoid Arthritis of Spine (Marie-Striimpell Arthritis, Spondylitis Rhizomelique). J.A.M.A. 117: 826, 1941. Stecher, R. M. and Hersh, A. H.: Familial Occurrence of Ankylosing Spondylitis. Brit. J. Phys. Med. 18: 176, 1955. Steinberg, V. L.: Ankylosing Spondylitis and Chronic Inflammatory Lesions of Intestines. Brit. Med. J. 2: 1157, 1957. StrCmpell, A.: Bemerkung iiber die chronische Ankylosirende entz~ndung der Wirbelsaule und der Hidtgelenke. Deutsche Ztschr. Nervenh. 11: 338, 1807. Toone, E. C., Pierce, E. L. and Henniger, G.: Aortic Insufficiency with Rheumatoid Spondylitis. In Talbott, J. H. and Lockie, L. M., eds.: Progress in Arthritis. New York and London, Grune & Stratton, 1958. Travis, D. M. and others: Lungs in Rheumatoid Spondylitis. Am. J. Med. 2fi: 623, ]960. West, H. F.: Aetiology of Ankylosing Spondylitis. Ann. Rheumat. Dis. 8: 143, 1949. Wilkinson. M. and Bywaters, E. G. L.: Clinical Features and Course of Ankylosing Spondylitis. Ann. Rheumat. Dis. 17: 209, ] 958. Zvaifler, N. J. and Martel, W.: Spondylitis in Chronic Ulcerative Colitis. Arthriti~ & Rheum. 3: 76, 1960.

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