S eminars

in and Rheumatism

Arthritis VOL.

VII,

FEBRUARY

NO. 3

1978

Diffuse Idiopathic Skeletal Hyperostosis (DISH) [An kylosing H yperostosis of Forestier and Rotes-Querol] By Donald

Resnick.

Robert F. Shapiro,

Peter D. Utsinger,

Kenneth

B. Wiesner.

and Stephen

R. Shaul

D

IFFUSE idiopathic skeletal hyperostosis (DISH) is a recently proposed name for a skeletal disorder producing characteristic alterations in both spinal and extraspinal structures.‘.2 Although the name is new, the disorder is not. having first been described over 35 years ago. This report summarizes historical, clinical, radiographic, and pathologic findings in this disorder and is based upon a review of pertinent literature and personal observations of a large number of patients with DISH. HISTORICAL

ASPECTS

DISH previously has been noted in the literature under a variety of names (Table 1). Spondylitis oss(jicans ligamentosa was described by Knaggs” and Oppenheimer.” Oppenheimer’ based his observations on a study of 282 patients with calcification or ossification of vertebral ligaments. Eighteen of these patients developed ligamentous changes in the absence of lesions of the vertebral bodies, intervertebral discs, and apophyseal joints. Patients in this subgroup were usually over 55 yr of age and asymptomatic. Calcification or ossification was most extensive in the anterior longitudinal ligament of the thoracic region, less complete in the lumbar region, and almost absent in the cervical segment. The anterior longitudinal ligament appeared increased in length, tortuous, and attached to the vertebral bodies. Oppenheimer k indicated that ligament ossification required two preexisting conditions: disuse related to vertebral immobility and rarefaction of the adjacent bone. His observations suggested that immobilization increased the

Seminars in Arthritis and Rheumatism,

Vol. 7. No. 3 (February). 1978

Gen Niwayama.

chance of transformation of dedifferentiated connective tissue into bone and that the lime salt deposited in new bone originated from the adjacent rarefied vertebral body. Ligamentous calcification was therefore not the cause but rather the consequence of decreased mobility. Thus spondylitis ossificans ligamentosa was not a distinct disease but a secondary phenomenon. Spondvlosis hyperostotica was introduced by Ott’ in a clinical and radiographic study of ligamentous ossification in 1I males and 4 females. He regarded the changes as severe spondylosrs deformans and noted the mild evolution of the disorder. Physiologic vertebral ligamentous calci$kation was described by Smith et al.” in 53 patients (36 males, 17 females). The patients were generally older than 60 yr, and the majority of them had spinal pain and stiffness. Vertebral abnormalities were most frequent in the thoracic spine and included the presence of an ossified anterior longitudinal ligament 5510 mm in thickness and osteophytosis. and the absence of osteoporosis. Smith et al. noted that the ossi-

From

the

Internal Diego,

and

partment and

Departments

Medicine.

University

of Medicine,

the

Department

Carolina,

Chapel

Donald

of

Veterans

Radiology,

AdminDtration

of California lJniversi/y of

at San

Pathology, Hospital.

Diego.- the De-

of California

Medicine.

and San

Universitv

at Davi.y. o/

North

Picker

Foun-

Hill.

Resnick,

M.D., is a

PickerScholar.

dation. Address Dept.

of

for

3350 La Jolla

c

reprint

Radiology,

Donald

Resnick,

Administration

M.D., Hospital.

Village Dr., San Diego, Calif: 9216 I.

1978 by Prune

ISSN

requests: Veterans

& Stratton,

Inc.

0049-0172/7XfO703-0005%05.000//)

153

RESNICK

154

Table 1.

Diffuse Idiopathic Skeletal

Hyperostosis:

Names in the Literature Spondylitis ossificans ligamentosa Spondylosis hyperostotica Physiologic vertebral ligamentous calcification Generalized juxtaarticular ossification of vertebral ligaments (Senile) ankylosing hyperostosis of the spine Spondylosis deformans Vertebral osteophytosis

fied ligament appeared increased in length or “flabby,” particularly at the level of the intervertebral disc, and was distinct from the anterior margins of the adjacent vertebrae. Mild degenerative changes of the sacroiliac joints were occasionally visible on radiographs, although in the majority of patients the sacroiliac, apophyseal, and costovertebral joints were normal. These authors speculated that limitation of spinal motion in older patients resulted in degenerative changes of the ligaments with subsequent calcification and ossification. Thus physiologic ligamentous calcification was the result of spinal immobility. Sutro et al.7 elucidated clinical and radiographic findings in this disorder, calling it generalized juxtaarticular oss$ication of ligaments of the vertebral column. Their patients were usually asymptomatic and without restricted motion, and radiographs outlined abnormalities both in the axial and extraaxial skeleton. No relationship to a specific etiology was found. Forestier and co-workers8*g introduced the term (senile) ankylosing hyperostosis of the spine. These authors evaluated over 200 patients with the disorder, noting that 65% were males. They enumerated characteristic roentgen features in the spine, including involvement of the anterior and right lateral aspect of the thoracolumbar region, undulating calcification and ossification, cortical hyperostosis, particularly in the cervical and lumbar regions, a cloudlike shadow at the level of the intervertebral disc, and thick irregular spur formation. Similar outgrowths at extraspinal sites were recorded. Utilizing pathologic specimens of the vertebral column, these investigators noted regional ossification within the anterior longitudinal ligament, intervertebral disc, and paravertebral connective tissue. It is obvious from this brief review of some of the more important reports describing this

ET AL

disorder that investigators have disagreed primarily in the appropriate name for the condition. The most popular term has been ankylosing hyperostosis of the spine, but the inadequacies of this name are immediately evident. As will be noted subsequently, vertebral ankylosis, although apparent radiographically, may not be found on pathologic examination. Furthermore, extraspinal manifestations are common and may be more extensive than spinal alterations. These extraspinal changes can exist without vertebral abnormality. This has led us to introduce the more appropriate term of diffuse idiopathic skeletal hyperostosis (DISH), emphasizing the widespread nature of the disorder.

CRITERIA

FOR DIAGNOSIS

Although many previous publications have noted general radiographic features of DISH, none has stressed specific roentgen criteria for establishing the diagnosis. Forestier and co-workers8,g described in great depth the characteristic abnormalities of the vertebral column. When radiographs reveal all of these typical findings, the diagnosis can be made with confidence. Difficulty arises when the roentgenograms outline mild or moderate alterations that do not encompass all the classical features; for example, the number of osteophytes that are necessary or the extent of ligament ossification that is required in order to arrive at a definite diagnosis is not stated. We have insisted upon three strict radiographic features of the spine as a prerequisite for diagnosis of DISH.2 As more is learned about extraspinal manifestations in this disorder, specific abnormalities at extravertebra1 sites will also allow definite diagnosis. Our three criteria for spinal involvement in DISH are as follows: (1) The presence of flowing calcification and ossification along the anterolateral aspect of at least four contiguous vertebral bodies with or without associated localized pointed excrescences at the intervening vertebral bodyintervertebral disc junctions; (2) relative preservation of intervertebral disc height in the involved area and the absence of extensive radiographic changes of “degenerative” disc disease, including vacuum phenomena and vertebral body marginal sclerosis; and

DISH

(ANKYLOSING

HYPEROSTOSIS)

(3) absence of apophyseal joint bony ankylosis and sacroiliac joint erosion, sclerosis, or intraarticular osseous fusion. All three radiographic criteria must be fulfilled to establish a definite diagnosis of DISH. The first criterion is particularly helpful in separating this condition from typical spondylosis deformans; the second criterion distinguishes DISH from intervertebral (osteo) chondrosis; the third criterion eliminates patients with ankylosing spondylitis. Three other points regarding these criteria must be stressed. Our choosing four contiguous vertebral bodies as the least extensive ossification compatible with the diagnosis of DISH is arbitrary. Had we chosen two or three contiguous vertebral bodies as the appropriate extent of ossification, the incidence of DISH would obviously increase. We decided upon four contiguous vertebral bodies to separate this entity from typical spondylosis deformans, yet separation of these two entities, spondylosis deformans and DISH, in this manner may not be correct or even useful (see below). Secondly, DISH is a disorder of middle-aged and elderly patients. In these individuals some degree of intervertebral disc degeneration [intervertebral (osteo) chondrosis] is usually apparent. Although our second criterion insists upon relative preservation of disc height and absence of extensive radiographic changes of intervertebral (osteo) chondrosis, we are obviously eliminating from consideration some patients who have both DISH and “degenerative” disc disease. Elimination of these patients enables us to more accurately define back complaints related to DISH. Thirdly, as will be discussed subsequently, sacroiliac joint abnormalities do occur in DISH. These may include osteophytes and coexistent osteoarthritis, particularly in older patients. Although these changes are associated with sacroiliac joint space narrowing and paraarticular bony bridging, they should not be confused with ankylosing spondylitis, since erosions and intraarticular bony ankylosis are not apparent. Furthermore, apophyseal joint space narrowing and sclerosis, particularly in the lumbosacral area, occur in DISH, but bony ankylosis of these articulations, which is seen in ankylosing spondylitis, is not observed in DISH.

155

CLINICAL ASPECTS Despite evidence that DISH is an extremely common entity,‘,‘” there is a relative paucity of information on the clinical features of patients with DISH. Numerous papers characterizing roentgen abnormalities in DISH have failed to delineate the broad clinical spectrum of this disorder. Presumably there are several reasons for this. DISH has long been regarded a radiographic entity whose clinical manifestations are minor and of little significance. Furthermore. since DISH is not uncommon, many patients with this entity are seen by a rheumatologist or orthopedic surgeon for coexistent rheumatic disorders, and symptoms and signs related to DISH are frequently obscured by clinical manifestations of these associated diseases. Thirdly, since many patients with DISH are elderly with “nonsignificant” complaints. the frequent clinicians may pay less attention to their symptomatology. Forestier and Rotes-Querol” expressed the concern of many earlier observers when they noted that “. . . these patients are elderly and suffer little pain or discomfort [so that] treatment of the spinal disease is seldom indicated.” Subsequently Forestier and Lagier” emphasized the mild clinical manifestations of the disorder, manifestations that included little spinal pain or discomfort without significant decrease in spinal mobility or deformity. Although cervical dysphagia was occasionally apparent, severe spinal rigidity, common in ankylosing spondylitis, was not seen, and any sciatic pain radiation was related to concomitant intervertebral disc disease. These same observations were noted by Sutro et al.,’ who emphasized the absence of complaints referable to the spine and sacroiliac joints and a similar absence of significant loss of motion in the cervical, thoracic, or lumbar segments. Harris et al.” noted variable symptoms and signs in an evaluation of 34 patients with the disorder. Most of these individuals had backache that was occasionally severe in nature. Some limitation of spinal movement was found but the spine was not entirely rigid. Dysphagia localized to the cervical region has been observed in this condition, related to spinal osteophytosis. I2 It is difficult to interpret clinical data from previously reported series of patients with DISH for several reasons:

156

(1) Studies vary in the criteria used to establish a definite diagnosis. Indeed, frequently no indication is given as to how the diagnosis of DISH was documented. (2) Studies report a particular age of onset of disease or age of first examination yet fail to indicate whether or not the patient fulfilled specific criteria for diagnosis when initially evaluated. (3) Studies fail to suggest any inherent biases in patient selection. More specifically, no indication is given as to whether patients were diagnosed by routine radiographic studies and subsequently interviewed and examined or whether they were seen in a clinical service because of specific symptomatology and physical signs. (4) Studies fail to specify the nature of the population from which the patients were selected. We wish to summarize our clinical observations in patients with DISH, since these observations differ somewhat from previous investigations, particularly in that we have noted a variety of symptoms and signs in this entity, some of which appear as specific as the associated radiographic findings. Our observations are based upon three separate series of patients, each of which had its own inherent bias: Series A. In this series 21 consecutive patients seen at the Veterans Administration Hospital in San Diego, California fulfilling our previously cited radiographic criteria for diagnosis were interviewed and examined by a rheumatologist.’ These patients were either inpatients or outpatients and were all males, reflecting in part the predominant male constituency at this hospital. Series B. In this series 40 patients who presented to and were followed by the Rheumatology Service at the University of North Carolina School of Medicine were determined to have DISH by our radiographic criteria.‘” This clinical population was predominantly female. Series C. This series comprised 24 patients who were referred to rheumatologists in Sacramento, California. The majority of these individuals presented with clinical findings associated with another systemic rheumatic disease and were later found by our radiographic

RESNICK ET AL.

criteria to have DISH. In only two of these patients was DISH unassociated with another rheumatic disease. The ages of patients in all three of these series was similar to those of patients in other large series.. X” The mean age in our populations was 66 yrs (range 48885 yr). DISH is thus a disease of older individuals. In reality, the advanced age of these patients with DISH reflects not that the disorder has its inception in elderly patients but rather that a lengthy period of time is necessary before the spinal abnormalities progress to such a degree that they fulfill specific radiographic criteria. In many of these patients, musculoskeletal complaints had been noted for many years, this duration even exceeding 40 yr in some individuals. Furthermore, patients between 20 and 40 yr of age occasionally demonstrated radiographic features that, although not fulfilling our criteria for diagnosis of DISH, were strongly suggestive of that entity (lower thoracic vertebral bony excrescences extending between two or three consecutive vertebral bodies, cervical spine bony masses, prominent calcaneal and olecranon spurs). DISH predominates in male patients (Table 2). Forestier and Lagierg noted that 65% of their patients were males. Our results are similar. In series B, 75% of patients with DISH were male; in series C, 67% were male. This male predilection becomes even more apparent when one notes that in both of these series referral populations were predominantly composed of women. Our series do not offer much insight into racial characteristics of patients with DISH. Blacks represented less than 10% of the referral population from which series C was collected; all patients with DISH in this series were white. Series A contained only one black patient; blacks comprised approximately 30% of all patients seen at that facility. Similarly, in series Table 2. Age and Sex Characteristics

in Four Series of

DISH Patients

SW

Age (vrl

No.of Patlt?lltSMeall Series A Series I3 Series C Forestier’ Harris”

21 40 24 245 34

66 67 65 67

Range 49-80 48-85 51-81 85%>50 47-83

MC&

Female

21 30 16 65% 17

0 10 8 35% 17

DISH (ANKYLOSING

157

HYPEROSTOSISI

Table 3. Symptomatology

Table 4.

in 40 Patients

(Series B) With DISH

Major Sites of Clinical Involvement With DISH (Series A)

PEXCent

____--

spine Morning stiffness Thoracolumbar Lumbar and/or cervical Recurring evening stiffness Stiffness aggravated by sitting Stiffness aggravated by cold Dysphagia Peripheral jomts Peripheral bone and jomt pain Acute synovitis of a single joint Gout CPPD’ Heel parn Elbow pain

in 21 Patients

80 80 28 30 40 38 15

33 18 5 13 23 13

Response to therapy Stiffness relieved by analgesics Stiffness relieved by local heat

58 28

‘CPPD: calcium pyrophosphate deposition disease.

B DISH was observed mainly in white patients (greater than 95%); the clinic population of black individuals was approximately 10%. In our experience, a majority of patients with DISH have symptoms and signs (Tables 3-5). Although in some instances these clinical findings may be unrelated to this disorder, there is evidence to suggest that such clinical manifestations may indeed be part of the disease spectrum. Some of the patients’ complaints, such as stiffness, restricted motion, and tendinitis, are certainly consistent with underlying radiographic alterations. In addition, close correlation of symptomatology and radiographic and radionuclide findings adds additional substance to the argument that DISH is associated with certain clinical abnormalities. Axial Skeleton The principal musculoskeletal complaints in patients with DISH are spinal stiffness and mild middle to low back pain. In series 9, spinal stiffness was apparent in 80% of the patients; in series A middle or low back pain was an initial complaint in 57% and an eventual complaint in 67 % of patients. Spinal stiffness and pain generally begins in middle age and may persist for many years. These complaints are initially apparent in the thoracolumbar spine and are characterized as mild intermittent and nonradiating discomfort. Stiffness may appear upon arising in the morn-

Sites Cervical spine Thoracolumbar spine Shoulders Elbows Knees Heels

Characterlstrcsof InYOIVement* __I c M

___-No Of Patlents D __________6 15 15 10 5 7 2

7 3

11 10 3 2 3

P 9 14 4 3 3

Other sites: hand (4). tibia1 tuberosity (I). hip (5). acromioclavicular joint (1). wrist (2). foot (1). subtalar joint (41. ankle (2). ‘D, dysphagia: C. crepitus: M. decreased range of motion; P. pain or tenderness.

ing and dissipate within an hour of mild activity. It can return in late evening”’ and become aggravated by sitting or cold, wet weather. Within several years of onset, thoracolumbar spinal stiffness and pain can progress with involvement of lumbar and cervical segments.‘” Cervical spine pain may occasionally be an initial complaint and eventually a prominent one.‘,‘” Spinal discomfort has been relieved by mild analgesics, such as aspirin or acetaminophen, and local heat.14 Cervical dysphagia may be an additional prominent symptom in patients with DISH. In series A, dysphagia was present in the histories of 28% of patients, an initial complaint in 4%, and required surgical removal of spinal osteophytes in 8%; in series B 17% of patients had dysphagia, and in 10% dysphagia was the chief complaint. Dysphagia is directly related to prominent cervical osteophytes. Exostoses that cause dysphagia are those located adjacent to areas of normal esophageal fixation such as at the level of the cricoid cartilage. Cervical dysphasia may improve with conservative therapy, although if this fails operative intervention may be necessary. Such surgery should be antedated by careful esophagoscopy. Absence of relief of dysphagia in patients with osTable 5. Clinical Features Found in Some Patients With DISH Recurrent Achrlles tendmitts Recurrent “tennis elbow” Progressive restriction of range of motion Palpable calcaneal spurs Palpable olecranon spurs Nodular masses adherent to quadriceps-patellar tendon Dysphagia Restricted motion following total ]omt replacement

156

--

RESNICK ET AL.

Table 6. Systemic Rheumatic Diseases Found in Association With DISH in 24 Patients (Series C) No of OCCWWlCeS

-

Chondrocalcinosis Gout Rheumatoid arthritis Osteoarthritis Scleroderma Amyloid arthropathy Psoriatic arthritis Erosive osteoarthritis No associated disease

4 4 6 4 1 1 2 1 2

-

teophytes may indicate a coexistent unrecognized esophageal carcinoma.“~‘“~” Although dysphagia, back pain, and stiffness are characteristic of DISH, these symptoms may be obscured by problems related to coexistent diseases. In series C, it was frequently difficult to differentiate clinical problems of DISH from those related to such coexistent systemic rheumatic disorders as rheumatoid arthritis, psoriatic arthritis, and calcium pyrophosphate deposition disease (Table 6). Physical findings in the axial skeleton in patients with DISH have been previously characterized.“X,g.“,‘4,1X In general, physical examination has revealed little change in normal spinal mechanics, with an occasional slight decrease in lumbar lordosis and a small increase in dorsal kyphosis, and mild distortion of spinal mobility in the lower dorsal area. Uncommon or exceptional findings have included lateral deviation or scoliosis, severe spinal rigidity, and significant restriction of thoracic cage motion. Our experience has further documented these previous observations. In series A, however, we did note decreased range of motion in the thoracolumbar (48%) and cervical (55%) segments and some restriction of thoracic cage motion. In series B a striking finding was the presence of normal spinal Aexion, extension, and lateral rotation in almost all patients. Tenderness to percussion over the middle part of the cervical spine (10%) and sacroiliac articulations (8 %) were occasionally observed. Extraaxial Skeleton Few authors have been particularly interested in peripheral musculoskeletal manifestations of DISH. Forestier and co-workers8sg previously noted the occasional occurrence of extraspinal radiographic manifestations in DISH

but did not emphasize associated clinical abnormalities. Sutro et a1.7 mentioned minimal complaints referable to the peripheral skeleton in patients with DISH, occasionally citing the presence of local pain or discomfort about ossific masses in the plantar fascia and Achilles tendon. Harris et al.” noted peripheral joint pain in these patients, particularly about the shoulder, knees, hips, feet, ankles, and hands, and generalized pain characteristic of polymyalgia rheumatica (6%). Our experience differs somewhat from that noted in these studies. In series A, 37% of patients had significant peripheral musculoskeletal complaints, and in half of these patients peripheral symptoms were the initial finding. Isolated extraspinal symptomatology was present in only two patients (8%). In those patients with prominent peripheral musculoskeletal symtomatology, the shoulders, knees, elbows, and heels were the most common symptomatic regions. In one patient with elbow pain, injections of corticosteroids and surgical removal of a prominent olecranon spur had been accomplished, while in another individual, local steroids had resulted in successful treatment of apparent epicondylitis. The pattern of musculoskeletal symptoms in these patients was not inflammatory, except in one patient in whom apparent rheumatoid arthritis developed a short time before death. In series B, 33% of patients complained of peripheral bone and joint pain; in 20% this pain was the predominant or sole complaint. Involved joints included the shoulder, hip, knee, and ankle. Discomfort was characterized as “aching” and was accentuated by both rest and exercise. There were no persistently abnormal physical findings related to the peripheral joints other than the presence of Heberden or Bouchard nodes. In an additional 18% of patients, acute synovitis of a single joint was associated with inflammatory fluids on joint aspiration characterized by the presence of either monosodium urate (5%) or calcium pyrophosphate dihydrate (13%) crystals. Following treatment with antiinflammatory medication, joint examination was normal. Twenty-three per cent of patients had heel problems; in 15% these problems were the chief complaint. There was no evidence of Achilles tendon rupture or retrocalcaneal bursitis. In each of these patients

DISH

(ANKYLOSING

159

HYPEROSTOSIS)

with heel problems, radiographically evident calcaneal spurs were present, although these spurs were not palpable. Thirteen per cent of patients had elbow pain; in 6%, this pain was the chief complaint. All of these patients had large olecranon spurs demonstrated on radiographs; in some these spurs were clinically detectable. It would appear from this analysis of our patients with DISH that certain significant historical features become evident. Histories of tendinitis (particularly appearing as Achilles tendinitis and “tennis elbow”), elbow and heel pain, swelling and erythema, and bone spurs, perhaps necessitating surgical intervention, are not uncommon in these patients. Furthermore, close clinical-radiographic correlation is evident; patients with clinically evident tendon and osseous problems about bony prominences often show significant local osseous proliferation or spurs when examined radiographically. Since peripheral musculoskeletal symptoms are not uncommon, it might be expected that some patients with peripheral manifestations of DISH might show physical findings in extraspinal locations. In series A diminished range of motion was observed in the hips (24%) subtalar joints (19%) shoulders (14%) knees (14%) elbows (IO%),), and ankles (10%). In one patient palpable firm nodular masses adherent to the quadriceps and patella tendons were noted. Obesity (22%) and Dupuytren contractures (10%) were also seen. In series B, in addition to evidence of occasional Heberden or Bouchard nodes and acute synovitis reflective of a coexistent rheumatologic disorder, palpable spurs were sometimes noted. LABORATORY

ASPECTS

Previous investigators noted few laboratory abnormalities in patients with DISH. Forestier and Lagier” observed that “there are no specific changes in laboratory tests and any present must be related to concomitant disease. Spinal hyperostosis is not in itself accompanied by any manifestations of inflammation or abnormalities in calcium and phosphorous metabolism.” Sutro et al.’ stated that “. . laboratory findings as noted in patients with juxta-articular ossification of ligaments are not specific for this entity. All routine tests show no evidence of any relationship . to any infectious process.” Harris et al.” investigated several laboratory

parameters, including serum growth hormone levels, in their patients and did not note any specific abnormalities. In our series A, laboratory determinations included hematocrit, leukocyte count, Westergren erythrocyte sedimentation rate (ESR), serum levels of calcium, phosphorus, alkaline phosphatase, uric acid, and glucose, and serologic testing for syphilis, rheumatoid factor (RF) (latex fixation), and antinuclear antibodies. Results of these studies included mild elevation of ESR in 22% and alterations in fasting and 2-hr postprandial serum glucose levels and/or glucose tolerance tests suggesting diabetes mellitus in 22%. RF tests were positive in 2 of the 21 patients (9%), one of whom had rheumatoid arthritis. The remainder of the laboratory evaluation showed no significant departures from norms. In series B, laboratory data on each patient included hematocrit, leukocyte counts, ESR, serum levels of calcium, phosphorus, magnesium, alkaline phosphatase, and glucose, and serum protein electrophoresis. Additional determinations of serum growth hormone levels in six patients and serum parathormone levels in five patients were accomplished. Air and water fluoride levels in the home towns of 30 patients were obtained. Results of these laboratory determinations included ESR ranging from 8 to 32 mm/hr (mean 19 mm/hr), hypercalcemia in 7% of patients, hyperphosphatemia in 10%;. elevated serum alkaline phosphatase levels in 13%, hypomagnesemia in 3%, fasting-state hyperglycemia in 17%, and hyperuricemia with clinical gout in 10%. Samples of home water supply showed no fluoride concentration levels greater than two parts per million; low levels of air fluoride were also found (less than one part per billion). Serum growth hormone and parathormone levels were uniformly normal. In series C, laboratory determinations frequently indicated the presence of an underlying rheumatic disorder, such as gout or calcium pyrophosphate deposition disease, but no other consistent laboratory abnormalities were apparent. RADIOGRAPHIC

ASPECTS

All previous investigators noted distinctive abnormalities on radiographic examination of the vertebral column in patients with DISH.

160

These abnormalities were characterized predominantly by peculiar ossification of the spine, described variously as a “crest attached to the ventral surface of the vertebrae,“4 “tortuous calcified ligament . . . homogeneous in density . . . distinct from the anterior margins of the vertebrae,“6 “smooth contour type . . . [or] curly type of ossification . . . characterized by the presence of ossific plaques which project ventrally about the region of the annulus fibrosus,“7 “continuous but irregular flowing outgrowths (coulee continue) along side the anterior aspect of the vertebrae,“s and “undulating appearance to the anterior vertebral contour.“‘* Extraspinal radiographic alterations have also been identified,7,s*” described as “fluffy” or “wooly” periostitis at sites of ligament attachment to bone. Our observations regarding spinal and extraspinal radiographic manifestations of DISH are based primarily on two patient populations: Series D. In this series 100 patients with spinal manifestations of DISH based upon our previously cited criteria were evaluated whenever possible with complete radiographic surveys of the cervical, thoracic, and lumbar spine.” These patients were selected in a prospective fashion from all individuals obtaining radiographs at the Veterans Administration Hospital in San Diego. Thus some patients were detected because of symptoms or signs related to spine disease that necessitated radiographic evaluation, whereas others were discovered during nonskeletal radiographic examinations such as chest, gastrointestinal, or genitourinary studies. There were 96 males and 4 females, reflecting in part the predominance of males in the patient population of the Veterans Administration Hospital. The age range was 49988 yr, (average 68 yr). Complete radiographic examination of the thoracic spine was accomplished in all 100 patients, complete evaluation of the cervical spine in 68 patients, and complete evaluation of the lumbar spine in 94 patients. Series A. As previously noted, this series consisted of 21 consecutive patients seen at the Veterans Administration Hospital in San Diego fulfilling our criteria for DISH in whom radiographic evaluation of both spinal and extraspinal areas was obtained. This evaluation included views of the cervical, thoracic, and lumbar vertebrae (anteroposterior-[API,

RESNICK

ET AL

lateral), pelvis (AP), femurs (AP, lateral), knees (AP, lateral), forelegs including ankles (AP, lateral), heels (lateral), feet (AP), humeri and shoulders (AP), elbows (AP, lateral), forearms (AP), and hands and wrists (posteroanterior). In addition, axial views of the patella and lateral projections of the skull were frequently available. Similar axial and extraaxial skeletal radiographs were obtained on 21 age- and sex-matched (all males) controls who were being evaluated for possible metastatic bone disease. Spinal Manifestations (Table 7) Thoracic spine. Radiographic abnormalities of DISH are most commonly encountered in the thoracic spine (Fig. I). Such thoracic abnormalities were present in 97% of patients in series D and 100% of patients in series A. They are most frequently noted between the 7th and 1 Ith thoracic vertebral bodies and generally decrease in incidence as one progresses craniad in the thoracic spine. The pattern of abnorTable 7.

Distribution of Spinal Abnormality

Level Cewcal Cl c2 c3 c4 c5 C6 c7

(Series D)

No of Patlents With Abnormalmes

spine (68 patients) 7 27 33 42 51 52 42

Thoracic spine (100 patients) Tl T2 T3 T4 T5 T6 T7 T8 T9 TlO Tll T12

24 33 44 56 70 78 91 94 96 93 a7 74

Lumbar spme (94 patients) Ll L2 L3 L4 L5

74 74 76 70 57

Sacrum (94 patients) Sl

27

DISH (ANKYLOSING

HYPEROSTOSIS)

161

Fig. 1. Thoracic spine abnormalities. (A) Findings include flowing anterior ossification (arrowhead) with a bumpy spinal contour, radiolucent disc extensions fd). and a radiolucency between the deposited bone and underlying vertebral bodies flu). (B) Note anterior spinal ossification (arrowhead). radiolucent disc extensions (d). radiolucency between deposited bone and subadjacent vertebrae flu). exaggerated anterior vertebral concavity fc). and horizontal bony struts fs). (Cl Bumpy spinal contour (arrowheads) reflects anterior hyperostosis with radiolucent disc extensions fdj. linear radiolucency flu). and horizontal struts of bone (5). (Figure 1 C reproduced with permission from Radiology.“)

mality is remarkably constant. Laminated calcification and ossification appear along the anterolateral aspect of the vertebral bodies and continue across the intervertebral disc spaces. The deposited bone varies considerably in thickness; in some patients it may be 1 or 2 mm in thickness, whereas in others it reaches over 20 mm in thickness. When broad, the deposited bone gives the appearance of a radiodense shield in front of the vertebral column. Although ossification may extend to involve both right and left lateral aspects of the vertebral column, it is more common and exuberant on the right side, presumably related to an inhibiting effect on ossification by a pulsating aorta on the left side. Posterior deposition of bone is rare, having been noted in 6% of patients in series D. The contour of the involved thoracic spine is generally bumpy (82% of patients in series D); occasional examples of a smooth “pseudospondylitic” pattern of ossification may be seen (I 5 RI of patients in series D). The bumpy spinal contour is particularly prominent at the level of the intervertebral discs related to two processes: increased deposition of bone at the

disc space, frequently merging with bony excrescences on the superior and inferior margins of the vertebra, and a more anterior position of the deposited bone at the level of the intervertebral disc. Several additional radiographic features of thoracic spine involvement in DISH are also characteristic. Radiolucencies within the ossified mass are common at the level of the intervertebral discs, related to anterolateral extension of disc material. These radiolucencies appear as L-, T-, or Y-shaped defects. A second pattern of radiolucency in the form of a linear defect is present between the newly deposited bone and subjacent vertebral body. This radiolucency may not be apparent at each thoracic level but is usually observed at some level; it was noted in 84% of patients in series D. This linear defect ends abruptly at the superior and inferior margins of the vertebral body where horizontal struts of new bone are deposited. An exaggerated concavity along the anterior aspect of the vertebral body in some individuals produces semicircular rather than linear radiolucencies.

162

Fig. 2.

RESNICK

Cervical spine abnormalities.

with a circular radiolucency extensions (d), bony ossicle intact apophyseal joints. (Cl reproduced with permission

(A) Observe cortical hyperostosis

fh). pointed excrescences

ET AL

fe). and linear ossification

flu). (6) Bony shield (large arrowhead) is evident along the cervical spine. Note also radiolucent disc (01 in front of the intervertebral disc, small posterior osteophytes (small arrowhead). and relatively Prominent anterior osteophytes (arrowheads.1 impinge upon the barium-filled esophagus. (Figure 28 from Radiology.‘)

Also, thoracic disc space narrowing is generally mild or absent. Occasional patients demonstrate diffuse narrowing of all thoracic intervertebral discs, but even in these patients the degree of deposited bone is exuberant compared to the mild nature of the disc space loss. In fact, the largest amount of bone frequently occurs at levels associated with the smallest degree of disc space loss. Calcification of intervertebral discs may also be seen. These thoracic spine abnormalities agree quite well with previous descriptions.8.g~“.‘8,‘a Some investigators have noted hyperostosis of the heads of the ribs at costovertebral articulations,20 but we have found it difficult in most individuals to separate this ossification from that adjacent to the intervertebral discs and vertebrae. Cervical spine alterations (Fig. 2) are also frequent in DISH; they were present in 78% of patients in series A. These abnormalities are more common in the lower cervical region (between the fourth and seventh cervical vertebral bodies) than they are in the upper cervical region. Bony excrescences in this area vary

from 1 to 12 mm in thickness. The initial finding is hyperostosis of the cortex along the anterior surface of the vertebral body. Gradually elongated bony outgrowths appear at the anterior margin of the vertebra and extend across the intervertebral disc space. These outgrowths are most commonly observed at the inferior lip of the vertebral body and extend downward. Progressive alterations include bone deposits, which are either smooth and homogeneous or bumpy and irregular. A flowing pattern of ossification may appear but is frequently interrupted by radiolucent disc extensions at the level of the intervertebral disc. These disc extensions may isolate a small triangular piece of bone or ossicle in front of the disc space. Radiolucent lines between the deposited bone and underlying vertebral body are less frequent in the cervical than in the thoracic spine, although small circular radiolucencies are observed in the cervical region. Posterior osteophytes are small and infrequent and disc space narrowing is generally mild. Associated apophyseal joint space narrowing and sclerosis and ligamentum nuchae ossification are sometimes apparent.

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Fig. 3. Lumbar spine abnormalities. (A) Radiographic fiindings include bony excrescences (e), cortical hyperostosis (h), and small radiolucencies (lo). Note preservation of the heights of intervertebral discs. (Et) More severe abnormalities in another patient are anterior linear ossificztion (arrowheads) and radiolucency both beneath the depositied bone (lu) and at the level of the intervertebral disc (d). (Figure 3A reproduced with permission from Radiology.‘)

These cervical spine changes agree with those in previous reports. The predilection for anterior deposition of bone in the cervical spine follows the general distribution of ossification throughout the vertebral column. Recently we have seen several patients with DISH who demonstrated ossification along the posterior aspect of several cervical vertebral bodies appearing as either hyperostosis of the vertebral cortex or posterior longitudinal ligament ossification. This appearance, which is not too disimilar to the previously reported pattern of bony outgrowth noted in the cervical spine in Japanese patients,“,Z2 has also been observed by others. Arlet et al.“” analyzed 40 patients with cervical myelopathy: they were impressed by the frequency of vertebral hyperostosis in these individuals. Seventeen of these patients had both DISH and acquired stenosis of the cervical canal related to bony proliferation along the posterior aspect of the vertebral bodies. Lumbar spine abnormalities in DISH are almost as frequent as thoracic spine abnormalities (Fig. 3). Ninety-three percent of patients in series D who had adequate radiographic examination of the lumbar spine showed typical abnormalities; 90% of patients in series A had similar lumbar findings. These findings are usually observed in the upper lumbar region, particularly between the first and third lumbar vertebral bodies. Lumbar changes re-

semble cervical spine alterations. Deposited bone may vary from I to 20 mm in thickness. The initial manifestation in this area is hyperostosis along the anterior aspect of the vertebral body. With progression, cloudlike increased bone density and pointed bony excrescences develop. These outgrowths are particularly frequent at the anterosuperior aspect of the vertebra, extending upward across findthe intervertebral disc space. Additional ings include radiolucent anterior disc extension, occasional radiolucency between the deposited bone and the vertebral body, and rare occurrence of posterior outgrowths. The predilection for right-sided involvement that is apparent in the thoracic spine is not so obvious in the lumbar region, and symmetrical right- and leftsided or isolated left-sided bony protuberances may be seen. Close apposition of spinous processes and/or ossification of interspinous ligaments may also be noted. Disc space narrowing is generally mild to moderate, and apophyseal joint space narrowing and sclerosis are not infrequent in the fourth lumbar through first sacral segments. Two additional radiographic findings of the spine in patients with DISH are noteworthy. Osteoporosis is not a feature of this disorder. On the contrary, skeletal radiodensity may appear excessive in view of the patients’ advanced age. Secondly, bony ankylosis is commonly ob-

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served in the thoracic spine and less frequently noted in the cervical and lumbar spine. In some instances, oblique projections show that true ankylosis has not occurred but rather close interdigitation of bony excrescences simulates bone fusion. These radiographic observations of spinal involvement in DISH are remarkably constant. In our experience, when the entire vertebral column was studied by radiography in patients with DISH, abnormalities were generally present in all three segments of the spine (68% of patients in series D who were so examined demonstrated alterations in all three spinal segments) or occasionally observed in the thoracic and lumbar segments without cervical involvement (21% of patients in series D). However, one must recall that we utilized strict radiographic criteria for diagnosis of DISH and we were largely encountering patients with severe spinal alterations. Certainly less stringent radiographic criteria would detect patients with mild or moderate alterations that might be isolated to one or two segments of the vertebral column. Radiographic manifestations of spine involvement in DISH are most distinctive in the thoracic spine. The flowing, undulating pattern of anterior spinal ossification is rarely confused with other disease entities. Occasionally smooth thoracic ossification may simulate the findings of ankylosing spondylitis. In the cervical and lumbar segments, pointed vertebral excrescences adjacent to the intervertebral disc may occur without extensive linear ossification, simulating other disorders such as spondylosis deformans (see below). Extraspinal

Manifestations

(Table 8)

Extraspinal radiographic manifestations of DISH have received little emphasis in the literature, yet in our experience they are frequent and distinctive, allowing accurate diagnosis of the disorder even in the absence of appropriate spinal radiographs. In fact, it is our contention that DISH may occur in the peripheral skeleton with minor or absent central skeletal abnormalities. In these instances the correct diagnosis is not suggested, because DISH is presently considered a spinal disorder. Despite our own particular interest in the extraspinal manifestations of DISH, our current

Table 8.

Distribution of Extraspinal Abnormality

(Series A)

No of Patnents With Abnormalltv DISH Site

Pelvis Femur Knee Foreleg, ankle Heel Foot Shoulder, humerus Elbow Forearm Hand. wrist

(21 patwltsl

21 3 6 6 16 15 b 12 3 8

COlMd I2 1 patEnts)

5 1 4 1 2

criteria for diagnosis require the presence of characteristic spinal abnormalities. Revised criteria for diagnosis are being developed. Although extraspinal radiographic features of DISH can occur at virtually any skeletal site, they are most characteristic in the following locations: Pelvis (Fig. 4). Osseous or soft-tissue radiographic abnormalities of the pelvis were observed in 100% of patients with DISH in series A and in 24% of the “normal” control population. These pelvic abnormalities consisted of bony proliferation or “whiskering,” ligament calcification and ossification, and paraarticular osteophytes. These findings have been observed by other investigators.8~“*‘1~‘X.‘g~2” Proliferation or “whiskering” has been seen at sites of ligament and tendon attachment to bone, particularly the iliac crest, ischial tuberosity, and trochanters, and is not unlike that occurring in ankylosing spondylitis. Ligament calcification and ossification have occurred in the iliolumbar and sacrotuberous ligaments. Paraarticular osteophytes have been noted along the inferior aspect of the sacroiliac joint,“” lateral and superior pubic margins,‘” acetabulum,y where they may apparently restrict motion and produce paraarticular osseous bridging and on rare occasions intraarticular bony ankylosis.“” We have additionally observed indistinctness of the superior portion of the space between sacrum and ilium and “whitening” or thickening of the entire iliac contour, particularly its superior margin. Heel (Fig. 5). Spurs on the posterior and inferior surfaces of the calcaneus in patients with DISH have occasionally been noted in previous reports.7,g We observed such findings in 76% of

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Fig. 4. Pelvis abnormalities. (A) Note sacrotuberous ligament ossification (open arrow), paraarticular sacroiliac joint osteophytes (closed arrow), and irregular bony excrescences above the acetabulum (arrowhead). (B) Radiographic abnormalities include paraarticular osteophytes about the sacroiliac joint (arrow) and iliolumbar ligament ossification (arrowhead). (C) Osseous bridge (arrow) extends across the symphysis pubis. (Figure 4C reproduced with permission from Radiology.‘)

patients with DISH in our series A, compared to 19% in “normal” controls. Calcaneal outgrowths in DISH are of variable size and frequently large; multiple spurs on either or both aspects of the calcaneus may be observed. These spurs are well demarcated, irregular in outline, and without adjacent reactive bone sclerosis or erosions, and are apparent at the sites of calcaneal attachment of the Achilles tendon and plantar aponeurosis. The cortex of the posterior and inferior surface of the calcaneus may appear diffusely thickened. Plantar ligament calcification may be rarely noted. Foot (Fig. 6 1. Bony excrescences of the foot in patients with DISH are most common at the dorsal surface of the talus, dorsal and medial tarsal navicular, and lateral and plantar aspects of the cuboid and base of the fifth metatarsal. Such abnormalities occurred in 7 I % of patients

Fig. 5. Heel abnormalities. Abnormalities in two different patients include irregular plantar and posterior calcaneal spurs (arrowheads) and ossification adjacent to the cuboid and base of the fifth metatarsal (arrow).

with DISH in our series A and were absent in the “normal” control population. Hyperostosis on the talus may result in a talar “beak” reminiscent of outgrowths occurring at the same site in patients with tarsal coalition or athletic injuries. Bony irregularity at the base of the fifth metatarsal may be associated with hyperostosis of adjacent sesamoid bones.2” Phalangeal changes may take the form of irregular periostitis along the shafts of the proximal and middle phalanges, perhaps associated with similar abnormalities of the metatarsals, and tuftal enlargement of the terminal phalanges, simulating the changes in acromegaly. Patrlla und knee (Fig. 7). Patellar and peripatellar alterations occur in DISH.‘,2’ These include ligamentous ossification within the quadriceps mechanism, with anterior patellar hyperostosis (best evaluated on tangential ra-

RESNICK

ET AL.

Fig. 6. Foot abnormalities. Note irregular excrescences at the dorsal surface of the navicular and cuneiform farrowheads) on a lateral radiograph of the foot.

diographs), and irregularities of the tibia1 tuberosity. These changes were observed in 29% of patients with DISH in series A as compared to 5% of “normal” controls. Additional lower extremity sites (Fig. 8). Evaluation of patients with DISH in series A showed additional sites of hyperostosis in the lower extremity. Findings included bone formation along the posterior or medial aspect of the femur (15%), osseous bridging between the lateral proximal tibia and fibular head (10%) bony protuberances along opposing surfaces of the tibia and fibula at the site of attachment of the interosseous membrane, and hyperostosis on the proximal medial tibia and about the ankle. Elbow (Fig. 9). Olecranon spurs are frequent, well-defined, and occasionally of considerable size. These spurs were observed in 48% of our patients with DISH and in 10% of controls. Hyperostosis along the “normal” distal medial humerus may be found.

Fig. 6. Additional lower extremity abnormalities. Observe the cortical irregularity (arrowheads) on the medial malleolus.

Findings in this loShoulder and humerus. cation may include prominence and exaggerated bony irregularity along the deltoid tuberosity, medial humeral shaft, inferior glenoid, inferior distal clavicle, and coracoclavicular ligament. Hand and wrist (Fig. 10). We have noted in these sites abnormalities such as hyperostosis along the distal radius, metacarpal, and phalangeal heads and prominence of terminal tufts. Similar observations have been made by Forgacs.28 Additional upper extremity sites. Irregularities at the site of attachment of the interosseous membrane along opposing surfaces of radius and ulna may be evident. Skull. Hyperostosis frontalis interna occasionally has been observed.g,“X ANATOMIC

Fig. 7. Patella abnormalities. Cortical thickening and adjacent ligamentous ossiffcation have resulted in increased radiodensity on the anterior surface of the patella (arrowhead) on this tangential radiograph.

AND

PATHOLOGIC

ASPECTS

Anatomic and pathologic aspects of skeletal involvement in DISH have received some preThese investigations were vious attention.‘,” based predominantly on axial skeleton abnormalities. Our data regarding anatomic and pathologic features in DISH is based primarily upon our series E, a study of 215 cadavers chosen at random during postmortem examination at the Veterans Administration Hospital in San Diego (average age at death: 72 yr).* The entire anterior vertebral column (first thoracic through

DISH

(ANKYLOSING

167

HYPEROSTOSIS)

been diabetic. We obtained pathologic and radiographic examination of the removed spines in all 25 cadavers and histologic evaluation in 17. Abnormalities in individual specimens varied in severity; when severe alterations were present in the central portion of the involved segment, mild changes were frequently noted at its periphery. This allowed us to outline a sequence and pattern of spinal abnormality in DISH. Pertinent

Anatomic

Observations

(Fig. 11 1

Anatomic features of the discovertebral junction are important in comprehending the pathology of DISH.2!‘+“” The intervertebral disc consists of two portions: the nucleus pulposus represents the central portion of the disc, and the anulus fibrosus is a concentric series of fibrous lamellae that enclose the nucleus pulposus, strongly uniting the vertebral bodies. A major function of the anulus fibrosus is to with-

Fig. 9. Elbow abnormalities. (A) Large olacranon spur is evident (arrowhead). (9) Calcification (arrow) is seen within the triceps tendon.

fifth lumbar segments) was removed intact, sectioned, radiographed, and photographed. In selected cases, histologic examination was performed. Twenty-five (12%) of the 2 15 cadaveric spines fulfilled our criteria for DISH; in 3, severe abnormalities of the entire thoracic and upper lumbar segments were noted. These 25 cadavers were all males, and 24 were white. The average age at death had been 75 yr (age range 46 -94 yr), agreeing closely with the average age of death of the entire group of cadavers. Common causes of the patients’ death in the 25 cadavers were pulmonary infection (8), cardiovascular disease (5), and neoplasm (4). Four had

Fig. 10. Hand abnormalities. There is periostaal new bone formation along the shaft of the first metacarpal tarrowheadsl.

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ET AL.

bral body, and narrows in the lumbar region to blend with the presacral fibers. Superficial fibers of the anterior longitudinal ligament connect four or five articular units, intermediate fibers unite two or three articular units, and deep fibers span only one intervertebral articulation. The anterior longitudinal ligament is adherent to the anterior surface of the vertebral body and forms its periostium, but it is more firmly attached to the articular lip at the edge of each vertebral body. The anterior longitudinal ligament is loosely attached to the connective tissue band that encloses the annulus fibrosus. Pathologic

Fig. 11. Anatomy of the discovertebral junction. Drawing of a sagittal section of the junction outlines two vertebral bodies separated by an intervertebral disc. The central portion of the disc is the nucleus pulposus (NP) and the outer portion is the anulus fibrosus (AF). Note the peripheral or Sharpay fibers of the anulus anchored into the anterior edge of the vertebrae (closed arrow), the cartilage-covered central vertebral depressions (open arrow). and the anterior longitudinal ligament (arrowheads) firmly attached to the surface of the vertebral body.

stand tension that may result from compression of the nucleus pulposus or separation of vertebral bodies. On the superior and inferior surfaces of each vertebral body are a concave central depression and an elevated ring of compact bone, the latter representing a traction apophysis for attachment of the anulus fibrosus and associated longitudinal ligaments. The strong peripheral fibers of the anulus are termed Sharpey fibers. They penetrate the outer bony ring, extend beyond the confines of the intervertebral disc, and blend with the anterior longitudinal ligament and periostium that covers the anterolateral surface of the vertebral body. The anterior longitudinal ligament extends the entire anterior length of the spine. It is narrow in the upper cervical region, expands in the thoracic area, where it covers much of the anterolateral surface of the verte-

Observations

(1) Thoracic spine. The pathologic aberrations of thoracic spine involvement in DISH can be conveniently separated into two types, both occurring simultaneously: Type I: These changes are purely ligamentous in nature and are apparently not dependent on discogenic abnormalities (Fig. 12). Initially, shaggy ribbonlike calcification is noted adjacent to the anterior aspect of the vertebral body, particularly at its midportion. Occasionally these collections are most prominent at the level of the intervertebral disc. These calcified collections progressively enlarge and thicken, extend across the intervertebral disc space, and contain visible bony trabeculae. Pathologically these deposits are within the fibers of the anterior longitudinal ligament. Enchondral bone formation is occasionally observed as islands of metaplastic cartilage within the ligament contribute to bone production. A radiolucency is generally recognized between the calcified and ossified deposits and underlying vertebral body. This lucency, which reflects unossified portions of the anterior longitudinal ligament, eventually may be segmentally obliterated as the ossified ligament fuses with the subjacent vertebral body. Type II: These changes are associated with intervertebral disc alterations, particularly within the anulus fibrosus (Fig. 13). Discoloration and defects in this area are associated with anterior extension of disc material. These disc extensions create radiolucent areas within the ossified mass. They are associated with an “umbrella” effect as disc material grows in and around the fibers of the anterior longitudinal

DISH (ANKYLOSING

Fig.

12.

HYPEROSTOSIS)

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DISH (ANKYLOSING

HYPEROSTOSISI

Fig. 14. Pathologic abnormalities of the lumbar spine. (A) Sagittal sectional radiograph IA, anterior) outlines radiolucent disc extensions(d). pointed axcrescences (e), and vertebral sclerosis (scl). (6, C) On two sagittal sections, observe disc extensions Id). osteophytes and excrescences (e). and an isolated ossicle (01 in front of the intervertebral disc.

ligament. These fibers appear stretched over the protruding fibrous tissue, and hyperostosis develops on the anterior surface of the vertebral body. This hyperostosis relates to periosteal new bone formation and is particularly marked adjacent to the site of attachment of the anterior longitudinal ligament to the vertebral body. Sclerosis may eventually involve large portions of the vertebra. Progressive ossification envelopes portions of the anulus fibrosus, anterior longitudinal ligament, and adjacent connective tissue. Hypervascularity and mild chronic inflammatory cellular infiltration may be seen surrounding the anterior longitudinal ligament adjacent to the degenerating anulus fibrosus. ii Lunrbar spinr. In the lumbar spine (and presumably in the cervical spine) pathologic changes resemble type-II abnormalities of the thoracic spine (Fig. 14). Anulus defects, protrusion of disc material, elevation of the anterior longitudinal ligament, traction hyperostosis, and sclerosis are sequential abnormalities. Pointed excrescences of variable size develop at the superior and inferior margins of the vertebra adjacent to the intervertebral disc. Anterior longitudinal ligament calcification is mild, becoming more prominent in advanced cases.

(3) Late thoracolumbar spinal change.v. The appearance of the spine with severe involvement is striking (Fig. 15). A shell or armor of bone extends across the anterior surface of the vertebral column. In the thoracic spine it predominates on the right side, and the advancing edge of deposited bone may appear sharp or well demarcated. In the lumbar spine, both right and left sides of the vertebral body may be equally involved. Although bony ankylosis is frequent in the thoracic spine, close inspection commonly shows areas in which true ankylosis is not present but rather the irregular osseous outgrowths interdigitate, their undulating surfaces being separated by thin layers of fibrous tissue representing extension of disc material. This pathologic description allows us to explain the more characteristic radiographic features of spinal involvement in DISH: Bumpy spinal contour. This contour reflects the increased thickness of deposited bone at the level of the intervertebral disc and, to a lesser extent, the varying thickness of periosteal bone formation at each vertebral level. The ossified areas at the level of the intervertebral disc may protrude far more anteriorly than at the midbody level and occur about the anterior extensions of disc material.

RESNICK

ET AL

Fig. 15. Pathologic abnormalities of advanced thoracolumbar disease. (A, B) Radiograph and photograph of the anterior aspect of the thoracolumbar spine reveal a shell of bone in front of the vertebral column. Bony deposition is greater on the right (RI side. The left side of the outgrowth is well defined (arrows). Note the excrescences fe) across lumbar intervertebral discs. (C) Close inspection demonstrates that bony outgrowths frequently interdigitate (arrows). (D, E) Radiograph and photograph of a transverse section through the thoracic spine demonstrate the nature of the linear radiolucency seen on spinal radiographs in patients with DISH. Ligament ossification (arrowheads) is noted along the anterior (A) aspect of the vertebral bodies. Nonossified segment (arrows) exists between the ossified ligament creating the characteristic radiolucency flu). (Figures 15D and 1 BE reproduced with permission from Radiology.*)

DISH (ANKYLOSING

HYPEROSTOSIS)

Rudiolucencies at the level oJ‘ the intervertebral discs. These lucencies reflect unossified portions of disc material, primarily anulus fibrosus. Such disc material may subsequently ossify, obscuring portions of the radiolucent extensions, although some residual lucency is usually apparent. Radiolucent linear shadow beneath deposited bone. This characteristic finding occurs when the deeper portion of the anterior longitudinal ligament is not completely ossified or, to a lesser extent, fibrous material from the disc extends between the anterior longitudinal ligament and vertebral body. Preservation of‘ intervertebral disc height. This degree of disc space loss is directly proportional to the extent of abnormalities in the nucleus pulposus. Normal disc height is commonly associated with an intact nucleus; mild to moderate disc space loss is occasionally observed related to dehydration and flattening of the nucleus pulposus. As will be subsequently described, these changes in the nucleus appear unrelated to DISH but rather represent coexistent intervertebral (osteo) chondrosis, although these changes do apparently influence and modify the extent ossification at the corresponding level in the spine-~ e.g., increased hyperostosis generally reflects an adjacent, (relatively) intact nucleus pulposus with normal intervertebral disc space; decreased hyperostosis reflects considerable alterations in the adjacent nucleus.

Fig. 16. Pathologic abnormalities of the celcanaus. Observe well-defined osteophytas extending into the plantar aponeurosis (arrowhead) and Achilles tendon (arrow). (Reproduced with permission from Radiology.‘)

113

Our pathologic observations on spinal involvement in DISH differ somewhat from previous descriptions. In comparison with one specific report,“’ the cadavers in our study did not show striking osteoporosis or a high incidence of cartilaginous (Schmorl) nodes. In fact, in most of the cadavers bone density was greater than that which might be expected in view of the patients’ advanced age at death, and and, when cartilaginous nodes were unusual present, generally of small size. If one speculates that the appearance of spinal osteophytes relates in some way to anterolateral disc herniation promoted by the tensile strength of a relatively intact nucleus pulposus (as has been suggested by many investigators), the appearance of cartilaginous or Schmorl nodes (reflecting intraosseous discal herniation), or, for that matter, degenerative nucleus alterations might reduce this tensile strength, thereby reducing osteophyte formation (see below). (4) Extraspinal sites. Observations regarding pathologic changes at extraspinal sites in patients with DISH are limited.‘“.“” Our own investigations have utilized several cadavers with DISH in which peripheral skeletal specimens were sectioned and radiographed. As previously noted, findings in the peripheral skeleton include hyperostosis at sites of tendon and ligament attachment to bone (pelvis. trochanters, calcaneus, olecranon, patella). paraarticular osteophytes (sacroiliac joint. acetabulum, symphysis pubis), and ligament

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RESNICK

ossification (sacrotuberous, iliolumbar). Tendons reveal fraying and irregularity, perhaps related to repetitive stress or trauma. These changes predominate at the zone of insertion of tendon to bone. Tendon necrosis with dystrophic calcification and periosteal spurs are apparent. In general, in the peripheral skeleton, periosteal spurs arising at the site of osseous attachment of the tendon are more prominent than true calcification of the tendon itself (Fig. 16). These ossifications extend into the fibers of the tendon, particularly the Achilles tendon and plantar aponeurosis, triceps, and quadriceps tendons. Mild thickening of the cortex of the underlying bone may be observed. Paraarticular osteophytes can extend from the margin of the joint and may even bridge the articulation. The adjacent joint space may appear normal radiographically, although degenerative cartilaginous and osseous changes are frequent. Bone sclerosis extends for variable distances beneath the osteophyte. Ligamentous calcification and ossification in the peripheral skeleton are analogous to type-1 changes occuring in the thoracic spine. The extent of such deposition is variable. In some instances only a small portion of a ligament appears calcified, whereas in others the entire ligament is involved. Hyperostosis of the underlying bone may be observed. CLINICAL

AND RADIOGRAPHIC

CONSEQUENCES

OF NEW

BONE FORMATION

Postoperative Heterotopic. Okjication (Fig. 17) We have recently reported the occurrence of excessive heterotopic ossification following hip surgery in three patients with DISH;34 in each instance there was restrictive hip motion. These three patients, who were males of ages 56, 75, and 79 yr, each fulfilled our criteria for diagnosis of DISH, and each had undergone total hip replacement. This was done because of osteoarthritis in two patients and for osteonecrosis in the third. No intraoperative technical difficulty was encountered in any of these patients, nor was there evidence of infection. In one patient femoral pinning had been done prior to joint replacement, but in none of the three had a previous prosthesis been utilized. One

ET AL

Fig. 17. Heterotopic ossification. Following a total hip arthroplasty, extentive ossification is seen lateral to the femoral prosthesis (arrow).

patient did dislocate the femoral prosthesis in the early postoperative period. One could argue that the presence of ossification following hip surgery in these three patients with DISH was a coincidental occurrence and does not necessarily imply an association with this skeletal disorder; however, one must at least acknowledge that exuberant new bone formation is characteristic of DISH, may occur throughout the axial and extraaxial skeleton, and may be related to stress. Postoperative heterotopic ossification may indeed represent one further indication of a bone-forming tendency in patients with DISH, although local environmental factors, including infection and hemorrhage, may be important in initiating such ossification. A similar tendency for heterotopic bone formation has been noted in patients with ankylosing spondylitis, another disorder characterized by deposition of bone in the vertebral column.35*36 This possible association of postoperative heterotopic ossification and spinal bone formation may indicate that a radiographic examination of the vertebral column in patients undergoing hip surgery could be a useful screening procedure. Furthermore, as discussed in the section on genetics, histocompatibility typing might be considered in the preoperative assessment of patients undergoing hip surgery.

DISH

(ANKYLOSING

HYPEROSTOSW

The authors have recently had an opportunity to examine an additional patient with DISH who demonstrated ossification in the postoperative period. This patient, a 65-yr-old male, developed extensor lag following a total knee replacement for osteoarthritis. There was fullness and swelling in the quadriceps region. Four months later, radiographs demonstrated heterotopic bone formation about the quadriceps musculature and radionuclide studies outlined generous aggregation of radioactivity in this region.

Rheumatoid

Arthritis

and DISH (Fig. IS)

Although rheumatoid arthritis (RA) and DISH may not be causally related, they are both common disorders and can coexist in the same patient. Our recent investigation of eight patients with clinical RA who additionally met the criteria for the diagnosis of DISH provided interesting observations.“’ The patients consisted of seven males and one female with an average age of 65 yr (range 55-78 yr) and with a history of longstanding arthritis (duration 5-40 yr). The articular distribution of radiographic abnormalities in these patients was typical for RA, as were the manifestations of DISH. Atypical radiographic features of RA were also encountered, including the absence of osteoporosis and the presence of bone sclerosis and pro-

Fig. 18. Rheumatoid arthritis and DISH. Note the bony proliferation about erosions of the distal radius. ulna, and carpal bones.

175

liferation about erosions, osteophytes, and intraarticular ankylosis. Each of the above atypical features of RA, when taken alone, is occasionally observed in the disease. The startling observation in our cases was the widespread distribution and prominence of the productive osseous alterations. All involved joints showed extensive bone eburnation. Furthermore, the degree of bony ankylosis was considerable, producing complete carpal and tarsal masses, resembling the alterations of ankylosing spondylitis or other “variant” diseases. Clinically these patients with RA and DISH had a typical spectrum of articular abnormality, although the frequency of Aexion contractures and marked limitation 01 motion in some patients was impressive. It appears reasonable to speculate that bone production might occur about involved articulations in patients with RA and DISH, the latter disorder being characterized by bone proliferation at sites of stress. Presumably, similar alterations may be seen when DISH accompanies any type of articular disorder producing bone damage. The osseous surface about the eroded area may attempt to heal in an exaggerated fashion. In RA, this bone response simulates the proliferative changes of “whiskering” accompanying “variant” diseases such as ankylosing spondylitis, psoriatic arthritis, and Reiter syndrome.

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TREATMENT

All obese patients are encouraged to lose weight, although there is no specific evidence per se that weight reduction will influence the development of hyperostosis. In addition, an active exercise program is encouraged, utilizing exercises specifically designed to promote flexion, extension, and lateral mobility of the spinal column. Some patients with thoracolumbar aching or stiffness note relief after a hot tub bath or after use of a heating pad or hot towel. Generally, however, discomfort recurs after several hours. Patients with dysphagia are instructed in diet modifications, emphasizing soft food, careful mastication, and frequent ingestion of liquids during meals. Patients with heel and elbow spurs may gain some comfort from encircling the exostoses with soft wrappings to minimize direct trauma. The use of soft crepe- or rubber-soled shoes is also helpful. Local injections of lidocaine into the soft tissues of the heel in the area of the exostosis may also bring pain relief. Patients with persistent spinal and/or peripheral skeletal symptoms may obtain benefit from mild analgesics or nonsteroidal antiinflammatory agents. Surgical excision of troublesome exostoses may be necessary, although it is not known if recurrent ossification may indeed be a problem in these patients. It is extremely important to evaluate fully all types of articular problems that occur in patients with DISH since it is not uncommon for these patients to develop a second rheumatologic disorder. Joint aspiration with examination of synovial fluid from inflammed joints may show evidence of crystal-induced arthritis related to monosodium urate or calcium pyrophosphate dihydrate crystals. Appropriate therapy can then be instituted. GENETICS

Recent studies have shown a remarkable association of the B-locus histocompatibility antigen HLA-B27 with a variety of seronegative (rheumatoid factor) arthropathies: idiopathic ankylosing spondylitis, Reiter syndrome, postsalmonella, postshigella, and postyersinia arthritis, juvenile rheumatoid arthritis, and the spondylitis accompanying inflammatory bowel disease and psoriasis. DISH presents certain features that distinguish it from ankylosing

ET AL

spondylitis, particularly the absence of characteristic apophyseal and sacroiliac joint abnormalities; however, DISH shares certain characteristics with the inflammatory forms of spondylitis, particularly the abundant new bone formation in the axial skeleton and at other sites of tendon insertions. Because of this apparent similarity, the prevalence of the HLA-B27 antigen was determined in 47 white patients (46 males, 1 female) ranging in age from 44 to 86 yr who satisfied the previously mentioned radiographic criteria for DISH.“% Evaluation included history, physical examination, and roentgenograms of cervical, thoracic, and lumbosacral spine, sacroiliac joints, shoulders, hands, pelvis, hips, knees, and feet. Complete histocompatibility typing (microdroplet lymphocytoxicity text) was performed on 27 patients and typing for the B27 antigen alone was done on 20 patients. Roentgenograms were read by two observers who had no prior knowledge of the clinical status of the patient or the results of the histocompatibility typing. Sixteen (34%) of the patients (1.5 males, I female) possessed B27 antigen (p < 0.0001). The frequencies of the other HLA antigens were determined in 27 of the patients with DISH and were found not to differ significantly from a goup of 1205 unrelated white controls. Similarly, features of B27positive and -negative patients were similar in respect to roentgenograms of the spine and peripheral joints. These data suggest that the demonstration of the B27 antigen in the patient with spinal symptomatology and roentgenographic evidence of osseous bridging between vertebral bodies does not confirm the diagnosis of ankylosing spondylitis. The differing therapeutic and prognostic implication of these two diseases demands that the diagnosis should be made based on clinical and roentgenographic features rather than the presence or absence of the B27 antigen. The highly significant association between the B27 antigen and DISH demonstrated in this study suggests to us that persons with this antigen are at substantial risk of developing the disorder. This conclusion is based on the following observations: (1) the B27 antigen was present in 8% of the control population; (2) DISH was present in 6%-12% of an autopsy population;“,‘” and (3) B27 was present in 34%

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HYPEROSTOSIS)

of patients with DISH. Therefore at least 25% of the white population possessing the B27 haplotype might be expected to develop DISH. The association between B27 and the spondyloarthropathies has seronegative resulted in several theoretical concepts regarding the pathogenesis of these conditions. These hypotheses are (I) the B27 gene is linked to specific immune response genes that are a prerequisite for the development of disease; (2) the B27 antigen, or a closely linked gene, has cross reactivity with a microorganism that causes the above conditions (“molecular mimicry”): and (3) the B27 allele, or a closely linked gene, controls the cell surface receptor for the pathogenctic microorganism. All of these hypothetical pathogenetic mechanisms would indicate an inflammatory reaction as the final common pathway for disease expression. While one cannot exclude the possibility that the initial abnormality in DISH is inflammatory, there is little clinical, radiographic, or pathologic evidence to indicate that continuing inflammation is a feature of this disorder. Rather, DISH shares with virtually all of the other B27-associated disorders the presence of abundant new bone formation, suggesting that the B27 gene is linked to or functions as a modifying gene that affects bone production.“” If this hypothesis is valid, patients with other ossifying diathesex, including hypertrophic osteoarthropathy, pachydermoperiostosis, acromegaly, and hypoparathyroidism, might be expected to show a positive association with the HLA-B27 antigen. Two recently published studies”‘.” have failed to confrm an increased prevalence of HLA-B27 in DISH patients; in one, an association with HL,\-B8 was suggested. It is not clear whether or not criteria that were used in these studies were similar to our own. In any case, further documentation of the presence or absence of an association between HLA-B27 antigen and DISH is required.

ETIOLOGY The etiology of DISH is unknown. One common factor in patients with DISH is advanced age. Some individuals relate a history of spinal trauma or occupational stress; in our series A, I2 patients (57%) had been involved in occupations requiring a moderate degree of physical

activity. Other individuals had no history 01 significant accidental or occupational trauma. Because of the similarity in the appearance of spinal outgrowths in DISH with outgrowths in a variety of other disorders, it has been attractive for previous investigators to relate these abnormalities of DISH to those in other disorders. Bony hyperostosis of the spine accompanies endocrine diseases such as acromegaly, hypoparathyroidism, and diabetes mellitus. Normal values for serum growth hormone”-“-” and parathormone’,’ levels have been noted in patients with DISH. Alterations in glucose metabolism in these individuals may indicate diabetes mellitus. ” In series A, 29%’ 01‘ patients had laboratory findings suggesting diabetes mellitus; in series B, 17% of patients had fasting hyperglycemia. Rosenthal et al.” noted that 32%’ of 50 patients with DISH had subclinically or clinically manifested diabetes mellitus. These investigators found an increased incidence 01 the antigen HLA-BX in their patients (42%). citing the accumulating evidence that HLA-BX is frequently present in various endocrine disorders. It would appear that diabetes mellitus is frequent in patients with DISH, although this frequency may be related to a chance occurrence of both disorders in older patients rather than a true association of these diseases. Hyperostosis of the spine also accompanies Ruorosis, unkylosing spondylitis and spondylitic “variants.” traumatic and infectious diseases, neuroarthropathy, and hypervitaminosis A. Air and water Huoride levels in the home towns 01 patients with DISH have been normal.‘” No definite evidence connecting hyperostosis in DISH with any of these other disorders has been accumulated. Thus at the present time the etiology for DISH remains unknown. DIFFERENTIAL DIAGNOSIS Although clinical and radiographic features of DISH are characteristic (Tables 5 and 9), certain other disorders enter into the differential diagnosis of this condition. Spinal

Man[festations

DISH must obviously be distinguished from other disorders of the vertebral column associated with hyperostosis (Tables IO and 1 I ). Intervertebral

Degenerative

(osteo)

disc disease,

chondrosis

(Fig.

osteoarthrosis

19).

of the

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Table 9.

Radiographic

Abnormalities

in DISH

Spinal Anterolateral flowing ossification Bumpy spinal contour Radiolucent disc extension Radiolucency beneath deposited bone Extraspinal Bony proliferation Ligament calcification, ossification Paraarticular osteophytes

Table 10.

Bony Outgrowths

of the Spine

DISH Spondylosis deformans Ankylosing spondylitis Spondylitic “variant” disorders Acromegaly Hypoparathyroldism Fluorosis Ochronosis Neuroarthropathy Trauma

anterior synarthrosis,43 and intervertebral (osteo) chondrosis44 are terms applied to alterations of the intervertebral disc related to physiologic and pathologic dehydration that occurs with advancing age. These changes predominate in the nucleus pulposus, resulting in discoloration and desiccation of the structure. Cleft formation in the nucleus may extend into the anulus fibrosus and is associated with vacuum phenomena on radiographs. Further destruction of the nucleus pulposus results in flattening of the intervertebral disc with disc space narrowTable 11.

-

Differential

Diagnosis of Radiographic

DISH

Vertebral bodies

“Flowing” ossification and hyperostosis: large osteophytes: bony ankylosis frequent radiographically, less frequent pathologically

Intervertebral discs

Normal or mild decrease m hetght

Apophyseal joints

Normal or mild sclerosis; occasional osteophytes Paraarticular osteophytes

Sacroiliac joints Peripheral skeleton

ing. With further progression of the disease, sclerosis and intravertebral disc herniation (cartilaginous or Schmorl nodes) are observed. These changes (vacuum phenomena, disc space narrowing, reactive bone sclerosis, and cartilaginous nodes) differ considerably from those of DISH. This comSpondylosis deformans (Fig. 20). mon condition results in spinal ostcophytosis.4” There are differing opinions regarding the pathogenesis of these osteophytes. Most investigators implicate increased mobility of the adjacent segment of the spine, resulting in stress on fibers that attach the anterior longitudinal ligament to the anterior edge of the vertebra. Schmorl and Junghanns4” demonstrated tears within the peripheral fibers (Sharpey fibers) of the anulus that they felt were the initial manifestation of spondylosis deformans. As these fibers continue to degenerate and separate from the adjacent vertebral body, the intervertebral disc is no longer anchored to the vertebral body. In the presence of a relatively normal nucleus pulposus (with considerable propulsive power), prolapse of a portion of the anulus occurs. This prolapse results in elevation of the anterior longitudinal ligament and traction osteophytes at its site of attachment to the anterior surface of the vertebral body. Type-II thoracic spine alterations in DISH include findings consistent with spondylosis deformans. Cleftlike defects in the anulus fibrosus, prolapse of the intervertebral disc ma-

“Whlskering,” paraarticular osteophytes: ligament calification and ossification, hyperostosls

Findings

Ankyloslng Spondyllfls Thin syndesmophytes, osteitis with “squaring;” extensive bony ankylosis radiographically and pathologically Normal or convex in shape

Erosions, sclerosis, and bony ankylosis Erosions. sclerosis, and bony ankylosis “Whlskering.” arthritis

intervertebral Osteochondrosis Sclerosis of superior and inferior surfaces

Moderate to severe decrease In height: “vacuum” phenomena Normal Normal Normal

DISH (ANKYLOSING

HYPEROSTOSIS)

Fig. 19. Intervertebral (osteol chondrosis. (R. right: L, left.) (A. 91 Note on this photograph and radiograph of a coronal section of the spine the presence of vacuum phenomena (VI. disc space narrowing (II), bony sclerosis kcl), and osteophyte formation (arrowhead). Extensive degeneration of the nucleus pulposus and anulus fibrosis has occurred. (C) Coronal section of the spine of another cadaver shows considerable degeneration of the nucleus pulposus and cartilaginous end plates, with cartilaginous (Schmorl) nodes (arrow). (Figures 19A and 199 reproduced with permission from Radiology.‘)

terial, and pointed bony excrescences at the vertebral body ~-intervertebral disc junction are present both in DISH and spondylosis deformans. The degree of disc prolapse, the size and number of osteophytes, and the presence of type-l thoracic spine changes with ligamentous calcification and ossification distinguish DISH from typical spondylosis deformans. Ankylosing spondylitis (Fig. 21). The clinical, radiographic, and pathologic features of ankylosing spondylitis differ from those of DISH. Ankylosing spondylitis predominantly affects young adults, producing considerable signs and symptoms; DISH affects middle-aged and elderly patients and may be asymptomatic or associated with mild to moderate restriction of motion. Syndesmophytes in ankylosing spondylitis are thin slender vertical bridges of bone connecting adjacent vertebral bodies representing ossification within the peripheral portion of the anulus fibrosus. Chondroid meta-

plasia and ossification may eventually involve large portions of the anulus and nucleus pulposus, but ossification of the anterior longitudinal ligament and adjacent connective tissue is not generally apparent. DISH produces exuberant bone formation encompassing anulus, anterior longitudinal ligament, and connective tissue. Outgrowths are broad and irregular with an anterior distribution. Furthermore, ankylosing spondylitis is characterized by vertebral body osteitis producing erosion and reactive sclerosis along the anterior corners of the vertebra, and insacroiliac joint erosion, sclerosis traarticular bony ankylosis, and apophyseal joint ankylosis. These manifestations are absent in DISH. Spondylitic “variants” (Fig. 22 J. Psoriatic arthritis, Reiter syndrome, and bowel disorders such as ulcerative colitis, regional enteritis, and Whipple disease are associated with bony abnormalities of the vertebral column. In psoriatic

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ET AL.

Fig. 20. Spondylosis deformans (sagittal drawings and sections of the anterior aspect of the spine). (A. B) Initial abnormality may be disruption (arrowheads) of Sharpey fibers attaching the anulus fibrosus to the vertebral rim. (C, D) Subsequent protrusion of disc material elevates the anterior longitudinal ligament (arrows), creating traction osteophytes (arrowheads) at the site of its attachment to the vertebral body. (E, F) Progressive protrusion of intervertebral disc leads to further osteophyte formation (arrowheads).

arthritis and, to a lesser extent, Reiter syndrome such abnormality consists of outgrowths that may resemble typical syndesmophytes of ankylosing spondylitis, asymmetric osteophytes, or paravertebral ossification. In some instances bone formation in these two disorders may resemble DISH, although an anterior linear pattern of ossification is generally not apparent. In general, outgrowths in psoriatic arthritis and Reiter syndrome are better demonstrated on frontal radiographs rather than lateral radiographs. Furthermore, paravertebral ossification in these two disorders is further from the vertebral surface than the new bone formation in DISH. In bowel disorders, spinal alterations resemble typical syndesmophytes and are more slender and delicate than abnormal bone formation in DISH. In psoriatic arthritis, Reiter syndrome, and bowel dis-

orders, sacroiliitis and apophyseal joint alterations may allow proper distinction for DISH. Acromegaly (Fig. 23). This disorder may be associated with osseous outgrowths of the spine. Periosteal new bone formation occurs on the anterior and lateral aspects of the vertebral body, producing apparent flattening of the vertebra related to increased anteroposterior diameter. Osteophytes may bridge the intervertebral disc space. Additional spinal findings in acromegaly are posterior concavity or scalloping of the vertebral body and increased intervertebral disc space height. Patients with DISH lack both peripheral skeletal manifestations of acromegaly (such as soft tissue enlargement with prominence of the terminal tufts, and joint space enlargement) and typical clinical features of acromegaly.46~47 Hypoparathyroidism. Hypoparathyroidism

DISH

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HYPEROSTOSIS)

Fig. 21. Ankylosing spondylitis. (A) Classic radiographic features include “squaring” of vertebral bodies, osteitis or “whitening” of the vertebral corners, and syndesmophytes (arrowheads). (B, Cj On a radiograph and photograph of a sagittal section of the spine (A, anterior), note syndesmophytes (arrowheads) representing ossification within the anulus fibrosus. (Dj In the cervical spine, radiographic abnormalities of ankylosing spondylitis include apophyseal joint ankylosis. syndesmophytes. and resorption of the anterior surface of the lower cervical vertebrae. (Figures 218 and 21C reproduced with permission from Radiology.‘)

may be associated with spur formation in the presence of normal intervertebral disc space as well as ossification of muscle and ligamentous insertions. Patients with DISH have no history of tetany or convulsions, and serum levels of calcium, phosphorus, alkaline phosphatase, magnesium, and parathormone are normal.

Fluorosis (Fig. 24). Fluorosis is associated with severe osteophytosis of the spine and ligament ossification, particularly of the sacrotuberous ligament. These findings may resemble DISH, a similarity further accentuated by the appearance of calcification in paraarticular ligaments, musculotendinous attachments, and

182

RESNICK

Fig. 22. volvement ossification tervertebral crascances, (arrow).

Fig. 23. Acromagsly. Bone deposition (arrowl on the an. terior aspect of the spine is apparent.

ET AL.

Psoriatic arthritis. Spinal inis characterized by bulky about multiple lumbar indiscs, cervical spine axand discovertebral erosions

interosseous membranes in fluorosis.48-“0 Allowing distinction between fluorosis and DISH is the presence of bone sclerosis in the former disorder. Clinically patients with chronic fluoride intoxication have vague, poorly localized pains with subsequent involvement of large joints and vertebral column. Additionally, patients complain of hyperesthesias of arms and legs, anorexia, and constipation. Advanced physical findings may include severe restriction of axial skeletal mobility. Ochronosis (Fig. 25). This rare disorder is associated with characteristic spinal changes that include osteophytosis and anterior disc ossification. The presence of extensive discal calcification and vertebral body osteoporosis allows accurate diagnosis.“1s52 Clinically patients with ochronosis complain of stiffness of the spine and large joints. Frequently, distinctive findings include pigmentation of the sclera and cartilage of the ear and nose. ‘4xial neuroarthropathy. Axial neuroarthropathy can be noted in lues, diabetes mellitus, and syringomyelia.“” Initial radiographic findings may simulate those of intervertebral (osteo) chondrosis, with loss of intervertebral disc space and vertebral body marginal sclerosis. Progressive alterations are

01s~ (ANKYLOSING HYPER~ST~SIS)

183

spine. Although currently used criteria do not allow diagnosis of this disorder in these patients with isolated peripheral findings, new criteria will necessarily be developed. The diagnosis of DISH confined to extraspinal structures is more difficult, since one cannot rely upon the presence of typical spinal alterations. The extraspinal manifestations of DISH may be confused with certain disorders that also involve the spine. We have already alluded to peripheral skeletal changes in fluorosis and hypoparathyroidism. In addition one must consider the following: Ankylosing

spondylitis

and

spond?~litic

These diseases produce abnormalities at sites of tendon and ligament attachment to bone, particularly about the pelvis and proximal femurs. These changes superficially resemble hyperostosis observed in DISH. In ankylosing spondylitis and spondylitic “variants,” osseous erosion and sclerosis are more prominent, and the newly formed bone is “variants.”

Fig. 24. Fluorosis. Radiographic findings include increased radiodensity of all of the bones and spinal osteophytes.

increasing sclerosis, subluxation, fragmentation, and bizarre osteophytosis. The presence of disc space loss, extreme sclerosis, and subluxation create a disorganized look that differs considerably from the findings of DISH. Extruspinal

Manifestations

Extraspinal manifestations in DISH such as ligament ossification, paraarticular osteophytes, and hyperostosis must be distinguished from a variety of other conditions. The importance of making this distinction is twofold: (1) Initial clinical manifestations of DISH may occur in the peripheral skeleton. In such instances radiographs of the axial skeleton are not available and changes in extraspinal sites must be properly distinguished from abnormalities accompanying other skeletal disorders. (2) It is probable that DISH may involve the extraspinal skeleton without involvement of the

Fig. 25. Ochronosis. Note widespread discal calcification, anterior discal ossification (arrow), and vertebral osteoporosis and osteophytes (arrowhead).

184

ill defined and irregular. In DISH proliferative changes frequently are sharply demarcated without signs of erosion or underlying bone sclerosis. Calcaneal spurs may also be observed in ankylosing spondylitis and spondylitic “variants,” but these, too, are frequently ill defined and associated with underlying bone eburnation. Acromegaly. Acromegaly alters the peripheral skeleton. Paraarticular osteophytes and bony hyperostosis may be observed in acromegaly, and tuftal enlargement is particularly characteristic; similar alterations occur in DISH. True articular abnormalities that do not occur in DISH are also noted. These articular findings include abnormalities of articular space and premature osteoarthritis. The extraspinal manifestations of DISH may also be confused with the following disorders that are isolated or predominant in extraspinal locations: Hypertrophic osteoarthropathy. Hypertrophic osteoarthropathy is a skeletal disorder characterized by symmetrical periostitis, particularly of the radius, ulna, tibia, and fibula, with lesser involvement of the femur, humerus, metacarpals, metatarsals, and phalanges.“? It is frequently associated with pulmonary and pleural processes, although its occurrence in patients with chronic liver, renal, gastrointestinal, and cardiac disease and nasopharyngeal tumors is well documented. Although occasional patients with DISH demonstrate diaphyseal periostitis, particularly in the femur, humerus, and metacarpals, that simulates hypertrophic ostcoarthropathy, these findings are usually not apparent in DISH. The more commonly observed well-defined paraarticular osteophytes and hyperostosis at sites of tendon attachments in DISH are easily distinguished from periostitis of hypertrophic osteoarthropathy. Pachydermoperiostosis. This familial disorder is characterized by the insidious development of digital clubbing, soft tissue thickening of the legs and forearms, thickening and greasiness of the skin, particularly of the face, excessive sweating, and radiographic evidence of symmetrical irregular periosteal new bone formation, with a predilection for the radius, ulna, tibia, and fibula.“s.“G These radiographic

RESNICK

ET AL.

features are similar to those of hypertrophic osteoarthropathy, although fluffy periostitis with metaphyseal extension is more frequent with pachydermoperiostosis. Some of the features in this syndrome simulate those occurring in acromegaly, including thickening of the skin, coarsening of facial structures, and tuftal enlargement. These clinical features are not noted in DISH, nor are the radiographic abnormalities of pachydermoperiostosis strikingly similar to those observed in DISH. Hypervitaminosis A. Although vitamin A intoxication may be associated with extensive bone formation in cats, it does not produce changes in humans that resemble DISH. Chronic poisoning may lead to periosteal reaction and no other abnormality of bone.“’ These changes, evident in infants and children, may be associated with permanent deformity of long bones.“* No difficulty in differential diagnosis between hypervitaminosis A and DISH is anticipated. Calcium pyrophosphate deposition disease. This disease is a common disorder that may even coexist with DISH. One of its radiographic features, tendon calcification, superficially resembles the findings of DISH.“g In the latter condition, mild to moderate calcification and ossification within the tendon substance are more frequent than widespread tendon calcification, as is observed in calcium pyrophosphate deposition disease. Other findings of calcium pyrophosphate deposition disease, including chondrocalcinosis and pyrophosphate arthropathy, are characteristic, allowing accurate diagnosis. DISH-A

DISEASE

ENTITY?

Is DISH a true disease entity? Certainly clinical, radiographic, and pathologic features of DISII distinguish it from ankylosing spondylitis, spondylitic “variants,” acromegaly, hypoparathyroidism, hypervitaminosis A, ochronosis, and fluorosis. There is a general tendency to attribute the peculiar pattern of spinal abnormality in DISH to “degenerative” or “discogenic” alterations. This tendency, at least in part, is misleading. DISH differs considerably from typical “degenerative” disease of the nucleus pulposus, intervertebral (osteo) chondrosis. DISH most resembles

DISH (ANKYLOSING

185

HYPEROSTOSIS)

spondylosis deformans, although there appear to be both qualitative and quantitative differences between the two entities. Spondylosis deformans is associated with spinal osteophytosis. The pathogenesis of these outgrowths probably relates to changes in the anulus fibrosus. Disc protrusion, elevation of the anterior longitudinal ligament, and traction osteophytes may be the sequence of events in spondylosis deformans. These findings are identical to those occurring as part (type II) of the spine abnormalities of DISH. Thus a part of the radiographic and pathologic picture of DISH is indeed that of spondylosis deformans, although a quantitative difference is observed the degree of disc protrusion, the extent of anterior longitudinal ligament elevaare tion, and the amount of bone formation greater in DISH than in spondylosis deformans. Furthermore, spinal ligament calcification and ossification occur in DISH and are not a prominent feature of spondylosis deformans. This could represent a true qualitative difrerence between the two disorders, although it may more accurately reflect that such ligamentous changes occur only when disc protrusion is great. Thus ligamentous changes in DISH might not be specific for this disorder but might accompany severe spondylosis deformans, although in some patients with DISH the occurrence of such ligamentous alterations as isolated phenomena without associated intervertebral disc abnormality or protrusion does provide some evidence that DISH truly does differ in a qualitative sense from spondylosis deformans. DISH may not represent a disease per se but rather a vulnerable state in which extensive ossification results from an exaggerated response of the body in some patients to stimuli that produce only modest new bone formation in others. As such, DISH would represent an ossifying diathesis that causes excessive bone formation at skeletal sites subject to normal or abnormal stresses. These sites are generally

those where tendons and ligaments attach to bone, both in the axial and extraaxial skeleton. Such bone production predominates in the but similar bone formation may occaspine, sionally predominate in or even be isolated to extraspinal sites. Further evidence that an ossifying diathesis or bone-forming tendency is present in patients with DISH includes the propensity of these individuals to develop ossification following surgery or in response to skeletal alterations accompanying coexistent diseases such as rheumatoid arthritis. Whether DISH is a distinct disorder or a modified host response to other disorders, it must be recognized as a common condition in middle-aged and elderly patients. Our diagnostic criteria are relatively strict, and yet the incidence of DISH in our routine autopsy population was 12%. Less stringent criteria utilizing both spinal and extraspinal features of DISH would obviously result in detection of even a greater number of patients. The incidence of DISH in the general population certainly justifies further research in an attempt to answer additional questions regarding this condition. For example, is there a true association between DISH and the histocompatibility antigen HLA-B27? If so, does this gene function as a modifying gene affecting bone production? Is DISH a manifestation of severe spondylosis deformans? Is there a definite relationship between postoperative heterotopic ossification and spinal osteophytes? If so, should screening examinations of the spine be a prerequisite for such surgery? These questions and others deserve attention as physicians attempt to place this common entity into proper prospective. ACKNOWLEDGMENT The authors thank Clark Neal and Bonnre Walker for processing the specimens, Peggy Mackey and Mary Gonsalves for preparing the histology, Sue Brown, Janet Julien, and Robert Turner for photography and illustration. and Liz Aguero for secretarial assistance.

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pathic skeletal hyperostosis (DISH). Radiology I 19559 568, 1976 3. Knaggs RL: Spondylitis deformans. Br J Surg I2:524- 546, 1925 4. Oppenheimer A: Calcification and ossification of

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vertebral ligaments (spondylitis ossificans ligamentosa): Roentgen study of pathogenesis and clinical significance. Radiology 38: 160-173, 1942 5. Ott VR: Uber die spondylosis hyperostotica. Schweiz Med Wochenschr 83:79&799, 1953 6. Smith CF, Pugh DG, Polley HF: Physiologic vertebral ligamentous calcification: An aging process. Am J Roentgen01 74:1049-1058, 1955. 7. Sutro CJ, Ehrlich DE, Witten M: Generalized juxtaarticular ossification of ligaments of the vertebral column and of the ligamentous and tendinous tissues of the extremities (also known as Bechterew’s disease, osteophytosis and spondylosis deformans). Bull Hosp Joint Dis 17:343-357, 1956 8. Forestier J, Rotes-Querol J: Senile ankylosing hyperostosis of the spine. Ann Rheum Dis 9:321-330, 1950 9. Forestier J, Lagier R: Ankylosing hyperostosis of the spine. Clin Orthop 74:65583, 197 I IO. Vernon-Roberts B, Pirie CJ, Trenwith V: Pathology of the dorsal spine in ankylosing hyperostosis. Ann Rheum Dis 33:28 l-288, 1974 I I. Harris J, Carter AR, Glick EN, et al: Ankylosing hyperostosis. I. Clinical and radiological features. Ann Rheum Dis 33:210- 215, 1974 12. Meeks LW, Renshaw TS: Vertebral osteophytosis and dysphagia. Two case reports of the syndrome recently termed ankylosing hyperostosis. J Bone Joint Surg 55A:l97-201, 1973 13. Utsinger PD, Resnick D, Shapiro RF: Diffuse skeletal abnormalities in Forestier’s disease. Arch Intern Med 136:763-768, 1976 14. Julkunen H, Heinonen OP, Pyorala K: Hyperostosis of the spine in an adult population, its relationship to hyperglycemia and obesity. Ann Rheum Dis 30:6055612, 1971 15. Spilberg I, Lieberman DM: Ankylosing hyperostosis of thecervical spine. Arthritis Rheum 15:2088212, 1972 16. Bauer F: Dysphagia due to cervical spondylosis. J Laryngol Otol67:615-630, 1953 17. Heck CV: Hoarseness and painful deglutination due to massive cervical exostoses. Surg Gynecol Obstet 102:657-660, 1956 18. Forestier J, Lagier R: Vertebral ankylosing hyin Hill AGS (ed): Modern Trends in perostosis, Rheumatology, vol II. London, Butterworths, 1971, pp 3233337 19. Forestier J, Lagier R, Certonciny A: Le concept d’hyperostose vertebrale ankylosante. Approche anatomoradiologique. Rev Rhum Mal Osteroartic 36:655-661, 1969 20. Fischer E, Stecher W: Die hyperostose der rippenkopfchen, ein teilbild der perivertebralen hyperostose. Fortschr Roentgenstr 117:336-342, 1972 21. Onji Y, Akiyama H, Shimonura Y, et al: Posterior paravertebral ossification causing cervical myelopathy. A report of 18 cases. J Bone Joint Surg49A:l314-1328, 1967 22. Minagi H, Gronner AJ: Calcification of the posterior longitudinal ligament: A cause of cervical myelopathy. Am J Roentgen01 105:365-369, 1969 23. Arlet J, Pujol M, But A, et al: Role de I’hyperostose vertebrale dans les myelopathies cervicales. Rev Rhum 43:167-175, 1976 24. Henrard JC, Bennett PH: Etude epidemiologique de

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