DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS 164 not receiving x-ray therapy was studied (S258). The number of cancer deaths in patients not treated with xray was not greater than that expected from national death rates. Specifically, there were no deaths from leukemia. In spondylitis patients treated with x-ray, deaths from leukemia and other forms of cancer were significantly increased above those not treated with x-ray. It was concluded that the excess of leukemia and cancer is a direct result of x-ray therapy and unrelated to the disease process itself. DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS Diffuse idiopathic skeletal hyperostosis (DISH) is a recently proposed name for a skeletal disorder producing characteristic alterations in both spinal and extraspinal structures (R62). Although the name is new, the disorder is not, having first been described over 35 years ago. A report appeared that summarized the historical, clinical, radiographic, and pathologic findings of DISH, based on a literature review and observations of a large number of patients (R62). Previous designations for DISH have included spondylitis ossificans ligamentosa, spondylosis hyperostotica, and (senile) ankylosing hyperostosis of the spine. While the latter has been the most popular term, vertebral ankylosis may not be found on pathologic examination, although it may be apparent radiographically. Furthermore, extraspinal manifestations are common and may be more extensive than spinal alterations. In fact, extraspinal abnormalities may exist without appreciable vertebral abnormalities. Consequently, the term DISH was introduced in order to emphasize the widespread nature of this disorder. Etiology and pathogenesis The etiology of DISH is unknown (R62). It has been proposed that DISH may not represent a true disease entity but rather a vulnerable state in which extensive ossification results from an exaggerated response of the body in certain patients to stimuli that produce only modest new bone formation in others. As such, DISH would represent an ossification diathesis that causes excessive bone formation at skeletal sites subject to normal or abnormal stress. These sites are generally those where tendons and ligaments attach to bone, both in the axial and extraaxial skeleton. Additional evidence for an ossifying diathesis includes the propensity of patients to develop ossification in response to surgery or to coexisting diseases such as rheumatoid arthritis (RA) (R53). HLA typing was performed in 47 white patients with DISH (R62); 16 (34%) had the B27 antigen, suggesting that B27-positive subjects may be at risk for developing DISH. Moreover, because DISH and other HLA-B27-associated arthropathies manifest abundant new bone formation, the authors suggested an association between this antigen and the genes controlling new bone formation. However, in 3 subsequent reports of HLA typing in DISH, with 50 patients in each, the frequency of B27 ranged from 4 to 8% (B241a,E61,R138). Conversely, other HLA associations were disclosed in these 3 reports. The frequency of B5 was found to be twice that of controls in one (E61), and 3 times that of controls in another (R138), while in the third report a significant decrease of the A9 and A l l specificities was disclosed (B241a). [While the weight of evidence is against an association between DISH and the B27 antigen, these conflicting data support the need for further study. Ed.] DISH is a common disorder among Pima Indians, with prevalence rates approximating 50% in men aged 55 and older (S300). Because of the increased prevalence of both DISH and the HLA-B27 in Pima Indians, a possible association between the 2 was believed to exist. However, when HLA testing was performed in 44 adult male Pima Indians age 55 or over with DISH and in 33 age-matched controls, no association was found. Specifically, the B27 antigen was found with similar frequency in both patients (16%) and controls (20%). Clinical features In order to diagnose spine involvement due to DISH, 3 radiographic criteria were proposed (R62): 1) the presence of flowing calcification and ossification along the anterolateral aspect of at least 4 contiguous vertebral bodies, 2) absence of extensive degenerative disc disease, and 3) absence of both apophyseal ankylosis and sacroiliac erosion, sclerosis, or fusion. The first criterion helps to separate DISH from typical spondy- REITER’S SYNDROME 165 losis deformans, the second to distinguish it from intervertebral (osteo) chondrosis, and the third to eliminate patients with ankylosing spondylitis. Although the spinal alterations in DISH are generally easy to recognize on x-ray, this disorder must be distinguished from other conditions of the vertebral column associated with hyperostosis (R52,62). The principal musculoskeletal complaints reported by patients were spinal stiffness and mild mid- to low-back pain (R62). Occasionally, cervical spine pain was an initial and eventually prominent complaint. Dysphagia may be an additional symptom, directly related to prominent cervical osteophytes. There appeared to be few changes on physical examination of the spine, except for a slight decrease of lumbar lordosis, minimal increase of dorsal kyphosis, or minor distortion of spinal mobility. Rarely were scoliosis, severe spinal rigidity, or restricted thoracic cage motion noted. Extraspinal complaints were frequent, particularly recurrent tendinitis or spurs of elbows and heels. Discomfort of other peripheral sites, such as shoulders, hips, knees, and ankles was less frequent. Patients with extraspinal problems often had significant local osseous proliferation or spurs when examined radiographically. There were no appreciable laboratory abnormalities, except for a low frequency of minimal elevation of both the erythrocyte sedimentation rate and serum glucose level. A report of 4 patients with DISH revealed exten- sive calcification and ossification of the posterior longitudinal ligament of the cervical spine (R55). A subsequent review of cervical spine x-rays in 74 additional patients with DISH revealed bony hyperostosis of the posterior aspect of the vertebrae in 41%, posterior spinal osteophytosis in 35%, and posterior longitudinal ligamentous calcification and ossification in 50%. These findings, previously described almost exclusively in Japanese patients, appear to be an additional skeletal manifestation of DISH. Although patients with posterior longitudinal ligamentous ossification may be asymptomatic, a variety of signs and symptoms may occur. Parathesias may vary from intermittent sensations, including numbness or tingling of several digits of one or both extremities, to extensive and severe anesthesia of the trunk and lower extremities. Motor disturbances such as weakness, incoordination, and instability may be encountered in upper and lower extremities. Additional symptoms may include head and neck pain and stiffness, urinary and rectal incontinence, and loss of libido. On physical examination, patients may have muscle atrophy, fasciculations, hyperreflexia, and sensory loss. Eight patients with both DISH and RA were described (R53). An admixture of x-ray features, some typical for RA and others for DISH, were observed. These included absence of osteoporosis, presence of bone eburnation and proliferation around erosions, osteophytosis, and bony ankylosis of joints. REITER’S SYNDROME A comprehensive and provocative review of Reiter’s syndrome (RS) appeared (S 160). Evidence showing a high correlation between RS, other seronegative arthropathies which share Reiter’s symptomatology, and the histocompatibility antigen HLA-B27 was reviewed. It was suggested that HLA-B27 can be used as a confirmatory test in diagnosis. It was also suggested that the correlation of HLA-B27 with similar arthropathies indicates that these conditions are not separate entities but are more than likely different manifestations of the same disease process. It was further urged that the name “Reiter’s disease” be abandoned and a new designation which more accurately describes the spectrum of this disorder be adopted. Etiology and epidemiology HLA-B27 was detected in 80% of 173 patients studies (K150). An increase in the frequency of HLAA2, in proportion to that of B27, was also noted. In another series, B27 was present in 34 patients (78%) and absent in 10 (A139). Of the 10 B27-negative patients, 7 had antigens of the B27-cross-reactive group (Creg), including B7 in 2, Qw22 in 4, and Bw42 in 1. Mechanisms to explain the association of HLA-B27 with RS and ankylosing spondylitis, including abnormal immune response genes linked to HLA or a direct role of HLA antigens in disease pathogenesis, were investigated (A 139). Data supporting the latter hypothesis were provided.