The Spondylitis Association of America has been the driving force behind a major research initiative in the US, having leveraged a substantial amount of money into a $4.5 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The grant last year established the North American Spondylitis Consortium to expedite the search for genes that determine susceptibility to ankylosing spondylitis. The German Ankylosing Spondylitis Society, which has more than 14,000 patient members, initiated in 1996 a professional survey of ankylosing spondylitis patients, with financial support from the German Federal Health Ministry. The results of this survey have recently been published, but only in the German language; a part of it is summarized here in English. Following are some of the important findings. The average age at disease onset does not differ significantly between men and women, but there is a significantly longer delay in disease diagnosis among female patients. The average delay in disease diagnosis is getting shorter; there was an average delay of 15 years for patients with disease onset in the 1950s, and it decreased to 7.5 years for patients with disease onset between 1975 and 1979. There was a relatively greater degree of underdiagnosis of the disease among female than male patients in the past; whereas only 10% of the patients in whom the disease was diagnosed in about 1960 were women, this percentage has progressively increased in the subsequent decades to reach 46% among those in whom the disease was diagnosed since 1990. The speed at which spinal ankylosis progresses is slower in female patients, but women are in a significantly worse situation than men in terms of pain and the need for drug therapy, even though the women in the German Ankylosing Spondylitis Society sample are, on average, younger than the men and have a shorter average disease duration. It is possible that the slower and relatively incomplete progression to spinal ankylosis in female patients impedes the occurrence of a decrease in pain with time, compared with that observed in male patients.

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Objective. To define the genetic basis of susceptibility to ankylosing spondylitis (AS), especially nonmajor histocompatibility complex (MHC) genes.Methods. The study group comprised 244 affected sibling pairs from 180 pedigrees of primarily European ancestry. Sibling pairs were concordant for AS by the modified New York criteria and had available sacroiliac radiographs. The subjects were genotyped for 400 markers in ABI PRISM linkage map MD-10 and for 17 additional markers on chromosomes 6p, 6q, and 11q (including HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles). Two-point and multipoint nonparametric linkage (NPL) analyses were conducted using the NPL statistic and 1-parameter allele-sharing model logarithm of odds (LOD) scores, calculated using the AlleleSharing Model (ASM) computer program.Results. Linkage of the MHC region was supported by both 2-point and multipoint analyses, with the strongest peak (45.90 cM) in the MHC at the HLA-DRB1 locus (NPL score 8.720, ASM LOD score 20.49; P ‫؍‬ 6.8 ؋ 10 ؊20 for 2-point analysis). A second region was found to have positive linkage at the q arm of chromosome 6 (D6S441) in 2-point analysis; this was supported by a 39.13-cM region (135.58-174.71 cM) in multipoint analysis, with the smallest P value (4.2 ؋ 10 ؊3 ) at 166.39 cM. A third region was found on chromosome 11q, with the strongest evidence for linkage for D11S4094 at 123 cM (NPL score 2.235, ASM LOD score 1.939) and, on transmission disequilibrium test analysis, D11S4090 at 105.74 cM (P ‫؍‬ 6.2 ؋ 10 ؊5 ). Linkage in this area was supported by multipoint analysis, spanning 22.19 cM continuously from 101.68 cM to 123.87 cM, with the strongest peak at 112.33 cM (P ‫؍‬ 0.014); this was confirmed by subsequent fine mapping studies.Conclusion. Thus, this genome-wide scan implicates, in addition to the MHC, regions outside the MHC in AS susceptibility, especially on chromosomes 6q and 11q.Ankylosing spondylitis (AS) is a common chronic inflammatory disorder primarily affecting the spine, although the peripheral joints and the attachments of ligaments and tendons to joints (the entheses) are also frequently involved, as well as the eyes, and, less com-

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Objective.Cauda equina syndrome (CES) is a rare neurologic complication of longstanding ankylosing spondylitis (AS). It is unclear what causes CES, and no proven or effective therapy has been reported to date. We have encountered 6 patients with longstanding AS diagnosed with CES. We set about to study their features, review the literature, and generate hypotheses regarding pathophysiology, as well as to speculate on the possibilities of early recognition and prevention.Methods.We obtained permission from 6 patients with longstanding AS and CES to access their medical records and imaging studies for research purposes related to this paper. We collected and reviewed each patient’s medical history, imaging studies, disease duration, past therapies especially those that relate to AS, laboratory data, as well as any treatment they received for CES and followup results of each case to the present time.Results.The 6 cases of CES with AS have remarkable similarity to each other in that several decades of the disease had passed before neurologic symptoms and later signs appeared. All cases have fused spines and facet joints without spinal fractures, spinal stenosis, or disc herniation.Conclusion.CES is a rare yet debilitating neurologic complication of longstanding AS. The pathophysiology and treatments are far from clear. We postulate that chronic enthesitis of the vertebral column initiates the process that results in dural stiffening and formation of ectasias, causing downstream nerve root damage.

Photosensitivity is the leading symptom of cutaneous and systemic lupus erythematosus (LE). The role of sunlight in the induction of LE lesions has long been recognized, based on the observation that lesions are predominantly localized to sun-exposed areas of the body, especially the face, but also the head and neck area. Moreover, LE worsens during the summer period or in the weeks following increased sun exposure (1,2). Definite proof for a causative role of ultraviolet (UV) irradiation in the induction of LE came from experimental photoprovocation testing in the early 1990s (3). Those studies unraveled the fact that the UV action spectrum that provokes LE in sensitive individuals includes both the ultraviolet B (UVB; 290-320 nm) and the UVA (320-400 nm) range. Moreover, the studies showed that LE does not develop immediately after UV exposure, but after a delay of 2-3 weeks.In view of the central role of sunlight in provoking LE, it is important for patients to establish efficient UV protection throughout the year. This is a particular challenge for areas of the skin that cannot effectively be covered by clothing. Over

transplant related mortality (TRM) of 9% overall was observed, with inter disease differences (12.5% in SSc and only one TRM in RA). Around 2/3 of patients responded with improvement or stabilisation. In SSc, 69% achieved a 25% or greater improvement in skin score, and in secondary progressive MS, 78% a 3 year progression free survival. Relapse was more common with RA and JIA, mostly being a synovitis easy to control with agents which were ineffective pre transplant. Randomised, controlled prospective trials are underway in SSc (ASTIS Trial: HSCT versus monthly pulse cyclophosphamide)), and planned for RA and MS. Trials in JIA are being discussed and further phase I/II data are required for SLE and vasculitis. These will be presented, together with immune reconstitution data, sometimes predicting relapse, and new developments in HSCT, especially non myeloablative "mini" allograft techniques. This may be applicable to full sibling matched selected patients. REFERENCE 1 Biggs M, Passweg J, Furst D, et al. PhaseI/I trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease. Ann Rheum Dis.

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