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Crohn's disease (CD) and multiple sclerosis (MS) share familial occurrence and similar epidemiological traits. Apart from one report of both diseases occurring among consanguineous relatives, only three cases of CD and MS in the same patient have thus far been described. We describe here a 29-year-old woman in whom MS developed in 1983 and CD in 1989. The MS may have been the result of a strongly HLA-associated genetic predisposition, while the additional development of CD may have been due either to genetic factors or perhaps simply to chance. Viewing this case in the context of epidemiological data, however, we suggest that the development of CD and MS is based on one or more common genetic factors acting in conjunction with other presumably exogenous factors and triggering HLA antigens to lead to one disease or the other.

Evidence of strong genetic markers in Crohn's disease (CD) is still absent. Many investigations have focused on HLA antigens, with conflicting results. To obtain more detailed information on the relation of HLA to the disease, we used the HLA data from 269 CD patients to compute the maximum-likelihood estimates of HLA gene and haplotype frequencies. These results provide further evidence that HLA B44 and Cw5 do indeed play a role in the development of CD. Furthermore, it is conceivable from our results that HLA Cw7 may protect against being affected with this disease.

Familial occurrence of Crohn's disease (CD) is well known, but the disease is rarely reported to occur in dizygotic twins. We present an additional case of dizygotic twins, both of whom developed CD, from a family in which two other members are affected. The 16-year-old son contracted the disease 2 years before his 50-year-old father, and 13 years before his twin sister. Another sister was affected 6 years after the onset of the disease in the propositus. HLA haplotyping of the three children matched the Mendelian ratio. The multiple occurrence of CD in blood relatives, especially in siblings, emphasizes the importance of genetic factors in the development of this disease. This family history, however, could point to psychic influences promoting the occurrence of CD on the basis of a polygenic disease susceptibility.

167 patients with Crohn's disease were investigated for joint and spine inflammation. Arthritis was observed in 23 patients (14%), sacroiliitis in 24 (14%), and sacroiliitis in combination with arthritis in 11 patients (7%). 15 patients (9%) had ankylosing spondylitis; 9 of them were HLA-B27 positive (60%). A parallel pattern in the course of bowel disease and joint inflammation was observed in 22 out of 34 patients with arthritis (59%). An association between the localization of Crohn's disease and the type of spondylarthritis could not be demonstrated. Patients with arthritis alone developed erythema nodosum (35%) or aphthous stomatitis more often (21%) than patients without spondylarthritis+ (6% and 12%, respectively). Other extra-intestinal manifestations of Crohn's disease did not reveal any association with the development of spondyloarthritis.

Inflammatory bowel diseases (IBD) as Crohn's disease (CD) and ulcerative colitis (UC) are believed to have a genetic basis. Additional factors are supposed to promote the development of IBD. However, apart from a few reports of HLA associations which await confirmation by other groups strong associations to (a) particular genetic marker(s) are still lacking. We here report on previously unobserved associations of CD to MNSS and UC to the immunoglobulin heavy chain allotype Gm 1,-2,10. We suggest that these factors play a role in a wider spectrum of genetic markers for the development of IBD.

Genetic influence on the development of Crohn's disease (CD) is commonly accepted. However, proof of definite genetic markers is still pending. Most investigations have focused on HLA antigens, and associations with HLA B12 and HLA A2 have been reported, but the design of these retrospective studies is open to criticism. We have undertaken a consecutive study of 96 patients with CD under well-defined conditions in order to test the hypothesis that CD is associated with particular HLA antigens. Our results identify a significant association of CD with the phenotype HLA B44,Cw5. But since a major proportion of the CD patients do not bear this phenotype, other predisposing genetic factors, which have not yet been defined, may exist in addition to environmental factors.

In a consecutive case study 231 patients with Crohn's disease were investigated for ankylosing spondylitis (AS) and HLA-A, B, C, DR antigen association. Eighteen patients (7.8%) had definite AS according to the New York criteria; 13 (72%) were HLA-B27 positive. The phenotype B27,B44 was seen in 8 patients (44%) compared to only 3 (1%) of 300 controls (p less than 10(-7), and 1 (0.5%) of 213 patients with Crohn's disease without AS (p less than 10(-7). We conclude that patients with the phenotype B27,B44 are highly at risk (relative risk = 68.8) for the common manifestation of Crohn's disease and AS.

Histocompatibility (HLA) antigen phenotypes have been studied in 169 patients with Crohn's disease. The following results could bei shown: HLA-Aw33, -B45 and -Cw3 showed a positive association and HLA-A26, -DR3 and -DRw8 a negative association with Crohn's disease compared to healthy controls. However, when the p-values were corrected by multiplying them by the number of determined antigens per gen-locus, the differences were not significant. Patients with a late onset of the disease (greater than 25 years) showed a statistical significant negative association with HLA-DR3. Numerous studies revealed no significant association between Crohn's disease and HLA-antigens except Smolen et al. (HLA-B12). The significant association of Crohn's disease and HLA-B12 reported by Smolen et al. could be caused by an increased frequency of HLA-B45 as we found in our patients.

Female monozygotic triplets all developed Crohn's disease within a period of 11 mo. The monozygosity was demonstrated by analysis of 24 genetic markers of different chromosomal localization. Crohn's disease was diagnosed using clinical, radiologic, and endoscopic findings. Histologic evaluation of bowel tissue was consistent with Crohn's disease. All 3 patients had colon involvement; the terminal ileum appeared normal. The patient in whom Crohn's disease was first diagnosed had the severest course. Our observations support the role of a genetic influence in the manifestation of Crohn's disease. Nevertheless, environmental factors or microorganisms, or both, have to be taken into account, perhaps as factors promoting the outbreak of Crohn's disease.

Among others, genetical factors have been discussed in the aetio-pathogenesis of inflammatory bowel diseases. This is supported by many studies reporting familial accumulation of Crohn's disease and ulcerative colitis. The use of HLA typing to demonstrate a genetical disposition has so far proved disappointing. Accordingly, if there is any association with definite HLA antigens, it is likely to be weak. We therefore investigated the HLA haplotypes in 13 families with multiple occurrences of Crohn's disease. Comparing observed and expected occurrences of HLA-haplotypes, we found a pronounced tendency towards common haplotypes in the affected siblings, uncles and nieces, and cousins. Although the data suggest a possible genetical disposition, additional factors such as microorganisms or possibly nutritional habits must be considered as causes for Crohn's disease.