deirdre earls rd
07-03-2007, 03:11 PM
hi folks,
here's an article that was found by our fearless leader, david bruce, in dallas. it points out yet another scientifically documented connection between gastrointestinal inflammation and systemic inflammation. psoriatic arthritis is mentioned. (the sections on whipple's disease and enteric reactive arthritis were taken out to make this article fit here. if you want to see the entire article, drop me a note but it may be a while before i have time to come back and post here again.)
whereas the connection between diet and gastrointestinal/systemic inflammation has long been recognized in naturopathic medicine, it's exciting to see practitioners in western medicine like rheumatologists and registered dietitians finally exploring the connection, too. from the winter 2007 newsletter of 'nutrition in complementary medicine', a dietetic practice group of the american dietetic association, comes the article "why not call antioxidants antifinflammatories if that's what they do?". julie hirsch, ph d, of wellgen inc, writes, "...fruits and vegetables and many functional foods contain vitamins and minerals as well as many polyphenolic compounds which can serve to prevent the triggers of inflammation. ... chronic inflammation ultimately accelerates the destruction of tissues via the cascade of release of many detrimental molecules such as the pro-inflammatory cytokines and enzymes of the arachidonic acid cascade. the production of such secreted proteins that mediate and regulate immunity and inflammation can lead to development of a multitude of chronic diseases, including cardiovascular disease, arthritis, cancer, alzheimer's, immune dysfunction, joint pain and diabetes. in fact, obesity is characterized by low-grade inflammation whereby the adipose tissue produces inflammatory cytokines..." you can go to www.complementarynutrition.org and for more information on arachidonic acid and how it's derived from dietary meat, eggs, dairy and more, there's a plentitude of scientific resources but there's a lay person's version at http://en.wikipedia.org/wiki/Arachidonic_acid.
in the meantime, the nationally broadcast documentary, 'the incurables', will be airing soon on the dish network. i'll let you know when the dates are finalized, if i'm told by the production company 'echo entertainment'. it features my story and how my training as a registered dietitian never taught me the connection between diet and my severe psoriasis. it also features testimonials from dermatologists who referred patients to me and these patients are now off chemotherapeutic grade drugs after changing their diet to resolve their psoriasis and eczema.
the point is this: there is a multitude of avenues on how to approach and practice a healty and affordable antiinflammatory diet that might significantly help p/pa.
best,
deirdre earls, rd, ld
This publication is made possible by an educational grant from Amgen Inc.
Volume 51, Number 2
Rheumatic Manifestations of Gastrointestinal Diseases
Ibrahim S. Alghafeer, MD
Fellow, Division of Rheumatology
University of Medicine and Dentistry of New Jersey
New Brunswick, NJ
Leonard H. Sigal, MD
Professor and Chief, Division of Rheumatology
University of Medicine and Dentistry of New Jersey
New Brunswick, NJ
Summary Points
Impairment of the gastrointestinal barrier function may play a role in the pathogenesis of arthropathies.
Arthritis is the most common extracolonic manifestation of chronic ulcerative colitis.
Reactive arthritis is one of the most common arthritides affecting young adults.
Introduction
Pathologic changes in the gastrointestinal tract may be associated with clinical complaints in multiple organs including the musculoskeletal system. Impaired barrier function and immunogenetic mechanisms are implicated (1). In some instances, the association between gastrointestinal pathology and extraintestinal disease is so strong that treatment of gastrointestinal disease resolves many of the patient’s extraintestinal complaints. This article will focus primarily on the rheumatic manifestations of the gastrointestinal diseases and the available treatment modalities.
Gastrointestinal Pathophysiology
The gut has multiple mechanisms to regulate the efficient absorption of nutrients while excluding bacterial and dietary antigens. Impairment of the gastrointestinal barrier function can be observed in several diseases including inflammatory bowel disease (IBD) and other spondyloarthropathies, and this defect may play a role in the pathogenesis of arthropathies.
Illeocolonoscopy and multiple biopsies were carried out in 96 patients with seronegative spondyloarthropathy, 17 patients with osteoarthritis taking nonsteroidal anti-inflammatory drugs (NSAIDs), and 19 patients with chronic abdominal discomfort. Inflammatory gut lesions were detected in two thirds of the patients with spondyloarthropathy, 12.5% of patients with osteoarthritis, and 16% of patients with abdominal discomfort. More recently, an Italian study confirmed microscopical mucosal inflammation on biopsy in 15 people with psoriatic arthritis but without bowel symptoms, 6 of whom had normal appearing mucosa by colonoscopy (2).
Altered gut permeability may also play a role in the pathogenesis of arthropathies. Permeability may be measured by oral feeding of different tracers (eg, 51Cr-labeled EDTA, lactoglobulin, lactalbumin, polyethylene glycol particles, lactulose, or mannitol) followed by urine analysis of excretion. Increased intestinal permeability was found in all subtypes of juvenile chronic arthritis with correlation between abnormalities in lactulose/mannitol test and the histopathological features of the gut mucosa (3). Another study showed an increase in the 24-hour urine excretion of 51Cr-EDTA in 34 patients with Behcet’s syndrome and 10 patients with ankylosing spondylitis (AS), when compared with 15 healthy controls (4).
Because the results obtained from such studies are entirely dependent on normal gastric emptying, normal renal function, and an accurate urine collection, they should be interpreted carefully. Also, the results may be altered by possible effect of the NSAIDs on prostaglandin synthesis and gut permeability.
Most recently, Salmi et al concluded that different leukocyte populations derived from inflamed gut of patients with IBD bind avidly to synovial vessels using a distinct repertoire of adhesion molecules, suggesting that their recirculation may contribute to the development of reactive arthritis in inflammatory bowel diseases (5). This study is the first experimental support of the homing of lymphocytes from the gut mucosa to joint tissue in enteropathic arthritis.
Inflammatory Bowel Disease (IBD)
Crohn’s disease and ulcerative colitis (UC) are both associated with a number of extra-intestinal chronic inflammatory diseases. Arthritis is the most common extracolonic manifestation of chronic UC (6). Patients with Crohn’s disease also have an increased prevalence of inflammatory joint disease although arthritis is more common in patients with colitic disease than small bowel inflammation alone (7).
The type of arthritis associated with IBD may be either axial or peripheral (Table 1). Peripheral joint disease occurs in 10% to 20% of patients with IBD and is not usually associated with HLA-B27. The onset of arthritis either accompanies or follows the onset of the colitis and the activity of the joint disease generally parallels the activity of the IBD. Patients can present with an oligoarthritis but no bowel symptoms and yet have IBD as the cause of their arthritis. The course is usually asymmetric oligoarthritis lasting 2 to 6 weeks and radiographic changes in the joints are rare (8).
In the case of UC, colectomy results in complete remission of the peripheral arthritis, whereas surgical therapy for Crohn’s disease results in remission of arthritis in only 50% of cases. In contrast, spondylitis and sacroiliitis occur in 2% to 7% of patients with IBD and are generally associated with HLA-B27. Isolated subclinical sacroiliitis has been reported in 24% of patients with IBD, suggesting that axial involvement may be more common than reported previously (9). The axial disease frequently precedes the onset of GI symptoms, and follows a chronic course which is independent of the activity of the IBD. Surgery has no effect on this axial arthropathy (8).
Orchard et al (10) retrospectively assessed 976 patients with UC and 483 with Crohn’s disease and found two types of enteropathic peripheral arthropathy. Type 1 is a self limited disease with presentation similar to post-dysenteric reactive arthritis, different from the polyarticular disease with a course independent of the IBD, type 2 (Table 2).
The same investigators have studied the association of peripheral arthropathies with certain HLA phenotypes (11). Fifty-seven patients with type 1 arthritis and 45 with type 2, who were identified by case note review and questionnaire, underwent genotyping by sequence-specific primer polymerase chain reaction. HLA-B27 was prevalent in 27% of type 1 patients, however, DR1 antigen was present in 33% of type 1 compared with none of type 2 and 3% of 603 controls (P<0.0001). In contrast, type 2 was associated with HLA-B44 in 62% (P=0.01). These data suggest that the clinical classification into type 1 and type 2 arthropathies is consistent with immunogenetically distinct entities and establishes that in polygenic disorders, genes may determine clinical phenotype without conferring overall disease susceptibility.
Management of arthritis in IBD patients relies on good control of the underlying gastrointestinal pathology. Sulfasalazine, azathioprine, glucocorticoids, and methotrexate are widely used; experience with cyclosporine is limited. The Food and Drug Administration has approved tumor necrosis factor-alpha antibody (infliximab) for the treatment of Crohn’s disease, which has resulted in a significant improvement of axial and peripheral arthritis related to this disease in early studies (12).
Low bone mineral density is a recognized complication of IBD. In a cross-sectional study by Abitbol et al (13), 34 patients with Crohn’s disease and 50 with UC (49 women and 35 men) underwent a metabolic bone assessment, including serum levels of osteocalcin, phosphate, calcium, parathyroid hormone, 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3. Bone mineral densities were measured by dual energy X-ray absorptiometry of the lumbar spine and femoral neck. Osteopenia was present in 36 patients (43%), 27 of whom were on glucocorticoid therapy. Although no patient complained of muscular or bone pain, 6 patients (7%) had vertebral crush fractures. Risk factors for the development of osteopenia were identified as age, cumulative glucocorticoid doses, increased erythrocyte sedimentation rate, and low osteocalcin level.
Another study (14) conducted on 119 patients with Crohn’s disease (ages 5 to 25 years) showed similar results with hypoalbuminemia, total glucocorticoid exposure, requirement for total parenteral nutrition, and prior use of 6-mercaptopurine being the most powerful risk factors for low bone mineral density (BMD). Patients with IBD should be advised to consume adequate vitamin D and calcium and to participate in a regular weight-bearing exercise program. Therapy with disphosphonates may be necessary as well.
Treatment with alendronate (10 mg daily) in 32 patients with Crohn’s disease and a bone mass T score of -1 or more significantly increased the bone mineral density of the lumbar spine by 5%, compared with a decrease of 0.9% in patients receiving placebo (P < 0.01) (15). Alendronate was safe, well tolerated, and there was no difference in adverse events among treatment groups. Bone densitometry should be performed, where possible, to identify those in need of treatment, to avoid unnecessary treatment, and to monitor the effect of treatment designed to prevent bone loss. The dose of glucocorticoids should be kept to a minimum, and vitamin D deficiency should be corrected.
Celiac Sprue
Also known as gluten enteropathy, celiac sprue is characterized by diffuse damage to the proximal small intestinal mucosa that results in villous atrophy and altered gut permeability. It is strongly associated with the HLA class II antigens: DR3 and DQw2. Arthritis is a well-known complication in children and adults. It was present in 52 of 200 adult celiac disease patients attending a routine gastroenterology follow-up clinic (16). The distribution of arthritis was peripheral in 19 patients, axial in 15, and an overlap in 18 subjects. The prevalence of joint disease was less common among patients on gluten free diet.
Recently, Usai et al found axial joint inflammation in 63% of patients with celiac disease (17); 22 patients with celiac sprue underwent bone scintigraphy using 99mTc methylene diphosphonate. Changes compatible with sacroiliitis were found in 14 cases, 11 of whom had low back pain. Five patients with low back pain had negative scintigraphy. Sacroiliac radiographs were obtained in only four patients, and all had bilateral sacroilitis. One patient had rheumatoid arthritis but all studied individuals were HLA-B27 negative.
Arthritis and other rheumatic complaints have been the presenting symptom in patients with gluten enteropathy with improvement in the clinical abnormalities on a gluten-free diet (18,19,20). An increased level of antigliadin antibodies was seen in 9 of 74 patients with spondyloarthropathies, 1 of whom had elevated antiendomysium antibodies and biopsy proven celiac disease (21). Thus, antiendomysial antibody testing is recommended as a screening tool in patients with suspected gluten enteropathy. Another study found that 3.3% of sprue patients had Sjogren’s syndrome (22).
Serial bone mineral density measurements of 55 patients with celiac disease detected osteoporosis (defined as a Z score equal or below 2) in 50% of the men and 47% of the women (23). Celiac disease was an independent risk factor for the development of osteoporosis.
Summary
The term “enteropathic arthritis” describes joint manifestations that occur in conjunction with gastrointestinal disease. The clinical picture of this entity is still evolving and has gained importance from advances in knowledge regarding gut pathophysiology and cell trafficking. It is very important to keep enteropathic arthritis in the differential diagnosis of patients with unexplained arthritis and to obtain detailed history, complete physical examination, and appropriate testing. These arthritic syndromes can be treated symptomatically, but long-term therapy should be directed at the underlying cause.
References
1. Wollheim FA. Enteropathic arthritis: how do the joints talk with the Gut? Curr Opin Rheumatol 2001;13:305-9.
2. Scarpa R. Microscopic inflammatory changes in colon of patients with both active psoriasis and psoriatic arthritis without bowel syndrome. J Rheumatol 2000;27:1241-6.
3. Picco P, Gattorno M, Marchese N, Vignola S, Sormani MP, Barabino A, Buoncompagni A. Increased gut permeability in juvenile chronic arthritides: a multivariate analysis of the diagnostic parameters. Clin Exp Rheumatol 2000;18:773-8.
4. Fresko I, Hamuryudan V, et al. Intestinal permeability in Behcet’s syndrome. Ann Rheum Dis 2001;60:65-6.
5. Salmi M, Jalkanen S. Human leukocyte subpopulations from inflamed gut bind to joint vasculature using distinct sets of adhesion molecules. J Immunol 2001;66:4650-7.
6. Bargen JA. Complications and sequelae of chronic ulcerative colitis, Ann Intern Med 1929;3:335-52.
7. Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine (Baltimore)1976;55:401-12.
8. Inman RD. Arthritis and enteritis - an interface of protean manifestations. J Rheumatol 1987;14:406-10.
9. Queiro R, et al. Subclinical sacroiliitis in inflammatory bowel disease: a clinical and follow-up study. Clin Rheumatol 2000;19:445-9.
10. Orchard TR, Wordsworth BP, Jewell DP. Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history. Gut 1998;42:387-91.
11. Orchard TR. Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gastroenterology 2000;118:274-8.
12. Van den Bosch F, et al. Crohn’s disease associated with spondyloarthropathy: effect of TNF-alpha blockade with infliximab on articular symptoms. Lancet 2000;356:1821-2.
13. Abitbol V, Roux C, Chaussade S, et al. Metabolic bone assessment in patients with inflammatory bowel disease. Gastroenterology 1995;108:417.
14. Semeao E, Jawad A, Stouffer N, et al. Risk factors for low bone mineral density in children and young adults with Crohn’s disease. J Pediatr 1999;135:593-600.
15. Haderslev KV, Tjellesen L, Sorensen HA, Staun M. Alendronate increases lumbar spine bone mineral density in patients with Crohn’s disease. Gastroenterology 2000;119:639-46.
16. Lubrano E, Ciacci C, Ames PR, et al. The arthritis of celiac disease: prevalence and pattern in 200 adult patients. Br J Rheumatol 1996;35:1314-8.
17. Usai P. Adult celiac disease is frequently associated with sacroiliitis. Dig Dis Sci 1995;40:1906-8.
18. Bagnato GF, Quattrocchi E, Gulli S, et al. Unusual polyarthritis as a unique clinical manifestation of celiac disease. Rheumatol Int 2000;20:29-30.
19. Borg AA, Dawes PT, Swan CH, Hothersall TE. Persistent monoarthritis and occult celiac disease. Postgrad Med J 1994;70:51-3.
20. Collin P, Korpela M, Hallstrom O, et al. Rheumatic complaints as a presenting symptom in patients with celiac disease. Scan J Rheumatol 1992;21:20-3.
21. Kallilorm R, Uibo O, Uibo R. Clin Rheumatol 2000;19:118-22.
22. Collin P, Reunala T, Pukkala E, et al. Celiac disease-associated disorders and survival. Gut 1994;35:1215-8.
23. McFarlane XA. Osteoporosis in treated adult celiac disease. Gut 1995;36:710-4.
24. Ratnaike RN: Whipple’s disease. Postgrad Med J 2000, 76:760-766
25. Durand DV, Lecomte C, Cathebras P, et al. Whipple disease. Clinical review of 52 cases. The SNFMI research group on Whipple disease. Medicine (Baltimore) 1997;76:170-84.
26. Puechal X. Whipple disease and arthritis. Curr Opin Rheumatol 2001;13:74-9.
27. O’Duffy JD, Griffing WL, Li CY, et al. Whipple’s arthritis: direct detection of Tropheryma whippelii in synovial fluid and tissue. Arthritis Rheum 1999;42:812-7.
28. Fantry GT, James SP. Whipple’s disease. Dig Dis 1995;13:108-18.
29. Ramaiah C. Whipple’s disease. Gastroenterol Clin North Am 1998;27:683-95.
30. Keat A. Reiter’s syndrome and reactive arthritis in perspective. N Eng J Med 1983;309:1606-12.
31. Finch W. Arthritis and the gut. Postgrad Med J 1986;86:229-34.
32. Marsal L, Winblad S, Wollheim FA. Yersinia enterocolitica arthritis in southern Sweden: a four-year follow-up study. Br Med J (Clin Res Ed) 1981;283:101-3.
33. Barth WF, Segal K: Reactive arthritis (Reiter’s syndrome). Am Fam Physician 1999;60:499-503, 507.
34. Scofield RH, et al. HLA-B27 binding of peptide from its own sequence and similar peptides from bacteria: implications for spondyloarthropathies. Lancet 1995;345:1542-4.
35. Pacheco-Tena C, et al. Bacterial DNA in synovial fluid cells of patients with juvenile onset spondyloarthropathies. Rheumatol 2001;40:920-7.
36. Lauhio A, Leirisalo-Repo M, Lahdevirta J, et al. Double-blind, placebo-controlled study of three-month treatment with lymecycline in reactive arthritis, with special reference to chlamydia arthritis. Arthritis Rheum 1991;34:6-13.
here's an article that was found by our fearless leader, david bruce, in dallas. it points out yet another scientifically documented connection between gastrointestinal inflammation and systemic inflammation. psoriatic arthritis is mentioned. (the sections on whipple's disease and enteric reactive arthritis were taken out to make this article fit here. if you want to see the entire article, drop me a note but it may be a while before i have time to come back and post here again.)
whereas the connection between diet and gastrointestinal/systemic inflammation has long been recognized in naturopathic medicine, it's exciting to see practitioners in western medicine like rheumatologists and registered dietitians finally exploring the connection, too. from the winter 2007 newsletter of 'nutrition in complementary medicine', a dietetic practice group of the american dietetic association, comes the article "why not call antioxidants antifinflammatories if that's what they do?". julie hirsch, ph d, of wellgen inc, writes, "...fruits and vegetables and many functional foods contain vitamins and minerals as well as many polyphenolic compounds which can serve to prevent the triggers of inflammation. ... chronic inflammation ultimately accelerates the destruction of tissues via the cascade of release of many detrimental molecules such as the pro-inflammatory cytokines and enzymes of the arachidonic acid cascade. the production of such secreted proteins that mediate and regulate immunity and inflammation can lead to development of a multitude of chronic diseases, including cardiovascular disease, arthritis, cancer, alzheimer's, immune dysfunction, joint pain and diabetes. in fact, obesity is characterized by low-grade inflammation whereby the adipose tissue produces inflammatory cytokines..." you can go to www.complementarynutrition.org and for more information on arachidonic acid and how it's derived from dietary meat, eggs, dairy and more, there's a plentitude of scientific resources but there's a lay person's version at http://en.wikipedia.org/wiki/Arachidonic_acid.
in the meantime, the nationally broadcast documentary, 'the incurables', will be airing soon on the dish network. i'll let you know when the dates are finalized, if i'm told by the production company 'echo entertainment'. it features my story and how my training as a registered dietitian never taught me the connection between diet and my severe psoriasis. it also features testimonials from dermatologists who referred patients to me and these patients are now off chemotherapeutic grade drugs after changing their diet to resolve their psoriasis and eczema.
the point is this: there is a multitude of avenues on how to approach and practice a healty and affordable antiinflammatory diet that might significantly help p/pa.
best,
deirdre earls, rd, ld
This publication is made possible by an educational grant from Amgen Inc.
Volume 51, Number 2
Rheumatic Manifestations of Gastrointestinal Diseases
Ibrahim S. Alghafeer, MD
Fellow, Division of Rheumatology
University of Medicine and Dentistry of New Jersey
New Brunswick, NJ
Leonard H. Sigal, MD
Professor and Chief, Division of Rheumatology
University of Medicine and Dentistry of New Jersey
New Brunswick, NJ
Summary Points
Impairment of the gastrointestinal barrier function may play a role in the pathogenesis of arthropathies.
Arthritis is the most common extracolonic manifestation of chronic ulcerative colitis.
Reactive arthritis is one of the most common arthritides affecting young adults.
Introduction
Pathologic changes in the gastrointestinal tract may be associated with clinical complaints in multiple organs including the musculoskeletal system. Impaired barrier function and immunogenetic mechanisms are implicated (1). In some instances, the association between gastrointestinal pathology and extraintestinal disease is so strong that treatment of gastrointestinal disease resolves many of the patient’s extraintestinal complaints. This article will focus primarily on the rheumatic manifestations of the gastrointestinal diseases and the available treatment modalities.
Gastrointestinal Pathophysiology
The gut has multiple mechanisms to regulate the efficient absorption of nutrients while excluding bacterial and dietary antigens. Impairment of the gastrointestinal barrier function can be observed in several diseases including inflammatory bowel disease (IBD) and other spondyloarthropathies, and this defect may play a role in the pathogenesis of arthropathies.
Illeocolonoscopy and multiple biopsies were carried out in 96 patients with seronegative spondyloarthropathy, 17 patients with osteoarthritis taking nonsteroidal anti-inflammatory drugs (NSAIDs), and 19 patients with chronic abdominal discomfort. Inflammatory gut lesions were detected in two thirds of the patients with spondyloarthropathy, 12.5% of patients with osteoarthritis, and 16% of patients with abdominal discomfort. More recently, an Italian study confirmed microscopical mucosal inflammation on biopsy in 15 people with psoriatic arthritis but without bowel symptoms, 6 of whom had normal appearing mucosa by colonoscopy (2).
Altered gut permeability may also play a role in the pathogenesis of arthropathies. Permeability may be measured by oral feeding of different tracers (eg, 51Cr-labeled EDTA, lactoglobulin, lactalbumin, polyethylene glycol particles, lactulose, or mannitol) followed by urine analysis of excretion. Increased intestinal permeability was found in all subtypes of juvenile chronic arthritis with correlation between abnormalities in lactulose/mannitol test and the histopathological features of the gut mucosa (3). Another study showed an increase in the 24-hour urine excretion of 51Cr-EDTA in 34 patients with Behcet’s syndrome and 10 patients with ankylosing spondylitis (AS), when compared with 15 healthy controls (4).
Because the results obtained from such studies are entirely dependent on normal gastric emptying, normal renal function, and an accurate urine collection, they should be interpreted carefully. Also, the results may be altered by possible effect of the NSAIDs on prostaglandin synthesis and gut permeability.
Most recently, Salmi et al concluded that different leukocyte populations derived from inflamed gut of patients with IBD bind avidly to synovial vessels using a distinct repertoire of adhesion molecules, suggesting that their recirculation may contribute to the development of reactive arthritis in inflammatory bowel diseases (5). This study is the first experimental support of the homing of lymphocytes from the gut mucosa to joint tissue in enteropathic arthritis.
Inflammatory Bowel Disease (IBD)
Crohn’s disease and ulcerative colitis (UC) are both associated with a number of extra-intestinal chronic inflammatory diseases. Arthritis is the most common extracolonic manifestation of chronic UC (6). Patients with Crohn’s disease also have an increased prevalence of inflammatory joint disease although arthritis is more common in patients with colitic disease than small bowel inflammation alone (7).
The type of arthritis associated with IBD may be either axial or peripheral (Table 1). Peripheral joint disease occurs in 10% to 20% of patients with IBD and is not usually associated with HLA-B27. The onset of arthritis either accompanies or follows the onset of the colitis and the activity of the joint disease generally parallels the activity of the IBD. Patients can present with an oligoarthritis but no bowel symptoms and yet have IBD as the cause of their arthritis. The course is usually asymmetric oligoarthritis lasting 2 to 6 weeks and radiographic changes in the joints are rare (8).
In the case of UC, colectomy results in complete remission of the peripheral arthritis, whereas surgical therapy for Crohn’s disease results in remission of arthritis in only 50% of cases. In contrast, spondylitis and sacroiliitis occur in 2% to 7% of patients with IBD and are generally associated with HLA-B27. Isolated subclinical sacroiliitis has been reported in 24% of patients with IBD, suggesting that axial involvement may be more common than reported previously (9). The axial disease frequently precedes the onset of GI symptoms, and follows a chronic course which is independent of the activity of the IBD. Surgery has no effect on this axial arthropathy (8).
Orchard et al (10) retrospectively assessed 976 patients with UC and 483 with Crohn’s disease and found two types of enteropathic peripheral arthropathy. Type 1 is a self limited disease with presentation similar to post-dysenteric reactive arthritis, different from the polyarticular disease with a course independent of the IBD, type 2 (Table 2).
The same investigators have studied the association of peripheral arthropathies with certain HLA phenotypes (11). Fifty-seven patients with type 1 arthritis and 45 with type 2, who were identified by case note review and questionnaire, underwent genotyping by sequence-specific primer polymerase chain reaction. HLA-B27 was prevalent in 27% of type 1 patients, however, DR1 antigen was present in 33% of type 1 compared with none of type 2 and 3% of 603 controls (P<0.0001). In contrast, type 2 was associated with HLA-B44 in 62% (P=0.01). These data suggest that the clinical classification into type 1 and type 2 arthropathies is consistent with immunogenetically distinct entities and establishes that in polygenic disorders, genes may determine clinical phenotype without conferring overall disease susceptibility.
Management of arthritis in IBD patients relies on good control of the underlying gastrointestinal pathology. Sulfasalazine, azathioprine, glucocorticoids, and methotrexate are widely used; experience with cyclosporine is limited. The Food and Drug Administration has approved tumor necrosis factor-alpha antibody (infliximab) for the treatment of Crohn’s disease, which has resulted in a significant improvement of axial and peripheral arthritis related to this disease in early studies (12).
Low bone mineral density is a recognized complication of IBD. In a cross-sectional study by Abitbol et al (13), 34 patients with Crohn’s disease and 50 with UC (49 women and 35 men) underwent a metabolic bone assessment, including serum levels of osteocalcin, phosphate, calcium, parathyroid hormone, 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3. Bone mineral densities were measured by dual energy X-ray absorptiometry of the lumbar spine and femoral neck. Osteopenia was present in 36 patients (43%), 27 of whom were on glucocorticoid therapy. Although no patient complained of muscular or bone pain, 6 patients (7%) had vertebral crush fractures. Risk factors for the development of osteopenia were identified as age, cumulative glucocorticoid doses, increased erythrocyte sedimentation rate, and low osteocalcin level.
Another study (14) conducted on 119 patients with Crohn’s disease (ages 5 to 25 years) showed similar results with hypoalbuminemia, total glucocorticoid exposure, requirement for total parenteral nutrition, and prior use of 6-mercaptopurine being the most powerful risk factors for low bone mineral density (BMD). Patients with IBD should be advised to consume adequate vitamin D and calcium and to participate in a regular weight-bearing exercise program. Therapy with disphosphonates may be necessary as well.
Treatment with alendronate (10 mg daily) in 32 patients with Crohn’s disease and a bone mass T score of -1 or more significantly increased the bone mineral density of the lumbar spine by 5%, compared with a decrease of 0.9% in patients receiving placebo (P < 0.01) (15). Alendronate was safe, well tolerated, and there was no difference in adverse events among treatment groups. Bone densitometry should be performed, where possible, to identify those in need of treatment, to avoid unnecessary treatment, and to monitor the effect of treatment designed to prevent bone loss. The dose of glucocorticoids should be kept to a minimum, and vitamin D deficiency should be corrected.
Celiac Sprue
Also known as gluten enteropathy, celiac sprue is characterized by diffuse damage to the proximal small intestinal mucosa that results in villous atrophy and altered gut permeability. It is strongly associated with the HLA class II antigens: DR3 and DQw2. Arthritis is a well-known complication in children and adults. It was present in 52 of 200 adult celiac disease patients attending a routine gastroenterology follow-up clinic (16). The distribution of arthritis was peripheral in 19 patients, axial in 15, and an overlap in 18 subjects. The prevalence of joint disease was less common among patients on gluten free diet.
Recently, Usai et al found axial joint inflammation in 63% of patients with celiac disease (17); 22 patients with celiac sprue underwent bone scintigraphy using 99mTc methylene diphosphonate. Changes compatible with sacroiliitis were found in 14 cases, 11 of whom had low back pain. Five patients with low back pain had negative scintigraphy. Sacroiliac radiographs were obtained in only four patients, and all had bilateral sacroilitis. One patient had rheumatoid arthritis but all studied individuals were HLA-B27 negative.
Arthritis and other rheumatic complaints have been the presenting symptom in patients with gluten enteropathy with improvement in the clinical abnormalities on a gluten-free diet (18,19,20). An increased level of antigliadin antibodies was seen in 9 of 74 patients with spondyloarthropathies, 1 of whom had elevated antiendomysium antibodies and biopsy proven celiac disease (21). Thus, antiendomysial antibody testing is recommended as a screening tool in patients with suspected gluten enteropathy. Another study found that 3.3% of sprue patients had Sjogren’s syndrome (22).
Serial bone mineral density measurements of 55 patients with celiac disease detected osteoporosis (defined as a Z score equal or below 2) in 50% of the men and 47% of the women (23). Celiac disease was an independent risk factor for the development of osteoporosis.
Summary
The term “enteropathic arthritis” describes joint manifestations that occur in conjunction with gastrointestinal disease. The clinical picture of this entity is still evolving and has gained importance from advances in knowledge regarding gut pathophysiology and cell trafficking. It is very important to keep enteropathic arthritis in the differential diagnosis of patients with unexplained arthritis and to obtain detailed history, complete physical examination, and appropriate testing. These arthritic syndromes can be treated symptomatically, but long-term therapy should be directed at the underlying cause.
References
1. Wollheim FA. Enteropathic arthritis: how do the joints talk with the Gut? Curr Opin Rheumatol 2001;13:305-9.
2. Scarpa R. Microscopic inflammatory changes in colon of patients with both active psoriasis and psoriatic arthritis without bowel syndrome. J Rheumatol 2000;27:1241-6.
3. Picco P, Gattorno M, Marchese N, Vignola S, Sormani MP, Barabino A, Buoncompagni A. Increased gut permeability in juvenile chronic arthritides: a multivariate analysis of the diagnostic parameters. Clin Exp Rheumatol 2000;18:773-8.
4. Fresko I, Hamuryudan V, et al. Intestinal permeability in Behcet’s syndrome. Ann Rheum Dis 2001;60:65-6.
5. Salmi M, Jalkanen S. Human leukocyte subpopulations from inflamed gut bind to joint vasculature using distinct sets of adhesion molecules. J Immunol 2001;66:4650-7.
6. Bargen JA. Complications and sequelae of chronic ulcerative colitis, Ann Intern Med 1929;3:335-52.
7. Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine (Baltimore)1976;55:401-12.
8. Inman RD. Arthritis and enteritis - an interface of protean manifestations. J Rheumatol 1987;14:406-10.
9. Queiro R, et al. Subclinical sacroiliitis in inflammatory bowel disease: a clinical and follow-up study. Clin Rheumatol 2000;19:445-9.
10. Orchard TR, Wordsworth BP, Jewell DP. Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history. Gut 1998;42:387-91.
11. Orchard TR. Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gastroenterology 2000;118:274-8.
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