You are in: eMedicine Specialties > Rheumatology > Spondyloarthropathies Enteropathic ArthropathiesArticle Last Updated: Jan 29, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Pierre Minerva, MD, Consulting Staff, Department of Rheumatology, Bryn Mawr Medical Specialists Association; Consulting Staff, Department of Rheumatology, Bryn Mawr Hospital, Lankenay Hospital, Paoli Hospital Pierre Minerva is a member of the following medical societies: American College of Rheumatology Editors: Kristine M Lohr, MD, Associate Chief, Program Director, Professor, Department of Internal Medicine, Division of Rheumatology, University of Tennessee School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Lawrence H Brent, MD, Associate Professor of Medicine, Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center; Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine; Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital Author and Editor Disclosure Synonyms and related keywords: enteropathic arthropathy, enteropathic arthropathies, rheumatologic conditions, gastrointestinal pathology, GI pathology, reactive arthritis, Shigella, Salmonella, Campylobacter, Yersinia, Clostridium difficile, C difficile, intestinal parasites, Strongyloides stercoralis, S stercoralis, Taenia saginata, T saginata, Giardia lamblia, G lamblia, Ascaris lumbricoides, A lumbricoides, Cryptosporidium, inflammatory bowel disease, Crohn disease, IBD, jejunoileal intestinal bypass, celiac disease, Whipple disease, collagenous colitis, HLA-B27, sacroiliitis, spondylitis, peripheral arthritis INTRODUCTIONSection 2 of 10
  BackgroundEnteropathic arthropathies comprise a collection of rheumatologic conditions that share a link to GI pathology. These conditions include reactive (ie, infection-related) arthritis caused by bacteria (eg, Shigella, Salmonella, Campylobacter, Yersinia species, Clostridium difficile), parasites (eg, Strongyloides stercoralis, Taenia saginata, Giardia lamblia, Ascaris lumbricoides, Cryptosporidium species), and spondyloarthropathies associated with inflammatory bowel disease (IBD). Other conditions and disorders include intestinal bypass (jejunoileal), arthritis, celiac disease, Whipple disease, and collagenous colitis. PathophysiologyThe precise causes of enteropathic arthropathies are unknown. Inflammation of the GI tract may increase permeability, resulting in absorption of antigenic material, including bacterial antigens. These arthrogenic antigens may then localize in musculoskeletal tissues (including entheses and synovium), thus eliciting an inflammatory response. Alternatively, an autoimmune response may be induced through molecular mimicry, in which the host's immune response to these antigens cross-reacts with self-antigens in synovium. Of particular interest is the strong association between reactive arthritis and HLA-B27, an HLA class I molecule. A potentially arthrogenic, bacterially derived antigen peptide could fit in the antigen-presenting groove of the B27 molecule, resulting in a CD8+ T-cell response. HLA-B27 transgenic rats develop features of enteropathic arthropathy with arthritis and gut inflammation. FrequencyUnited StatesIn patients with IBD, the prevalence of peripheral arthritis and/or sacroiliitis/spondylitis is 10-20%. The incidence of ulcerative colitis (UC) is 6-8 cases per 100,000 population per year, and prevalence is 70-150 cases per 100,000 population. The incidence of Crohn disease (CD) is 2 cases per 100,000 population per year; prevalence is 20-40 cases per 100,000 population. The incidence of IBD and Crohn disease is increasing, especially that of Crohn disease. InternationalThe incidence and prevalence rates of ulcerative colitis and Crohn disease are similar in northern and western Europe compared with those in the United States, but rates are lower in other regions of the world. RaceIncidence of IBD is higher in whites, especially those of Jewish descent, than in other racial groups. SexNo sexual predilection exists in peripheral arthritis of ulcerative colitis or Crohn disease. The incidence of spondylitis is higher in males than females. AgePeak incidence of IBD occurs in persons aged 15-35 years. CLINICALSection 3 of 10
History
Physical
Causes
DIFFERENTIALSSection 4 of 10
Behcet Disease Gonococcal Arthritis Gout Lyme Disease Rheumatoid Arthritis Sarcoidosis Septic Arthritis
|
| Drug Name | Indomethacin (Indocin, Indochron) |
|---|---|
| Description | Traditionally used for the spondyloarthropathy and peripheral arthritis associated with ankylosing spondylitis but has not been proven to be superior in efficacy or safety profile compared to other NSAIDs. |
| Adult Dose | 50-75 mg PO bid |
| Pediatric Dose | 1.5-3.0 mg/kg/d PO divided bid/tid |
| Contraindications | Documented hypersensitivity to NSAIDs or aspirin; peptic ulcer disease, recent GI bleed or perforation; renal insufficiency, anticoagulation, coagulopathy |
| Interactions | Coadministration with ACE inhibitors, angiotensin II receptor blockers, and potassium-sparing diuretics may result in hyperkalemia; coadministration with warfarin may increase PT because of displacement of warfarin from plasma proteins and may aggravate bleeding tendency because of antiplatelet effect of NSAIDs; may decrease the effect of diuretics |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | The most common toxicities include GI manifestations such as nausea, abdominal pain, peptic ulcer disease and renal insufficiency; may cause increased blood pressure in patients with hypertension because of blunting effects of antihypertensive medications; patients with congestive heart failure may have exacerbations due to fluid and sodium retention; closely monitor renal function in patients with diabetes mellitus |
| Drug Name | Celecoxib (Celebrex) |
|---|---|
| Description | Primarily inhibits COX-2. COX-2 is considered an inducible isoenzyme, induced by pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, incidence of GI toxicity, such as endoscopic peptic ulcers, bleeding ulcers, perforations, and obstructions, may be decreased when compared with nonselective NSAIDs. Seek lowest dose for each patient. Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates pro-inflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T cells and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%). Has a sulfonamide chain and depends primarily on cytochrome P450 enzymes (a hepatic enzyme) for metabolism. |
| Adult Dose | 100-200 mg PO qd |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration with fluconazole may cause increase in celecoxib plasma concentrations because of inhibition of celecoxib metabolism; coadministration of celecoxib with rifampin may decrease celecoxib plasma concentrations |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Pregnancy category D in third trimester of pregnancy; may cause increased blood pressure in patients with hypertension because of blunting effects of antihypertensive medications; patients with congestive heart failure may have exacerbations due to fluid and sodium retention; closely monitor renal function in patients with diabetes mellitus |
Second-line agents generally used for more aggressive disease inadequately controlled by NSAIDs and corticosteroids or as steroid-sparing agents. Because of their complex toxicities, second-line agents require administration and monitoring by an experienced physician/specialist.
| Drug Name | Sulfasalazine (Azulfidine, EN-tabs) |
|---|---|
| Description | Shown to reduce the peripheral inflammatory symptoms of spondyloarthropathies. Relatively safe, but toxicities (eg, GI, hypersensitivity) are common. |
| Adult Dose | 500 mg PO bid (with food) initially for 1 wk; increase dose by 500 mg/d each wk until a dose of 1500-3000 mg/d divided bid/tid or clinical improvement is reached |
| Pediatric Dose | 40-60 mg/kg/d PO divided bid/tid doses |
| Contraindications | Documented hypersensitivity to sulfasalazine, sulfonamides, or salicylates; porphyria (may precipitate acute exacerbations) |
| Interactions | Sulfasalazine absorption may be reduced by coadministration of oral iron |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | May cause nausea, dyspepsia, vomiting; avoid in G-6-PD deficiency; may rarely cause blood dyscrasias or liver problems; caution in renal or hepatic impairment; may cause yellow/orange discoloration of skin/sweat/urine; warn about potential severe skin rash |
| Drug Name | Methotrexate (Rheumatrex, Folex PFS) |
|---|---|
| Description | Unknown mechanism of action in treatment of inflammatory reactions; may affect immune function. Ameliorates symptoms of inflammation with peripheral disease. |
| Adult Dose | 7.5-25 mg PO/SC qwk; gradually adjust dose to attain satisfactory response |
| Pediatric Dose | 5-15 mg/m2/wk PO/SC qwk |
| Contraindications | Documented hypersensitivity; alcoholism; hepatic disease; documented immunodeficiency syndrome; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia) |
| Interactions | Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; indomethacin and phenylbutazone can increase methotrexate plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity of methotrexate; may increase plasma levels of thiopurine |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | Toxic effects on hematologic, GI, pulmonary, and neurological systems; caution in active infection, bone marrow suppression, underlying parenchymal lung disease; monitor CBC counts and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or with risk of elevated methotrexate levels, eg, dehydration); concomitant aspirin, NSAIDs, or low-dose steroids may be safely administered with methotrexate |
After NSAIDs and physical therapy, TNF inhibitors are uniquely recommended as the next line of treatment for inflammatory spinal disease in ankylosing spondylitis and the associated spondyloarthropathies. As do the second-line medications, these agents also reduce inflammatory signs and symptoms of peripheral disease.
| Drug Name | Infliximab (Remicade) |
|---|---|
| Description | Chimeric monoclonal antibody. Neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Has GI indications for fistulous Crohn disease and ulcerative colitis and rheumatologic indications for rheumatoid arthritis, psoriatic arthritis (and psoriasis), and ankylosing spondylitis. Shown to be effective for extra-articular manifestations such as refractory uveitis and pyoderma gangrenosum. |
| Adult Dose | 5 mg/kg as single IV infusion administered at weeks 0, 2, 6, then q6wk |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; active infection; history of demyelinating disease (MS); noncompensated CHF; SLE |
| Interactions | None reported |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | TNF-alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; patients should be screened for previous TB exposure and treated appropriately; caution advised in patients with history of malignancy |
| Drug Name | Etanercept (Enbrel) |
|---|---|
| Description | A fusion receptor protein that blocks TNF activity. Inhibits TNF binding to cell surface receptors, decreasing inflammatory and immune responses. Indicated for ankylosing spondylitis, psoriatic arthritis, psoriasis, RA, and JRA. |
| Adult Dose | 50 mg SC qwk or 25 mg twice weekly |
| Pediatric Dose | <4 years: Not established >4 years with active polyarticular-course JRA: 0.8 mg/kg/wk SC (up to a maximum of 50 mg/wk) Alternatively:<31 kg (68 lb): Single 0.8 mg/kg/wk SC injection |
| Contraindications | Documented hypersensitivity; sepsis; concurrent live vaccination; active infection; history of demyelinating disease (MS); noncompensated CHF; SLE |
| Interactions | None reported |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Serious infections may develop and the therapy should be discontinued if they occur; possible adverse effects include injection-site pain, redness and swelling at injection site, and headaches; rare cases of lupuslike symptoms and heart failure have been reported (discontinue treatment if symptoms develop); caution advised in patients with history of malignancy |
| Drug Name | Adalimumab (Humira) |
|---|---|
| Description | Recombinant human IgG1 monoclonal antibody specific for human TNF. Indicated to reduce inflammation and inhibit progression of structural damage in moderate-to-severe rheumatoid arthritis. |
| Adult Dose | 40 mg SC q2wk; may be increased to qwk if clinical response inadequate |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; active infection; history of demyelinating disease (MS); noncompensated CHF; SLE |
| Interactions | None reported |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | TNF-alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; patients should be screened for previous TB exposure and treated appropriately; caution advised in patients with history of malignancy |
Enteropathic Arthropathies excerpt
Article Last Updated: Jan 29, 2007
