eMedicine Specialties > Rheumatology > Spondyloarthropathies

Reactive Arthritis: Treatment & Medication

Author: Carlos J Lozada, MD, Director of Rheumatology Fellowship Program, Associate Professor, Department of Medicine, Division of Rheumatology and Immunology, Jackson Memorial Medical Center, University of Miami School of Medicine
Contributor Information and Disclosures

Updated: Oct 1, 2008

Treatment

Medical Care

The treatment of reactive arthritis is depends on the severity of symptoms.

  • Nonsteroidal anti-inflammatory drugs
    • NSAIDs are the foundation of therapy. These agents should be used regularly to achieve a good anti-inflammatory effect.
    • The choice of a specific agent depends on the individual response to treatment, although the general impression is that indomethacin has greater potency.
    • Physical therapy needs to be implemented to help reduce pain and to avoid muscle wasting in severe cases of reactive arthritis.
  • Corticosteroids
    • These agents can be used as either intra-articular injection or systemic therapy.
    • Joint injections can produce long-lasting symptomatic improvement and help avoid the use of other systemic therapy. Sacroiliac joints can be injected, usually under fluoroscopic guidance.8
    • Systemic corticosteroids can be used, particularly in patients in whom NSAIDs elicit a poor response or in those who develop adverse effects related to their use. The starting dose is guided by a patient's symptoms and objective evidence of inflammation. Prednisone 0.5-1 mg/kg/d can be used initially and tapered according to response.
  • Antibiotics
    • The current concepts on the pathogenesis of reactive arthritis indicate that an infectious agent is the trigger of the disease, but antibiotic treatment does not change the course of the disease, even when a microorganism is isolated. In these cases, antibiotics are used to treat the underlying infection, but specific treatment guidelines for reactive arthritis are lacking. However, in chlamydial-induced reactive arthritis, studies have suggested that the appropriate treatment of the acute urogenital infection can prevent reactive arthritis and that treatment of acute reactive arthritis with a 3-month course of tetracycline reduces the duration of illness. No evidence indicates that antibiotic therapy benefits enteric-related reactive arthritis or chronic reactive arthritis of any cause.
    • Quinolones have been studied because of their broad coverage, but no beneficial effect has been noted.
    • Lymecycline was studied in a double-blind placebo-controlled study of patients with chronic reactive arthritis for a treatment period of 3 months.4 The duration of illness was significantly decreased in patients with Chlamydia -induced disease, as opposed to those with disease triggered by enteric infections.
    • More studies are needed before definite recommendations can be made for the role of antibiotics in the management of reactive arthritis.
  • Disease-modifying antirheumatic drugs
    • In patients with chronic symptoms or in patients with persistent inflammation despite the use of the agents mentioned above, other second-line drugs may be used. Clinical experience with these so-called disease-modifying antirheumatic drugs (DMARDs) has been mostly in rheumatoid arthritis and in psoriatic arthritis. DMARDs have also been used in reactive arthritis, although their disease-modifying effects in the reactive arthritis setting are uncertain.
    • Sulfasalazine may be beneficial in some patients. The use of this drug in reactive arthritis is of interest because of the finding of clinical or subclinical inflammation of the bowel in many patients. Sulfasalazine is more widely used in ankylosing spondylitis. In a 36-week trial of sulfasalazine versus a placebo in the spondyloarthropathies, patients with reactive arthritis who were taking sulfasalazine had a 62.3% response rate compared to 47.7% for the placebo group in peripheral arthritis (P = 0.09).9
    • Methotrexate can be used in patients who present with rheumatoidlike disease. Several reports have shown good response, but controlled studies are lacking. Reports also describe the use of azathioprine and bromocriptine in reactive arthritis, but, again, large studies have not been published.10,11 Patients with reactive arthritis and HIV/AIDS should not receive methotrexate or other immunosuppressive agents.
    • Although biologic agents such as TNF-blockers have been demonstrated to be beneficial and formally approved for the treatment of psoriatic arthritis and ankylosing spondylitis, double-blind, randomized trials have not been performed to prove clinical benefit in reactive arthritis or in undifferentiated spondyloarthropathy. A recent uncontrolled study in patients with either undifferentiated spondyloarthropathy or reactive arthritis showed potential efficacy in symptom relief.

Surgical Care

No surgical treatment of reactive arthritis is recommended.

Consultations

A rheumatologist should be consulted for confirmation of diagnosis and formulation of management plan. Consultation with a urologist may be necessary if particularly prominent genitourinary manifestations develop. An ophthalmologist may be consulted to confirm the diagnosis and to treat the ophthalmologic manifestations of reactive arthritis.

Activity

Physical therapy may be instituted to avoid muscle wasting and to reduce pain. Activities should otherwise be as tolerated by the patient.

Medication

The goals of pharmacotherapy are to reduce morbidity, to prevent joint damage, and to alleviate extra-articular disease.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Several NSAIDs are available and have similar effectiveness, although indomethacin may be more effective in the spondyloarthropathies. These agents are used to treat symptoms. Cyclooxygenase-2 (COX-2)–specific inhibitors can be used in patients at high risk for GI complications.


Ibuprofen (Motrin, Advil)

Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Adult

400-600 mg PO qid or 800 mg PO tid

Pediatric

Not established

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in CHF, hypertension, and in PT with decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy


Indomethacin (Indocin, Indochron E-R)

Rapidly absorbed. Metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis.

Adult

25-50 mg PO bid/tid
75 mg SR PO bid; not to exceed 200 mg/d

Pediatric

1-2 mg/kg/d PO divided bid/qid; not to exceed 4 mg/kg/d or 150-200 mg/d

Coadministration with aspirin increases risk of inducing serious NSAID-related side effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Documented hypersensitivity; GI bleeding; renal insufficiency

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with pre-existing renal disease or compromised renal perfusion; reversible leukopenia may occur (discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia occurs)

Tetracyclines

These agents are used to treat urethritis or cervicitis caused by chlamydial organisms. Some evidence shows that, in Chlamydia -induced Reiter syndrome, tetracycline treatment may reduce duration and perhaps severity of illness. Collagenase inhibitors have been used to treat early rheumatoid arthritis.


Doxycycline (Bio-Tab, Vibramycin)

Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Adult

Urethritis or cervicitis: 100 mg PO bid 7d
Decrease severity: 100 mg PO bid for 8-12 wk

Pediatric

Not established

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy

Documented hypersensitivity; severe hepatic dysfunction

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (ie, <8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracycline

Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.


Prednisone (Deltasone, Meticorten, Orasone)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Adult

0.5 mg/kg/d PO initially, taper according to response

Pediatric

Not established

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia; edema; osteonecrosis; myopathy; peptic ulcer disease; hypokalemia; osteoporosis; euphoria; psychosis; myasthenia gravis; growth suppression; infections may occur with glucocorticoid use

Aminosalicylic acid derivatives

These agents are used to reduce inflammation.


Sulfasalazine (Azulfidine, EN-tabs)

Acts locally in colon to decrease the inflammatory response and systemically inhibits prostaglandin synthesis.

Adult

500 mg PO bid initially; 1000 mg PO bid

Pediatric

Not established

Decreases effects of iron, digoxin, and folic acid; conversely, increases effect of PO anticoagulants, PO hypoglycemic agents, and methotrexate

Documented hypersensitivity; hypersensitivity to sulfa drugs or any component; GI or GU obstruction

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with renal or hepatic impairment, blood dyscrasias, or urinary obstruction

More on Reactive Arthritis

Overview: Reactive Arthritis
Differential Diagnoses & Workup: Reactive Arthritis
Treatment & Medication: Reactive Arthritis
Follow-up: Reactive Arthritis
References

References

  1. Reiter H. Ueber cine bisher unbekannte spirochaeten-infektion (spirochaetosis arthritica). Dtsche Med Wschr. 1916;42:1535-6.

  2. Lu DW, Katz KA. Declining use of the eponym "Reiter's syndrome" in the medical literature, 1998-2003. J Am Acad Dermatol. Oct 2005;53(4):720-3. [Medline].

  3. Braun J, Laitko S, Treharne J, et al. Chlamydia pneumoniae--a new causative agent of reactive arthritis and undifferentiated oligoarthritis. Ann Rheum Dis. Feb 1994;53(2):100-5. [Medline].

  4. 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. Jan 1991;34(1):6-14. [Medline].

  5. Carter JD, Valeriano J, Vasey FB. Doxycycline versus doxycycline and rifampin in undifferentiated spondyloarthropathy, with special reference to chlamydia-induced arthritis. A prospective, randomized 9-month comparison. J Rheumatol. Oct 2004;31(10):1973-80. [Medline].

  6. Amor B, Santos RS, Nahal R, et al. Predictive factors for the longterm outcome of spondyloarthropathies. J Rheumatol. Oct 1994;21(10):1883-7. [Medline].

  7. De Vos M, Cuvelier C, Mielants H, et al. Ileocolonoscopy in seronegative spondylarthropathy. Gastroenterology. Feb 1989;96(2 Pt 1):339-44. [Medline].

  8. Maugars Y, Mathis C, Vilon P, et al. Corticosteroid injection of the sacroiliac joint in patients with seronegative spondylarthropathy. Arthritis Rheum. May 1992;35(5):564-8. [Medline].

  9. Clegg DO, Reda DJ, Weisman MH, et al. Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome). A Department of Veterans Affairs Cooperative Study. Arthritis Rheum. Dec 1996;39(12):2021-7. [Medline].

  10. Calin A. A placebo controlled, crossover study of azathioprine in Reiter's syndrome. Ann Rheum Dis. Aug 1986;45(8):653-5. [Medline].

  11. Bravo G, Zazueta B, Lavalle C. An acute remission of Reiter's syndrome in male patients treated with bromocriptine. J Rheumatol. May 1992;19(5):747-50. [Medline].

  12. Aho K. Bowel infection predisposing to reactive arthritis. Baillieres Clin Rheumatol. Aug 1989;3(2):303-19. [Medline].

  13. Ahvonen P, Sievers K, Aho K. Arthritis associated with Yersinia enterocolitica infection. Acta Rheumatol Scand. 1969;15(3):232-53. [Medline].

  14. Anandarajah A, Ritchlin CT. Treatment update on spondyloarthropathy. Curr Opin Rheumatol. May 2005;17(3):247-56. [Medline].

  15. Arnett F. Reactive arthritis and enteropathic arthritis. In: Klippel J, Weyand C, Wortmann R, eds. Primer on the Rheumatic Diseases. 11th ed. Atlanta, Ga: National Arthritis Foundation; 1997:184-8.

  16. Arnett FC. Incomplete Reiter's syndrome: clinical comparisons with classical triad. Ann Rheum Dis. 1979;38 Suppl 1:suppl 73-8. [Medline].

  17. Brower A. Arthritis in Black and White. 2nd ed. Philadelphia, Pa: WB Saunders; 1997:252.

  18. Fiessenger N, Leroy E. Contribution a l'etude d'une epidemie de dysenterie dans la Somme. Bull Mem Soc Med Hop Paris. 1916;40:2030-69.

  19. Flagg SD, Meador R, Hsia E, et al. Decreased pain and synovial inflammation after etanercept therapy in patients with reactive and undifferentiated arthritis: an open-label trial. Arthritis Rheum. Aug 15 2005;53(4):613-7. [Medline].

  20. Iliopoulos A, Karras D, Ioakimidis D, et al. Change in the epidemiology of Reiter's syndrome (reactive arthritis) in the post-AIDS era? An analysis of cases appearing in the Greek Army. J Rheumatol. Feb 1995;22(2):252-4. [Medline].

  21. Isomäki H, Raunio J, von Essen R, et al. Incidence of inflammatory rheumatic diseases in Finland. Scand J Rheumatol. 1978;7(3):188-92. [Medline].

  22. Keat A. Reiter's syndrome and reactive arthritis in perspective. N Engl J Med. Dec 29 1983;309(26):1606-15. [Medline].

  23. Kingsley G, Panayi G. Antigenic responses in reactive arthritis. Rheum Dis Clin North Am. Feb 1992;18(1):49-66. [Medline].

  24. Kvien TK, Gaston JS, Bardin T, et al. Three month treatment of reactive arthritis with azithromycin: a EULAR double blind, placebo controlled study. Ann Rheum Dis. Sep 2004;63(9):1113-9. [Medline].

  25. Lee AT, Hall RG, Pile KD. Reactive joint symptoms following an outbreak of Salmonella typhimurium phage type 135a. J Rheumatol. Mar 2005;32(3):524-7. [Medline].

  26. Leirisalo M, Skylv G, Kousa M, et al. Followup study on patients with Reiter's disease and reactive arthritis, with special reference to HLA-B27. Arthritis Rheum. Mar 1982;25(3):249-59. [Medline].

  27. Moll JM, Haslock I, Macrae IF, et al. Associations between ankylosing spondylitis, psoriatic arthritis, Reiter's disease, the intestinal arthropathies, and Behcet's syndrome. Medicine (Baltimore). Sep 1974;53(5):343-64. [Medline].

  28. Noer HR. An "experimental" epidemic of Reiter's syndrome. JAMA. Nov 14 1966;198(7):693-8. [Medline].

  29. Petersel DL, Sigal LH. Reactive arthritis. Infect Dis Clin North Am. Dec 2005;19(4):863-83. [Medline].

  30. Reveille JD, Arnett FC. Spondyloarthritis: update on pathogenesis and management. Am J Med. Jun 2005;118(6):592-603. [Medline].

  31. Rohekar S, Tsui FW, Tsui HW, Xi N, Riarh R, Bilotta R, et al. Symptomatic acute reactive arthritis after an outbreak of salmonella. J Rheumatol. Aug 2008;35(8):1599-602. [Medline].

  32. Sieper J, Fendler C, Laitko S, et al. No benefit of long-term ciprofloxacin treatment in patients with reactive arthritis and undifferentiated oligoarthritis: a three-month, multicenter, double-blind, randomized, placebo-controlled study. Arthritis Rheum. Jul 1999;42(7):1386-96. [Medline].

  33. Solitar BM, Lozada CJ, Tseng CE, et al. Reiter's syndrome among Asian shipboard immigrants: the case of The Golden Venture. Semin Arthritis Rheum. Apr 1998;27(5):293-300. [Medline].

  34. Toivanen A, Toivanen P. Aetiopathogenesis of reactive arthritis. Rheumatol Eur. 1995;24(1):5-8.

  35. Toivanen A, Toivanen P. Epidemiologic, clinical, and therapeutic aspects of reactive arthritis and ankylosing spondylitis. Curr Opin Rheumatol. Jul 1995;7(4):279-83. [Medline].

  36. Townes JM, Deodhar AA, Laine ES, Smith K, Krug HE, Barkhuizen A, et al. Reactive arthritis following culture-confirmed infections with bacterial enteric pathogens in Minnesota and Oregon: a population-based study. Ann Rheum Dis. Feb 13 2008;[Medline].

  37. van Bohemen CG, Lionarons RJ, van Bodegom P, et al. Susceptibility and HLA-B27 in post-dysenteric arthropathies. Immunology. Oct 1985;56(2):377-9. [Medline].

  38. Wakefield D, McCluskey P, Verma M, et al. Ciprofloxacin treatment does not influence course or relapse rate of reactive arthritis and anterior uveitis. Arthritis Rheum. Sep 1999;42(9):1894-7. [Medline].

Further Reading

Keywords

reactive arthritis, Reiter syndrome, Reiter's syndrome, RS, ReA, nongonococcal urethritis, conjunctivitis, oculo-urethro-synovial syndrome, Chlamydia reactive arthritis, chlamydial reactive arthritis , Shigella dysentery, gastrointestinal infections, Salmonella, Campylobacter, Chlamydia trachomatis, C trachomatis, Yersinia, ankylosing spondylitis, psoriatic arthritis, seronegative spondyloarthropathy, infectious diarrhea, genitourinary infection

Contributor Information and Disclosures

Author

Carlos J Lozada, MD, Director of Rheumatology Fellowship Program, Associate Professor, Department of Medicine, Division of Rheumatology and Immunology, Jackson Memorial Medical Center, University of Miami School of Medicine
Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology
Disclosure: Nothing to disclose.

Medical Editor

John Varga, MD, Professor, Department of Internal Medicine, Division of Rheumatology, Northwestern University
John Varga, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Central Society for Clinical Research, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Elliot Goldberg, MD, Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine
Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa
Disclosure: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; Merck, Amgen, Biogen, Zimmer, Wyeth, Johnson&Johnson, Stryker, Medtronic, Zimmer.Abbott,  Ownership interest Other; West Penn Allegheny Health System Consulting fee Consulting; Alpharma Honoraria Consulting; Proctor&Gamble Grant/research funds Independent contractor

 
 
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