Updated: Jun 18, 2009
In 1916, Hans Reiter described the classic triad of arthritis, nongonococcal urethritis, and conjunctivitis.1
What used to be known as Reiter syndrome is now referred to as reactive arthritis (ReA).1 This change has occurred in part because of Hans Reiter's affiliation and activities with the Nazis during WWII.
Reactive arthritis refers to acute nonpurulent arthritis complicating an infection elsewhere in the body.
Reactive arthritis falls under the rheumatic disease category of seronegative spondyloarthropathies, which includes ankylosing spondylitis, psoriatic arthritis, the arthropathy of associated inflammatory bowel disease, juvenile-onset ankylosing spondylitis, and juvenile chronic arthritis.2
A study by Kaarela et al reported that reactive arthritis and ankylosing spondylitis appear to be identical. They assessed long-term outcome of reactive arthritis and ankylosing spondylitis to identify similarities in manifestations of disease. A number of similarities were found; among them, sacroiliitis, peripheral arthritis, and iritis developed most often in both chronic reactive arthritis and ankylosing spondylitis.3
Reactive arthritis is triggered following enteric or urogenital infections. Reactive arthritis is associated with human leukocyte antigen (HLA)–B27, although HLA-B27 is not always present in an affected individual, particularly in the presence of HIV.
Rihl et al found a high proportion of proangiogenic factors accounting for a genetically determined susceptibility to reactive arthritis.4
Bacteria associated with reactive arthritis are generally enteric or venereal and include the following: Shigella flexneri, Salmonella typhimurium, Salmonella enteritidis,5 Streptococcus viridans, Mycoplasma pneumonia, Cyclospora,6 Chlamydia trachomatis, Yersinia enterocolitica, and Yersinia pseudotuberculosis. Bacteria or their components (RNA, DNA) have been identified in synovial fluid cells, synovial biopsy specimens, and circulatory monocytes.
Frequency is estimated at 3.5 cases per 100,000. (Because of uncertainty of diagnosis and variations in definitions, epidemiologic features are difficult to calculate.)
An estimated 1-3% of all patients with a nonspecific urethritis develop an episode of arthritis. Prevalence of inapparent chlamydial infections may make incidence even higher.
After outbreak of S enteritidis, 29% had reactive arthritis.
In Norway, an annual incidence of chlamydia-induced reactive arthritis of 4.6 cases per 100,000 population and an incidence of enteric bacteria–induced reactive arthritis of 5 cases per 100,000 population were reported in 1988-1990.
Occurrence appears to be related to the prevalence of HLA-B27 in a population and the rate of urethritis/cervicitis and infectious diarrhea.
Most patients have severe symptoms lasting weeks to 6 months. Approximately 15-50% have recurrent bouts of arthritis. Chronic arthritis or sacroiliitis occurs in 15-30% of cases.
Reactive arthritis is reported most frequently in whites. When reactive arthritis occurs in black persons, it is frequently B27-negative.
Occurrence appears to be related to HLA-B27 prevalence in the population.
The male-to-female postvenereal ratio is traditionally 5-10:1. The postenteric ratio is 1:1.
The peak onset is in persons aged 15-35 years; reactive arthritis is rarely seen in children. Cases in children are almost entirely postenteric.
| Arthritis, Rheumatoid | Rheumatic Fever |
| Conjunctivitis | Sarcoidosis |
| Gonorrhea | Syphilis |
| Gout and Pseudogout | Tendonitis |
| Inflammatory Bowel Disease | Tenosynovitis |
| Iritis and Uveitis | Tick-Borne Diseases, Lyme |
Septic arthritis
Other reactive arthritides and spondyloarthropathies
Mainstays of therapy for joint symptoms are nonsteroidal anti-inflammatory drugs (NSAIDs).
Sulfasalazine may be used for patients who do not experience relief with NSAIDs or who have contraindications to NSAIDs.
No published data are available on the effectiveness of selective COX-2 inhibitors; however, COX-2 inhibitors may be tried in patients who do not tolerate NSAIDs.
Extra-articular manifestations are treated individually. Second-line therapies for reactive arthritis, such as systemic or intra-articular steroids, are left to the discretion of the consulting rheumatologist. Antibiotic treatment is indicated for cervicitis or urethritis but not generally for postdysenteric cases.
Cytotoxic therapy, such as methotrexate or azathioprine, is reserved for severe cases and should not be started in the ED. HIV testing must be completed first.
Although most NSAIDs are used primarily for their anti-inflammatory effects, they are effective analgesics and are useful for relief of mild to moderate pain. To relieve joint symptomatology, a month's treatment at maximum dose is needed before full effectiveness can be evaluated.
DOC; however, other nonsteroidal drugs often are effective. Rapidly absorbed and metabolism occurs in the liver by demethylation, deacetylation, and glucuronide conjugation.
25 mg PO qid; increase to 50 mg qid prn
1-2 mg/kg/d PO, divided bid/qid; not to exceed 4 mg/kg/d or 150-200 mg/d
Probenecid may increase concentrations and possibly toxicity of NSAIDs; indomethacin may decrease effect of beta-blockers, hydralazine, and captopril; also may decrease diuretic effects of furosemide and thiazides; may prolong PT when coadministered with anticoagulants; monitor PT closely and instruct patients to watch for signs and symptoms of bleeding; indomethacin may increase serum lithium levels and risks of methotrexate toxicity, such as stomatitis, bone marrow suppression, and nephrotoxicity
Documented hypersensitivity (because of potential cross-sensitivity to other NSAIDs, do not give these agents to patients whom aspirin, iodides, or other NSAIDs induce hypersensitivity); GI bleed; renal insufficiency
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; low WBC counts occur rarely, are transient, and usually return to normal while therapy continues; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuing the drug
These agents are used for dermatologic manifestations, such as keratoderma blennorrhagica and circinate balanitis.
Topical corticosteroids are adrenocorticosteroid derivatives suitable for application to skin or external mucous membranes and have mineralocorticoid and glucocorticoid effects, resulting in a nonspecific anti-inflammatory activity.
Apply sparingly to affected areas bid/qid
Apply as in adults
None reported
Documented hypersensitivity; avoid as monotherapy in primary bacterial infections such as cellulitis, angular cheilitis, impetigo, erysipelas, erythrasma (clobetasol), paronychia, or treatment of rosacea, perioral dermatitis, or acne; do not use on face, groin, or axilla
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Systemic absorption of topical corticosteroids may cause reversible HPA-axis suppression, Cushing syndrome, hyperglycemia, and glycosuria; conditions that augment systemic absorption include application of potent steroids, prolonged use, use over large surface areas, and addition of occlusive dressings
Empiric antimicrobial should cover all likely pathogens in the context of the clinical setting.
Indicated for treatment of infections caused by susceptible strains of microorganisms and for prevention of corneal and conjunctival infections.
Apply 1-cm ribbon under lid; not to exceed q4h
Apply as in adults
None reported
Documented hypersensitivity; epithelial herpes simplex keratitis, fungal and mycobacterial infections of the eye, and patients using steroid combinations after uncomplicated removal of a corneal foreign body
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Do not use topical antibiotics in ocular infections that are likely to become systemic; prolonged or repeated antibiotic therapy may result in bacterial or fungal overgrowth of nonsusceptible organisms; such overgrowth may lead to a secondary infection; take appropriate measures if superinfection occurs
Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria.
100 mg PO bid for 3 mo
<8 years: Not recommended
>8 years: 2-5 mg/kg/d PO once or divided bid; not to exceed 200 mg/d
Antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate may decrease doxycycline bioavailability; tetracyclines may increase the hypoprothrombinemic effects of anticoagulants; prothrombin activity should be monitored in patients taking both of these types of medications concurrently; coadministration of tetracyclines may decrease pharmacologic effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Documented hypersensitivity; severe hepatic dysfunction
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Avoid prolonged exposure to sunlight or tanning equipment because a photosensitivity reaction may occur; use lower than usual doses in patients with renal impairment;
if therapy is prolonged, drug serum level determinations may be advisable; use of tetracyclines during tooth development (last one half of pregnancy through 8 y) may cause permanent discoloration of teeth; never administer outdated tetracyclines; degradation products of tetracyclines are highly nephrotoxic and have, on occasion, produced a Fanconilike syndrome
DOC for improvement in clinical parameters, except joint involvement, in enterogenic reactive arthritis. Ciprofloxacin is a bactericidal antibiotic that inhibits bacterial DNA synthesis and, consequently, growth by inhibiting DNA-gyrase in susceptible organisms.
250-500 mg PO bid
<18 years: Not recommended
>18 years: Administer as in adults
Antacids, iron salts, and zinc salts may interfere with GI absorption of fluoroquinolones, resulting in decreased serum levels (administer antacids 2-4 h before or after taking fluoroquinolones)
Cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin may reduce therapeutic effects of phenytoin; probenecid may reduce ciprofloxacin renal clearance by 50% and increase serum concentration by 50%; ciprofloxacin may increase theophylline and caffeine concentrations and prolong their duration of action; ciprofloxacin may increase nephrotoxic effect of cyclosporine; digoxin serum levels may be increased when used concurrently with ciprofloxacin; digoxin levels should be monitored; ciprofloxacin may increase effects of anticoagulants; prothrombin time should be monitored
Documented hypersensitivity
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
In prolonged therapy, perform periodic evaluations of organ system functions, including renal, hepatic, and hematopoietic; patients with renal function impairment may require a dose adjustment; prolonged or repeated antibiotic therapy may result in bacterial or fungal overgrowth of nonsusceptible organisms; such overgrowth may lead to a secondary infection; take appropriate measures if superinfection occurs
These agents are used when NSAIDs do not control arthritis and for inflammatory lesions of intestinal mucosa.
Useful in management of ulcerative colitis and acts locally in colon to decrease inflammatory response and systemically inhibits prostaglandin synthesis.
1000 mg enteric-coated PO bid
<2 years: Not established
>2 years: 40-60 mg/kg/d PO in 3-6 divided doses; follow with a maintenance dose of 20-30 mg/kg/d divided qid
Sulfasalazine decreases effect of iron, digoxin, and folic acid, and, conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and methotrexate
Documented hypersensitivity; GI or GU obstruction
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Use caution in patients with renal or hepatic impairment, blood dyscrasias, or urinary obstruction
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].
Kataria RK, Brent LH. Spondyloarthropathies. Am Fam Physician. Jun 15 2004;69(12):2853-60. [Medline].
Kaarela K, Jantti JK, Kotaniemi KM. Similarity between chronic reactive arthritis and ankylosing spondylitis.A 32-35-year follow-up study. Clin Exp Rheumatol. Mar-Apr 2009;27(2):325-8. [Medline].
Rihl M, Barthel C, Klos A, Schmidt RE, Tak PP, Zeidler H, et al. Identification of candidate genes for susceptibility to reactive arthritis. Rheumatol Int. Jun 9 2009;[Medline].
Dworkin MS, Shoemaker PC, Goldoft MJ, Kobayashi JM. Reactive arthritis and Reiter's syndrome following an outbreak of gastroenteritis caused by Salmonella enteritidis. Clin Infect Dis. Oct 1 2001;33(7):1010-4. [Medline].
Connor BA, Johnson EJ, Soave R. Reiter syndrome following protracted symptoms of Cyclospora infection. Emerg Infect Dis. May-Jun 2001;7(3):453-4. [Medline].
Amor B. Reiter's syndrome. Diagnosis and clinical features. Rheum Dis Clin North Am. Nov 1998;24(4):677-95, vii. [Medline].
Bauman C, Cron RQ, Sherry DD, Francis JS. Reiter syndrome initially misdiagnosed as Kawasaki disease. J Pediatr. Mar 1996;128(3):366-9. [Medline].
Cuttica RJ, Scheines EJ, Garay SM, Romanelli MC, Maldonado Cocco JA. Juvenile onset Reiter's syndrome. A retrospective study of 26 patients. Clin Exp Rheumatol. May-Jun 1992;10(3):285-8. [Medline].
Fan PT, Yu DTY. Reiters syndrome. In: Ruddy S, Harris ED Jr, Sledge CB, eds. Kelley's Textbook of Rheumatology. 6th ed. WB Saunders; 2001:1039-1067.
Hoogland YT, Alexander EP, Patterson RH, Nashel DJ. Coronary artery stenosis in Reiter's syndrome: a complication of aortitis. J Rheumatol. Apr 1994;21(4):757-9. [Medline].
Hughes RA, Keat AC. Reiter's syndrome and reactive arthritis: a current view. Semin Arthritis Rheum. Dec 1994;24(3):190-210. [Medline].
Kasper DL, ed. Reactive arthritis. In: Harrison's Online. Part 13. Section 2. Chap 305. McGraw Hill;2004.
Natarajan UR, Tan TL, Lau R. Reiter's disease following Mycoplasma pneumoniae infection. Int J STD AIDS. May 2001;12(5):349-50. [Medline].
Petersel DL, Sigal LH. Reactive arthritis. Infect Dis Clin North Am. Dec 2005;19(4):863-83. [Medline].
Rihl M, Klos A, Kohler L, Kuipers JG. Infection and musculoskeletal conditions: Reactive arthritis. Best Pract Res Clin Rheumatol. Dec 2006;20(6):1119-37. [Medline].
Reiter's syndrome, Reiter syndrome, reactive arthritis, ReA, peripheral arthritis, arthritis, nongonococcal urethritis, conjunctivitis, seronegative spondyloarthropathies, rheumatic disease, urogenital infections, chronic arthritis, Shigella flexneri, Salmonella typhimurium, Salmonella enteritidis, Streptococcus viridans, Mycoplasma pneumonia, Cyclospora, Chlamydia trachomatis, Yersinia enterocolitica, Yersinia pseudotuberculosis
Thomas Scoggins, MD, Consulting Staff, Department of Emergency Medicine, Blount Memorial Hospital
Thomas Scoggins, MD is a member of the following medical societies: American College of Emergency Physicians and Flying Physicians Association
Disclosure: Nothing to disclose.
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John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
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Robert E O'Connor, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Physician Executives, American Heart Association, American Medical Association, Medical Society of Delaware, National Association of EMS Physicians, Society for Academic Emergency Medicine, and Wilderness Medical Society
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Clinical guidelines
Chlamydial urethritis and cervicitis.
Finnish Medical Society Duodecim - Professional Association. 2001 Jun 5 (revised 2006 Jun 3). Various pagings. NGC:005276
Diagnostic imaging guideline for musculoskeletal complaints in adults - an evidence-based approach. Part 2: upper extremity disorders.
Canadian Protective Chiropractic Association - Professional Association l'Université du Québec à Trois-Rivières - Academic Institution. 2008 Jan. 31 pages. NGC:006702
Clinical trials
New Immunomodulatory Therapy Strategies in Chronic Reactive Arthritis
Lovastatin for the Treatment of Mildly Active Rheumatoid Arthritis
Related eMedicine topics
Reactive Arthritis (Dermatology)
Reactive Arthritis (Rheumatology)
Reactive Arthritis, Musculoskeletal (Radiology)
Reactive Arthritis (Ophthalmology)
Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy (Rheumatology)
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