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Reiter's syndrome                                                                                      REF:  DynaMed 2010  

SX |  DX | RX     
  1. classic triad of urethritis, arthritis (ankylosing spondylitis) and conjunctivitis (or iritis)
  2. asymmetric arthropathy and 1 or more of: urethritis/cervicitis, dysentery, inflammatory eye disease, mucocutaneous disease (nonpainful mouth ulcers, circinate balanitis)
  3. Reiter syndrome originally referred to clinical triad of nongonococcal urethritis, conjunctivitis and arthritis in young German officer after bout of bloody dysentery reported by Hans Reiter (Dische Med Wschr 1916;42:1535)

Also called:

  • Reiter's syndrome
  • "reactive arthritis" replacing Reiter syndrome as preferred designation
  • seronegative reactive arthritis
  • postinfectious arthritis

Organs Involved:

  • joints - asymmetric, pauciarticular, lower extremities
  • < 50% have sacroilitis or spondylitis, sacroilitis asymmetric, about 90% peripheral joint involvement, eye involvement common (predominantly conjunctivitis), 5-10% cardiac involvement, skin or nail involvement common
  • seronegative spondyloarthropathies affect spine, peripheral joints and/or periarticular structures, and variably associated with extra-articular manifestations such as acute or chronic gastrointestinal or genitourinary inflammation (sometimes due to bacterial infection), anterior ocular inflammation, psoriasiform skin and nail lesions and uncommonly lesions of aortic root, cardiac conduction system and pulmonary apices

Who is most affected:

  • ages 16-35 years; males 10 times post-urethritis, males 1-5 times post-dysentery


  • uncommon, 0.7-3% post-urethritis, 0.2-1.5% post-dysentery

Family History (FH):

  • seronegative spondyloarthropathy often genetically linked  


  • reactive arthritis, follows Chlamydial infection or dysentery (shigella, salmonella, Yersinia)


  • a few patients develop chronic uveitis that ultimately results in visual impairment
  • cardiac complications - 1-2% aortitis, aortic regurgitation (ultimately requires aortic valve replacement), heart block (may require cardiac pacemaker), mitral regurgitation
  • amyloidosis of serum amyloid A variety has been reported, usually presents with proteinuria or nephrotic syndrome
  • reported neurologic complications include peripheral neuropathies, encephalopathy, transverse myelitis
  • other rare complications - IgA glomerulonephritis, thrombophlebitis, purpura, livedo reticularis

Associated conditions:

  • venereal or intestinal infection, up to 80% chronic prostatitis
  • frequently associated with HIV infection (both conditions associated with sexually transmitted disease), likely to be more severe in HIV-infected patients with severe polyarticular arthritis, disabling enthesitis and extensive cutaneous manifestations


Chief Concern (CC):

mucocutaneous lesions, joint stiffness, myalgia, low back pain worse with rest; occasionally heel pain, red eyes, low grade fever; rarely high fever, weight loss, severe malaise, fatigue

History of Present Illness (HPI):

typically acute onset 1-4 weeks after venereal infection or gastroenteritis, venereal infection frequently asymptomatic

46% nongonococcal urethritis

  • usually first manifestation
  • occurs in both postvenereal and postenteric forms
  • men usually have mild dysuria and mucopurulent urethral discharge, occasionally prostatitis or epididymitis
  • women may have dysuria, vaginal discharge, purulent cervicitis or vaginitis
  • asymptomatic patients often have sterile pyuria, especially on first-voided morning urine sample
  • sterile genital inflammation may occur in postenteric reactive arthritis unrelated to any sexually acquired infection

31% conjunctivitis

  • usually occurs with or several days after urethritis
  • symptoms often mild and transient
  • ask patient about crusting of eyelids, especially in the morning, which suggests subtle inflammation
  • some patients develop bilateral obvious redness, burning sensation and exudation
  • 20% acute anterior uveitis (iritis) may occur with severe ocular erythema, pain and photophobia at any time during course of reactive arthritis; see further details under Consult section in Treatment below

articular manifestations

  • typically occur after urethral and ocular inflammation has subsided
  • usually additive, asymmetric, oligoarticular, affecting average 4 joints
  • lower limbs (especially knees, ankles and small joints of feet) affected more commonly than upper extremities (wrists, elbows, hand joints)
  • 39% exclusively lower limb disease, upper extremity disease alone is rare
  • 61% both upper and lower extremity limbs involved - 68% knees, 49% ankles, 64% small joints of feet, 42% small joints of hand, 25% wrists, 22% elbows, 19% shoulders, 6% temporomandibular joints, 6% sternoclavicular joints, < 1% hips
  • arthritis usually mild, rarely chronic

enthesitis (enthesopathy)

  • inflammation at bony sites where tendons, ligaments or fascia attach or insert
  • most commonly at insertions of plantar aponeurosis and Achilles tendon on calcaneus causing heel pain in 61% patients
  • other common sites are ischial tuberosities, iliac crests, tibial tuberosities, ribs

61% low back and buttock pain

  • only 20% develop radiographically demonstrable sacroiliitis, about 10% progress to ankylosing spondylitis
  • other potential causes of back pain are enthesitis or prostatitis

extra-articular manifestations

  • 43% mucocutaneous lesions: 23% keratoderma blennorrhagica ; 13% nail changes ; 26% circinate balanitis ; 14% oral ulcers
  • 19% weight loss > 4.5 kg (10 pounds), unexplained profound weight loss and even cachexia occurs in some patients
  • 32% fever > 101 degrees F (38.3 degrees C)
  • 12% uveitis
  • 6% aortitis
  • < 1% amyloidosis


Physical Exam:


  • 40% conjunctivitis (usually mild and transient), uveitis, keratitis rare, retinitis
  • oral ulcers - painless shallow ulcers of buccal mucosa, tongue or hard palate


  • 20% sacro-iliitis  


  • affected joints typically swollen, warm, tender, painful on active and passive motion, often dusky blue discoloration or frank erythema with exquisite tenderness suggestive of septic joint
  • Achilles tendonitis, plantar fasciitis, local enthesopathy
  • when toes or fingers affected, entire digit usually diffusely swollen - 52% sausage digit or dactylitis



  • 23% keratoderma blennorrhagica
    • papulosquamous rash
    • most commonly on soles or palms; also occurs on toes, scrotum, penis, trunk, scalp; can occur anywhere
    • starts as waxy papules that resemble mollusk shells or pustules
    • lesions then coalesce and become hyperkeratotic, scaly, often indistinguishable from psoriasis
    • copious discharge of mucus
    • histologic appearance of pustular psoriasis if biopsied; soles, palms, toes, scrotum, penis, trunk, scalp)
  • nail changes
    • nails may become thickened, opacified, and crumble
    • oncholysis (erosion of end of nails, lifting from bed)
    • no pitting
  • circinate balanitis  25% (glans penis or glans clitoris, painless erythematous erosion)
    • characteristic lesion of glans or shaft of penis
    • in uncircumcised men - moist, shallow ulcers; often serpiginous and surrounding meatus
    • in circumcised men - dry, plaque-like, hyperkeratotic rash resembling keratoderma or psoriasis
    • presence of distal interphalangeal joint involvement, nail pitting, plaque-like psoriatic lesions over elbows or knees suggests psoriatic arthritis



Diagnosis of reactive arthritis

  • criteria preliminary criteria developed by American College of Rheumatology
    - Reiter syndrome defined as nongonococcal urethritis or cervicitis and sterile peripheral arthritis occurring within 1 month  
  • these criteria insensitive as 40% patients have no symptoms or signs of genital inflammation
  • seronegative, asymmetrical oligoarthritis, especially in young person makes condition possible
  • antecedent diarrhea or venereal exposure makes condition more likely
  • heel pain or other symptoms of enthesitis, dactylitis, or mucocutaneous lesions increase likelihood of diagnosis
  • testing for HLA-B27 may have reasonable predictive value, but only if clinical data supports high likelihood of disease

Criteria for classification of spondyloarthropathy  

  • must have 1 of:
    • inflammatory spinal pain - history or present symptoms of spinal pain in back, dorsal, or cervical region with at least 4 of:
      onset before age 45 years; insidious onset ; improved by exercise ; associated with morning stiffness ; duration at least 3 months
    • synovitis - past or present asymmetric arthritis or arthritis predominantly in lower limbs
  • must have 1 of:
    • positive family history - any of the following conditions in any first-degree or second-degree relatives:
      ankylosing spondylitis ; psoriasis ; acute uveitis ; reactive arthritis ; inflammatory bowel disease
    • psoriasis diagnosed by physician in past or present
    • inflammatory bowel disease - past or present Crohn's disease or ulcerative colitis diagnosed by physician and confirmed by radiography or endoscopy
    • nongonococcal urethritis or cervicitis or acute diarrhea within 1 month before arthritis
    • buttock pain alternating between right and left gluteal areas - past or present
    • enthesopathy - past or present spontaneous pain or tenderness at site of insertion of Achilles tendon or plantar fascia
    • sacroilitis - bilateral grade 2-4 or unilateral grade 3-4 using radiographic grades 0 normal, 1 possible, 2 minimal, 3 moderate, 4 ankylosis
  • criteria yields 78.4% sensitivity and 89.6% specificity, addition of radiographic evidence of sacroilitis improves sensitivity to 87% with 86.7% specificity
  • Reference - European Spondylarthropathy Study Group preliminary criteria in Arthritis Rheum 1991;34:1218  

Rule out:

  • other seronegative spondyloarthropathies - primary ankylosing spondylitis, psoriatic arthropathy, enteropathic arthropathy, juvenile spondyloarthropathy
  • infectious arthritis (septic arthritis, gonococcal arthritis), crystal-induced arthritis (gout, pseudogout), rheumatic fever, gonorrhea

Blood tests:

  • no rheumatoid factors (RF), no ANA
  • 39% anemia - normochromic, normocytic, due to chronic inflammation
  • 34% leukocytosis - WBC 10-15,000/mm3 during acute phase
  • 27% thrombocytosis - platelet count 400-600,000/mm3
  • 72% elevated erythrocyte sedimentation rate (ESR), C reactive protein also elevated
  • 81% HLA-B27, less common in African Americans (30-50%); more likely in patients with chronic or relapsing course, sacroiliitis, spondylitis, iritis or aortitis
  • elevated serum globulins, especially IgA directed against specific bacterium triggering disease

Imaging studies:

  • x-ray abnormalities develop only after disease present for several months
  • fluffy periosteal reaction (periostitis) and new bone formation may be seen at symptomatic sites of enthesitis or around affected joints or adjacent bony shafts, for example, metatarsophalangeal bones of feet, occasionally "pencil-in-cup" deformities of small joints in feet or hands
  • 16% x-ray changes at calcaneus (calcaneal spurs or bony erosions due to enthesopathy)
  • 17% sacroiliitis on x-ray (unilateral early)
  • 7% spondylitis (spinal arthritis, syndesmophytes are atypical ossified ligaments) on x-ray

Testing to consider:

  • urethral or cervical specimens for Chlamydia and gonorrhea
  • culture synovial fluid for gonococci and other pathogens


  • Activity:  rest & joint immobilization  

Anti-inflammatory medications

  • NSAIDs
    • NSAID therapy needs to be individualized
    • newer NSAIDs generally more effective than salicylate
    • indomethacin or diclofenac up to 200 mg/day usually well tolerated
  • sulfasalazine
    • moderately effective (Arthritis Rheum 1995 May;38;618)
    • sulfasalazine 2000 mg/day vs. placebo in 134 patients inadequately controlled by NSAIDs had 62% vs. 48% response at 36 weeks (Arthritis Rheum 1996 Dec;39:2021 in J Watch 1997 Jan 15;17(2):18)
  • steroid injections
    • intra-articular corticosteroid injections into acutely inflamed joints do not have as dramatic or as sustained a response as in rheumatoid arthritis
    • steroid injection of sacroiliac joint usually done under fluoroscopic guidance, 79% response rate in series of 24 such injections (Arthritis Rheum 1992;35:564)
  • immunosuppressants
    • methotrexate contraindicated with alcohol
    • azathioprine useful in randomized crossover study of 8 patients (Ann Rheum Dis 1986 Aug;45(8):653)
  • bromocriptine beneficial in 4 patients (J Rheumatol 1992;19:747)
  • topical corticosteroids for conjunctivitis, oral mucosa and genital lesions, and keratoderma blennorrhagica


  • intravenous penicillin
  • 10 days oral antibiotics (tetracycline, erythromycin, TMP/SMX)
  • long-term tetracycline for persistent urethritis
  • lymecycline (form of tetracycline) decreased duration of illness in patients with Chlamydia-induced disease but not in patients with reactive arthritis triggered by enteric infection in 3-month placebo-controlled trial of 40 patients with chronic reactive arthritis (Arthritis Rheum 1991;34:6)
  • 6-month course of combination antibiotics may improve symptoms of chlamydia-induced reactive arthritis (level 2 [mid-level] evidence)

anti-TNF therapy may reduce symptoms and improve quality of life in patients unresponsive to NSAIDs or methotrexate (level 3 [lacking direct] evidence); systematic review of 2 randomized trials of infliximab (5 mg/kg IV over 2 hours at 0, 2 and 6 weeks) and 4 randomized trials of etanercept (25 mg subcutaneously twice weekly) for spondyloarthritis (ankylosing spondylitis, psoriatic arthritis, spondyloarthropathy); anti-tumor necrosis factor-alpha agents improved symptom control, physical function and quality of life; no direct evidence from patients with reactive arthritis, only case reports available (J Rheumatol 2003 Jun;30(6):1356 in ACP Journal Club 2004 May-Jun;140(3):71)

use of IV immunoglobulin (IVIG) not recommended (University HealthSystem Consortium guidelines on IVIG preparations which were withdrawn from National Guideline Clearinghouse on 2004 Dec 20 as no longer current)




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