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Radiology > MUSCULOSKELETAL
Reactive Arthritis, Musculoskeletal
Article Last Updated: Feb 21, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Anil Kumar Aribandi, MD, MRCP, Registrar, Department of Hematology, Royal Hallamshire Hospital, UK
Coauthor(s):
Oludare Adetokunbo Demuren, MD, FRCR, Consulting Staff, Department of Radiology, Colchester General Hospital
Editors: Amilcare Gentili, MD, Clinical Professor of Radiology, University of California at San Diego; Consulting Staff, Department of Radiology, Thornton Hospital; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Theodore E Keats, MD, Professor, Departments of Radiology and Orthopedics, University of Virginia School of Medicine; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Felix S Chew, MD, MBA, EdM, Professor, Department of Radiology, Vice Chairman for Radiology Informatics, Section Head of Musculoskeletal Radiology, University of Washington
Author and Editor Disclosure
Synonyms and related keywords:
Reiter syndrome, Reiter's syndrome, Reiter disease, Reiter's disease, reactive arthritis, human leukocyte antigen B27, HLA-B27, seronegative spondyloarthropathy
Background
Reiter syndrome was originally defined as a triad of arthritis, conjunctivitis, and urethritis. Hans Reiter first reported this triad of symptoms in 1916, and Bauer and Engelman formally described it as a syndrome in 1942.
A term frequently associated with Reiter syndrome is reactive arthritis. Ahvonen and coworkers introduced this term in 1969. Reactive arthritis is used to describe an acute arthritis complicating an infection elsewhere in the body in which the infecting organism cannot be cultured from the joint fluid or synovium.
Approximately 80% of patients are positive for the histocompatability antigen called human leukocyte antigen (HLA)-B27; therefore, reactive arthritis is strongly associated with HLA-B27. Reiter syndrome is now thought to be only 1 clinical manifestation of reactive arthritis. Because of its association with HLA-B27 and its clinical overlap with ankylosing spondylitis and psoriatic arthritis, reactive arthritis and Reiter syndrome are classified as types of seronegative (for rheumatoid factor) spondyloarthropathy.
Pathophysiology
Two factors are important in the pathogenesis of Reiter syndrome. First, in some patients, the arthritis is clearly induced by infection. Second, most patients share HLA-B27 typing.
Infection
Bacteria that have been identified as definite triggers include Shigella, Salmonella, and Yersinia species, Campylobacter jejuni; and Chlamydia trachomatis. Other pathogens are those related to lymphogranuloma venereum. Most of these organisms are thought to produce lipopolysaccharide, and they share a capacity to attack mucosal surfaces, to invade host cells, and to survive intracellularly.
Antigens from these organisms have been detected in the synovium or in synovial-fluid leukocytes in patients with reactive arthritis and/or Reiter syndrome for long periods after acute episodes. Antigen-specific T cells likely play an important role, though the precise mechanism remains to be determined.
Reiter disease is not uncommon after HIV infection. The spectrum of inflammatory and reactive arthropathies includes Reiter syndrome, psoriatic arthritis, and HIV-associated arthritis. Patients with atypical musculoskeletal complaints and a suspected history of exposure should be tested for HIV.
Reiter syndrome has also been reported as an uncommon complication after intravesical bacillus Calmette-Guérin (BCG) immunotherapy for bladder carcinoma.
HLA-B27
As with bacterial antigens, the role of HLA-B27 also remains to be determined. In vitro findings indicate that the presence of HLA-B27 significantly prolongs the intracellular survival of Yersinia enterocolitica and Salmonella enteritides in human and murine cell lines. One hypothesis suggests that prolonged intracellular bacterial survival promoted by HLA-B27 and other factors permit infected leucocytes to travel from the site of primary infection to the joints, where a T-cell response to persistent bacterial antigens promotes arthritis.
Frequency
United States
About 1-2% of patients with nonspecific urethritis who are examined at clinics for sexually transmitted diseases have reactive arthritis, and the rates after outbreaks of shigellosis are similar. A man with HLA-B27 has a 20% risk of developing reactive arthritis after an episode of Shigella-related dysentery.
The overall incidence and prevalence is difficult to assess because of the variable prevalence of the triggering infections and of the genetic susceptibility in different populations. For example, in Minnesota, the incidence has been estimated to be 3.5 cases per 100,000 population per year. In contrast, in a population with a high rate of genitourinary and gastrointestinal infections (eg, urban homosexual and bisexual men), the prevalence may approach 1 case per 1000 population.
International
See In the US above.
Mortality/Morbidity
- The arthritic episodes are short and self-limiting.
- Recurrences are frequent, and residual disability and deformity occurs in 5% of patients.
- Chronic changes are most common in the metatarsophalangeal joints, heel, lumbar spine, knee, and ankle.
Race
The prevalence of Reiter syndrome is higher in white people than in black people.
Sex
- Although Reiter syndrome is predominantly a disease of young men, the apparent male-to-female ratio of 50:1 is spuriously high.
- With the recognition that the initiating infectious episode might be silent cystitis or cervicitis, the male-to-female ratio is more likely to be 5:1.
- Postdysentery reactive arthritis has an equal sex distribution.
Age
The disease is most common in individuals aged 18-40 years, but it can occur in children as young as 5 years of age and in older adults.
Clinical Details
The clinical features of Reiter syndrome range from transient monoarthritis to severe multisystemic disease. In most cases, careful history taking elicits evidence of an antecedent infection 1-4 weeks before the onset of the symptoms of reactive disease. Buccal ulceration, balanitis, and sacroiliitis can also occur. The disease is often not self-limiting and may progress, with 80% of patients having symptoms at 5 years.
In about 50% of patients with Reiter disease, urethritis, conjunctivitis, and an inflammatory oligoarthritis simultaneously develops 1-3 weeks after sexual exposure or an episode of dysentery. The urethritis in Reiter disease is usually associated with mild dysuria, but occasional cases involve severe dysuria and hematuria resulting from acute hemorrhagic cystitis and prostatitis.
Constitutional symptoms are common. These include fatigue, malaise, fever, and weight loss. Musculoskeletal symptoms are usually acute in onset, and low backache is common.
Arthritis is asymmetric and additive, with involvement of new joints occurring over a few days to a few weeks. The joints of the lower extremities—especially the knee; ankle; and subtalar, metatarsophalangeal, and interphalangeal joints—are the most common sites of involvement. The arthritis is usually painful, and joint effusions are common in the knee. Dactylitis, or sausage digits, is another feature. Tendinitis with retrocalcaneal bursitis and plantar fasciitis are characteristic lesions.
Although Reiter disease is a common cause of plantar fasciitis, this finding is not pathognomonic. Plantar fasciitis can also be seen in other rheumatologic conditions such as ankylosing spondylitis, rheumatoid arthritis, and gout.
Urethritis may be a principal feature. As a precipitating event, it precedes the symptom of reactive arthritis by 1-3 weeks. Men experience frequency and dysuria. Examination of the penis shows meatal erythema and edema. Prostatitis is common and has been reported in up to 80% of patients.
Hemorrhagic cystitis may develop and resolve spontaneously. Similarly, females can have vulvitis, cervicitis, or salpingitis.
Ocular disease is common, ranging from transient asymptomatic conjunctivitis to an aggressive anterior uveitis that is occasionally refractory to treatment and causes blindness.
Mucocutaneous lesions are common. Oral ulcers are superficial, transient, and often asymptomatic. The characteristic skin lesion, keratoderma blennorrhagica, consists of vesicles that become hyperkeratotic and that ultimately form a crust before disappearing. They are most common on palms and soles. Lesions on glans penis, termed circinate balanitis, are common and consist of vesicles that rupture to form painless superficial erosions.
Nail changes are common and consist of onycholysis and distal yellowish discoloration.
Less frequent features include cardiac conduction defects, aortic insufficiency, lesions of the central nervous system and peripheral nervous system, and pleuropulmonary infiltrates.
Preferred Examination
Imaging study
Radiography is most important imaging technique for the detection of Reiter syndrome.
Laboratory studies
The erythrocyte sedimentation rate and C-reactive protein level are elevated during the acute phase of the disease. A moderate neutrophilic leukocytosis may be present. Chronic cases may show a mild normocytic anemia. Levels of C3 and C4, which are acute-phase reactants, are also increased. Results for antinuclear antibodies and rheumatoid factor are negative.
Synovial fluid has an elevated white blood cell count with a predominance of neutrophils. The fluid may contain large macrophages with vacuoles containing nuclear debris and whole leucocytes. These are called Reiter cells, but they are nonspecific for Reiter syndrome. The presence of HLA-B27 antigen is correlated with axial disease, carditis, and uveitis.
Ankylosing Spondylitis
Psoriatic Arthritis
Rheumatoid Arthritis, Spine
Other Problems to be Considered
Enteropathic arthritis
Findings
In early stage, radiographs are normal. The synovial joint, symphyses, and entheses are affected. An asymmetric distribution with predominant involvement of lower extremities is seen. The general radiographic changes are similar to those of psoriatic arthritis, but the characteristic sites of abnormality are the small joints of the foot, the calcaneus, the ankle, the knee, and the sacroiliac joint. Nonspecific soft-tissue swelling is frequently seen in the toes and fingers, resulting in sausage-shaped digits. Periarticular osteoporosis is seen with acute episode of arthritis. Diffuse loss of the articular space is characteristic and is frequently affects the small joints of the foot, hand, wrist, knee, and ankle. Bone erosions may also occur at these joints, resulting in sacroiliitis. Erosions initially occur at the joint margins and later progress to involve subchondral bone in the central portion. Bone proliferation is characteristic of all seronegative spondyloarthropathies and is the most helpful radiographic feature in distinguishing these conditions from rheumatoid arthritis. Linear and fluffy periosteal bone proliferations are common in Reiter syndrome, especially in the calcaneus; knee; and metacarpal, metatarsal, and phalangeal shafts. A second variety of bone proliferation occurs at the sites of tendon and ligament attachments to the bone. Intra-articular bony ankylosis is seen in small joints of hands and feet but is less common than with ankylosing spondylitis and psoriatic arthritis. Forefoot Radiographs of the foot show asymmetric involvement of the metatarsophalangeal and interphalangeal joints. Any joint may be affected; the joints of the great toe are commonly involved (see Image 1) Calcaneum Calcaneal enthesopathy is characteristic of Reiter syndrome and occurs in 25-50% of cases. Both the posterior and plantar aspects of the bone are affected (see Image 2). Bilateral changes are common. Ankle Radiographic findings are seen in 30-50% of patients. Changes include soft tissue swelling, linear or fluffy periostitis of the distal tibial and fibular diaphyses and metaphysis, and articular space loss and marginal erosions. Knee Knee changes are seen in 25-50% of patients. The most common abnormality is joint effusion. Hand and wrist Changes in the upper extremity are unusual and seen in 10-30% of cases. Abnormalities of the proximal interphalangeal joint are more common than changes in the metacarpophalangeal and distal interphalangeal joints. Involvement of the wrist is usually asymmetric (see Image 3). Manubriosternal joint and symphysis pubis Osseous erosions and adjacent bony proliferation at the manubriosternal joints are seen in Reiter disease and may be associated with local pain and tenderness. Similar changes are seen at the symphysis pubis. Temporomandibular joint Patients with Reiter disease often have condylar erosions that cause pain and dysfunction in the temporomandibular joints. These abnormalities can be demonstrated by plain radiography. When the radiographs are inconclusive, the changes can be depicted by MRI or CT. Sacroiliac joint Sacroiliitis is common in Reiter syndrome, seen in 5-10% of patients with acute disease and 40-60% of those with chronic severe disease. If supplemented with radionuclide investigation, sacroiliitis is found in 60-75% of patients. Bilateral asymmetric changes are most typical (see Image 4). Less commonly, unilateral abnormalities of the sacroiliac joint are seen in Reiter syndrome, particularly early in the disease process. Spine Spinal changes are less common than the other changes in Reiter disease and seen less often than in ankylosing spondylitis and psoriatic arthritis. An early finding in Reiter syndrome is the appearance of paravertebral syndesmophytes about the lower 3 thoracic and upper 3 lumbar vertebrae (see Image 5).
Degree of Confidence
Radiographs are a reliable means of diagnosing Reiter syndrome, particularly if the typical clinical features are present.
Findings
Sacroiliitis is demonstrable on CT earlier than on plain radiography. Early sacroiliitis manifests with small joint erosions and irregularities in the articular surfaces of the sacroiliac joint (see Image 6). Unilateral or asymmetric involvement of the sacroiliac joints is also common. Enthesopathies are also demonstrable. The high radiation dose to the patient makes CT an unattractive modality for screening large areas of the body in cases of suspected Reiter disease, but CT is useful in localized evaluations or in determining the extent of complications such as bony ankylosis when plain radiographs are inconclusive. CT is also useful in interventions such as CT-guided injections of the sacroiliac joint and in the management of chronic severe sacroiliac joint pain (see Image 7).
Degree of Confidence
CT is a reliable means of establishing diagnosis of sacroiliitis and in demonstrating enthesopathies. However, the findings are generally nonspecific and should be correlated with the clinical picture.
Findings
In Reiter disease, MRI reveals the extent of the process; the presence of bursitis and tenosynovitis, especially in the peroneal, anterior tibial, and posterior tibial tendons; and the presence of complications such as synovial cysts. Erosive arthritis and synovitis may develop in the hands and wrists. Synovitis and tenosynovitis are hypointense on T1-weighted images and hyperintense on T2-weighted spin-echo images. These appearances reflect the water content of the affected areas. Short-tau inversion recovery (STIR) images show strong hyperintensity is seen in the affected joints and adjacent marrow, as well as in sites of enthesitis (see Images 8-10).
Degree of Confidence
MRI has extremely high sensitivity for active Reiter disease but low specify. Correlation with the clinical and radiographic findings is usually necessary to differentiate Reiter disease from other seronegative arthropathies.
Findings
Plantar fasciitis is the most common cause of inferior heel pain, and Reiter disease is one of the causes of plantar fasciitis.
High-resolution ultrasonography reveals decreased echogenicity and increased thickness of the plantar fascia (normal thickness, 3-4 mm).
Degree of Confidence
In addition to Reiter disease, a variety of rheumatologic conditions can cause plantar fasciitis. Examples include rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, and gout. The sonographic findings of these conditions are identical. These other disease should be considered in the differential diagnosis and excluded with clinical history taking and other means.
Findings
Bone scintigraphy with bone-seeking radiopharmaceutical agents allows the early detection of Reiter syndrome and provides accurate details about the extent of the disease. The distribution of abnormal radionuclide accumulation parallels that obtained by radiographic examination and may occur before radiographic and clinical alterations are apparent.
Asymmetric involvement of lower extremity is usually seen. Increasing radioactivity related to the plantar and posterior aspects of the calcaneus is observed.
Degree of Confidence
Scintigraphy provides high sensitivity but low specificity for the diagnosis of sacroiliitis.
The interpretation of scintigraphic abnormalities at sacroiliac joints is difficult because prominent uptake at this site is a normal finding.
False Positives/Negatives
Abnormal radionuclide uptake in the sacroiliac joint and other locations may not be specific for Reiter syndrome. Other seronegative spondyloarthropathies, such as psoriatic arthritis, may have similar findings.
Radiologic intervention Limited intervention is described in CAT Scan. Treatment The treatment for Reiter syndrome is mainly symptomatic and supportive. Joint symptoms are best treated with nonsteroidal anti-inflammatory drugs. Antibiotic therapy is useful in some cases. Topical corticosteroids and keratolytic agents are useful for treating keratoderma blennorrhagica. Circinate balanitis should be treated with topical corticosteroids. Tendinitis and other enthesitic lesions occasionally benefit from intralesional glucocorticoids. Severe progressive arthritis and intractable keratoderma blennorrhagica may warrant cytotoxic therapy, and cardiac complications are managed conventionally. Patients should to be educated about the nature of the disease and about the factors that predispose them to recurrences. Comprehensive management also includes counseling to inform patients about sexually transmitted disease and exposure to enteropathies, as well as about the appropriate use of physical therapy, vocational counseling, and continued surveillance for those long-term complications such as bony ankylosis.
| Media file 1:
Radiograph of the feet in a 27-year-old man shows erosions in all the left metatarsophalangeal (MTP) joints with subluxation and valgus deformity of most of the toes. Smaller erosions in the four and fifth MTP joints of the right foot are also shown. |
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| Media file 2:
Lateral radiograph of the foot (same patient as in Image 1) reveals a calcaneal spur and enthesitis. |
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| Media file 3:
Radiograph of both hands shows small erosive changes in both first metacarpal heads associated with minimal subluxation. Bone density is normal. |
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Radiography of the pelvis reveals bilateral asymmetric sacroiliitis. |
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Image in 40-year-old man with nonmarginal syndesmophytes predominantly in the lower thoracic and upper lumbar spine. |
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| Media file 6:
Prone pelvic CT scan shows right unilateral sacroiliitis. |
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| Media file 7:
This scan was obtained in the same patient as in Image 6 shows a needle introduced into the right sacroiliac joint under CT guidance. An injection of 0.5% bupivacaine hydrochloride 5 mL (Marcaine) and methylprednisolone acetate 40 mg (Depo-Medrol) resulted in permanent relief of the patient's intractable sacroiliac pain. |
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| Media file 8:
Axial T1-weighted spin-echo image in a 47-year-old man shows widening and irregularity of upper right sacroiliac joint suggestive of unilateral sacroiliitis. |
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| Media file 9:
Coronal oblique short-tau inversion recovery (STIR) image through the sacroiliac (SI) joints in the same patient in Image 8 shows widening of the right SI joint, which contains fluid. These findings confirm right sacroiliitis. |
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| Media file 10:
Sagittal short-tau inversion recovery (STIR) image of the foot shows increased thickness of the plantar fascia (<8 mm) with edema in the fascia, surrounding soft tissues, and adjacent marrow. These findings are diagnostic of plantar fasciitis. |
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Reactive Arthritis, Musculoskeletal excerpt Article Last Updated: Feb 21, 2007
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