Approach Considerations
The diagnosis of reactive arthritis (ReA) is clinical, based on the history and physical examination findings. A high index of suspicion is required. No laboratory study or imaging finding is diagnostic of ReA. No specific tests or markers are indicated. Indicators of inflammation are usually abnormal.
Laboratory Studies
Blood tests and urinalysis
The values of acute-phase reactants, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are usually elevated markedly (eg, ESR of 50-60 mm/hr) but later return to the reference range when the inflammation subsides. C1, C4, and C5 levels are within the reference range. C1 inhibitor functional assay (C1INH) and C2 levels may be elevated.
Other laboratory findings include a normocytic normochromic anemia along with mild leukocytosis (up to 20,000/µL) and thrombocytosis during the acute phase. Immunoglobulin A (IgA) antibodies to specific bacterial antigens have been reported. Test results for rheumatoid factor and antinuclear antibodies are negative.
Referral for HIV should be considered in patients presenting with history, symptoms, or findings suggesting increased risk for the disease; certain therapies are contraindicated in these patients. [66] The incidence of ReA is high among patients with AIDS, and HIV testing is mandatory in patients in whom ReA is newly diagnosed, even if they do not have the risk factors.
White blood cells (WBCs), red blood cells (RBCs), and small amounts of protein are present in urinalysis findings, indicating pyuria. Urine culture findings may be positive for Chlamydia or Ureaplasma, though test results may be negative if obtained several weeks after the onset of symptoms.
Serology and cultures
Chlamydia should be sought in every case of ReA. Serology is useful in some cases; however, culture techniques may not be reliable, causative agents are only identified in only 58% of cases with genitourinary (GU) symptoms, and there is a high positive rate in control populations (people without ReA). [18]
If urethritis or cervicitis is present, cervical or urethral cultures should be obtained. Smears of urethral discharge may be sent for antichlamydial staining by direct fluorescent antibody (DFA) testing, enzyme immunoassay (EIA), culture, or nucleic acid probe. Polymerase chain reaction (PCR) assay may be considered. [86] A Giemsa stain or a Wright stain may reveal the classic gram-negative intracellular diplococci associated with gonorrhea. Many patients may experience simultaneous sexually transmitted diseases, particularly chlamydia and gonorrhea.
Results of routine urine cultures are negative. Stool cultures can be helpful for enteric pathogens (eg, Salmonella, Shigella, and Yersinia). Obtaining stool cultures even when bowel symptoms are inapparent or mild may help direct treatment; however, cultures are often negative by the time of presentation. [63]
The US Preventive Services Task Force (USPSTF) guidelines for screening for chlamydial infections and gonorrhea were updated in 2014. The USPSTF recommends screening in sexually active women age 24 years and younger and in older women who are at increased risk for infection. Evidence was insufficient to assess the balance of benefits and harms of screening for chlamydia and gonorrhea in men. [87]
HLA-B27 test
The presence of human leukocyte antigen (HLA)-B27 correlates with axial disease, carditis, and uveitis. HLA-B27 test results are positive in 65%-96% of ReA cases (67-92% of pediatric cases). HLA-B27 testing is not diagnostic of ReA and thus not required; however, it may be helpful for certain purposes (eg, supporting the diagnosis of ReA in patients with joint-restricted symptoms). The HLA-B27 test is moderately expensive and should not be ordered indiscriminately as a screen.
In a report by Shimamoto et al, a Japanese man with ReA was negative for HLA-B27 and other HLA-B27 cross-reactive major histocompatibility complex (MHC) class I antigens but was positive for HLA-B51. [88] Laboratory examination showed significant elevation of serum levels of IgA and IgG antichlamydial antibodies. The authors suggested that a combination of Chlamydia infection and HLA-B51 presence might play a role in the pathogenesis of ReA in this patient.
Tuberculin skin test
A tuberculin skin test may be appropriate in certain individuals, particularly those with demographics strongly suggestive of infectious tuberculosis (TB). TB is far more likely to occur in immigrants from Southeast Asia, Africa, and other endemic regions. Caution must be taken not to interpret a positive skin test as diagnostic of tuberculosis, particularly in individuals who have been given the bacille Calmette-Guérin (BCG) vaccine.
Radiography
Radiologic examination may demonstrate various arthritic changes. These changes tend to be asymmetric and oligoarticular and are more common in the lower extremities. However, radiologic signs are present in only 40-70% of cases, and they may be completely absent even in instances of severe disease. Early in the disease process, radiography often reveals no abnormalities at all.
In more advanced or long-term ReA, periosteal reaction and proliferation at sites of tendon insertion are visible. Exuberant plantar spurs are a common sign in long-term ReA. Changes consistent with chronic plantar fasciitis or Achilles tendinitis may be seen. In the hands and feet, marginal erosions with adjacent bone proliferation occur. The erosions typically have indistinct margins and are surrounded by periosteal new bone and periostitis (see the images below).
Radiograph of feet of 27-year-old man shows erosions in all left metatarsophalangeal (MTP) joints with subluxation and valgus deformity of most toes. Smaller erosions are also visible in fourth and fifth MTP joints of right foot.
Radiograph of both hands shows small erosive changes in both first metacarpal heads associated with minimal subluxation. Bone density is normal.
Spinal radiographic findings include sacroiliitis and syndesmophytes. Sacroiliitis (unilateral or bilateral) occurs in fewer than 10% of acute cases but develops in half of patients with chronic severe disease (see the image below). Specifically ordering a radiograph of the sacroiliac joint is advisable. Such a film provides a more sensitive tunnel view than a routine film of the lumbosacral spine does.
Syndesmophytes are asymmetric, paravertebral, bulky, discontinuous, comma-shaped ossifications that most commonly involve the lower thoracic and upper lumbar vertebrae (see the image below).
Radiograph in 40-year-old man shows nonmarginal syndesmophytes predominantly in lower thoracic and upper lumbar spine.
Severe ankylosing spondylitis occurs in fewer than 5% of cases.
Other Imaging Modalities
Whole-body scintigraphy is a sensible diagnostic tool for use in screening for enthesopathy and arthropathy. [89]
Positron emission tomography has been found to allow recognition of enthesitis in the early stage of ReA, before other modalities would be able to detect it. [90]
Magnetic resonance imaging (MRI) of the sacroiliac joints may reveal disease earlier than conventional radiography would. MRI is more sensitive than computed tomography (CT) or scintigraphy in detecting sacroiliitis and may be necessary in children who do not usually exhibit sacroiliac symptoms. MRI is also useful in assessing activity in the tendons and entheses. [91]
Ultrasonography may reveal enthesitis (as periosteal reaction and tendinosis) more accurately that physical examination would. [59, 55] Echocardiography may reveal carditis or valvular dysfunction in patients with poststreptococcal ReA. [92, 93]
Arthrocentesis, Synovial Fluid Analysis, and Synovial Biopsy
Arthrocentesis and fluid analysis are often needed to rule out an infectious process, especially in monoarticular arthritis with constitutional symptoms. Synovial fluid analysis reveals a high WBC count (10,000-40,000/µL), most often with polymorphonuclear leukocytes (PMNs) predominating. CH50, C1INH, C4, C5, and C3 levels are elevated. Gram stain and culture results are negative and are necessary to exclude septic arthritis. Microbial components and antigens have been identified in joint fluid using sophisticated laboratory techniques.
PCR assay has been used to detect Chlamydia and Yersinia antigenic DNA in synovial fluid, but these organisms are highly prevalent in the control population, and results have varied considerably from one institution to another. [44] Synovial fluid PCR has led to the detection of bacterial antigenic material in as many as 50% of patients previously diagnosed with undifferentiated spondyloarthropathy. [94]
Synovial biopsy typically yields nonspecific inflammatory changes; infectious antigens have been found in the synovium. Immunohistochemistry (IHC), PCR assay, and molecular hybridization may become more useful.
Other Studies
Antistreptolysin O (ASO) or anti-DNase B testing may be considered if poststreptococcal infection is suspected. [92, 93]
Electrocardiography (ECG) should be performed in patients with a prolonged course of ReA to evaluate for conduction disturbances.
Histologic Findings
Histopathologic findings of the early cutaneous lesions are essentially the same as in psoriasis. Early lesions of keratoderma blennorrhagicum and balanitis circinata feature a spongiform pustule in the upper dermis. Later lesions of keratoderma usually do not contain spongiform pustules but reveal the nonspecific findings of acanthosis, hyperkeratosis, and parakeratosis.
Reiter cells, large macrophages that contain engulfed lymphocytes, PMNs, and, rarely, plasma cells may be observed in synovial fluid. Such cells account for less than 1% of the synovial fluid WBCs. These cells are found in the synovium; however, extensive pannus formation is rare.
-
Balanitis circinata (circinate balanitis) in patient with reactive arthritis.
-
Plaques on soles of patient with reactive arthritis.
-
Painful erosions on fingers in patient with reactive arthritis.
-
Plaques and erosions of tongue in patient with reactive arthritis.
-
Radiograph of feet of 27-year-old man shows erosions in all left metatarsophalangeal (MTP) joints with subluxation and valgus deformity of most toes. Smaller erosions are also visible in fourth and fifth MTP joints of right foot.
-
Lateral radiograph of foot reveals calcaneal spur and enthesitis.
-
Radiograph of both hands shows small erosive changes in both first metacarpal heads associated with minimal subluxation. Bone density is normal.
-
Radiography of pelvis reveals bilateral asymmetric sacroiliitis.
-
Radiograph in 40-year-old man shows nonmarginal syndesmophytes predominantly in lower thoracic and upper lumbar spine.
-
Swelling of right knee with effusion caused by arthritis. Image courtesy of Gun Phongsamart, MD.
-
Remarkable tenderness of left sacroiliac joint caused by sacroiliitis. Image courtesy of Gun Phongsamart, MD.
-
Balanitis circinata (circinate balanitis). Image courtesy of Gun Phongsamart, MD.
-
Achilles tendinitis and swelling of retrocalcaneal bursa.
