Reactive arthritis (ReA), formerly termed Reiter syndrome, is an autoimmune condition that develops in response to an infection. It has been associated with gastrointestinal (GI) infections with Shigella, Salmonella, Campylobacter, and other organisms, as well as with genitourinary (GU) infections (especially with Chlamydia trachomatis). See the image below.
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Painful erosions on fingers in patient with reactive arthritis.
Signs and symptoms
The classic triad of ReA symptoms (found in only one third of patients) consists of the following:
Noninfectious urethritis
Arthritis
Conjunctivitis
In postenteric ReA, diarrhea and dysenteric syndrome (usually mild) is commonly followed by the clinical triad in 1-4 weeks. Some add a fourth component (mucocutaneous findings) to make up a diagnostic tetrad.
The following may be noted:
Acute onset of ReA, with malaise, fatigue, and fever
Asymmetrical, predominantly lower-extremity, oligoarthritis as the major presenting symptom, sometimes with early myalgias
Initial nongonococcal urethritis, with frequency, dysuria, urgency, and urethral discharge
In addition to conjunctivitis, ophthalmologic symptoms that include erythema, burning, tearing, photophobia, pain, and decreased vision (rare)
Mild recurrent abdominal complaints after a precipitating episode of diarrhea
In HIV-positive patients, severe psoriasiform dermatitis, commonly involving the flexures, scalp, palms, and soles
Physical findings in ReA may include the following:
Musculoskeletal system - Asymmetric oligoarthritis affecting the weight-bearing joints, predominantly of the lower extremities; sausage-shaped finger (dactylitis); enthesopathy; sacroiliitis
Skin and nails - Keratoderma blennorrhagicum; erythema nodosum (uncommon); onychodystrophy
GI tract - Diarrhea; abdominal pain; lesions resembling inflammatory bowel disease on ileocolonoscopy
Other systems - Cardiac (aortitis, aortic regurgitation, transient conduction abnormalities, myocarditis, pericarditis); renal (proteinuria, microhematuria, amyloid deposits, immunoglobulin A [IgA] nephropathy)
See Presentation for more detail.
Diagnosis
The diagnosis of ReA is clinical, based on the history and physical examination. No laboratory study or imaging finding is diagnostic.
The following laboratory studies may be helpful:
White blood cell (WBC) and red blood cell (RBC) counts
Erythrocyte sedimentation rate (ESR)
C-reactive protein (CRP) and other acute-phase reactants
IgA antibodies to specific bacterial antigens
Serology and cultures (blood, urine, stool, cervix, urethra), particularly for Chlamydia
Human leukocyte antigen (HLA)–B27
Tuberculin skin test
HIV
Urinalysis
Imaging modalities that may be considered include the following:
Plain radiography (reveals findings in only 40-70% of cases)
Whole-body scintigraphy
Positron emission tomography
Magnetic resonance imaging (MRI), especially of the sacroiliac joints
Computed tomography (CT)
Ultrasonography or echocardiography
Other studies to be considered include the following:
Arthrocentesis, synovial fluid analysis, and synovial biopsy (often needed to rule out an infectious process, especially in monoarticular arthritis with constitutional symptoms)
Antistreptolysin O (ASO) or anti-DNase B testing (if poststreptococcal infection is suspected)
Electrocardiography (ECG; in patients with a prolonged course of ReA)
See Workup for more detail.
Management
No curative treatment exists; instead, treatment aims at relieving symptoms and is based on symptom severity. Almost two thirds of patients have a self-limited course; as many as 30% develop chronic symptoms, posing a therapeutic challenge.
Pharmacologic agents that may be used in treating ReA include the following:
Nonsteroidal anti-inflammatory drugs (NSAIDs) - These are the mainstays of therapy
Corticosteroids (topical, intra-articular, and systemic)
Antibiotics (for Chlamydia-related ReA in particular) - Tetracyclines are commonly given
Disease-modifying antirheumatic drugs (DMARDs) - Typically given when NSAIDs are ineffective or contraindicated, these include sulfasalazine, methotrexate, and anti−tumor necrosis factor (TNF) medications, such as etanercept and infliximab
No specific surgical treatment is indicated, though ophthalmologic surgery may be warranted to treat certain ocular manifestations of disease.
Physical therapy may be instituted to avoid muscle wasting and to reduce pain.
Reactive arthritis (ReA) is an autoimmune condition that develops in response to an infection.[1, 2] ReA has been associated with gastrointestinal (GI) infections with Shigella, Salmonella, Campylobacter, and other organisms, as well as with genitourinary (GU) infections (especially with Chlamydia trachomatis).
ReA was described by the German physician Hans Reiter in 1916,[3] and for a time the disorder was known as Reiter syndrome. This eponym is no longer used, because of Reiter’s activities as a Nazi war criminal, and also because his was not the first description of ReA, and it mischaracterized the pathogenesis.[4, 5]
As currently understood, the term ReA encompasses the older concepts of complete and incomplete reactive arthritis and a clinical syndrome of arthritis with or without extra-articular features that develop within 1 month of infectious diarrhea or GU infection. The classic triad associated with this condition comprises noninfectious urethritis, arthritis, and conjunctivitis (though this triad is not found in all cases).
ReA is frequently associated with the human leukocyte antigen (HLA)–B27 (HLA-B27) haplotype and is classified in the category of seronegative spondyloarthropathies, which includes ankylosing spondylitis, psoriatic arthritis, the arthropathy of associated inflammatory bowel disease, juvenile-onset ankylosing spondylitis, juvenile chronic arthritis, and undifferentiated spondyloarthritis.[6]
A study by Kaarela et al reported that ReA and ankylosing spondylitis appear to be identical.[7] When assessing long-term outcomes of reactive arthritis and ankylosing spondylitis to identify similarities in manifestations of disease, the investigators found a number of similarities. Among these was the determination that sacroiliitis, peripheral arthritis, and iritis developed most often in both chronic ReA and ankylosing spondylitis.
Most ReA patients are young men. Young children tend to have the postdysenteric form, whereas adolescents and young men are most likely to develop ReA after a genitourinary infection. Some authors, interpreting the mucocutaneous findings as pustular psoriasis and the seronegative arthritis as psoriatic arthritis, believe that ReA is best classified as a type of psoriasis.[8]
Defining criteria
The classic triad of ReA—namely, arthritis, conjunctivitis, and noninfectious urethritis—occurs in only about one third of patients at onset. Less stringent diagnostic criteria from the American College of Rheumatology have specified a 1-month duration of arthritis in association with urethritis, cervicitis, or both.
It has been suggested, however, that the syndrome is better described as a triad consisting of arthritis, conjunctivitis or iridocyclitis, and nonbacterial urethritis or cervicitis. Some prefer to describe it as a tetrad, adding the mucocutaneous findings of balanitis circinata and keratoderma blennorrhagicum to the classic triad. In this view, the complete and incomplete forms of ReA can be identified by the presence or absence of the mucocutaneous involvement.
ReA is usually triggered by a GU or GI infection (see Etiology). Evidence indicates that a preceding Chlamydia respiratory infection may also trigger ReA.[9] The frequency of ReA after enteric infection averages 1-4% but varies greatly, even among outbreaks of the same organism. Although severely symptomatic GI infections are associated with an increased risk of ReA,[10, 11] asymptomatic venereal infections more frequently cause this disease.[10] About 10% of patients have no preceding symptomatic infection.
ReA is associated with histocompatibility leukocyte antigen B-27 (HLA-B27), a major histocompatibility complex (MHC) class I molecule involved in T-cell antigen presentation. Results for HLA-B27 are positive in 65-96% of patients (average, 75%) with ReA.[12] Patients with HLA-B27, as well as those with a strong family clustering of the disease, tend to develop more severe and long-term disease.[7]
Sun et al reported that susceptibility to ReA arthritis is affected by the levels of certain killer cell immunoglobulin-like receptors (KIRs), which correspond with specific HLA-C ligand genotypes. In individuals with high levels of activating and low levels of inhibitory KIR signals, pathogens can more easily trigger natural killer cell and T cell innate and adaptive immune responses, resulting in the overproduction of cytokines that contribute to the pathogenesis of ReA.[13]
Their study of 138 patients with ReA found that KIR2DS1, which is activating, is associated with susceptibility to ReA, when present alone or in combination with the HLA-C1C1 genotype. KIR2DL2, which is inhibitory, in combination with the HLA-C1 ligand is associated with protection against ReA. Patients with ReA had significantly lower frequencies of KIR2DL2 and KIR2DL5 than did controls. The presence of more than seven inhibitory KIR genes was protective.[13]
The mechanism by which the interaction of the inciting organism with the host leads to the development of ReA is not known. It is possible that microbial antigens cross-react with self-proteins, stimulating and perpetuating an autoimmune response mediated by type 2 T helper (Th2) cells. Chronicity and joint damage have been associated with a Th2 cytokine profile that leads to decreased bacterial clearance.[10]
Synovial fluid cultures are negative for enteric organisms or Chlamydia species. However, a systemic and intrasynovial immune response to the organisms has been found with intra-articular antibody and bacterial reactive T cells. Furthermore, bacterial antigen has been found in the joints. Thus, the elements for an immune-mediated synovitis are present.
Synovitis in ReA is mediated by proinflammatory cytokines. Native T cells under the influence of transforming growth factor (TGF)-β and other cytokines, such as interleukin (IL)-6, differentiate into Th17 effector cells, which then produce IL-17. IL-17 is one of the major cytokines elevated in the synovial fluid of these patients.[14, 15] Deficiencies in regulatory mechanisms can result in increased proinflammatory cytokine production and worse outcome.[16]
The Toll-like receptors (TLRs) recognize different extracellular antigens as part of the innate immune system.[17] TLR-4 recognizes gram-negative lipopolysaccharide (LPS). Studies in mice and humans showed abnormalities in antigen presentation due to downregulation of TLR-4 costimulatory receptors in patients with ReA. Subsequent studies implicated TLR-2 polymorphism associated with acute ReA; however, its role is still disputed.[10, 18]
Molecular evidence of bacterial DNA (obtained via polymerase chain reaction [PCR] assay) in synovial fluids has been found only in Chlamydia -related ReA, and a single placebo-controlled trial of a tetracycline derivative (ie, lymecycline) has shown a reduction in the duration of acute Chlamydia -related, but not enteric-related, ReA.[19] This suggests that persistent infection may play a role, at least in some cases of chlamydial-associated ReA.
In a subsequent trial, the combination of doxycycline and rifampin was superior to doxycycline alone in reducing morning stiffness and swollen and tender joints in patients with undifferentiated spondyloarthropathy.[20]
The role of HLA-B27 in this scenario remains to be fully defined. The following theories have been proposed:
Molecular mimicry - This hypothesis suggests that a similarity exists at the molecular level between the HLA-B27 molecule and the inciting organisms, allowing the triggering of an immune response and the subsequent development of clinical disease[21]
HLA-B27 as a receptor for certain bacteria - At present, there is little evidence either to confirm or to refute this hypothesis
Defective class I antigen-mediated cellular response - This hypothesis suggests that the HLA-B27 molecule may be a defective molecule associated with an aberrant cytotoxic T-cell response
ReA can occur in patients with HIV infection or AIDS—most likely because both conditions can be sexually acquired, rather than because ReA is triggered by HIV. The course of ReA in these patients tends to be severe, with a generalized rash resembling psoriasis, profound arthritis, and frank AIDS. HLA-B27 frequency is the same as that associated with non–AIDS-related ReA in a similar demographic group. This association points out the likely importance of CD8+ cytotoxic T cells as compared with CD4+ Th cells in the pathogenesis of ReA.
ReA is sometimes divided into epidemic and endemic forms. Whereas a triggering agent can be identified for epidemic ReA, none has been identified for endemic ReA. Differentiation between the 2 types of ReA may be difficult in some cases; however, it is not essential to either diagnosis or treatment.
ReA is usually triggered by a GU or GI infection and thus is sometimes classified as venereal or dysenteric. Such infections are mostly the result of gram-negative, obligate, or facultative intracellular pathogens.[22] Organisms that have been associated with ReA include the following:
C trachomatis/C pneumoniae[23]
Ureaplasma urealyticum
Lymphogranuloma venereum (L2 serotype)[24, 25]
Neisseria gonorrhoeae
Shigella flexneri
Salmonella enterica serovars Typhimurium, Enteritidis,[26] and Hadar[27]
Mycoplasma pneumoniae
Mycobacterium tuberculosis[28]
Cyclospora[29]
Yersinia enterocolitica and pseudotuberculosis
Campylobacter jejuni[30] and coli
Clostridium difficile
Beta-hemolytic[16] (eg, group A[31] ) and viridans streptococci
Data suggest that chlamydial ReA is underdiagnosed and that asymptomatic chlamydial infections might be a common cause.[32] An important difference between Chlamydia -induced (postvenereal) ReA and postenteric ReA is the presence of viable but aberrant chlamydial organisms in the synovial fluid[33] (so-called Chlamydia persistence[34] ). PCR assay to detect C trachomatis DNA in synovial samples may be a good method for establishing the diagnosis of Chlamydia -induced arthritis in patients with ReA.[35]
The prevalence of different serotypes of C trachomatis antibodies and the incidence of Chlamydia- induced ReA was studied among patients with early arthritis in a defined population in Finland.[12] Antibodies against C trachomatis were most common in patients with arthritis because cases with Chlamydia -induced ReA are included in this subgroup.
Ureaplasma organisms are known to be capable of causing experimental and clinical nongonococcal urethritis. Synovial mononuclear cells from arthritic joints of patients with ReA react with Ureaplasma antigens; this organism has been isolated from an ReA patient.
The enteric pathogen that most commonly results in ReA is Campylobacter (C jejuni, 90-95%; C coli, 5-10%).[36] ReA patients with arthritic symptoms are more frequently infected with C jejuni strains with sialic acid lipo-oligosaccharide. In addition, sialylation of C jejuni lipo-oligosaccharide is associated with more severe enteric disease.[37]
Group A streptococci are known to be capable of causing poststreptococcal ReA.[38] Patients with this condition demonstrate increase antistreptolysin O (ASO) antibodies and an increased erythrocyte sedimentation rate (ESR).[39] ReA can also be induced by tonsillitis. In one study, 13 of 21 patients were positive for ASO and 12 were positive for group A Streptococcus.[40]
Acute tuberculosis can sometimes cause ReA. The resulting condition is known as Poncet disease, which is a different entity from tuberculous arthritis.[41, 42, 43]
ReA following infection with C difficile has been reported.[44, 45] Intravesical instillation of bacillus Calmette-Guérin (BCG) for bladder cancer has been associated with ReA.[46, 47, 48] has also been shown to occur after tetanus and rabies vaccination.[49, 50]
Genetic factors
ReA has an important genetic component; it tends to cluster in certain families and almost exclusively affects males, and HLA-B27 is identified in 70-80% of patients.[12] HLA-B27 may share molecular characteristics with bacterial epitopes, facilitating an autoimmune cross-reaction instrumental in pathogenesis. HLA-B27 contributes to the pathogenesis of the disease and reportedly increases the risk of ReA 50-fold.[51] HLA-B51 and HLA-DRB1 alleles have also been shown to be associated with ReA.[35]
Rihl et al found a high proportion of proangiogenic factors accounting for a genetically determined susceptibility to ReA.[52] Sun et al reported increased susceptibility to ReA associated with the HLA-C1C1 genotype, which indicates the absence of the HLA ligands for the inhibitory killer cell immunoglobulin-like receptor (KIR) KIR2DL1; Imbalance between activating and inhibitory KIR signals may allow pathogens to trigger cytokine overproduction.[13]
Other factors
ReA triggered by adalimumab and leflunomide in a patient with ankylosing spondyloarthropathy and Crohn disease has been described.[53]
Duration of diarrhea and weight loss are also considered risk factors in the development of ReA after enteric infections.[11]
Data on the incidence and prevalence of ReA are scarce, partly because of a lack of a disease definition and classification criteria; these factors complicate differentiation of ReA from other arthritides.[54] The frequency is estimated to be 3.5-5 cases per 100,000. The incidence reported in US Navy personnel over a 10-year period was 4 cases per 100,000 men per year. The prevalence of ReA may be relatively high among patients with AIDS, especially men who are seropositive for HLA-B27. ReA develops in almost 75% of HIV-positive men with HLA-B27.
An estimated 1-3% of all patients with a nonspecific urethritis develop an episode of arthritis. The incidence is 1-4% after enteric infection. This number jumps to 20-25% after bacterial enteritis in HLA-B27-positive individuals.[36] Prevalence of asymptomatic chlamydial infections, underdiagnosis, and underreporting may make the incidence even higher.[55] It has been noted that worse functional capacity and higher disease activity are observed in the lower socioeconomic classes.[56]
A population-based study assessed ReA after culture-confirmed infections with bacterial enteric pathogens in Minnesota and Oregon.[57] The estimated incidence after culture-confirmed Campylobacter, Escherichia coli O157, Salmonella, Shigella, and Yersinia infections in Oregon was 0.6-3.1 cases per 100,000 population. ReA may occur in 1.5% of Shigella enterocolitis cases and 25% of HLA-B27–positive Shigella cases. After an outbreak of S enterica serovar Enteritidis, 29% had reactive arthritis.[26]
International statistics
The infections that incite ReA may vary with geographic location. For example, Y enterocolitica is more commonly identified in Europe than in North America and thus is responsible for more cases of ReA in countries such as Finland and Norway.[10] The occurrence of ReA appears to be related to the prevalence of HLA-B27 in a population and to the rate of urethritis/cervicitis and infectious diarrhea.
More than 40 subtypes of HLA-B27 are known; those associated with the spondyloarthropathies are HLA-B2702, B2704, and B2705.[22] These subtypes may be somewhat geographically segregated. For example, the subtype B2705 is found predominantly in Latin America, Brazil, Taiwan, and parts of India. It is noteworthy that subtypes HLA-B2706 and B2709—found in native Indonesia and Sardinia, respectively—may be partially protective against ReA.[58]
In Norway, an annual incidence of 4.6 cases per 100,000 population for chlamydial ReA and an incidence of 5 cases per 100,000 population for enteric bacteria–induced ReA were reported in 1988-1990. In Finland, nearly 2% of males were found to have ReA after nongonococcal urethritis; the incidence of HLA-B27 is higher in the Finnish population. In the United Kingdom, the incidence of ReA after urethritis is about 0.8%. In the Czech Republic, the annual incidence of ReA in adults during 2002-2003 was reported at 9.3 cases per 100,000 population.[59]
Age-, sex-, and race-related demographics
ReA is most common in young men, with the peak onset in the third decade of life. It rarely occurs in children; when it does, the enteric form of the disease is predominant. Most pediatric patients present with symptoms after the age of 9 years.[46]
In a study of 100 patients with ReA, Lahu and colleagues found that most patients were between 20 and 40 years old and that the first attack occurred earlier in males than females. Of the 100 patients studied, 66% were male. Urogenital and nasopharyngeal infections were more common among male patients.[60]
ReA after foodborne enteric infections is equally common in males and females. However, the male-to-female ratio for disease associated with venereally acquired infections has been estimated to range from 5:1 to 10:1. A possible prostatic focus of persistent infection is postulated to explain the male predominance of ReA.
The frequency of ReA appears to be related to the prevalence of HLA-B27 in the population. As with other spondyloarthropathies, HLA-B27 and ReA are more common in white people than in black people. When ReA occurs in black persons, it is frequently B27-negative.
ReA has a variable natural history[55] but typically follows a self-limited course, with resolution of symptoms by 3-12 months, even in patients who are acutely incapacitated. A fatal outcome is seldom reported, but death can occur, and it is usually related to the adverse effects of treatment. Postdysenteric cases are associated with a better prognosis than postvenereal cases. The presence of HLA-B27 may predict a more prolonged course and severe outcome, as may infections triggered by Yersinia, Salmonella, Shigella, or Chlamydia.[61]
ReA has a high tendency to recur (15-50% of cases), particularly in individuals who are HLA-B27–positive. A new infection or other stress factor could cause reactivation of the disease.
Approximately 15-30% of patients with ReA develop a long-term, sometimes destructive, arthritis or enthesitis or spondylitis. A 1994 study analyzed 7 factors as predictors of long-term outcome in spondyloarthropathies.[62] The number of patients with ReA in this study was low, and a valid subgroup analysis was impossible. The presence of hip-joint involvement, an ESR higher than 30, and unresponsiveness to nonsteroidal anti-inflammatory drugs (NSAIDs) probably portend a severe outcome or chronicity in ReA.
Poor health-related quality of life and impaired daily physical functioning are observed in patients with refractory or chronic ReA, and strategies focused on improving or maintaining functional status are important in treatment.[18] Educational measures that may be helpful include the following:
Encourage patients to monitor themselves for any changes in symptoms.
Help patients to become awareness of the chronic or recurrent nature of this syndrome and to accept the need for long-term medications
Inform patients that their condition places them at a higher than usual risk for elective ocular surgery
Discourage inactivity and immobilization
Encourage stretching exercises and range of motion
Provide adolescent patients with information on the prevention of sexually transmitted diseases and the use of condoms
For patient education resources, see the Arthritis Center, the Sexually Transmitted Diseases Center, and the Bacterial and Viral Infections Center, as well as Knee Pain, Chlamydia, and Gonorrhea. The American College of Rheumatology also provides patient information on reactive arthritis.
Reactive arthritis (ReA) usually develops 2-4 weeks after a genitourinary (GU) or gastrointestinal (GI) infection (or, possibly, a chlamydial respiratory infection[9] ). About 10% of patients do not have a preceding symptomatic infection. The classic triad of symptoms—noninfectious urethritis, arthritis, and conjunctivitis—is found in only one third of patients with ReA and has a sensitivity of 50.6% and a specificity of 98.9%.[63] In postenteric ReA, diarrhea and dysenteric syndrome (usually mild) is commonly followed by the clinical triad in 1-4 weeks.
In a large percentage of ReA cases, conjunctivitis or urethritis occurred weeks before the patient seeks medical attention. Patients may fail to mention this unless specifically asked. Musculoskeletal disease is evident in many of these patients.[64] Vague, seemingly unrelated complaints may obscure this diagnosis at times.[65]
The onset of ReA is usually acute and characterized by malaise, fatigue, and fever. An asymmetrical, predominantly lower-extremity, oligoarthritis is the major presenting symptom. Myalgias may be noted early on. Asymmetric arthralgia and joint stiffness, primarily involving the knees, ankles, and feet (the wrists may be an early target), may be noted. Low-back pain occurs in 50% of patients.[63] Heel pain associated with Achilles enthesopathies and plantar fasciitis is also common.
Both postvenereal and postenteric forms of ReA may manifest initially as nongonococcal urethritis, with frequency, dysuria, urgency, and urethral discharge; this urethritis may be mild or inapparent. Urogenital symptoms, whether resulting from GU infection or from GI infection, are found in 90% of patients with ReA.[63]
An estimated 0.5-1% of cases of urethritis evolve into ReA. Urethritis develops acutely 1-2 weeks after infection through sexual contact and is similar to gonococcal urethritis. A purulent or hemopurulent exudate appears, and the patient complains of dysuria.
In men, chlamydial urethritis is less painful and produces less purulent discharge than acute gonorrhea does, making it difficult to notice. Findings from microscopic examination and cultures can be used to rule out Neisseria gonorrhoeae infection. Coinfection with Chlamydia and Neisseria organisms is common in some areas. In women, urethritis and cervicitis may be mild, with dysuria or slight vaginal discharge, or asymptomatic, which makes diagnosis difficult.
Often, the initial urethritis is treated with antibiotics (especially wide-spectrum tetracyclines or macrolides) when findings suggest gonorrhea. Despite an apparent early cure, the manifestations of the disease appear several weeks later, and the patient may not relate them to a previous episode of urethritis.
Lymphogranuloma venereum infection may be asymptomatic; screening should be considered in all men who have sex with men (MSM) presenting with acute arthritis, particularly if they are infected with HIV.[66]
In addition to conjunctivitis, ophthalmologic symptoms of ReA include erythema, burning, tearing, photophobia, pain, and decreased vision (rare).
Patients may have mild recurrent abdominal complaints after a precipitating episode of diarrhea.
Association with HIV infection
ReA is particularly common in the context of HIV infection.[67, 68] Accordingly, patients with new-onset ReA must be evaluated for HIV. The existing immunodepression in patients with AIDS poses special management problems.
HIV-positive ReA patients are at risk for severe psoriasiform dermatitis, which commonly involves the flexures, scalp, palms, and soles. Frequently, psoriasiform dermatitis is associated with arthritis that involves the distal joints in a destructive pattern. The disturbances of immune homeostasis in AIDS could account for this peculiar expression of psoriasis in these patients.
Physical findings in ReA may involve the musculoskeletal system, the skin and nails, the eyes, the GU tract, the GI tract, and other systems (see below).
A scoring system for diagnostic points in ReA-like spondyloarthropathies exists. In this system, the presence of 2 or more of the following points (1 of which must pertain to the musculoskeletal system) establishes the diagnosis:
Asymmetric oligoarthritis, predominantly of the lower extremity[69]
Sausage-shaped finger (dactylitis),[63] toe or heel pain, or other enthesitis
Cervicitis or acute diarrhea within 1 month of the onset of arthritis
Conjunctivitis or iritis
Genital ulceration or urethritis
Joints, axial skeleton, and entheses
Articular involvement in ReA is typically asymmetric and usually affects the weight-bearing joints (ie, knees, ankles, and hips), but the shoulders, wrists, and elbows may also be affected. In more chronic and severe cases, the small joints of the hands and feet may be involved as well. Dactylitis (ie, sausage digits) may develop. In children, joint involvement is oligoarticular in 69% of cases, polyarticular in 27%, and monoarticular in 4%.
Joints are commonly described as tender, warm, swollen (see the image below), and, sometimes, red. Symptoms may occur initially or several weeks after onset of other symptoms. Migratory or symmetric involvement is also reported. Periostitis and tendinitis may occur, especially involving the Achilles tendon, which produces pain in the heel. The arthritis is usually remittent and rarely leads to severe limitation of functional capacity. Muscular atrophy can develop in severely symptomatic cases.
View Image
Swelling of right knee with effusion caused by arthritis. Image courtesy of Gun Phongsamart, MD.
Enthesopathy, or enthesitis (ie, inflammation of ligament and tendon insertions into bone), is thought to be a characteristic feature of ReA. The Achilles insertion is the most common site; other sites include the plantar fascial insertion on the calcaneus, ischial tuberosities, iliac crests, tibial tuberosities, and ribs.
Sacroiliitis (see the image below) frequently occurs in adults who are positive for human leukocyte antigen (HLA)–B27 (though it is apparently less common in children). It is typically self-limiting. Whereas 50% of patients with ReA may develop low-back pain, most physical examination findings in patients with acute disease are minimal except for decreased lumbar flexion. Patients with more chronic and severe axial disease may develop physical findings similar to, or even indistinguishable from, those of ankylosing spondylitis.
View Image
Remarkable tenderness of left sacroiliac joint caused by sacroiliitis. Image courtesy of Gun Phongsamart, MD.
Skin and nails
Skin and mucocutaneous lesions are commonly observed in ReA. The dermal lesions are typified by keratoderma blennorrhagicum,[63] in which hyperkeratotic skin begins as clear vesicles on erythematous bases and progresses to macules, papules, and nodules—found on the soles of the feet (see the image below), palms, scrotum, trunk, or scalp—and eventually coalescing to form a hyperkeratotic erythematous dermatitis resembling pustular psoriasis.[51]
View Image
Plaques on soles of patient with reactive arthritis.
Distal involvement with painful and erosive lesions in the tips of the fingers (see the image below) and toes, with pustules and subungual pustular collections, also occurs.
View Image
Painful erosions on fingers in patient with reactive arthritis.
In some patients, typical keratoderma blennorrhagicum develops 1-2 months after the onset of arthritis, with keratotic papules and plaques that are painful under pressure; sometimes, these can be disabling.
Erythematous macules and plaques, diffuse erythema, erosions, and bleeding can appear on the oral and pharyngeal mucosae in 30-60% of patients.[63] Circinate lesions on the tongue resemble geographic tongue (see the image below).
View Image
Plaques and erosions of tongue in patient with reactive arthritis.
Erythema nodosum may develop but is uncommon.
Nail dystrophy is present in 20-30% of patients. The nails can become thickened and ridged and may crumble, in a manner resembling mycotic infection or psoriatic onychodystrophy, but nail pitting is not observed. Nail shedding is common.
Eyes
Conjunctivitis is a component of the original triad and is one of the hallmarks of the disease, reported to appear in 33-100% of patients. It tends to occur early in the disease, especially during the initial attack; it may be missed if patients are seen only during subsequent attacks.
An intense red, velvetlike conjunctival injection characterizes the conjunctivitis. Bilateral involvement is common. Edema and a purulent discharge are not rare. The conjunctivitis may be mild and painless or may cause severe symptoms with blepharospasm and photophobia. It usually resolves spontaneously within 2 weeks.
Anterior uveitis (including iritis, iridocyclitis, or cyclitis) is the second most common ocular finding. Iridocyclitis may be the initial ocular manifestation in some patients. Uveitis may occur in 12-37%[63] (or possibly as many as 50%) of patients with ReA and is more frequently found in patients with HLA-B27 and those with sacroiliitis. At clinical examination, redness, pain, impaired vision, and exudation with hypopyon can suggest iritis. Rarely, an ReA patient may have permanent visual loss from macular infarction or foveal scarring.[70]
A particularly serious ocular manifestation is recurrent nongranulomatous iridocyclitis. Recurrences are usually associated with an acute iridocyclitis that has a rapid onset with conjunctival and episcleral edema and injection. The corneal endothelium has cellular debris and poorly defined, small- to medium-sized keratic precipitates. Heavy flare and cells and a very early tendency toward formation of posterior synechiae are characteristic, more so than in most other forms of acute iridocyclitis.
Even the most aggressive pupil-dilation management is sometimes inadequate to prevent synechiae formation. A peripheral iridectomy may be necessary to prevent iris bombé and angle closure if the synechiae cannot be broken.
Heavy flare is sometimes so plasmoid that cells are immobile, and a fibrinlike clot may be seen in the pupillary opening as the inflammation resolves. An acute hypopyon may occur. Cells and inflammatory debris may be seen in the vitreous, and blurring of the disc margins and macular edema may occur with severe or prolonged episodes. Spillover vitreitis may be more common in patients with reactive arthritis than those with ankylosing spondylitis.
Other ocular findings that may be noted in ReA include the following:
Scleritis
Episcleritis
Keratitis - Rarely (4% of cases), patients may develop a punctate epithelial keratitis that may lead to central loss of the corneal epithelium and subepithelial infiltrates[71]
Cataracts - Lens clouding and posterior subcapsular cataracts occur with prolonged or repeated episodes
Hypotony - This may occur after a severe or prolonged course and may persist after resolution
Glaucoma - Secondary open-angle glaucoma may occur because of the anterior chamber reaction and the trabecular obstruction or trabeculitis; it usually resolves with aggressive anti-inflammatory therapy; with repeated recurrences, damage to the trabecular meshwork may occur, resulting in secondary glaucoma
Corneal ulceration
Disc or retinal edema
Retinal vasculitis
Optic neuritis
Dacryoadenitis (occurs rarely in the setting of chlamydial urethritis)[72]
Genitourinary tract
Urogenital symptoms may be primary or postdysenteric and may include the following[63] :
Meatal edema and erythema and clear mucoid discharge
Prostatitis causing tenderness (up to 80%) and vulvovaginitis
Circinate balanitis (balanitis circinata)
Cervicitis
Cystitis
Salpingo-oophoritis
Circinate balanitis, consisting of small shallow painless ulcers of the urethral meatus or the glans penis (see the images below), is characteristic. The condition is characterized by circinate or gyrate white plaques that grow centrifugally and eventually cover the entire surface of the glans penis. The penile shaft and scrotum can be involved. On an uncircumcised penis, the lesions typically remain moist; on a circumcised penis, they may harden and crust, causing pain and scarring in 50% of patients.[63]
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Balanitis circinata (circinate balanitis) in patient with reactive arthritis.
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Balanitis circinata (circinate balanitis). Image courtesy of Gun Phongsamart, MD.
Circinate vulvitis is reported in women. Balanitis and vulvitis are rare in children; when they occur, they are suggestive of ReA.[73]
Prostatitis, cystitis, and pyelonephritis are rare but possible urogenital manifestations of reactive arthritis. Bartholinitis can be present in women. Proctitis caused by Chlamydia species can occur in both sexes after anal intercourse.
Urethritis is difficult to diagnose in children but is present in 30% of pediatric patients at onset. Obtaining a history of dysuria from children is difficult, possibly because the urinary abnormality is mild or absent. In patients with painless discharge, staining of the underpants may be evident. The recommended procedure is to obtain a detailed history and perform a careful clinical evaluation for urethritis, searching for pyuria, meatal inflammation, and small perimeatal ulcerations.
Gastrointestinal tract
Enteric infections may trigger ReA. Pathogens include Salmonella, Shigella, Yersinia, and Campylobacter species. The frequency of ReA after these enteric infections is about 1%-4%. Other enteric bacteria that have been associated with ReA include C difficile,[74] E coli, and Helicobacter pylori.[14] (See Etiology.)
Some patients with ReA continue with intermittent bouts of diarrhea and abdominal pain. Lesions resembling ulcerative colitis or Crohn disease have been described when ileocolonoscopy is performed in patients with established ReA.[74] Although enteritis is usually a prolonged diarrheal episode with frequent passage of bloody loose stools, it can also manifest as a 24-hour episode of increased bowel activity.
Other findings
Aortic regurgitation caused by inflammation of aortic wall and valve may occur. This proximal aortitis can be found in 1-2% of cases.[51] Aortitis may be accompanied by coronary inflammation, which can be fatal in rare cases. Transient conduction abnormalities may develop but are of little significance; rarely, patients may be affected by myocarditis or pericarditis.[51]
Other manifestations of ReA include mild renal pathology with proteinuria and microhematuria. In severe chronic cases, amyloid deposits and immunoglobulin A (IgA) nephropathy have been reported in association with reactive arthritis.[75] IgA nephropathy is the most common type of primary glomerulonephritis worldwide.
Ankylosing spondylitis (30-50% of HLA-B27–positive patients)
Urethral stricture
Aortic root necrosis
Secondary glaucoma
Cataracts
Cystoid macular edema
Posterior and anterior synechiae
Cyclitic membrane
Vitreous opacification
Ankylosing spondylitis, psoriatic arthritis, and sacroiliitis
Erythroderma (rare)
In severe cases, functional impairment may be severe, and a chronic and prolonged clinical course is followed by sequelae (eg, urethral stenosis, chronic arthritis, or ocular impairment).
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.
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.[58] 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).[12]
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.[78] 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.[55]
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.[79]
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.[80] 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.
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).
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Radiograph of feet of 27-year-old man shows erosions in all left metatarsophalangeal (MTP) joints with subluxation and valgus deformity of most toes. ....
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Lateral radiograph of foot reveals calcaneal spur and enthesitis.
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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.
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Radiography of pelvis reveals bilateral asymmetric sacroiliitis.
Syndesmophytes are asymmetric, paravertebral, bulky, discontinuous, comma-shaped ossifications that most commonly involve the lower thoracic and upper lumbar vertebrae (see the image below).
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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.
Whole-body scintigraphy is a sensible diagnostic tool for use in screening for enthesopathy and arthropathy.[81]
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.[82]
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.
Ultrasonography may reveal enthesitis (as periosteal reaction and tendinosis) more accurately that physical examination would.[51, 47] Echocardiography may reveal carditis or valvular dysfunction in patients with poststreptococcal ReA.[83, 84]
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.[36] Synovial fluid PCR has led to the detection of bacterial antigenic material in as many as 50% of patients previously diagnosed with undifferentiated spondyloarthropathy.[85]
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.
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.
No curative treatment for reactive arthritis (ReA) exists. Instead, treatment aims at relieving symptoms and is based on symptom severity. Almost two thirds of patients have a self-limited course and need no treatment other than symptomatic and supportive care. As many as 30% of patients develop chronic symptoms, posing a therapeutic challenge.[86]
Physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), and intralesional corticosteroids may be helpful for joint, tendon, and fascial inflammation. Low-dose prednisone may be prescribed, but prolonged treatment is not advisable. Antibiotics may be given to treat underlying infection. Disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine and methotrexate may be used safely and are often beneficial. No specific surgical treatment is indicated.
Hospitalization of a patient with uncomplicated ReA is not usually indicated. Inpatient care may be considered for patients who are unable to tolerate oral administration of medications, who are unable to ambulate because of significant joint involvement, who have intractable pain, or who have concomitant disease necessitating admission.
Few treatment options exist for HIV-infected patients with severe ReA. Treatment of ReA in the setting of HIV infection poses special problems. However, potentially immunosuppressive therapies (eg, cyclosporine, methotrexate, and psoralen plus ultraviolet A [PUVA]) have been used in some cases, with variable success and relatively few severe complications. A case report from the United Kingdom suggests that antiretroviral therapy may be considered in HIV-infected ReA patients who are unresponsive to standard therapy.[87]
No dietary limitations are necessary unless the patient is receiving steroid therapy. Efforts should be made to maintain joint function with physical activity, joint protection, and suppression of inflammation. Physical therapy may be instituted to avoid muscle wasting and to reduce pain in severe cases. Although no limitations on physical activity need be imposed, symptoms of arthritis will usually limit patients’ activity to some extent.
NSAIDs (eg, indomethacin and naproxen) are the foundation of therapy for ReA.[88] Etretinate/acitretin has been shown to decrease the required dosage of NSAIDs.[63] Sulfasalazine or methotrexate may be used for patients who do not experience relief with NSAIDs after 1 month or who have contraindications to NSAIDs. In addition, sulfasalazine-resistant ReA may be successfully treated with methotrexate.[89]
In a series of 22 pediatric ReA patients from the Republic of China, NSAIDs and sulfasalazine were the mainstays of treatment, with cyclophosphamide used in 14 patients and methotrexate and corticosteroids added in a few.[90] Most achieved full remission within 6 months.
Antibiotic treatment is indicated for cervicitis or urethritis but generally not for postdysenteric ReA. In Chlamydia-induced ReA, some data suggest that prolonged combination antibiotic therapy could be an effective treatment strategy.[34]
Case reports exist that demonstrate the effectiveness of anti−tumor necrosis factor (TNF) medications,[51, 91] such as etanercept and infliximab.[92, 61] No published data are available on the effectiveness of selective cyclooxygenase (COX)–2 inhibitors; however, a COX-2 inhibitor may be tried in patients who do not tolerate NSAIDs and in whom no preexisting contraindication to COX-2 use exists.
Symptom-specific approaches
Arthritis and enthesitis
Joint symptoms are best treated with aspirin or other short-acting and long-acting anti-inflammatory drugs (eg, indomethacin, naproxen). In one report, a patient became asymptomatic after 3 months of aspirin at a dosage of 80 mg/kg/day; the dosage was gradually reduced and eventually discontinued. A combination of NSAIDs is reportedly effective in severe cases. No published data suggest that any NSAID is more effective or less toxic than another (controlled treatment trials are difficult to conduct with an uncommon disease).
Varying success in treating severe cases of ReA with other medications (eg, sulfasalazine, methotrexate, etretinate, ketoconazole, azathioprine, or intra-articular steroid injections) has been reported. In a refractory case or a patient with HIV-associated ReA, the anti−TNF-α agent infliximab may be successful.[93] Depending on the culture results, a short course of antibiotics may be needed; however, treatment may not affect the disease course. Longer-term administration of antibiotics to treat joint symptoms provides no established benefits.
Conjunctivitis and uveitis
Transient and mild conjunctivitis is usually not treated. Mydriatics and cycloplegics (eg, atropine) with topical corticosteroids may be administered in patients with acute anterior uveitis. Patients with recurrent ocular involvement may require systemic corticosteroid therapy and immunomodulators to preserve vision and prevent ocular morbidity.[94]
Urethritis and gastroenteritis
Antibiotics may be considered for urethritis and gastroenteritis, depending on the cultures used and their sensitivity. In general, urethritis may be treated with a 7- to 10-day course of erythromycin or tetracycline. Antibiotic treatment of enteritis is controversial.
Mucocutaneous lesions
Only local care is necessary for mucosal lesions. Topical steroids may be needed for psoriasiform lesions; the use of hydrocortisone or triamcinolone may be beneficial. A topical keratolytic, such as 10% salicylic acid ointment, can be added if needed. Topical salicylic acid and hydrocortisone with oral aspirin has also been suggested.[73]
Hydrocortisone 2.5% cream and salicylic acid 10% ointment are effective in treating chronic keratoderma blennorrhagicum and circinate balanitis, though either condition may heal without medical treatment. Circinate balanitis usually responds to topical steroids; however, it can be recurrent and create a therapeutic challenge. Balanitis refractory to conventional therapy can be successfully treated with the complementary use of topical 0.1% tacrolimus.[20]
Systemic therapy, if required, consists of the administration of oral acitretin, PUVA, methotrexate, cyclosporine, or some combination thereof.
Nonsteroidal anti-inflammatory drugs
The choice of a specific NSAID depends on the individual response to treatment. Phenylbutazone may work in patients refractive to other NSAIDs. These agents should be used regularly to achieve a good anti-inflammatory effect. Patients must be instructed on compliance and the possible need to adjust the dosage or switch to another agent. Treatment must be continued for 1 month at maximum dosage before effectiveness can be fully evaluated.
NSAIDs may reduce the intensity and the frequency of recurrences of ocular inflammation and allow a decrease in the corticosteroid dosage, which helps decrease the chances of cataract formation and other associated corticosteroid effects.
The decreased awareness of pain sometimes seen with the use of NSAIDs may alter the patient’s recognition of recurrences. Patients should be examined whenever any change in symptoms occurs to evaluate for recurrence of an acute episode of inflammation. Ocular involvement may parallel systemic and joint disease relapses.
Corticosteroids
Corticosteroids may be given either via intra-articular injection or as systemic therapy. For ocular manifestations of ReA, they may also be given topically.
Joint injections can produce long-lasting symptomatic improvement and help avoid the use of systemic therapy. Sacroiliac joints can be injected, usually under fluoroscopic guidance.[95]
Systemic corticosteroids may be particularly useful in patients who do not respond well to NSAIDs or who experience adverse effects related to the use of NSAIDs. The starting dose is guided by a patient’s symptoms and objective evidence of inflammation. Prednisone can be used initially at a dosage of 0.5-1 mg/kg/day, tapered according to response.
Topical corticosteroids and mydriatics should be used early and aggressively to reduce tissue damage. Prolonged topical treatment is necessary for several weeks after the inflammation has cleared; early withdrawal of topical corticosteroids frequently results in the return of inflammatory changes. Keratolytics or topical corticosteroids may improve cutaneous lesions. Topical corticosteroids may be useful for iridocyclitis.
Antibiotics
The current view of the pathogenesis of ReA indicates 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 ReA are lacking.
However, in Chlamydia -induced ReA, studies have suggested that appropriate treatment of the acute genitourinary (GU) infection can prevent ReA and that treatment of acute ReA with a 3-month course of tetracycline reduces the duration of illness. Empiric antibiotics may be considered after appropriate cultures have been taken. Nongonococcal urethritis and other infections can be treated specifically with systemic antibiotics. In the absence of contraindications, treatment of urethritis is recommended, even if improvement is not certain.
Although urethritis and cervicitis are commonly treated with antibiotics, diarrhea generally is not. No evidence indicates that antibiotic therapy benefits enteric-related ReA or chronic ReA of any cause.
Long-term antibiotic therapy may be warranted in cases of poststreptococcal ReA; however, this is currently a controversial topic.[83, 84]
Lymecycline (a tetracycline available outside the United States) was studied in a double-blind placebo-controlled study of patients with chronic ReA for a treatment period of 3 months.[19] The duration of illness was significantly shorter in patients with Chlamydia -induced disease than in those with disease triggered by enteric infections.
Azithromycin was shown to be ineffective in a placebo-controlled trial.[96] Nevertheless, in another study, azithromycin or doxycycline in combination with rifampin for 6 months was reported to be significantly superior to placebo and significantly improved symptoms associated with Chlamydia-induced ReA.[97]
Quinolones have been studied because of their broad coverage, but no clear benefit has been reported.[98] In a randomized, double-blind, placebo-controlled study of 56 patients with recent-onset ReA, 3 months of treatment with a combination of ofloxacin and roxithromycin was not better than placebo in improving outcomes.
More studies are needed before definite recommendations can be made for the role of antibiotics in the management of ReA.[99]
Disease-modifying antirheumatic drugs
In patients who have chronic symptoms or have persistent inflammation despite the use of the agents mentioned above, other second-line drugs may be used. Clinical experience with these DMARDs has been mostly in rheumatoid arthritis and in psoriatic arthritis. However, DMARDs have also been used in ReA, though their disease-modifying effects in this setting are uncertain.
Sulfasalazine has been shown to be beneficial in some patients. The use of this drug in ReA 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 placebo to treat spondyloarthropathies, patients with ReA who were taking sulfasalazine had a 62.3% response rate, compared with a 47.7% rate for the placebo group in peripheral arthritis.[100]
Methotrexate may 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 ReA, but again, large studies have not been published.[101, 102] Patients with ReA who have HIV infection or AIDS should not receive methotrexate or other immunosuppressive agents.
Case reports have demonstrated the effectiveness of anti-TNF medications, such as etanercept and infliximab,[51, 91, 93, 103] though there remains a need for randomized, double-blind trials. The high concentrations of TNF-α in the serum and joints of patients with persistent ReA suggest that this cytokine could be targeted in patients who do not respond to NSAIDS and DMARDs. Anti−TNF-α therapy has been demonstrated to be effective treatment for ReA, with a corticosteroid-sparing effect.[104]
However, TNF-α antagonists can increase the risk of serious infection, and it is important to conduct infectious screening and monitoring with a high index of suspicion, as well as preemptive treatment, when such medications are used.[3] Anti-TNF medications can also be associated with severe glomerulonephritis, and it is recommended that renal function be closely monitored in patients treated with these agents.[9]
Interleukin (IL)-6 plays an important role in regulating immune response. Unregulated overproduction of IL-6, however, is pathologically involved in various immune-mediated inflammatory diseases, including ReA. Tocilizumab, a humanized anti–IL-6 receptor antibody, may provide clinical benefit in patients who are refractory to conventional therapy or anti-TNF therapy.[105] However, further clinical studies are required.
No surgical therapy for ReA is recommended. However, surgical intervention may be warranted for certain ocular manifestations of the disease.
The posterior spillover of inflammatory material in the chronic iridocyclitis associated with ReA may result in persistent vitreous opacification. The cumulative effects of secondary involvement of the vitreous may result in visually disabling vitreous debris and opacification, making these eyes good candidates for vitrectomy. Although vitrectomy should be considered only after prolonged follow-up care and thorough planning, it appears to offer a definitive improvement in vision in certain cases.
Because of the intense episodes of recurrent inflammation, it is essential to render the eyes as quiet as possible before surgery by using topical, periocular, or systemic corticosteroids. At least 3 months of cell-free slit lamp examinations—6 months for younger patients and severe cases—should be documented before elective surgical intervention.
Preoperative ultrasonography is helpful in determining the degree of vitreous opacification, the thickening of the choroid, and the presence of a cyclitic membrane, which can create significant problems at surgery.
The major objective of surgery in patients with complicated uveitic cataract and vitreous opacification is to improve vision. Vitrectomy may favorably modify the dynamics of the uveitic process, though lensectomy-vitrectomy does not reduce the inflammatory reaction in all cases.
Cystoid macular edema is the major cause of decreased visual acuity after surgery; however, this is a common and serious complication of chronic uveitis even without surgery. Vitrectomy may actually reduce cystoid macular edema with gradual resolution over 1 year and an improvement in vision in some patients.
In Chlamydia -induced ReA, studies have suggested that appropriate treatment of the acute GU infection can prevent ReA and that treatment of acute ReA with a 3-month course of antibiotics can reduce the duration of illness. Currently, there is no evidence to indicate that antibiotic therapy is effective for enteric-related ReA or chronic ReA of any cause.
Education on the prevention of the spread of sexually transmitted diseases with condoms has been associated with a decrease in the incidence of postvenereal ReA.
Appropriate consultations should be obtained as necessary.
A rheumatologist may be consulted to discuss appropriate additional tests and medications for symptomatic relief and to ensure follow-up treatment. In particular, the consulting rheumatologist may be extremely helpful in suggesting an appropriate oral NSAID or immunosuppressive agent to augment topical and periocular corticosteroid therapy.
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 ReA.
Consultation with a dermatologist is often helpful. For example, dermatologic involvement may occur with several uveitic syndromes; an accurate description of these lesions may help establish the diagnosis in some cases.
Consultation with and treatment by a dentist, an oral surgeon, or a periodontist may be useful for patients with aphthous ulcers.
An internal medicine consultation should be sought when prolonged systemic corticosteroid therapy is anticipated, especially in patients with concomitant diabetes or hypertension.
An infectious disease consultation may be sought when empiric antibiotic therapy is being considered or when the patient has manifestations of coincident AIDS-defining illnesses.
In cases of poststreptococcal ReA, a cardiology consultation is necessary because serial echocardiography and long-term antibiotic therapy may be of benefit to the patient. It should be kept in mind that patients with ReA symptoms who have evidence of preceding streptococcal infection are likely meet the Jones criteria for acute rheumatic fever. Many cardiologists elect to place these patients on long-term penicillin treatment.[83, 84]
It should be noted that current data show no increased risk of valvular heart disease in adult poststreptococcal ReA. On the basis of these findings, routine long-term antibiotic prophylaxis is not recommended in adult poststreptococcal ReA.[31, 49, 39, 38] The above recommendation is valid in pediatric patients with ReA.
Physical and occupational therapists may be consulted for assistance with maintenance of function and gait.
The goals of pharmacotherapy for reactive arthritis (ReA) are to reduce morbidity, to prevent joint damage, and to alleviate extra-articular disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstays of therapy for joint symptoms. Other types of agents used to treat ReA or its extra-articular manifestations include corticosteroids, antibiotics, and various disease-modifying antirheumatic drugs (DMARDs).
Clinical Context:
Aspirin is a short-acting anti-inflammatory agent with rapid absorption in the proximal gastrointestinal (GI) tract. It is optimally effective only when stable serum levels of 150-250 µg/L are achieved after 3-5 days of treatment. Serum aspirin levels can be checked after 5-10 days of treatment. Maximal anti-inflammatory action is generally achieved within 2-4 weeks, with some further benefit occurring up to 3 months.
Clinical Context:
Indomethacin is the NSAID of choice in ReA; however, other NSAIDs are often effective as well. It is rapidly absorbed; metabolism occurs in the liver via demethylation, deacetylation, and glucuronide conjugation. Indomethacin inhibits prostaglandin synthesis; it is also a potent COX inhibitor, and this action may decrease local production of arachidonic acid–derived chemotactic factors for eosinophils present in sebum.
Clinical Context:
Naproxen is used for relief of mild-to-moderate pain and is available in both short-acting and long-acting forms. It inhibits inflammatory reactions and pain by decreasing the activity of COX, which is responsible for prostaglandin synthesis.
Clinical Context:
Ketoprofen is used for relief of mild to moderate pain and inflammation. Small dosages are indicated initially in small patients, elderly patients, and patients with renal or liver disease. Doses higher than 75 mg do not increase the therapeutic effects. Administer high doses with caution, and closely observe the patient's response.
Several NSAIDs are available for relief of mild to moderate pain in ReA patients. They are similar with respect to effectiveness, though indomethacin may be more effective in the spondyloarthropathies. Cyclooxygenase (COX)-2–specific inhibitors can be used in patients at high risk for GI complications.
NSAIDs have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not fully known, but they may inhibit COX activity and prostaglandin synthesis. Other mechanisms, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions, may exist.
Aspirin and several NSAIDs are available for use in ReA patients and are comparably effective in treating symptoms.
Clinical Context:
Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity the activity of polymorphonuclear leukocytes (PMNs).
Clinical Context:
Prednisolone acetate is used mainly for acute iritis. The best approach is to treat aggressively early in the course of the disease, then to gradually taper and discontinue the drug on the basis of the patient's clinical response.
Clinical Context:
Topical corticosteroids are adrenocorticosteroid derivatives suitable for application to skin or external mucous membranes; they have mineralocorticoid and glucocorticoid effects, resulting in a nonspecific anti-inflammatory activity.
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body’s immune response to diverse stimuli. Topical corticosteroids are used for dermatologic manifestations of ReA, such as keratoderma blennorrhagicum and balanitis circinata (circinate balanitis). For ocular therapy, topical or subtenon injections of steroid have proven effective. Systemic steroids should only be used in cases of macular involvement and only for short periods.
Clinical Context:
Topical salicylic acid, by dissolving intercellular cement substance, produces desquamation of the horny layer of the skin, without affecting the structure of viable epidermis.
Clinical Context:
Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is indicated for treatment of infections caused by susceptible strains of microorganisms (eg, Mycoplasma pneumoniae and Staphylococcus, Streptococcus, and Chlamydia spp) and for prevention of corneal and conjunctival infections.
Clinical Context:
Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is indicated for the prevention of corneal and conjunctival infections.
Clinical Context:
Ciprofloxacin is the drug of choice for obtaining improvement in clinical parameters (except joint involvement) in postenteric ReA. It is a bactericidal antibiotic that inhibits bacterial DNA synthesis and, consequently, growth by inhibiting DNA gyrase in susceptible organisms.
Clinical Context:
Tetracycline is used to treat gram-positive and gram-negative infections, as well as mycoplasmal, chlamydial, and rickettsial infections. It inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits.
Clinical Context:
Doxycycline is used to treat infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma organisms. It inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Clinical Context:
Minocycline is used to treat infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma organisms. It inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Antibiotics may be used in ReA for antibacterial effects and for treatment of possible coexistent infection. Empiric antimicrobial therapy should cover all likely pathogens in the context of the clinical setting. Whenever feasible, antibiotic selection should be guided by blood culture sensitivity.
Tetracyclines are used to treat urethritis or cervicitis caused by chlamydial organisms. Some evidence shows that tetracycline treatment in chlamydia-induced ReA may reduce the duration, and perhaps the severity, of illness. Collagenase inhibitors have been used to treat early rheumatoid arthritis.
Clinical Context:
Sulfasalazine is used as a second-line therapy to treat ReA that is not controlled with NSAIDs alone. It is a conjugate of the salicylate 5-aminosalicylic acid (5-ASA) and the sulfonamide sulfapyridine (linked by an azo bond). Sulfasalazine is primarily excreted in the urine unchanged. Most of the 5-ASA remains in the colon and is not absorbed. Sulfasalazine acts locally to decrease the inflammatory response in the joints and systemically inhibits prostaglandin synthesis and folate metabolism.
Aminosalicylic acid derivatives are used to reduce inflammation when NSAIDs do not control arthritis or when inflammatory lesions of the intestinal mucosa are present.
Clinical Context:
Calcipotriene is a synthetic vitamin D-3 analogue that regulates skin-cell production and development. It is available as a 0.005% cream, ointment, or solution.
Clinical Context:
Azathioprine may be used alone or as a steroid-sparing agent. It antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. Azathioprine may decrease proliferation of immune cells, thereby reducing autoimmune activity. It is used more commonly for ReA and psoriasis. Thiopurine methyltransferase levels should be checked before azathioprine is used.
Clinical Context:
Methotrexate is an antimetabolite that is indicated for the symptomatic control of severe ReA and severe, recalcitrant, disabling psoriasis. It is also used alone or in combination with other anticancer agents in the treatment of advanced mycosis fungoides and cancer of the head, neck, or lung, particularly those of the squamous-cell and small-cell types.
Antineoplastic agents have immunosuppressive effects and inhibit cell growth and proliferation. They are used when the disease is aggressive and unremitting.
Clinical Context:
It is not clear how hydroxychloroquine works. It is known to interfere with TLR signaling, inhibit chemotaxis of eosinophils neutrophils, and impair complement-dependent antigen-antibody reactions. A 200-mg quantity of hydroxychloroquine sulfate is equivalent to 155 mg of hydroxychloroquine base and 250 mg of chloroquine phosphate.
Derivatives of 4-aminoquinoline are active against a variety of autoimmune disorders. They must be used with caution because hydroxychloroquine is known to be capable of exacerbating psoriasis. Because hydroxychloroquine is used for the joint involvement and not the skin involvement, it should probably be given only in conjunction with rheumatologic evaluation.
Clinical Context:
Oral agent used to treat serious dermatologic conditions. It is a synthetic 13-cis isomer of the naturally occurring tretinoin (trans-retinoic acid), and both agents are structurally related to vitamin A. Isotretinoin alters the pattern of keratinization, reduces bacterial flora, and has an anti-inflammatory effect.
A US Food and Drug Administration (FDA)–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin (see iPLEDGE). This registry aims to achieve further decreases in the risks of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
Clinical Context:
Acitretin is a retinoic acid analogue, similar to etretinate and isotretinoin. Etretinate is the main metabolite and has similar clinical effects. Acitretin's mechanism of action is unknown.
Retinoids decrease the cohesiveness of abnormal hyperproliferative keratinocytes and may reduce the potential for malignant degeneration. They also modulate keratinocyte differentiation.
Clinical Context:
Infliximab is a chimeric IgG1κ monoclonal antibody that binds specifically to the soluble and transmembrane forms of TNF-α and inhibits the binding of TNF-α to its receptors.
What is reactive arthritis (ReA)?What are the signs and symptoms of reactive arthritis (ReA)?Which physical findings are characteristic of reactive arthritis (ReA)?Which lab tests are performed in the workup of reactive arthritis (ReA)?Which imaging studies are performed in the workup of reactive arthritis (ReA)?Which studies may be considered in the workup of reactive arthritis (ReA)?How is reactive arthritis (ReA) treated?What is the role of surgery in the treatment of reactive arthritis (ReA)?What is reactive arthritis (ReA)?What are the diagnostic criteria for reactive arthritis (ReA)?What is the pathophysiology of reactive arthritis (ReA)?What is the role of synovitis in the pathophysiology of reactive arthritis (ReA)?What is the role of HLA-B27 in the pathophysiology of reactive arthritis (ReA)?What is the role of HIV infection in the pathophysiology of reactive arthritis (ReA)?What are infectious causes of reactive arthritis (ReA)?What is the role of genetics in the etiology of reactive arthritis (ReA)?Which factors increase the risk of reactive arthritis (ReA)?What is the incidence of reactive arthritis (ReA) in the US?What is the global incidence of reactive arthritis (ReA)?Which patient groups have higher incidence of reactive arthritis (ReA)?What is the prognosis of reactive arthritis (ReA)?What is included in patient information about reactive arthritis (ReA)?Which clinical history findings are characteristic of reactive arthritis (ReA)?What are the signs and symptoms of urethritis in patients with reactive arthritis (ReA)?What are the signs and symptoms of lymphogranuloma venereum infection in patients with reactive arthritis (ReA)?What are the ophthalmologic symptoms of reactive arthritis (ReA)?Which symptoms may be present in reactive arthritis (ReA) following an episode of diarrhea?What is the association of reactive arthritis (ReA) with HIV infection?What is the scoring system for diagnosing reactive arthritis (ReA)-like spondyloarthropathies?Which joints, axial skeleton, and entheses findings are characteristic of reactive arthritis (ReA)?Which skin and nail findings are characteristic of reactive arthritis (ReA)?Which ocular findings are characteristic of reactive arthritis (ReA)?Which urogenital findings are characteristic of reactive arthritis (ReA)?What are findings of circinate balanitis in patients with reactive arthritis (ReA)?What are findings of circinate vulvitis in patients with reactive arthritis (ReA)?Which GI findings are characteristic of reactive arthritis (ReA)?Which cardiac findings suggest reactive arthritis (ReA)?Which renal findings suggest reactive arthritis (ReA)?What are the possible complications of reactive arthritis (ReA)?How are other types of arthritis differentiated from reactive arthritis (ReA)?Which conditions should be included in the differential diagnoses of reactive arthritis (ReA)?How is reactive arthritis (ReA) diagnosed?What is the role of blood tests and urinalysis in the workup of reactive arthritis (ReA)?What is the role of serology and cultures in the workup of reactive arthritis (ReA)?What is the role of HLA-B27 testing in the workup of reactive arthritis (ReA)?What is the role of a tuberculin skin test in the workup of reactive arthritis (ReA)?What is the role of radiography in the workup of reactive arthritis (ReA)?Which radiographic findings are characteristic of reactive arthritis (ReA)?What is the role of imaging in the workup of reactive arthritis (ReA)?What is the role of arthrocentesis, synovial fluid analysis, and synovial biopsy in the workup of reactive arthritis (ReA)?Which tests are performed in the workup of reactive arthritis (ReA) when poststreptococcal infection is suspected?What is the role of ECG in the workup of reactive arthritis (ReA)?Which histologic findings are characteristic of reactive arthritis (ReA)?How is reactive arthritis (ReA) treated?What is included in the pharmacologic therapy for reactive arthritis (ReA)?How are the joint symptoms of reactive arthritis (ReA) treated?How are conjunctivitis and uveitis treated in patients with reactive arthritis (ReA)?How are urethritis and gastroenteritis treated in patients with reactive arthritis (ReA)?How are mucocutaneous lesions treated in patients with reactive arthritis (ReA)?What is the role of NSAIDs in the treatment of reactive arthritis (ReA)?What is the role of corticosteroids in the treatment of reactive arthritis (ReA)?What is the role of antibiotics in the treatment of reactive arthritis (ReA)?What is the role of DMARDs in the treatment of reactive arthritis (ReA)?What is the role of surgery in the treatment of reactive arthritis (ReA)?How is reactive arthritis (ReA) prevented?Which specialist consultations are beneficial to patients with reactive arthritis (ReA)?Which medications are used in the treatment of reactive arthritis (ReA)?Which medications in the drug class Tumor Necrosis Factor Blockers are used in the treatment of Reactive Arthritis?Which medications in the drug class Retinoid-like Agents are used in the treatment of Reactive Arthritis?Which medications in the drug class Antimalarials are used in the treatment of Reactive Arthritis?Which medications in the drug class Antineoplastic Agents are used in the treatment of Reactive Arthritis?Which medications in the drug class Vitamins, Fat-Soluble are used in the treatment of Reactive Arthritis?Which medications in the drug class Aminosalicylic Acid Derivatives are used in the treatment of Reactive Arthritis?Which medications in the drug class Antibiotics are used in the treatment of Reactive Arthritis?Which medications in the drug class Keratolytic Agents are used in the treatment of Reactive Arthritis?Which medications in the drug class Corticosteroids are used in the treatment of Reactive Arthritis?Which medications in the drug class Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are used in the treatment of Reactive Arthritis?
Carlos J Lozada, MD, Director of Rheumatology Fellowship Training Program, Professor of Clinical Medicine, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine
Disclosure: Received honoraria from Pfizer for consulting; Received grant/research funds from AbbVie for other; Received honoraria from Heel for consulting.
Coauthor(s)
Maria F Carpintero, MD, Assistant Professor of Clinical Medicine, Division Rheumatology/Immunology, University of Miami, Leonard M Miller School of Medicine
Disclosure: Nothing to disclose.
Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School
Disclosure: Nothing to disclose.
Chief Editor
Herbert S Diamond, MD, Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Disclosure: Nothing to disclose.
Acknowledgements
Mounir Bashour, MD, CM, FRCS(C), PhD, FACS Assistant Professor of Ophthalmology, McGill University; Clinical Assistant Professor of Ophthalmology, Sherbrooke University; Medical Director, Cornea Laser and Lasik MD
Mounir Bashour, MD, CM, FRCS(C), PhD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American College of International Physicians, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, American Society of Mechanical Engineers, American Society of Ophthalmic Plastic and Reconstructive Surgery, Biomedical Engineering Society, Canadian Medical Association,Canadian Ophthalmological Society, Contact Lens Association of Ophthalmologists, International College of Surgeons US Section, Ontario Medical Association, Quebec Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.
Igor Boyarsky, DO Emergency Room Physician, Kaiser Permanente Southern California
Igor Boyarsky, DO is a member of the following medical societies: American Academy of Anti-Aging Medicine, American Academy of Emergency Medicine, American College of Emergency Physicians, and American Osteopathic Association
Disclosure: Nothing to disclose.
Bo Burns, DO, FACEP, FAAEM Assistant Professor, Associate Residency Director, Medical Clerkship Director, Department of Emergency Medicine, University of Oklahoma School of Community Medicine; Attending Physician, Department of Emergency Medicine
Bo Burns, DO, FACEP, FAAEM, is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Gino A Farina, MD, FACEP, FAAEM Associate Professor of Clinical Emergency Medicine, Albert Einstein College of Medicine; Program Director, Department of Emergency Medicine, Long Island Jewish Medical Center
Gino A Farina, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
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.
William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: Nothing to disclose.
Lawrence K Jung, MD Chief, Division of Pediatric Rheumatology, Children's National Medical Center
Lawrence K Jung, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Rheumatology, Clinical Immunology Society, and New York Academy of Sciences
Disclosure: Nothing to disclose.
Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.
Jeffrey Meffert, MD Assistant Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio
Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society
Disclosure: Nothing to disclose.
Barry L Myones, MD Associate Professor, Departments of Pediatrics and Immunology, Pediatric Rheumatology Section, Baylor College of Medicine; Director of Research, Pediatric Rheumatology Center, Texas Children's Hospital
Barry L Myones, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American College of Rheumatology, American Heart Association, American Society for Microbiology, Clinical Immunology Society, and Texas Medical Association
Disclosure: Nothing to disclose.
Robert E O'Connor, MD, MPH Professor and Chair, Department of Emergency Medicine, University of Virginia Health System
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
Disclosure: Nothing to disclose.
Lluís Puig, MD, PhD Program Director, Assistant Professor, Department of Dermatology, Hospital De La Santa Creu I Sant Pau, Universitat Autónoma De Barcelona
Lluís Puig, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, European Academy of Dermatology and Venereology, and International Society of Dermatopathology
Disclosure: Nothing to disclose.
Jorge Romaní, MD Assistant Professor, Department of Dermatology, Hospital De Palamós Faculty of Medicine, Spain
Disclosure: Nothing to disclose.
Hampton Roy Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.
Nima Sarani, MD Resident Physician, Department of Emergency Medicine, Oklahoma University College of Medicine
Nima Sarani, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Physicians, and Congress of Neurological Surgeons
Disclosure: Nothing to disclose.
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.
John D Sheppard Jr, MD, MMSc Professor of Ophthalmology, Microbiology and Molecular Biology, Clinical Director, Thomas R Lee Center for Ocular Pharmacology, Ophthalmology Residency Research Program Director, Eastern Virginia Medical School; President, Virginia Eye Consultants
John D Sheppard Jr, MD, MMSc is a member of the following medical societies: American Academy of Ophthalmology, American Society for Microbiology, American Society of Cataract and Refractive Surgery, American Uveitis Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.
David D Sherry, MD Director, Clinical Rheumatology, Attending Physician, Pain Management, The Children's Hospital of Philadelphia; Professor of Pediatrics, University of Pennsylvania School of Medicine
David D Sherry, MD is a member of the following medical societies: American College of Rheumatology and American Pain Society
Disclosure: Nothing to disclose.
Dana A Stearns, MD Assistant Director of Undergraduate Education, Department of Emergency Medicine, Massachusetts General Hospital; Assistant Professor of Surgery, Harvard Medical School
Dana A Stearns, MD is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Akaluck Thatayatikom, MD Associate Professor and Chief, Department of Pediatrics, Division of Pediatric Allergy, Immunology, and Rheumatology, University of Kentucky College of Medicine
Akaluck Thatayatikom, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Rheumatology, Childhood Arthritis and Rheumatology Research Alliance, and Clinical Immunology Society
Disclosure: Nothing to disclose.
Robin Travers, MD Assistant Professor of Medicine (Dermatology), Dartmouth University School of Medicine; Staff Dermatologist, New England Baptist Hospital; Private Practice, SkinCare Physicians
Robin Travers, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Informatics Association, Massachusetts Medical Society, Medical Dermatology Society, and Women's Dermatologic Society
Disclosure: Nothing to disclose.
R Christopher Walton, MD Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, University of Tennessee College of Medicine
R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Carter JD et al. Combination Antibiotics as a Treatment for Chronic Chlamydia-Induced Reactive Arthritis. Philadelphia PA. (abstract 1152).: ACR/ARHP Annual Scientific Meeting; October 19, 2009.
Painful erosions on fingers in patient with reactive arthritis.
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.
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.
Balanitis circinata (circinate balanitis) in patient with reactive arthritis.
Balanitis circinata (circinate balanitis). Image courtesy of Gun Phongsamart, MD.
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.
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.
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