Reactive Arthritis

Robert D. Inman

KEY POINTS

In arthritis occurring after a recent infection, the first priority is to rule out a septic process in the joint.
The prognosis is good in most patients and most can be managed with nonsteroidal anti- inflammatory drugs (NSAIDs).
More refractory cases may need methotrexate, sulfasalazine, or on occasion anti-tumor necrosis factor (anti-TNF) treatment to bring the process under control.
The efficacy of antibiotics in modifying the natural history of reactive arthritis (ReA) is not resolved.

INTRODUCTION

Reactive arthritis (ReA) refers to a nonseptic arthritis that follows an extra-articular infection. The antecedent infection, usually gastrointestinal or genitourinary, can often be identified, but antibiotic treatment does not appear to predictably alter the course of the illness.
ReA has replaced Reiter’s syndrome (RS) as the name of choice for the clinical triad of arthritis, conjunctivitis, and urethritis. The term ReA now encompasses postinfectious seronegative asymmetric arthritis, either alone or in combination with one of the characteristic extra-articular features such as rash, uveitis, or conjunctivitis.
The most common pathogens implicated in such infections are Yersinia, Salmonella, Shigella, Campylobacter (gastrointestinal infections), and Chlamydia (genitourinary infections).
Although ReA occurs in children and the elderly, it is usually seen in young adults, with a significant male predominance. It is likely that ReA is under-recognized in female patients, because some clinical features (e.g., cervicitis) may be less symptomatic than the extra-articular features in male patients (e.g., balanitis). However, serious, and even refractory, ReA does occur in women, and the clinician should be alert to a typical constellation of symptoms in either of the sexes.
Despite the strong immunogenetic influence on the disease, a positive family history for ReA is uncommon. However, it has been observed that if there is a positive
family history, it tends to be for ReA, whereas patients with ankylosing spondylitis are more likely to have relatives with that disease than with ReA.
At present, there are no clinical features that will discriminate the patients who will develop systemic target organ involvement from those in whom the disease will be limited to the joints, nor are there features that will define a benign, self-limiting course (averaging 3 to 4 months) from a more chronic course.

ETIOPATHOGENESIS

Despite the strong association with the human leukocyte antigen (HLA-B27), the mechanism whereby this HLA gene might confer disease susceptibility to ReA remains unknown. There are several hypothetical routes by which HLA might interact with a triggering infectious agent.

The first is molecular mimicry, whereby an autoimmune response develops after the infection because of cross-reactivity between host and microbial antigens.
A second mechanism is a distinctive cellular immune response to the pathogen, determined by unique determinants in the antigen-binding groove of the HLA-B27 molecule, which specifically present “arthritogenic” peptides to a responding CD8+ T-cell population.
Another possibility is an altered microbial–host cell interaction, by which certain HLA alleles modulate host response to arthritogenic organisms.
Whatever the mechanism, it is likely that the synovitis that ensues is related to local deposition and persistence of microbial antigens, but definitive proof is lacking to resolve the issue.

CLINICAL MANIFESTATIONS

I. HISTORY

A careful history should be taken to address any recent exposure to an enteric pathogen (e.g., a diarrheal illness after travel abroad) or a sexually transmitted pathogen (e.g., a new sexual contact). The typical interval between the triggering infection and ReA is 1 to 4 weeks, but shorter or longer intervals have been reported. A past history of low back pain or recurrent tendinitis is not uncommon. A history of recent antibiotic therapy may alter culture results. Prior episodes of uveitis may not be mentioned by the patient unless specifically queried.

II. CONSTITUTIONAL SYMPTOMS

Fatigue may not be present in the acute phase, but can become significant in chronic ReA.

III. PHYSICAL EXAMINATION