Discussion:
We report a case of ReA occurring after urethritis. ReA is a form of
peripheral spondyloarthritis occurring after a distant bacterial
infection [6].
Causative agents of ReA are most commonly genitourinary (Ct, Neisseria
gonorrhea, Mycoplasma hominis, and Ureaplasma urealyticum) or
gastrointestinal (Salmonella, Shigella, Campylobacter, and Yersinia)
[7,8]. Bacillus Calmette-Guérin (BCG) therapy [9] or viral
triggers can also induce ReA [10].
ReA commonly affects young adults of 20 to 40 years, with a male
predominance in the post-venereal form [3,11]. The risk of
developing ReA after genitourinary or gastrointestinal infections is
about 1 to 4% in the general population. It increases to 25% in
patients with positive HLA-B27 [6].
HLA-B27 was found in 30% to 50% of ReA patients [8].
Clinical manifestations appear within one to six weeks after
genitourinary or gastrointestinal infection, such as urethritis,
cervicitis, or diarrhea [6]. Asymptomatic chlamydia trachomatis
infection can also induce ReA [7,12].
Rheumatological manifestations include asymmetric oligoarticular
arthritis of the lower limbs [12], dactylitis, enthesitis (42% of
patients) [6], and sacroiliitis (30% of cases) [6].
Dermatological manifestations are various. They may include Keratoderma
blenorrhagicum, circinate balanitis, ulcerative vulvitis, oral lesions,
and nail changes [13,14]. Keratoderma blenorrhagicum typically
appears as erythematous macules and papules in the plantar and palmar
area, rising into vesicular, often hyperkeratotic plaques and sterile
pustules [4].
Only 10% of ReA patients with positive HLA-B27 develop these lesions.
[13]
Ocular manifestations include conjunctivitis, anterior uveitis,
episcleritis, and keratitis [8]. Cardiac manifestations have also
been reported, including conduction abnormalities in the early stages of
the disease [15–17] and aortic insufficiency in advanced disease
[18,19].
The typical presentation of ReA, known as Reiter’s syndrome, has been
rarely reported. This form consists of urethritis, conjunctivitis, and
arthritis [20].
Inflammatory markers can be increased in the acute phase of ReA
[21].
Microbiologic investigation for C. trachomatis by PCR in urethral swabs,
synovial fluid [22], and synovial biopsy [23] are helpful to
make the diagnosis of ReA. However, these tests are negative in up to
half of the patients [22].
ReA is often misdiagnosed because of the lack of diagnostic criteria.
The diagnosis of ReA can be made if acute oligoarthritis or axial
involvement occurs after gastroenteritis or urogenital bacterial
infection [23].
In these cases, the diagnosis of ReA can be made based on
rheumatological manifestations occurring after genitourinary symptoms,
increased CRP, and positive HLA-B27. This association can predict the
diagnosis of ReA with a sensitivity of 69% and a specificity of 93.5%
[24].
Despite the negativity of microbiologic investigations in our case, the
diagnosis of ReA was made based on the history of urethral discharge
preceding rheumatological manifestations associated with plantar
papulosquamous plaques, dactylitis, and the positivity of HLA-B27.
Nevertheless, if gastrointestinal or urogenital infection cannot be
remembered by the patient, the triggering bacteria (Chlamydia,
Salmonella, Yersinia, Shigella, Campylobacter) should be identified at
the site of primary infection, serologic test, or PCR [23].
Using the Assessment of SpondyloArthritis International Society
classification criteria for peripheral spondyloarthritis, the diagnosis
of peripheral spondyloarthritis can be established when arthritis,
enthesitis, or dactylitis is associated with at least one of these
following criteria: psoriasis, inflammatory bowel disease, preceding
infection, HLA-B27, uveitis, or sacroiliitis on imaging [25]. These
criteria had a sensitivity and specificity of 79.5% and 83.3%.
The management of ReA is not yet codified [26]. Antibiotics can be
indicated [3], often for a long time [8]. Although their
efficacy is uncertain [26], long-term antibiotic treatment can
prevent recurrence and chronic progression of ReA [19,27].
Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line
treatment of articular manifestations. If NSAIDs are contraindicated or
have low efficacy, intra-articular glucocorticoids can be indicated.
Systemic steroids can be prescribed in patients with many swollen joints
[3].
The failure of the first-line treatment or persistent symptoms for more
than six months can lead to the prescription of conventional synthetic
disease-modifying anti-rheumatic drugs (csDMARDs) [3]. Sulfasalazine
is the main DMARDs used in ReA. Its efficacy has been proved in a
placebo-controlled prospective trial [28]. Other csDMARDs
(methotrexate, azathioprine, cyclosporin) are supported by less
experimental data [29]. Biologic DMARDs can be started if resistance
to csDMARDs [3] or severe dermatological lesions [12].
In our case, the prescription of antibiotics aimed to treat urethritis
and prevent recurrence and chronic progression of ReA. NSAIDs and
sulfasalazine were prescribed to alleviate rheumatological
manifestations.
The evolution of ReA depends on the triggering infection (Ct and
Ureaplasma Urealyticum), HLA-B27 positivity, gender, and the presence of
sacroiliitis [30,31].
ReA is often a self-limited disease [3] with a duration of 3 to 5
months for an acute ReA [32]. Nevertheless, 30% to 50% of patients
develop chronic symptoms [7,33]. Chronic gut inflammation and a
family history of spondyloarthropathy are risk factors for progression
to chronicity [34].