Table I.

Bacteria triggering ReA and the clinical findings they cause at the entry site Modified after [12, 13]

Reactive arthritis Entry site Infection Pathogen

Chlamydia trachomatis
Urethritis, cystitis, cervicitis,
Noémi Mosonyi Urogenital tract prostatitis, epidymitis, salpingitis,
Ureaplasma urealyticum
Mycoplasma hominis
Student, University of Medicine and Pharmacy "Iuliu Hațieganu", Cluj-Napoca endometritis

Yersinia enterocolitica
Diarrhea, gastroenteritis, Salmonella spp
Gastrointestinal tract
enterocolitis Shigella flexneri
Campylobacter jejuni
Abstract. Reactive arthritis occurs following a gastrointestinal or genitourinary infection. Incidence
varies between 0.6-30/100,000, frequently involving men aged between 20-40 years old with a history Sinusitis, bronchitis, pneumonia, Chlamydia pneumoniae
of genitourinary Chlamydia trachomatis infection. The most important symptom is arthritis of the lower Airways
tonsillitis Group A Streptococcus
limbs affecting the large joints, such as the knee or ankle. Viable microbes in the joint cavity have not yet
been found; only bacterial genetic material suggests their presence and metabolic activity. Other mani- Lyme disease Borrelia burgdorferi
festations include conjunctivitis, urethritis and mucocutaneous lesions similar to psoriasis. The triad of Other Skin, connective tissue infections Staphylococcus spp
arthritis, urethritis and conjunctivitis is known as Reiter’s syndrome. Most of the cases are self-limited,
but the chronic form also exists. Currently there are no validated diagnostic criteria, diagnosis relying
mainly on clinical findings and evidence of the initiating infection, along with exclusion of other diag-
noses through the workup. Differential diagnosis includes septic arthritis, rheumatoid arthritis, psoriatic Epidemiology of the lower limbs. The most frequently encoun-
arthritis, Crohn’s disease and disseminated gonococcal infection. First-line treatment is represented by Two main types of infections can trigger ReA: tered is the knee, followed by the ankle and the
non-steroidal anti-inflammatory drugs. Intra-articular glucocorticoids can reduce inflammation if one or gastrointestinal and genitourinary. Table I. de- metatarsophalangeal joint. Patients complain
few joints are affected. scribes the most common causative pathogens. about localized pain, swelling, tenderness, heat,
Keywords: reactive arthritis, Reiter’s syndrome, conjunctivitis, urethritis, Chlamydia trachomatis, From all these, Chlamydia trachomatis is the most with or without redness, and walking difficulties
mucocutaneous lesion frequent pathogen observed to trigger ReA [9-11]. [17, 18, 21]. In 30% of cases, after a prolonged
Population-based studies assess the annual course of the disease, patients develop inflamma-
incidence of ReA between 0.6-27/100,000 [13], tory low back pain, a symptom of possible sacroi-
so it can be considered a rare disease. Milder liitis that can further progress to ankylosing spon-
Introduction ing keratoderma blennorrhagica and circinate cases frequently go unreported, leading to un- dylitis (AS) [17, 22]. Enthesis is mainly present in
Reactive arthritis (ReA) is defined as a spon- balanitis are frequent [5, 6]. derdiagnosis of ReA [14, 15]. the plantar aponeurosis and Achilles tendon and
dyloarthropathy that consists of aseptic inflam- The clinical triad of arthritis, conjunctivitis A typical ReA patient is a 20-40 years old may cause limping [23]. The so-called “sausage
matory arthritis usually following an enteric or and non-gonococcal urethritis is known as Re- male, with a history of recent genitourinary in- digit” or dactylitis is swelling of the whole toe or
genitourinary microbial infection [1,2]. Spon- iter’s syndrome, but since the triad is not found fection. Regarding gastrointestinal infections, finger, with moderate pain and tenderness [23].
dyloarthropathies involve inflammatory arthri- in every patient and because of Reiter’s part in the male:female ratio is equal [11, 16, 17]. Conjunctivitis is found in 50% of patients
tis, enthesis (inflammation at the site where Nazi medical experimentation, the term Re- The correlation with HLA-B27 is still in de- with genitourinary infection and 75% of pa-
ligaments, tendons and joint capsules insert iter’s syndrome should be avoided and reactive bate. Supposedly, reported high HLA-B27 fre- tients with gastrointestinal infection, being the
into the bone), absence of the rheumatoid factor arthritis should be used instead [7, 8]. quencies are a result of including complex hos- most frequent extra-articular manifestation
referred to as seronegativity, and a strong cor- Due to the lack of validated diagnostic crite- pital based cases [2, 18, 19]. In contrast, around and also part of the classic triad [10, 21, 22].
relation with HLA-B27 [3]. ria for ReA [2], the definition is still evolving; 75% of HLA-B27 positive and human immu- Preceding arthritis, it is mild and appears in-
Initially, only antigens of the infectious agent thus, history taking and clinical exam play an nodeficiency virus-infected patients will develop termittently on both sides, patients experienc-
could be identified in the joint cavity; later on, ge- important role in the diagnostic process. Being ReA [20]. ing pain, irritation, redness, blurry vision, ster-
netic material of Chlamydia species was isolated, subjected to the physician’s personal opinion, ile ocular discharge for up to 4 weeks [17, 22].
suggesting its viability and metabolic activity [4]. the cases include a wide spectrum of symptoms Clinical presentation Mucocutaneous lesions appear either before
A series of extra-articular manifestations such and clinical signs. The main symptom is oligoarthritis with acute or after arthritis and are similar to psoriasis
as conjunctivitis, urethritis, skin changes includ- and asymmetrical onset, affecting the large joints macroscopically and microscopically [5, 17].

40 41
 Keratoderma blennorrhagica consists of hy-
perkeratotic lesions similar to pustular psoria-
sis. Initially clear plantar and palmar vesicles,
they gradually develop to macules and papules
that intertwine into hyperkeratotic plaques.
Nails are also affected, from red swelling to
thickening of the nail plate, similar to psoriatic
onychodystrophy or mycotic infection [5].
Circinate balanitis appears on the glans of
the penis or urethral meatus and is character-
ized by well-defined, painless erythematous
lesions accompanied by small ulcers that grow
centrifugally. It is present in a similar way on
the vaginal mucosa or vulva [5].
Urethritis is linked to sexually acquired in-
fections, but it can also occur after enteric in-
fection. It usually precedes conjunctivitis and
is marked by dysuria, urethral or vaginal dis-
charge and pollakiuria especially in men, but it
is not unusual to go unnoticed [17, 22, 24].
Subclinical acute gastrointestinal inflamma-
tion can also be found. The lesions are asymp-
tomatic, located in the terminal ileum or colon,
and are similar to Crohn’s disease when viewed
by colonoscopy [2, 23].
Diagnosis
Given the lack of validated diagnostic cri-
teria, the clinical exam plays a crucial role.
While the triggering infection is frequently
asymptomatic and the classical triad seldom
appears, it can be challenging to make an ac-
curate diagnosis.
Three objectives should be achieved during
workup [2, 12]: finding a typical or at least fit-
ting clinical picture, evidence of initiating in-
fection, and excluding other diagnoses.
Preliminary diagnostic criteria for ReA
were proposed during the Fourth International
Workshop on ReA, differentiating between a
definite and probable diagnosis, but since their
announcement no consensus has been reached
by the scientific community [2].
After the clinical exam and a presumptive
diagnosis, laboratory studies can be performed:
blood tests reveal inflammation, with elevat-
ed acute-phase reactants, such as erythrocyte
42 43
sedimentation rate (ESR), C-reactive protein
(CRP) and mild leukocytosis. The rheumatoid
factor (RF) and antinuclear antibodies (ANA)
are negative. Urinalysis shows pyuria and the
presence of red blood cells (RBC), white blood
cells (WBC), and proteins in small amounts.
In order to identify the involved pathogen, after
detailed history taking, cultures from urethral
exudate or stool samples should be performed
and the most frequent bacteria, mentioned in
Table 1, searched for [20].
Radiography can assess arthritis, revealing
periarticular osteoporosis, erosions, joint space
loss and soft tissue swelling [25].
Arthrocentesis and fluid sample analysis
should always be performed when dealing with
an inflamed joint, excluding most importantly
septic arthritis, an orthopedic emergency.
Differential diagnosis
ReA should always be considered for lower
extremity arthritis but only diagnosed for sure
if all other possible causes are ruled out.
The most important differential diagnosis is
septic arthritis. Elevated WBC count (10,000-
40,000/µL) and positive fluid culture sustain
the diagnosis [17, 20, 23].
Rheumatoid arthritis (RA) can resemble
dactylitis, but instead of joint swelling, the
whole fingers are swollen. Serologic testing
(positive RF and ANA) supports rheumatoid
arthritis [17].
Psoriatic arthritis presents in a similar way
to ReA due to the skin and mucosal lesions al-
ready discussed. Small joint involvement in a
symmetric manner and a younger age of onset
is more characteristic of psoriatic arthritis [5].
Conjunctivitis and arthritis occur together in
a number of inflammatory diseases such as RA,
psoriasis, Sjögren sindrome or Still’s disease.
Inflammatory bowel diseases such as Crohn’s
disease are accompanied, along with diarrhea,
by asymmetric arthritis of the lower limbs.
Medical history and gastrointestinal symptoms
should guide the diagnosis. In viral gastritis,
arthritis is non-specific and self-limited, its
etiology being suggested by fever and myalgias.
Disseminated gonococcal infection is trig-
gered by a sexually transmitted infection and
systemic spreading of Neisseria gonorrhoea. It
causes asymmetric polyarthralgia of small or
large joints in young patients after a symptom-
atic sexually transmitted infection. Urethral
exudate cultures rule out this diagnosis [20].
Course of ReA
Hypercalcemia has multiple causes and it is
often suspected when alterations in renal func-
tion, cardiac function and metabolic disorders
occur. However, hypercalcemia deserves to be
taken into consideration in patients with less
specific clinical manifestations linked to the
gastrointestinal function and nervous system.
Treatment
Although the course of ReA is usually self-
limited, management is aimed at reducing pain
and inflammation and at preventing relapses or
progression to chronicity. The indication of drugs
depends on the duration and extent of symptoms.
Alongside medication, physiotherapy seems to be
beneficial for a faster recovery [27].
First-line therapy for arthritis and enthesis
consists of non-steroidal anti-inflammatory
drugs (NSAIDs), in association with pure
analgesics if needed. The lowest dose for the
shortest time period should be administered.
Further, intra-articular administration of cor-
ticosteroids is suggested if one or few joints are
affected. In case of multi-articular involvement
or resistance to NSAIDs, systemic corticoste-
roids should be chosen [6, 12, 27]. These seem
to also improve the extra-articular features.
Conclusions
ReA is a post-infectious disease that is not a
serious life-threatening condition, patients re-
covering on their own fully or with some mo-
tor deficiencies in two thirds of cases. There is
a need to establish exact diagnostic criteria in
order to assess the true incidence and to bet-
ter identify the eligible cases for early treat-
ment initiation. Today, despite a challenging
diagnostic process, managing the symptoms
is more important than a precise diagnosis;
prompt initiation of treatment can prevent the
chronic form and further development to an-
kylosing spondylitis, thus improving the pa-
tients’ daily living and quality of life.
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