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\begin{document}

\title{Cutaneous and rheumatological manifestations of reactive arthritis: a
case report}



\author[1]{Maroua SLOUMA}%
\author[1]{Siwar Ben Dhia}%
\author[1]{Rim Dhahri}%
\author[1]{Noureddine Litaiem}%
\author[1]{Leila Metoui}%
\author[1]{Imen Gharsallah}%
\author[1]{Bassem Louzir}%
\affil[1]{University of Tunis El Manar Faculty of Medicine of Tunis}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Reactive arthritis is a rare form of spondyloarthropathies that develops
in response to a genital or intestinal infection. We report the case of
a reactive arthritis with skin manifestations, occurring after a
urethritis. Long term antibiotic treatment associated with sulfasalazine
and diclofenac led to the control of disease activity levels.%
\end{abstract}%



\sloppy


\textbf{Title:Cutaneous and rheumatological manifestations of reactive
arthritis: a case report}

\emph{Authors:}

Maroua SLOUMA\textsuperscript{1,4}, MD, Siwar BEN
DHIA\textsuperscript{1,4}, MD, Rim DHAHRI\textsuperscript{1,4}, MD,
Noureddine LITAIEM\textsuperscript{2,4}, MD, Leila
METOUI\textsuperscript{1,4}, MD, Imen GHARSALLAH\textsuperscript{1,4},
MD, Bassem LOUZIR\textsuperscript{3,4}, MD.

\emph{Authors Affiliation:}

\begin{enumerate}
\tightlist
\item
  Department of Rheumatology, Military Hospital, Tunis, Tunisia,
\item
  Department of Dermatology, Charles Nicolle Hospital, Tunisia
\item
  Department of Internal Medicine, Military Hospital, Tunis, Tunisia,
\item
  Tunis El Manar University -- Tunisia
\end{enumerate}

\emph{Corresponding author} : Maroua SLOUMA

Address: Department of Rheumatology, Military Hospital, Tunis, Tunisia,
1007

\emph{maroua.slouma@gmail.com}

Tel: + 216 55~117~316



\textbf{Authors' contributions~}

- Dr. Maroua SLOUMA: Methodology and Writing - review \& editing

- Dr. Siwar BEN DHIA: Roles/Writing - original draft

- Dr Noureddine LITAIEM and Dr. Rim DHAHRI: data analysis

- Dr. Imen GHARSALLAH: supervision

- Dr. Leila METOUI: conceptualization

- Dr. Bassem LOUZIR: validation

\textbf{DECLARATION}

\textbf{Conflict of interest:} none

\textbf{Funding:} The authors declare that they have no funding for this
study

\textbf{Written informed consent} was obtained from the patient to
publish this report in accordance with the journal's patient consent
policy.



\textbf{Abstract:}

Reactive arthritis is a rare form of spondyloarthropathies that develops
in response to a genital or intestinal infection. We report the case of
a reactive arthritis with skin manifestations, occurring after a
urethritis. Long term antibiotic treatment associated with sulfasalazine
and diclofenac led to the control of disease activity levels.

\textbf{Structured abstract:}

\textbf{Introduction:}

Reactive arthritis is a rare form of spondyloarthropathies occurring
after genital or enteric. It is most often self-limited but can progress
to chronic spondylarthritis.

\textbf{Case description:}

We report the case of a 30-year-old man who presented with acute
arthritis occurring two months after an episode of urethral discharge.
Physical examination revealed polyarthritis, dactylitis, sacroiliac
joint involvement, and plantar papulosquamous plaques. The human
leukocyte antigen B27 was positive. Detection of chlamydia trachomatis
and Gonococcus in the first catch urine specimen was negative. Hepatitis
B and C, chlamydia trachomatis, Human Immunodeficiency Virus and
syphilis serologic test results were negative. Pelvic magnetic resonance
imaging revealed left sacroiliitis. The patient was treated with
antibiotics, diclofenac, and sulfasalazine. After six months of
follow-up, a significant clinical improvement was obtained without
remission, suggesting an evolution to chronic spondylarthritis.

\textbf{Conclusion:}

Diagnosis of Reactive arthritis is difficult since microbiologic
examinations are commonly negative. This disease should be considered in
patients with rheumatologic manifestations occurring after a urogenital
or enteric infection, mainly when associated with skin manifestations
and human leukocyte antigen B27.

\textbf{Keywords} : Reactive arthritis, urethritis, Keratoderma
blennorrhagica, HLA-B27 Antigen

\textbf{Key clinical points}

Reactive arthritis should be considered when rheumatologic
manifestations follow genital or enteric infection

Negative microbiologic tests should not exclude the diagnosis

Plantar papulosquamous plaques, dactylitis, and HLA-B27 enhance the
diagnosis

\textbf{Introduction:}

Reactive arthritis (ReA) is aseptic arthritis occurring 1 to 4 weeks
after bacterial infection of the genitourinary and digestive tracts
{[}1,2{]}. It usually affects a genetically predisposed individual.

Clinical manifestations include mucocutaneous manifestations such as
keratoderma blenorrhagicum, circinate balanitis, ulcerative vulvitis,
nail changes (dystrophy and thickness), oral lesions, and conjunctivitis
{[}3,4{]}.

The main rheumatological manifestations are asymmetric oligoarticular
arthritis of the lower limbs, enthesitis, dactylitis, and inflammatory
back pain.

The diagnosis of ReA is challenging since no diagnosis criteria are
available.

We report a case of ReA occurring after urethritis. We emphasize
clinical signs, radiological features, and management of this disease.



\textbf{Case description:}

A 30-year-old man presented to the rheumatology department with a
20-day-history of inflammatory arthralgia. He had no medical history and
was a smoker.

The patient claimed to have had a urethral discharge one month before
the onset of articular manifestations. He also reported having
non-protected sexual intercourse.

Physical examination showed left knee joint effusion, synovitis of
metacarpophalangeal joints, and proximal interphalangeal (PIP) joints.

The left sacroiliac joint was tender with positive compression,
distraction, and sacral thrust provocation tests. The patient also had
right third finger dactylitis (figure 1) and plantar papulosquamous
plaques (figure 2).

The patient had no fever, urethritis, conjunctivitis, or uveitis.

Laboratory examinations reveal increased C-Reactive protein (CRP) level
(97 mg/L, Normal value (N) \textless{}8 mg/L), elevated erythrocyte
sedimentation rate (ESR) (83 mg/L, N\textless{}15 mm). Liver and renal
tests were within the normal range.

Anti-nuclear antibodies, rheumatoid factor, and anti-citrullinated
protein antibodies were negative.

Polymerase chain reaction (PCR) test for Chlamydia trachomatis (Ct) and
Gonococcus in the first catch urine specimen were negative. Detection of
Ct by PCR in blood sample was also negative. Hepatitis B and C, Ct,
Human Immunodeficiency Virus, and syphilis serologic test results were
negative.

The human leukocyte antigen (HLA) B27 was positive. Radiographs of hands
and feet did not reveal erosions or joint space narrowing.

The pelvis radiograph did not show sacroiliitis. Pelvic magnetic
resonance imaging (MRI) revealed subchondral bone marrow edema of the
left sacroiliac joint attesting to an active inflammation of sacroiliac
joints.

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.

Ceftriaxone (a single dose of 1 g) and doxycycline (200 mg daily for
three months) were indicated. Sulfasalazine (2 grams daily) and
diclofenac (150 mg daily) were also prescribed, leading to the
alleviation of clinical manifestations.

Plantar skin lesions regressed on the third day of antibiotic therapy.

After six months of follow-up, Bath ankylosing spondylarthritis disease
activity index (BASDAI) {[}5{]} fell from 4.9 to 2.1. Inflammatory
biomarkers became within the normal range.



\textbf{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-Gu\selectlanguage{ngerman}érin (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{]}\textbf{.}

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{]}.



\textbf{Conclusion:}

The diagnosis of ReA is challenging because of the high rate of negative
microbiologic examination and the lack of diagnostic criteria. The
diagnosis of ReA should be considered in patients with rheumatologic
manifestations occurring after a urogenital or enteric infection, mainly
when associated with skin manifestations and HLA B27.

The management of ReA is based on the treatment of the triggering
infection and the articular manifestations.



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\subsection*{Figures legend:}

{\label{figures-legend}}

\subsection*{Figure 1: Dactylitis of the right third finger
(arrow)}

{\label{figure-1-dactylitis-of-the-right-third-finger-arrow}}

\subsection*{Figure 2: Plantar papulosquamous
plaques}

{\label{figure-2-plantar-papulosquamous-plaques}}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}

\selectlanguage{english}
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