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\begin{document}

\title{Disseminated Gonococcal Infection with Dermatitis-Arthritis Syndrome}



\author[1]{Sara Humayun}%
\author[1]{Radhika Bahadur}%
\author[1]{Maryam Fatima}%
\author[2]{Atul Bali}%
\author[3]{SREEKANT AVULA}%
\author[1]{Roopa Naik}%
\affil[1]{Geisinger Wyoming Valley Medical Center}%
\affil[2]{Geisinger Health}%
\affil[3]{University of Minnesota Twin Cities}%


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  \date{May 25, 2024}


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\textbf{Disseminated Gonococcal Infection with Dermatitis-Arthritis
Syndrome}

\textbf{Sara Humayun\textsuperscript{1}, Radhika
Bahadur\textsuperscript{1}, Maryam Fatima\textsuperscript{1}, Atul
Bali\textsuperscript{1}, Sreekanth Avula\textsuperscript{2}, Roopa
Naik\textsuperscript{1}}

\textsuperscript{1}Deparment of Medicine, Geisinger Wyoming Valley
Medical Center, Wilkes-Barre, PA, USA

\textsuperscript{\textbf{2}} Department of Diabetes, Endocrinology and
Metabolism, University of Minnesota, Minneapolis, MN, USA

\textbf{Abstract} :

Gonorrhea is a sexually transmitted infection caused by gram-negative
diplococci, \emph{Neisseria gonorrhoeae} . Disseminated gonorrhea is
diagnosed infrequently, partly due to low suspicion at the time of
presentation, and at times, due to overlapping symptoms associated with
non-infectious conditions like systemic lupus erythematosus (SLE). In
this article, we present a 42-year-old sexually active female with knee
pain and swelling, fever, and rash. Knee aspirate showed the presence of
monosodium urate crystals, and the synovial culture grew gram-negative
diplococci, requiring multiple joint washouts. Urine nucleic acid
amplification test (NAAT) was indeterminate. She was treated with
high-dose intravenous ceftriaxone for 1 week post-joint washout with
rapid improvement in her condition and resolution of the rash.

\textbf{Key Words}

NAAT: nucleic acid amplification test, sexually transmitted infection

\textbf{Introduction:}

Gonorrhea is caused by gram-negative diplococci, \emph{Neisseria
gonorrhoeae} . It is one of the most common reportable, sexually
transmitted infections in the United States. Over 700,000 cases were
reported to the CDC in 2021 with about half of these infections
estimated to be resistant to at least one antibiotic (1), although most
strains remain susceptible to ceftriaxone. While the typical gonorrheal
infection leads to cervicitis in women and urethritis in men; untreated
infections often result in pelvic inflammatory diseases, ectopic
pregnancies, and infertility in both men and women (2). The disseminated
gonorrheal infection (DGI) is seen in less than 3\% of all gonorrheal
cases with complications ranging from polyarthritis to an overlap of
polyarthritis with cutaneous manifestations (3), and in rare instances,
endocarditis and meningitis have been reported (4,5).

\textbf{Case Description:}

A 42-year-old woman with a history of asthma and diet-controlled type 2
diabetes presented to the hospital with fever, skin rash, knee, and
ankle pain for four days. Prior to admission, the patient developed a
fever of 103.9 followed by the development of a generalized non-pruritic
rash and subsequently developed polyarticular swelling and erythema in
her right foot and bilateral knees. The patient reported unprotected
sexual intercourse with a new partner a week prior to the presentation.
Vitals on admission were blood pressure of 137/80 mmHg, pulse 88 beats
per minute, temperature 36.6 degrees Celsius, respirations 18 breaths
per minute, and oxygen saturation of 99\% on room air. On examination,
the skin showed the presence of diffuse vesiculopustular, non-tender,
non-pruritic rashes (Figure 1). The right foot was erythematous and
associated with ankle edema, and the left knee exhibited mild swelling
with a reduced range of motion due to tenderness. Labs on admission
showed a white count of 21,000/microL. HIV antigen and antibody testing
was negative. Two sets of blood cultures were negative. The urine NAAT
was indeterminate. She was started empirically on intravenous vancomycin
and ceftriaxone. Right knee swelling confirmed joint effusion on imaging
which was aspirated, revealing monosodium urate crystals in synovial
fluid analysis and the culture growing gram-negative diplococci. No
cervical motion tenderness was noted. Disseminated gonococcal infection
was suspected and the patient underwent recurrent synovial joint
washouts due to persistent symptoms of pain and reduced range of motion.
The patient's symptoms improved over the 5-day hospital course and
ultimately discharged home to continue ceftriaxone for a total of 7 days
post-final joint washout.

\textbf{Discussion:}

Gonorrhea is a sexually transmitted infection caused by \emph{N.
gonorrhoeae} with resultant genital infections, and rarely, pharyngeal
and anorectal infections (6). Bacteremia resulting in DGI is found to be
more common during pregnancy, menstruation, and with the use of
intra-uterine devices (IUDs) (7) and seen in about 0.5-3\% of the cases
(8). Other risk factors predisposing for dissemination include
homosexual or bisexual men, infection with resistant strains, and
complement deficiencies (9). Eculizumab, a monoclonal antibody to
complement protein 5, used for treatment of complement mediated
conditions like hemolytic-uremic syndromes has been associated with an
increased risk of meningococcal disease (10). DGI is more common among
females than males; this is likely due to a higher percentage of women
remaining asymptomatic, hence delaying treatment, along with subsequent
endometrial exposure of submucosal vessels to the bacteria, leading to
the dissemination of infection (11).

Blood cultures are found to be positive in less than one-third of
disseminated gonorrhea cases. Positive blood cultures are more often
seen in patients that present with cutaneous involvement as well as
gonococcal polyarthritis. Cutaneous manifestations in DGI along with
polyarthritis can also be accompanied by tenosynovitis. Cutaneous
findings are predmonantly noted on the trunk and extremities. Our
patient was found to have a generalized maculopapular, non-tender, and
petechial rash. Joint involvement in DGI is manifested by polyarthralgia
but never as suppurative arthritis (12).

Polyarthralgia is typically asymmetric and can affect all joints, large
and small. Our patient was also a newly diagnosed diabetic which likely
led to worsening of the underlying infection and~presentation of
cutaneous manifestations. A study of 55 patients with disseminated
infections from Neisseria gonorrhoeae revealed that this complication
occurs in young adults, with a predominance in women (80\%) with
arthritis being the most common manifestation (13).

\emph{N. gonorrhoeae} is isolated in about 25\% of the synovial fluid
obtained by arthrocentesis. Synovial cultures are less sensitive in
gonococcal arthritis compared to NAAT in the detection of \emph{N.
gonorrhoeae} . Whenever feasible, NAAT is recommended as the initial
test for patients, including asymptomatic patients, with a suspicion of
gonorrhea. One case study concluded that when DGI is considered as part
of the differential diagnosis, the gonococcal infection cannot be
excluded solely on negative urine NAAT. A thorough history, which
includes sexual history, testing of appropriate sites (rectal,
oropharyngeal) along with, NAAT of the joint aspirate should be
considered when suspicion is high (5). Cautious interpretation of a
negative NAAT must be done since some \emph{N. gonorrhoeae} subtypes can
have variations in the targeted sequences tested by NAAT resulting in a
false-negative test (14).

DGI has been reported in patients with SLE; likely mechanisms include
complement depletion, use of immunosuppressive medications, and an
association between SLE and inherited complement disorders (15). Given
the overlap of symptoms between DGI and SLE, a high degree of suspicion
is warranted to diagnose DGI in patients with SLE (16).

\textbf{Conclusion:} Early detection and appropriate treatment of
disseminated gonorrhea with cutaneous and joint involvement is the key
to the prevention of lifelong disability. Given its rare presentation,
low threshold must be held for prompt~testing of gonorrhea and
initiation of treatment, especially in patients with SLE and
immunosuppressed states. A detailed sexual history is indicated in all
the patients when DGI is considered a possible diagnosis to avoid delays
in the diagnosis and treatment. If DGI is suspected and considered a
likely differential, a negative urine NAAT should not dissuade the
clinicians from pursuing further diagnostic tests.

\textbf{Acknowledgments:}

The authors would like to thank the patient for their support in
gathering information and for their interest in publishing this case.

\textbf{Funding Statement:}

This research was not funded.

\textbf{Conflict of Interest Statement:}

The authors declare no conflict of interest.

\textbf{Data Availability Statement:}

Not applicable.

\textbf{Ethics Statement:}

This is a case report that does not require formal ethical committee
approval. Data were anonymously registered in our database.

\textbf{Consent:}

Written informed consent was obtained from the patient to publish this
report in accordance with the journal's patient consent policy.~ A copy
of the written consent is available for review by the Editor-in-Chief of
this journal on request.

\textbf{Clinical Trial Registration:}

This is not an interventional study. We only reported the patient's
findings from our database as a case report.

References:

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3. Burns JE, Graf EH. The Brief Case: Disseminated Neisseria gonorrhoeae
in an 18-Year-Old Female. J Clin Microbiol. 2018 Apr;56(4):e00932-17.

4. Humbert MV, Christodoulides M. Atypical, Yet Not Infrequent,
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5. Mathew R, Chahin M, Isache C. Neisseria gonorrhoeae: An Unexpected
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15. Walport MJ. Complement and systemic lupus erythematosus. Arthritis
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16. Gonococcemia mimicking a lupus flare in a young woman - M Dutertre,
D Tomasevic, Y Guillermin, S Durupt, C Grange, S Debarbieux, E Martin, I
Durieu, 2014 {[}Internet{]}. {[}cited 2023 May 30{]}. Available from:
https://journals.sagepub.com/doi/abs/10.1177/0961203313507989?journalCode=lupa\selectlanguage{english}
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