Neisseria gonorrhoeae infective endocarditis
- Marylou Fenech ,
- Thelma Xerri ,
- Paula Grech and
- Anette Portelli
- Infectious Diseases/ Haematology, Mater Dei Hospital, Msida, Malta
- Correspondence to Dr Marylou Fenech; marylou.fenech@gov.mt
Abstract
We present a case of endocarditis secondary to disseminated Neisseria gonorrhoeae infection affecting the native tricuspid valve. After a thorough workup, our patient was treated conservatively with appropriate intravenous antibiotic therapy for 6 weeks. A follow-up echocardiogram showed resolution of the vegetation without any residual valvular involvement. Literature review reveals 99 cases of infective endocarditis which occurred secondary to N. gonorrhoeae infection, of which, only 4 cases (6%) affected the tricuspid valve. Through this case report, we highlight the importance of thorough history taking including a sexual and social history, as well as careful recognition of the clinical signs, which helped us reach this uncommon diagnosis while always maintaining a high clinical suspicion of rare causes of endocarditis.
Background
Neisseria gonorrhoeae is the second most common reported sexually transmitted disease after chlamydia. Both infections pose increased challenges to public health. Reports of multidrug-resistant gonorrhoea, as well as rising asymptomatic cases, are also a cause of public health concern.1
Up to 3% of cases of infections with N. gonorrhoeae may become disseminated, usually causing a triad of arthralgia, tenosynovitis and skin lesions. In rarer cases, 1%–2% may result in infective endocarditis (ie,) with about 99 cases being reported in the literature.1 Women tend to have a higher frequency of gonococcal sepsis while men are noted to have a higher rate of gonococcal endocarditis.2
Case presentation
We report a case of a man in his 60s who presented with a 6-day history of myalgias and arthralgias, associated with fever, chills, and bilateral knee erythema. These were accompanied by weight loss and erythematous lesions over the dorsum of the left foot, bilateral palms and left thumb (figures 1, 2A,B and 3). The lesions were described as haemorrhagic bullae about 0.5 cm large, most evidently over the left medial dorsum of the foot and the left second toe (figure 1). Accompanying right-sided knee joint swelling was noted as well as tenderness over the right knee and bilateral proximal interphalangeal joints of the hands. Loss of finger flexion and elbow extension was also noted.
Haemorrhagic bullae over the second toe of the left foot around 0.5 cm in diameter and another smaller similar lesion superior to the medial malleolus of the left foot.
A and B- Small well-circumscribed haemorrhagic bullae over the right and left palm respectively.
Bulla over medial aspect of the left thumb.
He was otherwise healthy and suffered from no other medical comorbidities. He was a smoker and drank about six units of alcohol per day. On further history taking, the patient confirmed that he engaged in unprotected sexual intercourse with a sex worker prior to the presentation at clinic.
Investigations
Admission blood investigations showed an elevated white cell count of 20.29×109/ L (range 4.3–11.4×109/L) with a neutrophilia of 18.34×109/ L (range 2.1–7.2×109/ L and a lymphopenia of 0.68×109/ L (range 1.3–3.6×109/ L). Of note, he was found to have high inflammatory markers with a C reactive protein of 369.9 mg/L (range 0–6 mg/L) and an erythrocyte sedimentation rate of 127 mm first hour (range 12–16 mm first hour). He also had a slightly elevated alkaline phosphate of 243 U/L (upper limit of normal 129 U/L) and a gamma glutamyl transferase of 92 U/L (upper limit 61 U/L), with a normal bilirubin and alanine transaminase. Renal function and electrolytes were also within normal limits. A baseline chest X-ray was within normal limits.
Initially, the patient was admitted under a general medical firm and was started provisionally on ceftriaxone and metronidazole. Three sets of blood cultures were taken from different peripheral sites. Unfortunately, the blood cultures were taken after two doses of antibiotics had already been administered. A CT of the thorax, abdomen and pelvis was unremarkable.
In view of the peripheral skin lesions, possibly implying embolic phenomena, a transthoracic echocardiogram was performed to exclude infective endocarditis. The TTE showed a possible vegetation on the tricuspid valve (figure 4). This was followed up by a transoesophageal echocardiogram and this confirmed a 0.7×0.5 cm vegetation on the commissure between the anterior and posterior leaflets of the native tricuspid valve. Mild tricuspid regurgitation was noted, with a peak gradient of 33 mm Hg along with mild pulmonary regurgitation.
Small vegetation (marked with arrows) seen on transthoracic echocardiogram attached to commissure between anterior and posterior leaflets with mild tricuspid regurgitation
At this point, the infectious diseases team took over the patient’s care, and metronidazole was stopped. In view of the lymphopenia and sexual history, a viral screen including HIV serology, hepatitis C antibody and hepatitis B surface antigen were taken and resulted negative. Other blood investigations taken as part of the workup which also resulted as negative included syphilis serology, brucella antigen, coxiella serology (phases 1 and 2), legionella urinary antigen, mycoplasmaIgM antibody and bartonella serology. Urine samples for chlamydia and gonorrhea sent for PCR, taken as part of the genitourinary screen (GU), were also negative.
In view of the joint swelling and pain, an initial joint aspiration was attempted to exclude a septic joint, gout or pseudogout but no fluid could be acquired. An autoimmune profile including antinuclear antibody, rheumatoid factor, anticyclic citrullinated peptide and antineutrophil cytoplasmic antibodies all resulted negative.
Despite 2 weeks of treatment with ceftriaxone, the patient was still having worsening joint pains and hence a repeat aspirate was attempted. A 5 mL of serosanguinous fluid was acquired from the left knee and 5 mL of cloudy aspirate was acquired from the right knee. Abundant polymorphs were detected but no bacteria were cultured. The sample of synovial fluid was sent for gonorrhoea PCR in view of the clinical suspicion of disseminated gonorrhoea based on the patient’s cutaneous lesions, joint involvement and recent unprotected sexual exposure. The gonorrhoea PCR on the synovial fluid resulted as positive.
In view of persisting anaemia throughout the admission, further investigations were taken in the form of serum plasma electrophoresis which showed a positive monoclonal band at 9.5%. An IgG lambda monoclonal band was isolated. This result was discussed with the haematology specialist and a presumptive diagnosis of monoclonal gammopathy of unknown significance (MGUS) was made.
Differential diagnosis
Infective endocarditis complicated by reactive oligoarthritis. Other possible diagnoses included: septic knee joint with disseminated infection, gout or pseudogout in the setting of endocarditis and Reiter’s syndrome. A final diagnosis of tricuspid endocarditis secondary to disseminated gonorrhoea was made.
Treatment
A total of 6 weeks intravenous ceftriaxone was given, initially started as an inpatient and then continued after discharge by the home antibiotic therapy team.
Outcome and follow-up
A follow-up echocardiogram was performed after completion of 6 weeks of antibiotic treatment which showed normal left ventricular dimensions and systolic function, normal wall motion, ejection fraction estimated 59%, normal valve morphology including the tricuspid valve with no vegetations, mild TR was present.
Discussion
Right-sided infective endocarditis accounts for 5%–10% of all IE cases with the tricuspid valve being the most commonly site involved. It is mostly associated with intravenous drug use, intracardiac devices and central venous catheters. Prevalence is increasing in view of the increasing rate of intravenous drug use and implantable cardiac interventions.3
Non-functional embryonic remnants in the right atrium such as the crista terminalis, eustachian valve and Thebesian valve can also be a niche for infective endocarditis. A recently published case report on Methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis involving an automated implantable cardioverter-defibrillator and the eustachian valve, emphasises the importance of looking for rudimentary structures during echocardiography for the presence of vegetations in suspected IE cases.4
The typical microorganisms involved in right-sided IE include gram positive organisms, mostly Staphylococcus aureus and coagulase-negative Staphylococci. Streptococci have been reported at a higher prevalence in alcoholics.3 Pseudomonas aeruginosa and other gram-negative bacteria are also reported to have an increasing prevalence. Fungal endocarditis rarely involves the right heart but have been reported at a higher incidence in the literature in the immunocompromised population. Less common microorganisms include Proteus mirabilis, Bartonella spp and Coxiella burnetti.5
Other rarer causes of right-sided IE include non-infective aetiologies, referred to as marantic endocarditis. This can be secondary to hypercoagulable states, malignancies such as adenocarcinoma and autoimmune conditions including systemic lupus erythematosus and rheumatoid arthritis.6
In our case, cultures were sent for all the above-mentioned organisms which proved to be negative. In view of the patient’s clinical presentation, symptomatology and recent promiscuous exposure, although a rare cause of IE, N. gonorrhoeae was suspected.
Gonococcal endocarditis most commonly presents with a history of 2–4 weeks of non-specific symptoms of lethargy, fatigue and fever. This usually predates a triad of arthritis, rash and tenosynovitis, as well as heart murmurs. During this stage, bundle branch blocks may also be evident on ECGs.7
The most common presenting symptom of disseminated disease is an asymmetric polyarthralgia which may be migratory. In other cases, dermatological presentation occurs first, followed by localisation of infection within a particular joint, with the knee joint being most affected, as in this case. Rashes may vary from maculopapular, pustular, necrotic and vesicular. Some may present with haemorrhagic skin lesions (as in our patient), or possibly erythema nodosum or multiforme. These lesions usually resolve within 5 days.8
While in our case, the patient presented with a subacute presentation, gonococcal cardiac involvement may be quite aggressive, resulting in rapid valve destruction and large vegetations. These cases have a high mortality rate, and most patients require urgent valvular surgery. Most common involvement include, the aortic valve (50%), mitral valve (24%) and, as in our case, the tricuspid valve (6%).1
Causes which seem to favour dissemination of gonorrhoea includes consumption of alcohol, chronic corticosteroid use, intravenous drug use as well as haematological conditions. In our case, the possibility of an MGUS may have aided in the dissemination process.
However, there is some evidence that the patient’s immunity is not the only factor which controls dissemination risk. Certain subtypes of gonococci lack protein II on their cell surface membrane which may result in impaired chemotactic response, resulting in disseminated disease. The presence of protein 1A serotype also has a similar effect. These strains are noted to be more resistant against complement mediated immune responses but in turn are noted to be more penicillin sensitive.8
The difficulty with disseminated gonococcal infection is that they are frequently associated with sterile cultures and can be very fastidious to detect. Most diagnoses would hence require a high index of clinical suspicion. Only a third of blood cultures can detect gonorrhoea.8 A positive synovial fluid culture is very often associated with negative blood cultures. Skin biopsy and blood cultures may result in a higher diagnostic yield. In our case it took a PCR test on synovial fluid to discover the organism and clinch the final diagnosis.
Patients with the clinical features of disseminated gonococcal infection should have urogenital, rectal and pharyngeal specimens submitted for microbiologic testing for N. gonorrhoeae. Often, patients with disseminated gonococcal infection have evidence of infection at urogenital, rectal or pharyngeal sites despite lack of symptoms at these sites.8 However, our patient did not have confirmed gonococcal infection at these latter mentioned sites, which made diagnosis of disseminated gonococcal infection more challenging.
From the literature, the cases discussed to date showed that with the appropriate antibiotic regimen, complete recovery can be achieved without surgical intervention. The recommended treatment of choice at present is ceftriaxone in the first instance.8
Learning points
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The importance of not ruling out disseminated gonococcal infection despite having negative urogenital, rectal and pharyngeal gonococcal PCR tests.
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The importance of taking blood cultures prior to starting antibiotics.
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High clinical suspicion of rare causes of infective endocarditis such as gonorrhoea which can be very difficult to confirm in the laboratory.
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The importance of persisting in getting a microbiological diagnosis in culture-negative endocarditis.
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Fluids other than blood, and molecular tests besides cultures, may yield the eventual organism.
Ethics statements
Patient consent for publication
Acknowledgments
Acknowledgements go to the following physicians who were involved directly in the patient’s diagnostic work up and management—Dr. T. Piscopo (Consultant Infectious Diseases), Dr. B. Caruana Montaldo (Admitting General Medicine Consultant), Mr. R. Giordimaina (Consultant Orthopaedics) and Dr. A. Parascandolo (Specialist in Microbiology).
Footnotes
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Contributors MF and TX were responsible for the manuscript preparation and literature review. AP and PG contributed towards editing and review of the final manuscript. All authors were involved in the patient’s management and treatment.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
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