A rare presentation of disseminated gonococcal infection with pleuritis and pericarditis: a case report and comprehensive review.

A 48-year-old woman (born in Burundi) was admitted to the internal medicine ward after presenting to the emergency department with progressive lower left abdominal pain and dyspnea on exertion for one week. She also developed a fever the day before admission. The patient returned from a three-week visit to Tanzania four days prior to admission. Past medical history included adenomyosis with metrorrhagia for 4 months, a gastric bypass, and a resolved hepatitis B infection. On physical examination, she had tenderness of the left iliac fossa, diminished breath sounds in the left lung, and a subtle pericardial rub. Vital signs were otherwise normal, and the patient was afebrile and not hypoxemic. A gynecological examination revealed old blood in the discharge, but there was no cervical motion tenderness. A cervical swab was taken. Laboratory tests revealed an elevated C-reactive protein (CRP) level of 213 mg/L (N: < 8.2 mg/L) and a low haemoglobin level of 4.5 mmol/L (N: 7.5–10.0 mmol/L), with a mean corpuscular volume (MCV) of 89 fl. (N: 80–100 fl.). A transvaginal ultrasound revealed normal ovaries surrounded by prominent venous structures. An abdominal CT scan revealed several fluid collections in the left adnexa and infiltration of the surrounding fat tissue, suggestive of pelvic inflammatory disease (PID). Coincidentally, pericardial and bilateral pleural effusions were noted (Fig.  1 ). The electrocardiogram (ECG) was normal. The patient had been living in the Netherlands together with her husband and children, who were well. She reported having sexual contact solely with her husband. The sexual history of the husband was unknown. Fig. 1 Abdominal CT scan at admission showing pericardial and bilateral pleural effusions (predominantly in the left pleural cavity) Abdominal CT scan at admission showing pericardial and bilateral pleural effusions (predominantly in the left pleural cavity) The following day, approximately 1000 millilitres of exudative fluid was aspirated from the left pleural cavity, with a total leukocyte count of 6.11 × 10 9 /L, of which 69% were polymorphonuclear cells. Transthoracic echocardiography (TTE) showed minimal pericardial effusion without signs of tamponade, which was deemed insufficient for pericardiocentesis. Both the cervical swab and pleural fluid aspirate were polymerase chain reaction (PCR)-positive for N. gonorrhoeae , indicating disseminated infection. There were no clinical signs of arthritis or dermatitis. The patient was subsequently treated with intravenous ceftriaxone for two weeks (1 gram per day). She received a red blood cell transfusion to treat anaemia. A chest tube was placed four days later due to recurrent pleural effusion, and an additional 850 millilitres of fluid was drained (Fig.  2 ). Her clinical condition improved, and her CRP level decreased to 43 mg/L within several days. Blood and pleural cultures showed no growth. Extensive diagnostic tests performed for other infectious causes were either negative (HIV, tuberculosis, malaria, dengue, chikungunya, Zika infection, chlamydia, and syphilis) or indicated past infection (Epstein-Barr virus, cytomegalovirus, hepatitis B virus, parvovirus B19). The serum antinuclear antibody (ANA) test was dubiously positive, and extractable nuclear antigen antibodies and M protein were not present. After completing the intravenous antibiotic regimen, she became asymptomatic and her metrorrhagia subsided. Fig. 2 Chest X-rays performed to assess pleural fluid build-up. A  = at admission. B  = 5th hospital day (3rd day of ceftriaxone treatment). C  = after placement of the chest tube in the left pleural cavity Chest X-rays performed to assess pleural fluid build-up. A  = at admission. B  = 5th hospital day (3rd day of ceftriaxone treatment). C  = after placement of the chest tube in the left pleural cavity

Gonorrhoea is a sexually transmitted infection (STI) that is spread primarily through vaginal, anal or oral sex. It is caused by Neisseria gonorrhoeae , a gram-negative diplococcus that causes urogenital tract infections. Gonorrhoea is considered a significant public health problem by the World Health Organization (WHO), which estimated 82.4 million new infections among adults globally in 2020 [ 1 ]. Symptoms usually appear 1–14 days after exposure to an infected partner. Men with localized gonococcal infection often present with penile discharge, dysuria and swollen painful testes. Women are usually asymptomatic, delaying diagnosis and antibiotic treatment. This in turn increases the risk of disseminated gonococcal infection (DGI), which if left untreated, can lead to severe complications [ 1 ].

Our case report describes a woman with gonococcal pleuritis and presumed gonococcal pericarditis. Both are rare manifestations of DGI, but their combination has not been previously reported in the literature. Additionally, this is the first description of microbiologically proven gonococcal pleuritis, with N. gonorrhoeae detected in the pleural fluid by PCR. In sexually active patients presenting with nonspecific symptoms and signs of inflammation, a thorough clinical evaluation, including sexual history and microbiological testing, is essential. Clinicians should be aware of classical manifestations of DGI as well as the possibility of atypical presentations and multiple organ involvement.

In 2016, the estimated prevalence of gonorrhoea in the African region was 1.6% for men and 1.9% for women. In comparison, the estimated prevalence of gonorrhoea in the European region was 0.3% for both men and women [ 2 ]. Disseminated gonococcal infection (DGI) refers to a heterogeneous group of clinical syndromes caused by the hematogenous spread of N. gonorrhoeae to nonmucosal sites [ 3 ]. DGI occurs in 0.5 to 3% of patients with gonorrhoea, mostly affecting women under 40 years of age [ 4 ]. The predominance of DGI in females is a consequence of localized urogenital infections often being asymptomatic and left untreated. DGI develops within 2–3 weeks after the onset of gonococcal infection [ 3 ]. Menstruation and pregnancy are important precipitating factors for DGI [ 5 ]. This is caused by various factors, such as hormonal changes, a relatively alkaline pH of the cervical mucus, and reduced cell-mediated immunity, which together ultimately facilitate gonococcal growth [ 6 – 8 ]. Other risk factors associated with DGI include underlying complement deficiencies [ 9 ]. The most common clinical manifestations of DGI are arthritis and dermatitis, which occurred in 85.5% and 60% of patients, respectively, in a four-year retrospective cohort [ 5 ]. The literature describes two classic forms of DGI. First, the “septic” form is characterized by a triad of migratory polyarthralgias, tenosynovitis, and dermatitis [ 10 ]. It is typically accompanied by bacteremia and systemic symptoms (fever, chills, and generalized malaise). Second, the “nonseptic joint localization” form is characterized by monoarthritis, purulent joint effusions and positive joint cultures without systemic symptoms [ 11 ]. These two forms of DGI may represent successive stages of the same disease, or perhaps even a continuous spectrum in which certain “transition” patients exhibit symptoms of both stages [ 12 ]. The heterogenous clinical presentation of DGI may be explained by differences in host immune responses, bacterial virulence factors, and the pathogen’s capacity to evade complement-mediated killing [ 13 ]. The definite diagnosis of DGI is made by demonstration of N. gonorrhoeae in a nonmucosal site, such as blood, synovial fluid, or a skin lesion [ 4 ]. If microbiological tests are positive only at mucosal sites, the diagnosis can be made if there is a typical clinical presentation consistent with disseminated infection. Initial management of DGI consists of antibiotic treatment with ceftriaxone, a third-generation cephalosporin, in consultation with an infectious disease specialist. Antibiotic treatment should be continued for at least 7 days until there is clear clinical improvement [ 4 ]. In Europe, N. gonorrhoeae isolates displaying ceftriaxone resistance have been reported sporadically in recent years [ 14 ]. In a study in Tanzanian STI clinics, ceftriaxone-resistant N. gonorrhoeae was reported to have a prevalence of 0.6% (1 out of 163 isolates) [ 15 ]. Although ceftriaxone resistance has yet to be reported in the Netherlands, the average minimum inhibitory concentration (MIC) has been steadily increasing in recent years [ 16 ]. In the future, increasing antimicrobial resistance could lead to treatment failure and a greater disease burden. Testing antimicrobial susceptibility in obtained cultures is necessary to identify resistant strains and tailor the antibiotic regimen. Although aspiration/drainage is recommended for gonococcal arthritis with purulent joint effusions, there are currently no guidelines for the optimal management of pericardial or pleural effusions associated with DGI. Pericarditis is a rare manifestation of DGI. A comprehensive literature search in the PubMed database until September 2024 revealed only eight prior cases of pericarditis reported in English [ 17 – 23 ]. The literature findings are summarized in Table 1 . In two of the cases, pericardial dissemination was proven by the isolation of N. gonorrhoeae in the pericardial fluid. Bristowe et al. demonstrated N. gonorrhoeae using 16 S PCR [ 18 ], whereas Coe et al. observed gram-negative diplococci in pericardial tissue together with a positive synovial fluid culture for N. gonorrhoeae [ 19 ]. In both cases, the patient presented with chest pain and dyspnea, and the pericardial fluid cultures showed no growth. All remaining cases had electrocardiographic changes suggestive of pericardial inflammation, three of whom were symptomatic and three of whom were asymptomatic. One patient developed mild to moderate pericardial effusion without signs of tamponade [ 23 ]. Table 1 Summary of reported cases of gonococcal pericarditis Author Gender Age (years) Symptoms Diagnostics Disease evolution Microbiologic evidence N . gonorrhoeae Antibiotic regimen Trop. WBC ECG TTE Boone (probable) [ 16 ] M 32 - Fever/chills - Myalgia - Polyarthralgia -> 1 day later chest pain and dyspnea N ↑ (17,6) ST elevation and PTa depression Normal Skin lesions +  purulent monoarthritis knee Synovial fluid + pharyngeal cultures IV penicillin G 12 million units/day (7 days) -> oral penicillin (7 days) Bristowe (proven) [ 17 ] M 42 - Fever - Chest pain - Dyspnea N ↑ (48,3) ST elevation Moderate effusion Deterioration: AKI and tamponade requiring pericardiocentesis (700 ml) Pericardial fluid 16 S PCR . Negative cultures. Amoxicillin clavulanate -> IV ceftriaxone 2 g/day (4 weeks) *Coe (proven) [ 18 ] F 35 - Fever - Polyarthralgias - Chest pain - Dyspnea - Vaginal discharge 4 weeks prior to admission -> 1 week later monoarthritis wrist ? ↑ (20) Small Q waves (V1-V3) Significant effusion with early tamponade - Monoarthritis wrist after initiating prednisone for presumed lupus flare. - Purulent fluid aspirated from the joint. - Pericardiocentesis (450 cc). - Rapid improvement within days after starting AB. - Positive synovial fluid culture - Gram-negative diplococci in Gram stain of pericardial tissue - Negative pericardial fluid culture IV ceftriaxone 2 g/day -> IV high-dose penicillin G (24 million units per day) (2 weeks) Holmes (probable) [ 19 ] M ? - Urethritis - Chest pain - Pericardial rub ? ? ST elevation + peaked T-waves (I, II, aVF, V3-4) ? Pericardiocentesis was attempted unsuccessfully Positive culture (site not described) ? Vietzke (probable) [ 20 ] F 22 - Fever - Purulent monoarthritis knee ? ↑ (14,2) Nonspecific ST-T wave changes Day 5: inverted T-waves and coved ST-segments (II, III, aVF, V3-V6) ? Inflammation subsided without disability Cervical + synovial fluid cultures IV + intra-articular penicillin Vietzke (probable) [ 20 ] M 28 - Purulent monoarthritis wrist - Soft cardiac murmur ? ↑ (24,9) ST elevation (I, II, aVF, V4-V6) – Complete remission of symptoms/signs Synovial fluid culture Penicillin (10 days) **Watring (possible) [ 21 ] F 25 - Fever/chills - Polyarthralgia - Skin rash N N Unspecified changes consistent with pericarditis – Fever subsided after 5 days of IV antibiotics Cervical + urethral cultures IV + oral penicillin (total 3 weeks) Wilson (probable) [ 22 ] F 23 - Fever - Polyarthralgias -> 3 days later purulent monoarthritis knee ? ? ST elevation (diffuse) Mild-moderate effusion 2 days later chest pain and pericardial rub. Symptoms were treated with aspirin and subsided within 48 h. Synovial fluid culture IV ampicillin (2 weeks) M = male, F = female, trop. = troponin, WBC = serum white blood cell count, N = normal, ↑ = elevated, ? = not reported, ECG = electrocardiogram, TTE = transthoracic echocardiogram, AKI = acute kidney injury, AB = antibiotics, IV = intravenous *The patient had a known history of SLE **The patient was 34 weeks pregnant. The newborn experienced no morbidity after delivery Summary of reported cases of gonococcal pericarditis Boone (probable) [ 16 ] - Fever/chills - Myalgia - Polyarthralgia -> 1 day later chest pain and dyspnea ↑ (17,6) Bristowe (proven) [ 17 ] - Fever - Chest pain - Dyspnea ↑ (48,3) *Coe (proven) [ 18 ] - Fever - Polyarthralgias - Chest pain - Dyspnea - Vaginal discharge 4 weeks prior to admission -> 1 week later monoarthritis wrist ↑ (20) - Monoarthritis wrist after initiating prednisone for presumed lupus flare. - Purulent fluid aspirated from the joint. - Pericardiocentesis (450 cc). - Rapid improvement within days after starting AB. - Positive synovial fluid culture - Gram-negative diplococci in Gram stain of pericardial tissue - Negative pericardial fluid culture IV ceftriaxone 2 g/day -> IV high-dose penicillin G (24 million units per day) (2 weeks) Holmes (probable) [ 19 ] - Urethritis - Chest pain - Pericardial rub Vietzke (probable) [ 20 ] - Fever - Purulent monoarthritis knee ↑ (14,2) Nonspecific ST-T wave changes Day 5: inverted T-waves and coved ST-segments (II, III, aVF, V3-V6) Vietzke (probable) [ 20 ] - Purulent monoarthritis wrist - Soft cardiac murmur ↑ (24,9) **Watring (possible) [ 21 ] - Fever/chills - Polyarthralgia - Skin rash Wilson (probable) [ 22 ] - Fever - Polyarthralgias -> 3 days later purulent monoarthritis knee 2 days later chest pain and pericardial rub. Symptoms were treated with aspirin and subsided within 48 h. M = male, F = female, trop. = troponin, WBC = serum white blood cell count, N = normal, ↑ = elevated, ? = not reported, ECG = electrocardiogram, TTE = transthoracic echocardiogram, AKI = acute kidney injury, AB = antibiotics, IV = intravenous *The patient had a known history of SLE **The patient was 34 weeks pregnant. The newborn experienced no morbidity after delivery Pulmonary complications of DGI, including pleuritis, are similarly rare. Previous reports are scarce and date back to the late 19th century, at a time when current molecular techniques such as PCR were not available [ 24 – 26 ]. The literature findings are summarized in Table 2 . Although pleurisy was a presenting symptom in some cases, N. gonorrhoeae was only isolated from sputum samples and not from the pleural fluid itself. Additionally, pleural effusions can occur secondary to Fitz-Hugh-Curtis syndrome (FHCS) [ 27 ], a form of perihepatitis caused by chronic pelvic inflammatory disease (PID) and the intraperitoneal spread of N. gonorrhoeae. [ 28 ] In these cases, adhesions in the subphrenic spaces may lead to inflammation of the diaphragm, which can spread to the surrounding pleura of the right lung. It is unclear whether the pleural effusion in FHCS is reactive or caused by direct bacterial invasion [ 29 ]. Table 2 Summary of reported cases of (presumed) gonococcal pleuritis Author Gender Age (years) Symptoms Diagnostics Disease evolution Microbiologic evidence N . gonorrhoeea Antibiotic regimen Clinic X-ray Jicinsky (probable) [ 23 ] M 24 - Chills - Night sweats - Fever - Productive cough - Weight loss - Scrotal swelling and penile discharge for months - Tachypnea (40–42/min) - Left pleural friction rub and percussion dullness Pleuritic thickness in left lung (no infiltration or fluid described) - Dyspnea and cough worsened - Pleuritic process terminated within 8 weeks Large numbers of gonococci identified in microscopic examination of sputum culture ? Fisher [ 24 ] M 26 - Pleurisy (gonorrhoea 4 years prior to present disease) ? ? - Increased cough, followed by copious purulent expectoration - Pleurisy subsided 7 months after onset of symptoms Large numbers of gonococci identified in sputum ? *Irons [ 25 ] M = male, F = female, ? = not reported *Six cases are described, but none of them had pleural fluid. In the first case, dry pleurisy is mentioned The author mentioned two cases of gonococcus pneumonia with a consolidation and positive culture of gonococci in the sputum (authors: Bressel , Dieulafoy , there is no referral to the cases) . The pulmonary lesions were possibly due to infarctions secondary to endocarditis with valvular defects In addition, the author reported that pleurisy is more common than pneumonia due to N. gonorrhoeae. Prochaska described a case in which N. gonorrhoeae was isolated from pleural fluid, although no further information was given on this finding Summary of reported cases of (presumed) gonococcal pleuritis Jicinsky (probable) [ 23 ] - Chills - Night sweats - Fever - Productive cough - Weight loss - Scrotal swelling and penile discharge for months - Tachypnea (40–42/min) - Left pleural friction rub and percussion dullness - Dyspnea and cough worsened - Pleuritic process terminated within 8 weeks Fisher [ 24 ] - Increased cough, followed by copious purulent expectoration - Pleurisy subsided 7 months after onset of symptoms *Irons [ 25 ] M = male, F = female, ? = not reported *Six cases are described, but none of them had pleural fluid. In the first case, dry pleurisy is mentioned The author mentioned two cases of gonococcus pneumonia with a consolidation and positive culture of gonococci in the sputum (authors: Bressel , Dieulafoy , there is no referral to the cases) . The pulmonary lesions were possibly due to infarctions secondary to endocarditis with valvular defects In addition, the author reported that pleurisy is more common than pneumonia due to N. gonorrhoeae. Prochaska described a case in which N. gonorrhoeae was isolated from pleural fluid, although no further information was given on this finding To the best of our knowledge, the combination of gonococcal pleuritis and pericarditis is an unusual manifestation of DGI that has not been described previously. In contrast with the literature, our patient did not present with the classic manifestations of DGI, such as arthritis, tenosynovitis or dermatitis. Instead, imaging revealed left-sided PID as well as pleural and pericardial effusions. There were no clear radiologic signs of FHCS. N. gonorrhoeae was detected in the pleural fluid, making this the first description of microbiologically proven gonococcal pleuritis. Although several clinical features suggested pericardial involvement (dyspnea, pericardial rub, effusion), microbiological confirmation was not possible as no pericardiocentesis was performed. However, it is reasonable to assume that N. gonorrhoeae was the causative pathogen of the pericardial effusion, as no plausible alternative diagnosis was found after extensive diagnostic tests. Furthermore, our patient showed prompt clinical recovery with intravenous ceftriaxone, which further supported the diagnosis. As seen in the previous cases, confirming gonococcal pericarditis remains challenging, as significant effusion requiring pericardiocentesis for N. gonorrhoeae PCR or culture is often absent. No isolate was available for antibiotic susceptibility testing. Considering that the time between initial exposure to an infected partner and the onset of DGI can range between 2 and 5 weeks, our patient was likely infected either just before visiting or just after arriving in Tanzania. The patient’s adenomyosis and resulting metrorrhagia may have predisposed her to systemic dissemination of N. gonorrhoeae , and development of DGI. Another possibility is that, in retrospect, her metrorrhagia may have been an unrecognized symptom of (chronic) PID, with the initial infection occurring many months earlier.