Are You Confident of the Diagnosis?
Characteristic findings on physical examination
There are two recognizable syndromes that may overlap. In classic disseminated gonococcal infection (DGI), the patient presents with the triad of skin lesions, polyarthralgias, and tenosynovitis. Most patients are febrile and bacteremic. The skin lesions can be macular, maculopapular, or pustular (Figure 1). They tend to occur in the extremities and occasionally on the trunk. Tenosynovitis most commonly affects the flexor surface of the fingers, and the wrists, toes, and ankles. The organism can rarely be recovered from the skin lesions or joint fluid.
The other common presentation is monoarticular or pauciarticular septic arthritis, in which the organism is more likely to be recovered from synovial fluid. The clinical picture does not differ significantly from septic arthritis caused by the more common bacterial pathogens such Staphylococcus aureus. Therefore, gonococcal infection should be suspected in any young sexually active person with septic arthritis.
Other, less common, presentations include meningitis and endocarditis. A history of recent unprotected sexual activity and symptoms of urethritis should be elicited. Women should also be questioned about their menstrual history and tested for pregnancy. Evaluation should include blood cultures as well as synovial fluid cultures from any affected joint. Synovial fluid should be cultured on chocolate and blood agar.
Samples for cultures from any potentially infected mucosal surface such as the urethra, cervix, pharynx, and rectum should be obtained and cultured on selective media such as Thayer-Martin or New York City (NYC) . Samples of synovial fluid or pustular lesions should also be obtained for a nucleic acid amplification test, which has a higher sensitivity than culture.
Tests for chlamydial urethritis should also be performed and the sexual partner should be referred for testing as well. Individuals with recurrent DGI should be evaluated for total hemolytic complement activity (CH50).
Who is at Risk for Developing this Disease?
Individuals at higher risk for developing DGI include women, especially around the time of menses or during pregnancy. It is seen most commonly in young adults or teenagers, but can be seen in any sexually active person. It has been reported that individuals with complement deficiency in the classical pathway activation cascade, as well as in the terminal components that lead to the formation of the terminal complement complex or membrane attack complex, may also be at higher risk .
What is the Cause of the Disease?
Neisseria gonorrhea usually causes a urethritis or cervicitis by adhering to the mucosal epithelium via pili or other adhesion factors. After adherence, bacteria can penetrate the mucosal epithelium via endocytosis and migrate to the submucosa, where they induce an inflammatory response. If allowed to continue untreated, this process can lead to bacteremia and dissemination.
Both host and bacterial factors probably contribute to the pathogenesis. Most DGI strains of N. gonorrhea are of porin serotype 1A, have increased nutritional requirements (auxotype AUH), and are resistant to complement bactericidal activity. Some authorities believe that some strains of DGI may tend to be less inflammatory, allowing them to cause subclinical infection; however, the higher incidence in women, in whom gonococcal urethritis and cervicitis can often be subclinical, suggests that these strains may not differ in that respect.
The higher incidence with pregnancy and during menses suggests that breaks in the mucosa and greater access to blood vessels provide increased opportunity for dissemination. Some of the signs of DGI may be secondary to the inflammatory response against bacterial antigens rather than bacterial seeding, since in many cases, organisms cannot be recovered from the skin lesions, blood, or synovial fluid.
Systemic Implications and Complications
In rare cases, meningitis or endocarditis can result from the disseminated gonococcal infection.
Due to rising resistance to fluoroquinolones, the treatment of choice is ceftriaxone. Most patients respond rapidly to treatment within 24 to 48 hrs. Following this period, the patient can be switched to an oral agent to complete a 7-day course. However, patients with arthritis should probably be treated for approximately 14 days.
The choice of oral agent should be guided by antibiotic susceptibility if the organism was recovered in culture. Otherwise, cefixime should be prescribed. In patients with a history of severe allergy to penicillin, a fluoroquinolone is still the first choice. Individuals who cannot tolerate any of these medications should be evaluated by an infectious diseases specialist for alternative therapeutic options.
Antibiotic treatment options are summarized in Table I.
|Initial Empiric Therapy|
|Ceftriaxone||1g intravenously daily||24-48 hours|
|Cefotaxime||1g intravenously every 8 hours||24-48 hours|
|Ceftizoxime||1g intravenously every 8 hours||24-48 hours|
|Cefixime||400mg twice daily||5-6 days*|
|Cefpodoxime||400mg twice daily||5-6 days*|
|Ciprofloxacin†||400mg twice daily||5-6 days*|
*Treatment for septic arthritis should be extended to 14 days.
†Fluoroquinolones are no longer first-line therapy and should be used in patients with a history of severe allergy to penicillin or after confirmation of susceptibility by in vitro testing.
Optimal Therapeutic Approach for this Disease
Most patients should be treated initially with ceftriaxone, as outlined above, followed after 24-48 hours by oral cefixime to complete a 7-day course.
Patients with severe allergy to penicillin should be treated with ciprofloxacin. Sensitivity to ciprofloxacin should be confirmed by culture, if available.
Patients with complications such as septic arthritis should be treated for 2 weeks. Patients with meningitis should be treated with intravenous antibiotics for a minimum of 3 weeks. Patients with endocarditis should be treated with intravenous antibiotics for a minimum of 6 weeks.
Individuals with a suspected disseminated gonococcal infection should be admitted to the hospital. Blood cultures should be obtained, as well as cultures from synovial fluid and pustular fluid, and plated on nonselective chocolate and blood agar. If positive, blood cultures should be repeated until bacteremia is cleared.
Urethral and cervical swabs should be submitted for culture and DNA probe for N. gonorrhea and Chlamydia trachomatis. If gonococcal infection is confirmed, and as is the case with any other sexually transmitted disease, the patient should be tested for syphillis using a rapid plasma reagin (RPR) test, and for human immunodeficiency virus (HIV).
Unusual Clinical Scenarios to Consider in Patient Management
Patients with gonococcal septic arthritis may benefit from repeated joint aspiration. Rarely is open drainage required.
What is the Evidence?
Barlett, JG, Goldenberg, DL, Sexton, DJ. “Disseminated Gonococcal Infection”. (This is a succinct review of the pathophysiology, clinical presentation, and treatment of DGI.)
Rice, PA. “Gonococcal arthritis (disseminated gonococcal infection)”. Infect Dis Clin North Am. vol. 19. 2005. pp. 853-61. (More extensive review of the pathogenesis and clinical manifestations. Treatment recommendations were based on now outdated guidelines.)
“Fluoroquinolones no longer recommended for treatment of gonococcal infections”. MMWR Morb Mortal Wkly Rep. vol. 56. pp. 332-6. (This is the update to the sexually transmitted diseases treatment guidelines from the Centers for Disease Control [CDC].)
(These are the updated CDC guidelines for the treatment of gonococcal infections.)
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