Background
Gonococcemia is defined as the presence of Neisseria gonorrhoeae in the bloodstream, which can lead to the development of disseminated gonococcal infection (DGI). Gonorrhea is the second most often reported sexually transmitted disease (STD) in the United States behind chlamydia. About 600,000 people each year in the United States are infected, with only about half being reported.[1] Gonococcemia occurs in about 0.5-3% of patients with gonorrhea.
The clinical manifestations of this process are biphasic, with an early bacteremic phase consisting of tenosynovitis, arthralgias,[2] and dermatitis, followed by a localized phase consisting of localized septic arthritis. Other potentially severe clinical complications include osteomyelitis, meningitis, endocarditis, adult respiratory distress syndrome (ARDS),[3, 4] and fatal septic shock.[5] Polymyositis is also a rare complication of gonococcemia.
Patients who are pregnant or menstruating may be particularly prone to gonococcemia. Other populations that are at risk of infection include women and those with complement deficiencies, HIV disease, or systemic lupus erythematosus (SLE). DGI is an important, potentially life-threatening, and easily treatable clinical entity that remains the most common cause of acute septic arthritis in young sexually active adults.
Related Medscape Reference articles include Gonococcal Infections and Gonococcal Arthritis.
Pathophysiology
N gonorrhoeae organisms are spread from a primary site, such as the endocervix, the urethra, the pharynx, or the rectum, and disseminate to the blood to infect other end organs. Usually, multiple sites, such as the skin and the joints, are infected. Neisserial organisms disseminate to the blood due to a variety of factors. Such predisposing factors include host physiologic changes, virulence factors of the organism itself, and failures of the host's immune defenses.[6] For example, changes in the vaginal pH that occur during menses and pregnancy and the puerperium period make the vaginal environment more suitable for the growth of the organism and provide increased access to the bloodstream.[7, 8]
Organismal virulence factors, such as pili, aid in adherence of the organism to mucosal surfaces and impede phagocytosis by host macrophages. Outer membrane proteins (ie, proteins 1, 2, and 3) are also involved in determining the virulence of the strain of organism and are used to type the strain (ie, protein 2 is involved in adhesion to host cells). Lipo-oligosaccharides of the organism's cell membrane have marked endotoxic action and are also believed to be related to resistance to serum bacteriocidal action. Additionally, some strains of Neisseria species that are particularly pathogenic produce immunoglobulin A (IgA) proteases that aid in the survival of the organism in mucosal tissues.
Defects in the host's immune defenses are also involved in the pathophysiology, with certain patients more likely to develop bacteremia. Specifically, patients with deficiency in terminal complement components are less able to combat infection, as complement plays an important role in the killing of neisserial organisms. As many as 13% of patients with DGI have a complement deficiency. A study of 22 patients with DGI revealed that total serum complement activity was greater than 25% below the normal mean. Other causes of immunocompromise (eg, HIV, SLE) also predispose to dissemination of infection.
Epidemiology
Frequency
United States
The incidence of DGI naturally parallels the incidence of gonococcal infection. In the United States, the number of gonococcal infections peaked in the 1970s, the era of the sexual revolution. With the onset of the HIV epidemic and the practicing of safe sex techniques, the incidence has dramatically decreased from 468 cases per 100,000 population in 1975 to 100-150 cases per 100,000 population at the turn of the century. A review of women with disseminated gonococcal infection at Parkland Memorial Hospital in Texas from 1975 through 2008 showed 112 women hospitalized for treatment during the study period, 71% of whom were not pregnant.[9] Regardless, the frequency of disseminated infections declined substantively, paralleling the decreasing prevalence of mucosal N gonorrhoeae infections reported nationwide.
N gonorrhoeae infection, the second most commonly reported notifiable disease in the United States, has incidence rates that have been either declining or stable since 1996. However, in 2005, the national rate (115.6 cases per 100,000 population) increased for the first time since 1999. Further, from 2000-2005, rates in the western United States increased 42%, from 57.2 cases to 81.5 cases per 100,000 population, whereas rates in the 3 other US regions decreased (South, -22%; Northeast, -16%; Midwest, -5%).[10]
International
The incidence in developing countries is much greater than that of the United States and Western Europe, where higher levels of education and better access to health care are available. DGI develops in about 0.5-3% of persons with mucosal infection. Azariah and Perkins report increasing prevalence in New Zealand, with the primary risk factors being age younger than 25 years and Māori or Pacific ethnicity.[11]
Sex
DGI is more likely to occur in women because of a higher incidence of occult infection (difficulty in diagnosis) and also because of menstruation and pregnancy.
Age
Gonococcemia remains an important disease in the adolescent and young adult population, with a peak incidence in males aged 20-24 years and females aged 15-19 years. Symptoms and/or diagnosis in young children should raise the issue of potential child abuse.[12] Martin et al report on the identification of N gonorrhoeae from a piece of clothing, which was subsequently used to convict a man in the child sexual abuse case .[13]
Little JW. Gonorrhea: update. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Feb 2006;101(2):137-43. [Medline].
Dawe RS, Sweeney G, Munro CS. A vesico-pustular rash and arthralgia. Clin Exp Dermatol. Jan 2001;26(1):113-4. [Medline].
Belding ME, Carbone J. Gonococcemia associated with adult respiratory distress syndrome. Rev Infect Dis. Nov-Dec 1991;13(6):1105-7. [Medline].
Walters DG, Goldstein RA. Adult respiratory distress syndrome and gonococcemia. Chest. Mar 1980;77(3):434-6. [Medline].
Thiéry G, Tankovic J, Brun-Buisson C, Blot F. Gonococcemia associated with fatal septic shock. Clin Infect Dis. Mar 1 2001;32(5):E92-3. [Medline].
Cucurull E, Espinoza LR. Gonococcal arthritis. Rheum Dis Clin North Am. May 1998;24(2):305-22. [Medline].
Watring WG, Vaughn DL. Gonococcemia in pregnancy. Obstet Gynecol. Oct 1976;48(4):428-30. [Medline].
Angulo JM, Espinoza LR. Gonococcal arthritis. Compr Ther. Mar 1999;25(3):155-62. [Medline].
Bleich AT, Sheffield JS, Wendel GD Jr, Sigman A, Cunningham FG. Disseminated gonococcal infection in women. Obstet Gynecol. Mar 2012;119(3):597-602. [Medline].
Centers for Disease Control and Prevention (CDC). Increases in gonorrhea--eight western states, 2000--2005. MMWR Morb Mortal Wkly Rep. Mar 16 2007;56(10):222-5. [Medline].
Azariah S, Perkins N. Risk factors and characteristics of patients with gonorrhoea presenting to Auckland Sexual Health Service, New Zealand. N Z Med J. Apr 13 2007;120(1252):U2491. [Medline].
Harth W, Linse R. Dermatological symptoms and sexual abuse: a review and case reports. J Eur Acad Dermatol Venereol. Nov 2000;14(6):489-94. [Medline].
Martin IM, Foreman E, Hall V, Nesbitt A, Forster G, Ison CA. Non-cultural detection and molecular genotyping of Neisseria gonorrhoeae from a piece of clothing. J Med Microbiol. Apr 2007;56:487-90. [Medline].
Driessen CM, de Jong SA, Bastiaens MT, Hissink Muller W, Weenink JJ, Spooren PF. [Dermatitis or arthritis as a sign of gonorrhoea.]. Ned Tijdschr Geneeskd. 2011;155(1):A2250. [Medline].
Ackerman AB. Hemorrhagic bullae in gonococcemia. N Engl J Med. Apr 2 1970;282(14):793-4. [Medline].
Walters N, Butani L. A 16-year-old girl with recent disseminated gonococcemia now presenting with a facial rash. Ann Allergy Asthma Immunol. Feb 2005;94(2):224-7. [Medline].
Muralidhar B, Rumore PM, Steinman CR. Use of the polymerase chain reaction to study arthritis due to Neisseria gonorrhoeae. Arthritis Rheum. May 1994;37(5):710-7. [Medline].
Verzijl A, Berretty PJ, Erceg A, Krekels GA, Van den Brule AJ, Boel CH. [A pseudo-outbreak of pharyngeal gonorrhoea related to a false-positive PCR-result]. Ned Tijdschr Geneeskd. Mar 24 2007;151(12):689-91. [Medline].
Kimmitt PT, Kirby A, Perera N, et al. Identification of Neisseria gonorrhoeae as the causative agent in a case of culture-negative dermatitis-arthritis syndrome using real-time PCR. J Travel Med. Sep-Oct 2008;15(5):369-71. [Medline].
Meyers D, Wolff T, Gregory K, et al. USPSTF recommendations for STI screening. Am Fam Physician. Mar 15 2008;77(6):819-24. [Medline].
Wada K, Uehara S, Mitsuhata R, Kariyama R, Nose H, Sako S, et al. Prevalence of pharyngeal Chlamydia trachomatis and Neisseria gonorrhoeae among heterosexual men in Japan. J Infect Chemother. Apr 11 2012;[Medline].
Chen PL, Hsieh YH, Lee HC, et al. Suboptimal therapy and clinical management of gonorrhoea in an area with high-level antimicrobial resistance. Int J STD AIDS. Apr 2009;20(4):225-8. [Medline].
Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. Aug 4 2006;55:1-94. [Medline].
Centers for Disease Control and Prevention. Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep. Apr 13 2007;56(14):332-6. [Medline]. [Full Text].
Unemo M, Shipitsyna E, Domeika M. Recommended antimicrobial treatment of uncomplicated gonorrhoea in 2009 in 11 East European countries: implementation of a Neisseria gonorrhoeae antimicrobial susceptibility programme in this region is crucial. Sex Transm Infect. May 10 2010;[Medline].
Kirkcaldy RD, Ballard RC, Dowell D. Gonococcal resistance: are cephalosporins next?. Curr Infect Dis Rep. Apr 2011;13(2):196-204. [Medline].
Kunz AN, Begum AA, Wu H, D'Ambrozio JA, Robinson JM, Shafer WM, et al. Impact of Fluoroquinolone Resistance Mutations on Gonococcal Fitness and in vivo Selection for Compensatory Mutations. J Infect Dis. Apr 5 2012;[Medline].
Chacko MR, Wiemann CM, Kozinetz CA, et al. New sexual partners and readiness to seek screening for chlamydia and gonorrhoea: predictors among minority young women. Sex Transm Infect. Feb 2006;82(1):75-9. [Medline].
Fletcher PS, Shattock RJ. PRO-2000, an antimicrobial gel for the potential prevention of HIV infection. Curr Opin Investig Drugs. Feb 2008;9(2):189-200. [Medline].
Owusu-Edusei K Jr, Bohm MK, Chesson HW, Kent CK. Chlamydia screening and pelvic inflammatory disease: Insights from exploratory time-series analyses. Am J Prev Med. Jun 2010;38(6):652-7. [Medline].
Stefanelli P. Emerging resistance in Neisseria meningitidis and Neisseria gonorrhoeae. Expert Rev Anti Infect Ther. Feb 2011;9(2):237-44. [Medline].

