AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

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, 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 eMedicine articles include Gonococcal Infections and Gonococcal Arthritis. Additionally, the Medscape CME course Highlights of the 17th ISSTDR: International Society for Sexually Transmitted Diseases Research Annual Meeting may be of interest.

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.

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.

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%).⁹

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.

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.¹⁰

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

History reflects the classic clinical manifestations of gonococcemia—cutaneous lesions, arthritis, and, possibly, pericarditis, discussed in Physical. A dramatic increase in the incidence of gonorrhea has been observed, emphasizing the increasing importance of its complications, particularly in pregnancy.⁷

Physical

The clinical evolution of DGI is biphasic consisting of a bacteremic phase and a localized, suppurative phase.

• Bacteremic phase
• • In this phase, which occurs during the first 2-3 days of gonococcemia, the patient experiences polyarthralgias and constitutional symptoms, such as malaise, fever, and weakness.
  • The classic skin lesions are acral hemorrhagic pustules.
  • This phase is associated with a clinical picture of polyarthritis, dermatitis, and tenosynovitis. The joints most commonly involved include those of the extremities, including the wrists, the fingers, the elbows, the knees, and the ankles, with 70% of patients experiencing a migratory polyarthralgia of 1-3 joints and the remaining 30% having involvement of more than 3 joints. This arthritis is believed to be a sterile arthritis with negative culture results. Certain patient populations, such as patients infected with HIV, can experience involvement of unusual joints, such as the sternoclavicular joint and the hips, and the arthritis may have a more aggressive course, with potential destruction of the joint.
  • About 75% of patients experience a dermatitis that can vary from macular/papular to vesicular/pustular to necrotic or hemorrhagic erythema. The dermatitis is nonscarring.
  • Vasculitis has also been reported.
  • Skin lesions are often in multiple stages of development, and 5-50 individual lesions can be present. They are mostly located on the distal extremities. The face, the scalp, the palms, the soles, and the trunk are classically spared. Lesions can be painful but are usually asymptomatic, and they resolve in 4-7 days even without treatment.
  • In this bacteremic phase, the possibility of pericarditis, endocarditis, perihepatitis (Fitz-Hugh-Curtis syndrome), osteomyelitis, glomerulonephritis, as well as other end-organ involvement must be considered, but the occurrence of these conditions is rare and continues to decrease with effective treatment and earlier diagnosis of disease.
• Localized, suppurative phase
• • This phase usually occurs on days 3-6 of the infection and consists of mainly arthritis. In contrast to the arthritis/arthralgia of the bacteremic phase, this arthritis is a septic arthritis with purulent joint fluid and a positive culture result in 50% of patients. WBC counts in aspirated joint fluid are typically 50-100,000 cells/μL and consist of more than 90% neutrophils.
  • Skin findings in this phase are minimal; only 15-20% of patients have active skin lesions, and the remaining 80-85% of patients have resolved dermatitis or resolving dermatitis.

Causes

Risk factors for both mucosal infection and disseminated infection include sexual activity/promiscuity, lower socioeconomic status, ethnic minority, male homosexuality, drug use, lower educational level, and past history of other STDs. See Pathophysiology.

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Other causes of arthritis and dermatitis may display a clinical picture similar to that of DGI, with some notable differences.

Reactive arthritis is a human leukocyte antigen B27 (HLA-B27)–associated condition that predominantly occurs in young men and has the clinical triad of urethritis, conjunctivitis, and arthritis. However, the distribution of the arthritis is different, occurring predominantly in the joints of the axial skeleton. The clinical picture is less acute, occurring over the course of weeks rather than days and with less severe fever. This syndrome does not respond to antibiotic therapy, and it does not have the associated dermatitis that occurs in gonococcemia.

Rheumatic fever is a rare illness in the modern era and can present with high fever, rash, arthritis, and endocarditis. This condition follows a streptococcal infection and requires long, emergent intravenous antibiotic therapy for endocarditis; it also responds well to anti-inflammatory medications.

Syphilis, an STD that commonly occurs in sexually active young adults, can also produce a rash, symptoms of arthritis, and genital lesions. However, genital involvement is usually in the form of an ulcer and not urethritis, and the rash can involve the palms and the soles. Laboratory tests, including rapid plasma reagin (RPR) titers, can aid in distinguishing syphilis from gonococcemia.

Nongonococcal septic arthritis can be caused by a variety of organisms, but it presents with an acute onset of joint swelling and pain. Culture of joint fluid commonly reveals organisms. This type of arthritis is a destructive form of arthritis that is usually monoarticular. It most frequently occurs in children and elderly persons. Immediate treatment with antibiotics is indicated.

Other conditions to consider in a patient with arthritis and skin lesions include the following: meningococcemia, hepatitis, bacterial endocarditis, SLE, tenosynovitis (eg, de Quervain disease, infectious), and other seronegative arthritides (eg, ankylosing spondylitis, Sweet syndrome, related dermal vasculitides).

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

The diagnosis of DGI should be based on clinical findings and confirmed with laboratory investigations if possible.

• CBC count: Patients with gonococcemia may have an elevated WBC count, in the range of 10,000-15,000/µL.
• Erythrocyte sedimentation rate: The rates are usually mildly elevated, with values from 20-50 in most patients. Less than 50% of patients have erythrocyte sedimentation rates higher than 50.
• Culture: The highest yield of N gonorrhoeae organisms is from mucosal sites, including the pharynx, the urethra, the cervix, or the rectum. Urethral and cervical cultures are typically the most revealing. Blood cultures yield positive culture results in 10-30% of patients and joint fluid in 20-30% of patients. Skin lesions yield organisms in only about 10% of patients. Immunofluorescence studies may improve the effectiveness in skin and joint fluid.
• Polymerase and/or ligase chain reaction: These methods have a high sensitivity and a high specificity (78.6% and 96.4%, respectively). They are easily performed on urethral specimens and can even be performed on first-void urine specimens. These methods are noninvasive, rapid, sensitive, and specific, and they have facilitated the diagnosis of gonococcal infection. However, these methods cannot report antibiotic sensitivities; therefore, they do not eliminate the need for culture in these patients.
• • Nucleic acid amplification tests, including the polymerase chain reaction, are sensitive and specific tests, as noted above. A pseudo-outbreak of pharyngeal gonorrhea in a group of prostitutes was determined to be the result of false-positive test results due to commensal oropharyngeal Neisseria species.¹¹
  • Specific molecular tests may produce erroneous results. In certain circumstances, it may be advisable, in consultation with a medical microbiologist, to take a sample for culture or to perform a second molecular test aimed at a different part of the bacterial genome.
• Serologic tests: These tests include latex agglutination, enzyme-linked immunosorbent assay, immunoprecipitation, and complement fixation tests. Because of their lower sensitivity and specificity, especially in populations with a low prevalence of disease, these tests are not routinely used for diagnosis, but they can be used as adjuncts to the other laboratory tests and may help in making the diagnosis.
• Other screenings: The US Preventive Services Task Force recommends that women at increased risk of gonorrhea also be screened for chlamydia, HIV, and syphilis.¹²

Other Tests

• Because of the potential severity of pericarditis and endocarditis, a cardiologic examination, including echocardiography, is recommended, even though these conditions are rare.

Histologic Findings

Histopathologic examination reveals a vasculitislike picture with a perivascular neutrophilic infiltrate and neutrophils containing pustules in the epidermis.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical Care

• Hospitalization is recommended for the initial treatment of DGI.
• Intravenous antibiotics are indicated for at least 24-48 hours, after which time therapy may be switched to oral antibiotics.
  

MEDICATION

Section 7 of 12  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Initial empiric therapy consists of a third-generation cephalosporin, such as ceftriaxone. Once sensitivities are obtained, therapy can be switched to less expensive medications, such as penicillin G or ampicillin. Patients with true penicillin allergies are treated with spectinomycin (spectinomycin not effective against pharyngeal gonococcal infection).

The Centers for Disease Control and Prevention recommend that all patients with gonorrheal infection are also treated for presumed co-infection with Chlamydia trachomatis. This treatment can be easily accomplished with a tetracycline antibiotic (eg, doxycycline) or a macrolide antibiotic (eg, azithromycin). Current state and Centers for Disease Control and Prevention guidelines should be consulted for the treatment of uncomplicated and disseminated disease. Disseminated disease typically needs more prolonged treatment.¹³

• CDC's Antibiotic-Resistant Gonorrhea Web site; CDC Updated Gonococcal treatment recommendations (April 2007)
• Medscape Medical News on CDC Issues - New Treatment Recommendations for Gonorrhea.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Further Inpatient Care

• Hospitalization is recommended for the initial treatment of DGI.
• Many young women are not undergoing screening for chlamydia and gonorrhea after sex with a new partner and therefore may be at increased risk of an untreated sexually transmitted disease.¹⁵ Enhancing the level of perceived seriousness of acquiring an STD from a new partner may encourage a woman to seek screening after initiating a new sexual relationship.

In/Out Patient Meds

• See Medication.

Deterrence/Prevention

• PRO-2000, an antimicrobial gel for the potential prevention of HIV infection, is in phase III trial for the prevention of sexually transmitted infections, including HIV, herpes, chlamydia, and gonorrhea, in Africa.¹⁶

Complications

• Clinical complications may include osteomyelitis, meningitis, endocarditis, ARDS, and fatal septic shock. Polymyositis is also a rare complication of gonococcemia.

Patient Education

• For excellent patient education resources, visit eMedicine's Sexually Transmitted Diseases Center. Also, see eMedicine's patient education article Gonorrhea.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Missing this diagnosis and thus not treating the patient with correct therapy can have disastrous results, including meningitis and ARDS.

ACKNOWLEDGMENTS

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Dr. Neal Ammar, to the development and writing of this article.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  Disseminated gonococcemia, acral pustules.
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Media type:  Photo

Media file 2:  Cytologic smear of cutaneous acral pustule showing gram-negative intracellular diplococci.
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Media type:  Photo

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

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Article Last Updated: Apr 28, 2008