Hospital Medicine

Disseminated gonorrhea

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I. What every physician needs to know.

Disseminated gonococcal infection (DGI) is a common cause of acute polyarthralgias, polyarthritis, or oligoarthritis in healthy young patients. Gonorrhea is the second most commonly reported infectious disease in the United States. It is major cause of pelvic inflammatory disease which can lead to infertility and chronic pelvic pain. It is believed that gonococcal infections may facilitate transmission of human immunodeficiency virus (HIV).

II. Diagnostic Confirmation: Are you sure your patient has disseminated gonorrhea?

DGI presents as two syndromes: 1) a bacteremic form that includes a triad of tenosynovitis, dermatitis, and polyarthralgias without purulent arthritis and 2) a septic arthritis form characterized as a purulent arthritis without associated skin lesions. Many patients will have overlapping features of both syndromes. Time from infection to clinical manifestations may range from 1 day to 3 months.

A. History Part I: Pattern Recognition:

The typical patient with DGI is young (less than 40 years old), with asymmetrical migratory polyarthralgias, tenosynovitis, and dermatitis. There is usually a recent history of sexual activity especially in women during time of menses, pregnancy, or immediate postpartum period. Congenital or acquired complement deficiency as well as systemic lupus erythematosus, which is associated with complement deficiency, may increase the risk of developing DGI. Skin lesions may be present such as tiny papules, pustules, or vesicles with erythematous base, erythema nodosum, or erythema multiforme.

B. History Part 2: Prevalence:

There are 2 million cases of Neisseria gonorrhoeae worldwide each year. In 2013 there were more than 330,000 cases reported in the United States by the Centers for Disease Control and Prevention (CDC). The actual number of cases during the time period is thought to be 820,000. Dissemination may occur in 0.5%-3% cases. Women are affected more than men (3:1). Many affected women had no prior symptoms of infections.

C. History Part 3: Competing diagnoses that can mimic disseminated gonorrhea

DGI may be confused with bacterial arthritis (especially meningococcal arthritis), hepatitis B, reactive arthritis, rheumatoid arthritis, psoriatic arthritis, lupus, acute rheumatic fever, infective endocarditis, acute HIV infection, and secondary syphilis. Clinicians should also consider parvovirus, measles, rubella, some arboviral infections, Lyme disease, and gout and other crystal diseases in the differential diagnosis.

D. Physical Examination Findings.

Physical examination should be thorough and may often help to confirm the diagnosis. Typical lesions seen in DGI are painless tiny papules, pustules, or vesicles with erythematous base. The number of lesions may range from few to up to 50. Most patients have between 2 and 10 lesions. Other skin findings may include urticarial lesions, erythema nodosum, and erythema multiforme. Skin lesions are transient. They may last up to 4 days and will resolve with or without treatment. Musculoskeletal exam may show tenosynovitis that can be identified based on swelling of the tendon sheath with pain on movement. Joint swelling may be present. An asymmetric polyarthritis may occur. The most common joints involved are the wrists, fingers, ankles, and toes.

E. What diagnostic tests should be performed?

If available and validated for the specific specimen being tested, a nucleic acid amplification test (NAAT) is the preferred diagnostic test for gonococcal (as well as chlamydial) infection. A NAAT can be used to test specimens collected from the endocervix (women), vagina (women), urethra (men), and urine (men and women). If a NAAT is not available then culture is the preferred alternative.

Blood culture tends to be positive in the bacteremic form while synovial culture is positive frequently in the septic arthritis form. Blood should be cultured in enriched broth medium. Synovial fluid should be submitted on Thayer-Martin media. Arthrocentesis of the involved joint should be performed along with fluid analysis including cell count, crystal analysis, and culture.

Besides synovial fluid analysis and culture on Thayer-Martin media, a patient with symptoms suggestive of DGI should have skin, oropharyngeal, urethral (males), cervical (females) and rectal cultures performed on Thayer-Martin media. Pregnancy testing should be performed.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Patients suspected to have DGI are at risk for other sexually transmitted diseases such as HIV and syphilis. Testing for chlamydial infection is not necessary since treatment for DGI should include concurrent treatment for possible coinfection with Chlamydia trachomatis.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Radiographic joint changes may include swelling and joint effusion. If there is destruction of cartilage or osteomyelitis, the diagnosis of DGI should be reconsidered. Ultrasonography may be useful in evaluating swollen joints for evidence of effusion and inflammation. Tenosynovitis can also be identified on ultrasound.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

None

III. Default Management.

Patients should be treated with parenteral antibiotic therapy for N. gonorrhoeae to cover the resistance seen in the specific community. If a patient refuses to be admitted, still try to give initial dose parenterally. There is widespread resistance of N. gonorrhoeae to agents other than parenteral cephalosporins therefore it is recommended that the initial therapy be ceftriaxone 1gram (g) daily or another third-generation cephalosporin (spectinomycin is used for penicillin allergic patients and is available outside of the United States). Patients with IgE-mediated hypersensitivity reaction to beta-lactams should receive desensitization so that they can be treated with parenteral cephalosporins.

Patients with the septic arthritis form of DGI require 7-14 days of therapy along with drainage of the involved joint via recurrent needle aspiration or surgical drainage. Patients with the bacteremic form may respond within 3 days of therapy and at that time can be converted to oral therapy with cefixime, ciprofloxacin, or another quinolone if cultures show full susceptibility to the specific antibiotic and if not then parenteral therapy must be continued. If DGI is complicated by meningitis then treat for 10-14 days with parenteral therapy. If it is complicated by endocarditis the patient must receive at least 4 weeks of parenteral therapy.

There should be Concurrent treatment with a 7 day course of doxycycline 100 milligrams (mg) twice a day or one dose of azithromycin 1 g to treat for possible coinfection with Chlamydia trachomatis. Avoid doxycycline use in pregnant wormen.

A. Immediate management.

Immediate management should include:

  • Arthrocentesis of any joint effusions

  • Blood cultures using enriched broth medium and not sodium polyanethol sulfonate which inhibits neisserial growth

  • Culture of possible sites of infection using Thayer-Martin media (synovial, skin lesion, urethral, cervical, throat, and rectal)

  • Appropriate antibiotic therapy

B. Physical Examination Tips to Guide Management.

A thorough skin examination to identify classic lesions can help lead to the correct diagnosis.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Recurrent arthrocentesis is required for those patients with the septic arthritis form of DGI. If patient continues to have effusion, severe joint pain, fever or elevated white blood cell (WBC), then the patient may require arthroscopic or open surgical drainage.

D. Long-term management.

All sexual partners of the patient will need to be treated even if asymptomatic. If symptomatic, then treat as DGI. Asymptomatic patients should receive ceftriaxone 125mg intramuscular (IM) or cefixime 400mg per os (PO) for 7 days with chlamydial coinfection therapy of one dose of azithromycin 1 g orally or doxycycline 100 mg PO twice a day.

E. Common Pitfalls and Side-Effects of Management

Patients with DGI may be co-infected with chlamydia, syphilis and/or HIV. Treatment for possible coinfection with chlamydia is standard. Patients should be evaluated for HIV, syphilis, and illicit drug use.

Initial treatment for DGI is one of the following:

  • Ceftriaxone 1 g daily intravenously (IV)/(IM) every 24 hours

  • Cefotaxime 1 g IV every 8 hours

  • Ceftizoxime 1 g IV every 8 hours

  • Spectinomycin 2 g IM every 12 hours for penicillin-allergic patients (this was discontinued in USA in 2006 but is available in other countries)

Treat DGI parentally for 24-48 hours beyond improvement in clinical symptoms, then switch if cultures show susceptibility to oral agent, such as cefixime 400 mg twice a day, ciprofloxacin 500 mg twice a day, doxycycline 100 mg twice daily (if not pregnant), or amoxicillin 500 mg four times a day, for 7-10 days.

IV. Management with Co-Morbidities

Comorbidities do not require any change in the standard management of DGI. Possible complications arising from DGI are set out in the sections below.

A. Renal Insufficiency.

Emboli to the kidneys may result if the rarely seen complication of gonococcal endocarditis occurs.

B. Liver Insufficiency.

Fitz-Hugh-Curtis syndrome or gonococcal perihepatitis presents as acute abdominal pain with liver tenderness on palpation and elevated liver function tests. It may result from hematogenous spread, which is seen more in men, or by spread of infection via the retroperitoneal lymphatic system NAAT can be used the fallopian tubes in women.

C. Systolic and Diastolic Heart Failure

Prior to antibiotic therapy for DGI gonococcal endocarditis was seen and made up a quarter of bacterial endocarditis cases. Now gonococcal endocarditis is rare but the complications can be severe. Patients may have numerous skin lesions as well as emboli to various areas such as the brain, the kidneys and the extremities. Rarely patients may develop myocarditis, pericarditis, friction rub and pericardial fluid that is purulent in nature.

D. Coronary Artery Disease or Peripheral Vascular Disease

A patient can develop emboli to the extremities as the result of gonococcal endocarditis, a rare complication of DGI.

E. Diabetes or other Endocrine issues

None

F. Malignancy

None

G. Immunosuppression (HIV, chronic steroids, etc).

None

H. Primary Lung Disease (COPD, Asthma, ILD)

None

I. Gastrointestinal or Nutrition Issues

None

J. Hematologic or Coagulation Issues

None

K. Dementia or Psychiatric Illness/Treatment

None

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

While hospitalized, if a patient continues to be febrile or symptoms persist despite antibiotic therapy, then the diagnosis should be questioned or the patient may need surgical drainage of the involved joint to prevent joint destruction.

B. Anticipated Length of Stay.

At least 2-3 days to allow for continued parental therapy for 24-48 hours after clinical symptoms resolve.

C. When is the Patient Ready for Discharge.

Patients can be discharged 1-2 days after symptoms resolve.

D. Arranging for Clinic Follow-up

Patient should be followed in the outpatient setting 1 week after completing antibiotic therapy.

1. When should clinic follow up be arranged and with whom?

Follow-up should be arranged for a week after completing antibiotic therapy, and prior culture positive sites should be re-cultured. Patient should see orthopedics for evaluation and further management of the infected joint.

2. What tests should be conducted prior to discharge to enable best clinic first visit?

Prior to discharge patient should have HIV and syphilis evaluation.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

None

E. Placement Considerations.

None

F. Prognosis and Patient Counseling.

Prognosis is good. Patients should be instructed on need to prevent reinfection by using condoms and spermicide.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.

N/A

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

To avoid recurrence of DGI, patients should be educated on ways to prevent sexually transmitted diseases.

VII. What's the evidence?

Deguchi, T, Nakane, K, Yasuda, M, Maeda, S. "Emergence and spread of drug resistant Neisseria gonorrhoeae". J Urology. vol. 184. pp. 851-2010.

Garcia-De LaTorre, I, Nava-Zavala, A. "Gonococcal and nongonococcal arthritis". Rheum Dis Clin N Am. vol. 35. 2009. pp. 63-73.

Tapsall, JW. "Neisseria gonorrhoeae and emerging resistance to extended spectrum cephalosporins". Curr Opin Infect Dis. vol. 22. 2009. pp. 87-91.

Hochberg, MC. "Rheumatology". 2014.

Rice, PA. "Gonococcal arthritis (disseminated gonococcal infection)". Infect Dis Clin North Am. vol. 19. Dec 2005. pp. 853-61.

Rapp, JR, Schacter, J. "Centers for Disease Control and Prevention. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae 2014". MMWR Recomm Rep. vol. 63. 2014. pp. 1.

Workowski, KA, Bolan, GA. "Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015". MMWR Recomm Rep. vol. 64. 2015. pp. 1-37.

Lancaster, J. "Update on treatment options for gonococcal infections". Pharmacotherapy. vol. 35. 2015. pp. 856-868.

Wise, CM. "Gonococcal arthritis in an era of increasing penicillin resistance. Presentations and outcomes in 41 recent cases (1985-1991)". Arch Intern Med. vol. 154. Dec 12-16 1994. pp. 2690-5.

O'Brien, JP, Goldenberg, DL, Rice, PA. "Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms". Medicine. vol. 62. Nov 1983. pp. 395.

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