Continuing Education Activity

Gonococcal arthritis is arthritis that results from the bacteremic spread of Neisseria gonorrhoeae, a sexually transmitted pathogen. It comprises localized septic arthritis and arthritis-dermatitis syndrome. This activity reviews the evaluation and treatment of gonococcal arthritis and explains the role of the interprofessional team in managing patients with this condition.

Objectives:

• Outline the etiology of gonococcal arthritis.
• Review the pathophysiology of gonococcal arthritis.
• Describe the use of ceftriaxone in the treatment of gonococcal arthritis.
• Explain the importance of improving care coordination among the interprofessional team to improve outcomes for patients with gonococcal arthritis.

Introduction

Gonococcal arthritis is a bacterial arthritis that results from the bacteremic spread of Neisseria gonorrhoeae, a sexually transmitted pathogen. It is a clinical manifestation of disseminated gonococcal infection. It comprises two major clinical forms: localized septic arthritis and arthritis-dermatitis syndrome.[1][2][3]

Etiology

Neisseria gonorrhoeae, a gram-negative diplococcus, is the etiologic pathogen in gonococcal arthritis. It is usually transmitted sexually and is an important cause of bacterial arthritis in sexually active adolescents. However, it may also be acquired perinatally during childbirth and may cause gonococcal infection in newborns.[4][5]

Epidemiology

Approximately 0.5% to 3% of patients who are infected with N. gonorrhoeae develop disseminated gonococcal infection (DGI). There is a paucity of recent epidemiologic data that looks into the incidence of DGI in patients with arthritis, but historical data in the 1980s show that N. gonorrhoeae were associated with up to 14% of patients who have arthritis. Gonococcal arthritis is more commonly seen in young healthy individuals although it may occur in any age group.[6][7][8]

Pathophysiology

Host risk factors that are associated with disseminated gonococcal infection (DGI) include complement deficiencies, menstruation, pregnancy, history of pelvic surgery, and intrauterine devices (IUD). Specific strains of N. gonorrhoeae have virulence factors that have been associated with dissemination. These include strains containing a specific outer membrane called the porin 1A serotype that promotes resistance, diminished host inflammatory response, and host cell invasion and strains that require specific substrates for growth. It is also hypothesized that the pathogenesis of DGI may be partly immune-mediated. This is supported by the fact that the pathogen is frequently not isolated from both the synovial fluid and blood of patients with clinical manifestations of dissemination.[9]

History and Physical

Disseminated gonococcal infection (DGI) usually comprises two major clinical syndromes: the arthritis-dermatitis syndrome and localized purulent arthritis without associated skin lesions. There are, however, patients who present with symptoms that overlap between these two classic presentations. Although localized infection of the genitourinary tract, rectum, or pharynx by N. gonorrhoeae is a prerequisite for dissemination, patients with clinical manifestations of DGI often do not manifest symptoms of localized gonococcal infection.

• Arthritis-dermatitis syndrome: This is a form of DGI that usually comprises a triad of manifestations which include tenosynovitis, dermatitis, and polyarthralgia. It is also often associated with constitutional symptoms such as fever, chills, and body malaise. Approximately 60% developed a fever in one study in women with DGI. Tenosynovitis is a unique finding in gonococcal arthritis and is usually not seen in other forms of septic arthritis. It is demonstrated by tenderness along the flexor sheath and pain on a passive extension during a physical examination. It usually affects multiple tendons, more commonly the fingers, wrists, toes, and ankles. Polyarthralgia is typically asymmetric and may affect both large and small joints. Skin lesions occur in up to 75% of cases and are frequently seen in the trunk and extremities and usually spares the face. Although a large variety of skin lesions have been observed, DGI is most commonly associated with pustular or vesicular lesions. Other skin manifestations that occur less frequently include macules, papules, bullae, or nodules. Skin lesions are characteristically transient and may disappear after several days even without treatment.
• Localized septic arthritis: This syndrome usually presents as a monoarthritis or asymmetric oligo- or polyarthritis with pain and swelling of one or more joints. Most patients do not present with systemic symptoms such as fever or chills. Joints that are commonly affected include knees, ankles, wrist, and elbow.

Evaluation

A high clinical suspicion is necessary for patients who present with joint pain or swelling that is concerning for septic arthritis especially in those who are sexually active and younger than 40 years old and in certain at-risk populations such as men who have sex with men (MSM). A thorough history and physical examination including an emphasis on sexual history are needed in patients with suspected gonococcal arthritis. Menstrual history and pregnancy need to be assessed in premenopausal patients. Skin and joint examination may provide information that heightens clinical suspicion, especially in patients who present with the typical triad of tenosynovitis, arthralgia, and skin lesions.[1][4][10]

Definitive diagnosis of disseminated gonococcal infection (DGI) or gonococcal arthritis is made through the identification of the etiologic pathogen in a specimen taken from a non-mucosal site (such as blood, synovial fluid, or skin lesions). Microbiologic tests, however, are not always positive and in such cases, diagnosis is made clinically. A clinical diagnosis may be supported by evidence of N. gonorrhoeae infection from specimens obtained from mucosal sites. Screening for other sexually transmitted illnesses such as HIV, syphilis, and chlamydia is often recommended since these frequently co-exist with gonococcal infection.

Two sets of blood cultures should be obtained, and a positive result helps distinguish gonococcal arthritis from other pathogens that cause septic arthritis. Positive blood cultures, however, are only positive in less than one-third of cases and are more frequently seen in patients who present with arthritis-dermatitis syndrome. Specimens from mucosal sites should also be obtained and are frequently helpful in patients who have a high clinical suspicion of DGI but who have sterile synovial fluid or blood specimens. Nucleic acid amplification testing (NAAT) of either urine specimens in both men and women or vaginal swabs in women is preferred, if available. The culture of a urogenital specimen is an alternative.

In patients who demonstrate joint swelling and effusion, arthrocentesis and synovial fluid analysis should be performed. Typically, a synovial fluid analysis will show a white blood cell (WBC) count of 50,000 cells/mm3 or more; although, a cell count below 10,000 cells/mm3 is not uncommon. This may be associated with reduced glucose concentration and elevated LDH levels but these findings are non-diagnostic and of limited value. In patients who present with localized purulent arthritis, N. gonorrhoeae will be isolated in only about 50% (range of 25% to 75%) of synovial fluid specimens. This is even less in patients who present with the arthritis-dermatitis syndrome. NAAT of synovial fluid is more sensitive (greater than 75%) than culture and should be performed if available.

Obtaining skin lesion specimens is usually not done because of the difficulty of sampling and its very poor yield. The culture of skin lesions is often negative. NAAT of skin specimens may be slightly more sensitive, but this is not widely available.

Treatment / Management

Initial management in the inpatient setting is recommended for patients with a presumptive diagnosis of disseminated gonococcal infection (DGI) or gonococcal arthritis. Ceftriaxone as a parenteral therapy, either given intravenously or intramuscularly, is the preferred initial antibiotic of choice. Intravenous administration of 1 gm every 24 hours is usually preferred in patients presenting with purulent arthritis. Doxycycline 100 mg twice a day for seven days is usually added to cover potential coinfection with Chlamydia trachomatis. Alternative antimicrobial agents include third-generation cephalosporin such as cefotaxime and ceftizoxime, which are given as 1 gm every 8 hours. A dose of azithromycin 1 g orally is an alternative to azithromycin.[11][12][13]

Widespread resistance to oral cephalosporins such as cefixime has been documented. Oral cephalosporins are therefore not recommended as initial therapy. Although not always possible, the microbiologic diagnosis should be attempted, and antimicrobial susceptibility testing should be performed to guide antibiotic therapy. After 1 to 2 days of clinical improvement with ceftriaxone as parenteral therapy, a seven-day course of antibiotics may be completed with daily intramuscular ceftriaxone given at 250 mg daily. Patients with septic arthritis or those who are immunocompromised or slower to respond to treatment may require a longer course of therapy (7 to 14 days). De-escalation to oral antibiotic therapy (such as cefixime, fluoroquinolones, or penicillin) may be done only in patients who do not have septic arthritis and only if culture and susceptibility results are available. However, not all laboratories are capable of performing N. gonorrhoeae culture and sensitivity testing. In cases wherein the microbiologic diagnosis is not established, the course of therapy should be completed with a parenteral cephalosporin.

Partners of patients diagnosed with DGI within 2 months should be contacted and treated whenever possible. Patients with recurrent DGI or gonococcal arthritis will require further evaluation for complement deficiency.

Patients with a history of beta-lactam allergy are often able to tolerate ceftriaxone. Due to the absence of effective alternative parenteral agents, patients who have a history of IgE mediated hypersensitivity reaction to beta-lactams may undergo either skin testing or graded challenge testing. Patients who test positive for these tests should undergo desensitization. Those with a history of severe, non-IgE mediated reaction will require consultation with an infectious disease specialist.

Patients presenting with localized purulent arthritis should undergo joint drainage, either arthroscopically or through repeated joint aspirations until there is evidence of response such as the resolution of fever, leukocytosis, joint pain, and effusions. Open surgical drainage may be necessary if aspiration is not adequate.

Differential Diagnosis

• Septic arthritis: Acute purulent arthritis due to other bacteria may present similarly. They may be distinguished from gonococcal arthritis through microbiologic identification from synovial fluid culture.
• Poststreptococcal arthritis: Acute rheumatic arthritis may present with both polyarthritis and rash. The rash, however, is transient and is typically not vesicular or pustular.
• Crystal arthropathy: This may also present as mono- or oligo-arthritis and may be distinguished through synovial fluid analysis.
• Other inflammatory arthritis: Rheumatoid arthritis, reactive arthritis, and psoriatic arthritis may be mistaken for gonococcal arthritis, but these disease entities are usually associated with other clinical or radiologic manifestations not seen in disseminated gonococcal infection.
• Several other infections such as Lyme disease, infective endocarditis, and certain viruses may also present with some form of joint involvement.

Prognosis

Disseminated gonococcal arthritis has an excellent prognosis if appropriate therapy is given. Rare complications such as meningitis, perihepatitis, osteomyelitis, and endocarditis may occur if treatment is delayed or inadequate. 

Complications

• Meningitis
• Joint damage
• Perihepatitis
• Endocarditis
• Osteomyelitis

Postoperative and Rehabilitation Care

After the patient has completed treatment, re-evaluation is necessary. Patients also need to be screened for other sexually transmitted infections in 3 to 6 months. More importantly, the partners need to be contacted and treated.

Consultations

• Orthopedic surgeon
• Infectious disease

Enhancing Healthcare Team Outcomes

Gonococcal arthritis is ideally managed with an interprofessional team of healthcare professionals. While the acute joint problem is managed by a physician, many patients may require a short program in physical therapy to regain their joint mobility and muscle strength. The nurse should educate the patient on sexually transmitted infections and how to practice safe sex. Once a patient has been diagnosed with one STD, the nurse should inform the patient about getting tested for other STDs. The pharmacist should ensure compliance with antibiotics to ensure that full healing occurs. Finally, the social worker should recommend that the partner be examined and treated, otherwise the cycle of infection transmission will continue. [14][15](Level V)

Outcomes

When patients with gonococcal arthritis are treated with antibiotics, there is usually full recovery without any sequelae. For those who have other manifestations besides the arthritis, the prognosis may depend on the severity of the infection. For example, if a patient has gonococcal endocarditis, antibiotics may be required for 4 to 6 weeks and if the valve is damaged, valve replacement may be required. In general, complications following gonococcal arthritis are rare. [8][16] [Level 5]