Cervicitis

Etiology

The etiology can be broadly classified into infectious and non-infectious. Infectious agents include Neisseria gonorrhea, Chlamydia trachomatis, and less commonly, herpes simplex, Trichomonas vaginalis, and Mycoplasma genitalium. Neisseria and chlamydia primarily infect the columnar epithelium of endocervix, whereas HSV and trichomonas affect the squamous epithelium of ectocervix.[2][3] Bacterial vaginosis has also been associated with cervicitis.[4] 

Non-infectious causes include mechanical and chemical irritants. Surgical instruments or foreign objects like pessaries, condoms, diaphragms, cervical caps, or tampons can cause mechanical trauma. Chemical irritants cause allergic reactions and include soaps, laundry products, spermicides, latex, vaginal douches, and contraceptive creams.[1][5] 

Systemic inflammatory diseases like lichen planus and Behcet syndrome have also been implicated in cervicitis. The hypoestrogenic state seen with natural or surgical menopause can mimic cervicitis. This is due to the atrophy of the vaginal and uterine lining.[1] However, the exact etiology cannot be determined in more than half the cases.[6] It is not clinically possible to differentiate the inflammation caused by mechanical or chemical irritants from that caused by infectious etiologies.

Epidemiology

The exact prevalence of cervicitis is difficult to determine due to the lack of a standard definition and variation by population. Since sexual activity is the main risk factor for the infectious causes, it may affect about 30%-40% of the patients seen in sexually transmitted infection (STI) clinics.[3][7] 

The highest incidence is in sexually active women aged 15 to 24.[8] It is more common in human immunodeficiency virus (HIV) positive women, with an estimate of 7400 per 100,000 women diagnosed with HIV. Mycoplasma is the commonly implicated agent in this population.[9] Chlamydia cervicitis is 4 to 5 times more common than gonococcal cervicitis.[10] 

It was demonstrated by Taylor et al. that 61% of women enrolled in a randomized trial were negative for chlamydia, Neisseria, trichomonas, or mycoplasma by nucleic acid amplification testing (NAAT).[6] Many such studies have proven that we are unable to determine the etiological agent for cervicitis in many of the cases.[4][11]

Histopathology

When viewed microscopically, cervical Gram stains with more than 30 white blood cells (WBCs) per high power field (HPF) are labeled as cervicitis.[3] Histopathology and Gram staining have no clinical utility in the diagnostic evaluation of women with physical findings of cervicitis because they show non-specific inflammatory infiltrate.[12]

History and Physical

A thorough medical history is instrumental in the identification of risk factors. Both symptomatic and asymptomatic women who come in for screening should be asked their sexual history in detail with the use of the 5 Ps: partners, practices, prevention of pregnancy, protection from STIs, and previous STIs. Typical symptoms reported include purulent or mucopurulent vaginal discharge and intermenstrual or post-coital bleeding. Dyspareunia has also been reported. An in-depth inquiry should also be carried out for the associated symptoms, i.e., urinary symptoms (for concomitant urethritis), and abdominal pain (for PID or endometritis).

All women with suspicion of cervicitis should undergo pelvic and vaginal examinations. The classic signs include yellow or mucoid discharge from the os and easy bleeding of the endocervix on touching with cotton applicator (also called friability). However, a normal physical exam does not rule out an infection. Additionally, punctate hemorrhages (strawberry vagina) is suggestive of trichomonas, while vesicles and ulcers indicate an HSV infection. Mycoplasma cervicitis is asymptomatic in many patients; therefore, many cases remain undiagnosed.[13] 

Upper genital involvement should be suspected in the case of high fever, abdominal or adnexal tenderness, and cervical motion tenderness.

Evaluation

Once a clinical diagnosis has been established after a thorough history and physical exam, the initial investigation is for the identification of the causative organism. The most sensitive and specific test is the nucleic acid amplification testing (NAAT) for the most common organisms, chlamydia, and Neisseria. NAAT can be performed on endocervical, vaginal fluid, or urine samples.[14] 

In the case of concurrent vaginal infection, testing for trichomonas, and bacterial vaginosis (BV) should be done. Saline microscopy, amine whiff test, and vaginal pH are performed for BV, whereas NAAT is the preferred test for trichomonas.[2] If these organisms are not identified, NAAT for mycoplasma may be done. Testing for HSV is not recommended unless there is high clinical suspicion.

Treatment / Management

The resolution of symptoms is dependent on the etiology of cervicitis. According to the CDC guidelines, empiric treatment is recommended for women at higher risk of STIs, which include women <25, those with a new sexual partner, a partner with an STI, or multiple concurrent sexual partners. For these women, antimicrobials to cover for chlamydia and gonorrhea is given. Empiric treatment is also suggested for women with no identifiable pathogen on testing. Treatment can be deferred until the confirmatory tests are available for women at lower risk of STIs. According to the guidelines published by Institut national d’excellence en Sante et en services sociaux (INESSS), the empiric regimens are as follows:

• 1g single oral dose azithromycin PLUS either 800 mg cefixime in a single oral dose or 250 mg intramuscular ceftriaxone in a single dose
• 100 mg oral doxycycline twice daily for 7 days PLUS either 800 mg cefixime in a single oral dose or 250 mg intramuscular ceftriaxone in a single dose
• For severe allergy to penicillins/cephalosporins: 2g oral azithromycin in a single dose[2][3][15]
(B3)

For infectious agents identified by laboratory investigations, the treatment is as follows:

• Chlamydia: A single oral dose of 1g azithromycin OR 100mg doxycycline twice daily for 7 days
• Gonorrhea: 250mg intramuscular ceftriaxone PLUS a single oral dose of 1g azithromycin
• Mycoplasma: 400mg moxifloxacin after treatment failure with 1g oral azithromycin
• Trichomonas: A single oral 2g dose of metronidazole OR tinidazole
• Bacterial vaginosis: Twice daily 500mg metronidazole for 7 days OR intravaginal 0.75% metronidazole gel once daily for 5 days
• HSV: Oral 400mg acyclovir three times daily for 7 to 10 days

Treatment of sexual partners is also recommended, and sexual activity should be stopped until completion of therapy and resolution of treatment.[2] HIV positive women with cervicitis are given the same treatment as HIV negative. Prompt treatment in these women reduces viral shedding and may reduce the risk of HIV transmission.[16]

Differential Diagnosis

Women with cervicitis usually have a high risk of concurrent STIs and should be evaluated for them. If testing for infection is negative, then non-infectious causes are investigated, including tests for contact dermatitis and systemic diseases like lichen planus. In postmenopausal women, genitourinary syndrome of menopause may mimic cervicitis. However, it presents with other symptoms of the syndrome, including atrophic vaginitis.[17]

Prognosis

The overall prognosis of infectious causes cervicitis is good. Recovery is within a week, or two and a test of cure is not required. 

In the case of treatment failure and recurrent infection, the first step is to confirm the eradication of the causative organisms by repeat testing. A thorough history is taken for an assessment of re-exposure (e.g., new or untreated sexual partner) and for non-infectious causes (e.g., chemical irritants and systemic diseases). Once the infection has been ruled out, there are no clear options for further management. Persistent antibiotic therapy is also not recommended due to lack of evidence of benefit and concerns for antibiotic resistance.[2]

The term chronic cervicitis is used for women with persistent discharge for three months despite the resolution/exclusion of infection. Usually, it is caused by non-infectious sources, and there is no standard approach to these cases. This cervicitis of unknown etiology may respond to antibiotics, silver nitrate, or loop electrosurgical excision procedure.[18]

Complications

Ascension of infection into the upper genital tract and development of pelvic inflammatory disease is the feared complication of this cervicitis. PID can cause inflammation and scarring of the fallopian tubes and can further have both acute and chronic sequelae, which include abscess formation, chronic pain and infection, ectopic pregnancy, and infertility. One study showed that with a delay of care, PID due to chlamydia can increase the risk of infertility by three-fold.[19]