9. Sorting out pelvic inflammatory disease

Transcription

1 Sorting out STIs 31 PART-WORK The ninth in a series of articles on diagnosing and managing genitourinary infections 9. Sorting out pelvic inflammatory disease NINA VON KNORRING AND JANET WILSON Pelvic inflammatory disease is a major threat to the reproductive health of young women and has a large impact on healthcare resources. Immediate treatment is necessary to prevent long-term complications such as tubal factor infertility and ectopic pregnancy. The authors emphasise the importance of a pragmatic approach to management. Dr N. von Knorring, MRCOG, Specialist Registrar in Genitourinary Medicine, Dr Janet Wilson, FRCP, Consultant in Genitourinary Medicine, The General Infirmary at Leeds. Pelvic inflammatory disease (PID) is defined as the clinical syndrome associated with upper genital tract inflammation, and includes endometritis, salpingitis, tubo-ovarian abscess and pelvic peritonitis. Long-term sequelae are mainly a result of tubal damage: rates of tubal factor infertility are 8 per cent after a single episode, 20 per cent after two episodes, and 40 per cent or more after three episodes. There is also a five- to ten-fold increased risk of ectopic pregnancy, and about 20 per cent of women have chronic pelvic pain. Chlamydia trachomatis is the most common cause of PID. The National Chlamydia Screening Programme has been implemented in England, as screening for and treating asymptomatic genital chlamydia infections may reduce PID and ectopic pregnancy. Problems arise because the clinical diagnosis of PID is imprecise and appears to be accurate in only two-thirds of cases when compared with laparoscopy. Also, many cases of PID with no, or minimal, symptoms go unrecognised and untreated. Delay in treatment, even by only a few days, 1 or re-infection from untreated sexual partners, increases the risk of long-term complications. Consequently, a pragmatic approach to the management of young women presenting with symptoms suggestive of PID is needed, with a low threshold for treatment. A substantial number of cases of PID are seen and treated in primary care. From figures published by the Health Protection Agency in 1999, the rate of PID diagnosis was 1.7 per cent in women aged years attending GP surgeries, accounting for one in 60 consultations. 2 Causes of pelvic inflammatory disease Ascending infections from the lower genital tract cause most cases of PID. Hence the incidence of PID correlates with the prevalence of sexually transmitted infections (STIs). Figure 1. Cervicitis with mucopurulent discharge. Most cases of pelvic inflammatory disease are caused by ascending infections from the lower genital tract. The main organisms, causing up to 60 per cent of infections, are C. trachomatis and Neisseria gonorrhoeae. The normal colonising bacteria of the vagina, such as anaerobes, Gardnerella vaginalis, Mycoplasma hominis, Escherichia coli and other enteric organisms, may also play a role. It is thought that C. trachomatis and N. gonorrhoeae damage the protective mechanisms of the genital tract, allowing endogenous bacteria from the vagina to ascend. Hence cultures taken from the upper genital tract at laparoscopy usually yield polymicrobial growth; however, no bacterial cause can be found in a significant proportion of women with PID. The absence of any organisms does not exclude PID, as it may be impossible to isolate the infective agent from the endocervical canal. Also, a relatively newly recognised sexually transmitted bacterium, Mycoplasma genitalium, has been shown to be associated with cervicitis and PID, but clinically available tests for this have yet to be established (Figure 1). 3 Pelvic inflammatory disease is rare in women who are not sexually active. It can affect any women of reproduc-

2 Sorting out STIs 33 Box 1. Main symptoms suggestive of pelvic inflammatory disease. Dull lower abdominal pain, usually bilateral Onset during or soon after menstruation Abnormal vaginal discharge Irregular vaginal bleeding or change in menstrual pattern such as intermenstrual bleeding, postcoital bleeding, menorrhagia, dysmenorrhoea Deep dyspareunia Dysuria Nausea/vomiting Fever tive age but the highest risk is in women under the age of 25 years and in those with multiple sexual partners. The combined oral contraceptive pill does not protect against PID but women taking it tend to have milder symptoms and signs. Insertion of an intrauterine device (IUD) may increase the risk of PID, especially if chlamydia or gonorrhoea is present at the time of insertion, but only for the first three weeks after insertion. Otherwise the risk of PID in IUD users appears to be similar to that in women using no contraception. 4,5 Other instrumentation of the uterus, such as surgical termination of pregnancy, as well as recent delivery or miscarriage (within four weeks), may increase the risk of PID. Clinical features There is a wide spectrum of disease presentation with PID, ranging from no (or intermittent) to very severe symptoms. PID caused by chlamydia is usually milder, whereas women with gonococcal PID generally have a more acute onset. The main symptom suggestive of PID is dull lower abdominal pain, which is usually bilateral. The character of the pain is similar to menstrual or mild labour pains. The onset is often during, or soon after, menstruation. Several other symptoms are also common (Box 1). The abdominal pain may be unilateral, but as this has been reported in fewer than 10 per cent of women with confirmed salpingitis on laparoscopy, it should lead to a high index of suspicion of another potential cause for the pain (Box 2). Peritoneal spread of infection may cause perihepatitis, which can lead to right upper quadrant pain. On bimanual examination of the pelvis, most women with PID will have lower abdominal, adnexal, uterine and cervical motion tenderness. In addition, there may be evidence of an abnormal vaginal and/or cervical discharge with contact bleeding suggestive of cervicitis (Figure 2). In more severe cases, the woman may have a palpable adnexal mass and fever. Box 2. Main differential diagnoses of pelvic inflammatory disease. Ectopic pregnancy (pregnancy should be excluded in all women suspected of having pelvic inflammatory disease) Acute appendicitis (right iliac fossa pain, more gastrointestinal symptoms, nausea/vomiting, fever) Urinary tract infection (urinary frequency, urgency, nocturia and haematuria) Endometriosis (symptoms tend to be related to the menstrual cycle) Irritable bowel syndrome (general abdominal colicky pain with abdominal distension, exacerbation of pain by food or stress, more disturbance in bowel habit) Corpus luteum haemorrhage Ovarian cyst accidents (often sudden onset) Various other gynaecological and surgical conditions may present with lower abdominal pain; these should be considered in the differential diagnosis (Box 2). 6 Investigations Investigations for women suspected of having PID are shown in Box 3. Table 1 gives the sample sites and tests for infections that are recommended by the British Association for Sexual Health and HIV. 7 These may vary according to local laboratory guidelines, and liaison with the local microbiology service is recommended. GP practices that have opted out of screening for, and treating, STIs should immediately refer such women to genitourinary medicine or gynaecology departments. Nucleic acid amplification tests (NAATs) are far superior to the older enzyme immunoassays (EIAs) for the detection of chlamydia. Consequently, EIAs should no longer be used, as their sensitivities are low (40 80 Figure 2. Abnormal vaginal discharge and cervicitis with contact bleeding.

3 34 Sorting out STIs Recommended test Culture NAAT Gram stain of smear of vaginal Culture discharge on microscopy slide Alternative test NAAT None Vaginal swab None Recommended sample site Endocervical canal Endocervical canal Vaginal wall Posterior fornix of vagina Alternative sample site None Vaginal or vulval swab None None or first-pass urine sample acceptable Transportation issues Swab for culture in None Allow smear to air-dry Swab for culture in transport media Swab in transport media transport media (eg Amies, Stuarts) (eg Amies, Stuarts) (eg Amies, Stuarts) Refrigerate Refrigerate Refrigerate Rapid transport to lab Rapid transport to lab Rapid transport to lab within 24h within 24h within 6h NAAT, Nucleic acid amplification test. Table 1. Sample sites and tests recommended in primary care. 7 Gonorrhoea Chlamydia Bacterial vaginosis Trichomoniasis per cent) and negative tests cannot be relied upon. There is some variation in the sensitivities of NAATs from different sites, with samples from the endocervix being slightly better than vulval or vaginal swabs, and all swabs being better than first-pass urine samples. Culture is still the preferred method of detection for gonorrhoea but rapid transport to the laboratory is needed. An alternative test that does not require rapid transport is a NAAT. It is currently recommended that a positive NAAT for gonorrhoea be confirmed by culture because of high false-positive rates. As empirical treatment of PID is recommended before the results of the microbiology tests are available, NAATs are not routinely suitable in this condition. However, a pragmatic approach to situations such as women presenting on Friday evenings would be to request a NAAT test for gonorrhoea in addition to chlamydia. Guidelines recommend a vaginal swab for Trichomonas Box 3. Investigations for women suspected of having pelvic inflammatory disease. Samples for detection of gonorrhoea, chlamydia, ± bacterial vaginosis and trichomoniasis (see Table 1) Pregnancy test Urinalysis (and midstream urine specimen if protein, leukocytes or nitrites positive) Temperature Pulse and blood pressure vaginalis (TV) and, in practice, most primary care clinicians perform this, but its value in the management of PID is questionable. TV appears to have little, if any, role in the aetiology of PID, and TV rates are low in the UK. Bacterial vaginosis (BV) has been associated with PID, so an air-dried smear of vaginal discharge on a glass slide, Gram-stained and read for BV by the laboratory, would be a better predictive test. The presence of BV and leukocytes on vaginal slides is associated with a five-fold risk of PID. 8 Management of pelvic inflammatory disease Empirical treatment of PID should be initiated in sexually active young women with acute onset of lower abdominal pain, if no other cause for the pain can be identified, and if there is tenderness of at least one of: cervical motion, the uterus or adnexa (Figure 3). Outpatient therapy is as effective as inpatient therapy in women with mild to moderate PID. The treatment regimen must provide broad-spectrum coverage of all the likely pathogens, but particularly chlamydia, gonorrhoea and anaerobes, and should be started as soon as the microbiological specimens have been taken (Box 4). Treatment of PID with doxycycline and metronidazole alone has a significantly lower clinical cure rate and should not be used. 9 Because of high levels of gonococcal quinolone resistance, it is recommended that a thirdgeneration cephalosporin should be prescribed rather than a quinolone if there is a high risk of gonorrhoea. Indicators of a high risk of gonorrhoea are clinically severe disease, Trends in Urology Gynaecology & Sexual Health September/October

4 Sorting out STIs 35 Sexually active woman Acute lower abdominal pain ± other symptoms (see Box 1) Examination and investigations impossible Urgent referral to genitourinary medicine Speculum examination Abnormal vaginal discharge or cervicitis? Take samples for infections pregnancy test and urinalysis temperature, pulse and blood pressure bimanual examination Cervical motion, uterine or adnexal tenderness? Possible gynaecological/ surgical emergency or pregnant or severe infection Cervical motion or uterine or adnexal tenderness present No other cause for pain identifed Investigations completed Urgent referral to gynaecology or surgery Refer to genitourinary medicine Start outpatient treatment Advise sexual abstinence No response to treatment or intolerant of medication Screen and treat sexual partner(s) No Follow up after treatment Compliance? Symptoms resolved? Sexual abstinence? Partner treated? Figure 3. Management of pelvic inflammatory disease. sexual contact abroad, or if the patient s partner has gonorrhoea. The ceftriaxone/doxycycline combination should also be chosen in women in whom early pregnancy cannot be excluded (no contraception, pregnancy test negative but unprotected sex since last menstrual period). In patients with mild to moderate PID, metronidazole may be stopped in women who are unable to tolerate it. Good compliance with the prescribed treatment needs to be emphasised, as well as the importance of abstaining from sex until treatment has been completed by the woman and her sexual partner. Appropriate analgesia should be provided. A detailed explanation of the condition, with particular emphasis on the long-term implications, should be provided and reinforced with clear and accurate written information. A patient information leaflet is available from the Royal College of Obstetrics and Gynaecology ( Referral to hospital should be considered when a gynaecological/surgical

5 36 Sorting out STIs Box 4. Recommended outpatient treatment regimens for pelvic inflammatory disease. Intramuscular ceftriaxone 250mg single dose Oral doxycycline 100mg twice daily for 14 days Oral metronidazole 400mg twice daily for 7 14 days or Oral ofloxacin 400mg twice daily for 14 days Oral metronidazole 400mg twice daily for 7 14 days emergency cannot be excluded, in pregnancy, with severe disease or suspected pelvic abscess, or when there is failure to respond to or tolerate oral treatment. There is limited evidence regarding the removal of IUDs. Although removal may be associated with a better short-term outcome, 10 the risk of iatrogenic pregnancy needs to be assessed beforehand, and emergency contraception may be required. Patients should be followed up after completion of treatment to assess clinical response and compliance, and to ensure that partners have been treated. The chances of reinfection are high with unprotected sex with an untreated partner; re-treatment may be necessary. This is also a good opportunity to discuss and start contraception in those not using any and to promote future condom use to all, as consistent condom use has been shown to reduce acquisition of STIs. Sexual partners The current male partner should be screened for chlamydia and gonorrhoea, even if he is asymptomatic. This may be difficult in primary care if the partner is not a patient of the same practice, so referral to genitourinary medicine is an alternative. It is standard practice to treat the male partners epidemiologically for chlamydia (regardless of the chlamydia results) with azithromycin 1g as a single oral dose. If either partner tests positive for gonorrhoea, treat with oral cefixime 400mg as a single oral dose or ciprofloxacin 500mg as a single oral dose, depending on sensitivities. Tracing of other contacts within a six-month period of PID symptoms is also recommended. References 1. Hillis SD, Joesoef R, Marchbanks PA, et al. Delayed care of pelvic inflammatory disease as a risk factor for impaired fertility. Am J Obstet Gynecol 1993; 168: Simms I, Rogers P, Charlett A. The rate of diagnosis and demography of pelvic inflammatory disease in general practice: England and Wales. Int J STD AIDS 1999; 10: Ross JD. Is Mycoplasma genitalium a cause of pelvic inflammatory disease? Infect Dis Clin North Am 2005; 19: Mohllajee AP, Curtis KM, Peterson HB. Does insertion and use of an intrauterine device increase the risk of pelvic inflammatory disease among women with sexually transmitted infection? A systematic review. Contraception 2006; 73: Paladine HL, Blenning CE, Judkins DZ, et al. What are the contraindications to IUDs? J Fam Pract 2006; 55: Lea R, Bancroft K, Whorwell PJ. Irritable bowel syndrome, chronic pelvic inflammatory disease and endometriosis: a comparison of symptomatology. Eur J Gastroenterol Hepatol 2004; 16: British Association for Sexual Health and HIV. Primary care testing guidelines, December Yudin MH, Hillier SL, Wiesenfeld HC, et al. Vaginal polymorphonuclear leukocytes and bacterial vaginosis as markers for histologic endometritis among women without symptoms of pelvic inflammatory disease. Am J Obstet Gynecol 2003; 188: Piyadigamage A, Wilson J. Improvement in the clinical cure rate of outpatient management of pelvic inflammatory disease following a change in therapy. Sex Trans Infect 2005; 81: Altunyurt S, Demir N, Posaci C. A randomized trial of coil removal prior to treatment of pelvic inflammatory disease. Eur J Obstet Gynecol Reprod Biol 2003; 107: Further reading Royal College of Obstetricians and Gynaecologists. Guideline no. 32: Management of acute pelvic inflammatory disease, May British Association for Sexual Health and HIV. UK national guideline for the management of pelvic inflammatory disease, February KEY POINTS Pelvic inflammatory disease accounts for one in 60 GP consultations of women of reproductive age. The highest risk is in women under the age of 25 years. Ascending infection from the lower genital tract causes most cases of pelvic inflammatory disease. Clinical presentation can range from no symptoms to very severe disease. Delay in treatment increases the risk of long-term complications. Treatment must provide broad-spectrum coverage to include chlamydia, gonorrhoea and anaerobes and should be started as soon as microbiological specimens have been taken. Screening and treating sexual partners is essential to prevent re-infection. Advise sexual abstinence until the woman and her sexual partner have completed treatment. Long-term sequelae include tubal factor infertility, ectopic pregnancy and chronic pelvic pain. Trends in Urology Gynaecology & Sexual Health September/October