Introduction and epidemiology of Pelvic Inflammatory Disease

Pelvic inflammatory disease is a common, serious and yet poorly understood condition. It is characterized by inflammation of some or all of the following sites: the endometrium, salpinges (fallopian tubes), ovaries and peritoneum (thus leading to periappendicitis and perihepatitis). However, the term pelvic inflammatory disease is only used if the infection ascended through the cervix.

Symptoms can vary from non-existent to very severe and it can occasionally be fatal. It is a multifactorial problem — numerous organisms are implicated as causative but the role of host immunity is also important.

The incidence of pelvic inflammatory disease is hard to estimate; the definition varies between countries and even between clinics. Many cases are mild and go unnoticed by the patient or are mistakenly diagnosed as other conditions. When pelvic symptoms occur in conjunction with a confirmed diagnosis of chlamydia or gonorrhoea, it is easier to estimate incidence, although the adoption of more sensitive tests for both infections has made modern figures hard to compare with historic data.

The data provided by UK genitourinary medicine clinics provides some useful clues as to how common pelvic inflammatory disease is. Chlamydia and gonorrhoea are recorded as uncomplicated or complicated cases. Complicated cases include conditions such as reactive arthritis, septic arthritis and disseminated gonorrhoea, but in women the main condition that these figures represent is pelvic inflammatory disease. In 2003 there were 2094 female cases of complicated chlamydia recorded by English genitourinary medicine clinics, 313 cases of complicated gonorrhoea and 10 736 cases of complicated ‘non-specific genital infection’. Of course, these figures do not count the women who were so ill that they were admitted straight to hospital or those who saw their GP, nor does it count those whose symptoms were so mild that they did not seek medical attention.

The age group most likely to have pelvic inflammatory disease is the age group that is most likely to have chlamydia or gonorrhoea, i.e. sexually active teenagers.

Causation of Pelvic Inflammatory Disease

Chlamydia trachomatis and Neisseria gonorrhoeae are the two organisms most often implicated in cases of pelvic inflammatory disease, although the proportion of cases caused by each organism varies widely round the world and even around the UK. From the English figures above it can be seen that only 15.9% and 2.4% of complicated cases were caused by chlamydia and gonorrhoea respectively. In the majority of cases (81.7%) no specific diagnosis was made. This is for a number of possible reasons:

• The pelvic infection was due to chlamydia or gonorrhoea and there were organisms on the cervix, but tests done on specimens from cervix were falsely negative. Test sensitivity has improved but even with the best tests 1 in 20 of those with chlamydia will get a falsely negative result

• The pelvic infection was due to chlamydia or gonorrhoea but no infection was present on the cervix. It is unclear how often this happens but it is theoretically possible.

• The pelvic infection was due to another organism for which tests are not available. A wide variety of other organisms have been implicated including Mycoplasma hominis and anaerobes. M. hominis can cause salpingitis in experimental situations and has been isolated from women with pelvic inflammatory disease, but the extent of its contribution is unclear. Anaerobes appear to cause secondary infection, involving salpinges chronically infected by chlamydia and sometimes resulting in a tubal abscess. Bacterial vaginosis is associated with pelvic inflammatory disease and most regimens include antibiotics that provide anaerobic cover.

• It was not a pelvic infection at all. The differential diagnosis of pelvic pain is wide including gastrointestinal problems, urinary tract infections, ectopic pregnancy and appendicitis.

What proportion of women who catch chlamydia or gonorrhoea will get pelvic inflammatory disease? Again this is hard to say. Looking at the English genitourinary medicine clinic data, the complicated chlamydia and gonorrhoea cases represented 4.24% and 4.16% of total female cases of those infections, respectively. Experimental evidence suggests that around 60% of cases of pelvic inflammatory disease are subclinical, so overall a woman stands about a 10% chance of developing a pelvic infection if she acquires chlamydia or gonorrhoea.

Numerous factors can increase or reduce the chance of an ascending infection:

• Exogenous progestogens, e.g. Depo-Provera or the progestogen-only pill, thicken cervical mucus and thus present a barrier to ascending infection.

• Combined oral contraceptives appear to modulate the immune response to Chlamydia thus reducing the chance of tubal damage. Although, interestingl in vitro oestrogens increase the adhesion and growth of C. trachomatis.

• Tissue type, Chlamydial pelvic inflammatory disease is more common in women with HLA-A31

• Uterine instrumentation. Procedures including insertion of an intra-uterine contraceptive device/system, termination of pregnancy and hysteroscopy are all associated with an increased risk of pelvic inflammatory disease.

Presentation of Pelvic Inflammatory Disease

The asymptomatic majority will of course not present and will remain undiagnosed. In general, gonorrhoeal pelvic inflammatory disease has a more acute onset than chlamydial pelvic inflammatory disease and is less likely to become chronic. Symptomatic women present with a wide range of complaints of varying severity. These symptoms include:

• Pelvic discomfort or pain (often trilateral) and usually described as a dull ache. Cramping pain is more likely to represent gastrointestinal pathology.

• Deep dyspareunia.

• Fever is uncommon — suggestive of severe pelvic inflammatory disease.

• Symptoms of peritonitis are unusual.

Complications of Pelvic Inflammatory Disease

Early complications include generalized peritomtis, tubal abscess and death. Deaths are very unusual in the West and usually happen as a result of a ruptured tubal abscess.

Late sequelae of pelvic inflammatory disease include subfertility, ectopic pregnancy and chronic pelvic pain. It is unclear what the chances are of a woman with pelvic infection developing one of these complications since the numerous women with subclinical disease who do not have a complication will not be counted. There are a number of factors that affect the chance of sequelae. These include:

• The number of times a woman has pelvic inflammatory disease. In one study, women with one episode of pelvic inflammatory disease were seven times more likely than controls to have tubal factor infertility, and following two episodes this relative risk increased to 16.2.

• The severity of inflammation. In the same study, women were 5.6 times more likely to have tubal factor infertility following severe pelvic inflammatory disease than those with mild disease. However, even those with severe pelvic inflammatory disease were still more likely to be fertile than infertile following the infection.

• The age of the woman. Older women were more likely to have tubal factor infertility than younger women. This might be because of generally reduced fecundity in older women or because they had had previously undiagnosed pelvic inflammatory disease,

• Use of combined oral contraceptives reduced the chance of tubal factor infertility by a third compared to non-users of contraceptives.

Diagnosis of Pelvic Inflammatory Disease

Most women are diagnosed clinically — very few will get as far as having a laparoscopy, and although laparoscopy is the gold standard test for salpingitis it is less sensitive for milder disease.

A variety of diagnostic criteria for pelvic inflammatory disease are variable. In general, the more precise the criteria are the less sensitive they become. However, one cannot treat every woman for pelvic inflammatory disease so the following clinical diagnostic criteria give a useful guide:

Symptoms:

• pelvic pain/discomfort and/or deep dyspareunia in the absence of urinary symptoms.

Plus examination findings:

• adnexal tenderness on bimanual examination

• and/or cervical motion tenderness.

Plus near-patient tests:

• temperature over 38°C

• not pregnant. Always do a pregnancy test unless the patient has not had vaginal sex for several months. Missing an ectopic pregnancy would be a disaster for the patient and for your future employment

• presence of Trichomonas vaginalis. gonorrhoeae on Gram-stained smear from cervix

• presence of an excess of polymorphs on Gram-stained smear from cervix. Conversely the absence of polymorphs makes pelvic inflammatory disease unlikely

• mid-stream specimen of urine (MSSU) dipstick urinalysis normal.

Plus laboratory tests:

• positive chlamydia test

• positive gonorrhoea test

• raised white cell count

• raised C reactive protein (CRP).

Treatment of Pelvic Inflammatory Disease

Treatment depends on the severity of the condition and aims to cover the likely organisms: C. trachomatis, N. gonorrhoeae, M. hominis and anaerobes. There is debate as to whether every woman needs to have anaerobic or gonorrhoea cover, particularly if her symptoms are mild. However, unless you are experienced in managing pelvic inflammatory disease and know your local STI epidemiology, it is probably best to assume she has all of them. The following regimens are from the 2005 UK pelvic inflammatory disease management guideline: For inpatients (i.e. severe symptoms, unable to tolerate oral agents):

• i.v. cefoxitin 2 g t.d.s. for at least 48 hours

• plus i.v. or oral doxycycline 100 mg b.d.

followed by

• oral doxycycline 100 mg b.d.

• plus oral metronidazole 400 mg b.d. for a total of 14 days.

For outpatients:

• i.m. ceftriaxone 250 mg stat followed by

• oral doxycycline 100 mg b.d. for 14 days

• plus metronidazole 400 mg b.d. for 14 days.

Pregnancy

pelvic inflammatory disease in pregnancy is associated with miscarriage or pre-term labour. Treatment should therefore be parenteral to maximize efficacy, but doxycycline cannot be used. An alternative is erythromycin 50 mg/kg per day given in divided doses every 6 hours.

Sexual contacts

If specific causative organisms are found, e.g. chlamydia or gonorrhoea, then sexual contacts should be treated for those infections. In the common situation in which the woman’s microbiology lab tests are all negative, the sexual contacts should be seen, assessed, have an STI screen and be given epidemiological treatment for uncomplicated chlamydia pending results.

Other management of Pelvic Inflammatory Disease

• Admit if symptoms are severe.

• Unless symptoms are extremely mild, any intra-uterine contraceptive device or system should be removed.

• Patients should be given written information about the condition and advised to not have sex while undergoing treatment and to avoid sex with untreated partners.

Follow-up

Women should be seen again after a few days to ensure that symptoms are resolving. If they are not resolving, consider an alternative diagnosis and/or refer for a pelvic ultrasound scan in case of tubal abscess.

Further follow-up depends on the need for partner notification progress and symptoms.

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