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MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS Vaginal discharge Phillip Hay Abstract Vaginal discharge is

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS

Vaginal discharge

Phillip Hay

Abstract

Vaginal discharge is a common presentation in sexual health clinics, gynaecology clinics and general practice. The three common causes with vaginal pathology e candidiasis, bacterial vaginosis and trichomo- niasis e are diagnosed with the aid of relatively simple diagnostic tests. Cervicitis caused by organisms such as Chlamydia can cause a purulent discharge. Other causes include atrophic vaginitis, desquamative in- ammatory vaginitis, cytolytic vaginosis and rarely neoplasia. Candidi- asis is treated initially with oral or topical azoles. Bacterial vaginosis and trichomoniasis are treated with metronidazole, and partner notication is required for the latter. Frequently recurrent candidiasis and bacterial vaginosis are problematic, and specialist advice should be sought.

Keywords Bacterial vaginosis; MRCP; trichomoniasis; vaginal candidiasis; vaginal discharge; vaginal microscopy

Introduction

Vaginal discharge is a common presentation, and most women develop an abnormal discharge at some point in their life. Symptoms can be concealed because of embarrassment, so sensitivity is needed when taking a history. A few have frequent recurrences, and the condition can come to dominate their lives. Important questions for the history are shown in Table 1 . The diagnosis can readily be confirmed by microscopy and culture of appropriate swabs. It is important for practitioners to have an understanding of normal physiology, changes with age and pathological conditions. The two most common causes of abnormal discharge e candidiasis and bacterial vaginosis (BV) e are not regarded as sexually transmitted, whereas trichomoniasis and cervicitis are.

Physiology

In pre-menarcheal girls, the vagina is lined with a simple cuboidal epithelium. The pH is neutral, and the epithelium is colonized with skin commensals. Under the influence of oestrogen at pu- berty, stratified squamous epithelium develops and lactobacilli become the predominant organism. The pH falls to 3.5 e 4.5. After the menopause, atrophic changes occur, with a return to flora more similar to those of the skin. The pH again rises to 7.0.

Physiological discharge Normal vaginal discharge is white or yellowish. It consists of epithelial cells, mucus, bacteria and fluid transudate. Lactic acid

Phillip Hay MBBS FRCP is Reader and Honorary Consultant HIV Medicine Decommissioned Consultant in Sexual Health at St Georges University Hospitals NHS Foundation Trust, UK. Competing interests:

within the last ve years, Dr. Hay has received payment for advice, speaking at meetings and attendance at conferences from Bayer Consumer Healthcare, Hologic, Becton-Dickinson.

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Key Points

 

C

Vaginal discharge can be diagnosed clinically, supported by microscopy, culture and nucleic acid amplification tests

C

Uncomplicated candidiasis and bacterial vaginosis are readily treated with oral or topical azoles and metronidazole, respectively

C

Cervicitis associated with gonorrhoea, chlamydia or Myco- plasma genitalium can present as discharge

C

Less common causes include desquamative inflammatory vaginitis, cytolytic vaginosis and cervical ectropion

C

Recurrent vaginal discharge is best managed through specialist referral

comes from glycogen being metabolized by vaginal epithelium and lactic-acid-producing bacteria e lactobacilli or bifidobac- teria. Physiological discharge increases mid-cycle. It also in- creases in pregnancy and sometimes when women start a combined oral contraceptive pill. Cervical ectropion can be associated with excess mucus production causing persistent discharge, which can be treated by cervical cautery.

Abnormal discharge Vaginal discharge can originate from anywhere in the upper or lower genital tract. Discharge arising from the vagina itself can be physiological or pathological ( Table 1 ). Uncommon causes are summarized in Table 2 . The key points in history-taking are:

the characteristics of the discharge: colour, consistency, amount (use of pads or tampons), smell and whether it is bloodstained associated symptoms such as dyspareunia, either superfi- cial or deep, itching or soreness

whether there have been similar occurrences, whether there were trigger factors, and the relationship to the menstrual cycle self-treatment, previous treatments and response to them, and recent antibiotic use washing practices, douching and antiseptics.

a standard sexual history, as described in other chapters

Diagnostic tests

In specialized sexual health clinics candidiasis, BV and tricho- moniasis can be diagnosed by microscopy of a saline wet mount and a Gram-stained vaginal smear. This allows immediate diag- nosis, subsequently supported by laboratory culture and nucleic acid detection tests as needed. In the absence of microscopy, vaginal pH can be measured simply with narrow-range pH paper. BV and trichomoniasis are excluded by a pH <4.5, but a pH >4.5 is not very specific for a positive diagnosis.

2018 Published by Elsevier Ltd.

Please cite this article in press as: Hay P, Vaginal discharge, Medicine (2018), https://doi.org/10.1016/j.mpmed.2018.03.006

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS Differential diagnosis of the principal causes of abnormal

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS

Differential diagnosis of the principal causes of abnormal vaginal discharge

 
   

Symptoms and signs

Candidiasis

Bacterial vaginosis

Trichomoniasis

Cervicitis

Itching or soreness Smell Colour Consistency pH Confirmed by

þþ May be ‘yeasty’ White Curdy

e Offensive, fishy White or yellow Thin, homogenous

þþþ May be offensive Yellow or green Thin, homogenous 4.5e 7.0 Microscopy and NAAT test culture if NAAT not available

e e White or green Mucoid Any Microscopy, tests for chlamydia, gonorrhoea and Mycoplasma genitalium

<4.5

4.5e7.0

Microscopy and

Microscopy

 

culture

NAAT, nucleic acid amplification test.

 

Table 1

Other causes of abnormal vaginal discharge

 

Infective conditions

C

Upper genital tract infection, e.g. pelvic inflammatory disease, postpartum endometritis

C

Primary syphilitic chancre

C

Primary herpes Non-infective

C

Desquamative inflammatory vaginitis

C

Atrophic vaginitis

C

Cytolytic vaginosis

C

Retained tampon or condom

C

Cervical ectropion or endocervical polyp

C

Intrauterine contraceptive device

C

Allergic vaginitis, chemical irritation

C

Physical trauma

C

Fistula: rectovaginal or vesicovaginal

C

Vault granulation tissue

C

Neoplasia

Table 2

Nucleic acid amplification tests (NAATs) are also performed for gonorrhoea and chlamydia, as discussed in other chapters. NAAT tests for Mycoplasma genitalium and Trichomonas are increasingly being performed: the sensitivity of microscopy for Trichomonas is <50% compared with NAAT testing.

Vaginal candidiasis

Over three-quarters of women have at least one episode of vaginal candidiasis in their lifetime. At any point, 25% women have candidal colonization of the vagina, but only a minority get symptoms. Candida albicans is found in > 80% cases. Sexual acquisition is rarely important, although intercourse is an established risk factor: the physical trauma of intercourse can trigger an episode. It is oestrogen-dependent so rarely seen in prepubertal girls or postmenopausal women. The invasiveness of C. albicans is increased by oestrogen.

Predisposing factors for candidiasis Immunosuppressive therapy, for example corticosteroids.

2

Diabetes mellitus and gliflozin-class drugs, which increase

glycosuria. Vaginal douching, bubble baths, shower gel, tight clothing

and tights. Increased oestrogen:

e

pregnancy

e

high-dose combined oral contraceptive pill. Underlying dermatosis, for example eczema.

Broad-spectrum antibiotic therapy.

Principal clinical features Itching, soreness and redness of the vagina and vulva.

Curdy white discharge that can smell yeasty but not unpleasant. Sometimes fissuring and excoriations. Not all candidiasis presents in the same way; in some cases, particularly with non-albicans strains, there can be itching and redness with a thin watery discharge. The diagnosis can be confirmed by microscopy and culture of the vaginal fluid. Asymptomatic women from whom Candida is grown on culture do not require treatment.

Treatment Licensed treatments produce cure rates of 80 e95% in non- pregnant women. Some women have a preference for oral

therapy, particularly if required at the time of menstruation. Vaginal creams and pessaries can be prescribed in a variety of doses and duration of treatment. Commonly prescribed treat- ments are:

a single dose of a topical azole, for example a clotrimazole pessary 500 mg in a single dose

oral fluconazole 150 mg tablet as a single dose. Longer courses of treatment, for example clotrimazole 100 mg daily for 6 e7 days, are indicated:

when there are predisposing factors that cannot be elimi-

nated, such as corticosteroid therapy for women with frequent recurrences.

in pregnancy

Complications and pregnancy Oral azoles are not recommended in pregnancy because of teratogenicity.

2018 Published by Elsevier Ltd.

Please cite this article in press as: Hay P, Vaginal discharge, Medicine (2018), https://doi.org/10.1016/j.mpmed.2018.03.006

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS Complications are uncommon. Women occasionally become

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS

Complications are uncommon. Women occasionally become allergic to topical agents after regular application. In some women, a severe episode of candidiasis can trigger long-term vulvodynia. Symptomatic candidal infection of male partners is uncom- mon, but they sometimes react to candidal antigens, developing soreness and balanitis after intercourse.

Persistent or recurrent candidiasis Recurrent Candida infection and Candida not responding to treatment are uncommon. Individuals presenting as ‘treatment- resistant candidiasis’ usually have an alternative diagnosis such as herpes simplex, vulvodynia or a dermatological condition such as eczema or lichen sclerosus. Genuine recurrent Candida can be suppressed by various regimens such as weekly fluconazole 150 mg for 6 months. 1 Unfortunately, this does not prevent further recurrences, and treatment may need to be continued for longer. If resistance to treatment is shown clinically and in vitro , referral to a specialist clinic is advised; here new antifungal agents such as voriconazole may be used, or unlicensed boric acid applied intravaginally.

Bacterial vaginosis

BV is the most common cause of abnormal vaginal discharge in women of childbearing age. Studies in antenatal and gynaecology clinics show a prevalence of approximately 12% in the UK. The reported prevalence has varied widely from as low as 5% in a selected group of asymptomatic college students to 50% of women in a large study in rural Uganda. It is more common in black women and women who have an intrauterine contracep- tive device in place. It is also more common in women with sexually transmitted infections but has been reported in virgins, and may be particularly common in lesbian women. The condi- tion often arises spontaneously around the time of menstruation and can resolve mid-cycle. When BV develops, predominantly anaerobic organisms in- crease in concentration up to a thousand-fold and overwhelm the lactobacilli (Figure 1 ). Vaginal pH rises to between 4.5 and 7.0.

( Figure 1 ). Vaginal pH rises to between 4.5 and 7.0. Figure 1 Phase contrast

Figure 1 Phase contrast

cation.

organism with four anterior

microscopy of

uid

seen as an ovoid or pear-shaped

vaginal

at 400 magni-

Trichomonas

vaginalis is

agellae

(arrows).

The bacteria most often found by culture are Gardnerella vagi- nalis , Prevotella spp., Mycoplasma hominis and Mobiluncus spp. Molecular techniques have more recently found Atopobium vaginae , BV-associated bacteria (BVAB1 eBVAB3: Clostridiales ), Megasphaera , Sneathia and Leptotrichia . Additionally, a biofilm consisting predominantly of Gardnerella and A. vaginae has been described, which places these organisms at the centre of pathogenesis.

Clinical features Offensive fishy-smelling discharge.

Discharge that is characteristically thin and homogenous, and adheres to the walls of the vagina. White or yellow discharge.

A smell that is particularly noticeable around the time of menstruation or after intercourse. Semen itself can give off a weak fishy smell. The diagnosis was traditionally made in clinical practice

identifying at least three of the composite (Amsel) criteria:

release of a fishy smell on addition of alkali (10% potas-

vaginal pH > 4.5

sium hydroxide) a characteristic discharge on examination

the presence of ‘clue cells’ on microscopy. Clue cells are vaginal epithelial cells so heavily coated with bacteria that the border is obscured ( Figure 2 ). In sexual health clinics, BV is now diagnosed from a Gram-stained vaginal smear. Large numbers of Gram-positive and Gram-negative cocci are seen, with reduced or absent large Gram-positive bacilli ( Lactobacilli ). Culture is not useful for diagnosis as, for instance, Gardnerella can be grown from 50% of women who do not have BV.

Treatment BV resolves on treatment with antibiotics with good anti-

anaerobic activity. A comprehensive review was used to guide the 2006 Centers for Disease Control guidelines. 2 The preferred treatment is:

metronidazole 400 mg twice a day for 5 days. Alternative treatments are:

metronidazole vaginal gel 0.75% applied nightly for 5

metronidazole 2 g as a single dose

nights clindamycin cream 2% applied nightly for 5 e7 nights

dequalinium chloride 10 mg pessary for 6 nights, which has more recently been licensed in the UK. Initial cure rates are > 80%, but up to 30% of women relapse within 1 month of treatment. Metronidazole causes nausea and an unpleasant metallic taste. It is best taken after food. Clindamycin cream has rarely been associated with Clostridium difficile diarrhoea.

Complications During pregnancy, women with BV are at greater risk of second- trimester miscarriage and preterm delivery. This can result in perinatal mortality or cerebral palsy. The results of studies treating BV with metronidazole or clindamycin have been con- flicting, so current guidelines do not recommend routine screening and treatment.

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Please cite this article in press as: Hay P, Vaginal discharge, Medicine (2018), https://doi.org/10.1016/j.mpmed.2018.03.006

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS Figure 2 Microscopy of Gram-stained vaginal smears at

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS Figure 2 Microscopy of Gram-stained vaginal smears at

Figure 2 Microscopy of Gram-stained vaginal smears at 1000 magnication. (a) Normal ora: lactobacilli are seen as large Gram-positive rods and there are intact epithelial cells. (b ) Candidiasis: Gram-positive spores and hyphae are seen. ( c) Cytolytic vaginosis: cytoplasmic debris and isolated nuclei are seen, with lactobacilli. Occasional polymorphs are present. ( d ) Bacterial vaginosis: numerous small bacteria, mixed Gram- positive and Gram-negative, including some curved rods. (All 800 magnication).

BV should be treated with metronidazole before termination of pregnancy to reduce the subsequent incidence of endometritis and pelvic inflammatory disease.

Recurrence In many women, the vaginal flora is in a dynamic state, with BV developing and remitting spontaneously. Symptomatic women with recurrent BV can become frustrated as although the condi- tion responds rapidly to treatment with antibiotics, it may quickly relapse. Our inability to alter this process reflects our current lack of knowledge of the factors that trigger BV. Regular treatment with 0.75% metronidazole gel twice a week for 6 months reduces the rate of recurrence. 3 Some women need simultaneous suppressive treatment for Candida .

Trichomoniasis

This sexually transmissible infection can be carried for several months before causing symptoms. It is diagnosed in approxi- mately 1% women attending sexual health clinics in the UK. However, its prevalence is higher in many tropical countries, with rates of 10 e20% in some settings. In men, it is usually asymptomatic but can present as non-gonococcal urethritis.

Clinical features Vulvovaginitis, which can be severe, with inflammation sometimes extending onto the labia majora and adjacent skin.

Purulent, green or yellow discharge, which is sometimes offensive. In many cases, additional BV.

Sometimes punctate haemorrhages on the cervix, giving the appearance of a ‘strawberry cervix’. The diagnosis is traditionally confirmed by microscopy of vaginal secretions mixed with saline, or culture in a specific medium such as FienbergeWhittington medium. Numerous poly-

morphonuclear cells are seen, and the motile organism is iden- tified from its shape and four moving flagella. Microscopy has a 60% sensitivity compared with culture. NAATs are now avail- able and offer greater diagnostic sensitivity.

Management Metronidazole is given, either 2 g as a single dose, or 400 mg twice a day for 5 days. Partner notification is needed, and the woman should not resume sexual intercourse until her sexual partner(s) has been treated. Tinidazole 2 g as a single dose is more expensive but occasionally works when metronidazole has failed. Patients allergic to metronidazole should be managed by desensitization, in collaboration with an allergy specialist.

Complications and pregnancy Trichomonas has occasionally been identified in the upper gen- ital tract of women with pelvic inflammatory disease, but is probably not an important cause of upper genital tract pathology. It can be isolated from the bladder.

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2018 Published by Elsevier Ltd.

Please cite this article in press as: Hay P, Vaginal discharge, Medicine (2018), https://doi.org/10.1016/j.mpmed.2018.03.006

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS Although Trichomonas is a risk factor for preterm

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS

Although Trichomonas is a risk factor for preterm birth, treating asymptomatic infection has not been shown to improve outcome. Symptomatic women should be treated with a 5-day course of metronidazole.

Recurrence and resistance Persistent trichomoniasis is occasionally seen. This can be caused by poor compliance with medication, poor absorption, reinfection or, rarely, a resistant organism. The usual approach is to use higher doses of metronidazole, initially 400 mg three times a day, increasing to 1 g per rectum twice a day or intravenously. Neuro- logical toxicity can be encountered with high doses. Some clini- cians prescribe a broad-spectrum antibiotic such as co-amoxiclav to eliminate bacteria such as group B streptococci that might be metabolizing metronidazole, thereby diminishing its efficacy. Alternative treatments are unfortunately limited and unli- censed, but include arsphenamine pessaries, clotrimazole and boric acid. Referral to a specialist is advised.

Cervicitis: Neisseria gonorrhoeae, Chlamydia and M. genitalium

Cervicitis can be caused by these organisms or be non-specific in a similar way to urethritis in men. A purulent discharge origi- nates from the cervix, and numerous white cells are seen on vaginal microscopy. The discharge can be white, yellow or green, and can be bloodstained and associated with intermenstrual and post-coital bleeding. On speculum examination, a mucopurulent discharge may be seen coming from the cervix, and contact bleeding after swabbing is common. Treatment should be prescribed as for men with urethritis:

doxycycline 100 mg twice daily for 7 days, or azithromycin 1 g as a single dose.

Vaginal discharge in children

Vaginal infections are common in childhood and usually not related to sexual abuse. Causes include streptococcal infections and Shigella , which can cause a chronic haemorrhagic vaginitis, often with no history of diarrhoea. Recurrent vaginal infections should lead to a foreign body being suspected. Pinworms (Enterobius vermicularis ) migrate from the anus at night, causing intense irritation and inevitably scratching. The clue to the diagnosis is the nocturnal pattern. The cuboidal epithelium lining the vagina in children is sus- ceptible to infection by Chlamydia or N. gonorrhoeae , which means that if sexual abuse occurs that then leads to infection, a generalized vaginitis with purulent discharge occurs.

Other conditions affecting the vagina

Atrophic vaginitis is common in postmenopausal women. This can lead to superficial dyspareunia and vaginal soreness. Oes- trogen replacement with topical oestrogen is effective. There is an overlap with desquamative inflammatory vaginitis, a condi- tion of unknown aetiology that also shares some features of vaginal erosive lichen planus. Occasionally, a true bacterial vaginitis is encountered that is caused by a Streptococcus or other organism. This responds to appropriate antibiotic therapy such as co-amoxiclav 375 mg three times a day for 7 days. Toxic shock syndrome is a rare condition

associated with retention of tampons or foreign bodies in the vagina. An overgrowth of toxin-producing staphylococci causes systemic shock with fever, diarrhoea, vomiting and an erythematous rash. More frequently, a foreign body or retained tampon merely causes an offensive BV discharge. Cytolytic vaginosis is recognized by the cyclical nature of irritant symptoms developing during the luteal phase of the menstrual cycle. 4 It is often initially misdiagnosed as candidiasis that is failing to respond to treatment. On microscopy, there is extensive cytolysis with free nuclei and cellular debris, and polymorphs are usually absent. Treatment is with baking soda douches, as described on the University of Virginia website. 5

Self-help and over-the-counter treatments

Women should be advised to avoid douching and other washing practices that will disturb the endogenous flora. Use of over-the- counter Candida treatments without a confirmed diagnosis can lead to delays in being given the correct diagnosis and treatment. Probiotics and lactic acid gels have not been sufficiently rigorously evaluated to allow a recommendation to be made, but some women derive symptomatic relief from them. Anecdotally, reducing sugar intake, stopping oestrogen-containing contraception and avoiding tight clothing can reduce the frequency of Candida recurrences.A

KEY REFERENCES

5 University of Virginia Department of Student Health. https://health. students.vcu.edu/media/student-affairs/ushs/docs/ CYTOLYTICVAGINOSIS.pdf (accessed 03 April 2018).

FURTHER READING American Centers for Disease Control and Prevention. Sexually transmitted diseases (STDs). http://www.cdc.gov/std/treatment/.

USEFUL WEBSITES British Association for Sexual Health and HIV: http://www.bashh.org.uk. Royal College of Obstetrics and Gynaecology: http://www.rcog.org.uk.

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Please cite this article in press as: Hay P, Vaginal discharge, Medicine (2018), https://doi.org/10.1016/j.mpmed.2018.03.006

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS TEST YOURSELF To test your knowledge based on

MANAGEMENT OF INFECTIVE AND NON-INFECTIVE GENITAL CONDITIONS

TEST YOURSELF

To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the

end of the issue or online here.

Question 1

A 29-year-old woman presented with abnormal vaginal

discharge. She had a history of metronidazole allergy with rash,

facial oedema and tightness in the throat.

Investigation

Wet-mount

examination

showed motile Trichomonas

vaginalis

What is the best management plan?

A. Tinidazole 2 g single dose orally

B. Clotrimazole pessaries 100 mg at night for 6 days

C. A course of desensitization followed by metronidazole 400 mg 12-hourly for 5 days

D. Co-amoxiclav 625 mg 8-hourly daily for 5 days

E. She should be told that she cannot be treated safely but it

should resolve within 6 months

Question 2 A 26-year-old woman presented with vaginal itching, soreness and discharge at 18 weeks’ gestation in her first pregnancy. She was found to have candidiasis.

What is the most appropriate treatment?

A. Clotrimazole 500 mg pessary, single dose

B. Fluconazole 150 mg orally, single dose

C. Nystatin pessaries 100,000 IU at night for 6 days

D. Clotrimazole pessaries 100 mg at night for 6 days

E. Fluconazole 100 mg at night for 6 days

Question 3 A 16-year-old woman presented with a 1-week history of an offensive thin discharge that had started at the end of menstruation.

Which of the following findings is not a criterion for a diag- nosis of bacterial vaginosis?

A. Vaginal pH of 5.5

B. Clue cells seen on wet-mount microscopy

C. Numerous polymorphonuclear cells seen on wet-mount microscopy

D. Replacement of lactobacilli with numerous Gram-positive and Gram-negative bacteria on Gram staining

E. Release of a fishy odour on mixing of vaginal fluid with 10% potassium hydroxide

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Please cite this article in press as: Hay P, Vaginal discharge, Medicine (2018), https://doi.org/10.1016/j.mpmed.2018.03.006