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LITERATURE REVIEW

CLINICAL ASPECTS FLUOR ALBUS OF FEMALE AND TREATMENT


Monalisa, Abdul Rahman Bubakar, Muhammad Dali Amiruddin Departement of Dermatovenereology Medical Faculty of Hasanuddin University / Wahidin Sudirohusodo Hospital Makassar

ABSTRACT
Vaginal discharge is an excessive secretion of fluid from the female reproductive canal (vagina). Vaginal discharge can be either physiological or pathological. Physiological vaginal discharge consists of fluid, that sometimes is mucous with numbers of epithelial cells and few leukocytes, whereas in pathological conditions, consists of a lot of leukocytes. Several physiological conditions are newborn, late menarche, pregnancy, sexual stimulation and chronic diseases. Vaginal discharge was found ranging from childhood to adulthood. Discomfort, low self-esteem, anxiety caused by vaginal discharge lead some women to seek help at the doctor but mostly soluble in an attempt to self-medication. Most pathologic vaginal discharge was caused by infection. This paper will discuss clinical picture of the vaginal discharge and its management. Keywords : vaginal discharge, clinical manifestation, treatment.

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PREFACE
Fluor albus / leucorrhea / white discharge is a state of vaginal discharge and/or cervix in women. Fluor albus can be either physiological or pathological. Fluor albus was determined as pathological vaginal discharge or cervix discharge , if accompanied by changes in odor and color as well as the amount that is not normal. Complaints may be accompanied by intense itching, genital edema, dysuria, lower abdominal pain or low back pain. (1) In normal conditions, the glands in the cervix produce a clear liquid that comes out mixed with bacteria, the cells are separated and vaginal secretions from bartholins gland. In women, vaginal discharge is a natural thing from the body to cleanse itself, as a lubricant and the defense of various infections. Under normal conditions, it seems clear vaginal discharge, cloudy white or yellowish when dry on clothing. This discharge of nonirritant, not interfere, there is no blood and has a pH of 3.5 to 4.5. (2, 3) The most common cause of pathological fluor albus is infected. Various pathogens can cause vaginal discharge that is transmitted through sexual intercourse. Leucorrhea can be differentiated into vaginitis and cervicitis. Vaginitis can be caused by Candida albicans, Gardnerella vaginalis, Mycoplasma genital and anaerobic germs and Trichomonas vaginalis. While cervicitis often caused by Neisseria gonorrhoeae and Chlamydia trachomatis. (1) To established a diagnosis, it takes some laboratory examinations. Among others are the direct microscopic examination with saline solution dripped into the vaginal secretions (wet preparation), direct microscopic examination with 10% KOH solution, with gram staining, culture methods/breeding.
(4)

disease history, physical examination and investigation to STI etiological diagnosis is frequently encountered problems. Related to time constraints, resource availability, financing and affordability of treatment. (5)

EPIDEMIOLOGY
Bacterial vaginosis (BV) is the commonest cause of vaginal discharge and odor, but more than 50% of women with asymptomatic BV. More often found in women who check their health another types of vaginitis. Frequency depends on socioeconomic level population, we had mentioned that 50% of sexually active women infected with Gardnerella vaginalis, but few cause symptoms. (5) Candidiasis Vulvovaginalis (CVV) of mostly women at least once during their lifetime, most often in the productive age, with estimated between 70-75%, of which 40-50% will experience recurrence. Most studies indicate that the KVV is a frequent diagnosis among young women, are about as many as 15-30% of symptomatic women who visit the doctor. (6) Reports for trichomoniasis prevalence varies widely, depending on the techniques used in the diagnosis and the population studied. In general, prevalence estimates ranging from 5% to 74% in women and 5-29% in men, with the highest number of both sexes reported among STD clinic patients and other highrisk populations. (7) Chlamydia infection of the genital organs are distributed worldwide and prevalent in industrialized countries and developing countries. World Health Organization (WHO) estimates that 89 million new cases of genital chlamydia infections occurred worldwide in 2001. The number of reported cases occur in womenmore than men. (8) The incidence of gonorrhea varies according to age, 75% of cases reported in the age 15-29 years, with the highest rates occurred in the age group 15-19 years. Demographic risk factors for

Components of the management of sexually transmitted infections (STIs) among others are covering history,

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Clinical Aspects Fluor Albus of Female and Treatment

gonorrhea include low socioeconomic status, early onset of sexual activity, without marital status, and past history of gonorrhea. (9)

ETIOPATHOGENESIS
Fluoralbus can be caused by manythings, fluor albus physiologically canbe found in some circumstances following, newborn babies until approximately age 10 days because of the influence of estrogen from the placenta to the uterus and vagina fetus, before menarche because of the influence of the hormone estrogen and canbe lost own, adult women are aroused by spending transudation of vaginal wall. (2) Although many variations of color, consistency, and amount of vaginal discharge can be considered a normal, but the change is are always interpreted as an infection patients ,especially caused by the fungus . Some women also have a lot of vaginal discharge. Under normal conditions, discharge from the vagina containing vaginal discharge, vaginal cells are separated and cervical mucous, which will vary due to age, menstrual cycle, pregnancy, use of birth control pills. Normal vaginal environment is characterized by a dynamic relationship between Lactobacillus acidophilus with other endogenous flora, estrogen, gly-cogen, pH of the vagina and the other metabolites. Lactobacillus acidophilus produces endogenous peroxide is toxic to bacterial pathogens. Because the action of estrogen on the vaginal epithelium, the production of glycogen, lactobacillus (Dderlein) and lactic acid production that produces a low vaginal pH to 3.8 to 4.5 and at this level can inhibit the growth of other bacteria. (3) Pathological fluor albus can be caused by sexually transmitted infections (Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis), other infections such vulvovaginalis can-didiasis (Candida albicans), bacterial vaginosis (Gardnerella vaginalis), because of foreign

objects and the process of malignancy. (10) The most common cause of pathological fluor albus is infected. Here the fluid containing many leukocytes and slightly yellowish color to green, often more thick and smelly. (2)

CLINICAL PICTURE
Pathological fluor albus body can be caused by Trichomonas vaginalis, Candida albicans and mixed infections of Gardnerella vaginalis and vaginal anaerobs. Neisseria gonorrhoeae and Chlamydia trachomatis cause cervical discharge and cervicitis. (11) Fluor albus caused by Trichomoniasis is usually asymptomatic or appear with a picture of a vaginal discharge is thick, foulsmelling, greenish yellow color, and accompanied by pruritus on the vulva. In addition there is an infection also occurs inflammation of the vagina and cervix, sometimes also found in minor bleeding with ulceration of the cervix. (4, 12, 13) Fluor albus caused by Candida albicans is white, odorless or smell sour, the vaginal wall is normally the picture of a lump of cheese (cottage cheese), sometimes accompanied by a sense of hot/burning, and dysuria and dispareuni. (6, 10, 14) Fluor albus caused by Gardnerella vaginalis and vaginal anaerobes in the form snoring discharge, dilute, homogeneous, white-gray to yellowish with foul or fishy odor and attached to the walls of the vagina, often appear on the labia.
(10, 12, 15)

Fluor albus caused by Neisseria gonorrhoeae from endocervicitis is purulent, thin and somewhat smelly. In addition vaginal discharge complaints, the infection

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is some times accompanied by complaints dysuria, dyspareunia and lower abdominal pain, fever, nausea and vomiting. (4, 9, 12) Fluor albus caused by Chlamydia trachomatis is characterized by a purulent exudate or mukopurulen seen in endocervical and cervical fragile and bleed easily be postcoitus or intermenstrual bleeding.
(12)

Fluor albus caused by foreign bodies sometimes accompanied by blood. Vaginal discharge that occurs in children, the very suspicion caused by foreign objects. If there is infection, especially by anaerobic bacteria, purulent discharge may form. (12)

EXAMINATION SUPPORT
To assist in the diagnosis of sexually transmitted infections, there are several laboratory tests, namely: Wet specimen examination (0.9% Nacl) In this examination of the vaginal discharge swab taken from the posterior fornix mixed at Nacl solution droplets on the glass object. Microscopic examination of wet preparations to see the movement of trichomonas, PMN leukocytes, vaginal epithelium.(16) Examination of specimens should not be postponed, since when it has dried to change the outcome. For exampleTrichomonas vaginalis to lose motility when wet has dried preparations, which is then difficult to distinguish from leukocytes. 10x magnification for counting leukocytes, epithelial cells, the movement of Trichomonas vaginalis and pseudohifa. Greater magnification to see the clue cells, Trichomonas vaginalis, and blastospora. If found 1

Trichomonasvaginalis with the form of a kite and move to say(+) trichomoniasis. (4, 16, 17) Examination preparation 10% KOH Addition of KOH in wet preparations to dissolve the epithelial cells and make more visible hyphae. Blastospora can also be seen. If found 1 or blastospora pseudohifa and said (+) vulvovaginalis candidiasis. (4, 16, 17) GramStaining To manufacture these preparations taken discharge smear from the cervix and vagina. On gram staining that examined the number of PMN leukocytes and epithelium, Candida (pseudohifa and blastospora), diplococcus intracellular gram negative. In cervical smear if obtained 1 PMN-containing gram-negative diplococcus with typical morphology, 5PMN/field of view of immersion oil is said (+) gonococcal infection. Vaginal swabs from the discharge said (+) if earned pseudohifa candida and orblastospora, whereas bacterial vaginosis was found morphotype for lactobacil. (4, 12, 17) Whifftest / Amin test At the end of the examination in spekulo, speculum removed carefully and then the liquid was poured speculum10% KOH solution. Are sought on this exami-nation is fishy odor or smell of amine were detected after the addition of10% KOH to vaginal discharge. (4, 17) Examination Vaginal Fluid pH Vaginal discharge in the lateral part of the vagina using pH indicator paper. Checking the pH mustbe careful to avoid contact with the mucosal of the cervix have a high pH.(17)

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Bacterial Culture Inspection To see the bacterial aerobic and anaerobic what is the cause of the infection. Polymerase Chain Reaction (PCR) PCR is used to identify microorganisms that cause infections with certainty. (4, 17)

Complications common in cervisitis gonorrhea is pelvic inflammatory disease. It was about10-20% of acute gonorrhea infection. Another complication is bartholinitis. (4, 9)

TREATMENT
Management fluor albus depends on the underlying cause of fluor albus. Treatment vaginal discharge caused by Trichomonas aginalis (Trichomoniasis). The recommended therapy is metronidazole 2 grams orally single dose or tinidazole 2 g oral single dose. As for the alternative regimens can be administered orally 2 x 500 mg metronidazole for seven days, or tinidazole 2 x 500 mg for five days. (5,18) Metronidazole has antiparasitic and antimicrobial effects, which are effective against trichomoniasis and some other obligate bacteria. Randomized clinical trials using metronidazole showed 90-95% cure rate, while the use of tinidazole provide 86 - 100% cure rate. Provision of therapy in patients and sexual partners will eliminate the symptoms, healing microbiology and reduced transmission. (5) Metronidazole gel in the treatment of trichomoniasis is less effective than oral preparations. Application of topical anti-microbials can not reach therapeutic levels in the urethra or glans perivaginal, therefore the use of topical preparations are not recommended. However, in patients with recurrent trichomoniasis with metronidazole therapy, additional therapy can be given topical therapy of intra-vaginal metronidazole 500 mg every night for 3-7 days. Follow-up after therapy is not needed

COMPLICATION
In trichomoniasis complications that can happen is cystitis, skenitis and Bartholin abscess. In pregnant women can cause premature birth, low birth weight. Infertility can occur in Trichomonas vaginalis that is transmitted through sexual intercourse. In the vagina or cervix in ascending infect the endometrium, fallopian tubes and adjacent structures causing pelvic inflammatory disease and almost always left sequele of scarring or adhesions and infertility asa result.
(4, 7)

In VVC most disturbing complication is recurrent infections, especially in patients who have a predisposition to infection. In pregnant women the complications that can occur spreading infection to the upper(ascending infection) and cause hematogenous dissemination. Babies born to mothers who suffer VVC can be infected through direct contact with contaminated amniotic fluid or direct contact through the birth canal. (4, 6, 14) Complications of BV is an increased risk of urinary tract infection. High incidence of BV in women with pelvic inflammatory disease. Although no studies showing that treatment of BV reduce the risk of pelvic inflammatory disease later in life. (4, 13, 15)

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anymore when it does not have symptoms. (18) Sexual partners of patients with trichomoniasis should also be treated. Patients are also advised to abstain from sexual relations until cured (treatment has been completed and the patient / asymptomatic sexual partner). (18) Some special considerations that need to be considered on the following conditions: Gestation Trichomonas vaginalis may cause complications in pregnancy such as premature rupture of membranes, premature delivery and low birth weight. Therapy can eliminate symptoms vaginal discharge pregnant woman, preventing the infant genital infection. Provision of metronidazole is not recommended in the first trimester of pregnancy, but canbe used on the second and the third trimesters. Minimum dose (2gr single oral dose), whereas the incoming tinidazole preformance category C.(5, 18) Lactating women treated with metronidazole, should stop breastfeeding during treatment and 12-24 hours after the last dose will reduce exposure to metronidazole in infants. While the use of tinidazol breastfeeding cessation is recommended during therapy and 3 days after last dose.(5, 18)
Allergy Or Intolerance

Recommended regimen : Miconazole or clotrimazole 200mg intravaginal /day 3 days Clotrimazole 500 mg intravaginal single dose Fluconazole 150 mg oral single dose Alternative regimen : Nystatin 100.000 IU intravaginal / day 14 days Canadian Guideline 2008(19) Azole Intravaginal Clotrimazole orMiconazole Fluconazole 150 mg oral single dose Sexually Transmitted Diseases Treatment Guidelines 2006(5) Intravaginal : Butoconazole 2% cream 5 g intravaginal 3 days Butoconazole 2% cream 5 g (Butaconazole1-sustained release), single intravaginal application Clotrimazole 1% cream 5 g intravaginal 714 days Clotrimazole 100 mg vaginal tablet 7 days Clotrimazole 100 mg vaginal tablet 2 tablet for 3 days Miconazole 2% cream 5 g intravaginal 7 days Miconazole 100 mg vaginal suppositoria, 1 suppositoria for 7 days Miconazole 200 mg vaginal supositoria, one suppositoria for 3 days Miconazol 1,200 mg vaginal supositoria, one suppositoria for 1 day Nystatin 100.000-unit vaginal tablet, one tablet for 14 days Tioconazole 6.5% ointment 5 g intravaginal in a single application

Metronidazole and tinidazole is a class of nitroimidazoles. Topical therapy with drugs other than nitroimidazoles group can try, but the cure rate is low (<50%). For example clotrimazole pesari intravaginal 100mg for 6 days.(18) Fluor albus therapy caused by Candida albicans(Candidiasis Vulvovaginalis). WHO Guideline 2001(18)

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Terconazole 0.4% cream 5 g intravaginal for 7 days Terconazole 0.8% cream 5 g intravaginal for 3 days Terconazole 80 mg vaginal suppositoria, 1 suppositoria for 3 hari mg oral

week, clotrimazole (vaginal supp 500 mg once a week) or other topical therapy is intermittent. Topical therapy effective for reducing recurrent VVC.However, about 30-50% of women with recurrence afte rcompletion of treatment maintenance.(5, 6,
12)

Oral : Fluconazole 150 single dose

Some special conditions to consider : Gestation Vulvovaginal candidias is often occur during pregnancy. Only topical groups azole (for 7 days) is recommended for pregnant women. (5, 14, 18) Allergy, intolerance and side effects Topical agents are generally not a systemic effect, but local burning or irritation may occur. Oral agents occasionally cause nausea, abdominal pain and headaches. Azole group of oral therapy is rarely associated with abnormal liver enzyme elevations. Clinically important interactions with other drugs may occur in astemizole class drugs, calcium antagonists, cisapride, Coumadin, cyclosporine A, oral hypoglycemic drugs, phenytoin, protease inhibitors, tacrolimus, terfenadine, theophylline, trimetrexate, and rifampin. (5) Vulvovaginal candidiasis Nonalbicans
(19)

Patients are advised to control if the symptoms persist or recur with in two months after the initial symptoms. Clinical signs and symptoms will disappear within 48-72 hours after therapy, and mycological cure in 4-7 days after therapy.(5)VVC is not transmitted through sexual contact, so it is not recommended therapy of sexual partners, unless the woman is having recurrent infections. A small percentage of male sexual partners of patients suffering from balanitis characterized by erythematous areas on the glans penis due to pruritus or irritation.Therapy given to relieve symptoms is a topical antifungal. (5) Recurrent VVC is said when symptoms repeated four times or more a year. The cause of recurrence is still unclear and most of th ewomen who experienced it have no predisposing factors or other factors underlying. Vaginal culture examination should be performed to confirm the clinical diagnosis and identification of unusual species such as species,especially C.nonalbicans glabrata. Where these species are founding10-20% of patients recurrent VVC.(6, 14) The recommended therapy for recurrent VVC are topical and oral therapy azole short term as long as 7-14 days topical/oral dose of fluconazole100 mg, 150 mg or 200mg every three days to three doses to get the mycological remission before starting maintenance therapy. The first choice is oral fluconazole(100mg, 150mg, 200mg) every week for six months. If not available to be replaced with clotrimazole 200 mg twice a

Most commonly caused by C. labrata, hich is 10-100 times less susceptible to azoles than C. albicans. First Therapy : Boric acid 600 mg intravaginal capsuleoncea day during 14 days (Efficacy 64-81%) Flusitocine crim 5 g intravaginalonce a day during 14 days(Efficacy 90%) Amphotericine B 50 mg intravaginal suppositoriaonce a day during 14 days (Efficacy 80%)

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Flusitocine 1gr + Ampothericine B

100 grcombination in lubricant gel intravaginal once a day during 14 days(Efficacy 100%) If recurrent symptoms: Boric acid 600mg intravaginal capsuleoncea day during 14 days followed administration boric acid for several weeks Nistatin 100.000 unit vaginal supositoriaonce a day during 36 months. Immunocompromise patients Patients with uncontrolled diabetes mellitus or takingc orticosteroids do not respond well to short-term therapy, so that needs to be given conventional anti-fungal longer(7-14 days). (5, 19) Fluor albus treatment caused by Gardnerella vaginalis and vaginal anaerobes. Gardner after25 years shows that only antimicrobial that has activity against anaerobic bacteria are effective in the treatment of bacterialvaginosis. (15) Indication of therapy on bacterial vaginosis are :(5, 18) 1. All women are asymptomatic, pregnant or not. 2. Pregnant women who are asymptomatic with a highrisk of premature deliver. 3. Women who are asymptomatic before a surgical procedure or curettage.

Alternative regimen : Metronidazole 2gr oral single dose Clindamycin 2 x 300mg oral 7 days Clindamycin ovula 100mg intravaginal, nightday 3 days The principle of management of bacterial vaginosis(5, 13, 15, 18) Clinical trials have shown that intravaginal metronidazole gel 0.75% once daily compared with twice daily showed similar cure rates 1 month after therapy. Bacterial vaginosis with metronidazole therapy 2 gr single dose has the lowest effectiveness for BV and so far no longer recommended as well as for alternative therapies. FDA recommends metronidazole 750mg once daily for 7 days and a single dose of clindamycin intravaginal cream. Clindamycine is an antimicrobial derivative lincomisine, which works to inhibit the synthesis of proteins with bacteriostatic effect. Clindamycine and oilbased cream may weaken condoms and diaphragms. There was no difference in cure rates between clindamycin cream intravaginal with clindamycin ovules. Several studies evaluating the clinical and microbiological effectiveness of the use of Lactobacillus intravaginal to restore normal vaginal flora and BV treatment. There are no data supporting the use douching as a therapy to relieve symptoms.(5) Control is not recommended when no complaints. For recurrent BV metronidazole 500 mg canbe given orally for 10-14 days or metronidazole gel 0.75% one applicator 5 gr once a day metronidazole intravaginal for 10 days followed gel twice a week for 4-6 months.Therapy on sexual partners is recommended and not to prevent recurrence.(5,19)

Recommended regimen : Metronidazole 2 x 500 mg oral 7 days Metronidazole gel 0,75% 1 application 5g intravaginal at nightday 5 days Clindamycin krim 2% 1 application 5g intravaginal nightday 7 days

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Some special conditions to consider: Gestation Therapy aims to eliminate BV symptoms and signs of infection, reduce the risk of infectious complications in pregnancy such as preterm labor, premature rupture of membranes, amniotic infection, postpartum endometritis. The recommended therapy is oral metronidazole for 7 days 2 x 500 mg or 3 x 250 mg orally for 7 days or 2 x 300mg oral clindamycin for 7 days. Provision of metronidazole in the first trimester is not recommended. (5, 18, 20) Therapy of BV should be initiated early in the second trimester of pregnancy and should be completed before the age of 16 weeks of pregnancy. (20) Allergy or Intolerance Clindamycin intravaginal cream is preferred in cases of allergy or tolerance to metronidazole. Intravaginal metronidazole gel canbe considered for patients who do not tolerate systemic metronidazole, but patients allergic to oral metronidazole should not be administered intravaginal metronidazole. (5) Fluor albus treatment causedby Neisseria gonorrhoeae : Recommended therapy : Ciprofloxacin 500 mg oral single dose Azitromycin 2 gr oral single dose Ceftriaxone 125 mg intramuscular single dose Cefixime 400 mg oral single dose Spectinomycin 2 gr intramuscular single dose Alternative theraphy : Kanamycin 2 gr intramuscular single dose Trimethoprime 80 mg / sulfametoxazole 400 mg 10

tablet oral single dose for 3 days Many health centers also provide therapy advocated for Neisseria gonorrhoeae to sexual partners. In this case it is recommended to provide treatment to all sexual partners within 60 days before the diagnosis of gonorrhea. This kind of therapy even in patients with asymptomatic gonorrhea proven to give better results.(9)Because all treatment regimens recommended for gonorrhea have a cure rate of almost 100%, then the culture examination test for recovery criteria are no longer needed. But the test of cure still be necessary if patient adherence to therapy is unknown. (9) Fluor albus treatment caused by Chlamydia trachomatis WHO Guideline : Recommended therapy : Doxycycline 2 x 100mg oral 7 days Azithromycine 1gr oral single dose Alternative Regimen : Amoxycillin 3 x 500mg 7 days Erithromycin 4 x 500mg oral 7 days Ofloxacine 2 x 300mg oral 7 days Tetracycline 4 x 500mg oral 7 days Sexual partners should be examined to assess the presence or absence of urethritis, because it is often asymptomatic. Failures in sexual partner treatment can cause recurrence. Compliance therapy in running for 7 days is veryimportant. Chlamydia trachomatisis resistant to treatment regimens has not been found until now.(8, 13, 18) The drugs recommended for pregnant women is erythromycin 4 x 500 mg orally for 7 days, or 3 x 500 mg orally amoxycillin for 7days. Tetracycline, doxycycline and other groups and

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ofloxacine are contraindicated in pregnant women. Safety and efficacy of azithromycin in pregnant and lactating women is unknown. Erythromycin estolat contraindicated during pregnancy because of hepatotoxic, so only erythromycin or erythromycin etil sucsinat sole that can be used. (5, 18) Fluor albus treatment caused by a foreign object is to remove foreign objects. In addition, appropriate antibiotics canbe given. (10)

8.

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