Case 11

Villegas, Jose Bernabe Vinluan, Joseph David Wong, Deo Adiel Yague, Glenn Yang , Caprice

GYNECOLOGY Dr. August 22, 2007 Section 3 – D

___________________________________________________ Case # 11 A 22-year old single nulligravid factory worker in Taiwan consulted because of vulvar pruritus for 4 days. On PE, there were multiple warty growths, 0.7 – 1.5 cm diameter, on the fourchet and medial aspect of the labia majora and minora. On speculum examination, the vaginal mucosa was hyperemic. The cervix was smooth with yellowish green foul discharge. IE: Cervix – firm, long, closed; Uterus – normal in size; Adnexae - (-)mass/tenderness. ___________________________________________________ 1. What additional information (on the genital warts) should be inquired about? a. Character of the lesion: How did the patient notice the warty growths? When did they start to appear? At their onset, did they have the same appearance as in the present or did they progressively change in shape, texture, size, color or odor, and increase in number? Were there any discharges from the lesions? b. Occupational History: This includes inquiry about her sexual partner’s occupation. Certain occupations such as sexual workers increase the risk of acquiring STDs. Does her partner’s occupation involve engaging in sexual intercourse with customers? c. Medical History: Medical conditions that suppress the immune system, such as DM and HIV infection, increase the risk of acquiring any infection, including STDs. People with normal immune systems may be able to ward off infections better than immunosuppressed people. Poor nutrition and hygiene may also be a source of the infection. d. Sexual History: Asking, without judgment, about specific sexual practices enables physicians to identify potential health risks and needed screening tests. The Centers for Disease Control and Prevention recommends asking about the "five Ps": partners, practices, prevention of sexually transmitted diseases (STDs), past history of STDs, and prevention of pregnancy. Thus, in eliciting

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information, possible questions such as the following would be of much help. Are you having or have you ever had sex with men or women? How many partners have you had in the past six months? past five years? Does your partner have sex with someone other than yourself? What kind of sexual contact do you have? Oral, including mouth on vagina, anus, or penis? Vaginal penetration, including with hands, latex sex toy, or penis? Anal penetration, including with hands, latex sex toy, or penis? Have you had sexual contact with someone who uses injection drugs or a man who has sex with other men? Do you use barrier protection like condoms or gloves during sexual contact? What kind? Has she had any previous history of warts or STD? Has she had any other symptoms such as vaginal ulcers, excoriations, discharge, dryness, itchiness, abnormal odor emanating from her genitalia? Has she experienced any pain on urination or during sexual intercourse? Does her partner also have or had genital warts or some other form of STD?

What additional information (on the vaginal discharge) should be inquired about? A patient who complains of vaginal discharge, itching, frequent urination and/or irritation should be evaluated for vaginitis. The first step is to obtain a directed history. The patient should be asked about specific symptoms and their duration, any previous diagnosis and previous treatment and its effects. A general medical review, dermatologic review, social history and contraceptive history can also be helpful. It is also important to inquire about abdominal or pelvic pain, fever, recurrent or resistant infections, urinary symptoms, menstrual history, pregnancy and sexual practices. The nature of the discharge (i.e., amount, consistency, color, odor, accompanying pruritus) may also provide important clues. Dysuria is a common

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symptom of vaginitis. It is usually external and is defined as pain and burning when urine touches the vulva. In contrast, internal dysuria, defined as pain inside the urethra, is usually a sign of cystitis. A physical examination can help to identify the anatomic site of involvement (vulva, vagina or cervix). Inspection of the external genitalia for inflammation, lesions, masses, atrophic tissue and enlarged lymph nodes is important. The physician should also assess the patient for uterine or tubo-ovarian tenderness and perform a speculum examination to detect erythema, edema or lesions. The pooled vaginal discharge should be assessed for color, consistency, volume and adherence to the vaginal walls. Because the diagnostic tests and treatments for cervicitis are different from those for vaginitis, it is important to differentiate these conditions. Several clues can help to rule out cervical infection as the cause of a vaginal discharge. Almost 90 percent of symptomatic or asymptomatic women with chlamydial cervicitis meet at least two of the following criteria: (1) younger than 24 years, (2) sexual intercourse with a new partner in the previous two months, (3) presence of mucopurulent cervicitis, (4) cervical bleeding induced by swabbing the endocervical mucosa and (5) no form of contraception. If cervicitis is suspected, cultures for Chlamydia species and Neisseria gonorrhoeae should be obtained. If the findings of the history and/or physical examination suggest that the patient has vaginitis, a sample of the vaginal discharge should be obtained for gross and microscopic examination. Standard office examinations include a wet-mount preparation using saline, a slide prepared with 10 percent potassium hydroxide (KOH), a "whiff" test to detect amines and a litmus test of the pH level of vaginal fluid.

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Diagnosis of Vaginitis

Evaluation of patients with suspected vaginitis. (KOH = potassium hydroxide) 2. What is the probable diagnosis? Our patient presented with vulvar pruritus for 4 days and on physical examination, there were multiple warty growths, 0.7 – 1.5cm in diameter, on the fourchet and medial aspect of the labia majora and minora. These presenting signs are indicative of Genital Warts.

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On speculum exam, the vaginal mucosa of our patient was hyperemic. The cervix was smooth with yellowish green foul discharge which is suggestive of Trichomonas Vaginitis. External genital warts area a manifestation of human papillomavirus (HPV) infection. The non-oncogenic HPV types 6 and 11 are usually responsible for external genital warts. The warts tend to occur in areas most directly affected by coitus, namely the posterior fourchet and lateral areas on the vulva. Less frequently, warts can be found throughout the vulva, in the vagina, and on the cervix. They are highly contagious. More than 75% of sexual partners develop this manifestation of HPV infection when exposed. Trichomonas vaginitis is caused by the sexually transmitted, flagellated parasite, Trichomonas vaginalis. Transmission rate is high. The parasite, which exists only in trophozoite form, is an anaerobe that has the ability to generate hydrogen to combine with oxygen to create an anaerobe environment. It often accompanies Bacterial Vaginosis, which can be diagnosed in as many a 60% of patients with thichomonas vaginitis. 3. Give differential diagnoses. On physical exam, the patient had multiple warty growths and yellowish green foul discharge was noted. The differential diagnosis of warts are the following: A.

B.

C.

D. E.

Molluscum contagiosum: a benign viral disease of the skin that is caused by a member of the poxvirus group, molluscum contagiosum virus (MCV). The virus is one of the largest that causes human disease, measuring 240320 nm in diameter. The lesions have a waxy appearance and a central umbilication. They may appear migratory, as individual lesions usually spontaneously resolve over weeks, while new lesions appear elsewhere. Bateman first described the disease in 1817. The term molluscum was used to describe the pedunculated appearance, and the term contagiosum was used to connote that the disease is transmissible. Bowenoid papulosis consists of rough papular eruptions and is considered a carcinoma in situ. Eruptions can be red, brown, or flesh colored and may regress or become invasive. Seborrheic keratoses previously were considered a benign skin manifestation. These consist of rough plaques and have an infectious and an oncogenic potential. Buschke-Lowenstein tumor (giant condyloma) is a fungating, locally invasive, low-grade cancer attributed to HPV. Condylomata lata: Typical early lesions are usually less than 20, round, discrete, nonpruritic, and symmetric macules distributed on the trunk and

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proximal extremities. Red papular lesions also may appear on the palms, soles, face, and scalp and may become necrotic. Patchy and nonpatchy alopecia may occur. In intertriginous areas, papules may coalesce to form highly infectious lesions called condylomata lata. Lesions usually progress from red, painful, and vesicular to "gun metal grey" as the rash resolves. Mucous patches are superficial mucosal erosions, usually painless, that may develop on the tongue, oral mucosa, lips, vulva, vagina, and penis. Vaginitis is defined as the spectrum of conditions that cause vulvovaginal symptoms such as itching, burning, irritation, and abnormal discharge. The most common causes of vaginitis in symptomatic women are bacterial vaginosis (BV) (22-50%), vulvovaginal candidiasis (17-39%), and trichomoniasis (4-35%); yet, 7-72% of women with vaginitis may remain undiagnosed. Accurate diagnosis may be elusive and must be distinguished from other infectious and noninfectious causes. A complex balance of microorganisms maintains the normal vaginal flora. Important organisms include lactobacilli, corynebacteria, and yeast. Hormones further influence this microenvironment. A state of decreased estrogen, as occurs in prepuberty and postmenopause and following oophorectomy, can result in an altered risk of infection. The normal postmenarchal and premenopausal vaginal pH is 3.8-4.2. At this pH, growth of pathogenic organisms usually is inhibited. Disturbance of the normal vaginal pH can alter the vaginal flora, leading to overgrowth of pathogens. Factors that alter vaginal environment include feminine hygiene products, contraceptives, vaginal medications, antibiotics, sexually transmitted diseases (STDs), sexual intercourse, and stress. •

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Bacterial vaginosis: characterized by thin, homogenous, malodorous white-togrey vaginal discharge and pruritus. Vaginal pain or vulvar irritation is uncommon. Bacterial vaginosis: BV discharges are frothy and white to grey. The discharge appears adherent to the vaginal mucosa. As many as 50% of women with BV are asymptomatic. For diagnosis of BV, 3 out of the following 4 criteria must be present: a. Homogenous, white, adherent discharge b. Vaginal pH higher than 4.5 c. Release of fishy odor from vaginal discharge with potassium hydroxide d. Clue cells on wet mount Vaginal candidiasis: Pruritus is the most common symptom of vaginal candidiasis. This is accompanied by thick, odorless, white vaginal discharge (with an appearance similar to cottage cheese) that can be minimal. Usually, associated vulvar candidiasis is present, commonly with vulvar burning, dyspareunia, and vulvar dysuria (burning sensation when urine comes into contact with vulva skin). Erythema and swelling of the labia and vulva with satellite lesions (discrete pustulopapular lesions). Vaginal erythema with

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adherent thick, cottage cheese–like vaginal discharge (the cervix usually appears normal) T vaginalis infection: Many patients (20-50%) are asymptomatic. Symptoms include profuse vaginal discharge that can be white, gray, yellow, or green. The yellow and green colors are due to the presence of WBCs. Dysuria (20%), pruritus (25%), and postcoital bleeding due to cervicitis are other possible symptoms. The vulva may appear erythematous and edematous, with excoriation. Look for homogenous vaginal discharge that can be white, gray, yellow, or green. Small punctate cervical and vaginal hemorrhages with ulcerations may be observed. "Strawberry cervix" or "colpitis macularis" is very specific for Trichomonas infection, and 2-5% of patients will have this finding on examination. Diagnosis of Trichomonas infection based on clinical signs and symptoms is unreliable, so laboratory confirmation is mandatory. 4. What diagnostic procedures are necessary? Appearance of vaginal secretions is assessed, pH of the secretions is measured, and microscopy with isotonic sodium chloride solution and 10% potassium hydroxide (KOH) is performed along with a whiff test. Diagnosis should be inferred by placing a small cotton swab into the endocervical canal and the cervical mucus is extracted. The cotton swab is inspected against a white or black background to detect the green or yellow color of the mucopus. In addition, touch the ectropion with a cotton swab or spatula to see if it is friable or easily induced to bleed. Ectocervical secretions on the other hand should be obtained using a large swab. Since the cause of cervical epithelium depends on the epithelium affected, the former procedure will be presumptive of the organism causing inflammation (mostly gram-positive cocci, e.g. streptococci in ectocervix; trichomonas, candida, and herpes in endocervix). Both secretions are placed on a slide and Gram-stained. The observation of more than 30 leukocytes per oil immersion field is highly suggestive of chlamydia and gonorrhea. The acetic acid test is done by soaking acetic acid into suspicious lesion. This can enhance the degree of suspicion in lesions without classic features. The method involves applying a 3-5% acetic acid–moistened gauze pad for 5-10 minutes on suspected lesions of the cervix, labia, or perianal area. Inconspicuous, flat, genital lesions that might be difficult to assess become visible. Dysplastic and neoplastic tissues turn white (acetowhite). False-positive results are common and can result from anything that causes parakeratosis (eg, candidiasis, psoriasis, lichen planus, healing epithelium, sebaceous glands). This technique can be combined with the use of colposcopy to examine cervical lesions. The acetic acid test is reserved only for suspicious lesions and should not be used for routine screening. Histopathology can elucidate diagnosis in most cases. Verrucae consist of acanthotic epidermis with papillomatosis, hyperkeratosis, and parakeratosis. Elongated rete ridges may point to the center of the wart and dermal capillary vessels may be thrombosed. Koilocytes are indicative of HPV infection. These are

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large keratinocytes with an eccentric, pyknotic nucleus surrounded by a perinuclear halo. Immunohistochemical staining with the peroxidase-antiperoxidase technique stains cells infected by viral particles. Certain screening tests are available with a relatively high sensitivity and specificity; they include the following: ViraPap, ThinPrep Pap and Hybrid capture II. 5. Give treatment options. The primary goal of treatment for genital warts is their removal. For most patients, treatment could bring about wart-free periods. However, if the warts are left untreated, they could spontaneously remit, remain the same, or even multiply in number and increase in size. The treatment of genital warts could possibly diminish but not entirely remove HPV, the main cause. Whether the reduction in HPV viral DNA, resulting from treatment, impacts future transmission remains unclear. No evidence indicates that the presence of genital warts or their treatment is associated with the development of cervical cancer. Treatment of genital warts should be chosen on the basis of the preference of the patient, costs, and the experience of the physician. No definitive data suggests that one is superior to any other and no single treatment is ideal for all patients or all warts. The use of locally developed and monitored treatment algorithms has been associated with improved clinical outcomes and should be encouraged. Because of uncertainty about effects of treatment on future transmission of HPV and the possibility of spontaneous resolution, an acceptable alternative for some persons is to forego treatment and wait for spontaneous resolution. On the other hand, if the patient showed no substantial improvement, a change of therapy is suggested. The majority of genital warts respond within 3 months of therapy. The response to treatment and its side effects should be evaluated throughout the course of therapy. Recommended Regimens for External Genital Warts Patient-Applied: Podofilox 0.5% solution or gel. An antimitotic drug that destroys warts, is relatively inexpensive, easy to use, safe, and self-applied by patients. They should apply podofilox solution with a cotton swab, or podofilox gel with a finger, to visible genital warts twice a day for 3 days, followed by 4 days of no therapy. This cycle may be repeated, as necessary, for up to four cycles. The total wart area treated should not exceed 10 cm2, and the total volume of podofilox should be limited to 0.5 mL per day. The majority of patients experience mild-to-moderate pain or local irritation after treatment. Imiquimod 5% cream. Is a topically active immune enhancer that stimulates production of interferon and other cytokines. Patients should apply imiquimod cream once daily at bedtime, three times a week for up to 16 weeks. The treatment area should be washed with soap and water 6–10 hours after the application. Local inflammatory reactions are common with the use of imiquimod; these reactions include redness and irritation and are usually mild to moderate.

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Conservatively, follow-up is not required for patients using self-administered therapy. However, it might be useful several weeks into therapy to determine the appropriateness of medication use and the response to treatment. Physician-Administered: Cryotherapy with liquid nitrogen or cryoprobe causes thermal-induced cytolysis. Physicians must be trained on its proper use because over- and undertreatment might result in complications or low efficacy. Pain after application of the liquid nitrogen, followed by necrosis and sometimes blistering, is common. Local anesthesia (topical or injected) might facilitate therapy if warts are present in many areas or if the area of warts is large. Repeat applications every 1–2 weeks. Podophyllin resin 10%–25% in a compound tincture of benzoin. A small amount should be applied to each wart and allowed to air dry. The treatment can be repeated weekly, if necessary. To avoid the possibility of complications associated with systemic absorption and toxicity, two important guidelines should be followed: 1) application should be limited to <0.5 mL of podo-phyllin or an area of <10 cm2 of warts per session, and 2) no open lesions or wounds should exist in the area to which treatment is administered. Some specialists suggest that the preparation should be thoroughly washed off 1–4 hours after application to reduce local irritation. Trichloroacetic acid (TCA) or Bichloroacetic acid (BCA) 80%–90% are caustic agents that destroy warts by chemical coagulation of proteins. Although these preparations are widely used, they have not been investigated thoroughly. TCA solutions have a low viscosity comparable with that of water and can spread rapidly if applied excessively; therefore, they can damage adjacent tissues. Both TCA and BCA should be applied sparingly and allowed to dry before the patient sits or stands. A small amount is put only to the warts and allowed to dry, at which time a white “frosting” develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate (i.e., baking soda), or liquid soap preparations to remove unreacted acid. Surgical removal either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery. Surgical therapy has the advantage of usually eliminating warts at a single visit. However, such therapy requires substantial clinical training, additional equipment, and a longer office visit. After local anesthesia is applied, the visible genital warts can be physically destroyed by electrocautery, in which case no additional hemostasis is required. Care must be taken to control the depth of electrocautery to prevent scarring. Alternatively, the warts can be removed either by tangential excision with a pair of fine scissors or a scalpel or by curettage. Because the majority of warts are exophytic, this procedure can be accomplished with a resulting wound that only extends into the upper dermis. Hemostasis can be achieved with an electrocautery unit or a chemical styptic. Surgical therapy is most beneficial for patients who have a large number or area of genital warts. Carbon dioxide laser and surgery might be useful in the management of extensive warts or

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intraurethral warts, particularly for those patients who have not responded to other treatments. Alternative Regimens Interferons, both natural or recombinant, have been used for the treatment of genital warts. They have been administered systemically (i.e., subcutaneously at a distant site or IM) and intralesionally (i.e., injected into the warts). Systemic interferon is not effective. The efficacy and recurrence rates of intralesional interferon are comparable to other treatment modalities. Administration of intralesional interferon is associated with stinging, burning, and pain at the injection site. Interferon is probably effective because of its antiviral and/or immunostimulating effects. Interferon therapy is not recommended as a primary modality because of inconvenient routes of administration, frequent office visits, and the association between its use and a high frequency of systemic adverse effects. Because of the shortcomings associated with all available treatments, some clinics employ combination therapy. No data support the use of more than one therapy at a time to improve efficacy of treatment, and some specialists believe that combining modalities might increase complications. For the concomitant Trichomoniasis: Recommended Regimens Metronidazole 2 g orally in a single dose or Tinidazole 2 g orally in a single dose Alternative Regimen Metronidazole 500 mg orally twice a day for 7 days

References: Harrison’s Principles of Internal Medicine 16th edition Berek et al., eds. Novak’s Gynecology. 14th ed. USA: Lippincott Williams & Wilkins. 2007. http://www.aafp.org/afp/20060715/279.html http://www.aafp.org/afp/20000901/1095.html http://www.cdc.gov/std/treatment/2006/genital-warts.htm http://www.cdc.gov/std/treatment/2006/vaginal-discharge.htm#vagdis3

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