STD Grand Rounds: Genital Dermatology

Question and Answer Summary

Rounds: Genital Dermatology" is posted below. This Q and A summary is also available on

CDC's faxback system -(888) 232-3299; document # 130035

The following responses provide general information. They should not be interpreted as diagnostic or treatment recommendations for specific cases.

Question 1: What can cause hairline fissures near the hood of the clitoris or introitus? What can be used to treat these areas?
Answer: In the presence of fissures it would be important to rule out trauma, HSV and candida with this clinical presentation. Treatment would obviously be dependent upon the cause.

Question 2: Is an RPR needed for all cases of pityriasis rosea? I was taught that if a patient has negative adenopathy in axilla and groin and no lesions on the palms and soles and no significant risk factors then an RPR/VDRL is not needed.
Answer: Although syphilis cases have reached an all time low in the United States, pityriasis rosea remains indistinguishable from secondary syphilis. It is important to remember, most, but not all secondary syphilis cases will present with generalized adenopathy or a macular papular eruption on the palms and/or soles. Other signs of secondary syphilis include: mucous patches, condyloma lata, constitutional symptoms and alopecia. An RPR is an inexpensive, easy, and readily available means of excluding early syphilis in any patient at risk.

Question 3: I recently saw a young woman in my clinic who had a 3-year history of recurring genital lesions, which she describes as usually singular, non-painful but itchy lesions, which occur around the time of her menses. She denies history of oral ulcers. She has had two negative HSV cultures. On examination I found a singular moist ulceration and felt certain it was HSV, however, the culture result was once again negative. I plan to do an HSV antibody test next. Given this history, if the antibody test is negative, do I assume that this is an aphthous ulcer or are there other diagnostic tests? Can this condition have the typical HSV recurrence pattern? How concerned should I be about a Behcet's disease diagnosis in someone with aphthous ulcers?
Answer: This patient certainly has a history consistent with herpetic outbreaks. It would be important to know when the herpes cultures were performed and how old the lesions were because the sensitivity of an HSV culture dramatically decreases with the age of the lesion. An antibody test would be very helpful if the result was negative. If it is positive, it does not add much definitive information as to the cause of the ulcers. With a recurring genital ulcer in the same area it would also be important to ask what medications and/or foods she is consuming at the time of these occurrences. A fixed drug eruption may be one diagnosis to consider with acetaminophen, aspirin, salicylates, tetracyclines, sulfonamides, oral contraceptives, metronidazole, NSAIDs, penicillins, phenolphthalein and phenothiazides being implicated most often. ---- Another important question would be to ask the patient what, if any, cleaning methods of the genitals this patient employs? For example, does she utilize any soaps or topically applied products and what

types are used? Consideration should be given to a biopsy if all results are negative. ---- Behcet's disease is characterized by oral and genital ulcers (aphthous major), and ocular inflammation. A history of uveitis, skin rashes, arthritis, thrombophlebitis, gastrointestinal symptoms, psychiatric problems and neurological symptoms would also be important information to elicit. One distinguishing characteristic with this patient is the absence of oral ulcers, which occur essentially in all patients with Behcet=s disease. This patient may indeed have a recurrent aphthous ulcer in the absence of Behcet=s disease. A Rheumatology consult may also be helpful.

Question 4: Are skin tags on the penis shaft a common finding? How can they be differentiated from HPV and/or Molluscum Contagiosum?
Answer: It is very difficult to definitively differentiate HPV from a skin tag without a biopsy. A biopsy is indicated if the diagnosis is uncertain, the lesions do not respond to standard therapy, the patient is immunocompromised, or warts are pigmented, indurated, fixed and ulcerated. In the presence of a skin tag and/or HPV you would not find the molluscum body or core, after opening the lesion via skin curette. Direct microscopic examination of this central semisolid core reveals these entities easily via light microscopy.

Question 5: What would the differential be for a blue, bruised like area found between the vagina and anus?
Answer: Trauma and pigmented nevi would be high in the differential, however, a more detailed history and description of the lesion is needed. Such as, the length of time the lesion has been present. Is the lesion, raised, flat, indurated, or scaly? Has there been any recent trauma? Is it tender, etc.

Question 6: Other than antibiotics, what are the other (long-term) treatments for a patient suffering from furunculosis of the genitalia?
Answer: Antibiotics, topical and oral, are certainly the mainstay of treatment for recurrent folliculitis/furuncles in the groin. In addition, keratolylitics such as salicylic acid or benzoyl peroxide may be helpful. But, you must be cautious concerning irritation in the groin. In severe or recalcitrant disease, systemic retinoids can be used in medically appropriate patients. Obese patients may gain some benefit from weight reduction.

Question 7: Does hypopigmentation have to be biopsied? Is there any treatment for vitiligo or post-HSV hypopigmentation? Are there symptoms besides visual discoloration? If you didn=t biopsy what could you be missing that would be serious?
Answer: Post-inflammatory hypopigmentation and vitiligo account for the majority of cases of genital hypopigmentation. The history (e.g., recent outbreak or treatment procedure in the area) as well as physical examination findings often establish the diagnosis without biopsy. In the absence of epidermal surface changes (e.g., scaling, hyperplasia, erythema) or dermal alterations (e.g., induration, atrophy) little else enters the differential. A variant of cutaneous T-cell lymphoma can present as hypopigmented macules/patches and represents an example of a serious condition that would require a biopsy for the diagnosis. It would, however, be unusual for its sole presentation to be in the genitals. Any time the diagnosis is uncertain, a biopsy is the correct thing to do. Post-inflammatory hypopigmentation usually improves with time. Low potency topical corticosteroids (e.g., hydrocortisone or desonide) have been beneficial in some patients with vitiligo (and acute post-inflammatory hypopigmentation). Caution should be stressed as striae are a possible adverse effect of corticosteroid application in intertriginous areas.

Question 8: What management have you found effective for the treatment of pubic hair folliculitis?
Answer: Many of the points discussed for furuncles also apply for patients with pubic hair folliculitis. More often these are acute outbreaks and oral antibiotics are the treatment of choice. In addition, intralesional corticosteroids (usually triamcinolone acetonide 2-5 mg/cc) can be helpful to speed up the resolution of individual lesions. Patients with more chronic or recurrent pubic hair folliculitis should use an antibacterial soap when showering, for prophylaxis, as well as chronically apply a topical antibiotic.

Question 9: Other than testosterone cream, what else can be used in the treatment of lichen sclerosis?
Answer: High-potency steroid preparations can be used to treat lichen sclerosis. In particular, Clobetasol Propionate 0.05 percent is the treatment of choice. This is applied to the affected skin once daily, usually at night, until there is an improvement, after which the frequency can be gradually reduced. A 30 gram tube should last three months, but considerably less is required once the disease is under control. Ointments are more effective than creams. There seems to be less contact dermatitis with the ointment formulation. --- Despite the high incidence of lichen sclerosis at the time of menopause, and the apparent improvement in pregnancy, both systemic and topical exogenous estrogens are ineffective in the treatment of lichen sclerosis. A soap substitute, such as an aqueous cream, is a useful adjunct treatment. ---- The fluorinated high-potency creams can increase vulvar atrophy over time. Clearly, there will be some systemic absorption from steroid creams and, therefore, I would recommend that they be used intermittently as opposed to chronically. ----- Finally, a word of caution, even with a biopsy coming back showing lichen sclerosis, if you see a lesion that is raised and discrete, it is very important to excise it. Commonly, lichen sclerosis can be associated with underlying invasive cancer. Sometimes this is missed on a biopsy which is only getting the edge of the lesion. While lichen sclerosis has a classic look of resorption of the vulvar appendages, a cancer will appear as an exophytic mass.

Question 10: I have been noticing an erythematous or pale rash of the vulva/perineum in many women, who often report a history of using feminine pads or panty liners. Contact dermatitis is high on the differential. Is a mild corticosteroid appropriate if symptomatic, or just avoidance of synthetic material?
Answer: There is an extensive list of preservatives in these products including formaldehyde. In the absence of severe symptoms it would be reasonable to discontinue the offending agent and monitor the recovery. There are many health food stores and pharmacies that are now offering 100% cotton and preservative-free products as alternatives to this increasingly common problem.

Question 11: Is there a collection procedure available that could be shared with health departments to assure optimal samples are collected for Tzanck smears?
Answer: Your state or local Health Department could provide you with a copy of their protocol. I have included our Standard Operating Procedure for acquisition of Tzanck smear utilized by the STD Center for Excellence at Montefiore Medical Center, (I am sure they are very similar).

PURPOSE:

Tzanck smears stained by Volu-sol Giemsa (Dif-Quick) or Wright stain demonstrating multinucleated giant cells due to Herpes virus.

REAGENTS AND MATERIALS:

"Stat Stain" -- Distilled/De-ionized Water -- Sodium Hypochlorite Solution -- Glass slides --Scalpel blades -- Gauze pads

SPECIMEN PREPARATION AND COLLECTION:

(1) Label the slides with the patient's initials (2) Select the lesion site (3) Using gloves, cleanse the site with gauze or swab soaked in water (4) Incise the top of a vesicle with a sterile scalpel and lightly apply the specimen to the middle of a glass slide (5) Lightly scrape the base of the vesicle and apply the lesion material to the middle of another glass slide. Smear an area about the size of a U.S. dime, i.e., just enough to be covered by a No. 1 (22 X 22mm) cover slip

(6) Prepare two or more smears if necessary.

SPECIAL CASES:

b) Erosive Lesions: Lightly scrape and prepare smear

STAINING PROCEDURE:

(1) Wearing gloves, carefully add sodium hypochlorite solution (diluted 1:10) into the disinfectant vessel until it is one-fourth full (2) Place the labeled (smeared) slides on the disinfectant vessel (3) Air dry the slides for no less than five minutes (4) Using the dropper bottle add 2 or 3 drops of stat stain on the smear (or just enough to cover the smear) and let stand for exactly 20 seconds (5) DO NOT DRAIN (6) Add an equal number of drops of distilled or de-ionized water to the staining smears (i.e., dilute 1:1) and let stand for an additional 10 seconds (7) Pour off stain/water mixture into the disinfectant and (8) Quickly wash slides (over the disinfectant) by gently squirting distilled water (or de-ionized water) via wash "squeeze bottle"

(9) Wipe the underside of each slide with an isopropyl alcohol pad or tissue moistened with 70% isopropyl alcohol (10) DRAIN DRY over an absorbent surface (DO NOT BLOT).

Question 12: How often does a positive Tzanck smear turn out to be something other than HSV?
Answer: A positive Tzanck smear almost always indicates a diagnosis of herpes simplex virus. However, it is important to remember that other members of the herpes family can also result in a positive smear, including: herpes zoster and cytomegalovirus. The clinical manifestation should help with the diagnosis as will a culture for confirmation of HSV.

Question 13: Should follow-up cultures be done on negative Tzanck smear samples if available?
Answer: Tzanck smears have a sensitivity of only 50%, and that is highly dependent upon the age of the lesion, therefore, cultures would be very helpful in this clinical setting.

Question 14: Assuming that Tzanck smears are relatively insensitive and that your clinic has a positivity rate of 10-15%, what could you assume your true positivity rate to be?
Answer: It would be important to compare them to your herpes culture positivity rate.

Question 15: How common are ulcers (genital) with mono? (EBV)
Answer: Although Epstein-Barr virus is the causative organism in most cases of mononucleosis and is part of the herpes family of viruses, I could find no reference to ulcers in the genitalia as presenting symptoms of this illness.

Question 16: Dr. Gilbert mentioned seeing 5-6 patients who presented with lesions on male and female genitalia that contained M. tuberculosis. Knowing that the common route of transmission of TB is through the air (with manifestation of TB disease in the reproductive organs via the bloodstream), has the panel seen secondary spread of TB through sexual contact? Is it conceivable that the lesions could erupt and cause localized infection in the partner?
Answer: Primary infection of TB can result from direct inoculation of the skin. This results in a shallow ulcer with an irregular base and local lymph node enlargement. Hematogenous spread from a distant site of TB can also cause a cutaneous infection, known as lupus vulgoris. Patients with genital lesions of TB that were seen were quite ill and were not engaging in sexual activity but may well have acquired the infection from direct inoculation from partners= genital TB lesions.

Question 17: What is the cause of aphthous ulcers, oral or genital?
Answer: Although almost 50% of the population have developed aphthous ulcers at some point in their lifetime, the exact etiology remains an enigma. Some postulated theories include, immunologic, genetic, and psychological factors. No definitive method of transmission is currently known.

Question 18: What is the recommended treatment regimen for aphthous ulcers in patients who are not HIV infected? Would the same treatment be recommended for aphthous ulcers of the mouth and genital area?
Answer: Generally small lesions can be left untreated. If comfort is a concern, topical lidocaine can be applied several times per day. Topical and systemic steroids are the treatments most often employed. When ulcers in the mouth, especially in hard to reach areas, are present, (i.e: posterior pharynx, uvula), an inhaled, steroid-metered dose inhaler may be helpful. Instead of having the patient inhale the medication, ask them to perform a valsalva maneuver upon releasing the medication, to concentrate the spray on areas in the back of the throat. Other treatments with anti-inflammatory properties that have been used are: tetracyclines, dapsone, cholcicine, azathioprine and intralesional triamcinalone injections. In cases where a patient is immunocompromised and the lesions have not responded to conventional therapy, thalidomide has been utilized.

Question 19: Was the woman with Seborrheic Dermatitis of the vulva, HIV+?

Answer: This patient=s HIV status is unknown.

Question 20: I would like to know your technique/advice on obtaining samples from lesions for Darkfield study, such as in condyloma lata with its white velvety top, and other lesions which cause the lesion to bleed and render the specimen unsatisfactory.
Answer: The technique for obtaining samples for Darkfield interpretation requires a fresh preparation of a lesion in order to view the organism actively mobile. The test requires much skill and experience and is recommended only in those places where it is routinely performed. If the test is deemed unsatisfactory on a particular day, serial Darkfield on several days=succession may be useful. Below is the protocol we utilize for our Darkfield specimen acquisition:

NECESSARY EQUIPMENT AND SUPPLIES:

Microscope with Darkfield condenser -- Frosted end microscope slides -- Cover glass, size No. 1 (22 x 22 mm square) -- Microscope immersion oil -- Disposable bacteriological loop -- Disposable scalpel -- Capillary with rubber bulb (1 ml capacity) -- Saline (physiologic) -- Cotton-tipped applicator

COLLECTION OF SPECIMENS:

The objective in collecting a specimen for Darkfield examination is to obtain serous fluid that is rich in Treponema pallidum and as free as possible of red blood cells and tissue or other organisms, which may obscure the treponemes. ----- When collecting specimens follow all the biohazard precautions. Select the lesion for Darkfield examination and clean it with a gauze pad or swab moistened with physiological saline. Remove any scab or crust covering the lesions. Abrade the lesion with a dry gauze pad to provoke slight bleeding or use a scalpel. As oozing occurs, wipe away the red blood cells and await the appearance of clear serous exudate. Sometimes it is necessary to apply pressure at the base of the lesion by gently squeezing with the thumb and index finger to promote the appearance of serous fluid. ----- For direct examination, apply clear-cover glasses or slides to the oozing lesion or use the bacteriological loop to transfer the fluid from the lesion to glass slides. Flatten the cover glass evenly on the slide with the blunt end of the applicator stick to remove air bubbles. Prepare three slides to maximize the specificity. Use the capillary tube for the collection of the serum if Darkfield examination of the slide is delayed >15 minutes. ------ If darkfield examination is negative on a lesion and you suspect that local therapy is needed, the physician can collect fluid from the palpable lymph node using a 20-gauge needle syringe and prepare the slide as above.

EXAMINATION OF THE SPECIMEN FOR TREPONEMA PALLIDUM:

(1) Adjust the microscope with the Darkfield condenser and align it by focusing 4X, 10X, 40X and 100X by centering the round dark area (2) Place a drop of immersion oil on the top of the condenser or the bottom of the slide (3) Place slide on the stage and center specimen over the condenser with mechanical stage (4) Raise slowly the substage until there is an oil contact between the top of the condenser and the bottom of the slide (5) Bring specimen in focus by using 10X objective lens and search the entire specimen methodically by using high dry (40-45X) objective lens (6) Search all the slides for the spiral organisms having morphology and motility characteristic of Treponema pallidum before making a negative report (7) If a suspected organism is observed, center it in the field for subsequent examination with the oil immersion objective (8) Rotate the objective turret halfway so that a small drop of immersion oil can be placed on the cover glass and rotate again until the oil immersion objective is in place over the specimen and in contact with the oil on the cover glass (9) Examine the organism carefully for identification; focus with the fine adjustment knob only (10) If organisms are found that have the characteristic morphology and motility of T. pallidum, make a positive report.

CHARACTERISTICS OF T. PALLIDUM:

(a) Delicate spirilliform (corkscrew-shaped) organisms with an average of 8-14 regular, rigid, tightly wound, deep spirals (b) Usually 6-14 microns in length, averaging slightly larger than the diameter of a red blood cell (c) Very thin, approximately 0.25 - 0.30 microns (d) Spiral amplitude (distance from the top of one coil to the top of the next coil) of 1.1 micron (e) Spiral depths (distance from the top of one coil to the bottom of the same coil) of 0.5 - 1.0 micron (f) Slow rotation about the long axis (like a corkscrew) and forward and backward movement (g) Coiled appearance retained despite active motility.

INTERPRETATION OF DARKFIELD:

Presence of single treponemes with characteristic morphology and motility in Darkfield examinations for T. pallidums constitutes a positive diagnosis of syphilis in the Darkfield column of logbook to be reported as "positive.@ ------ If all three slides were negative for T. pallidums, report in the column of Darkfield as "negative.@ ----- Presence of any other spiral, specifically Borrelia spa. To be reported to clinicians, and the characteristics are as follows under the Darkfield: Variable number of loosely wound spiral (3 to 20) -- Variable length of 2-30

microns -- Thick and course appearance -- Spiral amplitude of 2 microns and above -- Extreme flexibility and frequent relaxation of coils during active motility -- Rapid movement across or on the field with a twisting motion.

REFERENCES:

U.S. Department of Health, Education and Welfare: Darkfield microscopy for the detection and identification of Treponema pallidum PHS publ. No. 990 Washington D.C., U.S. Government Printing Office, 1962.

Question 21: Please provide clarification and more information on genital warts that may be congenital? How should these be managed? Please address counseling and treatment implications.
Answer: Recurrent respiratory papillomatosis (RRP) is a condition in which papillomata (benign growths) can occur at sites in the respiratory tract from the nasal vestibule to the lung. It is often found in the triad of a first-born child delivered from a woman vaginally with condyloma. This is not a common occurrence. Risk seems to be greatest in the presence of clinical rather than sub-clinical disease at the time of delivery. At present there is no documented benefit of delivering a child via C-section in a mother with HPV lesions. Management of these cases is dependent upon the clinical manifestation of illness, which often begins, with a history of hoarseness and upper airway obstruction in varying degrees of severity. Laryngoscope is often needed. The disease may never recur once a lesion is removed, may recur at varying intervals, may distribute to previously non-diseased sites, may undergo malignant transformation, and rarely, may undergo spontaneous regression. If your question is asking if congenital HPV lesions can occur on the skin, anus, genitals of infants born to women with HPV the answer is yes, and treatment would be dependent upon the age and area of involvement.

Question 22: Please elaborate on fusospirochetal co-infection of HSV lesions (vulvar, anal), which was discussed, but I would like to hear it again, plus more. Answer: HSV infection of the oral cavity (herpetic gingivostomatitis) was observed in children who had severe overgrowth with Fusobacterium and Borrelia. This is reported in an article by Craig Tendler, M.D. and Edward J. Bottone, Ph.D., entitled "Fusospirochetal ulcerative gingivitis in children" in The Jl of Pediatrics, Sept 1987, pp., 400-403. We observed patients with genital and HSV infections which did not respond to antiviral therapy for HSV. The patients had co-infection with fusospirochetes seen on gram stain. Treatment with penicillin cleared these organisms and rapidly improved the HSV infection.