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Home , Adenomyosis, Desonide, Irritation

SECOND OF 2 PARTS ON OFFICE MANAGEMENT OF BENIGN VULVAR CONDITIONS Chronic vulvar irritation, itching, and . What is the diagnosis?

Five cases of dermatoses, vaginal abnormalities, and pain syndromes that may masquerade as

Libby Edwards, MD, and Beth E. Goldbaum, MD

hronic irritation, itching, and pain CASE 1 Introital burning and a fear are only rarely due to infection. of breast cancer C These symptoms are more likely to A 56-year-old woman visits your office for be caused by dermatoses, vaginal abnormali- management of recent-onset introital burn- ties, and pain syndromes that may be difficult ing during sexual activity. She reports that to diagnose. Careful evaluation should in- her commercial lubricant causes irritation. clude a wet mount and culture to eliminate Topical and oral antifungal therapies have not infection as a cause so that the correct diag- been beneficial. She has a strong family his- IN THIS nosis can be ascertained and treated. tory of breast cancer. ARTICLE In Part 2 of this two-part series, we focus On examination, she exhibits small, When a woman on five cases of vulvar dermatologic disrup- smooth labia minora and experiences pain is reluctant to use tions: when a cotton swab is pressed against the local • atrophic vestibule. The vagina is also smooth, with page 32 • irritant and allergic contact scant secretions. Microscopically, these • complex vulvar aphthosis secretions are almost acellular, with no • desquamative inflammatory increase in white blood cells and no clue A teenager • inverse . cells, yeast forms, or lactobacilli. The pH is with vulvar pain greater than 6.5, and most epithelial cells are and sores parabasal (FIGURE 1, page 32). page 34 You prescribe topical estradiol cream Dr. Edwards is Chief of for vaginal use three nights per week, but Dermatology at Carolinas Medical A case of inverse Center, Charlotte, North Carolina. when the patient returns 1 month later, her psoriasis condition is unchanged. She explains that page 36 she never used the cream after reading the package insert, which reports a risk of breast cancer. Dr. Goldbaum is Clinical Instructor of Obstetrics and Gynecology Diagnosis: Atrophic vagina (not atrophic vag- at Harvard Medical School, initis, as there is no increase in white blood Boston, Massachusetts. cells). ›› Read Part 1: Chronic Treatment: Re-estrogenization should relieve vulvar symptoms her symptoms. and dermatologic disruptions (May 2014), The authors report no financial relationships relevant to this article. at obgmanagement.com Several options for local estrogen replace- ment are available. Creams include estradiol

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FIGURE 1 Atrophic vagina When a woman is reluctant to use local estrogen We counsel women that small doses of vagi- nal estrogen used for limited periods of time are unlikely to influence their breast cancer risk and are the most effective treatment for symptoms of atrophy. Usually, this explana- tion is sufficient to reassure a woman that topical estrogen is safe. Otherwise, use of commercial personal lubricants (silicone- based lubricants are well tolerated) and moisturizers such as Replens and RePhresh can be comforting. The topical anesthetics lidocaine 2% jelly or lidocaine 5% ointment (which sometimes burns) can minimize pain with sexual activity for those requiring more than ­lubrication. Ospemifene (Osphena) is used by some clinicians in this situation, but this medica- This wet mount of an atrophic vagina shows many parabasal cells with no tion is labeled as a risk for all of the same lactobacilli and no increase in white blood cells. Figure courtesy of Libby Edwards, MD. contraindications as systemic estrogen, and it is much more expensive than topical es- trogen. Ospemifene is an estrogen agonist/ (Estrace) and conjugated equine estrogen antagonist. Although it is the only oral (Premarin), the latter of which is arguably medication indicated for the treatment of The risk of vaginal slightly more irritating. These are prescribed -related , the long- candidiasis is fairly at a starting dose of 1 g in the vagina three term effects on breast cancer risk are un- high during the first nights per week. After several weeks, they known. Also, it has an agonist effect on the 2 or 3 weeks of can be titrated to the lowest frequency that and, again, the long-term risk re-estrogenization controls symptoms. is unknown. The risk of vaginal candidiasis is fair- Fluconazole use is contraindicated ly high during the first 2 or 3 weeks of re- with ospemifene, as is the use of any estro- estrogenization, so patients should be gen products. warned of this possibility. Also consider prophylactic weekly fluconazole or an CASE 2 Recalcitrant itching, burning, azole suppository two or three times a week and redness for the first few weeks. Estradiol tablets A 25-year-old woman reports anogenital - (Vagifem) inserted in the vagina are effec- ing, burning, and redness, which have been tive, less messy, and more expensive, as is present for 3 months. She says she devel- the estradiol ring (­Estring), which is insert- oped a yeast infection after antibiotic therapy ed and changed quarterly. for a dental infection; the yeast infection was It is not unusual for a woman to avoid treated with terconazole. She reports an aller- use of topical estrogen out of fear, or to use gic reaction to the terconazole, with immedi- insufficient amounts only on the , or to ate severe burning, redness, and swelling. use it for only 1 or 2 weeks.1 The cream she was given to use Women should be scheduled for a re- twice daily also caused burning, so she dis- turn visit to ensure they have been using the continued it. Her symptoms improved when estrogen, their wet mount has normalized, she tried cool soaks and applied topical ben- and discomfort has cleared. zocaine gel as a local anesthetic. However,

32 OBG Management | June 2014 | Vol. 26 No. 6 obgmanagement.com FIGURE 2 exposed to an irritating substance in suf- ficient quantity or frequency. Irritant con- tact dermatitis is characterized mostly by sensations of rawness or burning and generally is caused by urine, feces, perspi- ration, friction, alcohols in topical creams, overwashing, and use of harsh soaps. • Allergic contact dermatitis—This form is characterized by itching, although second- ary pain and burning from scratching and blistering can occur as well. Common aller- gens in the genital area include benzocaine, diphenhydramine (Benadryl), neomycin in triple antibiotic ointment (Neosporin), and latex. Allergic contact dermatitis occurs after 1 or 2 weeks of initial exposure or 1 or 2 days after re-exposure. The diagnosis of an irritant or allergic contact dermatitis can be based on a history of incontinence, application of high-risk sub- stances, or inappropriate washing. Manage- Redness and erosions are typical of an acute contact ment generally involves ­discontinuation of dermatitis, and eroded papules are especially all panty liners and topical agents except for common in contact dermatitis of benzocaine. Figure courtesy of Libby Edwards, MD. water, with a topical ointment used twice a day and pure petroleum jelly used as often as necessary for comfort. Nighttime se- 2 weeks later, she experienced increasing red- dation to allow a reprieve from rubbing and Diagnosis of an ness, itching, and burning. Although the ben- scratching may be helpful, and narcotic pain irritant or allergic zocaine relieved these symptoms, it required medications may be useful for the first 1 to contact dermatitis almost continual reapplication for comfort. 2 weeks of treatment. can be based A physical examination of the vulva Women who fail to respond to treatment on a history of reveals generalized, poorly demarcated should be referred for patch testing by a incontinence, redness, edema, and superficial erosions dermatologist. application of high- (FIGURE 2). risk substances, Diagnosis: Irritant contact dermatitis (as CASE 3 Teenager with vulvar pain and sores or inappropriate opposed to allergic contact dermatitis) asso- A woman brings her 13-year-old daughter washing ciated with the use of terconazole and clo- to your office for treatment of sudden-onset betasol. This was followed by allergic contact vulvar pain and sores. The child developed a dermatitis in association with benzocaine. sore throat and low-grade fever 3 days ear- Treatment: Withdrawal of benzocaine, with lier, with vulvar pain and vulvar dysuria the reinitiation of cool soaks and a switch to clo- next day. The pediatrician diagnosed a her- betasol ointment rather than cream. Night- pes simplex virus infection and prescribed time sedation allows the patient to sleep oral acyclovir, but the girl’s condition has through the itching and gradually allows her not improved, and the mother believes her skin to heal. daughter’s claims of sexual abstinence. The girl is otherwise healthy, aside from Contact dermatitis is a fairly common cause a history of trivial oral canker sores without of vulvar irritation, with two main types: arthritis, headaches, abdominal pain, eye • Irritant contact dermatitis—The most pain, or vision changes. common form, it occurs in any individual Physical examination of the vulva reveals

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FIGURE 3 Vulvar aphthae transmitted disease, but the large, well- demarcated, painful, nonindurated deep nature of the ulcer is pathognomonic for an aphthous ulcer. The presence of oral and genital aphthae does not constitute a diagnosis of Behçet disease, an often-devastating systemic in- flammatory condition occurring almost- ex clusively in men in the Middle and Far East. The diagnosis of Behçet disease requires the identification of objective inflammatory dis- ease of the eyes, joints, gastrointestinal tract, or neurologic system. True Behçet disease is incredibly uncommon in the ­United States. When it is diagnosed in Western countries, it takes an attenuated form, most often oc- curring in women who experience multi- system discomfort rather than identifiable inflammatory disease. End-organ damage is uncommon. Evaluation for Behçet disease in women with vulvar aphthae generally is Well-demarcated ulcerations with a white fibrin not indicated, although a directed review of base are pathognomonic of aphthae when they systems is reasonable. The rare patient who occur in an immunocompetent teenage girl. experiences frequent recurrence and symp- Figure courtesy of Libby Edwards, MD. toms of systemic disease should be referred to an ophthalmologist and other relevant Aphthae are soft, painful, well-demarcated ulcers with a specialists to evaluate for inflammatory uncommon and white fibrin base FIGURE( 3). disease. underrecognized on Diagnosis: Complex aphthosis. Further test- The treatment of vulvar aphthae consists the vulva, and genital ing is unnecessary. of systemic such as predni- aphthae are usually Treatment: 40 mg/day plus sone 40 mg/day for smaller individuals and much larger than hydrocodone in usual doses of 5/325, one or 60 mg/day for larger women, with follow-up two tablets every 4 to 6 hours, as needed; to ensure a good response. Often, the predni- oral aphthae topical petroleum jelly (especially before sone can be discontinued when pain relents urination); and sitz baths. When the patient rather than continued through complete returns 1 week later, she is much improved. healing. Reassurance, without discussing Behçet disease, is paramount, as is pain con- Aphthae are believed to be of hyperimmune trol. The heavy application of petroleum jelly origin, often precipitated by a viral syn- can decrease pain and prevent urine from drome. They are most common in girls aged touching the ulcer. 9 to 18 years. Vulvar aphthae are triggered by Some patients experience recurrent ul- various viral , including Epstein- cers. A second prescription of prednisone Barr.2 The offending virus is not located in can be provided for immediate reinstitution the ulcer proper, however, but is identified with onset of symptoms. However, frequent serologically. recurrences may require ongoing suppres- Aphthae are uncommon and under- sive medication, with dapsone being the recognized on the vulva, and genital aph- usual first choice. Colchicine often is used, thae are usually much larger than oral and thalidomide and tumor necrosis factor-a aphthae. Most patients initially are mis- blockers (adalimumab, ­etanercept, and takenly evaluated and treated for sexually infliximab) also are extremely beneficial.3,4

34 OBG Management | June 2014 | Vol. 26 No. 6 obgmanagement.com FIGURE 4 Desquamative inflammatory vaginitis

A B A. Note the redness of the introitus and the medial labia minora, with yellowish vaginal secretions visible at the introitus. B. This wet mount is notable for the marked increase in neutrophils and parabasal cells, with no lactobacilli. Figure courtesy of Libby Edwards, MD.

CASE 4 Increased neutrophils Diagnosis: Desquamative inflammatory and no lactobacilli ­vaginitis. A 36-year-old woman visits your office Treatment: Clindamycin vaginal cream, 1/2 reporting introital itching, vulvar dysuria, to 1 full applicator nightly, with a weekly oral and superficial dyspareunia that have lasted fluconazole tablet (200 mg is more easily 6 months. She has tried over-the-counter covered by insurance) to prevent secondary antifungal therapy, with only slight improve- candidiasis. You schedule a follow-up visit in ment while using the cream. Her health is 1 month. normal otherwise, lacking pain syndromes or abnormalities suggestive of pelvic floor Desquamative inflammatory vaginitis (DIV) dysfunction. She experienced comfortable is described as noninfectious inflamma- sexual activity until 6 months ago. tory vaginitis in a setting of normal estrogen The only abnormalities apparent on phys- and absence of skin disease of the mucous ical examination are redness of the vestibule, membranes of the vagina. The condition is medial labia minora, and vaginal walls, with characterized by an increase in white blood edema of the surrounding skin and no oral cells and parabasal cells, and absent lac- lesions (FIGURE 4A). Copious vaginal secre- tobacilli, with relatively high vaginal pH. tions are visible at the introitus. A wet mount DIV is thought to represent an inflamma- shows a marked increase in neutrophils with tory dermatosis of the vaginal epithelium.5 scattered parabasal cells (FIGURE 4B). There Although some clinicians believe that DIV are no clue cells, lactobacilli, or yeast forms. is actually lichen planus, the latter exhibits The patient’s pH level is greater than 6.5. erosions as well as redness, nearly always af- Routine and fungal ­cultures and ­molecular fects the mouth and the vulva, and produces studies for chlamydia, trichomonas, and ­remarkable scarring. DIV does not erode, af- gonorrhea are returned as ­normal. fect any other skin surfaces, or scar. CONTINUED ON PAGE 36

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FIGURE 5 Inverse psoriasis vagina nightly, or it can be compounded at 100 or 200 mg, if needed. If the condition is re- calcitrant, combination therapy can be used. When signs and symptoms abate, the frequency of use can be decreased, or hydro- can be discontinued and restarted again with any recurrence of discomfort. Many clinicians also prescribe weekly fluco- nazole to prevent intercurrent candidiasis.

CASE 5 5 Plaques on vulva and in skin folds A 43-year-old woman reports a recalcitrant yeast infection of the vulva, with itching and irritation. She is overweight and diabetic, with mild incontinence. Physical examination reveals a fairly well-demarcated plaque of redness of the vulva and labiocrural folds, with satellite red papules and peripheral peeling (FIGURE 5). Psoriasis of the vulva typically presents as a well-demarcated red, rough An examination of other skin surfaces reveals plaque that encompasses the dry, keratinized skin of the vulva, with similar plaques in the gluteal cleft, umbilicus, maceration of skin folds suggestive of candidiasis. and axillae as well as under the breasts. A Figure courtesy of Libby Edwards, MD. fungal preparation of the vagina and skin is negative. You obtain a fungal culture and pre- Other rare skin diseases that produce scribe topical and oral antifungal therapy and erosions and scarring also can be ruled out see the patient again 1 week later. Her condi- by the presence of erosions, absence of oral tion is unchanged. disease, and absence of other mucosal in- Diagnosis: You make a presumptive diagno- volvement. These diseases include cicatricial sis of inverse psoriasis and do a confirmatory pemphigoid, pemphigus vulgaris, Stevens- punch biopsy. Johnson syndrome, and toxic epidermal Treatment: Clobetasol ointment applied to necrolysis. Infectious diseases characterized the skin folds, along with continuation of the by are excluded by culture or topical cream. A week later, the molecular studies, and and patient’s condition is remarkably improved, retained foreign bodies (especially retained and her biopsy shows psoriasiform dermati- tampons) can produce a similar picture. tis. You reduce the potency of her corticoste- The vulvar itching and irritation that oc- roid, switching to desonide cream sparingly cur with DIV most likely represent an irritant applied daily. contact dermatitis, with vaginal secretions serving as the irritant. Psoriasis is a common skin disease of im- munologic origin. The skin is classically red How to treat DIV and thick, with heavy white scale produced The management of DIV consists of either by rapid turnover of epithelium. Howev- topical clindamycin cream (theoretically for er, there are several morphologic types of its anti-inflammatory rather than antimi- psoriasis, and anogenital psoriasis is most crobial properties) or intravaginal cortico- often of the inverse pattern. Inverse pso- , especially acetate.6 riasis preferentially affects skin folds and is Hydrocortisone can be tried at the low com- ­frequently ­mistaken for (and often initially mercially available dose of 25-mg rectal sup- superinfected with) candidiasis. Scale is thin positories, which should be inserted into the and unapparent, and there often is a shiny,

36 OBG Management | June 2014 | Vol. 26 No. 6 obgmanagement.com glazed appearance to the skin. Tiny satellite skin folds. It also is difficult for many patients lesions often are visible as well. A skin biopsy to manage with a busy life. Systemic therapy, of inverse psoriasis often is not diagnostic, including methotrexate and oral retinoids showing only nonspecific psoriasiform der- are often used, as are newer biologic agents matitis; this does not disprove psoriasis. such as etanercept, adalimumab, infliximab, Psoriasis is a systemic condition and is and ustekinumab. associated with metabolic syndrome, car- rying an increased risk of overweight, hy- References 1. Kingsberg SA, Krychman ML. Resistance and barriers to pertension, diabetes, and cardiovascular local estrogen therapy in women with atrophic vaginitis. disease. Management of these conditions is J Sex Med. 2013;10(6):1567–1574. 2. Huppert JS, Gerber MA, Deitch HR, et al. Vulvar ulcers very important in the treatment of the pa- in young females: A manifestation of aphthosis. J Pediatr tient overall. Adolesc Gynecol. 2006;19(3):195–204. Unlike lichen planus and lichen scle- 3. O’Neill ID. Efficacy of tumour necrosis factor-a antagonists in aphthous ulceration: Review of published individual patient rosus, scarring is rare with psoriasis, and data. J Eur Acad Dermatol Venereol. 2012;26(2):231–235. squamous cell carcinoma generally is 4. Sanchez-Cano D, Callejas-Rubio JL, Ruiz-Villaverde R, 7,8 Ortego-Centeno N. Recalcitrant, recurrent aphthous unassociated. stomatitis successfully treated with adalimumab. J Eur Acad Anogenital psoriasis is treated with Dermatol Venereol. 2009;23(2):206. topical corticosteroids and, when needed, 5. Stockdale CK. Clinical spectrum of desquamative inflammatory vaginitis. Curr Infect Dis Rep. 2010;12(6):479–483. topical vitamin D preparations. Generally, 6. Sobel JD, Reichman O, Misra D, Yoo W. Prognosis and inverse psoriasis is controlled with low- treatment of desquamative inflammatory vaginitis. Obstet Gynecol. 2011;117(4):850–855. potency topical corticosteroids, with man- 7. Albert S, Neill S, Derrick EK, Calonje E. Psoriasis associated agement of secondary infection and irritants. with vulvar scarring. Clin Exp Dermatol. 2004;29(4):354–356. Otherwise, light is a time-honored 8. Boffetta P, Gridley G, Lindelöf B. Cancer risk in a population- based cohort of patients hospitalized for psoriasis in Sweden. therapy for psoriasis but not practical for J Invest Dermatol. 2001;117(6):1531–1537.

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