FIRST OF 2 PARTS ON OFFICE MANAGEMENT OF BENIGN VULVAR CONDITIONS Chronic vulvar symptoms and dermatologic disruptions: How to make the correct diagnosis

When a patient reports chronic symptoms, it’s important to look beyond yeast and other common causes to accurately identify her condition and select the optimal treatment

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

early one in every six women will ex- in on diagnosis and treatment. In this first perience chronic vulvar symptoms part, we describe five patient scenarios illus- N at some point, from ongoing itching trating the diagnosis and treatment of: to sensations of rawness, burning, or dyspa- • lichen sclerosus reunia. Regrettably, clinicians generally are IN THIS • ARTICLE taught only a few possible causes for these • symptoms, primarily such as yeast, • Even asymptomatic bacterial vaginosis, , or • hidradenitis suppurativa. lichen sclerosus can anogenital . However, infections rarely progress produce chronic symptoms that do not re- In many chronic cases, page 38 spond, at least temporarily, to therapy. more than one entity is the cause In this two-part series, we focus on a to- Specific skin diseases, sensations of rawness Is it really chronic tal of 10 cases of vulvar symptoms, zeroing from various external and internal irritants, yeast infection? neuropathy, and psychological issues are all much more common causes of chronic page 40 vulvar symptoms than infection. Moreover, Dr. Edwards is Chief of most women with chronic vulvar symptoms Oral and Dermatology at Carolinas Medical Center, Charlotte, North Carolina. have more than one entity producing their vulvar involvement discomfort. of lichen planus Very often, the cause of a patient’s symp- page 42 toms is not clear at the first visit, with non- specific redness or even normal skin seen on Dr. Goldbaum is Clinical Instructor of Obstetrics and Gynecology examination. Pathognomonic skin findings at Harvard Medical School, can be obscured by irritant contact derma- Boston, Massachusetts. titis caused by unnecessary medications or overwashing, atrophic vaginitis, and/or rub- bing and scratching. In such cases, obvious

The authors report no financial relationships abnormalities must be eliminated and the relevant to this article. patient reevaluated to definitively discover and treat the cause of the symptoms. CONTINUED ON PAGE 38

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FIGURE 1 Lichen sclerosus sclerosus, the symptoms and clinical ­abnormalities usually can be well managed with ultra-potent topical corticosteroids. However, scarring and architectural changes are not reversible. Moreover, poorly con- trolled lichen sclerosus exhibits malignant transformation on anogenital skin in about 3% of affected patients. The standard of care is application of an ultra-potent topical corticoste- roid ointment once or twice daily until the skin texture normalizes again. The most common of such corticosteroids are clobetasol, halobetasol, and betamethasone dipropionate in an augmented vehicle (beta- methasone dipropionate in the usual vehicle is only a medium-high medication in terms of potency.) One of us (L.E.) finds that some women experience irritation with generic clobetasol. The exhibits a white, edematous, crinkled The ointment form of the selected corti- plaque, with fragility manifested by purpura from rubbing and scratching. costeroid is preferred, as creams are irritat- Figure courtesy of Libby Edwards, MD. ing to the vulva in most women because they contain more alcohols and preservatives than ointments do. The amount to be used CASE 1 Anogenital itching and is very small—far smaller than the pea-sized Use corticosteroid A 62-year-old woman schedules a visit to amount often suggested. By using this small- ointment rather than address her anogenital itching. She reports er amount, we avoid spread to the surround- cream for lichen pain with scratching and has developed ing hair-bearing skin, which is at greater risk sclerosus to avoid introital dyspareunia. On physical exami- for steroid dermatitis and than the vulvar irritation nation, you find a well-demarcated white modified mucous membranes. caused by higher plaque of thickened, crinkled skin (FIGURE 1). A wet mount shows parabasal cells and no Even asymptomatic lichen sclerosus amounts of alcohols lactobacilli. can progress and preservatives in Diagnosis: Lichen sclerosus and atrophic Most vulvologists agree that when the skin creams vagina. normalizes (not when symptoms subside), Treatment: Halobetasol ointment, an ultra- it is best to either decrease the frequency of potent topical corticosteroid, once or twice application of the ultra-potent corticosteroid daily; along with estradiol cream (0.5 g intra- to two or three times a week, or to continue vaginally) 3 times a week. daily use with a lower-potency corticoste- roid such as ointment 0.1%. Lichen sclerosus is a skin disease found Discontinuation of therapy usually results in most often on the vulva of postmenopausal recurrence.2 women, although it also can affect prepuber- Treatment should not be based solely tal children and reproductive-age women. on symptoms, as asymptomatic lichen scle- Lichen sclerosus is multifactorial in patho- rosus can progress and cause permanent genesis, including prominent autoimmune scarring and an increased risk for squamous factors, local environmental factors, and ge- cell carcinoma. netic predisposition.1 Although no studies have shown a de- Although there is no cure for lichen creased risk for squamous cell carcinoma

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with ongoing use of a corticosteroid, FIGURE 2 Vulvodynia ­vulvologists have observed that malignant transformation occurs uniformly in the set- ting of poorly controlled lichen sclerosus. Immune dysregulation and inflammation may play an important role, so careful man- agement to minimize inflammation may help prevent a malignancy.3

Secondary treatment choices Secondary choices for lichen sclerosus in- clude the topical calcineurin inhibitors tacrolimus (Protopic) and (Elidel) but not testosterone, which has been shown to be ineffective. Tacrolimus and The vulva is normal except for patchy macular pimecrolimus are useful but often burn upon redness of the vestibule. application, and they are “black-boxed” for Figure courtesy of Libby Edwards, MD. cutaneous squamous cell carcinoma and lymphoma. Therefore, although squamous CASE 2 Is it really chronic yeast infection? cell carcinoma associated with their use is A 36-year-old woman consults you about her extraordinarily uncommon, patients should history of chronic yeast infection that mani- be advised of these risks, particularly be- fests as introital burning, discharge, and dys- cause lichen sclerosus already exhibits this pareunia. She is otherwise healthy, except for association. irritable bowel syndrome and fibromyalgia. Most postmenopausal women with li- Physical examination reveals a mild chen sclerosus also exhibit hypothyroidism, patchy redness of the vestibule and sur- Monitor so they should be monitored for this. How- rounding modified mucous membranes postmenopausal ever, function testing in 18 children (FIGURE 2). Gentle probing with a cotton women who have showed no evidence of hypothyroidism in swab triggers exquisite pain in the vestibule, lichen sclerosus for that age group (L.E. unpublished data). with slight extension to the labia minora. A hypothyroidism, a wet mount shows no evidence of increased Estrogen replacement may be advised white blood cells, parabasal cells, clue cells, common comorbidity Postmenopausal women who have promi- or yeast forms. Lactobacilli are abundant. in this population nent introital lichen sclerosus or dyspareu- Diagnosis: Vulvodynia, with a nearly vestibu- nia should receive estrogen replacement of lodynia pattern. some type so that there is only one cause, Treatment: Venlafaxine and pelvic floor phys- rather than two, for their dyspareunia, thin- ical therapy. ning, fragility, and inelasticity. Women with well-controlled lichen Vulvodynia is a genital pain syndrome de- sclerosus should be followed twice a year to fined as sensations of chronic burning, irri- ensure that their disease remains suppressed tation, rawness, and soreness in the absence with ongoing therapy, and to evaluate for ac- of objective disease and infection that could tive disease, adverse effects of therapy, and explain the discomfort. Vulvodynia occurs in the appearance of dysplasia or squamous approximately 7% to 8% of women.4 cell carcinoma. Vulvodynia generally is believed to be a Women with lichen sclerosus occasion- multifactorial symptom, occurring as a result ally experience discomfort after their clini- of pelvic floor dysfunction and neuropathic cal skin disease has cleared. These women pain,5,6 with anxiety/depression issues now have developed vulvodynia triggered by ­exacerbating symptoms. Some recent stud- their lichen sclerosus. ies have shown the presence of biochemical

40 OBG Management | May 2014 | Vol. 26 No. 5 obgmanagement.com mediators of inflammation in the absence of • venlafaxine XR 150 mg daily clinical and histologic inflammation.7 Dis- • pregabalin 150 mg twice a day comfort often is worsened by infections or • duloxetine 60 mg a day. the application of common irritants (creams, Compounded amitriptyline 2% with ba- panty liners, soaps, some topical anesthet- clofen 2% cream applied three times daily ics). Estrogen deficiency is another common is beneficial for many patients, and topical exacerbating factor. lidocaine jelly 2% or ointment 5% (which Women tend to exhibit other pain syn- often burns) can help provide immediate dromes such as chronic headaches, fibro- temporary relief. myalgia, temperomandibular disorder, or Most patients require sex therapy and premenstrual syndrome, as well as promi- counseling for maximal improvement. nent anxiety, depression, sleep disorder, and Women with vestibulodynia in whom these so on. therapies fail are good candidates for vesti- Almost uniformly present are symptoms bulectomy if their pain is strictly limited to of pelvic floor dysfunction, such as consti- the vestibule. Fortunately, most women do pation, irritable bowel syndrome, and in- not require this aggressive therapy. terstitial cystitis or urinary symptoms in the absence of a urinary tract infection. These CASE 3 Severe itching disrupts sleep women also are frequently unusually intol- A 34-year-old patient reports excruciating erant of medications. itching, with disruption of daily activities and sleep. She has been treated for on Classifying vulvodynia multiple occasions, but in your office her wet There are two primary patterns of vulvodyn- mount and confirmatory culture are negative. ia. The first and most common is vestibulo- Physical examination reveals a pink, licheni- dynia, formerly called vulvar vestibulitis. The fied plaque with excoriation FIGURE( 3). term vestibulitis was eliminated to reflect the Diagnosis: Lichen simplex chronicus. absence of clinical and histologic inflam- Treatment: Ultra-potent corticosteroid oint- mation. Vestibulodynia refers to pain that is ment applied very sparingly twice daily and CONTINUED ON PAGE 42 always limited to the vestibule. Generalized vulvodynia, however, extends beyond the FIGURE 3 Lichen simplex chronicus vestibule, is migratory, or does not include the vestibule. Several vulvologists have found that many patients exhibit features of both types of vulvodynia, and these patterns probably exist on a spectrum. The difference is prob- ably unimportant in clinical practice, except that vestibulodynia can be treated with ves- tibulectomy.

How we manage vulvodynia We focus on pelvic floor physical therapy and on the provision of medication for neu- ropathic pain, which is initiated at very small doses and gradually increased to active dos- es.8 The medications used and the ultimate doses often required include: • amitriptyline or desipramine 150 mg The hair-bearing skin is covered with a poorly demarcated, lichenified plaque, with an excoriation on the anterior right labium majus. • gabapentin 600 to 1,200 mg three times Figure courtesy of Libby Edwards, MD. daily

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covered with petroleum jelly. You also order Restart therapy immediately upon re- nighttime sedation with amitriptyline to break currence to prevent lichenification and the itch-scratch cycle. When the patient’s itch- chronic problems. ing resolves and her skin clears, you taper her Second-line medications include calci- off the corticosteroid, warning her that recur- neurin inhibitors (tacrolimus or pimecrolim- rence is likely, and instruct her to restart the us). Although these agents do not contribute medication immediately should itching recur. to atrophy, they are less effective than topical corticosteroids,9 cost more, and can cause Lichen simplex chronicus (formerly burning upon application. called squamous hyperplasia or hyperplas- Unlike lichen sclerosus, lichen simplex tic dystrophy, and also known as eczema, chronicus does not always recur upon ces- neurodermatitis, or localized atopic derma- sation of treatment, and there is no need for titis) occurs when irritation from any cause concern about an increased risk of malig- produces itching in a predisposed person. nancy or significant scarring. The subsequent scratching and rubbing both produce the rash and exacerbate the CASE 4 4 Oral and vulvar involvement irritation that drives the itching, even after A 73-year-old patient seeks your help in alle- the original cause is gone. The rubbing and viating longstanding introital itching and raw- scratching perpetuate the irritation and itch- ness, with dyspareunia. She has tried topical ing, producing the “itch-scratch” cycle. estradiol cream intravaginally three times The appearance of lichen simplex chron- weekly in combination with weekly fluco­ icus is produced by rubbing (where the skin nazole, to no avail. thickens and lichenifies) or scratching (where Physical examination reveals deep red the skin becomes red with linear erosions, patches and erosions of the vestibule, with called excoriations, caused by fingernails). complete resorption of the labia minora The initial trigger for lichen simplex (FIGURE 4). Patchy redness of the vagina Yeast is often the chronicus often is an infection—often yeast— initial trigger for but overwashing, stress, sweat, heat, urine, FIGURE 4 Lichen planus lichen simplex irritating lubricants, and use of panty liners chronicus of also may precipitate the itching. At the office the vulva, but visit, the original infection or other cause of overwashing, stress, irritation often is no longer present, and only lichen simplex chronicus can be identified. sweat, heat, urine, irritating lubricants, How to treat lichen simplex chronicus and use of panty Management of lichen simplex chronicus liners also may cause requires very sparing application of an ultra- the itching potent topical corticosteroid (clobetasol, halobetasol, or betamethasone dipropionate in an augmented vehicle ointment) twice daily, with the ointment covered with petro- leum jelly. Care also must be taken to avoid irritants. In addition, nighttime sedation helps to interrupt the itch-scratch cycle by prevent- ing rubbing during sleep. Superficial erosion of the vestibule extends to the When the skin appears normal and anterior modified mucosal membranes, with loss ­itching has resolved, taper the medication of the labia minora, and edema and scarring of the clitoral hood. down or off, warning the patient that recur- Figure courtesy of Libby Edwards, MD. rence is common with any future irritation.

42 OBG Management | May 2014 | Vol. 26 No. 5 obgmanagement.com is apparent as well, so you examine the oral retinoids, can be added for more recal- patient’s mouth and find deep redness of the citrant disease.11 gingivae and erosions of the buccal muco- sae, with surrounding white, lacy papules. A How to manage disease that affects wet mount shows a marked increase in lym- the vagina phocytes and parabasal cells, with a pH of When the vagina is involved in lichen planus, more than 7. treatment is important to prevent scarring, as Diagnosis: After correlating the vulvar and well as rawness and pain from irritant contact oral findings, you make a diagnosis of lichen dermatitis caused by purulent vaginal secre- planus. tions. Occasionally, a 25-mg hydrocortisone Treatment: You initiate halobetasol ointment acetate rectal suppository inserted into the twice daily, to be applied to the vulva. You vagina nightly improves vaginal lichen pla- also continue vaginal estradiol cream but add nus, but sometimes more potent supposi- hydrocortisone acetate 200 mg compounded tories, such as doses of 100 to 200 mg, may vaginal suppositories nightly, as well as clo- be compounded. Dilators should be inserted betasol gel to be applied to oral lesions three daily to prevent vaginal synechiae. times a day. You follow the patient closely for secondary yeast of the mouth and vagina. Oral involvement requires targeted treatment Erosive multimucosal lichen planus is The mouth is almost always involved - inli a disease of cell-mediated immunity that chen planus. If a dermatologist is not in- overwhelmingly affects menopausal wom- volved in patient care, a prescription for en. The most common surfaces involved are dexamethasone/nystatin elixir (50:50) (5 mL the mouth, vagina, rectal mucosa, and vulva; swish, hold, and spit four times daily) can usually, at least two surfaces are affected. improve oral symptoms remarkably. Alter- The esophagus, extra-auditory canals, nasal natively, clobetasol gel applied to affected mucosa, and eyes also can be involved. Dry, areas of the mouth three or four times daily Careful clinical extragenital skin usually is not affected in the can be helpful. Secondary yeast of the vagina surveillance of setting of erosive vulvovaginal lichen planus. and mouth are common with the use of topi- women with lichen Vulvar lichen planus most often is cal corticosteroids. planus is warranted controlled with ultra-potent topical corti- because of the Careful clinical follow-up is advised costeroids (again, clobetasol, halobetasol, potential for scarring or betamethasone dipropionate in an aug- Like uncontrolled lichen sclerosus, erosive and squamous cell mented vehicle), but other mucosal surfaces lichen planus of the vulva produces scarring carcinoma often are more difficult to manage. Although and sometimes eventuates into squamous there is no definitive cure for this condition, cell carcinoma. Therefore, careful clini- careful local care, estrogen replacement, and cal surveillance is warranted. And therapy suppression of oral and vulvovaginal candi- must be continued to prevent recurrence of diasis usually provide relief. lichen planus (as it must be for lichen scle- Calcineurin inhibitors (tacrolimus, rosus), scarring, and to decrease the risk of pimecrolimus) sometimes are useful in squamous cell carcinoma. And like lichen patients who improve only partially af- sclerosus, lichen planus sometimes triggers ter treatment with a topical corticosteroid, vulvodynia. provided burning with application is tol- erable.10 Systemic immunosuppressants CASE 5 Multiple in the groin such as hydroxychloroquine, methotrexate, A 31-year-old morbidly obese African Ameri- mycophenolate mofetil, azathioprine, cy- can woman comes to your office with con- closporine, cyclophosphamide, and tumor tinually evolving boils in the groin. A culture necrosis ­factor (TNF) alpha blockers (etan- shows Bacterioides spp, Escherichia coli, ercept, adalimumab, infliximab), as well as and Peptococcus spp. In the past, multiple CONTINUED ON PAGE 44

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FIGURE 5 Hidradenitis suppurativa brisk foreign-body response ­produces a non- infectious . Hidradenitis suppurativa affects more than 2% of the population.12 It appears only in areas of the body that contain apocrine glands and in individuals who have double- or triple-outlet follicles that predispose them to follicular occlusion. Therefore, this -dis ease has a genetic component. Other risk factors include male sex, Afri- can genetic background, obesity, and smok- ing. The prevalence of metabolic syndrome is significantly higher in individuals with hidradenitis suppurativa than in the general population.13

Recommended management Treatments include: • chronic antibiotics with nonspecific anti-inflammatory activity (tetracyclines, Red, draining nodules, erosions, , and sinus tracts on the hairbearing erythromycin, clindamycin, and trime- vulvar and perianal skin are classic signs of hidradenitis suppurativa. thoprim-sulfamethoxazole) Figure courtesy of Libby Edwards, MD. • intralesional injection of cortico- steroids for early nodules (which often courses of various antibiotics have provided aborts their development) only modest relief. • TNF alpha blockers (etanercept, adali- Physical examination reveals fluctuant mumab, infliximab)14–16 Hidradenitis nodules, scars, and draining sinus tracts • surgical removal of affected skin—the suppurativa appears of the hair-bearing vulva and crural crease definitive therapy. only in areas of the (FIGURE 5). The axillae are clear. Note, however, that anogenital hidradenitis body that contain Diagnosis: Hidradenitis suppurativa. often is too extensive for surgery to be prac- apocrine glands Treatment: The patient begins taking mino- tical. In patients who have localized hidrad- cycline 100 mg twice daily. Because she is enitis, primary excision is an excellent early a smoker, you refer her to an aggressive pri- therapy, provided the patient is advised that mary care provider for smoking cessation recurrence may occur in apocrine-contain- and weight loss management. ing nearby skin. Aggressive curettage of the Three months later, the patient is devel- roof of the cysts has been performed by oping only about two nodules a month, man- some clinicians with good response. aged by early intralesional injections of tri- amcinolone acetonide. Don’t overlook adjuvant approaches Smoking cessation and weight loss often are Hidradenitis suppurativa is sometimes useful. called inverse because the underlying Other therapies backed by anecdotal pathogenesis is similar to cystic acne. Follicu- evidence include oral contraceptives or spi- lar plugging with keratin debris occurs, with ronolactone for their anti-androgen effect, additional keratin, sebaceous material, and as well as metformin, a more recently stud- normal skin trapped below the occlu- ied agent. sion and distending the follicle. As the follicle Local care with antibacterial soaps and wall stretches, thins, and allows for leakage topical antibiotics may be useful for some of keratin debris into ­surrounding , a women.

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6. Hampson JP, Reed BD, Clauw DJ, et al. Augmented More cases to come central pain processing in vulvodynia. J Pain. 2013;14(6): In Part 2 of this series, which will appear in 579–589. 7. Omoigui S. The biochemical origin of pain: the origin of the June 2014 issue of OBG Management, all pain is inflammation and the inflammatory response. we will discuss the following cases: Part 2 of 3: Inflammatory profile of pain syndromes. Med • atrophic vagina and atrophic vaginitis Hypotheses. 2007;69(6):1169–1178. 8. Haefner HK, Collins ME, Davis GD, et al. The vulvodynia • guideline. J Low Genit Tract Dis. 2005;9(1):40–51. • vulvar aphthae 9. Frankel HC, Qureshi AA. Comparative effectiveness of topical calcineurin inhibitors in adult patients with atopic • desquamative inflammatory vaginitis dermatitis. Am J Clin Dermatol. 2012;13(2):113–123. • . 10. Samycia M, Lin AN. Efficacy of topical calcineurin inhibitors in lichen planus. J Cutan Med Surg. 2012;16(4):221–229. 11. Mirowski GW, Goddard A. Treatment of vulvovaginal lichen References planus. Dermatol Clin. 2010;28(4):717–725. 1. Doulaveri G, Armira K, Kouris A, et al. Genital vulvar lichen 12. Vinding GR, Miller IM, Zarchi K, et al. The prevalence of sclerosus in monozygotic twin women: A case report and inverse recurrent suppuration: A population-based study of review of the literature. Case Rep Dermatol. 2013;5(3):321–325. possible hidradenitis suppurativa [published online ahead 2. Virgili A, Minghetti S, Borghi A, Corazza M. Proactive of print December 16, 2013]. Br J Dermatol. doi:10.1111 maintenance therapy with a topical corticosteroid for vulvar /bjd.12787. lichen sclerosus: Preliminary results of a randomized study. 13. Gold DA, Reeder VJ, Mahan MG, Hamzavi IH. The prevalence Br J Dermatol. 2013;168(6):1316–1324. of metabolic syndrome in patients with hidradenitis 3. Brodrick B, Belkin ZR, Goldstein AT. Influence of treatments suppurativa. J Am Acad Dermatol. 2014;70(4):699–703. on prognosis for vulvar lichen sclerosus: Facts and 14. Scheinfeld N. Hidradenitis suppurativa: A practical review of controversies. Clin Dermatol. 2013;31(6):780–786. possible medical treatments based on over 350 hidradenitis 4. Harlow BL, Kunitz CG, Nguyen RH, Rydell SA, Turner RM, patients. Dermatol Online J. 2013;19(4):1. MacLehose RF. Prevalence of symptoms consistent with a 15. Kimball AB, Kerdel F, Adams D, et al. Adalimumab for the diagnosis of vulvodynia: Population-based estimates from treatment of moderate to severe hidradenitis suppurativa: two geographic regions. Am J Obstet Gynecol. 2014;210(1): A parallel randomized trial. Ann Intern Med. 40.e1–e8. 2012;157(12):846–855. 5. Morin M, Bergeron S, Khalife S, Mayrand MH, Binik YM. 16. Chinniah N, Cains GD. Moderate to severe hidradenitis Morphometry of the pelvic floor muscles in women with and suppurativa treated with biological therapies [published without provoked vestibulodynia using 4D ultrasound. J Sex online ahead of print January 23, 2014]. Australas J Dermatol. Med. 2014;11(3):776–785. doi:10.1111/ajd.12136.

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