Research

Case Report/Case Series With Vaginal Involvement Report of 2 Cases and Review of the Literature

Kate Zendell, MD; Libby Edwards, MD

Invited Commentary IMPORTANCE Lichen sclerosus (LS) is an uncommon chronic inflammatory disease that most page 1203 commonly affects anogenital skin of postmenopausal women. It typically manifests as atrophic white plaques, which may be accompanied by purpura or fissuring. Rarely, LS has been observed to affect mucosal tissues in the mouth and the penile . It is generally taught that LS does not affect the , unlike . To our knowledge, only one case report of LS with vaginal involvement exists in the literature.

OBSERVATIONS Two cases of severe vulvar LS with vaginal involvement are reported. Both cases exhibited characteristic features of LS on vaginal biopsy, and both patients were followed up clinically without further treatment of the vagina.

CONCLUSIONS AND RELEVANCE Vaginal LS may be more common than previously thought Author Affiliations: Department of and may be underdiagnosed. Patients with more severe disease or with significant vaginal Dermatology, Thomas Jefferson may be more likely to have involvement of the vagina. In addition, patients with University Hospital, Philadelphia, Pennsylvania (Zendell); Carolinas pelvic organ laxity may be at increased risk if their vaginal walls are chronically exposed Medical Center and Southeast Vulvar because of prolapse. Physicians managing patients with vulvar LS should be aware of the Clinic, Charlotte, North Carolina possibility of vaginal involvement so that vaginal lesions may be diagnosed and followed up (Edwards). appropriately. Corresponding Author: Kate Zendell, MD, Department of Dermatology, Thomas Jefferson JAMA Dermatol. 2013;149(10):1199-1202. doi:10.1001/jamadermatol.2013.4885 University Hospital, 833 Chestnut St, Published online August 7, 2013. Ste 740, Philadelphia, PA 19107 ([email protected])

ichen sclerosus (LS) is a chronic inflammatory skin dis- ditional cases to the scant existing literature to learn more about ease of unknown origin. It was first described by Hallo- the pathogenesis and natural history of this disease entity. L peau in 1887 as an atrophic form of lichen planus, al- though now it is believed to represent a separate disease entity.1 likely has a role in the pathogenesis. Over the Report of Cases years, LS has gone by multiple names, including “circumscribed ,”“,”“leukoplakic ,”“hy- Case 1 poplastic vulvar dystrophy,”“lichen sclerosus et atrophicus,” A 59-year-old white woman was seen with vulvovaginal itch- and (when seen in male patients) “ xerotica obliterans.”2 ing and vulvar rash associated with a sensation of rawness Lichen sclerosus most commonly affects the anogenital skin and and burning for 1½ years. Physical examination revealed is more prevalent among women than among men. It typically several well-demarcated white, atrophic plaques with a manifests as atrophic white plaques. Purpura and fissuring are crinkled appearance on the upper back and inner thighs. Her also commonly seen because of skin fragility. In women, a entire , perineal body, and perianal area were covered figure-eight pattern is classically described involving the vul- by a well-demarcated red and hypopigmented plaque with var and perianal skin. In a case series from the Southeast Vul- superficial erosions (Figure 1). Areas of fissuring and purpura var Clinic, Charlotte, North Carolina (L.E., unpublished data, were also present. Agglutination of the minora and par- 2006), extragenital lesions were seen in approximately 6% of tial of the were observed. On internal patients. Rarely, LS has been reported to affect the oral and pe- examination, her vagina was smooth and dry, consistent nile urethral mucosa as well. It is generally taught that LS does with postmenopausal atrophy. She had marked pelvic organ not affect the vagina, unlike lichen planus. laxity, and a was present. A wet mount demon- We report 2 cases of LS involving both the vulva and the strated normal vaginal secretions. No oral lesions were vagina. Using PubMed, a review of the English literature since present. June 1937 revealed one case report of LS with vaginal involve- A punch biopsy specimen of an atrophic plaque on the right ment by Longinotti et al3 in 2005. Our objective is to add 2 ad- medial thigh revealed effacement of the normal rete ridge pat-

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Figure 1. Vulvar Examination Before Treatment Demonstrates a Figure 2. Purpuric Patch on the Distal Anterior Vaginal Wall Hypopigmented, Atrophic Patch on the Vulva and Perineum With Focal Purpura

The patch was observed on routine examination several years after the initial visit. Resorption of the has occurred. Pelvic organ laxity is notable.

Figure 3. Biopsy Specimen Obtained From the Anterior Vaginal Wall Shows Overlying the Mucosal , With tern. Also present were hyalinization of the papillary Hyalinization of the Subepithelium and a bandlike infiltrate in the upper reticular dermis, diag- nostic of LS. During the next 4 years, the patient was treated with a com- bination of potent topical corticosteroid ointments, intral- esional corticosteroid injections, and vaginal therapy. She had significant difficulty achieving and maintaining con- trol of her symptoms because of the severity of her disease and multiple socioeconomic factors. She also experienced sev- eral cutaneous adverse effects during her therapy, including in response to medication use, corticoste- roid dermatitis and atrophy, and secondary , which were treated as needed. Several years after her initial visit, routine examination re- vealed a purpuric patch on the distal anterior vaginal wall (Figure 2). Biopsy of this lesion was performed and showed clas- sic features of LS (Figure 3). She has continued a maintenance regimen of topical corticosteroid therapy 3 times weekly and Hematoxylin-eosin, original magnification ×100. vaginal estrogen therapy, with fairly good control. The pur- pura resolved after biopsy. period, including vaginal estrogen cream, topical and vaginal antifungal creams, topical corticosteroid creams, and hydroxy- Case 2 zine hydrochloride. A 76-year-old white woman was seen with vulvovaginal itch- Physical examination revealed a purpuric plaque with a ing, pain, rawness, and occasional bleeding of 2 years’ dura- thin, crinkled border covering the vulva, with hypopigmen- tion. She had tried multiple ineffective therapies during this tation of the perineal body. Significant scarring was present,

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Figure 4. Vulvar Examination After Extensive Therapy Reveals Patchy Figure 5. The Posterior Vaginal Wall Shows a White, Cobblestoned Hypopigmentation and Hyperpigmentation and Areas of Focal Purpura Plaque With Focal Areas of Purpura

Extensive scarring is present, with loss of almost all normal external anatomic The plaque was observed on routine internal examination about 3 years after structures. the initial presentation.

with resorption of the labia minora (Figure 4). Vaginal exami- nosing? Significantly more case reports of mucosal LS involv- nation showed mild redness of the vaginal mucosa but no other ing the oral cavity exist in the dental literature. Oral lesions are abnormalities. A rectocele was present. Her wet mount showed most commonly found on the lip or buccal mucosa, and ap- normal vaginal secretions. No oral lesions were present. A clini- proximately half of the patients are symptomatic.4 Mucosal LS cal diagnosis of LS was made. is also described in the urologic literature. Barbagli et al5 dem- During the next 3 years, the patient was managed with ul- onstrated histologic involvement not only of the squamous ure- trapotent topical corticosteroid ointments and vaginal estro- thral epithelium but also of the penile mucosal urethra in 12 gen cream. She used oral fluconazole and oral antibiotics as of 16 male patients with LS. needed for yeast and secondary bacterial infection, respec- In the same article, Barbagli et al5 propose that when LS tively. Control of her waxed and waned. About involves a mucous membrane, it is always after the mucous 3 years after her initial presentation, routine internal exami- membrane has become “squamatized.”It is postulated that in nation revealed a 2-cm white, cobblestoned plaque on the dis- this process chronic irritation changes the mucosal epithe- tal posterior vaginal wall (Figure 5). Biopsy of this lesion re- lium to a metaplastic squamous epithelium. With continued vealed abnormal hyperkeratosis, with hyalinization of the or irritation, the squamatized epithelium be- mucosal subepithelium, diagnostic of LS (Figure 6). comes hyperkeratotic and -like. If their theory is true, this may be a permissive factor in the ability of LS to affect mu- cosal tissues. Notably, both of our patients had significant pel- Discussion vic organ prolapse so that the affected portions of their vagi- nal wall were more chronically exposed than would be normal. Two cases of LS involving not only the vulva but also the va- This brings into question whether squamatization of the vagi- gina are reported, adding to the one previous case report by nal mucosa may have had a role in the development of their Longinotti et al.3 Histologic features of vaginal biopsy in each vaginal lesions. case were diagnostic of LS. This brings into question the true The risk of scarring and malignant neoplasm in vaginal LS incidence of vaginal lesions in this disease. Is vaginal involve- is unknown but is likely small because neither has been re- ment as rare as the literature suggests, or are we underdiag- ported to occur. Therefore, optimal management has not yet

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Figure 6. Architectural Features Diagnostic of Lichen Sclerosus Include Figure 7. Evaluation and Management of Vaginal Lichen Sclerosus Compact Hyperkeratosis, Epithelial Atrophy, Focal Vacuolization Along the Zone, and Hyalinization of the Subepithelium At initial evaluation for vulvar LS, patient should have speculum examination either in office or by gynecology referral if necessary

Assess for any abnormal white or purpuric lesions on vaginal mucosa; also assess for signs of atrophic including pallor, dryness, and loss of normal vaginal rugae.

If vaginal lesion is identified, biopsy for diagnosis

Begin appropriate treatment for Follow up any vaginal LS lesion vulvar LS, including topical clinically with repeat speculum or intralesional steroids examination at each follow-up with or without estrogen therapy visit (at least every 6 months); if present consider repeat biopsy if lesion changes or becomes symptomatic The basement membrane is thickened, and extravasated erythrocytes are present focally below the zone of hyalinization (hematoxylin-eosin, original magnification ×100). LS indicates lichen sclerosus. tinue to be on achieving compliance and control of their vul- been defined. In general, if a vaginal lesion is identified, an ini- var disease. In addition, a speculum examination should be per- tial biopsy specimen should be obtained for diagnosis formed at each visit to improve detection and surveillance of (Figure 7). The lesion should then be followed up clinically to vaginal lesions. Ideally, this would be done by a dermatolo- assess for early signs of malignant transformation. Therapy gist, who is more likely to recognize inflammatory skin dis- with topical or intralesional corticosteroids or vaginal estro- ease. However, if this is impossible, patients should be re- gen therapy may be considered if patients are symptomatic. ferred to a gynecologist for complete speculum examination. In our opinion, attempts at self-monitoring of vaginal le- In conclusion, LS of the vagina occurs and may be more sions in this patient population would be of low yield and would common than previously thought because the vagina may not likely invoke unnecessary patient anxiety. The incidence of be examined carefully for LS or because lesions may be subtle vaginal squamous cell carcinoma is exceedingly low. Even in or atypical. Lichen sclerosus may be more likely in patients with the setting of vulvar lichen planus, a disease that routinely in- vaginal mucosa that is exposed because of prolapse. The risk volves vaginal inflammation and scarring, there are no re- of scarring and malignant neoplasm is unknown. Therefore, ports of vaginal squamous cell carcinoma. No evidence exists patients should be followed up carefully, including routine that vaginal lesions in LS lead to scarring or have any medical speculum examination, with the goal of optimizing patient out- significance. Therefore, the focus for these patients should con- comes and further defining the clinical spectrum of LS.

ARTICLE INFORMATION Conflict of Interest Disclosures: None reported. 4. Azevedo RS, Romañach MJ, de Almeida OP, et al. Accepted for Publication: April 18, 2013. Additional Contributions: Jason C. Reutter, MD, Lichen sclerosus of the oral mucosa: and Russell A. Ball, MD, provided the histologic clinicopathological features of six cases. IntJOral Published Online: August 7, 2013. Maxillofac Surg. 2009;38(8):855-860. doi:10.1001/jamadermatol.2013.4885. photographs. 5. Barbagli G, Mirri F, Gallucci M, Sansalone S, Author Contributions: Drs Zendell and Edwards REFERENCES Romano G, Lazzeri M. Histological evidence of had full access to all the data in the study and take urethral involvement in male patients with genital responsibility for the integrity of the data and the 1. Powell JJ, Wojnarowska F. Lichen sclerosus. Lancet. 1999;353(9166):1777-1783. lichen sclerosus: a preliminary report. J Urol. accuracy of the data analysis. 2011;185(6):2171-2176. Study concept and design: All authors. 2. Meffert JJ, Davis BM, Grimwood RE. Lichen Acquisition of data: Edwards. sclerosus. J Am Acad Dermatol. 1995;32(3): Analysis and interpretation of data: All authors. 393-418. Drafting of the manuscript: All authors. 3. Longinotti M, Schieffer YM, Kaufman RH. Lichen Critical revision of the manuscript for important sclerosus involving the vagina. Obstet Gynecol. intellectual content: All authors. 2005;106(5, pt 2):1217-1219. Study supervision: Edwards.

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