JAMA CLINICAL CHALLENGE

CLINICIANS CORNER

Vulvar Swelling, Plaques, and Nodules in a Young Adult Woman

Figure 1. Swelling, plaques, and nodules on the patients vulva and perianal region

Shu-li Li, MD Chunying Li, MD, PhD 26-YEAR-OLD WOMAN PRESENTS WITH 5 WEEKS OF VULVAR SWELLING, PRURITUS, and progressively enlarging vulvar plaque accompanied by 2 months of occasional constipation and recurrent bloody, mucoid diarrhea. She has no history of anogenital warts and is monogamous with her husband. She has had no blood transfusions, contact with trichloroacetic acid, spermicides, or any other toxic agents or irritants. Physical examination reveals bilateral purple swelling of the labium majora and multiple moist, edematous, 1- to 8-mm wart-like skin nodules on the perineal and perianal surfaces (FIGURE 1). A 2-mm ulcer is observed inside the right labium minus. Digital rectal examination shows bloody mucus mixed with loose stool. White blood cell count is normal (4 109/L), as is neutrophil count (2.07 109/L); hemoglobin level is slightly decreased (10.2 g/dL). Erythrocyte sedimentation rate is 71 mm/h (reference range, 0-20 mm/h), and C-reactive protein level is 28 mg/L (reference range, 0-5 mg/L). Bacterial and fungal swab cultures from the ulceration are negative. Vaginal and urethral swabs are negative, with moderately increased polymorphonuclear leukocytes. Results of serologic testing for Treponema pallidum and human immunodeficiency virus are negative.

What Would You Do Next? A. Obtain a biopsy of the lesion for pathological examination B. Perform human papilloma virus detection from the lesion C. Perform laser therapy D. Prescribe topical steroids See www.jama.com for online Clinical Challenge.

Author Affiliations: Department of Dermatology, Xijing Hospital, The Fourth Military Medical University, Xian, Shaanxi, China. Corresponding Author: Chunying Li, MD, PhD, Department of Dermatology, Xijing Hospital, The Fourth Military Medical University, No 127 of West Changle Rd, Xian, Shaanxi, 710032, China (lichying@fmmu.edu.cn). JAMA Clinical Challenge Section Editor: Huan J. Chang, MD, Contributing Editor. We encourage authors to submit papers for consideration as a JAMA Clinical Challenge. Please contact Dr Chang at tina.chang@jamanetwork.org. 2596 JAMA, June 26, 2013Vol 309, No. 24

2013 American Medical Association. All rights reserved.

Downloaded From: http://jama.jamanetwork.com/ by a Marshall University User on 09/01/2013

JAMA CLINICAL CHALLENGE

Diagnosis Vulvar Crohn disease What to Do Next A. Obtain a biopsy of the lesion for pathological examination The key clinical feature is the association of multiple vulvar lesions with gastrointestinal tract dysfunction. The bloody, mucoid diarrhea is consistent with Crohn disease, and the concomitant vulvar lesions raise the suspicion of vulvar Crohn disease. A skin biopsy would support the diagnosis and, more importantly, would distinguish it from other diseases with similar presentation, including a fistulizing diverticulitis, flat condyloma of secondary syphilis, condylomata, sarcoidosis, and tuberculosis. Discussion Cutaneous manifestations of Crohn disease are reported in Hispanic (9.1%13%), African American (2.6%13.5%), and Asian (0%-3.2%) populations.1 Vulvar involvement in these patients is unusual. It can occur in children or adults; approximately 0.3% of Crohn disease cases in females may develop into vulvar dysplasia or carcinoma.2 Vulvar Crohn disease most commonly presents as swelling, edema, ulcers, pain, and erythema.2-4 Skin tags, fissures, fistulae, and abscesses, frequently seen in the perianal region, are less common in vulvar disease.3-5 There is no association between the appearance of vulvar lesions and intestinal Crohn disease activity.2,4 In approximately 25% of cases, vulvar Crohn disease precedes the onset of gastrointestinal tract involvement.2 The diagnosis of vulvar Crohn disease is often delayed because it is rarely included in the differential diagnosis of vulvar lesion, owing to its variable and atypical clinical presentations. Skin biopsy is important because it establishes the diagnosis and rules out other differential diagnoses. Vulvar Crohn disease is established by the presence of noncaseating granulomas with dermal lymphocytic and

Figure 2. Histopathology of the vulvar nodule. A, Noncaseating epithelioid granulomas in the dermis (hematoxylin-eosin, original magnification 20). B, The granulomas were composed of multinucleated giant cells and a cellular infiltrate of lymphocytes and plasma cells (hematoxylin-eosin, original magnification 400).

plasmocellular infiltration. 6 Ulceration, eosinophil infiltration, and vasculitis may be present.6 Care should be taken to look for lymphatic lesions and high-grade dysplasia or carcinoma.2 It is necessary to exclude other diseases, such as tuberculosis, sarcoidosis, and fungal infections, and venereal diseases such as syphilis.6 Medical therapy for vulvar Crohn disease consists of metronidazole alone or in combination with ciprofloxacin.4 Corticosteroids, the 5-aminosalicylic acid drugs, immunosuppressants, infliximab, or adalimumab are alternative treatments for vulvar and perianal Crohn disease.4,7 Surgery may be advisable for abscess and fistula or when medical treatment has failed.5,7 Patient Outcome Biopsy specimens taken from the vulvar papule showed granulation tissue with noncaseating, epithelioid granulomas in the dermis reaching very close to the epidermis (FIGURE 2A). The granulomas were primarily composed of multinucleated giant cells and a nodular and diffuse infiltrate rich in lymphocytes and plasma cells (Figure 2B). Results of tuberculosis testing (polymerase chain reaction and acid-fast staining) of the tissues were negative. Colonoscopy revealed macroscopic features of Crohn disease, with a cobblestone-like appearance of the descending and sigmoid colon mucosa along with strictures and proctitis. Co-

lonic tissue biopsies showed nonspecific acute-on-chronic inflammation, hyperplastic granulation tissue with poorly formed granulomas, and noncaseating necrosis. The patient was treated with mesalazine in combination with a hydrocortisone enema for 2 weeks, followed by oral mesalazine for 2 months. Her vulvar lesions and gastrointestinal symptoms significantly improved after treatment.
Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Additional Contributions: We thank Zheyi Han, MD, PhD (Xijing Hospital of Digestive Disease, The Fourth Military Medical University), for her help in evaluating the gastrointestinal condition. We also thank the patient and her guardian for providing permission to publish the information. REFERENCES 1. Hou JK, El-Serag H, Thirumurthi S. Distribution and manifestations of inflammatory bowel disease in Asians, Hispanics, and African Americans: a systematic review. Am J Gastroenterol. 2009;104(8):2100-2109. 2. Foo WC, Papalas JA, Robboy SJ, Selim MA. Vulvar manifestations of Crohns disease. Am J Dermatopathol. 2011;33(6):588-593. 3. Selim MA, Hoang MP. A histologic review of vulvar inflammatory dermatoses and intraepithelial neoplasm. Dermatol Clin. 2010;28(4):649-667. 4. Amankwah Y, Haefner H. Vulvar edema. Dermatol Clin. 2010;28(4):765-777. 5. Sandborn WJ, Fazio VW, Feagan BG, Hanauer SB; American Gastroenterological Association Clinical Practice Committee. AGA technical review on perianal Crohns disease. Gastroenterology. 2003;125(5): 1508-1530. 6. Emanuel PO, Phelps RG. Metastatic Crohns disease: a histopathologic study of 12 cases. J Cutan Pathol. 2008;35(5):457-461. 7. Van Assche G, Dignass A, Reinisch W, et al; European Crohns and Colitis Organisation (ECCO). The second European Evidence-based Consensus on the Diagnosis and Management of Crohns Disease: special situations. J Crohns Colitis. 2010;4(1):63-101. JAMA, June 26, 2013Vol 309, No. 24 2597

2013 American Medical Association. All rights reserved.

Downloaded From: http://jama.jamanetwork.com/ by a Marshall University User on 09/01/2013