Conflicts of interest. Genital Lichen Planus. Objectives. Lichen Planus. Genital Lichen Planus. Author Up To Date. Vulvar Lichen Planus Patterns
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1 Genital Lichen Planus Lynette J. Margesson MD FRCPC AAD Washington Mucous Membrane Symposium Saturday, March 2, 2019 Conflicts of interest Author Up To Date Little evidence based treatment Too few studies done in vulvar disease. Most treatments discussed are off-label Objectives 1. Diagnose genital lichen planus 2. Choose the best treatments 3. Locate more in depth information Lichen Planus Autoimmune or cutaneous hypersensitivity reaction Onset years Affects - Skin, scalp, nails Mucous membranes - oral, genital, anus esophageal, urinary tract 1-3 % SCC in genital area Always Examine the Genital Area & Mouth Genital Lichen Planus Women: vulva and/or the vagina Mostly have erosive disease; red, raw surface Lacy white pattern is less common than in the mouth Labia minora often lost; vaginal stenosis Vulvar Lichen Planus Patterns Variable and can be mixed - Can have normal vulva and active vaginal LP Erosive 85% Lacy 10% Hypertrophic 4% Men: glans, prepuce and shaft of the penis Seldom have erosive disease Therefore little structural damage Red papules, plaques and lacy white pattern 1
2 Hypertrophic Vulvar LP Path VIP LP Clinical subtypes: Differential Diagnosis: -Lichen simplex chronicus -Lichen sclerosus -Psoriasis -Extra mammary Paget s Papular Reticular Plaque-like Atrophic Hypertrophic Erosive Bullous variants Classic and Hypertrophic Vulvar Lichen Planus. Day T, J Low Genit Tract Dis Oct Lichen Planus Vulvar Lichen Planus Symptoms: On vulva, vagina, mouth often erosive Sore, burn, %, severe 35% Itch 50-60% Dyspareunia 60-70% Apareunia 30-40% Dysuria Asymptomatic % On vulva typically non descript erosions with itching, burning, irritation and sexual dysfunction 10 times less common than LS A cause of asymptomatic scarring Vaginal Lichen Planus Erosive Vulvovaginal LP Deep red erosions, glazed erythema with thin gray edge Fern-like or lacy white pattern Variable scarring / loss of architecture Pain plus burning Often asymptomatic Inflammatory Vaginitis With mucopurulent vaginal discharge yellow, green, bloody Narrowed and / or shortened vagina Ring stenosis or total occlusion work with gynecology and examine vagina Vaginal involvement in genital erosive lichen planus. Helgesen AL et al, Acta Obstet Gynecol Scand Jul;89(7):
3 Diagnosis of Lichen Planus For Diagnosis: Morphology Biopsy - Perilesional Site Number 1-2 size 3-4 mm H&E Onset gradual, chronic Location Correlate with biopsy that can be reported as lichenoid Pathology often non specific Erosive vulval lichen planus Lewis FM, Bogliatto F. Eur J Obstet Gynecol Reprod Biol Dec;171(2):214-9 Lichen Planus + Squamous cell carcinoma Do more than 1 biopsy Concurrent conditions DIF 56% shaggy fibrin,plus IgG, IgM, IgA, C3 at DEJ Kulthanan K, Jaimtom S, Varothai S et al. Direct immunofluorescence study in patients with lichen planus. Int J Dermatol Dec;46(12): Genital Lichen Planus Differential diagnosis: Lichenoid drug reactions Lichen Sclerosus Psoriasis Lichen Simplex Chronicus Vesiculobullous disorders (ie PV, BP, BMMP, LABD) Graft vs Host Disease Squamous Cell Carcinoma Connective tissue disease (ie SLE, DLE) Erythema multiforme Epidermolysis bullosa acquisita LS MANAGEMENT PRINCIPLES LP DDX Lichen Sclerosus Cicatricial Pemphigoid Drug reaction Graft vs Host Pemphigus EM Explanation of the disease process, treatments, expectations Handouts Photographs Treat all factors Cicatricial Pemphigoid 3
4 Diagnostic Work-up for Genital Lichen Planus Punch biopsy: H & E, DIF studies Hepatitis C serologies and liver enzymes Discontinuation of any suspected drugs Referral to gynecologist for vaginal assessment Endoscopic examination, if indicated Clinical surveillance for malignant transformation Lichen Planus Treatment Confirm diagnosis biopsy - Stop irritants - Educate patient - Stop scratching - Control infection - Stop meds associated with lichenoid of fixed eruptions mimicking LP if appropriate Control inflammation - - Topical, intralesional, vaginal or systemic corticosteroids - topical calcineurin inhibitors Lichen Planus Treatment Topical therapy Topical/IL, vaginal steroids Topical immunomodulators Topical retinoids Systemic medications Topical Steroids for Genital LP Clobetasol, halobetasol ointment - use daily on non- keratinized skin until controlled. - for keratinized skin and perianal- 2-3 weeks and taper - if burning use Triamcinolone 0.5% ointment - slow or very thick add tazarotene 0.1% cream 2-5 times a week - lack of estrogen add estradiol 0.01% cream daily - add / substitute tacrolimus ointment if possible can be used in vagina 1 gm applicator full hs (No safety data!) Symptom control up to 90% Remission possible No Compliance Effectiveness of LP Treatment Clobetasol Ointment - 3 months - 94% improved and 71% symptom free on Rx In another study with a triamcinolone mix - - erosions healed in 50% - remission in 9% Overall 30% may not respond?? Maintain on least potent corticosteroid Intravaginal Corticosteroids Hydrocortisone base or acetate: Dose depends on severity - suppository 25mg (available) or mg (compounded) - 10% compounded vaginal cream, 1-5g per dose ( mg/dose) - Use nightly for 14 days then Mon Wed Fri - use with dilators prn - Note: risk of adrenal suppression and candidiasis Intralesional Triamcinolone to 10 mg/ml after local anesthesia - for refractory areas 4
5 Topical Immunomodulators steroid sparing - pimecrolimus (Elidel) 1% cream bid for mild LP - topical tacrolimus (Protopic) 0.03%, 0.1% ointment bid - vaginal tacrolimus hs 2 mg suppositories or 0.1% vaginal cream 1-2 gms = 1-2 mg/dose Systemic Therapy for Genital LP - Use if severe or topicals not effective in 4-6 months do not wait too long - Systemic corticosteroids and cyclosporine usually effective quickly - Most others take 2-3 months to start working Note use after control with topical steroid - all can burn Systemic Therapy for Genital LP Triamcinolone IM Prednisone Hydroxychloroquine 200 mg bid Methotrexate mg/week PO or SC + folate Mycophenolate mofetil 500mg g bid Cyclosporine 4-5 mg/kg/d 3-4months Azathioprine mg/d to bid Acitretin (10 mg 5-7 d/wk) Adalimumab Prednisone for Severe, Chronic, Recalcitrant LP Tapered dose of 40 to 60 mg/d over 1-3 weeks Cumulative dose of mg Indications Dose am with food - 40 mg 4-5d, 30 mg 4-5d, 20 mg 5d, 10 mg 5d - 60mg 2d, 50 mg 2d, 40 mg 4d, 30 mg/4d, 20 mg 4d, 10 mg 4d Consider 1 to 2 repeat courses 4-6 weeks apart Consider combination with steroid sparing agent Do not inject into fat Use 1.5 inch (38mm) Needle On a 3cc syringe Intramuscular (IM) Triamcinolone 40 mg/ml gluteus muscle If obese rectus femoris muscle 1mg/kg up to 80 mg/dose 3-4 doses/year tricepts muscle Site for IM injection Results of fat injection Poor absorption Fat Atrophy Mycophenolate mofitil Dosing: mg bid Starting dose: 500 mg Incremental increases by 500 mg over 6-8 weeks to 1.5 gm bid Reports of sustained remission Duration of therapy: minimum 1 year Intramuscular Triamcinolone: a safe, effective and underutilized dermatologic therapy. Robins DN. J Drugs Dermatol Jun;8(6):
6 Severe Lichen Planus Treatment Hydroxychloroquine 200 mg bid Methotrexate 5-15 mg/week PO or SC + folate Cyclosporine 4-5 mg/kg/d 3-4months Azathioprine mg/d to bid Acitretin (10-25 mg 5-7 d/wk) Adalimumab About 30-40% vulvovaginal LP need systemic Rx Surgery may be needed for reconstruction and cancer Treatment of Cutaneous Lichen Planus (Part 2): A Review of Systemic Therapies. Thandar Y, Maharajh R, Haffejee F, Mosam A. J Dermatolog Treat Nov 17:1-40 REBIOPSY Prior biopsy nonspecific Squamous Cell Carcinoma (in LS) Histiocytosis Dr Nina Madnani Vulvar Langerhan s Cell Histiocytosis Squamous Cell Carcinoma (in LP) Whole area firm In severe pain Risk of Cancer in Vulvar LP A small increased risk of vulvar malignancy in vulvar LP is suggested but more data needed In one cohort (mean follow-up of 72 months), 2.4% of patients with LP had a history of or current genital malignant neoplasm Another series of 100-3% had vulvar dysplasia SCC in vulvar LP aggressive Complications of Vulvovaginal Lichen Planus - Chronic pain, rarely itch vulva, vagina - Scarring variable Loss of labia minora, Clitoris - clitoral scarring, phymosis, buried clitoris, clitoral pseudocyst, hypo or supersensitivity Introital Scarring / narrowing Vaginal Scarring - partial, total, ring stenosis - Dysuria, rarely urethral stenosis - Vaginal discharge inflammatory vaginitis - Vulvar pain / sexual dysfunction and psychosexual problems - Squamous cell carcinoma Prognosis Waxes and wanes! Remission variable. Women often give up on treatment as too difficult with associated depression - poor QOL Comorbid Vulvar Lichen Planus and Lichen Sclerosus. Day T, Moore S, Bohl TG, Scurry J. J Low Genit Tract Dis Jul;21(3):
7 Vulvar LP - Why not Better Her Reasons Clobetasol too expensive Clobetasol ointment burns Treatment messy and not a cure Not using it anyway! Causes of Treatment Failure 1) Incorrect diagnosis was a biopsy done? 2) Missed concurrent conditions LS, LP, contact, Candida, HSV, estrogen loss, SCC 3) Ineffective treatment plan 4) Noncompliance poor education fear of topical steroids limited mobility Look for Concurrent Conditions Infection: Candida, Staph /Strep, HSV Rashes: Contact dermatitis Lichen Simplex Chronicus Mix LS and LP Cancer: SCC, VIN III Other: Lack of Estrogen, Trauma (scratching) All cause sexual dysfunction Summary for Genital LP 1) Look carefully at all skin and mucous membranes note subtle scarring. 2) Always check vulva and vagina in LP cases in women do not rely on history 3) Biopsy may be non- specific find an interested pathologist 4) Do not rely on topical treatment alone - use systemic treatment if needed 5) Recognize causes of treatment failure References Comorbid Vulvar Lichen Planus and Lichen Sclerosus. Day T, Moore S, Bohl TG, Scurry J.J Low Genit Tract Dis Jul;21(3): Vaginal involvement in genital erosive lichen planus.helgesen AL, Gjersvik P, Jebsen P, Kirschner R, Tanbo T.Acta Obstet Gynecol Scand Jul;89(7): Is Vulvovaginal Lichen Planus Associated With Squamous Cell Carcinoma?Day T, Otton G, Jaaback K, Weigner J, Scurry J.J Low Genit Tract Dis Apr;22(2): Unexpectedly high frequency of genital involvement in women with clinical and histological features of oral lichen planus. Di Fede O, Belfiore P, Cabibi D, De Cantis S, Maresi E, Kerr AR, Campisi G.Acta Derm Venereol. 2006;86(5): Lichen planus affecting the female genitalia: A retrospective review of patients at Mayo Clinic. References Fahy CMR, Torgerson RR, Davis MDP.J Am Acad Dermatol Dec;77(6): Treatment of Cutaneous Lichen Planus (Part 2): A Review of Systemic Therapies.Thandar Y, Maharajh R, Haffejee F, Mosam A. J Dermatolog Treat Nov 17:1-40 Classic and Hypertrophic Vulvar Lichen Planus.Day T, Weigner J, Scurry J.J Low Genit Tract Dis Oct;22(4): Interpretation of Nondiagnostic Vulvar Biopsies.Day T, Knight V, Dennerstein G, Pagano R, Scurry J.J Low Genit Tract Dis Jan;22(1): Erosive Lichen Planus. Mauskar MObstet Gynecol Clin North Am Sep;44(3): Pre- malignant nature of oral and vulval lichen planus: facts and controversies. Ramos-e-Silva M, Jacques CDMC, da Silva Carneiro SC. Clin. Dermatol. 2010; 28:
Conflicts of interest
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