9 October 2012
Pedro Vieira Baptista
Portugal
No conflicts of interest to declare
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PV
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Lichen
"(…) symbiotic relationship between thephotosynthetic (green alga orcyanobacterium; photobiont) and fungal(mycobiont) partnership (…)”
Lichenification"(…) classical term used to describe a
thickening of the skin and a morepronounced reticulate (…)”
“(…) is characterized clinically by apalpable thickening of the tissue andincreased prominence of skin markings.Scale may or may not be detectable (…)”
Esteves J, Baptista P et al, Tratado de Dermatologia, 1992
Lynch PJ, Moyal-Barracco M, Scurry J, Stockdale C. Dermatological Disorders: An Approach to Clinical Diagnosis, JLGTD, 16,(4), 2012
Piercey-Normore MD, Deduke C. Fungal farmers or algal escorts: lichenadaptation from the algal perspective. Mol Ecol. 2011 Sep; 20(18):3708-10
Lichen sclerosus
ISSVD 2006 Lichenoid pattern or Dermal homogenization/sclerosis pattern
ISSVD 2011 White lesions (4) with patches and plaques (B)
Older terms: Kraurosis vulvae (1885) Leucoplakia (1897) Vulvar dystrophy Lichen sclerosus et atrophicus Etc.
Introduction
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Bimodal distribution
Pre-pubertal
Post-menopausal
Epidemiology
0
5
10
15
20
25
30
35
40
Symptoms Diagnosis
Mean age±SD (years)Symptoms 53±16,3 Diagnosis 59±15,3
n=226
Vieira-Baptista P, 2012, unpublished data
Incidence Male:Female 1:6-10 1:70-1.000 (Friedrich EG Jr , 1976, Wallace HJ, 1971 Burrows LJ et al, 2010)
1:30 in older women (Jones RW at al, 2008)
Geographical variation? Rare in Africa vs underdiagnosed
Vulvar cancer less frequent in Asia than in Europe Probably due to less frequency of LS rather than HPV infection
Africans, Caribbeans and Asians underrepresented among LS patient in a London clinic
Epidemiology
Jacyk WK, Isaac F. Lichen Sclerosus et Atrophicus in Nigerians. Jour Nat Med Assoc, 71 (4), 1979
MacLean AB, Chan M, Ramos K. Why is There a Geographic Variation in LichenSclerosus and Vulval Cancer? XXI World Condgress of the ISSVD, Paris 2011
Real prevalence unknown!Up to 50% assymptomatic
A role for alimentary factors?
25% of symptomatic patients referred worsening with specific food
Epidemiology
n %
Worsening with foodPorkAcidic fruitFried foodSpicy foodVegetablesOthers
4322141311106
25%51%33%30%26%23%14%
Vieira-Baptista P, 2012, unpublished data
Symptoms
Presentation
n=192
n=3415%
8%
13%
28%
30%
75%
0 20 40 60 80 100 120 140 160 180
Asymptomatic
Discharge
Pain
Dysuria
Burning
Pruritus
Vieira-Baptista P, 2012, unpublished data
Signs
Presentation
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4%
7%
10%
12%
13%
15%
17%
19%
23%
23%
33%
34%
42%
47%
65%
75%
0 20 40 60 80 100 120 140 160 180
Pseudocysts
Isomorfic phenomenon
Ecchymosis
Oedema
Hyperpigmentation
Erosions
Stenosis
Perianal
Erythema
Figure of 8
Fissures
Hyperqueratosis
Cigarette paper
Hypopigmentation
Phymosis/paraphymosis
Atrophy
Vieira-Baptista P, 2012, unpublished data
Autoimmune disease
Birembaum DL et al, 2007
Simpkin S etal, 2007
Cooper SM et al, 2008
Vieira Baptista P, unpublished, 2012
Autoimmune disease - - 28,4% ** 23%
Thyroid disease 29,9% - 16,3% ** 25%
Alopecia areata - - 2,6% 4%
Vitiligo - - 10,5% 1%
Psoriasis - 17% - 5%
Rheumatoid arthritis - - 1,5% 4%
Crohn’s disease - - - 2%
Lupus - - - 1%
Auto-antibodies - - 21% -
Antithyroid - - 9% 25%
** Statistically significant
Autoimmune disease prevalence in the family 21-56%
Higher than in LS patients!
Data supports the screening for autoimmunedisease, specially thyroid disease.
Autoimmune disease
Harrington CI, Dunsmore IR. An investigation into the incidence of auto-immune disorders in patients with lichen sclerosus and atrophicus. Br J Dermatol May 1981;104(5):563-6
Powell J Wojnarowska F Winsey S et al. Lichen sclerosus premenarche: autoimmunity and immunogenetics. Br J Dermatol 2000 Mar; 142:481-4
Sexual (dys)function
n=226
With intercourse: 125
With dyspareunia: 64
Without dyspareunia: 59
Apareunia: 2Without
intercourse: 73
Unknown:
2863% have intercourse51% of these with dyspareunia<2% witn apareunia
Vieira-Baptista P, 2012, unpublished data
Diagnosis
Clinical history Examination DIAGNOSIS+
?
Biopsy
SymptomsMedicationWorsening factorsAssociated conditionsFamily history
Vulvar examinationSpeculum examinationSkin, nails, mouth
When to perform it? Differentiate LS from lichen planus Thickened epidermis/erosions/ulcerations/erythema (Jones RW et al, 2004)
Lack of response to the treatment Rule out VIN/carcinoma
Where to perform it? Transition from affected to normal skin Areas of ecchymosis or fine crinkling
Pitfalls of biopsy Treatment with topical steroids changes the typical histological appearance Biopsy taken in wrong places Insufficient clinical data given to the pathologist Pathologist without experience
Biopsy
LS associated with vulvar squamous cell carcinoma 5% risk – possibly overestimated
LS increases the 246-300x the relative risk of SCC
Extra genital lesions not associate with malignancy
60% of vulvar SCC develop in a background of LS
Incidence of vulvar cancer rising in the last years
Weaker association with: Melanoma (Friedman RJ et al, 1984)
Basal cell carcinoma (Meyrick Thomas RH et al, 1985)
Verrucous carcinoma (Brisgotti M et al, 1989)
LS and malignancy
Renaud-Vilmer C, Cavelier-Balloy, B, Porcher R. Vulvar Lichen Sclerosus: Effect of Long-term Topical Application of a Potent Steroid on the Course of the Disease. Arch Dermatol, Vol 140, June 2004
MacLean AB; Jones RW, Scurry J, Neill S. Vulvar Cancer and the Need for Awareness of Precursor Lesions. J Low Genit Tract Dis. 2009 Apr;13(2):115-7
LS and malignancy
Differentiated VIN
Usual type VIN
VULVAR CANCER
HPV
Lichen sclerosus
Walkden V, Chia Y, Wojnarowska F. The association of squamous cell carcinoma and lichen sclerosus; implications for follow up. J Obstet Gynecol 1997; 17: 551–3
Vilmer C, Cavelier-Balloy B, Nogues C et al. Analysis of alterations adjacent to invasive vulvar cancer and their relationship with the associated carcinoma: a study of 67 cases. Eur J Gynecol Oncol 1998; 19: 25–31.
60%
40%
Objectives:
1. Stop/control symptoms
2. Prevent anatomic distortion
3. Avoid progression to malignancy?
Management
Intimate hygiene Water Reduce frequency
Clothes Skirts or loose pants Natural fabrics
Underpants White Natural fabrics Not to use it at night
Tampons rather than sanitary napkins Avoid panty liners
Induce amenorrhea
Control/correct urinary incontinence and other irritant factors
Avoid scratching
Management
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There is no consensus on the schemes to be used in terms of duration or frequency
Testosterone, dihydrotestosterone and progesterone –without interest!
Ultrapotent topical corticosteroid are the first choice Cobetasol propionate 0,05% Betamethasone valerate 0,1% Ointment rather than cream
Less sensitizing More occlusive Better tolerated if fissures or erosions
Management
Chi CC, Kirtschig G, Baldo M, Brackenbury F, Lewis F, Wojnarowska F. Topical interventions for genital lichen sclerosus. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD008240
Initial management:
30 g of ointment should be enough
Maintenance therapy: Ultrapotent corticosteroids
Lowest dose that controls symptoms No more than 2-3 times/week Spend less than 60 g of ointment/year (Edwards L et al, 2011; Neill SM et al, 2002)
Lower potency corticosteroids
Management
Twice a weekEveryother dayEvery day
Month 3Month 2Month 1
Calcineurin inhibitors (pimecrolimus, tacrolimus)
Pimecrolimus vs clobetasol
Identical efficacy in the control of itching and burning Less efficacy in terms of improvement of the skin Less efficacy controlling inflammation No difference in terms of adverse effects
Second line treatment Non-responders to corticosteroids Intolerance to corticosteroids
Reactivation of HPV and HSV infections? Carcinogenesis?
Management
Goldstein AT, Creasey A, Pfau R, Phillips D, Burrows LJ. A double-blind, randomized controlled trialof clobetasol versus pimecrolimus in patients with vulvar lichen sclerosus. J Am Acad Dermatol. 2011 Jun;64(6):e99-104
Visits
Ideally, first visit should be one month after starting treatment (no lately than 3 months)
Visit at 6 months after first scheme of treatment
Visits at least once a year Vulvar cancer rare in diagnosed and treated patients with LS Progression from VIN to cancer occurs very quickly Ideally, patients should be assessed every 3 months!
Management
• Response to treatment•Correct application of the treatment• Superimposed infection•Corticosteroid atrophy• Identify suspect lesions
Others
Antihistamines (control itch, sedative effect)
Antidepressants/antiepileptic drugs (pain)
Topical anaesthetics (ex. lidocaine)
Topical estrogens
Lubricants and emollients
Treat secondary infections (mostly fungal infections)
Management
What to do with asymptomatic patients?
Some of them might have inactive disease (active disease in childhood?)
If hyperkeratosis, ecchymosis , fissures or progressive atrophy should be treated
Management
Neill SM, Tatnall FM, Cox NA. Guidelines for the management of lichen sclerosus. British Journal of Dermatology 2002; 147: 640–649
Other options
Oral retinoids (Bousema MT et al, 1994)
Triamcinolone (subcutaneous/ointment) (Mazdisnian F et al, 1999; LeFevre C, 2011)
Cryotherapy (Kastner U et al, 2003)
Photodynamic therapy/Psoralen plus UVA (Kroft EB et al, 2008)
Laser (Aynaud O et al, 2010)
Potassium para-aminobenzoate (Penneys NS et al, 1984)
Antimalarials (Wakelin SH et al, 1994)
Antibiotics (Shelley WB et al, 2006)
Management
Who should manage these patients?
Primary care? Simple cases
Gynaecologist/Dermatologist with training in vulvar disease1. Patients requiring potent corticosteroids more than 3x/week
2. Patients requiring more than 30 g of corticosteroids ointment in 6 months
3. VIN
4. (Hyperkeratosis or thickened skin – for biopsy)
Management
MacLean AB, Jones RW, Scurry J, Neill S. Vulvar Cancer and the Need for Awareness of Precursor Lesions. Journal of Lower Genital Tract Disease, Volume 13, Number 2, 2009, 115Y117
Management
Surgery
Benign conditions Pseudocysts: total or subtotal circumcision Phymosis/paraphymosis: circumcision; hydrodissection
Vulvar synecheae: lyses Stenosis: perineotomy, vulvoperineoplasty
Improvement of dyspareunia in 90% of cases
Malignant and pre-malignant conditions
Rouzier R et al. Perineoplasty for the treatment of introital stenosis related to vulvar lichen sclerosus. Am J Obstet Gynecol. 2002 Jan;186(1):49-52
Goldstein AT et al. Surgical treatment of clitoral phimosis caused by lichen sclerosus. Am J Obstet Gynecol. 2007 Feb;196(2):126.e1-4
Surgery - hydrodissection
Management
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Phymosis with apareunia
Treatment failure?
1. Non-compliance
2. Correct diagnosis, but associated /superimposed conditions
Candidosis, contact dermatitis, psoriasis, etc.
3. Secondary sensory condition
4. Anatomical distortion
Management