9 October 2012

Pedro Vieira Baptista

Portugal

No conflicts of interest to declare

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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Vieira-Baptista P, 2012, unpublished data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Vieira-Baptista P, 2012, unpublished data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