Xeroderma Pigmentosum (XP) Sally Turner XP CNS Feb 27 th 2014 St. John’s Institute of Dermatology

Introduction What is Xeroderma Pigmentosum (XP)? How is XP inherited? Diagnosis of XP Symptoms What can we do? National XP Service

What is XP?  Dry (xeroderma) pigmented (pigmentosum) skin (1874)  Very rare (2.3 million per live births in UK)  Unable to repair DNA damaged by ultraviolet radiation (UVR)  Complementation groups XP-A to XP-G and XP variant depending on which genes/proteins in nucleotide excision repair pathway are affected.

infraredUVA UVB - sunburn and photocarcinogenesis

infraredUVA UVA – photocarcinogensis and photoageing UVAUVA

UV damages DNA

How is XP inherited? Genetic condition – from birth, not acquired “Spelling mistake” from both parents Recessive – can carry gene without having XP Autosomal – not linked to sex chromosome More common in cousin-cousin marriages Same parents have 1 in 4 chance of each child having XP

Main Signs and Symptoms  Skin 50% easy sunburn, freckling from early age, skin cancers: >10,000 fold increase non melanoma on exposed sites, 2000 fold increase melanoma.  Eye problems: 40%  Neurological problems: 20-30%  Prognosis varies - main causes of death malignant skin cancer and neurological degeneration

Diagnosis of XP Punch skin biopsy from non sun-exposed site (usually buttock, local anaesthetic) Sample sent to University of Sussex Results take 2-3 months blood test for DNA analysis Pre-natal options for families 2468

Skin  50% easy, severe sunburn (takes longer to recover)  Freckling from early age (especially before age 2) on sun-exposed sites  Skin cancers SCC, BCC, Melanomas

hours days Sunburn NORMAL SUNBURN SEVERE AND EXAGGERATED SUNBURN IN XP

Not all cases of XP present with exaggerated sunburn reaction ~50% present with increase freckling but no photosensitivity

Eyes  40% with XP have eye problems  photophobia  eye surface problems (dryness)  eye cancer (but not as common as skin cancer)

What can we do? Protect eyes from UVR Eye drops (if prescribed) Observe eye discomfort / symptoms Wear glasses

UVR and Photoprotection WHO/SDE/OEH/ Suggested that all patients diagnosed with XP should practice complete protection from UVA and UVB – This is challenging for many.

Photoprotection Complete avoidance of UV light on exposed skin Sun behaviour and lifestyle Clothing: hat, gloves, long sleeves Glasses / visor Sunscreen SPF 50+ and UVA protection (applied regularly) UV meter to check UVR levels

Sun Protective Clothing Weave structure and denier Good heavy weight natural fibres cotton, linen, denim. Darker colours, more dye= better protection Pre treated with UV inhibiting ingredients during manufacturing Laundry additives – can last up to 20 washes UPF (Ultraviolet Protection Factor). A fabrics ability to prevent transmission of UVR, UPF 50+ blocks 97.5% UVR

UV filters Window filter film UV Visor

Glass Window glass and car glass tends to block most UVB UVA transmission- depends on type of glass. 75.7% - 0% ( Duarte et al 2009)and colour of glass( Hampton et al 2004) Laminated glass has generally good UVA blocking properties, car windscreens. Grants available

Light Bulbs Any element heated to a sufficient temperature can produce some UVR Many variety of light bulbs,each individual in risk Health protection agency, compact fluorescent light (CFL) can emit UVR,some types should not be used closer 30cm for long periods. Better using double envelope saving bulbs for those with severe photosensitivity in UVA and B spectrum

Variety of Bulbs CFL Halogen Incandescent Light emitting diode (LED)Double envelope CFL Fluorescent

Brain and nerves  20-30% with XP have problems  poor hearing  loss of reflexes  loss of sensation in limbs  unsteady walk  memory loss

What can we do? Observe for any neurological signs Observe mobility, e.g. falls, and report to parents / health services Hearing aids if necessary Psychological support Communication between local services / educational support/social support.

National XP Service Based at St Thomas’ Hospital, London Only specialist centre in UK NSCT (National Specialised Commissioning Team now called NHS England) designated and funded from April 2010 Access to expert XP care for all patients around the country Shared care with local dermatologist Opportunity to take part in XP research XP specialist nurses – outreach work

XP multidisciplinary team  Dermatologist  Dermatology surgeon  Neurologist  Geneticist  Genome Scientist  Clinical Psychologist  Clinical Nurse Specialist  Administrator  Medical photographer  Histopathologist  Medical Physics  XP Support Group

Where do our XP patients live?

Role of the XP CNS Key worker for XP patients Organise all-day multi-disciplinary XP clinics Ensure equitable access to service Outreach visits to homes, schools, colleges Promote awareness of XP Develop patient pathways Patient information leaflets Research Service evaluation and development

XP Support group Set up by a parent (Sandra Webb)1999 Support for those affected by XP Website with information re XP Help with travel and hotel to attend clinic Presence in XP clinic Grants for UV protective equipment Funds for research Owl Patrol- yearly camp International links

How to contact us Sally Turner Clinical Nurse Specialist in XP Children (under 16) Tel: Mobile: Hermanus Louw Clinical Nurse Specialist in XP Adults (16 and over) Tel: Mobile:

Acknowledgements XP support group Hiva Fassihi Consultant Dermatologist, XP Clinical lead David McGibbon Consultant Dermatologist Hermanus Louw Adult XP CNS