What are the treatment and prevention strategies for a patient with Xeroderma pigmentosum?

Xeroderma Pigmentosum: Treatment and Prevention Strategies

Patients with Xeroderma pigmentosum require strict lifelong UV avoidance combined with intensive dermatologic surveillance every 3 months, as this is the only proven strategy to reduce their 10,000-fold increased risk of nonmelanoma skin cancers and 2,000-fold increased risk of melanoma. 1, 2

UV Protection: The Cornerstone of Management

Complete UV avoidance is non-negotiable and directly impacts mortality. 1, 2 This requires:

• Eliminate all UV exposure from both outdoor (UVA and UVB) and indoor sources, including uncovered fluorescent lights 1
• Use UV meters to measure and identify all UV sources in the home, school, and workplace environments that need replacement 1
• Apply high SPF sunscreen to all exposed skin surfaces daily, regardless of indoor/outdoor status 1
• Wear UV-protective clothing, hats, and UV-blocking glasses whenever outside 1
• Install UV-resistant films on all windows in home and vehicles 1

The American Academy of Dermatology emphasizes that screening effectiveness is entirely dependent on pairing it with these UV minimization strategies. 1, 2

Mandatory Surveillance Protocol

Dermatologic examination every 3 months is required starting from diagnosis, as the median age of nonmelanoma skin cancer diagnosis is 9 years (range 1-32 years). 1, 2

Ophthalmologic and oral examinations by specialists at least twice yearly to detect ocular tumors, keratitis, and oral cancers early. 1, 2

Otolaryngology monitoring for progressive sensorineural hearing loss, which occurs in approximately 25% of patients. 1, 2

Neurology assessment for cognitive impairment, neuropathy, and contractures, particularly in patients with XPA variants who commonly develop neurologic symptoms. 1

For patients with XPC variants specifically: CBC once or twice yearly and annual bone marrow examination due to >1,000-fold increased risk of AML. 1

Nutritional Management

Vitamin D supplementation is mandatory due to complete sun avoidance, which would otherwise cause severe deficiency. 1

Endocrinology consultation for monitoring and managing vitamin D levels and potential endocrine complications. 1

Treatment of Skin Lesions

For actinic keratoses and premalignant lesions:

• Cryotherapy remains first-line for discrete lesions 3
• Topical 5-fluorouracil for field treatment of multiple actinic keratoses 3, 4
• Topical imiquimod as an alternative immunomodulator 3, 4
• Chemical peeling, CO2 laser resurfacing, or fractional laser therapy for extensive involvement 3

For established skin cancers:

• Surgical excision is the gold standard for basal cell carcinoma, squamous cell carcinoma, and melanoma 3
• Mohs surgery for high-risk or recurrent tumors 5
• Photodynamic therapy can be used for multiple superficial lesions, though carries risk given UV sensitivity 3, 4

Research suggests topical podophyllin 25% may be effective for keratoacanthoma and small skin cancers, though this is not yet standard practice. 5

Chemoprevention Strategies

Oral isotretinoin can reduce the rate of new skin cancers, though requires monitoring for side effects. 3, 4

Oral nicotinamide shows promise in reducing actinic keratoses and nonmelanoma skin cancer rates. 3

Topical imiquimod or 5-fluorouracil can be used prophylactically in high-risk areas. 3, 4

Critical Pitfalls to Avoid

Never use standard myeloablative chemotherapy dosing if cancer treatment is needed—XP patients require dose-reduced regimens and avoidance of DNA-damaging agents due to extreme sensitivity. 2

Do not delay dermatologic surveillance even if the patient appears to be adhering to UV protection—skin cancers develop despite best efforts. 1

Avoid photodynamic therapy and laser treatments unless absolutely necessary, as these can cause severe reactions in XP patients despite theoretical benefits. 3, 4

Multidisciplinary Care Coordination

Centralized centers of excellence should be involved directly or through consultation, as XP requires coordinated care across dermatology, ophthalmology, otolaryngology, neurology, endocrinology, and nutrition. 1

Psychosocial support is essential to ensure adherence to the demanding UV avoidance measures required for survival. 1

Family resources: Direct patients to the Xeroderma Pigmentosum Society (www.xps.org) for patient education and support. 1