Xeroderma pigmentosum

Kaposi 1874

Moonlight disease, XP, atrophodermia pigmentosa (Crocker), light-shrinking skin, lioderma essentialis congenita (Auspitz).

Autosomal recessive inherited genodermatosis in which disruption of the nucleotide excision repair system leads to the expression of multiple tumours, premature skin ageing, neurological and ocular diseases.

• Worldwide
• Affects all breeds
• Incidence: 1/250'000/year (Europe)
• Prevalence: 1/1,000,000 (worldwide)
• Patients' parents are obligate mutation carriers in one of the XP genes
• Occurrence already in childhood, first manifestation at ½ - 1 ½ yrs.
• Females = males
• Tumours can show as early as 2 yrs

• Depending on the subtype, there is a different enzymatic defect in DNA repair, which leads to increased sensitivity, especially to UVB. There is an accumulation of somatic mutations in the course, which trigger cutaneous neoplasia.

• 7 complementation groups A-G as well as XP variant (V)

• Neurological changes
  • In approx. 20%
    • DeSanctis-Cacchione syndrome [1932]
      • Complementation group A patients
      • Severe mental retardation
      • Dwarfism
  • Ocular changes
    • In approx. 40%
    • Keratoconjunctivitis with photophobia, corneal ulceration, ocular neoplasia.
  • XP-A
    • Dermatological symptoms ↑↑↑
    • Mostly there is expression of spinocellular carcinoma
    • Neurological symptoms ↑↑
    • Ocular symptoms ↑↑
  • XP-.B
    • Dermatological symptoms ↑↑↑
    • Mostly there is expression of basal cell carcinoma and spinocellular carcinoma
    • Neurological symptoms ↑
    • Ocular symptoms ↑↑
  • XP-.C
    • Dermatological symptoms ↑
    • Mostly basal cell carcinomas and spinocellular carcinomas occur
    • Neurological symptoms ↑
    • Ocular symptoms -.
  • XP-D
    • Dermatological symptoms ↑↑
    • Mostly malignant melanomas
    • Neurological symptoms ↑↑
    • Ocular symptoms ↑
    • XP-.E
      • Dermatological symptoms ↑
      • Mostly basal cell carcinoma expression
      • Neurological symptoms -
      • Ocular symptoms -
    • XP-F
      • Dermatological symptoms ↑↑
      • Mostly there is expression of basal cell carcinoma and spinocellular carcinoma
      • Neurological symptoms ↑
      • Ocular symptoms -
    • XP-.G
      • Dermatological symptoms ↑↑
      • Mostly there is expression of basal cell carcinoma and spinocellular carcinoma
      • Neurological symptoms ↑
      • Ocular symptoms -.
    • XP-V
      • Dermatological symptoms ↑
      • Mostly there is expression of basal cell carcinoma
      • Neurological symptoms -
      • Ocular symptoms -

• Histories
  • UV sensitivity (sunburns)
• Clinical diagnosis
• Laboratory
  • Determination of complement types
    • Detection of the absence of an endonuclease in fibroblast culture
  In specialised centres:
  • Measurement of fibroblast survival post-UV exposure
  • Measurement of DNA repair capacity
  • Prenatal diagnosis. in specialised laboratories

Especially sun-exposed areas.

• ↑ or reduced melanin incorporation (Str. basal, dermal pigment incontinence)
• Solar elastosis
• Teleangiectasia
• Changes corresponding to actinic keratoses, BCC, SCC and MM (in XP-D)

General measures

• UV protection (risk of suffering from skin cancer is increased 1000-fold)
• Genetic counselling
• Psychological care
• No nicotine consumption (the pulmonary immunological repair mechanisms are also disturbed in this case)

Prophylaxis

• Acitretin p.o
  • Initial: 0.5 mg/kg bw 1x tgl.
  • Maintenance dose: 0.1-0.2 mg/kg bw 1x tgl.
• Isotretinoin p.o. 0.5-2 mg 1x tgl.

Surgical measures

• When cutaneous neoplasia
occurs

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