Xeroderma pigmentosum Q82.1

Authors: Prof. Dr. med. Peter Altmeyer, Prof. Dr. med. Martina Bacharach-Buhles

All authors of this article

Last updated on: 24.11.2022

Dieser Artikel auf Deutsch

Synonym(s)

atrophodermia pigmentosa (Crocker); Light shrink skin; Lioderma essentialis congenita (Auspitz); Melanosis lenticularis progressive; Moonlight Sickness; OMIM 278700; OMIM 278720; OMIM 278730; OMIM 278740; OMIM 278750; OMIM 278760; OMIM 278780; OMIM 610651

History
This section has been translated automatically.

Kaposi, (1863)1882 - Comment: Moriz Kaposi described the first patient with dry skin and pigmentary disorders in 1863. It was not until 20 years later that the term "xeroderma pigmentosum" was coined. In 1968, it was demonstrated by James Cleaver that the cells of these patients had a defect in DNA repair genes, the nucleotide excision repair (NER) system.

Definition
This section has been translated automatically.

Rare, genodermatosis with abnormal response of the skin to UV radiation with premature development of senile skin and formation of malignant skin tumors as a result of disruption of DNA repair in process of nucleotide excision repair (NER). This repair mechanism repairs major DNA damage caused by UV radiation.

Classification
This section has been translated automatically.

Depending on the defect of the excision repair mechanism, 8 complementation groups are distinguished: type A-G (see table).

Clinical manifestations in the individual types (XP-A - XP-V) of Xeroderma pigmentosum (XP) (varies according to Herouy et al.)
Types Dermatological symptoms Dermatological tumors Neurological symptoms Ocular symptoms
XP-A

+++

SK

++

++

XP-B

+++

SK/B

+

++

XP-C

+

SK/B

+

-

XP-D

++

MM

++

+

XP-E

+

B

-

-

XP-F

++

SK/B

+

-

XP-G

++

SK/B

+

-

XP-V

+

B

-

-

KS = carcinoma, spinocellular; B = basal cell carcinoma; MM = malignant melanoma; + = mild; ++ = moderate; +++ = severe

Occurrence/Epidemiology
This section has been translated automatically.

Worldwide occurrence; all ethnicities; incidence in Europe and North America approximately 1/250,000 population/year, in Japan approximately 1/22,000 population/year. The parents of XP patients are obligate carriers of a mutation in one of the XP genes.

Etiopathogenesis
This section has been translated automatically.

Autosomal recessive inherited disorder of the nucleotide excision repair system. The mutations are distributed among different genes on different chromosomes.(XP-A: 9q22; XP-B: 2q21, XP-C: 3p25; XP-D: 19q13; XP-E: 11; XP-F: 19q13; XP-G: 13q32; XP-V: 6p12-21).

Thus, there is a so-called heterogony of a phenotype, i.e. mutaions in versch. (XP-A / XP-G as well as the VXP-V gene polymerase), which trigger an identical phenotype. The individual gene segments encode repair proteins involved in different substeps of the nucleotide excision repair system.

Affected repair systems in xeroderma pigmentosum and their original function (varied n. Herouy et al.)
Repair proteins Function
XP-A, XP-C, XP-E DNA damage recognition
XP-B, XP-D helicase, local despiralization of DNA
XP-G, XP-F Incision of the DNS
XP-V Polymerase

In XP-V, in contrast to the other variants, there is a defect in the DNA polymerase.

Manifestation
This section has been translated automatically.

Earliest childhood: 6 to 18 months of age, for type E only 6 to 9 years of age. No gender preference, manifestation of malignant tumours in the 2nd to 20th year of life.

Clinical features
This section has been translated automatically.

Acute early clinical leading symptom: At first, only the severe sensitivity to sunlight is impressive, which is already noticeable in the first weeks of life. However, XP-C, XP-E XP-V patients can also tan without sunburn. All other types are characterized by severe sunburn with blistering even behind glass panes during the first sun exposure. After exposure to the sun, regular healing takes place within 4-6 days with scaling and formation of light brown to black, ephelid-like or lentiginous melanotic spots. The sensitivity to sunlight remains for the rest of the life.

Chronic sequelae (progression over years): poikiloderma, dyschromas and malignancies. Further: skin atrophy with eyelid ectropion and microstomy, keratosis actinica as cumulative long-term effects of (normal) sunlight exposure. Infestation of eyelids, conjunctiva, cornea and iris.

Malignancies of the skin; development of:

Neurological disorders: with about 20% involvement of the nervous system (especially type A, hyper- and areflexia). As the disease progresses, increasing inner ear hearing loss, speech, gait and balance disorders develop.

Miscellaneous: Typically more frequent caries development, less frequent development of leukaemia.

Laboratory
This section has been translated automatically.

Detection of the absence of endonuclease in fibroblast culture (also prenatally).

Histology
This section has been translated automatically.

Light-damaged cells in the epithelium, increased melanin deposition in the stratum basale. Pigment incontinence with intra- and extracellular pigment accumulation in the upper corium. The long term damage is according to the clinical constellation (tumor formation, lentiginous changes).

The pathological anatomical substrate of the neurological disorders is a primary neuronal degeneration with loss of neurons.

Diagnosis
This section has been translated automatically.

Suspected clinical diagnosis. Typical anamnesis and clinic with extreme sensitivity to sunlight already in the first days of life! The later poikilodermatic clinical picture is pioneering.

Human genetic examination with molecular genetic diagnostics.

Differential diagnosis
This section has been translated automatically.

  • A distinction must be made between the early infantile state, in which acute sun damage is at the forefront of the pathophysiological process. Only the later
  • Polymorphic light dermatosis: first manifestation much later (between 10 and 30 years of age). Women are affected about 10 times more frequently than men. No detectable pigmentation disorders, no increased carcinogenesis.
  • Lupus erythematosus, more systemic: "butterfly erythema" as persistent, blurred erythema on the face. Furthermore, erythemato-papulo-vesicular foci, pityriasiform, firmly adhering scaling or atrophy occur. The light reaction will rarely occur as acute "Dermatitis solaris" but only after a time delay of days. Histology, immunohistology and serology are conclusive.
  • Urticaria pigmentosa: Here the signs of excessive light sensitivity are generally absent. Discovered in infancy rather as an "accidental finding". Darian sign positive in Urticaria pigmentosum. No increased carcinogenesis. Histology is conclusive.
  • Peutz-Jeghers syndrome (important DD): No excessive sensitivity to light. Perioral and also periorbital lentigines are typical in early childhood; intestinal polyps in adolescence. Lentiginosis also of the oral mucosa and the conjunctiva.
  • Hidroa vacciniformia: Sudden circumscribed erythema, usually a few hours after exposure to the sun, with formation of partially umbilical blisters up to 2.0 cm in size with serous or hemorrhagic content. Bowl-shaped, varioliform, often depigmented scars are characteristic. No pigmentation disorders; no increased carcinogenesis.
  • Erythropoietic porphyria (CEP): onset in infancy, itching, burning, edematous erythema, vesicles, possibly haemorrhagic ulcerations. Formation of varioliform scars, severe mutilation, hyper- and depigmentation, scarred alopecia, sclerosis, hypertrichosis, hemolytic anemia, splenomegaly, red urine. Laboratory evidence: red urine, red fluorescence, uroporphyrin I highly elevated.
  • Goltz-Gorlin syndrome: very rare, poicilodermatic lesions and scars and pigmentation anomalies or pigmentation disorders. Characteristic extracutaneous manifestations are: skeletal involvement (90% of cases): syn- and polydactylia, hypo- and aplasia of fingers and toes.
  • FAMM Syndrome(Familial Atypical Multiple Birthmark and Melanoma Syndrome): Uniform clinic with multiple melanocytic nevi and malignant melanomas. Genetic detection of the gene mutation.
  • Progeria (Werner syndrome): Very rare syndrome of senescence. Occurs mainly between 20 and 30 years of age; not before 10 years of age. Postpubertal growth retardation with premature graying of the hair (20 to 30 years), regressive laryngeal changes (hoarseness) and complete atrophy of the subcutaneous fatty tissue in the distal tibia and in the entire foot area. Clinical premature senescence (bird face), lack of excessive light sensitivity and the poicilodermatic picture of XP.
  • Bloom Syndrome: Extremely rare clinical picture. Symptoms beginning in the 1st year of life. Androtrophy. Typical is a butterfly-shaped, teleangiectatic (reminiscent of lupus erythematosus) facial erythema. Intensification under the influence of sunlight, possibly blistering of the lips and eyelids. Often café-au-lait stains. Proportioned dwarfism with a final size of less than 150 cm. Frequent infections. Early development of neoplasia, especially lymphatic and myeloid leukaemias, lymphomas, carcinomas of the oral cavity and gastrointestinal tract.

General therapy
This section has been translated automatically.

Lifelong, absolute avoidance of UV rays by shifting the day-night rhythm. Complete physical and chemical sun protection (clothing, sun protection preparations). Skin check-ups in 3-6 month intervals. Specialist medical supervision of the patients. Genetic counselling!

External therapy
This section has been translated automatically.

Systematic light protection with application of all necessary measures.

Internal therapy
This section has been translated automatically.

Prophylactic success is described with the oral administration of retinoids: Acitretin (e.g. neotigason) or isotretinoin (e.g. isotretinoin-ratiopharm; acne normin) 0.5-2 mg/kg bw/day.

Cave! Due to high dosage often early incompatibilities (see AI or NW under Acitretin or Isotretinoin).

Operative therapie
This section has been translated automatically.

Timely surgical removal of malignant tumours already formed by means of excision, curettage, cryosurgery.

Progression/forecast
This section has been translated automatically.

The risk of developing skin tumors is increased 1000 times! Furthermore, XB patients have an increased risk of developing internal neoplasms (CNS tumors; sarcomas, leukemias, lung carcinomas - note: smoking - sun for the lungs! - leads to DNA damage (see below DNA repair), which is also repaired by the NER).

Note(s)
This section has been translated automatically.

Self-help group D (www.xerodermapigmentosum.de)

Literature
This section has been translated automatically.

  1. Berking C (2007) Photocarcinogenesis. dermatologist 58: 398-405
  2. Berneburg M, Krutmann J (2003) Xeroderma pigmentosum and related syndromes. dermatologist 54: 33-40
  3. Cox SE et al (1993) Prevention of skin cancer in xeroderma pigmentosum: the physician as advocate. J Am Acad Dermatol 29: 1045-1046
  4. Dupuy A et al (2015) DNA damage and gene therapy of xeroderma pigmentosum, a human DNA repair-deficient disease. Mutate Res 776: 2-8.
  5. Emmert S et al (2002) Relationship of neurologic degeneration to genotype in three xeroderma pigmentosum group G patients. J Invest Dermatol 118: 972-982
  6. Emmert B et al (2011) Xeroderma pigmentosum. dermatologist 62: 91-97
  7. Ettinger M et al (2017) Light protection for Xeroderma pigmentosum. dermatologist 68:359-363
  8. Fassihi H et al(2016) Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect. Proc Natl Acad Sci U S A 113:E1236-1245.
  9. Herouy Y et al (2003) Xeroderma pigmentosum: Moonshine children. JDDG 3: 191-198
  10. Kaposi M (1882) About Xeroderma pigmentosum. Medical Yearbooks (Vienna) 619-633
  11. Khatri ML et al (1992) Xeroderma pigmentosum. J Acad Dermatol 26: 75-78
  12. Kraemer KH et al (1987) Xeroderma pigmentosum. Cutaneous, ocular and neurologic abnormalities in 830 published cases. Arch Dermatol 123: 241-250
  13. Lindenbaum Y et al (2001) Xeroderma pigmentosum/cockayne syndrome complex: first neuropathological study and review of eight other cases. Eur J Paediatr Neurol 5: 225-242
  14. Lynch HT et al (1984) Xeroderma pigmentosum. Arch Dermatol 120: 175-179
  15. Moriwaki S, Kraemer KH (2001) Xeroderma pigmentosum--bridging a gap between clinic and laboratory. Photodermatol Photoimmunol Photomed. 17: 47-54
  16. Moriwaki S (2016) Human DNA repair disorders in dermatology: A historical perspective, current concepts and new insight. J Dermatol Sci 81:77-84.
  17. Poblete-Gutiérrez P et al (2006) Hereditary photodermatoses. Dermatologist 57: 1067-1082
  18. Stone N et al (2000) Xeroderma pigmentosum: the role of phototesting. Br J Dermatol 143: 595-597

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.