Xeroderma Pigmentosum (XP)

At a glance

A syndrome characterized by a defect in ultraviolet radiation-induced deoxyribonucleic acid (DNA) repair mechanisms and by a severe sensitivity to all sources of ultraviolet radiation (especially sunlight). XP is categorized into seven complementation groups according to the capacity of the body to repair DNA (XPA to XPG) and XPV (variant, second decade of life). The DNA damage is cumulative and irreversible. Skin, eyes, and nervous system affected depending on group. Major risk of skin cancers.

Synonyms

Xerodermic Idiocy; Kaposi Disease.

History

A group of rare autosomal recessive inherited disorders that were first described by Ferdinand Ritter von Hebra, Austrian dermatologist, and Moritz Kohn Kaposi, Hungarian dermatologist, in 1874.

Incidence

1:250,000 in general population; higher in Japan and Middle East (1:40,000).

Genetic inheritance

A rare autosomal recessive genetic defect.

Pathophysiology

Caused by a defect in nucleotide excision repair (NER), leading to an inability to repair DNA damaged by ultraviolet radiation. There are two types of NER: global genome (GG-NER) and transcription coupled (TC-NER). There are seven XP repair genes (XPA to XPG), with seven principal complementation groups of XP corresponding to defects (four other subcategories have been described). Frequency and severity varies among forms; XPA and XPC are the most common.

Diagnosis

Clinically evocated by the skin lesions with a three-stage evolution. Skin is normal at birth. After the age of 6 months, a diffuse erythema, scaling, and freckle-like areas of increased pigmentation, initially on the face can be seen. The second stage is characterized by poikiloderma and the third stage by the appearance of numerous malignancies. Diagnosis may be suspected and can be made during the first stage. It is confirmed in vitro and by a skin biopsy.

Clinical aspects

Normally, it involves the skin (photosensitivity, skin hypoplasia, increased patchy skin pigmentation, decreased or increased irregular skin pigmentation, hyperkeratosis, hemangioma capillary, telangiectasia skin, neoplasia), eyes (photophobia, optic disc atrophy, conjunctival telangiectasia, paresis of ocular muscles), and central nervous system (CNS) (more common in XPA and XPD: eg, abnormality, seizures, areflexia, cerebral cortex atrophy, microcephaly, deafness, and mental retardation). Other possible features include ectopic testes and teeth anomalies.

Precautions before anesthesia

Evaluate the neurological function (clinical, electroencephalogram, CT) and ocular lesions. Avoid radiographs because of photosensitivity.

Anesthetic considerations

Patient behavior in the operating room may be affected by photophobia. It is, therefore, recommended to dim the light. As with other dermatological illness, intraoperative padding (pressure points) and positioning is very important. Difficult airway management is possible because of skin atrophy, retractive scarring, and macroglossia. Difficult peripheral venous access.