Xeroderma pigmentosum ( XP Or Children of the Night )

Xeroderma pigmentosum, commonly known as XP Or Children of the Night
This is an inherited condition characterized by an extreme sensitivity to ultraviolet (UV) rays from sunlight.
It is rare disorder transmitted in an autosomal recessive manner, characterized by excessive sensitivity to sunlight (photosensitivity),  pigmentary(skin colour) changes, premature skin aging, and malignant tumor development.
Formerly called DeSanctis-Cacchione syndrome.

Xeroderma Pigmentosa (Picture Credit; witbanknews.)

Was first described in 1874 by Hebra and Kaposi.

With an incidence of 1:250,000 in the United States,
                                  1:40,000 population in Japan, (roughly 6 times more common in Japanese                                                                people than in others)
                                   approximately 100 diagnosed cases in the UK.

Affects all races, and found to be more common in Japan, North Africa, and the Middle East.
Both sexes are equally affected.
Usually detected at age 1-2 years.

Cause
Caused by mutations in genes that are involved in repairing damaged DNA. DNA can be damaged by UV rays from the sun and by toxic chemicals such as those found in cigarette smoke. Normal cells are usually able to fix DNA damage before it causes problems.
However, in people with xeroderma pigmentosum, DNA damage is not repaired normally. As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die.
Many of the genes related to xeroderma pigmentosum are part of a DNA-repair process known as nucleotide excision repair (NER)
When nucleotide excision repair (NER) enzymes undergo mutation, it leads to reduction in or elimination of NER and if this is unchecked, results in Mutation of the individuals cell DNA following exposure to ultraviolet light.

Patients who have XP, inherited two recessive xeroderma pigmentosum genes (one from each parent); If both parents are only carriers of the xeroderma pigmentosum trait (each have one xeroderma pigmentosum gene and one normal gene), they will not show signs or symptoms of the disease. By having the two xeroderma pigmentosum genes this causes the patients to have an extreme sensitivity to UV light and as a result experience a range of signs and symptoms of xeroderma pigmentosum.

There are 7 different types/groups of XP (XP-A to XP-G)


Signs and Symptoms
A history of severe persistent sunburn can be found in many patients.
no family history is present; the parents, being heterozygotes, are healthy.

XP (Picture Credit; dermaamin.)

 The disease usually progresses through 3 stages.

1.  The first stage occurs around 6 months after birth (skin appears normal at birth) with the following signs: Areas exposed to the sun such as the face show a reddening of the skin (diffuse erythema), scaling, and freckle like areas of increased pigmentation. appearing initially on the face. With progression of the disease, the skin changes appear on the lower legs, the neck, and even the trunk in extreme cases. While these  features tend to diminish during the months with decreased sun exposure, as time passes, these findings become permanent. Irregular dark spots may also begin to appear.

     2.  Continued sun exposure will lead to the second stage, which is characterized by poikiloderma.              This is where there are irregular patches of lightened or darkened skin        
           (mottled hyperpigmentation and hypopigmentation), a spider web-like collection of blood        spots and vessels are seen through the skin (telangiectasias) , and there is  thinning of the skin (skin atrophy).

     3. The third stage is the development of actinic keratoses and skin cancers (including squamous     cell carcinomas, malignant melanoma, basal cell carcinoma, and fibrosarcoma) . These may occur as early as age 4-5 years and are more prevalent in sun-exposed areas such as the face.

The photosensitivity in Xeroderma Pigmentosa maybe acute in nature (50% of cases).

Complications

Eye (Ocular) problems occur in nearly 80% of xeroderma pigmentosum patients.

    Eyes become painfully sensitive to the sun (photophobia).
    Eyes easily irritated, bloodshot and clouded. Conjunctivitis may occur.
    Non-cancerous and cancerous growths on the eyes may occur.(Eyelid solar lentigines,malignant melanoma, Ectropion, symlepharo,vascular pterygia, fibrovascular pannus etc)

Neurological problems occur in about 20% of xeroderma pigmentosum patients.

    These can be mild or severe and include;microcephaly, spasticity, poor coordination,developmental delay, deafness, and short stature. hyporeflexia, arefleixa, ataxia, chorea, segmental demyelination, sensorineural deafness, supranuclear ophthalmoplegia, and mental retardation. The neurologic problems might overshadow the cutaneous manifestations in some patients with xeroderma pigmentosum.
    May develop in late childhood or adolescence. Once they do occur they tend to worsen over time.


Diagnosis;
An eye exam may show:
    Clouding of the cornea
    Keratitis
    Lid tumors
    Blepharitis
The following tests can help diagnose the condition in a baby before the birth:
    Amniocentesis
    Chorionic villous sampling
    Culture of amniotic cells
The following tests can help diagnose the disorder after the birth of the child:
    Culture of skin fibroblasts
    Skin biopsy

Differential Diagnosis
Acute Lupus Erythematosus
Ataxia-Telangiectasia
Bloom Syndrome
Congenital erythropoietic porphyria
Cockayne's syndrome
Fanconi anemia
Hartnup disease
LEOPARD Syndrome


Treatment
   Prevention is the most important part of treatment here.Restricting outdoor activities to night time,

Sunscreen for XP (Picture Credit; look for diagnosis.)

•    Sunscreens; Physical sunscreens (protective clothing, hats, eyewear))which scatter and reflect  radiation. They contain large particles,such as titanium dioxide, zinc oxide, red ferric oxide,  talc and kaolin .  Chemical sunscreens absorb UV radiation; PABA esters, salicylates, and cinnamates, mainly block UV-B. Broad-spectrum chemical sunscreens include a combination of ingredients designed to block both UV-B and UV-A.

•    Genetic counseling

       Support and counseling for patients and families, because of the severe lifestyle restrictions
             involved.

•     Avoid smoking, because cells from individuals with XP are also hypersensitive to environmental mutagens, such as benzo(a)pyrene found in cigarette smoke.

  Drug;

•     Vitamin D supplements may be needed, since sunlight (a major source of vitamin D) is excluded.

•     Emollients for dry skin.

•     Artificial tears for dry eyes.

•     Oral retinoids have been shown to decrease the incidence of skin cancer in patients with xeroderma pigmentosum

•     5-fluorouracil may be useful for actinic keratose

•     A new approach to photoprotection is to repair DNA damage after UV exposure. This can be accomplished by delivery of a DNA repair enzyme into the skin by means of specially engineered liposomes

•     Gene therapy for xeroderma pigmentosum is still in a theoretical and experimental stage.

Surgery;
     The malignancies associated with xeroderma pigmentosum should be completely excised.



Prognosis;
Less than 40% of individuals with the disease survive beyond the age of 20. Some XP victims with less severe cases do manage to live well into their 40s.

NOTES;
1. Alapetite C, Benoit A, Moustacchi E, Sarasin A. The comet assay as a repair test for prenatal diagnosis of Xeroderma pigmentosum and trichothiodystrophy. J Invest Dermatol. Feb 1997;108(2):154-9

2. DermaNet NZ | xeroderma pigmentosum.

2. Hoesl M, Dietz K, Rocken M, et al; Vitamin D levels of XP-patients under stringent sun-protection. Eur J Dermatol. 2010 Jul-Aug;20(4):457-60. Epub 2010 May 21

  
3. Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol. Feb 1987;123(2):241-50

4. Kraemer KH, DiGiovanna JJ, Moshell AN, Tarone RE, Peck GL. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med. Jun 23 1988;318(25):1633-7

5. Lehmann AR, McGibbon D, Stefanini M (2011). "Xeroderma pigmentosum". Orphanet J Rare Dis 6: 70. doi:10.1186/1750-1172-6-70. PMC 3221642. PMID 22044607.

6. Lim HW, Hawk JLM. Photodermatologic disorders. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, Pa: Elsevier Saunders; 2012:chap 87.

7. Medical Biochemistry at a Glance. John Wiley & Sons. 28 November 2011. ISBN 1118292405.

8. Mescape; | article 1119902

9. Nouspikel T. Nucleotide excision repair and neurological diseases. DNA Repair (Amst). Jul 1 2008;7(7):1155-67

10. Schadt C, Fine JD. Genetic disorders predisposing to skin malignancy. In: Rigel DS, Robinson JK, Ross M, et al. eds. Cancer of the Skin. 2nd ed. Philadelphia, Pa: Elsevier Saunders; 2011:chap 33

11. Wikipedia | Xeroderma Pigmentosum