Xeroderma pigmentosum is a rare disorder transmitted in an autosomal recessive manner. It is characterized by photosensitivity, pigmentary changes, premature skin aging, and malignant tumor development.
Xeroderma pigmentosum is a rare disorder transmitted in an autosomal recessive manner. It is characterized by photosensitivity, pigmentary changes, premature skin aging, and malignant tumor development.
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Xeroderma pigmentosum is a rare disorder transmitted in an autosomal recessive manner. It is characterized by photosensitivity, pigmentary changes, premature skin aging, and malignant tumor development.
Copyright:
Attribution Non-Commercial (BY-NC)
Available Formats
Download as PPT, PDF, TXT or read online from Scribd
transmitted in an autosomal recessive manner. It is characterized by photosensitivity, pigmentary changes, premature skin aging, and malignant tumor development .These manifestations are due to a cellular hypersensitivity to ultraviolet (UV) radiation resulting from a defect in DNA repair. Pathophysiology The basic defect in xeroderma pigmentosum is in nucleotide excision repair (NER), leading to deficient repair of DNA damaged by UV radiation. Mortality/Morbidity Individuals with this disease develop multiple cutaneous neoplasms at a young age. Two important causes of mortality are metastatic malignant melanoma and squamous cell carcinoma _ace ases of xeroderma pigmentosum are .reported in persons of all races Sex An equal prevalence has been reported in .males and females Age The disease is usually detected at age 1-2 .years linical
The disease typically passes through 3 stages.
The skin is healthy at birth. Typically, the first stage appears after age 6 months. This stage is characterized by diffuse erythema, scalingseen over light-exposed areas.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 winter months with decreased sun exposure, as time passes, these findings become permanent. The second stage is characterized by poikiloderma. Poikiloderma consists of skin atrophy, telangiectasias, and mottled hyperpigmentation and hypopigmentation, The third stage is heralded by the appearance of numerous malignancies, including squamous cell carcinomas, malignant melanoma, basal cell carcinoma, and fibrosarcoma. These malignancies may occur as early as age 4- 5 years and are more prevalent in sun- exposed areas. Neurologic problems are seen in nearly 20% of patients with xeroderma pigmentosum, Òistologic Findings
Òistologic features of actinic keratosis in an
individual with xeroderma pigmentosum. Note the .atypia of the keratinocytes and the parakeratosis ïreatment ïhe goal of treatment is to protect the patient from sunlight. ïhe use of sunscreens in conjunction with other sun-avoidance methods. Oral retinoids have been shown to decrease the incidence of skin cancer. hemical therapy with 5-fluorouracil may be useful for actinic keratoses. The malignancies associated with xeroderma pigmentosum should be completely excised. chthyosis Ichthyosis refers to a relatively uncommon group of skin disorders characterized by the presence of excessive amounts of dry surface scales. It is regarded as a disorder of keratinization or cornification, and it is due to abnormal epidermal differentiation or metabolism. The ichthyosiform dermatoses may be classified according to clinical manifestations, genetic presentation and histologic findings. Inherited and acquired forms of ichthyosis have been described. Five distinct types of inherited ichthyosis are noted, as follows: ichthyosis vulgaris, lamellar ichthyosis, epidermolytic hyperkeratosis, congenital ichthyosiform erythroderma, and X-linked ichthyosis. _ace In general, all races may be affected in the inherited and acquired forms of ichthyosis. Sex X-linked recessive ichthyosis is much more prevalent in males. linical n ichthyosis vulgaris, dry skin and follicular accentuation (keratosis pilaris) usually appear at puberty. Scaling is most prominent over the trunk, abdomen, buttocks, and legs. ïhe flexural areas, such as the antecubital fossa, are spared. An association may be present between ichthyosis vulgaris and atopic diseases. ýamellar ichthyosis is a rare, autosomal recessive, genetically heterogeneous skin disease caused by mutations involving multiple genetic loci. In classic lamellar ichthyosis, children with the disease are referred to as collodion babies and are covered at birth by a thickened membrane that subsequently is shed. The scaling of the skin involves the whole body with no sparing of the flexural creases. In epidermolytic hyperkeratosis, the skin is moist, red, and tender at birth. Bullae formation may occur, which may become infected and give rise to a foul skin odor. Thick, generalized, verrucous scaling occurs within a few days. ýocalized scaling may be seen, especially in the flexural creases. In X-linked ichthyosis, generalized scaling is present at or shortly after birth. This scaling is most prominent over the extremities, neck, trunk, and buttocks. The flexural creases, palms, and soles are spared. ongenital ichthyosiform erythroderma (IE) is a milder form of the disease that is autosomal recessive in inheritance. IE has been found to be caused by mutations in the genes coding for transglutaminase. Acquired ichthyosis usually occurs in adults and manifests as small, white, fishlike scales that frequently are concentrated on the extremities but may be seen in a generalized distribution. This form of ichthyosis may be associated with Hodgkin lymphoma ,internal neoplasia eg HIV ,sarcoidosis ,leukemia, systemic illness eg chronic hepatitis ,hypothyroidism ,infection or ,bone marrow transplantation ,malabsorption the intake of certain medications that interfere with sterol synthesis in epidermal cells eg, nicotinic acid. ýaboratory Studies ichthyosis vulgaris - Skin biopsy X-linked recessive ichthyosis ± Steroid sulfatase (SïS) activity or levels of cholesterol sulfate and genetic testing of amniotic fluid. Epidermolytic hyperkeratosis - Skin biopsy and keratin gene studies. ýamellar ichthyosis ± Genetic analysis for mutations in the gene for transglutaminase 1. Acquired ichthyosis may be a marker of various autoimmune disorders or malignancy. Acquired ichthyosis may also be a marker of concomitant infection with HIV in intravenous drug users . B count with differential and bone marrow aspirate. Thyroid function tests ie, hypothyroidism. Serum angiotensin converting enzyme and lysozyme ie, sarcoidosis. hest radiography ie, sarcoidosis, lymphoma, HIV, tuberculosis. Serum antinuclear antibody (ANA), ie, systemic lupus erythematosus [SýE], systemic sclerosis. Òistologic Findings In ichthyosis vulgaris, the affected skin displays mild hyperkeratosis and a diminished granular layer in the epidermis, while the dermis has normal features. ïreatment Medical are Systemic Oral retinoids display an impressive antikeratinizing action in ichthyosiform dermatoses. Etretinate (1 mg/kg/d) and isotretinoin (2 mg/kg/d) have been shown to reduce scaling, discomfort, and disfigurement. Topical Keratolytics,Emoilents. Epidermolysis Bullosa
Epidermolysis bullosa (EB) is a group of inherited
bullous disorders characterized by blister formation in response to mechanical trauma. Epidermolysis bullosa is classified into 3 major categories, including (1) epidermolysis bullosa simplex (intraepidermal skin separation), (2) junctional epidermolysis bullosa (skin separation in lamina lucida or central BMZ), and (3) dystrophic epidermolysis bullosa (sublamina densa BMZ separation). Onset of epidermolysis bullosa is at birth or shortly after. The exception occurs in mild cases of epidermolysis bullosa simplex, which may remain undetected until adulthood or occasionally remain undiagnosed. Epidermolysis bullosa simplex
Epidermolysis bullosa simplex is a
collection of keratin disorders characterized by intraepidermal blistering with relatively mild internal involvement. ýesions typically heal without scarring. Most commonly, these diseases are dominantly inherited, Epidermolysis bullosa simplex localized blistering at sites of trauma ëunctional epidermolysis bullosa
Junctional epidermolysis bullosas is a
collection of diseases characterized by intralamina lucida blistering. Primary subtypes include a lethal subtype termed Herlitz or junctional epidermolysis bullosa letalis, a nonlethal subtype termed junctional epidermolysis bullosa mitis, and a generalized benign type termed generalized atrophic benign epidermolysis .bullosa Òerlitz subtype. ïhis severe disease is characterized by generalized blistering at birth, significant internal involvement, and a poor prognosis. Nonlethal junctional epidermolysis bullosa Patients are manifested by generalized blistering ,survive infancy and clinically improve with age. They have scalp, nail, and tooth abnormalities. Periorificial erosions and hypertrophic granulation tissue can be present. Mucous membranes often are affected by erosions, resulting in strictures. Some patients with junctional epidermolysis bullosa mitis can present with blistering localized to the intertriginous regions. |eneralized atrophic benign epidermolysis bullosa
This is a relatively mild subtype
characterized by generalized cutaneous blistering and presenting at birth. Blistering activity is worsened by increased ambient temperature, and blisters heal with a distinctive atrophic appearance. Oystrophic epidermolysis bullosa
This is a group of diseases caused by
defects of anchoring fibrils. Blisters heal followed by dystrophic scarring. Formation of milia (1- to 4-mm white papules) results as a consequence of damage to hair .follicles Dominantly inherited dystrophic epidermolysis bullosa
The onset of disease usually is at birth or
during infancy, with generalized blistering as a common presentation. With increasing age, an evolution to localized blistering is present. Oominantly inherited dystrophic epidermolysis bullosa. ïhe blistering in this disease often is localized and is characterized by scarring and milia in healed blister sites. Recessively inherited epidermolysis bullosa
This group of diseases ranges from mild to
severe in presentation. A localized form, termed recessively inherited epidermolysis bullosa mitis, often involves acral areas and nails but shows little mucosal involvement. Severe recessively inherited epidermolysis bullosa, usually shows generalized blistering at birth and subsequent extensive dystrophic scarring that is most prominent on the acral surfaces _ecessively inherited dystrophic epidermolysis bullosa Histopatology ïreatment
Prevention of infection is the preferred strategy.
With extensive areas of crusting and denudation, a strict wound care regimen should be followed. Such a regimen entails regular whirlpool therapy followed by application of topical antibiotics. The wound should be covered with semiocclusive nonadherent dressings. Do not apply adhesive tape directly to the skin. Self-adhering gauze or tape is a better choice for keeping dressings in .place ï