Genodermatosis

By Dr. Nouran abou khedr

Xeroderma Pigmentosum
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 .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

Race Cases 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

Clinical 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 45 years and are more prevalent in sunexposed areas. Neurologic problems are seen in nearly 20% of patients with xeroderma pigmentosum,

Histologic Findings

Histologic features of actinic keratosis in an individual with xeroderma pigmentosum. Note the .atypia of the keratinocytes and the parakeratosis

Treatment The goal of treatment is to protect the patient from sunlight. The use of sunscreens in conjunction with other sun-avoidance methods. Oral retinoids have been shown to decrease the incidence of skin cancer. Chemical therapy with 5-fluorouracil may be useful for actinic keratoses. The malignancies associated with xeroderma pigmentosum should be completely excised.

Ichthyosis
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.

Race 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.

Clinical In ichthyosis vulgaris, dry skin and follicular accentuation (keratosis pilaris) usually appear at puberty. Scaling is most prominent over the trunk, abdomen, buttocks, and legs. The flexural areas, such as the antecubital fossa, are spared. An association may be present between ichthyosis vulgaris and atopic diseases.

Lamellar 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. Localized 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.

Congenital ichthyosiform erythroderma (CIE) is a milder form of the disease that is autosomal recessive in inheritance. CIE 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.

Laboratory Studies ichthyosis vulgaris - Skin biopsy X-linked recessive ichthyosis ± Steroid sulfatase (STS) activity or levels of cholesterol sulfate and genetic testing of amniotic fluid. Epidermolytic hyperkeratosis - Skin biopsy and keratin gene studies. Lamellar 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 . CBC count with differential and bone marrow aspirate. Thyroid function tests ie, hypothyroidism. Serum angiotensin converting enzyme and lysozyme ie, sarcoidosis. Chest radiography ie, sarcoidosis, lymphoma, HIV, tuberculosis. Serum antinuclear antibody (ANA), ie, systemic lupus erythematosus [SLE], systemic sclerosis.

Histologic Findings In ichthyosis vulgaris, the affected skin displays mild hyperkeratosis and a diminished granular layer in the epidermis, while the dermis has normal features.

Treatment Medical Care 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. Lesions typically heal without scarring. Most commonly, these diseases are dominantly inherited,

Epidermolysis bullosa simplex localized blistering at sites of trauma

Junctional 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

Herlitz subtype. This 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.

Generalized 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.

Dystrophic 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.

Dominantly inherited dystrophic epidermolysis bullosa. The 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

Recessively inherited dystrophic epidermolysis bullosa

Histopatology

Treatment
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

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