Incontinentia pigmenti. Bloch-Shulzberger\'s disease.
Incidence
X-linked dominant inherited syndrome. The disorder is lethal for male infants. Incontinentia pigmenti (IP) is a rare, genetic disorder characterized by unusual patterns of discolored skin.
Clinical Characteristics
Bloch-Shulzberger\'s incontinentia pigmenti is an X-linked dominant inherited syndrome. Causal genes are located on Xp11-21 for incontinentia pigmenti 1 and Xq28 for incontinentia pigmenti 2. Children have a 50% risk of being affected, but the disorder is lethal for male infants. This condition is considered a neurocutaneous syndrome or phakomatosis. The attack of skin is characterized by linear or geometric lesions with asymetric splatter-like that develop by stages: first they appear as erythema and bullae, then as verrucous and lichenoid papulas, and finally they become hyperpigmented. Plaques of cicatricial alopecia are common findings. Dental, ocular and neurological disorders are frequently associated. Diagnosis is established on clinical, biological, and histological grounds. Treatment is symptomatic. IP is divided into 4 stages, which frequently overlap or appear together. During the first stage, which begins between birth and 6 months of age, there is inflammation accompanied by skin redness and spiral lines of small fluid-filled blisters. The second stage gradually develops with rough, warty skin growths which appear on the arms or legs and, sometimes, on the head or trunk. These growths, which are often arranged in the same spiral or linear pattern as in the first stage, usually resolve during infancy or early childhood. The third stage begins between 3 months and 2 years of age and is characterized by discolorations appearing in unusual patterns. The fourth stage consists of diminished pigmentation or atrophy in areas of previous discoloration. The hallmark of incontinentia pigmenti (Bloch-Sulzberger syndrome) in the neonatal period is the presence of an erythematous vesicular rash. The rash may be present at birth or may develop shortly after, usually during the first 2 weeks of life. The vesicles usually form a linear pattern following the Blaschko lines but isolated lesions with no particular pattern may also occur. The evolutive changes that characterize incontinentia pigmenti (verrucous eruption and hypopigmented lesions) do not usually occur in the neonatal period. The most important entity to differentiate from incontinentia pigmenti is herpes simplex encephalitis. They both may produce seizures and have skin vesicles. The distinction is based on the location and cytology of the vesicles. The vesicles in herpes simplex infection tend to occur on the scalp or presenting body part (sites of trauma) and the scrapings from the base of the vesicles show multinucleated giant cells with intranuclear inclusion (Sank smear). The vesicles in incontinentia pigmenti tend to occur on the limbs or lateral trunk, and the scrapings from the base of the vesicles show large numbers of eosinophils. Neonates with incontinentia pigmenti have leukocytosis and a high blood eosinophils count. Neonates with incontinentia pigmenti should undergo ophthalmological evaluation for retinal dysplasia, uveitis, keratitis, cataracts, and retrolental dysplasia. Incontinentia pigmenti occurs in females. Incontinentia pigmenti is transmitted as an X-linked trait and is lethal in homozygous males. The gene loci are Xp11 (sporadic) and Xp28 (familial). Prenatal diagnosis is possible by DNA analysis. Males born with lesions of incontinentia pigmenti should have chromosomal studies to determine if an XXY karyotype is present. In rare cases of IP, hair loss with scarring and non-dermatological symptoms such as dental problems (delayed tooth growth or decay, missing or malformed teeth), diminished vision, seizures, muscle spasms, or slight paralysis may occur. Developmental abnormalities including dwarfism or short stature, club foot, spina bifida, skull and ear deformities, cleft lip or palate, atrophy on one side of the body, abnormal development of cartilage, congenital dislocation of hip, incomplete development of one side of the spinal bones, and extra ribs or webbed fingers may occur with the disorder but are not characteristic. In a few cases of IP, extremely wooly or kinky hair and an immune system dysfunction may also appear.
Precipitants
none
Provocation Tests
none
Diagnostic Procedures
Diagnosis/testing. The diagnosis of IP is established by clinical findings and occasionally by corroborative skin biopsy. Molecular genetic testing of the IKBKG gene (chromosomal locus Xq28) reveals disease-causing mutations in about 80% of probands. Such testing is available clinically. In addition, females with IP have skewed X-chromosome inactivation; testing for this can be used to support the diagnosis. The diagnosis of incontinentia pigmenti (IP) relies upon detection of the characteristic clinical findings of the skin, teeth, hair, and nails. In an individual with no family history of IP, the clinical diagnosis of IP relies upon the presence of at least one of the following major criteria. The presence of minor criteria supports the clinical diagnosis, and the complete absence of minor criteria should raise doubt about the diagnosis. When a family history of IP or a history of multiple male miscarriages exists, the diagnosis of IP can be made based upon defined major and minor criteria: Major criteria (skin lesions that occur in stages from infancy to adulthood): Erythema, followed by blisters (vesicles) anywhere on the body except the face, usually in a linear distribution. The blisters clear within weeks and may be replaced by a new crop. First weeks of life to four months of age (stage 1). Hyperpigmented streaks and whorls that respect Blaschko\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'s lines, occur mainly on the trunk, and fade in adolescence. Four months to 16 years (stage 3). Pale, hairless, atrophic linear streaks or patches. Adolescence through adulthood (stage 4). Minor criteria: Teeth: hypodontia/anodontia (missing or absent teeth), microdontia (small teeth), abnormally shaped teeth. Hair: alopecia, woolly hair (lusterless, wiry, coarse). Nails: mild ridging or pitting; onychogryposis. Retina: peripheral neovascularization.