Pseudoxanthoma elasticum This is a generalized condition in which elastic fibers are degenerative. Clinical signs of the phenomenon can be recognized in the skin and eyes. In the skin, patches of yellowish discoloration and general laxness or redundancy develop on the neck (“chicken skin”), in the axillae, and in other places, such as the fossae of limbs and the inguinal folds, where considerable movement of skin is normal. In the eye, angioid streaks can be seen. They represent the result of faulty elastic fibers in Bruch membrane and generally precede the cutaneous changes. These eye changes frequently result in the loss of central vision and sometimes result in almost complete blindness. Peripheral vision is maintained.

Pseudoxanthoma elasticum Gastrointestinal hemorrhage is the most serious acute consequence, but slower structural damage in various organs may result in hypertension, coronary artery occlusion, diabetes mellitus, thyroid dyscrasia, or ectopic calcinosis. The disease may be inherited in autosomal recessive or autosomal dominant fashion. This entity is caused by mutations in the ABCC6 gene mapped to chromosome 16p13.1.

Cutis laxa This disorder may be caused by mutations in genes that are responsible for the formation, assembly, or function of elastic fibers, or may be later in life and related to the destruction of elastic fibers. As seen in this patient, the skin hangs in folds and produces an appearance of premature aging. Because elastic fibers are affected in all organ systems, intestinal and urinary bladder diverticula, rectal prolapse, inguinal hernias, and pulmonary emphysema occur frequently. The last of these is associated with significant mortality.

Ehlers-Danlos syndrome This syndrome is actually a collection of six major genetic types with the common features of hyperextensible skin and joints, easy bruising, defective wound healing, and blood vessel fragility. Distinct abnormalities in collagen synthesis have been identified in some of the varieties of Ehlers-Danlos syndrome. The result of the anomaly is extreme stretchability but unimpaired elasticity (ie, the ability to return to normal after stretching). The figures illustrate the phenomenon; Fig. 14-5 shows skin of the neck and Fig. 14-6 shows skin of the elbow extended several times more than normal skin can be pulled out.

Ehlers-Danlos syndrome In these illustrations, more of the hyperextensible phenomena and the consequences of functional abnormality of elastic fibers and collagen are shown. Figure 14-7 shows hyperextensibility of joints, from which it may be inferred that skin, ligament, tendon, and to some extent bone are also abnormally stretchable. Another way in which softness of muscle and related structures can be appreciated is in the feel of a handshake with a patient who has Ehlers-Danlos syndrome. No matter how hard one presses, there is a feeling that one is not quite through with the handshake. Figures 14-8 illustrates the result of incisions and shearing trauma in the skin of a patient with Ehlers-Danlos syndrome. The result is hemorrhage, failure of healing by primary intention, and finally broad, friable scars.

Ehlers-Danlos syndrome Small “pseudotumors” on easily traumatized areas such as the elbows and knees, illustrated in Figs. 14-9 and 14-10, are actually subcutaneous lesions that develop from fibrosis or calcification of hematomas.

Fat-containing cysts that become calcified, known as spheorids, are usually found on the forearms and shins. Depending on the type of Ehlers-Danlos, inheritance may be autosomal dominant, autosomal recessive, or X-linked recessive.

Ehlers-Danlos syndrome Gastrointestinal perforation and rupture of a large artery are the most severe complications of some forms of this syndrome. Premature birth (probably due to fragility of the fetal membranes) is a common event in patients with Ehlers-Danlos syndrome. Figure 14-11 shows another example of the disfiguring scars that are seen in this condition.

Focal dermal hypoplasia (Goltz syndrome) This syndrome is caused by heterozygous mutation in the PORCN gene on chromosome Xp11.23. The syndrome is transmitted in an X-linked dominant fashion. The most common cutaneous lesions are linear or reticulate areas of hypoplasia with telangiectasia, atrophy, and abnormal pigmentation. Figure 14-12 shows some lesions of this type, as well as the nodular fat tumors that are typically present.

Figure 14-13 shows the whorled nature of the lesions on the trunk following the lines of Blaschko. Ulcers may be present initially in the areas of congenital absence of skin and heal with atrophy. The range of clinical presentation varies from minor involvement on the limbs to extensive distortion of the skin and bony skeleton.

Focal dermal hypoplasia (Goltz syndrome) When bone is involved, syndactyly, polydactyly, oligodactyly with lobster claw deformity (as seen in Fig. 14-14), skeletal asymmetry, and scoliosis may occur. Ocular abnormalities include colobomas, microphthalmia, and strabismus.

Figure 14-15 shows skin and eye defects that may occur in this syndrome. Note the atrophy on the forehead, the ocular defect in the right eye, and the papillomatous changes on the chin. Papillomas may be present on the lips or in the axillae, periumbilical area, or perineum.

Focal dermal hypoplasia (Goltz syndrome) Figure 14-16 illustrates the frequent involvement of the perioral skin and teeth. Patients may present with hypodontia, oligodontia, or small teeth with dysplastic enamel.

Incontinentia pigmenti This rare condition is characterized by linear and whorled lesions and a wide variety of systemic manifestations. Incontinentia pigmenti is inherited as an X-linked dominant trait linked to the NEMO gene and is seen almost exclusively in girls. The cutaneous eruption is usually present at birth and evolves through three stages.

Lesions typical of the first two stages, vesicular and verrucous, are seen in Figs. 14-17 and 14-18. The vesicular phase of incontinentia pigmenti can be quite extensive and lasts for about 2 weeks. Recurrence of vesicular lesions during childhood has also been reported to occur.

Incontinentia pigmenti The vesicular lesions in this disorder must be differentiated from herpes simplex and other causes of blistering in newborn infants. A skin biopsy often provides definitive evidence of the diagnosis.

Vesicular and verrucous lesions following the lines of Blaschko are shown in Fig. 14-20. The disorder may also result in scarring alopecia of the scalp, dystrophic nails, and abnormalities of the teeth.

Incontinentia pigmenti A combination of vesicular and verrucous lesions are seen in this newborn girl.

The verrucous phase lasts for about 6 weeks, although it may go on for many months or even for years in rare cases.

Incontinentia pigmenti Over several months the raised areas flatten, and the patient develops whorled, or “marble-cake,” hyperpigmentation, as pictured in Figs. 14-23,14-24,14-25. In turn, the lesions of this third, hyperpigmented stage fade over a period of several years.

The patients represented in Figs. 14-23 and 14-24 both show details of the marbled hyperpigmentation as well as remnants of the previous papular verrucous stage. A fourth, hypopigmented stage can develop in the second and third decade.

Incontinentia pigmenti This illustration is a good representation of extensive dyschromia. Central nervous system and ocular abnormalities are the most serious aspects of this disease. Some patients will develop seizures, mental retardation, or spastic paralysis. Eye involvement may include the presence of a retrolental mass, retinal detachment, cataracts, and optic atrophy. Skeletal anomalies are sometimes seen.

Incontinentia pigmenti The most common extracutaneous abnormality in incontinentia pigmenti involves teeth and occurs in about two-thirds of patients. There may be a marked delay in the eruption of deciduous teeth. Dental defects such as partial or complete absence of teeth as well as conical teeth may be seen.

Wiskott-Aldrich syndrome This is another severe immunologic defect with X-linked recessive inheritance. The classic symptoms of this disease, which occurs only in males, are thrombocytopenia, recurrent infection, and a generalized eczematous or exfoliative dermatitis. Children with this disorder have impaired humoral and cell-mediated immunity, with deficient IgM and elevated IgA, and are at risk for sepsis and hemorrhage. Figure 14-27 shows the kind of petechiae that are evidence of the persistent thrombocytopenia.