Section 12. Ichthyoses and Disorders of Keratinization

This is the mildest and most common form of ichthyosis, with an incidence in school-aged children as high as 1:250. It is inherited as an autosomal dominant trait and is present in a significant percentage of individuals with atopic dermatitis. It is not present at birth. The clinical appearance of this ichthyosis varies, depending on location. Figure 12-1 illustrates the fine, bran-like scaling on the upper chest. On the anterior lower leg, there are often larger, plate-like scales that resemble the skin of a fish (Fig. 12-2). Facial involvement is usually minimal, and flexural areas are typically spared. Children with ichthyosis vulgaris are likely to have increased skin markings on the palms and soles and a high incidence of keratosis pilaris (see Figs. 8-46–8-48). Ichthyosis vulgaris tends to worsen in winter when there is less sweating and lower humidity.

This figure illustrates the fine scaling of ichthyosis vulgaris and the conspicuous sparing of the flexures. Treatment of ichthyosis vulgaris entails the use of emollients and creams and ointments containing urea, lactic acid, and other alpha-hydroxy acids. Excessive bathing and the use of alkaline soaps should be avoided. The exacerbation that frequently occurs in winter months can be lessened if a humidifier is used in the child's room.

This condition is a rare, chronic, and often severe genodermatosis that is inherited in an autosomal dominant fashion. The appearance of bullous ichthyosis in the newborn is illustrated in Fig. 12-4. Typically, there are large areas of denuded skin, and sometimes there are intact blisters. The differentiation from epidermolysis bullosa can usually be made by positive family history, the presence of subtle areas of hyperkeratosis, and, most important, the characteristic skin biopsy. The genetic defect lies in mutations in genes encoding keratins 1 and 10. Treatment in the newborn period should focus on gentle handling to avoid new blister formation, the maintenance of fluid and electrolyte balance, and the prevention of bacterial superinfection.

Over time, the generalized blistering resolves, and widespread areas of thick hyperkeratosis and scale develop. In Fig. 12-5, there is a mixed picture; focal erosions are present on the arms and abdomen, and there are areas of thick, discolored, furrowed hyperkeratosis. Note the predilection, which is not seen in ichthyosis vulgaris, for the antecubital fossae and intertriginous spaces. Figure 12-6 shows the process in typical areas: the palms, wrists, and knees. For some patients, severe involvement of the palms and soles creates a particular disability. Figure 12-7 shows bullous ichthyosis in its most severe and generalized form. Patients with this kind of extensive disease face a very difficult set of problems.

Bacterial colonization of this thickened and furrowed skin may result in an extremely unpleasant body odor. The foul smell, along with the disfigurement caused by the disease itself, may interfere enormously with social adaptation. Finally, some children remain prone to mechanically induced blisters in areas of friction or trauma. Antibacterial soaps are of some help in reducing odor. Treatment with keratolytics will often induce painful superficial erosions, and the use of oral retinoids, with all of their side effects, has met with little success. Fortunately, in many patients the disease tends to localize to smaller, usually flexural, areas with advancing age.

This figure illustrates the abdomen of a patient with epidermolytic hyperkeratosis. Note the dark, thickened scale with areas of desquamation that appear to have somewhat more normal skin than the surrounding areas that appear to have a slightly lichenified appearance. This figure shows a localized lesion in the popliteal space. Note the degree of hyperkeratosis and the sculptured character of the skin markings. When there is only local involvement, the clinical picture can be indistinguishable from epidermal nevus. Patients with minimal involvement, like this, may have relatives with severe generalized disease. Prenatal diagnosis is now possible.

This rare autosomal recessive condition may present with a collodion membrane at birth. The severity of the disease during infancy and later childhood is extremely variable. The most typical appearance features widespread scaling and moderate to severe erythroderma. The children with most severe involvement may experience difficulty with temperature regulation. Improvement sometimes occurs at puberty.

This is a rare autosomal dominant condition characterized by migratory areas of erythema and distinct plaques of hyperkeratosis. From an early beginning in infancy, there occur figurate and rapidly (within days) shifting areas of bright erythema on the face, anterior trunk, buttocks, and extensor aspects of the limbs. These may be brought on by changes in environmental temperature. In addition, there are fixed and localized hyperkeratotic plaques.

This rare disorder develops in early childhood. The lesions are symmetrical large, sharply circumscribed, hyperkeratotic plaques with brownish or orange-red discoloration. The most common locations are the extensor limbs, shoulders, buttocks and fingers. As illustrated here, facial involvement may also occur. In contrast to patients with erythrokeratoderma variabilis, these lesions are nonmigratory.

In about half of the patients, palms and soles are involved. This essentially autosomal dominant disease tends to progress until adolescence, and then may improve spontaneously during adult life. Therapeutic options are limited and the use of oral retinoids may be considered.

The newborn infant is covered with thick plates of scale that are often described as resembling a coat of armor. After birth, deep erythematous fissures form between areas of scale. There is also severe facial disfigurement due to eclabium, ectropion, and edema of the conjunctiva. The texture of the skin results in restriction of the respiratory movements of the chest and interferes with normal feeding. Although some infants with this condition are carried to term, the majority are born prematurely.

Collodion baby is a descriptive term for the child who is born encased in a taut, parchment-like membrane, accompanied by ectropion and eclabium. The outcome of this process is unpredictable. A small group of infants shed their membrane and develop completely normal skin; their condition is termed lamellar exfoliation of the newborn. Some go on to develop nonbullous congenital ichthyosiform erythroderma, Conradi's disease, or lamellar ichthyosis (see Figs. 12-27, 12-28, 12-29, 12-30, 12-31, 12-32).

Collodion babies, irrespective of the cause, are very often born prematurely. In addition, they are at risk for cutaneous infection, sepsis, pneumonia, and hypernatremic dehydration and require careful supportive therapy. This infant was formerly a collodion baby and has gradually sloughed his membrane. When the baby was several months of age, one detected the beginning of generalized hyperkeratosis and scaling. This infant has the chronic and severe autosomal recessive disease of lamellar ichthyosis.

This figure shows in detail the kind of ichthyosis that gradually becomes established after the disappearance of the collodion membrane. Note the mosaic pattern of the scales and tendency of the edges of the scale to curl away from the surface. The scales are sometimes compared with armored plates. Bulla formation does not occur in this condition. Note that the entire skin surface, including the face, is affected by the hyperkeratotic, scaly, dyschromic dyskeratinization. Involvement tends to be most severe in flexural areas, as in the axilla pictured here. Topical therapy with the α-hydroxy acids, such as lactic acid, is somewhat helpful in reducing the amount of scale and improving the appearance.

The child in Fig. 12-23 has the severe degree of involvement that is an almost invariable feature of lamellar ichthyosis. Note the ectropion and tightness of the facial skin as a result of hyperkeratosis. The same compromised mobility of skin obtains on other parts of the body. Figure 12-24 illustrates involvement of the palms with thick hyperkeratosis and deep grooves. Not pictured here are the changes that may involve hair and nails. Scaliness of the scalp may be accompanied by partial hair loss. In addition, the nails may be ridged or thickened, and there may be thick subungual hyperkeratosis. Defects in keratinocyte transglutaminase have been reported in patients with lamellar ichthyosis.

There is a long list of genodermatoses that includes thickening of the palms and soles as either the principal or an associated abnormality. The most common among all of these is Unna-Thost palmoplantar keratoderma. Well-demarcated hyperkeratosis is noted on the palms and soles with a red band noted at the periphery of the area and is sharply demarcated. The autosomal dominant inheritance of this condition is illustrated by the mother–son involvement in Fig. 12-25. Treatment consists of the use of keratolytic agents to remove callus.

This rare autosomal recessive syndrome manifests itself in a unique ichthyosis and hair shaft abnormality. At birth, these patients may have a generalized ichthyosiform erythroderma sometimes resembling generalized seborrheic dermatitis, as seen in Fig. 12-27. Severe hypernatremic dehydration is common. The most distinctive cutaneous feature is termed ichthyosis linearis circumflexa, a collection of circinate, erythematous, and hyperkeratotic lesions with a very characteristic double-edged scale along the margin (Fig. 12-28). Patients with Netherton's syndrome tend to have an atopic diathesis, with some combination of asthma, allergic rhinitis, and eczematous dermatitis. Finally, there is a tendency toward impaired cellular immunity and developmental delay.

The associated hair abnormality is seen in Fig. 12-29. Microscopic examination of these “bamboo hairs” (Fig. 12-30) most often reveals a hair shaft abnormality termed trichorrhexis invaginata, a ball-and-socket insertion of the distal hair shaft into the proximal hair. There may also be pili torti (Fig. 26-32) or trichorrhexis nodosa (Fig. 26-30). The hair disorder is not evident at birth and may sometimes be first found upon examination of eyebrow hairs. The hair disorder tends to correct itself with the passage of time.

Conradi's disease, or chondrodysplasia punctata, is actually a group of related syndromes that have differing prognoses and modes of inheritance. Skin changes are seen in some of the patients with each of the disease subtypes. The newborn may present as a collodion baby (see Fig. 12-19). In early infancy, there develops a generalized, whorled ichthyosiform erythroderma, as illustrated in these two figures. Over time, the areas of ichthyosis are replaced by blotchy hyperpigmentation and then, sometimes, by follicular atrophoderma. Patchy alopecia may also occur. Systemic features of chondrodysplasia punctata include stippling of the epiphyses, shortening of the femur and humerus, congenital cataracts, and saddle nose. The autosomal recessive form, also termed rhizomelic dwarfism, is most severe and usually causes psychomotor retardation and seizures. Those patients with the autosomal dominant disease (Conradi-Hünermann syndrome) have a generally better prognosis.

This is a rare autosomal recessive genodermatosis that is characterized by spasticity, mental retardation, and congenital ichthyosis. A combination of scaling and erythroderma is seen in the newborn. Over time, the ichthyosis tends to localize to the lower abdomen (Fig. 12-33) and flexural areas (Fig. 12-34). There may be mild involvement of the palms and soles. The combination of spasticity and psychomotor developmental delay is often quite severe and may be accompanied by a seizure disorder. A specific retinal lesion, the so-called glistening dots, is present in almost all patients with Sjögren-Larsson syndrome after 1 year of age. This syndrome is due to the deficient activity of fatty aldehyde dehydrogenase (FALDH).

This disorder is characterized by ichthyosis that begins at or shortly after birth and persists through adult life. The “dirty” brown and tightly adherent scales are illustrated in both figures. The scaling tends to favor the trunk and the extensor surfaces of the extremities. There is relative sparing of the face and flexural areas. The palms and soles are also spared, and the hair and teeth are normal. Most patients note marked improvement during the summer months, probably related to improved skin hydration. Asymptomatic corneal opacities on the posterior membrane serve as an adult marker for this disease. In addition, there is a significant incidence of cryptorchidism in individuals with this syndrome. The locus for this rare genodermatosis is now known to be on the distal short arm of the X chromosome, and the disease is inherited in X-linked recessive fashion. The underlying metabolic disorder is a deficiency in the enzyme steroid sulfatase. Diagnosis can be confirmed by serum lipoprotein electrophoresis.

Widespread epidermal nevi occur, with the lesions following the lines of Blaschko. This condition was formerly termed ichthyosis hystrix. Patients with extensive lesions are especially prone to abnormalities in a variety of other organ systems—the epidermal nevus syndrome. Associated cutaneous lesions include hemangiomas, café-au-lait spots, and areas of hypopigmentation. Mental retardation and a seizure disorder may also be present. Skeletal abnormalities seen in the epidermal nevus syndrome include limb hypertrophy, bone cysts, and incomplete formation of certain bones. A higher-than-normal incidence of malignancy, particularly Wilms' tumor, has also been associated with this disorder. All children with epidermal nevi should have a careful physical examination, and laboratory evaluation should be pursued as indicated. Occasionally, patients with epidermal nevi are genetic mosaics for bullous congenital ichthyosiform erythroderma.

These lesions consist of verrucous, hyperkeratotic papules that are closely grouped in a linear array following the lines of Blaschko. Epidermal nevi are often present at birth but may arise during the first year of life, and occasionally later. They may occur on the head and neck, trunk, or extremities. Lesions of the appearance illustrated in Fig. 12-39 are sometimes termed nevus unius lateris.Figure 12-40 shows an extensive epidermal nevus on the face and neck following the lines of Blaschko. Epidermal nevi have no malignant potential, except for the rare development of basal cell carcinoma in a preexisting lesion. Surgical treatment is required only when indicated for cosmetic considerations.

This linear array of pruritic papules arises most often during childhood. The lesions are erythematous and scaling and are usually localized to the lower extremities or perineum. Sometimes this entity may be difficult to distinguish from psoriasis. The persistence of inflammation in one anatomic area and the absence of psoriatic lesions elsewhere favor the diagnosis of ILVEN. Histologically, it may resemble psoriasis or nonspecific chronic dermatitis.

This is a descriptive term for a velvety or verrucous brown-to-black area of hyperkeratosis. The axilla and posterior are the most common locations, but lesions are also seen on the anterior neck and in the groin. Less commonly, there is involvement in the antecubital and popliteal fossae, on the knuckles, and in other, nonflexural areas. Onset may occur during childhood or adult life. The histologic pattern is that of hyperkeratosis and papillomatosis; the brownish discoloration seems to be caused by these surface changes rather than by any local increase in the amount of melanin. Illustrated here are lesions of acanthosis nigricans on the anterior neck and in the axilla.

Based on the varying etiologies, acanthosis nigricans is divided into several types. The title benign acanthosis nigricans is used to describe an autosomal dominant genodermatosis. The condition may develop at birth or during childhood and often intensifies after puberty. A second type, which heralds the presence of an associated malignancy (usually adenocarcinoma), is extremely rare during childhood. The term pseudoacanthosis nigricans refers to the form that is directly related to obesity. It is not unusual to see this condition on the nape of the neck or in the axilla and groin in an obese adolescent. This form of acanthosis nigricans sometimes abates or with dieting and weight loss. Finally, acanthosis nigricans may occur as a manifestation of several unrelated syndromes. These include Rud's syndrome, Bloom's syndrome, and Crouzon's syndrome. The relationship between acanthosis nigricans and insulin-resistant diabetes mellitus is discussed in the legend to Fig. 19-12.

The keratitis-ichthyosis-deafness (KID) syndrome is a multisystem disorder that, in its most severe forms, may be disabling. Cutaneous changes consist of thick keratoderma of the palms and soles, keratotic plaques on the face and extremities, and a diffuse ichthyosis with follicular accentuation. Abnormal keratinization may be present at birth. Alopecia, nail dystrophy, and hypoplastic teeth are all part of this disorder. The hearing impairment in this disease is progressive and due to neurosensory deafness. Keratitis begins during childhood and is accompanied by neovascularization. Visual loss may be severe. Recurrent and atypical cutaneous infections may also be seen in KID syndrome.

This autosomal dominant disorder is characterized by numerous flat-topped or verrucous hyperkeratotic papules that are usually localized to the dorsa of the hands and feet. They tend to recur after surgical removal. Histologically, there are distinctive elevations of the epidermis that resemble church spires. It should be noted that patients with Darier's disease (see Figs. 9-52, 9-53, 9-54) may have identical acral lesions.

The lesions in this condition consist of numerous clustered papules, each with a dark, central hyperkeratotic plug. The individual papules are clinically and histologically identical to the comedones seen in acne vulgaris. However, these nevoid plaques, which are often linear in configuration, do not necessarily occur in the ordinary sites of predilection of comedonal acne. Lesions may be single or multiple, and palm and sole involvement occurs. This may be a form of epidermal nevus.