A group of hereditary disorders characterized by an excess accumulation of cutaneous scale, varying from very mild and asymptomatic to life threatening.
A relatively large number of types of hereditary ichthyoses exist; most are extremely rare and often part of multiorgan syndromes. The four most common and important types are discussed here plus a brief discussion of two syndromic ichthyoses and ichthyosis affecting the newborn.
Acquired ichthyosis can be a manifestation of systemic disease, malignancy, drugs, endocrine disease, autoimmune disease, and HIV and other infections.
Support groups such as Foundation for Ichthyosis and Related Skin Types (FIRST) exist.
For an in-depth discussion of ichthyoses, see P Fleckman, JJ DiGiovanna, in L Goldsmith et al (eds): Fitzpatrick’s Dermatology in General Medicine, 8th ed. New York, McGraw-Hill, pp 507-538, 2012.
Dominant ichthyosis vulgaris (DIV)
X-linked ichthyosis (XLI)
Lamellar ichthyosis (LI)
Epidermolytic hyperkeratosis (EH)
Dominant Ichthyosis Vulgaris (DIV) ICD-9: 701.1 ICD-10: Q 80.0
Characterized by usually mild generalized xerosis with scaling, most pronounced on lower legs; in severe cases large, tessellated scales.
Hyperlinear palms and soles.
Perifollicular hyperkeratosis (keratosis pilaris) usually on arms and legs.
Frequently associated with atopy.
Age of Onset. 3 to 12 months.
Sex. Equal incidence in males and females. Autosomal dominant inheritance.
Incidence. Common (1 in 250).
Etiology unknown. There is reduced or absent filaggrin. Epidermis proliferates normally, but keratin is retained with a resultant thickened stratum corneum.
Very commonly associated with atopy. Cosmetic concern to many patients, particularly when hyperkeratosis is severe.
Skin Lesions. Xerosis (dry skin) with fine, powdery scaling but also larger, firmly adherent tacked-down scales in a fish-scale pattern (Figs. 4-1 and 4-2). Diffuse general involvement, accentuated on the shins, arms, and back, buttocks, and lateral thighs; axillae and the antecubital and popliteal fossae spared (Figs. 4-2 and 4-4); face usually spared but cheeks and forehead may be involved. Keratosis pilaris is perifollicular hyperkeratosis with little, spiny hyperkeratotic follicular papules of normal skin color either grouped or disseminated, mostly on the extensor surfaces of the extremities (Fig. 4-3); in childhood, also on cheeks. Hands and feet usually spared, but palmoplantar markings are more accentuated (hyperlinear).
Associated Diseases. More than 50% of individuals with DIV also have atopic dermatitis, rarely keratopathy.
Figure 4-1. Ichthyosis vulgaris: chest Fine fish scalelike hyperkeratosis of the pectoral area. This is a mild form of ichthyosis vulgaris.
Figure 4-2. Ichthyosis vulgaris: legs Grayish tessellated (tilelike), firmly bound down scales. The similarity to fish skin or the skin of an amphibian is quite obvious. Note sparing of popliteal fossae. This is a more severe form of ichthyosis vulgaris.
Figure 4-3. Ichthyosis vulgaris. Keratosis pilaris: arm Small, follicular, horny spines occur as a manifestation of mild ichthyosis vulgaris; arising mostly on the shoulders, upper arms, and thighs. Desquamation of the nonfollicular skin results in hypomelanotic (less pigmented) spots similar to pityriasis alba (compare with Fig. 3-18).
Figure 4-4. Distribution of ichthyosis vulgaris Dots indicate keratosis pilaris.
Xerosis/Hyperkeratosis. Xerosis; acquired ichthyoses, all other forms of ichthyosis.
Dermatopathology. Compact hyperkeratosis; reduced or absent granular layer; small, poorly formed keratohyalin granules by electron microscopy, germinative layer flattened.
By clinical findings; abnormal keratohyalin granules in electron microscopy.
Course and Prognosis
Improvement in the summer, in humid climates, and in adulthood. Keratosis pilaris occurring on the cheeks during childhood usually improves during adulthood.
Hydration of Stratum Corneum. Best accomplished by immersion in a bath followed by the application of petrolatum. Urea-containing creams bind water in the stratum corneum.
Keratolytic Agents. Propylene glycol-glycerin-lactic acid mixtures. Propylene glycol (44-60% in water); 6% salicylic acid in propylene glycol and alcohol, used under plastic occlusion (beware of hypersalicism). α-Hydroxy acids (lactic acid or glycolic acid) control scaling. Urea-containing creams and lotions (2-10%) are effective.
Systemic Retinoids. Isotretinoin and acitretin are very effective, but careful monitoring for toxicity is required. Only severe cases may require intermittent therapy.
X-Linked Ichthyosis (XLI) ICD-9: 701.1 ICD-10: Q 80.1
Occurs in males, x-linked recessive; gene locus Xp22.32.
Steroid sulfatase deficiency. Accumulation of cholesterol sulfate resulting in retention hyperkeratosis associated with normal epidermal proliferation.
Incidence 1:2000 to 1:6000.
Onset soon after birth.
Prominent, dirty brown scales on the neck, extremities, trunk, and buttocks (Fig. 4-5).
Involvement of flexural regions (Fig. 4-6).
Absence of palm and sole involvement.
Comma-shaped stromal corneal opacities (asymptomatic) in 50% of adult males. Present in some female carriers.
Laboratory: cholesterol sulfate level ↑; increased mobility of β-lipoproteins in electrophoresis. Steroid sulfatase decreased or absent. Dermatopathology: hyperkeratosis and granular layer present.
Prenatal diagnosis: amniocentesis, steroid sulfatase ↓ in chronic villus samples.
Course: no improvement with age. Worse in temperate climates and winter.
Management: Hydration of stratum corneum and keratolytic agents as in ichthyosis vulgaris. Marked improvement with systemic retinoids (acitretin and isotretinoin), intermittent treatment with careful monitoring of toxicity.
Figure 4-5. X-linked ichthyosis: trunk, buttocks, and arms Dark hyperkeratosis with tessellated scales gives a dirty appearance in this 12-year-old boy of African brown ethnicity.
Figure 4-6. Distribution of X-linked ichthyosis.
Lamellar Ichthyosis (LI) ICD-9: 701.1 ICD-10: Q 80.2
Onset at birth, usually as collodion baby (see Fig. 4-12).
Equally in both sexes; incidence ≤1:300,000.
Autosomal recessive. Three types: (1) mutation of gene encoding transglutaminase 1; (2) mutation of gene encoding ATP-binding cassette, subfamily A, number 12; and (3) mutation of gene encoding arachidonate lipoxygenase.
Soon after birth collodion membrane shed with subsequent large, coarse, tessellated scales involving entire body (Figs. 4-7 to 4-9). Scales are thick, brown, accumulated on lower extremities, flexural areas involved (Fig. 4-9).
Hands, feet involvement varies; accentuation of palmar/plantar creases.
Eyes: extropium (Fig. 4-7) and eclabium.
Scalp: hairs bound down by scales; scarring alopecia (Fig. 4-8).
Mucous membranes spared; nails: occasional dystrophy secondary to nail fold inflammation.
Heat intolerance; obstruction of eccrine glands impairs sweating.
Laboratory: acanthosis; hyperkeratosis, granular layer present. Epidermal transglutaminase ↓ in transglutaminase-deficient subtype.
Course: persists throughout life, no improvement with age.
Management: newborn: see collodion baby, p. 81. Adults: emollients, keratolytics, systemic retinoids as in DIV and XLI: Instruct about overheating.
Figure 4-12. Ichthyosis in the newborn (A) “Collodion baby” shortly after birth with a parchment-like membrane covering the entire body. In some areas, the membrane has ruptured and is being shed leaving oozing, raw-looking skin. (B) At 8 months of age, the same infant is a beautiful baby with minimal residual scale and erythema.
Figure 4-7. Lamellar ichthyosis Parchment-like hyperkeratosis gives the impression of the skin being too tight on the face of this 6-year-old Arab boy. There is lamellar scaling hyperkeratosis, pronounced ectropium, and beginning alopecia.
Figure 4-8. Distribution of lamellar ichthyosis.
Figure 4-9. Lamellar ichthyosis: Shoulder tesselated (tilelike) hyperkeratosis gives the appearance of reptilian scales on the shoulder and back. The entire body was involved, and there was ectropium.
Epidermolytic Hyperkertosis (EH) ICD-10: Q 80.8
Autosomal dominant. Mutation of genes that encode epidermal differentiation keratins, keratin 1 and 10.
Presents at or shortly after birth with blistering, generalized or localized.
With time becomes keratotic and verrucous (Fig. 4-10) but blisters continue (Fig. 4-10).
Shedding of hyperkeratotic masses results in circumscribed areas of normal-appearing skin.
Involvement of flexural areas and palmar and plantar skin (Fig. 4-11).
Associated with unpleasant odor (like rancid butter).
Secondary pyogenic infections.
Dermatopathology: giant coarse keratohyalin granules, vacuolization of granular layer → subcorneal blisters.
Management: topical α-hydroxy acids, systemic acitretin, or isotretinoin that initially lead to increased blister formation but later improve skin dramatically. Determine dose carefully, monitor side effects, and observe contraindications.
Figure 4-10. Epidermolytic hyperkeratosis: arms and hands Mountain rangelike hyperkeratosis of the dorsum of hands with blistering that results in erosions and shedding of large sheets of keratin.
Figure 4-11. Distribution of epidermolytic hyperkeratosis.
Ichthyosis in the Newborn
Collodion Baby ICD-9: 701.1 ICD-10: Q 80.2
Encasement of entire baby in a transparent parchment-like membrane (Fig. 4-12A) impairs respiration and sucking.
Breaking and shedding of the collodion membrane initially leads to difficulties in thermoregulation and increased risk of infection.
Skin is bright red and moist (Fig. 4-12A). After healing, skin appears normal for some time until signs of ichthyosis develop.
Collodion baby may be the initial presentation of lamellar ichthyosis or some less common forms of ichthyosis not discussed here.
Collodion baby also may be a condition that, after the collodion membrane is shed and the resultant erythema has cleared, will progress to normal skin for the rest of the child’s life (Fig. 4-12B).
Management: keep newborn in incubator and monitor temperature and fluids, and nutrient replacement. Aggressive antibiotic therapy for skin and lung infection.
Harlequin Fetus ICD-9: 757.1 ICD-10: Q 80.4
Harlequin fetus is an extremely rare condition in which the child is born with very thick plates of stratum corneum separated by deep cracks and fissures (Fig. 4-13).
Eclabium, ectropion, and absence of or rudimentary ears result in a grotesque appearance.
These babies usually die shortly after birth, but there are reports of survival for weeks to several months.
This condition is different from collodion baby and the other forms of ichthyosis, with an unusual fibrous protein within the epidermis.
Figure 4-13. Harlequin fetus Stratum corneum consists of thick plates separated by deep cracks. (Courtesy of Benjamin Solky, MD.)
Syndromic Ichthyoses ICD-9: 701.1 ICD-10: Q 80.9
These are a number of rare syndromic ichthyoses where ichthyotic skin changes are associated with metabolic and/or functional and structural abnormalities.
For erythroderma variabilis (Fig. 4-14), keratitis-ichthyosis-deafness (KID) syndrome (Fig. 4-15), Child syndrome, and Netherton syndrome (Fig. 4-16), see P Fleckman, JJ DiGiovanna, in L Goldsmith et al: Fitzpatrick’s Dermatology in General Medicine, 8th ed. New York, McGraw-Hill, pp 507-538, 2012.
Figure 4-14. Erythrokeratodermia variabilis Note hyperkeratotic plaques on the face associated with migrating erythemas on the neck (arrow).
Figure 4-15. Keratitis-ichthyosis-deafness (KID) syndrome Hyperkeratosis on the cheeks and the tip of the nose and sparse hair are characteristic for this syndrome as are hyperkeratosis in the flexural folds, dorsa of hands. In addition, there is keratitis and loss of hearing.
Figure 4-16. Netherton syndrome Ichthyosis linearis circumflexa consists of serpiginous psoriasiform erythemas with scaling and is associated with trichorrhexis nodosa (bamboo hairs).
Acquired Ichthyoses ICD-9: 701.1 ICD-10: L 85.0
Occurs in adults.
Associated with malignancies (Hodgkin disease but also non-Hodgkin lymphomas and other malignancies).
Associated with AIDS.
Associated with sarcoidosis.
Associated with systemic lupus erythematosus, dermatomyositis, mixed connective tissue disease, and eosinophilic fasciitis.
Associated with graft-versus-host disease.
Associated with drugs (nicotinic acid, triparanol, butyrophenone, dixyrazine, nafoxidine).
Occurs in Kava drinkers: Kava dermopathy.
Inherited Keratodermas of Palms and Soles ICD-10: Q 82.2
Palmoplantar keratodermas (PPK) are a rare and diverse group of keratinization disorders.
There exist more than 20 different PKK that are either confined to palms and soles or concomitant with (related) lesions elsewhere on the body or are part of more complex syndromes.
The genetic basis of most PPK involves mutations of keratin genes or genes encoding connexin or desmosomal proteins.
Clinical classification distinguishes between diffuse (Fig. 4-17), punctate (Fig. 4-18), striate (Fig. 4-19), and focal PPK (callus-like circumscribed hyperkeratoses).
Histopathologic distinction is made between epidermolytic and nonepidermolytic PPKs.
Symptoms vary from inconvenience to functional disability. Plantar pain in focal PPK and hyperhidrosis may be debilitating.
PPK do not improve with age, lifelong companion.
Management: physical debridement, topical keratolytic agents, systemic acitretin, or isotretinoin may be associated with increased sensitivity, difficulties with normal work and walking, particularly in the epidermolytic forms of PKK.
Figure 4-17. Plantar keratoderma, diffuse type Yellow waxy diffuse hyperkeratosis on both soles.
Figure 4-18. Punctate plantar keratoderma Multiple, discrete droplike keratoses resembling plantar warts. Lesions had been present since late childhood and have become worse, particularly in the pressure areas.
Figure 4-19. Striate palmar keratoderma There are linear verrucous hyperkeratoses extending from the palm onto the fingers. Manual work aggravates these lesions, which can become fissured and painful. In focal palmar and plantar keratoderma, there are large hyperkeratoses on pressure sites of soles and palms that can become quite painful.