Section 4. Disorders of Epidermal Proliferation

Psoriasis is a hereditary disorder of skin characterized by chronic scaling papules and plaques in a characteristic distribution, largely at sites of repeated minor trauma. The HLA types most frequently associated with psoriasis are HLA-B13, -B17, -Bw16, -B37, -Cw6, and DR7.

Insight

It can be difficult to distinguish between atopic dermatitis and psoriasis in infancy. If family history and cutaneous findings are not helpful, one hint is atopic dermatitis usually spares the diaper area and psoriasis favors that location.

Epidemiology

Age 10% have onset of lesions before age 10, and 37% have onset before age 20.

Gender F > M, 2:1.

Prevalence 2% of the world’s population. United States and Canada: 4% to 5% of the population.

Race Low incidence in Asians, Africans, African Americans, American Indians, and Japanese.

Other Features Multifactorial inheritance. Minor trauma is a major factor (45% of patients) in eliciting lesions (Koebner’s phenomenon). Infection (particularly streptococcal) also plays a role. Many episodes of psoriasis follow sore throats or upper respiratory infections. Stress, cold weather, hypocalcemia, and lack of sunlight exposure aggravate the condition. Certain drugs (lithium, interferon, β-blockers, alcohol, antimalarials, corticosteroid withdrawal) can also precipitate psoriasis.

Pathophysiology

Psoriasis is likely a polygenic disease caused by the inappropriate activation of T cells (the adaptive immune system) as well as abnormal keratinocyte proliferation (the innate immune system).

History

Onset of Lesions Usually, months but may be sudden as in acute guttate psoriasis and generalized pustular psoriasis (von Zumbusch).

Skin Symptoms Pruritus is reasonably common, especially in scalp and anogenital psoriasis.

Constitutional Symptoms In 5% of cases, psoriasis can be associated with arthritis, fever, and/or an “acute illness” syndrome (weakness, chills, fever) with generalized erythroderma.

Physical Examination

Skin Findings

Type Well-delineated, erythematous, thickened plaques with a characteristic silvery-white scale (Fig. 4-1A). Removal of scale results in the appearance of miniscule blood droplets (Auspitz sign).

Color Salmon pink to red.

Size Can range from pinpoint 1-mm papules to large 20- to 30-cm plaques.

Shape Round, oval, polycyclic, or annular.

Distribution Localized (e.g., elbows), regional (e.g., scalp), generalized (e.g., guttate psoriasis or erythroderma).

Sites of Predilection Favors elbows (Fig. 4-1B), knees, facial region, scalp, and intertriginous areas (axillae, inguinal folds, intergluteal cleft).

Other Scalp involvement is common (Fig. 4-1C). Hair loss (alopecia) is not a common feature even with severe scalp involvement. Fingernails and toenails are sometimes involved. Nail changes include pitting, subungual hyperkeratosis, onycholysis, and yellow spots under the nail plate “oil spot” (Fig. 4-1D).

General Findings

Psoriatic arthritis is rare before age 40 and occurs in 5% to 30% of the patients with skin findings. Arthritis may be mono- and symmetric oligoarthritis of the DIPs and PIPs, arthritis exclusively DIPs, rheumatoid arthritislike in medium-sized joints (PIP, MCP, wrists, ankles, and elbows), arthritis mutilans with severe joint destruction or spondylitis, and sacroiliitis.

Differential Diagnosis

Psoriasis may be confused with seborrheic dermatitis. The two entities may be indistinguishable and often an overlap, so-called sebopsoriasis presentation can be seen. Psoriasis must also be distinguished from atopic dermatitis, lichen simplex chronicus, pityriasis rosea, tinea corporis, contact dermatitis, psoriasiform drug eruptions (from β-blockers, gold, and methyldopa), and cutaneous T-cell lymphoma.

Laboratory Examinations

Dermatopathology Skin biopsy reveals (1) epidermal hyperplasia with thinning of the suprapapillary plates and elongation of the rete ridges; (2) increased mitosis of keratinocytes, fibroblasts, and endothelial cells; (3) parakeratotic hyperkeratosis (nuclei retained in the stratum corneum); and (4) inflammatory cells in the dermis (usually lymphocytes and monocytes) and in the epidermis (polymorphonuclear cells), forming microabscesses of Munro in the stratum corneum.

Throat Culture Throat culture for β-hemolytic streptococcus is indicated in cases of guttate psoriasis or in cases that are precipitated by a sore throat. If positive, antibiotic may be needed to clear both the infection and the psoriasis.

Course and Prognosis

Psoriasis typically has a chronic course with numerous remissions and exacerbations. Some children progress to mild disease with intermittent asymptomatic flares. Other children have a more severe course with recurrent extensive flares, and 5% may develop an associated arthritis in adulthood.

Management

The treatment of psoriasis depends upon the extent and severity of the disease, as well as the site involved. While not usually as itchy as atopic dermatitis, many patients complain of pruritus. Patients should be instructed never to rub or scratch the areas since trauma can precipitate psoriatic plaques (Koebner’s phenomenon).

1. 1. Emollients such as petrolatum, mineral oil, Vaseline, or moisturizers (CeraVe, Eucerin, Moisturel, and Aquaphor creams) should be used to keep the skin well hydrated.

   2. Ambient sunlight exposure helps psoriasis, and children should be encouraged to cautiously expose the affected areas to the sun for short periods during the day. Sunscreen should be used, and sunburning should be avoided.

   3. Baths are helpful in soothing the pruritus and removing the scale. They should be lukewarm and limited to 10 minutes in duration. For some, it may be helpful to add bath oil, salt, or tar (Balnetar bath oil) to the water.

   4. Tar preparations can be suggested to reduce the skin inflammation. Bath emulsions, creams (Elta tar), and ointments (MG217) can be used twice daily, but are not recommended for prolonged periods of time.

   5. Topical steroid creams are effective if used in appropriate strengths:

   • a. Low-potency steroids (desonide 0.05%, 1% or 2.5% hydrocortisone) can be used on the face and groin area, no more than bid × 2 wks/mo.
   • b. Medium-potency steroids (mometsaone 0.1%, fluticasone 0.05%, triamcinolone 0.1%) can be used on the extremities or body no more than bid × 2 wks/mo.
   • c. High-potency steroids (clobetasol 0.05%, diflorasone 0.05%, betamethasone dipropionate 0.05%) should be reserved for older children/adults on severely affected areas bid for no more than 2 weeks (see Topical Corticosteroids).

   6. Oral antibiotics may be effective, especially in guttate psoriasis flares precipitated by Streptococcus pharyngitis. Certain antibiotics also possess anti-inflammatory properties and can help if there are signs of secondary infection—open moist areas that weep or become crusted. Some commonly prescribed antibiotics include penicillin VK (25–50 mg/kg/d divided qid, not to exceed 3 g/d), cephalexin (25–50 mg/kg/d divided qid, not to exceed 4 g/d), dicloxacillin (25–50 mg/kg/d divided qid, not to exceed 2 g/d), cefadroxil (30 mg/kg/d divided bid), and erythromycin (30–50 mg/kg/d divided qid, not to exceed 2 g/d).

   7. Steroid-sparing topical creams include the following:

   • a. Vitamin D analogs (calcipotriene 0.005%) typically used bid to affected areas. It may also be used in conjunction with topical steroids. A commonly used maintenance schedule recommends calcipotriene applied bid to affected areas Monday through Friday and a topical steroid applied bid Saturday and Sunday.
   • b. Retinoids (tazarotene 0.1% cream or gel) can be used to decrease epidermal proliferation and is applied qhs to affected areas. The retinoids typically help reduce the psoriatic scale, but often are too irritating for use in younger children.
   • c. Anthralins (Drithrocreme, Dritho-Scalp) have an antiproliferative effect and can be used qid to affected areas, but often are too irritating for use in younger children.

   8. For the scalp, tar (T/Gel, DHS) selenium sulfide (Selsun), zinc pyrithione (Head & Shoulders), or ketoconazole (Nizoral) shampoos used two or three times per week can help reduce scaling. Topical steroid solutions (fluocinolone 0.01% scalp solution) can be applied qam sparingly to the affected areas to help decrease erythema and itching.

   9. Phototherapy with UVB, narrow band UVB, or PUVA (psoralen with UVA) works well, but increases the lifetime risk of skin cancer, and is usually not recommended for children.

   10. Methotrexate, cyclosporin, systemic retinoids (acitretin), and systemic biologic agents (alefacept, efalizumab, etanercept, infliximab, adalimumab) are typically not used in children and reserved for severe, refractory cases with careful prescreening and close blood monitoring.

Psoriasis Vulgaris, Guttate Type

Guttate psoriasis is an acute flare of multiple generalized small psoriatic plaques that often follows streptococcal pharyngitis. This form is relatively rare (2% of all psoriasis cases), but commonly seen in children and often clears. Guttate psoriasis may be more chronic, especially in adults, and may be unrelated to streptococcal infection.

Physical Examination

Skin Lesions

Type Papules 2 mm to 1 cm.

Color Salmon pink.

Shape Guttate (Latin, “spots that resemble drops”).

Arrangement Scattered discrete lesions (Fig. 4-2).

Distribution Generalized, usually sparing the palms and soles and concentrating on the trunk, less on the face, scalp, and nails.

Differential Diagnosis

Guttate psoriasis needs to be differentiated from pityriasis rosea, viral exanthem, psoriasiform drug eruption, and secondary syphilis.

Laboratory Examination

Serologic An increased antistreptolysin O, anti-DNase B, or streptozyme titer in those patients with antecedent streptococcal infection.

Throat Culture May be positive for β-hemolytic Streptococcus aureus.

Course and Prognosis

Often, but not always, this type of psoriasis spontaneously disappears in a few weeks, especially with antibiotic treatment.

Management

The resolution of lesions can be accelerated by judicious exposure to sunlight. For persistent lesions, treatment is same as for generalized plaque psoriasis. Penicillin VK (25–50 mg/kg/d divided qid, not to exceed 3 g/d) if group A β-hemolytic Streptococcus is cultured from throat.

Palmoplantar Pustulosis

Palmoplantar pustulosis is a rare, relapsing eruption limited to the palms and the soles characterized by numerous sterile yellow, deep-seated pustules that evolve into crusts and scales.

Physical Examination

Skin Lesions

Type Pustules that evolve into crusts and scaling.

Color Dusky red base, yellow pustules.

Size 2 to 5 mm.

Distribution Localized to palms (Fig. 4-3A) and soles (Fig. 4-3B).

Differential Diagnosis

Palmoplantar pustulosis needs to be differentiated from tinea manuum, tinea pedis, dyshydrotic eczema, and contact dermatitis.

Laboratory Examination

Dermatopathology Skin biopsy reveals edema and exocytosis of mononuclear cells forming a vesicle. Later, neutrophils form a pustule.

Course and Prognosis

Palmoplantar pustulosis can recur for years and is difficult to treat. Infrequently, psoriasis vulgaris may develop elsewhere. Pustulosis of the palms and soles can very rarely be associated with sterile inflammatory bone lesions (chronic recurrent multifocal osteomyelitis, pustulotic arthroosteitis, and SAPHO syndrome: synovitis, acne, pustulosis, hyperostosis, and osteitis).

Management

The resolution of lesions can be accelerated by judicious exposure to sunlight. Steroids under occlusion at night can hasten resolution.

Psoriasis Vulgaris, Erythrodermic

Erythrodermic psoriasis is a serious, often life-threatening condition in patients with psoriasis, characterized by full-body redness (erythroderma) and scaling. A preexisting dermatosis can be identified in 50% of patients and psoriasis is the second most common cause of erythroderma after atopic dermatitis.

Insight

Erythroderma is one of the true dermatologic emergencies. An etiology should be sought quickly and supportive care initiated immediately.

Synonyms Dermatitis exfoliativa, erythroderma of Wilson–Brocq.

Epidemiology

Age Any age.

Gender M > F.

Incidence Rare.

Etiology In childhood, erythroderma is more likely owing to preexisting dermatitis such as atopic dermatitis or psoriasis.

Classification Acute phase with generalized scaly erythema and fever, lymphadenopathy. Chronic form characterized by nail dystrophy but no loss of scalp and body hair (compared to other forms of erythroderma, e.g., drugs, mycosis fungoides).

History

Duration of Lesions Acute onset of systemic symptoms and red swollen patches and plaques that evolve into a widespread exfoliative erythema in the setting of previous psoriasis.

Skin Symptoms Generalized pruritus.

Generalized Symptoms Chills, malaise, fatigue, anorexia, weight loss.

Physical Examination

Skin Findings

Type of Lesions Confluent diffuse erythema covered by laminated scales. Skin becomes dull, scarlet, swollen, with areas of oozing (Fig. 4-4). Desquamation usually occurs after a few days. The palms and soles are covered by thick scales and have deep fissures. Secondary infections by bacteria can develop.

Color Bright red.

Arrangement Confluent.

Distribution Generalized.

Hair Normal.

Nails Onycholysis, shedding of nails with dystrophy.

General Findings

Generalized lymphadenopathy.

Diagnosis and Differential Diagnosis

Diagnosis Clinical diagnosis of psoriatic erythroderma is not always easy, especially in the absence of previous history of psoriasis. Cutaneous signs of psoriasis are helpful, such as pitting of the nails, psoriasiform plaques on the scalp, or intergluteal erythema.

Differential Diagnosis Other causes of erythroderma include pityriasis rubra pilaris, seborrheic dermatitis, drug hypersensitivity, atopic dermatitis, cutaneous T-cell lymphoma, lichen planus, pemphigus foliaceous, epidermolytic hyperkeratosis, and acute graft-versus-host disease.

Laboratory Examinations

Hematology Elevated sedimentation rate.

Chemistry Low serum albumin and increased γ-globulins.

Microbiology Blood cultures will be negative (usually obtained to rule out infection in the setting of high fever).

Dermatopathology Psoriasiform dermatitis with elongated and thickened ridges, marked parakeratosis, absent granular layer, intra- and intercellular edema, epidermal invasion by leukocytes, and a dermal perivascular inflammatory infiltrate.

Course and Prognosis

Variable. Can be very prolonged and recurrent.

Management

Supportive care often requiring hospitalization is necessary to maintain fluid–electrolyte homeostasis and body temperature. Skin biopsy should be performed if the cause of the erythroderma is not known (no known predisposition to psoriasis). Topical treatment includes emollients and steroids under wraps. Systemic steroids, retinoids, or immunosuppressives (methotrexate or cyclosporin) may be necessary. In older children, phototherapy with UVB, narrow band UVB, or PUVA may be helpful.

Pityriasis amiantacea (“asbestoslike”) refers to the condition of large, adherent flakes of thick scale that coat the scalp and hair. It may be associated with hair loss which is generally not permanent.

Synonyms Tinea amiantacea.

Physical Examination

Type Erythematous plaques with adherent, thick yellowish scale (Fig. 4-5).

Color Yellow to white or gray.

Distribution May be localized or present throughout the scalp and the scale may be adherent to the hair.

Differential Diagnosis

Pityriasis amiantacea is generally thought to be a subset of scalp psoriasis or seborrheic dermatitis; it needs to be differentiated from tinea capitis.

Course and Prognosis

Pityriasis amiantacea is chronic, remitting, and difficult to treat.

Management

Topical tar (T/Gel) selenium sulfide (Selsun), zinc pyrithione (Head & Shoulders), or ketoconazole, salicylic acid (T/Sal, Sebulex) shampoos used 2 or 3 × per week can help reduce scaling.

Often the adherent scale can be difficult to remove, especially in individuals with long hair. In such cases, warm towel wraps to loosen the scale, and fine tooth combing may be helpful.

Topical steroid solutions (fluocinolone 0.01% or flucinonide 0.05%) can be applied sparingly to the affected areas to help decrease erythema and itching, but then should be tapered to avoid adverse effects.

The ichthyosiform dermatoses and erythrokeratodermas are disorders of cornification. The ichthyosis are a group of hereditary disorders, characterized by generalized scaling of the skin. The erythrokeratodermas are a groups of inherited conditions characterized by erythema and hyperkeratosis, with no scale. The clinical severity for all these disorders varies from very mild and asymptomatic to life-threatening.

Classification

Ichthyosis vulgaris: Autosomal dominant.

• X-linked ichthyosis (XLI): Recessive X-linked, only expressed in males.
• Bullous congenital ichthyosiform erythroderma: Autosomal dominant.
• Congenital ichthyosiform erythroderma: Autosomal recessive.
• Lamellar ichthyosis (LI): Autosomal recessive.

Pathophysiology

LI shows increased germinative cell hyperplasia and increased transit rate through the epidermis. In ichthyosis vulgaris and X-linked ichthyosis, the formation of thickened stratum corneum is caused by increased adhesiveness of the stratum corneum cells and/or failure of normal cell–cell separation. Epidermolytic hyperkeratosis shows increased epidermal cell turnover with vacuolization because of intracellular edema.

History

All types of ichthyosis tend to be worse during the dry, cold winter months and improve during the hot, humid summer. Patients living in tropical climates may remain symptom free, but may experience symptomatic appearance or worsening on moving to a more temperate climate.

Diagnosis

Usually, the diagnosis can be made based on clinical findings.

Management

Hydration of Stratum Corneum Pliability of stratum corneum is a function of its water content. Hydration is best accomplished by immersion in bath followed by the application of petrolatum (petroleum jelly, hydrated petrolatum, or Aquaphor).

Keratolytic Agents Propylene glycol with lactic acid (Epilyt) is effective without occlusion. Combinations of salicylic acid and propylene glycol (Keralyt) can be used alone or under plastic occlusion. α-Hydroxy acids such as lactic acid bind water or control scaling. Urea-containing preparations (2%–20%) (Aquacare, Carmol) help to bind water in the stratum corneum. Lac-hydrin contains buffered lactic acid.

Systemic Retinoids Retinoids such as isotretinoin and acitretin are reserved for severe cases of LI, but careful monitoring for toxicity is required. Severe cases may require intermittent therapy over long periods of time. Continuous long-term use in children is contraindicated.

Collodion Baby

Ichthyosis in the newborn often presents as a collodion baby (Fig. 4-6). It is not a distinct disorder, but can be the first presentation of several (usually autosomal recessive) ichthyoses. At birth, the collodion baby is encased in a clear, parchmentlike membrane, which may impair respiration and sucking. When the membrane is shed 2 to 3 weeks later, the infant may have difficulties with thermal regulation and an increased susceptibility to infections. After healing the skin will appear normal. Sixty to seventy percent of these babies will go on to develop some form of ichthyosis later in life.

Insight

Some 20% of collodion babies will go on to have totally normal skin.

Synonyms Self-healing collodion fetus, desquamation of the newborn, ichthyosis congenita, lamellar exfoliation of the newborn.

Epidemiology

Age Newborn.

Gender M = F.

Incidence Rare.

Etiology Unclear.

Pathophysiology

Collodion membranes can be seen in various forms of ichthyoses, but the mechanism behind the formation of the membrane is not clear. In the case of lamellar ichthyosis, transglutaminase-1 deficiency leads to abnormal cornification which causes the membrane, but in other ichthyoses, the pathogenesis in unclear.

History

Onset Membrane is present at birth.

Duration of Lesions Desquamation of the membrane is usually complete by 2 to 3 weeks of life.

Physical Examination

Skin Findings

Type Transparent, parchmentlike membrane encasing the newborn.

Color Skin-colored.

Distribution Membrane covers the entire body surface.

General Findings

Collodion babies are often premature with an increased morbidity and mortality. If the membrane is thin, it can spontaneously resolve leaving normal or dry skin in the newborn. If the membrane is thick, it can impair respiration, sucking, and the infant’s mobility. The stiffness of the membrane can also cause an ectropion, eclabion, and hypoplasia of the nose and ear cartilage. In severe cases, when the membrane sheds, the infant can experience temperature and fluid–electrolyte instability.

Laboratory Examination

Dermatopathology Skin biopsy shows a thickened stratum corneum, but the collodion membrane is generally not diagnostic of the underlying ichthyotic condition, thus deferring skin biopsy until the membrane is shed may be preferable.

Differential Diagnosis

Clinical findings are diagnostic. A collodion baby needs to be clinically differentiated from a harlequin fetus, a more severe frequently lethal condition. The skin in a harlequin baby has a thickened stratum corneum with deep cracks and fissures (Fig. 4-6).

Course and Prognosis

The collodion membrane breaks up and peels during the first 2 weeks of life predisposing the infant to difficulties in thermal regulation and an increased risk of infection. The final appearance of the skin depends on the etiology of the condition. The collodion baby may be the initial presentation of lamellar ichthyosis or congenital ichthyosiform erythroderma. In rare instances, the collodion baby progresses to Sjogren-Larssen syndrome, trichothiodystrophy, infantile Gaucher disease, or Netherton syndrome.

Management

The management of the collodion baby are primarily supportive. Collodion babies require hospitalization and incubation at birth. The infant should be kept in a high-humidity incubator to maximize membrane hydration. Wet compresses and lubricants or emollients can also increase skin pliability. Clear fluids or IV hydration may be needed until the infant’s ability to eat has been ascertained. Respiratory efforts may also need external support. As the membrane begins to shed 2 to 3 weeks later, the infant should be frequently monitored for temperature and electrolyte instability. Throughout the shedding process, careful monitoring for skin and lung infections is also recommended.

Harlequin Fetus

A harlequin baby is very rare, severe form of congenital ichthyosis with thickened stratum corneum that cracks and fissures shortly after birth. The condition is associated with premature delivery and poor fetal outcome.

Synonyms Harlequin fetus, harlequin ichthyosis, ichthyosis congenita gravior.

Epidemiology

Age Newborn.

Gender M = F.

Incidence Fewer than 100 case reports.

Etiology Molecular basis is unclear.

Genetics Possibly autosomal recessive.

Pathophysiology

The abnormally thickened stratum corneum is thought to be caused by a defect in lipid synthesis or protein dephosphorylation which leads to defective lamellar body formation and secretion in the skin.

History

Onset Thickened skin is present at birth and cracks forming large adherent plates of skin separated by deep fissures.

Skin Symptoms Skin is rigid and thick.

Physical Examination

Skin Findings

Type Polygonal/triangular/diamond-shaped plaques because of skin fissuring.

Color Gray/yellow cracked skin forming plaques, deep red fissures.

Distribution Whole-body is involved with a marked ectropion (turning out of the eyelids), eclabium (fish-mouth deformity), distorted flat ears, and sometimes microcephaly (Fig. 4-7).

General Findings

Most infants are stillborn or die in the neonatal period. Newborns exhibit poor feeding and difficulties with temperature and electrolyte regulation. The rigidity of the skin impairs movement and respiration. The large fissures in the skin can lead to infection and sepsis.

Differential Diagnosis

The clinical presentation of a harlequin fetus is diagnostic. It should be differentiated from the less severe form of congenital ichthyosis—a collodion baby.

Laboratory Examinations

Histopathology Skin biopsy reveals a characteristic thick and compact orthokeratotic stratum corneum, absent granular layer, plugged sweat ducts, and sebaceous follicles filled with hyperkeratotic debris. Hair follicles have a characteristic marked accumulation of keratin material around the hair shaft, which can be used to diagnose the condition prenatally.

Ultrastructural Findings Abnormal or missing lamellar bodies in the granular layer, absent lipid lamellae, and/or lipid inclusions in the stratum corneum.

Course and Prognosis

The course and prognosis for a harlequin fetus is very poor. Most infants die early because of prematurity, infection, or thermal or electrolyte imbalance.

Management

Intensive supportive measures are necessary to provide adequate nutrition, manage body temperature, monitor fluid and electrolyte balance, and prevent infections in the perinatal period. Systemic retinoids such as isotretinoin and acetretin may increase survival, but the harlequin skin is permanent and the resultant quality of life is poor.

Ichthyosis Vulgaris

Ichthyosis vulgaris (IV) is characterized by mild, generalized hyperkeratosis with xerosis (dry skin) most pronounced on the lower legs. It is frequently associated with atopy.

Insight

The pretibial area usually shows prominent scaling; many of these patients also have keratosis pilaris.

Synonyms Ichthyosis simplex, autosomal dominant ichthyosis

Epidemiology

Age of Onset Childhood.

Gender M = F.

Mode of Inheritance Autosomal dominant, variable clinical presentation.

Incidence Common, 1/250 people.

Etiology Decreased or absent profillagrin leads to decreased keratohyaline granules and an abnormal granular layer.

History

Very commonly associated with atopy (atopic dermatitis, allergies, hay fever, asthma). Xerosis and pruritus worse in winter months. Hyperkeratosis and less commonly xerosis are of cosmetic concern to many patients.

Physical Examination

Skin Findings

Type Xerosis (dry skin) with fine powdery scale (Fig. 4-8). Increased accentuation of the palmar and plantar skin markings.

Color Normal skin color, white powdery scale.

Distribution Diffuse involvement, accentuated on the shins, arms, and back, but sparing the body folds (axillae, antecubital, and popliteal fossae); face is also usually spared.

General Findings

IV may be seen with other signs of atopy: atopic dermatitis, asthma, allergies, hay fever, and keratosis pilaris.

Differential Diagnosis

IV needs to be differentiated from xerosis, X-linked ichthyosis, lamellar ichthyosis, and drug-induced ichthyoses.

Laboratory Examinations

Dermatopathology Mild orthokeratotic hyperkeratosis with a thickened stratum corneum and a reduced or absent granular layer.

Electron Microscopy May demonstrate abnormal or decreased keratohyaline granules.

Course and Prognosis

May show improvement in the summer and in adulthood.

Management

1. 1. Emollients such as petrolatum, mineral oil, Vaseline, or moisturizers (Lubriderm, Eucerin, Moisturel, and Aquaphor creams) should be used to keep the skin well hydrated.

   2. Ceramide-containing creams seem particularly effective (Cerave).

   3. Moisturizing cleansers can be helpful (Dove, Cerave).

   4. Keratolytic agents containing urea (Carmol), α-hydroxy (Aquaglycolic), lactic acid (AmLactin, Lac-hydrin), and salicylic acids can be used bid to the affected areas to help exfoliate the diffuse scale, but should be avoided in young children because the stinging sensation is usually not well tolerated. The face and groin areas should also be avoided.

X-Linked Ichthyosis

X-linked ichthyosis occurs in males and is characterized by prominent dirty brown scales occurring on the neck, trunk, and extensor surfaces with onset soon after birth. Female carriers may exhibit mild skin findings.

Insight

Because of placental sulfatase deficiency, the delivery of these patients may be complicated by failure of initiation and/or progression of labor.

Synonym Ichthyosis nigricans, steroid sulfatase deficiency.

Epidemiology

Age of Onset Usually appears in the first 3 to 12 months of life.

Gender Males only. Female carriers may exhibit partial abnormalities.

Incidence 1 in 2000 to 9500 males.

Mode of Inheritance X-linked recessive. Gene has been cloned; prenatal diagnosis is possible.

Genetic Defect Reduced or absent steroid sulfatase caused by the deletion of STS gene on chromosome Xp22.32.

Pathophysiology

X-linked ichthyosis is caused by a deficiency or absence of steroid sulfatase. Impaired hydrolysis of cholesterol sulfate and DHEAS leads to an increased accumulation of cholesterol-3-sulfate in the epidermis. This, in turn, leads to increased cellular adhesion and clinically apparent hyperkeratosis.

History

In addition to the discomfort caused by xerosis, the dirty brown scales on the neck, ears, scalp, and arms are a major cosmetic disfigurement, causing the patient to appear “dirty” all the time.

Physical Examination

Skin Findings

Type Large firmly adherent scales separated by zones of normal-appearing skin gives the area a cracked appearance (Fig. 4-9).

Color Scales are light to dark brown.

Shape Fish-scale pattern.

Distribution Lateral neck, back, upper arms, chest, and abdomen; prominent scalp scaling may occur. Palms, soles, and face are spared.

General Findings

During the second or third decades, deep corneal opacities develop in 10% to 50% of affected males and some female carriers for X-linked ichthyosis. In women pregnant with an affected male fetus, the decreased estrogen levels can cause the cervix not to dilate during labor, necessitating C-section. Affected males have an increased risk of cryptorchidism, putting them at higher risk for testicular cancer and hypogonadism.

Differential Diagnosis

X-linked ichthyosis needs to be differentiated from xerosis, ichthyosis vulgaris, lamellar ichthyosis, and drug-induced ichthyoses.

Laboratory Examinations

Dermatopathology Skin biopsy will show hyperkeratosis with a moderately increased stratum corneum and a granular layer present in contrast to ichthyosis vulgaris.

Laboratory Findings High levels of cholesterol sulfate can be measured in the serum, stratum corneum, nails, placenta, or amniotic fluid. A biochemical assay for steroid sulfatase activity can also be performed. In pregnant women with an affected fetus, decreased estrogen or nonhydrolyzed sulfated steroids in the urine can be detected. Finally, a Southern blot, FISH, or PCR assay can be used to detect the exact genetic defect.

Course and Prognosis

X-linked ichthyosis is chronic and persistent but may wax and wane with the seasonal variation in humidity. It does not improve with age. The skin findings do not cause physical limitations, but can be cosmetically distressing.

Management

1. 1. Emollients such as propylene glycol, petrolatum, mineral oil, Vaseline, or moisturizers (Lubriderm, Eucerin, Moisturel, and Aquaphor creams) should be used to keep the skin well hydrated.

   2. Keratolytic agents such as Epilyt, Keralyt, Lac-Hydrin, and Carmol can be used bid to the affected areas to help exfoliate the diffuse scale, but should be avoided in young children because the stinging sensation is usually not well tolerated. The face and groin areas should also be avoided.

   3. Topical retinoids such as tazarotene may be helpful, but may be too irritating in young children.

Bullous Congenital

Ichthyosiform Erythroderma

Bullous congenital ichthyosiform erythroderma is a chronic disfiguring disorder that initially presents with blistering and erosions. Gradually, the skin changes to a more diffuse, hyperkeratotic, almost verrucous appearance.

Synonym epidermolytic hyperkeratosis, bullous ichthyosis, bullous congenital ichthyosiform erythroderma of Brocq.

Epidemiology

Onset The disease is present at or shortly after birth.

Gender M = F.

Prevalence One in 200000 to 300000

Etiology Genetic mutation of keratin 1, 10 (or 2e in ichthyosis bullosa of siemens).

Inheritance The disease has an autosomal dominant inheritance, but 50% of patients exhibit new mutations.

Pathophysiology

Mutations in keratins 1 and 10 localized on chromosome 12q11–q13 and 17q12–q21, respectively. The genetic mutations affect keratin alignment, oligomerization, and filament assembly resulting in a weakened cellular skeleton and skin blistering.

History

The major complaint early in life is blistering, which is painful and can cause widespread denudation. Later, the hyperkeratosis becomes disfiguring and malodorous.

Physical Examination

Skin Findings

Type Early flaccid blisters (Fig. 4-10) can lead to peeling, erosions, and large denuded areas. Later, there is erythematous hyperkeratosis with verrucous plaques.

Color Early, skin is erythematous. Later, thick scales are dark brown.

Distribution All surfaces of the body can be involved, and flexural areas are accentuated. Many patients have palmar and plantar involvement (keratoderma).

General Findings

Hair, nails, and teeth are usually normal.

Differential Diagnosis

Bullous congenital ichthyosiform erythroderma at birth needs to be differentiated from other blistering disorders such as epidermolysis bullosa, staphylococcal scalded skin syndrome, toxic epidermal necrolysis, and bullous impetigo. The clinical appearance of the later verrucous form may be confused with lamellar ichthyosis but the pathology is usually diagnostic.

Laboratory Examinations

Dermatopathology Skin biopsy reveals dense orthokertotic hyperkeratosis and keratinocytes show intracellular vacuolization with keratin intermediate filament clumping described as “epidermolytic hyperkeratosis”.

Electron Microscopy Reveals clumping of keratin intermediate filaments.

Other Genetic screening for keratin 1 and 10 defects can be used prenatally.

Course and Prognosis

The blistering ceases during the second decade, but hyperkeratosis persists for life. Later, the hyperkeratosis is a problem because of the disfigurement, malodor from secondary infection, and discomfort from limitation of motion. Severe scalp involvement can lead to hair loss.

Management

Early in the blistering stage of the disease, supportive care is needed to prevent infection, dehydration, fluid/electrolyte imbalances, and temperature fluctuations. Once denuded, lubricants and careful handing is necessary.

The following are helpful in the later verrucous form:

1. 1. Keratolytic agents with urea (Carmol), salicylic acid (Salex), and α-hydroxy acids (Aquaglycolic) can be used to help exfoliate the diffuse scale, but should be avoided in young children because the stinging sensation is usually not well-tolerated. The face and groin areas should also be avoided.

   2. Systemic retinoids such as isotretinoin and acitretin are useful in controlling the hyperkeratosis, but they may cause flares of the blistering. The side effects of the drugs on bones and tendons are a concern and long-term use is generally not recommended.

Lamellar Ichthyosis

LI often presents at birth with the infant encased in a collodion membrane (see “Collodion Baby,”  Fig. 4-6), which is soon shed with subsequent formation of large, coarse scales in a generalized distribution.

Synonyms Nonbullous, congenital, ichthyosiform erythroderma, ichthyosis congenita 2, nonerythrodermic AR lamellar ichthyosis.

Epidemiology

Age of Onset A collodion baby at birth is usually the initial presentation (Fig. 4-6). In some cases, the disease is not evident until 3 months of age.

Gender M = F.

Incidence One in 200000 to 300000.

Mode of Inheritance Most families exhibit an autosomal recessive inheritance. Autosomal dominant cases have been reported.

Pathophysiology

Mutation of transglutaminase-1 (chromosome 14q11.2) has been found in a number of patients, but at least two other genetic loci (on chromosomes 2q33–q35 and 19p12–q12) have been identified. Transglutaminase-1 helps cross-link the structural proteins (involucrin, loricrin, keratin intermediate filaments) in the upper epidermis, malfunction leads to abnormal skin cornification and desquamation.

History

Lamellar ichthyosis typically presents at birth as a collodion baby. After 2 to 3 weeks, the collodion membrane is shed and replaced by large scales. During exercise and hot weather, hyperthermia may occur because of a decreased ability to sweat. Fissuring of stratum corneum may result in excess water loss and dehydration. Young children have increased nutritional requirements because of excessive shedding of stratum corneum. Fissures on hands and feet are painful.

Physical Examination

Skin Lesions

Type At birth, infant typically presents with a collodion membrane which is shed in 2 to 3 weeks. Subsequently, large parchmentlike scales develop over the entire body (Fig. 4-11A). Scales are large and very thick. Fissuring of hands and feet is common.

Distribution Generalized. Hyperkeratosis around joints may be verrucous (Fig. 4-11B). Patients may have ectropion (eyelids are turned outward) and eclabium (lips turned outward).

Hair and Nails Hair bound down by scales; frequent infections result in scarring alopecia. Nails show ridges and grooves.

General Findings

Tightness of facial skin leads to ectropion, eclabium, and hypoplasia of the nose and ear cartilage. Hyperkeratosis results in obstruction of eccrine sweat glands with resultant impairment of sweating and risk of overheating. Scale accumulation in the ear canal can lead to occlusion and infection.

Laboratory Examinations

Dermatopathology Skin biopsy shows dense hyperkeratosis, patchy parakeratosis, increased granular layer (in contrast to ichthyosis vulgaris), acanthosis, and papillomatosis.

Other Tranglutaminase-1 activity of the kerotinocytes can be measured. Genetic testing for the Transglutaminase-1 gene mutation can be performed for prenatal diagnosis.

Differential Diagnosis

At birth, the collodion baby presentation can precede a number of icythyotic disorders and the differential is long (see “Collodion Baby”). Later in life, the dark platelike scale is clinically diagnostic.

Course and Prognosis

For lamellar ichthyosis, the collodion membrane present at birth is shed. However, platelike, diffuse scales persist throughout life and there is no improvement with age.

Management

Patients with lamellar ichthyosis should avoid situations that may lead to overheating. Their skin appearance can be improved with:

1. 1. Topical calcipotriene has anecdotally been shown to be somewhat helpful.

   2. Topical retinoids (tazarotene) can increase skin turnover with reported success.

   3. Topical lactic acid and propylene glycol have also shown some improvement in decreasing scale.

   4. Systemic retinoids such as isotretinoin and acitretin are useful in controlling the hyperkeratosis and clinical improvement of the ectropion and eclabium. The side effects of the retinoids on bones and tendons are a concern and long-term use is not recommended.

Keratosis Pilaris

Keratosis pilaris (KP) is a common benign skin condition characterized by follicular-based hyperkeratosis with mild erythema. It is most prominent on the lateral upper arms and thighs, but can also be seen on the cheeks of children. It is commonly seen in individuals with a personal or family history of atopy.

Epidemiology

Age Appears in early childhood.

Gender M = F.

Incidence Common.

Etiology Excessive keratinization within hair follicles.

Genetics Autosomal dominant inheritance.

Season Worse during cold seasons.

Physical Examination

Skin Findings

Type of Lesion Discrete follicular papules often with superimposed keratotic plug. (Fig. 4-12A).

Color Red or brown.

Distribution Lesions are prominent on the outer aspects of upper arms and thighs, sometimes on the cheeks of children.

Palpation Skin has a rough texture reminiscent of gooseflesh or plucked chicken skin.

General Findings

Often associated with other signs of atopy: atopic dermatitis, asthma, allergies, hay fever, or ichthyosis vulgaris.

Differential Diagnosis

The diagnosis of KP is made clinically. KP is common, but there are rare KP-like variants:

1. 1. Ulerythema ophryogenes (KP rubra atrophicans faciei). X-linked condition notable for widespread KP that begins with follicular-based keratotic papules on the lateral eyebrows that resolve with depressed pits and alopecia.

   2. Keratosis rubra faciei. Similar to ulerythema ophryogenes, except that the lesions begin on the cheeks and temples (Fig. 4-12B).

   3. Atrophoderma vermiculata (folliculitis ulerythema reticulata). Characterized by symmetric atrophic pits on the cheeks, forehead, and eyebrows.

Laboratory Examinations

Dermatopathology Skin biopsy reveals follicular hyperkeratosis and a sparse inflammatory infiltrate in the dermis.

Course and Prognosis

KP is benign but persistent and chronic. Occasionally, it subsides after the age of 20 years. Patients are most distressed by its rough texture and cosmetic appearance.

Management

1. 1. Emollients such as petrolatum, mineral oil, Vaseline, or moisturizers (CeraVe, Eucerin, Moisturel, and Aquaphor creams) should be used to keep the skin well hydrated.

   2. Keratolytic agents such as Epilyt, Keralyt, Lac-Hydrin, and Carmol may be used bid to the affected areas to help exfoliate the diffuse scale, but should be avoided in young children because the stinging sensation is usually not well tolerated. The face and groin areas should also be avoided.

   3. Topical steroid creams can be used intermittently to decrease the erythematous appearance of the rash:

   • a. Low-potency steroids (2.5% hydrocortisone) can be used on the face or body no more than 2 wks/mo.
   • b. Medium-potency steroids (triamcinolone 0.1%) can be used on the extremities or body no more than 2 wks/ mo.

Pityriasis Rubra Pilaris

Pityriasis rubra pilaris (PRP) is a chronic disease characterized by follicular papules, orange to pink scaly plaques, and a palmoplantar keratoderma.

Epidemiology

Age Two peaks: before the age of 20 years, and after the age of 60 years.

Classification (1) Familial, an autosomal disorder presenting at birth or with onset during infancy or childhood and (2) acquired type, seen in individuals older than 15-years-old.

Gender M = F.

Incidence Uncommon.

Inheritance Nearly all cases are acquired. Some reports of autosomal dominant or autosomal recessive inheritance.

Pathophysiology

Genetic abnormal cornification of unclear pathogenesis. Possible mechanisms hypothesized include abnormal vitamin A metabolism, physical (UV exposure, infections), superantigens, or autoimmune triggers.

History

Skin Symptoms Mild-to-moderate pruritus or burning sensation. Pain in areas of fissured skin.

Physical Examination

Skin Findings

Type Follicular hyperkeratosis on an erythematous base. Ranges from scale and erythema of the face, scalp, and ears (often the initial presentation) to punctate papules on the body coalescing into large plaques with characteristic “islands of normal skin” (Fig. 4-13A).

Color Reddish-brown papules, orange and salmon-colored plaques.

Distribution In some children: focally on the elbows and knees, in other children and adults: generalized form with plaques on the trunk and extremities. Punctate keratoses (resembling a “nutmeg grater”) on the dorsal aspects of first and second phalanges, hands, wrists, knees, ankles, feet, sides of neck, and trunk.

General Findings

Thickened hyperkeratotic palms and soles (forming “sandal” like scleroderma). Nail dystrophy (thickening, opacification, subungual hyperkeratosis; pitting not common) (Fig. 4-13B).

Disease can rarely progress into an exfoliative erythroderma associated with fever, chill, malaise, and diarrhea.

Differential Diagnosis

The differential diagnosis for PRP includes psoriasis, seborrheic dermatitis, lichen planus, atopic dermatitis, and viral exanthem. Clinically, the classic “islands of spared normal skin” differentiate PRP from all other dermatoses.

Laboratory Examinations

Dermatopathology Skin biopsy reveals irregular “checkerboard pattern” hyperkeratosis with alternating vertical and horizontal parakeratosis, follicular plugging, a mononuclear cell infiltrate in the dermis, and focal acantholytic dyskeratotic cells or acantholysis within the epidermis can be seen.

Course and Prognosis

Childhood PRP has a persistent course characterized by spontaneous remissions and exacerbations.

Management

1. 1. Emollients such as petrolatum, mineral oil, Vaseline, or moisturizers (CeraVe, Eucerin, Moisturel, and Aquaphor creams) should be used to keep the skin well hydrated.

   2. Keratolytic agents such as Epilyt, Keralyt, Lac-Hydrin, and Carmol can be used bid to the affected areas to help exfoliate the diffuse scale, but should be avoided in young children because the stinging sensation is usually not well tolerated. The face and groin areas should also be avoided.

   3. Topical steroids creams can be used intermittently to decrease the erythematous appearance of the rash:

   • a. Low-potency steroids (2.5% hydrocortisone) can be used on the face or body no more than 2 wks/mo.
   • b. Medium-potency steroids (triamcinolone 0.1%) can be used on the extremities or body no more than 2 wks/mo.
   • c. High-potency steroids (clobetasol 0.05%, diflorasone 0.05%, betamethasone dipropionate 0.05%) should be reserved for older children/adults on severely affected areas bid for no more than 2 weeks.

   4. Less toxic regimens are recommended for the childhood form of PRP, but in severe refractory cases oral retinoids (isotretinoin, acitretin), systemic steroids, and/or methotrexate may be necessary.

Darier Disease

Darier disease is a rare autosomal dominant disorder of defective intracellular Ca2+ signaling of the endoplasmic reticulum and mitochondria in keratinocytes. Clinically, the patients present with keratotic crusted brown malodorous follicular-based papules and plaques on the scalp, face, neck, and trunk.

Synonyms Keratosis follicularis, Darier- White disease.

Epidemiology

Age Seventy percent of patients have disease onset between 6 and 20 years.

Gender M = F.

Incidence One in 55000 to 100000.

Genetics Autosomal dominant disease with complete penetrance, but varying clinical severity. Genetic mutation localized to the ATP2A2 gene on chromosome 12q23–24.

Season Exacerbation during summer months/sun exposure (photo-Koebner phenomenon).

Pathophysiology

The disease has been localized to the ATP2A2 gene on chromosome 12q23–24. The defective gene leads to abnormal functioning of an endoplasmic reticulum Ca2+ ATPase (SERCA2) resulting in abnormal intracellular Ca2+signaling. The inadequate Ca2+ stores impairs correct protein synthesis of molecules necessary for good cell-to-cell adhesion. This causes acantholysis (loss of suprabasilar cellular adhesion) and apoptosis (increased cellular death).

Physical Examination

Skin Lesions

Type Small keratotic crusted papules and plaques with greasy scale coalescing into warty plaques (Fig. 4-14A).

Color Skin-colored to yellow-brown or red.

Palpation Rough.

Distribution Follicular distribution on face, scalp, chest. Intertriginous lesions (axillae, groin) are common.

Sites of Predilection Seborrheic areas (trunk scalp, face, neck) are sites of predilection. Keratotic papules on dorsal surface of hands and feet and punctate lesions on palms/soles.

Nail Findings Red, gray, or white longitudinal streaks with V-shaped notch at end and subungual hyperkeratosis (Fig. 4-14B).

Mucous Membranes White painless cobblestone papules coalescing into plaques. Oropharynx (palate, gingiva, mucosa, and tongue), larynx, or anorectal mucosa may be involved.

General Findings

Skin lesions are malodorous and patients have an increased susceptibility to infections. Rarely, mental deficiency, schizophrenia, epilepsy, small stature reported.

Differential Diagnosis

Darier disease may be confused with seborrheic dermatitis, transient acantholytic dermatosis, pemphigus foliaceous, and Hailey-Hailey disease. These can be differentiated clinically or histopathologically.

Laboratory Examinations

Dermatopathology Skin biopsy shows suprabasal acantholysis and dyskeratotic cells because of apoptosis. Hyperkeratosis is present and can be quite thick. Darier disease has characteristic findings:

1. 1. Corps ronds (acantholytic keratinocytes with partially fragmented nuclei surrounded by clear cytoplasm and a ring of collapsed keratin bundles) in the Malpighian layer.

   2. Corp grains (oval cells with bright eosinophilic cytoplasm of collapsed keratin bundles and shrunken nuclear remnants) in the stratum corneum.

Electron Microscopy Ultrastructurally, skin lesion demonstrate a loss of desmosomes and detachment of the keratin filaments from the desmosomes.

Course and Prognosis

Darier disease persists throughout life, but does have periods of exacerbation and partial remission. The most distressing aspects of the condition are the odor, disfigurement, and pruritus. Fifteen percent have oral involvement. Patients report worsening of the skin symptoms in the summer months and aggravation by sun exposure, heat, sweat, and humidity. Additionally, individuals are more susceptible to infections with bacteria, yeast, or fungus.

Management

1. 1. Lightweight clothing and sun protecting help prevent exacerbations of Darier disease, which can be triggered by heat, sun, or sweating.

   2. Antimicrobial cleansers (Panoxyl, Hibiclens) can be used to decrease malodorous bacterial colonization. Secondary bacterial infections can be treated with oral antibiotics (cephalexin 25–50 mg/kg/d divided qid, not to exceed 4 g/d, dicloxacillin 25–50 mg/kg/d divided qid, not to exceed 2 g/d, and erythromycin 30–50 mg/kg/d divided qid, not to exceed 2 g/d).

   3. Keratolytic agents such as Epilyt, Keralyt, Lac-Hydrin, and Carmol can be used to reduce scaling and irritation, but should used cautiously in young children because stinging may not be tolerated. The face and groin areas should also be avoided.

   4. Topical retinoid creams may also be helpful (tretinoin, tazarotene, adapalene) but are limited by their irritating side effects.

   5. Topical steroid creams can be used intermittently but are often not effective:

   • a. Low-potency steroids (2.5% hydrocortisone) can be used on the face or body no more than 2 wks/mo.
   • b. Medium-potency steroids (triamcinolone 0.1%) can be used on the extremities or body no more than 2 wks/mo.
   • c. High-potency steroids (clobetasol 0.05%, diflorasone 0.05%, betamethasone dipropionate 0.05%) should be reserved for older children/adults on severely affected areas bid for no more than 2 weeks.

   6. Patients need to be cautioned about topical steroid side effects. Continued use can cause thinning of the skin, striae formation, and systemic absorption, especially in younger children and infants. Steroids used around the eye area for prolonged periods can lead to glaucoma and/or cataract formation.

   7. Systemic retinoids such as isotretinoin and acitretin are effective at smoothing the keratotic surface; however, long-term use of these agents is not recommended.

   8. In severe refractory cases of disfiguring disease, reports of cyclosporine dermabrasion, CO2, or erbium:YAG laser resurfacing have yielded some clinical success.