ACP medicine, 3rd Edition
Eczematous Disorders, Atopic Dermatitis, and Ichthyoses
Seth R. Stevens MD1
1Director, Global Medical Affairs, Amgen Inc
The author has no commercial relationships with manufacturers of products or providers of services discussed in this chapter.
Eczematous dermatitis, or eczema, is a skin disease that is characterized by erythematous vesicular, weeping, and crusting patches. Although the term eczema is often used as a diagnosis, it can in fact be used appropriately to describe lesions seen in several diseases. Itching is a characteristic symptom, and epidermal intercellular edema (spongiosis) is a characteristic histopathologic finding of eczematous conditions. The term eczema is also commonly used to describe atopic dermatitis [see Atopic Dermatitis, below].
Contact dermatitis, a paradigmatic example of an eczematous disorder, is common and well studied [see 2:V Contact Dermatitis and Related Disorders]. Contact dermatitis can be either allergic or irritant in etiology. Allergic contact dermatitis differs from other eczematous disorders in that determination of the offending contactant is an important part of the evaluation. If the patient's history does not provide the answer, the body site of the lesion may (e.g., head involvement in allergy to paraphenylenediamine in hair dye). Patch testing may be required to confirm the diagnosis.1
The manifestations of irritant contact dermatitis are similar to those of allergic contact dermatitis2; in the irritant form, however, the mechanism is not immunologic. Given sufficient concentration and duration of contact, offending agents will induce irritation in anyone's skin. Detergents, acids, alkalis, solvents, formaldehyde, and fiberglass are common causes.
Seborrheic dermatitis is another common eczematous condition [see 2:II Papulosquamous Disorders]. Clinically, seborrheic dermatitis may exist without vesicle formation. Lesional morphology is usually a greasy scale on erythematous patches; however, the scale may be dry and the patches may have an orange hue. Scalp, eyebrows, mustache area, nasolabial folds, and chest are typical areas of involvement. Psoriasis may be part of the differential diagnosis. Treatment is with shampoos containing selenium sulfide, zinc pyrithione, tar, or ketoconazole; emollients; and mild (nonfluorinated) topical steroids. Antimicrobial therapy directed at the commensal yeast Pityrosporum ovale can be effective, although a causative role of the organism remains unproved.
OTHER ECZEMATOUS DERMATITIDES
Two other eczematous dermatitides are nummular eczema and dyshidrotic eczema (pompholyx). Nummular eczema describes well-demarcated, coin-shaped eczematous patches that are usually 2 to 4 cm (rarely more than 10 cm) in diameter. The lesions are quite pruritic and require potent topical steroids, antihistamines, and, occasionally, intralesional or systemic corticosteroids for treatment. Dyshidrotic eczema presents as a vesicular eruption of the hands and feet, accompanied on rare occasions by hyperhidrosis. Typically, 1 to 2 mm vesicles appear on the sides of fingers, although more extensive involvement can occur. Treatment is with compresses and soaks, antipruritics, topical steroids, and, in severe recalcitrant cases, systemic corticosteroids. Photochemotherapy with topical psoralen and ultraviolet A irradiation (PUVA) may also be effective.
Atopic dermatitis (AD) is a common chronic inflammatory dermatosis that generally begins in infancy. The term atopy was coined in the early 1920s to describe the associated triad of asthma, allergic rhinitis, and dermatitis.3 Children with AD are at increased high risk of developing asthma and allergic rhinitis, and the risk is further increased for patients with a family history of atopy.4 The role of reaginic antibodies and allergies in the etiology of AD is controversial; in 80% of patients with AD, however, serum immunoglobulin IgE is elevated, sometimes markedly.
ETIOLOGY AND PATHOGENESIS
The expression of AD is a complex integration of environmental and genetic factors. The lifetime prevalence is estimated to be 30% of the population,5,6,7 possibly because of increasing contact with causative agents in the environment. Epidemiologic data suggest a genetic influence—25% of dizygotic twins and 75% of monozygotic twins are concordant for AD.8 The condition develops in 60% of children who have one affected parent and in 80% of children with two affected parents.9 The defect is likely carried in the immune system, because both antigen-specific IgE reactivity and AD have been transplanted from an AD-affected bone marrow donor to a previously unaffected recipient.10 Candidate genes continue to be investigated.11
AD can be quickly exacerbated by environmental trigger factors.12 Wool, lanolin, and harsh detergents are particularly irritating. Emotional stress can also lead to flares, which are characterized by increased itch, erythema, vesiculation, and excoriation, as well as expanded area of involvement. The role of airborne and foodborne allergens is difficult to assess. Although patients with AD frequently have circulating dust mite antigen-specific IgE and Th2 CD4+ T cells,13 hyposensitization infrequently results in improvement. Contact urticaria to food occurs in AD,14 but generalized exacerbation after eating is rare. In the absence of a strong supporting history, elimination diets are rarely effective in treating AD. A role has been frequently suggested for cow's milk in inducing AD; however, studies examining the association of AD and early feeding with cow's milk have shown varying results.15,16 Meta-analyses indicate that exclusive breast-feeding during the first 3 months of life is associated with lower incidence rates of atopic dermatitis during childhood in children with a family history of atopy.17
Gut microflora may be a natural source of immune modulation that prevents atopic dermatitis. In a double-blind, randomized, placebo-controlled trial, a probiotic containing a strain of Lactobacillus was administered prenatally to mothers who had at least one first-degree relative with atopy and 6 months postnatally to their infants; the frequency of AD in the group receiving Lactobacillus was half that of the placebo group.18 These findings suggest that impairment of the intestinal mucosal barrier may be involved in the pathogenesis of AD, and strengthening of the mucosal barrier with probiotic bacteria may help prevent AD in high-risk infants. Although intriguing, these results await confirmation.
Mechanisms have been proposed to explain a link between Staphylococcus aureus and exacerbations of AD,19 including effects of cell wall constituents to increase expression of IgE, IgE receptor, and enterotoxin B, a superantigen that activates T cells in an antigen-independent fashion.20
The apparent paradox of reduced cell-mediated immunity21,22 and hyperimmunoglobulinemia E seen in AD is addressed by the so-called Th1/Th2 model of helper T cells. In this model of the murine immune system, CD4+ T cells are divided into two mutually exclusive classes on the basis of cytokine secretion: Th1 cells, which secrete cytokines that promote cell-mediated immunity (e.g., interleukin-2 [IL-2], interferon gamma), and Th2 cells, which secrete cytokines that promote humoral immunity and eosinophil function (e.g., IL-4 and IL-5). Atopy, including AD, has been seen as the paradigmatic condition of a so-called Th1-deficient state. Refinements have shown a heterogeneity of responses within different AD lesions, however. The current model is that blood and acute lesions of AD patients are more often dominated by Th2 cells, whereas chronic lesions are more often dominated by Th1 cells.23
Hyperstimulatory dendritic antigen-presenting cells (Langerhans cells) are present in patients with AD.24 One proposed mechanism for the augmented function of Langerhans cells in AD is the binding of antigen-specific IgE and antigen to the IgE receptors on Langerhans cells as a means of antigen focusing.25 Another antigen-presenting cell, the monocyte, also manifests altered function in AD. Cyclic adenosine monophosphate (cAMP) phosphodiesterase has increased activity in monocytes of patients with AD—leading to hyperproduction of prostaglandin E2, among other effects. Increased cAMP phosphodiesterase in AD may explain aberrant adrenergic responses, and the increased prostaglandin E2 leads to diminished interferon-gamma production. Additionally, monocytes secrete IL-10 in AD, which further augments the so-called Th2 responses.26 Altered cyclic nucleotide metabolism leads to excessive release of histamine by basophils and, potentially, to mast cell degranulation. High levels of cAMP phosphodiesterase are found in the umbilical cord blood of infants of AD-affected parents.27 This finding may indicate an early, if not primary, defect in the disease that may become the basis of a diagnostic laboratory test.
Because IL-5 is a critical eosinophil growth factor and activating cytokine, blood eosinophilia may be expected to occur in a Th2 disease such as AD28; tissue eosinophilia, however, is variable. Cutaneous endothelial cells are also activated in AD, leading to increased expression of adhesion molecules and recruitment of leukocytes into the skin (i.e., dermatitis).
AD remains a clinical diagnosis. Major diagnostic criteria are (1) personal or family history of atopy (AD, allergic rhinitis, allergic conjunctivitis, allergic blepharitis, or asthma); (2) characteristic morphology and distribution of lesions; (3) pruritus; and (4) chronic or chronically recurring dermatosis. Several minor features can be added [see Table 1].14 Pruritus is a consistent feature of AD. The lack of itching or of another major diagnostic criterion should prompt consideration of alternative diagnoses [see Differential Diagnosis, below]. Cutaneous signs can vary, depending on the age of the lesions.
Table 1 Diagnostic Criteria for Atopic Dermatitis14
Acute lesions of AD are eczematous—erythematous, scaling, and papulovesicular. Weeping and crusted lesions may develop [see Figure 1]. Scratching results acutely in linear excoriations, presenting as erosions or a hemorrhagic crust. In extremely severe cases, exfoliative dermatitis (erythroderma) may occur, with generalized redness, scaling, weeping, and crusting. There may be accompanying systemic toxicity, sepsis, lymphadenopathy, altered thermoregulation (either hyperthermia or hypothermia), and high-output cardiac failure. Erythroderma is a potentially life-threatening condition.
Figure 1. Severe Eczematous Patches in Infant
Extensive, severe, weeping, crusted acute eczematous patches on the face of this infant are characteristic of patients in this age group.
Chronic lesions tend not to be eczematous (thus, atopic eczema is not an ideal synonym for AD). Instead, lichenified plaques [see Figure 2] or nodules predominate. Lichenification denotes areas of thickened skin divided by deep linear furrows. Lichenified plaques result from repeated rubbing or scratching and thus often occur in areas of predilection, such as the popliteal and antecubital fossae. As is typical of lesions in AD, lichenification is poorly demarcated. There may be accompanying acute signs. Lichenified lesions are very difficult to treat; once established, they may persist for months even with adequate therapy and avoidance of rubbing or scratching.
Figure 2. Lichenified Patches
Lichenified patches appear after chronic rubbing of eczematous patches. These lesions are characteristic of chronic allergic contact dermatitis and atopic dermatitis.
Clinical expression of AD also varies with the age of the patient. The infantile stage of AD occurs up to approximately 2 years of age. Of all cases of AD, approximately 90% arise before the fifth year and 60% in the first year of life; onset before 2 months of age is unusual, however.8 During infancy, ill-defined, erythematous scaling patches and confluent, edematous papules and vesicles are typical. These lesions may become crusted and exudative. Intense pruritus leads to scratching, which induces linear excoriations and, with time, lichenification. Before the infant begins to crawl, the scalp and face are most often involved [see Figure 3], although lesions may be seen anywhere. After the child begins crawling, the extensor surfaces—particularly the knees—become involved. Involvement of fingers can be severe if the child sucks them frequently. Intense pruritus can lead to sleep disturbances of child and parents. Other features may arise [seeTable 1]. Perifollicular accentuation and papules are commonly seen at any point in the life of an atopic patient, particularly in persons of Asian or African ancestry.
Figure 3. Erythroderma in Infant
Erythroderma (total body erythema) and extensive scaling are seen in this infant with congenital ichthyosiform erythroderma.
During childhood, the clinical features evolve into those seen in adults. Lesions tend to become less eczematous and drier, with increasing flexural and neck involvement. Scaling, fissured, and crusted hands may become especially troublesome. Infraorbital folds (sometimes called Morgan lines or the Dennie sign) and pityriasis alba can appear. Chronic or chronically relapsing pruritic, erythematous, papulovesicular eruptions that progress to scaling, lichenified dermatitis in a flexural distribution typify adult AD. Extensive areas of skin may be involved, including the face, chest, neck, flanks, and hands. Areas of dyspigmentation may result from repeated skin trauma. Approximately 10% to 15% of childhood AD persists after puberty.8
AD that begins after 20 years of age has been termed adult-onset atopic dermatitis.29 This condition should be considered in patients with characteristic features of AD.
There are many associated features of AD. Asthma and allergic rhinitis, the major and minor criteria, respectively, have already been mentioned. Another important association, cutaneous infection, is related to diminished cutaneous cell-mediated immunity and defective chemotaxis. S. aureus is usually found on AD skin, and its density correlates with lesion severity.30 Although such observations have implicated S. aureus as a cause of AD,19,31 it is also clear that reduction in AD lesions reduces bacterial colonization.32 Regardless, the high bacterial counts in lesional skin and the relative ease of their reduction suggest the desirability of extra efforts (e.g., use of topical steroids) to reduce the presence of S. aureus before elective procedures are performed through involved skin. Frank infection also occurs more commonly in AD, which results in pustules and oozing, crusted lesions.
Cutaneous fungal and viral infections also occur frequently and with increased severity in patients with AD. Eczema herpeticum, an extensive eruption of 2 to 3 mm vesicles, pustules, and punched-out erosions caused by herpes simplex virus, may coalesce into extensive areas of eroded skin. Frequently, the condition is most severe on the face (where it often arises from a herpetic lesion) and diminishes as it progresses to the trunk and extremities. Secondary bacterial infection is common. Lymphadenopathy, fever, and malaise may develop. Antiviral and antibiotic therapy can be lifesaving and should be started empirically upon presentation. Tzanck test, viral culture, and direct fluorescent antibody detection of viral antigens can confirm the diagnosis.
Molluscum contagiosum and common warts are also problematic in patients with AD, as are dermatophyte infections. Because of similar appearance, foot eczema must be distinguished from tinea pedis by potassium hydroxide preparation or fungal culture.
Numerous ocular complications of AD exist.33 These include anterior subcapsular cataracts, retinal detachment, keratoconus, blepharitis, conjunctivitis, and iritis.
The differential diagnosis of AD includes the eczematous conditions and ichthyoses described in this chapter and other immunologic, metabolic, neoplastic, and rheumatologic disorders [see Table 2]. Because 80% to 85% of patients with occupational hand dermatitis have AD, the possibility of coexisting AD and contact dermatitis needs to be considered. Another important element of the differential diagnosis is cutaneous T cell lymphoma. Cutaneous T cell lymphoma can arise clinically as scaling, erythematous patches or exfoliative erythroderma. The classic distribution—near axillae, buttocks, and groin—is distinct from that of AD, and patches are frequently well demarcated. There is often sufficient clinical overlap between the two conditions, however, to necessitate further investigation, including histology, immunophenotyping, and gene-rearrangement analysis of T cell receptors. Cutaneous T cell lymphoma can arise in patients with AD, and the lack of conclusive clinical or laboratory tests for either disease can make distinction difficult. Reassessment from time to time in such cases is recommended.34
Table 2 Differential Diagnosis of Atopic Dermatitis
Reduction of Trigger Factors
Reduction of trigger factors (e.g., harsh chemicals, detergents, and wool) and avoidance of occupations that require contact with trigger factors (e.g., hairdressing, nursing, and construction) can be helpful.35 Appropriate behaviors should be taught to patients and parents early during life, when habits are more easily formed.36,37
The use of mild, nonalkali soaps and frequent use of emollients are important elements in the long-term management of AD. Because moisture evaporating off the skin can trigger flares, bathing is sometimes discouraged. A better approach is the prompt application of an emollient such as petrolatum (finishing within 3 minutes of the end of the bath), which can serve to seal the moisture from the bath. Lotions and creams containing high amounts of water are usually inadequate, however, and can actually worsen AD. Products containing hydroxy acids, phenol, or urea can reduce dryness and scaling, but these can sting inflamed skin and should therefore be used with caution. Because of a specific reduction of ceramides in AD, a lotion that provides excess ceramides relative to other lipids has been shown to have a therapeutic advantage in AD.38 Bubble baths and scented salts and oils can be irritating. Scalp care should include a bland shampoo. Topical tar products, such as shampoos and bath solutions, and topical creams and lotions containing 5% to 10% liquor carbonis detergens can help. Baths, soaks, and compresses with Burow solution can ameliorate crusted, infected, eczematous patches. Cotton clothing, washed to remove finishing (which often releases formaldehyde), is preferable to wool or synthetics.
Topical corticosteroids are another mainstay of therapy. Application immediately after bathing improves cutaneous penetration. Lowering the risk of side effects with less potent preparations must be balanced against gaining control of a flare quickly with more potent preparations. Long-term use of inadequately potent topical corticosteroids may pose a greater risk of adverse effects than brief use of more potent agents followed by a rapid taper to bland emollients. Because steroid-induced cutaneous atrophy is a greater risk on the face, in intertriginous areas (e.g., groin, axillae, and inframammary folds), and under diapers, less potent steroids (e.g., hydrocortisone and desonide) should be used in these areas, and they should be used with particular caution. For the remainder of the body, midpotency preparations, such as 0.1% triamcinolone acetonide, are helpful. More potent ointments, such as fluocinonide and desoximetasone, are useful for lichenified plaques. Flurandrenolide tape is useful for nodular prurigo (so-called picker's nodules) because it also physically protects the area from manipulation. For the scalp, solutions are preferred.
Systemic corticosteroids (e.g., prednisone, 20 to 80 mg/day orally) may be useful to treat severe, acute flares. Because of the risks of gastrointestinal, endocrine, skeletal, central nervous system, and cardiovascular complications, however, they should not be used more than twice yearly.
The steroid-free topical calcineurin inhibitors, tacrolimus ointment and pimecrolimus cream, are effective alternatives to topical corticosteroids. These agents do not cause the skin atrophy associated with prolonged use of topical corticosteroids and, therefore, are useful for treating skin on the face and neck.
The macrolide antibiotic tacrolimus (formerly FK506) has been found to be effective in treating moderate to severe atopic dermatitis. The efficacy of tacrolimus has been shown in several randomized, controlled trials.39,40,41 The most common adverse side effects are skin burning, flulike symptoms, skin erythema, and headache.41 Topical tacrolimus is available in 0.1% and 0.03% concentrations. In children with moderate and severe AD, treatment with tacrolimus ointment (0.03%) was shown to be superior to conventional 1% hydrocortisone acetate.42
The ascomycin derivative pimecrolimus (ASM 981) cream is a cell-selective cytokine inhibitor that was specifically developed for treatment of inflammatory skin diseases. Its mechanism of action is similar to that of topical tacrolimus. Two independent randomized, multicenter studies found pimecrolimus to be effective in infants and children with AD.43 Another randomized, multicenter study found that pimecrolimus was effective in preventing AD flares, which reduced the need for topical corticosteroids.44 In adults, pimecrolimus was found to be effective and well tolerated, and it reduced the incidence of AD flare.45
A meta-analysis of 16 trials involving more than 5,300 patients showed success rates of tacrolimus and pimecrolimus to be statistically similar; however, tacrolimus success rates were numerically higher than those of pimecrolimus, and tacrolimus was used in patients with more severe disease.46 The efficacy of these drugs must be balanced against a potential cancer risk. The Food and Drug Administration recently issued a warning that these drugs should be used only as directed and only after other eczema treatments have failed to work.47
Antihistamines can sometimes be helpful in breaking the itch-scratch cycle in AD. Sedating antihistamines, such as hydroxyzine and diphenhydramine, are particularly useful—especially when itching prevents sleep48; however, the sedative properties of antihistamines may limit their use in AD. Cetirizine, a sedating antihistamine, appears to be well tolerated in infants. A multinational, randomized, placebo-controlled trial examined the effects of long-term treatment with cetirizine on infants with AD; the drug proved to be safe, and it reduced the need for topical corticosteroids in patients with more severe disease.49 Nonsedating antihistamines such as fexofenadine and loratadine are less useful. Doxepin, a tricyclic antidepressant known to have antihistaminic effects, can be beneficial when applied topically in a 5% cream.50
Virtually every phototherapy regimen has been reported to ameliorate AD. Some patients cannot tolerate the heat generated by the equipment, however—particularly that used in UVB irradiation. In addition to UVB, the following can be beneficial: UVA, longwave UVA1, narrow-band UVB, UVA-UVB, and PUVA. Extracorporeal photochemotherapy (photopheresis) is reported to be effective therapy for recalcitrant disease.51 Phototherapies are expensive, and prolonged use of PUVA has been linked to an increased risk of melanoma.52Although some patients may benefit from natural sunlight, the risk of sunburn and induction of malignancy by ultraviolet light must be considered.
Antimicrobials are obviously important for patients with infection. Less clear is whether antimicrobial agents can directly treat AD by reducing bacterial products thought to exacerbate the condition. Antistaphylococcal therapy has been advocated for use in patients with AD; however, a double-blind, placebo-controlled study of flucloxacillin did not show improvement in AD despite reduced bacterial counts.53Ketoconazole, likewise, has been used; its success, however, may be the result of anti-inflammatory, rather than antifungal, effects.
More advanced therapeutic options exist for severe, recalcitrant AD. The altered expression of cytokines in AD [see Etiology and Pathogenesis, above] has led investigators to explore the use of interferon gamma. Clinical trials have demonstrated that for some patients, daily subcutaneous administration of interferon gamma is effective in reducing both signs and symptoms of AD54,55 and that long-term treatment can maintain the benefit.56 However, moderate results and high costs make interferon gamma less viable as a treatment option.
Oral cyclosporine (2.5 to 5 mg/kg/day orally),57,58 methotrexate (15 to 25 mg/wk orally), and azathioprine (100 to 200 mg/day orally) can be used in severe,59 recalcitrant disease provided that patients are monitored for adverse effects specific to those agents.
Traditional Chinese herbal medicine has been found to be effective in the treatment of AD, both in children60 and in adults,61 although the efficacy of this treatment remains controversial.62 The mechanisms of action of these preparations are unclear. A small, randomized, placebo-controlled study found topical treatment with St. John's wort to be significantly superior to placebo in patients with moderate AD.63Although evening primrose oil has for many years been proposed to be effective in AD, a well-controlled study failed to show any benefit to patients taking either evening primrose oil or a combination of evening primrose oil and fish oil, as compared with those receiving placebo.64 Patients should be cautioned that herbal remedies are not risk free and may carry a potential for hepatotoxicity, cardiomyopathy, and other adverse effects; such remedies should be monitored, as should any other treatment. To avoid potential adverse drug reactions, physicians should identify any herbal remedies used by patients.65
Topical vitamin B12 was found to be significantly superior to placebo in reducing the extent and severity of AD in a randomized, multicenter phase III study66; however, larger trials are needed to establish the efficacy of this therapy. The cAMP phosphodiesterase inhibitor cipamfylline in cream form has been shown to be more effective than placebo but significantly less effective than hydrocortisone cream in the treatment of AD.67 The importance of well-controlled studies to assess efficacy of treatments must be stressed because AD patients on the placebo arms of most controlled studies tend to show benefit, sometimes marked.
The ichthyoses are a group of diseases of cornification that are characterized by excessive scaling.68 Etiologies of the ichthyoses are diverse, including genetic defects of structural proteins and enzymes, as well as acquired forms. Only the major clinical variants will be discussed here.
Ichthyosis vulgaris, the most common form of ichthyosis, is found in approximately one in 300 births. This autosomal dominant condition presents as dry skin with fine scaling. The extensor surfaces of extremities are the most commonly affected areas. Ichthyosis vulgaris can occur concomitantly with keratosis pilaris and can also be associated with AD. Age at onset is typically between 3 months and 12 months. Implicated etiologic factors include reduced filaggrin (filament-aggregating protein) and its precursor profilaggrin, whose normal functions are to allow for aggregation of keratin filaments and to serve as sources of compounds that hydrate the skin. The clinical severity of ichthyosis vulgaris correlates with the degree of reduction in filaggrin and profilaggrin. Another possible etiologic factor is the reduced activity of proteases that normally lead to dissociation of keratinocytes.69
Recessive X-linked ichthyosis occurs in approximately one in 2,000 to one in 6,000 male infants. Although collodion membrane may be present at birth, the skin is usually normal, with fine scaling beginning at 1 to 3 weeks of life. Typically, the scales are thick and dark, giving the skin a dirty appearance. Extensor distribution—combined with involvement of the sides of the neck and preauricular skin and sparing the flexural areas—is typical. Steroid sulfatase deficiency is an etiologic factor, causing an increase in cholesterol sulfate and a decrease in cholesterol in the stratum corneum.70 The accumulated cholesterol sulfate may inhibit proteolysis—a process similar to the inhibition seen in ichthyosis vulgaris. Prenatal diagnosis is available, and gene therapy may be on the horizon.
Lamellar ichthyosis occurs in one in 300,000 births. It is inherited in an autosomal recessive pattern. Collodion membrane may be present at birth but is then shed, revealing characteristic large, platelike scales. Erythroderma may be present, albeit difficult to discern because of the thickness of the scales. Ectropion is present in most patients and can give rise to ophthalmic complications. Lamellar ichthyosis is often caused by mutations in the gene encoding the enzyme transglutaminase 1.71
Congenital Ichthyosiform Erythroderma
Formerly, congenital ichthyosiform erythroderma [see Figure 3] was considered to be a variant of lamellar ichthyosis. Both are inherited as autosomal recessive traits, and collodion membrane may be present at birth in both conditions. Ectropion, eclabion (eversion of the lip), and erythroderma can also occur. Like patients with lamellar ichthyosis, patients with congenital ichthyosiform erythroderma may have platelike scales on the lower extremities, but scales are fine and white on other parts of the body. Also in contrast to lamellar ichthyosis, X-linked ichthyosis, and ichthyosis vulgaris—whose lesions are scaly because of an abnormal ability to desquamate (so-called retention hyperkeratoses)—the lesions of congenital ichthyosiform erythroderma are scaly because of increased production of keratinocytes (so-called hyperproliferative ichthyosis).
Epidermolytic hyperkeratosis (formerly called bullous congenital ichthyosiform erythroderma) is autosomal dominant in inheritance. The combinations of large blisters and erythema with denuded skin that appear at birth may be confused with epidermolysis bullosa, staphylococcal scalded skin syndrome, or toxic epidermal necrolysis. Several months to 1 year after birth, the blisters become less prominent, and thick, verrucous plaques comprising rows of hyperkeratotic ridges develop. Flexural skin is usually involved, but the disease can be more extensive. Bacterial colonization leads to a clinically significant foul odor. Abnormal keratin gene expression is the etiologic basis of this condition.71
Acquired ichthyoses have been associated with numerous systemic diseases and medications. Although the onset of scaling is commonly a manifestation of dryness or ichthyosis vulgaris, patients with unusual manifestations or with severe or recalcitrant disease warrant further investigation. Endocrinopathies (e.g., thyroid disease), autoimmune diseases, infectious diseases (e.g., HIV), and malignancies such as lymphomas [see Figure 4] and other carcinomas have been associated with the onset of ichthyosiform dermatosis.
Figure 4. Acquired Ichthyosis
This patient developed marked scaling (acquired ichthyosis) over a 6-month period. Investigation revealed non-Hodgkin lymphoma.
The standard therapy for the ichthyoses is emollients (e.g., petrolatum) and keratolytics (e.g., lactic acid with or without propylene glycol).72 Lactic acid should be used cautiously in neonates to avoid causing excess absorption. Oral retinoids (which require lipid monitoring) can be helpful, particularly in the management of X-linked ichthyosis, congenital ichthyosiform erythroderma, and lamellar ichthyosis. Epidermolytic hyperkeratosis is the most difficult of these conditions to treat because of the risk of blistering induced by therapeutic agents. Antimicrobial agents can be useful to reduce the odor caused by bacterial colonization.
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Editors: Dale, David C.; Federman, Daniel D.