Eczema

Eczema is a common condition where there is inflammation of the skin, usually causing itching and sometimes scaling or blisters. There are several different types of eczema and some forms are better known as dermatitis (such as contact dermatitis and photodermatitis). Eczema is sometimes the result of an allergy, but is often of unknown cause.

Types

Atopic eczema.

Atopic eczema is a chronic, superficial inflammation that occurs in people who have an inherited tendency towards allergy. The condition is common in babies. An intensely itchy rash occurs, usually on the face, in the elbow creases, and behind the knees. The skin often scales and small red pimples may appear. Infection may occur if the rash is scratched, breaking the skin. For mild cases, emollients (such as petroleum jelly) help to keep the skin soft. In severe cases, ointments containing corticosteroid drugs may be used. Antihistamine drugs may be prescribed to reduce itching. Excluding certain foods from the diet may help to control the condition. Atopic eczema often clears up on its own as a child grows older.

Nummular eczema

Nummular eczema usually occurs in adults and is of unknown cause. It produces round, itchy, scaling patches on the skin that are similar to those of tinea (ringworm). Topical corticosteroids may reduce inflammation, but the eczema is often persistent.

Hand eczema

Hand eczema is usually caused by irritant substances such as detergents, but it may occur for no apparent reason. Itchy blisters develop, usually on the palms, and the skin may become scaly and cracked. Hand eczema usually improves if emollients are used and if cotton gloves with rubber gloves over them are worn when coming into contact with irritants. If the eczema is severe, corticosteroids may be prescribed.

Stasis eczema

Stasis eczema occurs in people with varicose veins. The skin on the legs may become irritated, inflamed, and discoloured. The swelling of the legs may be controlled with compression bandages or stockings. Application of ointments containing corticosteroids may give temporary relief.

General Treatment

To reduce irritation and the risk of scratching, a soothing ointment should be applied to the affected areas; these may then be covered with a dressing to prevent scratching. Absorbent, non-irritating materials (such as cotton) should be worn next to the skin; irritants (such as wool, silk, and rough synthetics) should be carefully avoided.

Introduction to eczema

What is eczema?

Dermatitis/eczema in detail - technical

Essentials

Eczema is a characteristic pattern of skin inflammation that has many subtypes, with some induced by external factors such as irritants or skin sensitizers. Atopic eczema is due partly to a genetic susceptibility, which programmes altered immune responses and skin physiology, together with reactions to exogenous allergens and microbes, but a number of eczema patterns do not appear to have external causes.

The key points in the recognition of eczema are that the skin is reddened, may be thickened as a result of the inflammatory infiltrate and oedema, and the affected areas have ill-defined margins that break up into tiny red papules. Acute or severe eczema bubbles, blisters, and weeps. The distribution of the rash may be diagnostic, both of the type of eczema and the key causal factors.

Management requires identification and avoidance of provoking factors. The inflammation is treated with topical steroids of different potencies, supplemented with moisturizers. Newer therapies include topical calcineurin antagonists, with a range of systemic therapies being used to control the most severe types of disease.

Introduction

The term eczema is used to describe a pattern of skin inflammation characterized clinically by ill-defined areas of redness (erythema) made up of tiny individual papules (bumps). At the edges of eczema lesions the individual papules often become visible, which accounts for the lack of sharp definition (Fig. 1). Eczemas are characteristically very itchy. Microscopically, eczematous inflammation shows infiltration of T lymphocytes in both the dermis and epidermis, and the generation of oedema in the dermis, but also particularly in the epidermis. The oedema separates the epidermal cells from each other like the air spaces in a sponge (called spongiosis), but the oedema may coalesce into blisters, giving the appearance of a bubbly surface; these may leak or rupture producing serous oozing and crusting. There are many different types of eczema, some with known causation and others remaining cryptic.

Poorly defined margins of eczema

Figure 1: Poorly defined margins of eczema.

Classification

There is no completely accepted classification of eczema, but it can be helpful to group eczemas in relation to what is known of their aetiology: those with mainly exogenous causation, often called dermatitis rather than eczema, and those with no known external causes (endogenous eczemas) (Bullet list 1). The exogenous eczemas are nevertheless the consequence of interactions between external factors and host susceptibility, which may be largely genetically determined.

Bullet list 1 Classification of eczema

Exogenous

  • Contact dermatitis
    • ◆ Irritant
    • ◆ Allergic
    • ◆ Photoinduced
  • Atopic eczema
  • Seborrhoeic eczema/dermatitis
  • Photodermatitis

Endogenous

  • Asteatotic eczema
  • Dyshidrotic eczema
  • Varicose eczema

Contact dermatitis/eczema

This form of dermatitis/eczema is induced by external agents of different physicochemical types: substances with irritant properties that are not immunogens, those that induce T-cell-mediated allergic contact sensitivity, and ultraviolet light.

Irritant contact dermatitis

Aetiology/pathogenesis

Irritants are substances that inflict toxic damage on the epidermis. There are many types of irritant, but from a practical point of view they can be classified as surfactants (soaps/detergents), solvents (petrol, paraffin, oils), caustics (acids, alkalis, chemicals such as phenol), and miscellaneous chemicals that include nonanoic acid and dithranol (used in the treatment of psoriasis). Irritants vary greatly in their potency and hence the level of exposure required to induce an inflammatory response in skin. Individuals also vary greatly in their intrinsic resistance or susceptibility to the effects of irritants. A single exposure to mild irritants such as soaps and detergents is often insufficient to cause a clinically apparent irritant effect, which usually requires multiple exposures having a cumulative effect.

The general effect of irritants is a perturbation of the epidermal microenvironment, which is detected as a danger signal. This results in the activation of essential components of the innate immune response. Keratinocytes produce a wide range of cytokines, including interleukin (IL)-8, IL-18, and tumour necrosis factor-α; epidermal Langerhans’ cells become activated and up to 30% may migrate into the dermis; the dermal microvasculature expresses increased levels of the adhesion molecules ICAM1, E-selectin (ELAM1), and VCAM1; and there is infiltration of lymphocytes and often neutrophil leucocytes. Repeated exposure may augment the microscopic response until it becomes clinically apparent inflammation. Most of the changes resulting from cumulative irritant insult are indistinguishable from those that follow the specific immunologically mediated process of allergic contact dermatitis.

Epidemiology

Irritant dermatitis is a major occupational skin disease. A survey in Sweden indicated that of 16 600 people who responded to a questionnaire about hand eczema, 11% had experienced eczema in the last year. Thirty five per cent of cases were irritant hand eczema, 19% allergic contact dermatitis, and 22% atopic hand eczema. In northern Germany, a large study from 1990 to 1999 examined compensation claims for occupational skin disease. The annual incidence of occupational irritant dermatitis was 4.5 cases per 10 000, compared with 4.1 cases per 10 000 of allergic contact dermatitis.

Clinical manifestations of irritant dermatitis

Under most circumstances the hands are the body site most likely to come into contact with irritants. One notable exception is the napkin area of infants, which may be in prolonged contact with alkaline (ammoniacal) urine or faecal material, and can develop irritant napkin dermatitis as a result.

The rash is erythematous with poorly defined margins, accompanied by scaling or fissures, and if more severe or acute, by eczematous blisters. The dorsa of the hands are usually more severely affected than the palmar surfaces, which probably reflects the thicker stratum corneum permeability barrier of the palms (Fig. 2). Once an irritant dermatitis has been initiated it seems to require very little and only occasional exposure to irritants to maintain a chronic dermatitis. Many patients who try to protect themselves by wearing rubber gloves find that when the hands become sweaty inside the gloves, this actually irritates and aggravates the dermatitis.

Dorsal hand involvement in dermatitis

Figure 2: Dorsal hand involvement in dermatitis.

Those with a past or present history of atopic eczema are significantly more susceptible to developing irritant dermatitis from surfactants and solvents. This may reflect an impaired stratum corneum barrier and/or summation/synergism of the irritant effects and low-level subclinical inflammation of atopic eczema.

Treatment

The most important principle is avoiding further contact with irritants. The medical treatment is as for other eczemas, as outlined in ‘Treatment of atopic eczema’ below.

Allergic contact dermatitis

Aetiology

Contact hypersensitivity is an acquired immune response in which T lymphocytes recognize and react to the causative molecules. Contact allergens are mostly small xenobiotic molecules, although under some circumstances proteins can act as contact sensitizers. Several factors are involved in determining whether an individual will develop contact sensitivity to a given molecule. These include the intrinsic immunogenicity of the chemical, the dose to which the individual is exposed, and the individual’s susceptibility to sensitization.

Sensitizing potency of chemicals

Of the thousands of chemicals in the environment, some are clearly highly potent immunogens capable of sensitizing everyone, while others may be defined as moderate, weak, or even nonsensitizers. For small molecules to become recognizable by the T-cell receptor, they have first to act as haptens, which become bound to protein carriers. The hapten–carrier complex will be processed by dendritic antigen-presenting cells such as epidermal Langerhans’ cells. Processing involves loading haptenated peptides into the major histocompatibility molecules (mainly MHC class II, but in some instances also Class I) on the surface of the antigen-presenting cell.

The sensitizing potency of chemicals is generally proportional to their protein-binding reactivity. Some compounds (haptens) are intrinsically protein reactive, others (prohaptens) are converted to protein-reactive metabolites through the actions of phase I xenobiotic metabolizing enzymes such as the cytochrome P450 family. The overall phenotype of xenobiotic detoxification systems, including P450 and other antioxidant systems, may be an important contributor to an individual’s susceptibility to sensitization. They may either detoxify reactive compounds and prevent immunogenicity, analogous to high acetylator status and resistance to drug allergy, or possibly through the failure of normal detoxification, may generate protein-reactive immunogenic intermediates.

Lessons from experimental work

The use of 2,4-dinitrochlorobenzene (DNCB) as an experimental contact sensitizer in healthy human volunteers has revealed that the human immune system obeys very reproducible dose-response relationships. Groups of individuals received different sensitizing doses of DNCB (62.5–1000 µg) on a 3 cm diameter circle of forearm skin. In proportion to the log of the sensitizing dose, there was a classical sigmoid dose-response curve for the proportion of individuals showing clinical sensitization, as detected by positive elicitation challenges applied 4 weeks later, with 100% being sensitized by 500 µg or more. Furthermore, as the sensitizing dose increased there was a log-linear increase in the strength of the response to the elicitation challenge; in other words, as the sensitizing dose increases on a log scale, so proportionately more people are sensitized, and to a greater extent.

For a chemical to induce allergic contact sensitization it must penetrate the stratum corneum. Most sensitizers are lipophilic and hence penetrate readily, but metals such as nickel, cobalt, and chromate are water soluble. Hence a major factor in augmenting sensitization by metals is mechanical penetration of the stratum corneum, as in body piercing.

The induction of contact sensitization involves the activation of hapten-specific T cells, which undergo clonal expansion resulting in the establishment of immunological memory. The next time the sensitizer is in contact with the skin it will be recognized by the memory T cells, which respond by releasing interferon-γ and other proinflammatory cytokines. This recruits other T cells to the site in a non-antigen-specific fashion. The combination of cells and cytokines generates the oedema and swelling accompanied by itch that is characteristic of allergic contact dermatitis.

Individual susceptibility

Very little is known of how individual susceptibility is controlled. There are clearly individuals who develop contact sensitivity to environmental substances more easily than others. Thus individuals who developed contact sensitivity to three or more unrelated chemicals could be sensitized experimentally by DNCB to a much greater degree than individuals with no pre-existing contact allergy. Individuals with only one contact sensitivity were intermediate in reactivity. These differences are not qualitative, but reflect the high-responder end of the normal distribution of responsiveness. The corollary of this is that there is a low-responder end of the normal distribution—individuals who appear resistant to the spontaneous development of contact sensitivities, and who give the lowest responses to any given sensitizing dose of DNCB.

There do not appear to be any major HLA associations with increased susceptibility to contact sensitization. As indicated above, one level at which susceptibility may be determined is that of intermediate metabolism, which can either detoxify or generate reactive intermediates. A second level, which has been shown at least with regard to nickel sensitivity, is the fundamental control of immunological tolerance, mediated by regulatory T lymphocytes.

Prevalence

Allergic contact sensitization and dermatitis are common; about 10% of women are sensitized to nickel. The total prevalence of contact dermatitis among the population of many countries is estimated at between 6 and 11%. The incidence of occupational contact dermatitis has been estimated to be around 0.5 to 1.9 cases per 1000 full-time workers per year.

Clinical features of allergic contact dermatitis

Allergic contact dermatitis can vary from a low-grade minor nuisance—the pierced earlobes that become mildly inflamed and itchy if the earrings are left in for too long—to catastrophic and disabling acute blistering and weeping with severe oedema of the sites to which the sensitizer was applied. The key points in diagnosis are the recognition that the inflammatory process is eczematous in nature, and that the distribution on the body raises the suspicion that there is an exogenous source. Thus contact dermatitis from nickel in the metal studs and buttons of denim jeans has a characteristic distribution around the lower abdomen and hips (Fig. 3). However, in strongly sensitized individuals nickel in most metal objects, such as money, keys, cutlery, and door handles, can transfer from the fingers to other places, resulting in ill-defined eczematous areas on the face and abdomen. The relationship of these distant areas to contact sensitivity may be much less obvious.

Allergic contact dermatitis to nickel

Figure 3: Allergic contact dermatitis to nickel.

Common sensitizers in everyday products include metals; dyes (paraphenylenediamine and other azo dyes) used for hair and clothing; preservatives (often formaldehyde releasers) found in many personal products; rubber accelerators found in rubber gloves and glue/cement used in shoe manufacture; colophony, extracted from pine resin and used to facilitate adhesion, as in the rubbery adhesive of sticking plasters, but also in mascara and felt-tipped pens; and fragrances used in personal and domestic products.

Confirmation of causality

Contact allergens are applied to the skin of the back in patch tests. Patients are normally screened by an initial application of 40 substances (some individual, others as mixtures of a class) referred to as the European standard battery. These compounds have been selected by the International Contact Dermatitis Research Group and the European Environmental and Contact Dermatitis Research Group because they represent the groups of the most frequent sensitizers. The patch tests are applied on aluminium disc chambers held in place with hypoallergenic adhesive tape for 48 h, after which the chambers are removed and the skin assessed. Each compound or mixture is used at the highest concentration that does not normally induce a nonspecific irritant reaction. Many centres read the patch tests a second time at 72 or 96 h after application; this is said to reduce the number of false-positive tests that may result from irritant effects, and may detect responses that are slower to evolve.

The final interpretation of causality depends not only on the presence of a positive patch test, but also on the demonstration of relevance in terms of the person actually being exposed to the culprit, and it making contact with them in the areas where there is clinical dermatitis. The use of patch tests in elucidating the presence of contact allergy in patients with hand dermatitis is of great importance, as there may be major implications for the person in terms of their occupation.

Treatment

The general approach is first to identify the causal agent(s) through careful history taking, examination, and patch tests, and then avoid it. The treatment of the eczematous inflammation is summarised in ‘Treatment of atopic eczema’ below.

Atopic dermatitis/eczema

Definitions

The atopic state is defined when an individual’s immune system responds to certain antigens by producing antibodies of the IgE class rather than the IgG class. There is considerable disagreement among dermatologists, paediatricians, and allergists over how best to define atopic eczema/dermatitis. Dermatologists define it as a diffuse symmetrical eczematous eruption that is characterized by onset in early life (infancy or childhood), and typically affects flexural sites such as the antecubital and popliteal fossae, and the hands and face. There is characteristically a personal and/or family history of allergic syndromes of asthma or rhinitis.

The main point of controversy is whether it is found only in individuals who are atopic. Among European dermatologists, atopic dermatitis is classified as extrinsic: associated with IgE-mediated allergies of mucosal systems, or intrinsic: usually of onset in adult life and not associated with the formation of allergen-specific IgE or clinical mucosal allergies. The extrinsic type accounts for around 80 to 95%, and the intrinsic type for 5 to 15% of cases of atopic eczema.

Incidence, prevalence, and natural history of atopic eczema/dermatitis

Over the last 40 years there has been a steady increase in the frequency of the atopic state and all the associated allergic syndromes of eczema, asthma, and rhinitis. While assessments for different national groups vary somewhat, it is now estimated that one-third of the population of the Western World is atopic. In the United Kingdom up to 15% of children will develop atopic eczema by the age of 12 years. The maximum incidence is during the first 2 years of life. Atopic eczema is usually the first of the atopic syndromes to develop, whereas asthma comes later, and rhinitis last—a sequence that has been called the atopic march. There are a number of patterns to the natural history, the most common being early onset and spontaneous remission during childhood. Atopic eczema affects up to 0.5% of the adult population. In some of these, the eczema has been present from early childhood, in others it recurs after a period of remission.

Clinical features

The distribution of atopic eczema varies with age. In precrawling infants it is often a diffuse symmetrical erythema with dryness affecting the head and neck, torso, and even the limbs. Once the baby starts crawling the eczema is usually distributed on the extensor surfaces of the arms, knees, and ankles, all of which are in physical and frictional contact with the floor surface on which the child is crawling. As the child becomes ambulatory the eczema tends to be distributed in the flexural areas, particularly the antecubital and popliteal fossae.

In some adults, the eczema may be localized predominantly or exclusively to the head, neck, and upper chest, a pattern possibly related to the distribution of the saprophytic skin microbe Malassezia furfur (previously called Pityrosporum orbiculare).

In addition to the flexural pattern, there is a pattern comprising circular or discoid patches of eczema, sometimes called nummular (coin-shaped), scattered on the torso and limbs. This pattern is not well associated with allergic sensitization (Fig. 4).

The extent of skin involvement is one of the indicators of the overall severity, others being the degree of redness, the presence of weeping/oozing and crusting, as well as the presence of excoriation. The main symptom of eczema is itch, which can be very intense; a child can work itself into a complete frenzy of scratching, which can be almost as distressing for the parents/carers because of the difficulty of relieving the symptom.

Discoid eczema

Figure 4: Discoid eczema.

Pathogenesis of atopic eczema

The pathogenesis of atopic eczema is still remarkably obscure. There is clearly genetic programming of susceptibility, with the atopic state being determined in a polygenic manner. Twin studies show that in monozygotic twins there is a 75% concordance rate, while it is only 21% in dizygotic twins. However, what causes the susceptibility to become manifest as disease is unknown. Many observations have been made of abnormalities in the physiological functions of the skin and the immune system, but it is not clear how they fit together.

The dominant hypothesis is that the atopic state is primarily a dysregulation of the immune system, in which characteristics of the fetal immune system aimed at avoiding immune rejection between the mother and fetus somehow fail to mature into the adult immune responses designed to give protection against the extrauterine world. Thus in the fetus, T-helper cells differentiate towards the Th2 phenotype. Following delivery, as the postnatal infant is colonized by microbes and exposed to endotoxin-producing pathogens, there is a change in the drivers of T-cell differentiation, resulting in the redirection of T-helper cells towards the Th1 phenotype. Lack of exposure to endotoxins from enteral pathogens is regarded as a major factor in the increase in the incidence of the atopic phenotype; the so-called hygiene hypothesis. So in early postnatal life the immune response of atopic individuals is directed via the Th2-derived cytokines IL-4, -5 and -13 to generate IgE, causing the activation of mast cells and eosinophils. This pattern of immune response correlates with the development of clinical atopic allergies, but it is not clear what causes the orientation to either the skin or mucosae.

Additional factors that may contribute to the altered immune response include constitutive overproduction of prostaglandin E2 and IL-10 by monocyte-macrophages, which favours Th2 differentiation. There is also evidence of constitutive overactivity of the cAMP-degrading enzyme phosphodiesterase 4. This results in the attenuation of intracellular signalling mediated via cAMP, but the consequences of this on the immune system or skin are not yet known.

Two main alterations have been detected in the skin itself. The first suggests an impaired contribution to innate immune responses. Thus, atopic eczematous skin produces decreased quantities of the antimicrobial peptides β-defensins, which have homologies with chemokines such as IL-8. This appears crucial in the increased susceptibility of atopic eczematous skin to infection by a range of microbes (see ‘Microbes’ below). The second alteration is the observation of a strong genetic association with mutations in the filaggrin gene. Filaggrin is a crucial component involved in the formation of the stratum corneum permeability barrier. This finding has not been confirmed in all populations studied, but it raises the important concept that altered permeability of the epidermis may be a primary factor in the development of atopic eczema.

The current working hypothesis is that atopic eczema, like other forms of eczematous inflammation, is a T-cell-mediated inflammation. However, the range of cells and mediators contributing to the pathogenesis is more complex than for other types of eczema. Thus, at the microscopic level atopic eczema is characterized by the infiltration of CD4+ T cells, and eosinophils. In acute lesions, degranulated mast cells can be seen. A factor thought to be of importance is the presence of IgE on the epidermal Langerhans’ cells. Antigen-specific cell-bound IgE is thought to facilitate the presentation of very low levels of antigen to T cells, so-called antigen focusing. Atopic eczema is regarded as multifactorial; some of the recognized triggering or aggravating factors include airborne and dietary allergens, microbial colonization and infection, emotional factors, and climatic factors (temperature and humidity). There are probably other as yet unrecognized factors.

Role of allergy

There are two sides to allergy in atopic eczema: the demonstration of allergic sensitization by skin tests, and the ascertainment of the clinical significance of allergy in the provocation of an individual’s eczema. There is clear evidence that immunological sensitization, reflected by the presence of specific IgE, occurs not only early in life, but even in utero. The pattern of allergen-specific IgE changes during the first 2 years of life from predominantly food-directed to airborne allergen-directed IgE.

Allergy to environmental airborne and/or food allergens is an important triggering factor in some, but not all individuals. There are major difficulties in determining which patients have clinically significant allergies contributing to driving the eczema. Different types of allergic response can be demonstrated with skin tests. Thus immediate, Type I, weal and flare responses can be elicited by prick tests in 80 to 95% of people with eczema. If allergens are administered by intradermal challenge, up to 30% will exhibit both immediate and late phase (6–12 h) responses. If allergens are administered by application as patch tests, depending on whether or not the stratum corneum permeability barrier is breached by prior stripping with cellophane tape, eczematous responses that replicate the clinical and histological features of eczema can be generated in up to 80% of patients. Also, if the patch-test challenge sites are inspected at the appropriate time, immediate (15 min) weal and flare responses are seen, and sometimes late phase (6 h) responses.

The practical difficulty is in determining whether these positive skin tests correlate with clinically significant allergic provocation. Most patients have current or previous mucosal allergies of asthma or rhinitis, and immediate reactions in prick tests generally correlate well with the allergic provocation of those symptoms rather than the eczema. However, very strongly positive prick-test responses to a given allergen often indicate that the allergen will aggravate the eczema. Positive patch tests with atopic allergens are reported to occur only in individuals with current or past eczema, and not in people with mucosal allergies and no eczema. Again, a strong patch-test response to a given allergen often indicates that the allergen has a significant role in provoking the eczema. Historical enquiry into which agents clearly exacerbate the eczema is usually unrewarding. One approach to establishing clinical relevance is allergen avoidance.

Allergen avoidance

This is only seriously practicable for house-dust mites, and foods. There is controversy in the literature as to the value of allergen avoidance measures. Tan et al. showed highly significant beneficial effects, whereas two other studies failed to show any benefit. The difference between the studies was the rigour of the dust-mite exclusion measures. Tan encased all the bedding components (duvet, pillows, and mattress) in sealed encasements, treated the carpets with a spray combining acaricidal and allergen-denaturing activity, and used a high-power high-filtration vacuum cleaner. Gutgesell used bedding encasements and a vacuum cleaner, and Oosting et al. only used bedding encasements. In fact in Tan’s study, the combination of allergen-denaturing spray and vacuum cleaning resulted in a great reduction in the allergen load in the carpets, but the overall effect was not significantly better than that from the simple vacuum cleaner alone. So it is hard to explain why there are such differences in the results of the three studies. Dietary allergen exclusion has been explored in many studies, with the best effects being reported for infants and small children.

Microbes

Atopic eczema is highly susceptible to colonization and infection by coagulase-positive staphylococci. This was thought to result from the high relative humidity at the skin surface; even though the skin is dry to the touch the permeability barrier is defective, and there is a high transepidermal water loss. It is now known that an additional factor in the poor resistance to staphylococci is deficient production of the antimicrobial peptides β-defensins. Colonization by staphylococci that produce superantigens may lead to a general exacerbation of the eczematous inflammation. Infection by staphylococci results in folliculitis and/or acute exacerbations of eczema with weeping and crusting. Also, the development of fissures of the eyelids and/or ear lobes is usually a sign of staphylococcal infection.

Eczema is also susceptible to infection with herpes viruses, either herpes simplex or varicella–zoster. Eczema herpeticum is a potentially very serious condition that may lead to ocular damage, herpes encephalitis, or pneumonitis.

The head and neck pattern of eczema is thought to be provoked by the ubiquitous skin-surface yeast Malassezia furfur. Evidence is circumstantial, but is derived from the therapeutic response following treatment with imidazole antifungal agents.

Treatment of atopic eczema

The general approach is to: (1), avoid any provoking factors, i.e. irritants, contact sensitizers, or atopic allergens; (2), suppress inflammation with topical steroids; and (3), give supporting symptomatic treatment.

Bullet list 2 Treatment of eczema

  • Moisturizers/emollients
    • ◆ Liquid oils or creams
    • ◆ Greasy ointments
  • Topical steroids
    • ◆ See Bullet list 3
  • Topical calcineurin antagonists
    • ◆ Tacrolimus
    • ◆ Pimecrolimus
  • Systemic drugs
    • ◆ Azathioprine
    • ◆ Ciclosporin
  • Additional treatments
    • ◆ Antibiotics if infected
    • ◆ If wet/oozing, potassium permanganate soaks (1/10 000)

Allergen avoidance

If clear allergic provoking factors can be identified then avoidance measures can make a significant contribution to the control of atopic eczema. Dust-mite avoidance must be done properly; ideally, all three elements of the bedding (mattress, top covers, and pillows) should be encased in bags of the appropriate dust-proof material. However, these are often hot and intolerable, and replacing duvet/quilts with cotton cellular blankets that can be washed frequently is an alternative. Similarly, acrylic pillows and duvets can be subjected to hot washing and tumble drying every 3 months.

The avoidance of dietary provocations is often practised, particularly in babies and children, on an empirical basis. This should only be continued if good evidence that it is contributing can be obtained by provocation challenge.

Infection

Staphylococcal infection requires antibiotics; it is better to use systemic antibiotics for 7 to 10 days than topical forms, to reduce bacterial resistance. In patients with recurrent skin infection the use of moisturizers containing antiseptic agents in the bath or applied directly to the skin is helpful.

Itch

The mediators of itch in atopic eczema are not known, but the contribution of histamine is minimal. Although antihistamines are often given, it is more likely that the sedating effects of older antihistamines such as chlorpheniramine or trimeprazine make them better at symptom relief than nonsedating modern forms.

Skin inflammation

A crucial part of topical therapy is the use of emollient moisturizers (Bullet list 2). These are available as liquid oils, thin creams, and thick ointments, with varying degrees of water miscibility. The application of moisturizers that the patient finds agreeable can have excellent anti-itch and soothing effects, thus reducing scratching and hence contributing to controlling the eczema. The technique of wet wrapping can be very helpful, particularly in babies and small children. This involves the initial application of a moisturizer to the limbs and torso, followed by the application of a double layer of tubular bandages, the inner layer being wetted with tepid water.

Bullet list 3 Topical steroids

  • Category 1: mild
    • ◆ Hydrocortisone
  • Category 2: moderate
    • ◆ Clobetasone butyrate
  • Category 3: potent
    • ◆ Betamethasone valerate
  • Category 4: super potent
    • ◆ Clobetasol propionate

Topical steroids are the mainstay of treatment of the skin inflammation (see Bullet list 3). In many patients, the chronic use of topical steroids may be ineffective or can result in steroid-induced side effects of striae, skin atrophy, and telangiectasia. In this case the topical calcineurin antagonists tacrolimus or pimecrolimus are indicated. If these are ineffective, a range of systemic drugs may be used. These include azathioprine, ciclosporin, methotrexate, and mycophenolate mofetil. Systemic steroids are reserved for acute rescue therapy of acute flares, but should not be used for long-term therapy.

Other forms of dermatitis/eczema

Seborrhoeic eczema

Seborrhoeic eczema is a response to the ubiquitous saprophytic skin yeast Malassezia furfur. The rash comprises erythematous dry areas, most classically affecting the nasolabial folds, scalp, and ears. The most minimal form of seborrhoeic eczema is dandruff; if it is more active the scalp becomes itchy and finally inflamed, with red scaly areas most typically around the hair margin. There may be circular coalescing areas on the central chest and/or upper back. Seborrhoeic eczema can mimic psoriasis, and indeed there is an entity termed sebopsoriasis, which behaves like psoriasis, but is in the distribution of seborrhoeic eczema. Most people experience minimal seborrhoeic eczema at some time. It is not known what causes the relationship with the fungus to change so that it induces an inflammatory reaction. People infected with HIV are prone to developing florid seborrhoeic eczema.

Treatment

The main treatment is with antifungal agents such as imidazoles in shampoo and topical forms; for severe cases systemic agents such as fluconazole may be used. For very symptomatic cases, low-potency topical steroids in combination with antifungal agents can be used to gain control, after which imidazole antifungals are usually sufficient for long-term control.

Dyshidrotic (pompholyx) eczema

This is an intensely itchy eruption affecting the palms and/or soles. It is characterized by tiny vesicles and blisters (pompholyx), which initially appear as small grey dots. The affected areas then become reddened, with hyperkeratotic scale that can fissure leading to painful splits. This is often a very chronic eczematous condition. It is thought that there is an associated disturbance of the structure or function of the sweat glands in the affected areas, hence the term dyshidrotic.

Differential diagnosis

It is important to exclude the presence of allergic contact dermatitis by careful history taking and diagnostic patch tests. It is also important to avoid irritants such as soaps; greasy moisturizers should be used as substitutes. Potent topical steroids are normally required, but often the condition is only poorly controlled. Systemic agents such as azathioprine may be required for the long-term control of severe cases.

Asteatotic eczema

Asteatosis indicates lack of oil/grease, a condition that develops gradually with increasing age, and that preferentially affects the lower legs. The epidermal surface becomes dry, and cracks develop in the scale. These cracks can become red and itchy, a characteristic appearance called eczema craquelé, one pattern of asteatotic eczema (Fig. 5). The other main pattern is a more typical eczematous inflammation, usually distributed on the lower legs in association with a generalized dryness and hyperkeratosis.

Asteatotic eczema

Figure 5: Asteatotic eczema.

Treatment

The main component of treatment is replacement of the epidermal oils by the application of greasy moisturizers. In the acute phase, moderate-potency topical steroids in ointment base may be required to bring the symptoms under control.

Varicose eczema

Following deep venous thrombosis in the leg veins, the valves in the veins are damaged, causing a rise in the venous pressure gradient down the legs. Any cause of venous hypertension may reverse the direction of flow, channelling returning blood into the superficial veins. The raised pressure transmitted to the small veins and postcapillary venules results in plasma transudation, deposition of fibrin (which produces sclerosis and skin tethering), and leakage of erythrocytes, generating haemosiderin. The haemodynamic changes alter the nutritional provision to the skin. As part of this, perhaps by analogy with the processes underlying asteatotic eczema, there may develop a rather diffuse eczematous process. If the skin’s nutritive blood supply is sufficiently compromised the tissue may break down, resulting in venous ulcer disease.

Differential diagnosis

It is common for allergic contact dermatitis to develop on the lower legs affected by venous ulcers. The contact allergy is in response to ingredients of the many medicaments and impregnated bandages that are applied as part of the treatment.

Treatment

The most important component of therapy is external compression with stockings or bandages. This can improve the haemodynamics and restore the direction of venous return, with associated improvement in nutritive skin blood flow. The eczema is treated with moisturizers and a range of topical corticosteroids.

Ultraviolet-induced eczema or photodermatitis

Some people develop eczema in areas exposed to sunlight, mainly the face, neck, and dorsa of hands. There are two types of this photodermatitis; an apparently spontaneous reactivity to light, and chemically sensitized photoallergy. Many drugs can act as photoallergens, becoming converted to allergens by the combined effect of ultraviolet (UV) radiation and as yet undefined metabolic factors in the individual. Well-known examples are thiazide diuretics and quinine. The causal role is demonstrated by photopatch tests, in which the suspect chemical is applied to the back in duplicate; one test site is irradiated with long-wavelength ultraviolet (UVA), and the other is simply occluded. The role of photoallergy is shown by a positive response only at the UV-irradiated test site.

Even in people who develop apparently spontaneous photodermatitis, there is often the suspicion that plant-derived substances such as sesquiterpene lactones from the chrysanthemum family may be involved.

Treatment

This involves minimizing exposure to sunlight by wearing thick clothing and hats. Sunblock creams are only helpful if they are very thick and opaque. Potent topical steroids and even systemic agents such as azathioprine may be required.

Further reading

Top

Calnan CD, Fregert S, Magnusson B (1976). The International Contact Dermatitis Research Group. Cutis, 18, 708–10.

Cavani A, et al. (2003). Human CD25+ regulatory T cells maintain immune tolerance to nickel in healthy, nonallergic individuals. J Immunol, 171, 5760–8.

Coenraads PJ, Smit J (1995). Epidemiology. In: Rycroft RJG, et al. (eds) Textbook of contact dermatitis, 3rd edition, pp. 133–50. Springer-Verlag, Berlin.

David TJ, et al. (2000). Dietary factors in established atopic dermatitis. In: Williams HC (ed) Atopic dermatitis: The epidemiology, causes and prevention of atopic dermatitis, pp. 193–201. Cambridge University Press, Cambridge.

de Jongh GJ, et al. (2005). High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis. J Invest Dermatol, 125, 1163–73.

Dickel H, et al. (2002). Importance of irritant contact dermatitis in occupational skin disease. Am J Clin Dermatol, 3, 283–9.

Diepgen T (2000). Is the prevalence of atopic dermatitis increasing? In: Williams HC (ed) Atopic dermatitis: The epidemiology, causes and prevention of atopic dermatitis, pp. 96–109. Cambridge University Press, Cambridge.

Diepgen TL, Coenraads PJ (1999). The epidemiology of occupational contact dermatitis. Int Arch Occup Environ Health, 72, 496–506. 

Friedmann PS (1991). Graded continuity, or all or none—studies of the human immune response. Clin Exp Dermatol, 16, 79–84.

Friedmann PS (2006). Contact sensitisation and allergic contact dermatitis: immunobiological mechanisms. Toxicol Lett, 162, 49–54.

Friedmann PS, et al. (1993). Early time course of recruitment of immune surveillance in human skin after chemical provocation. Clin Exp Immunol, 91, 351–6.

Gerberick GF, et al. (2000). Local lymph node assay: validation assessment for regulatory purposes. Am J Contact Dermatitis, 11, 3–18.

Gutgesell C, et al. (2001). Double-blind placebo-controlled house dust mite control measures in adult patients with atopic dermatitis. Br J Dermatol, 145, 70–4.

Kusel MM, et al. (2005). Support for 2 variants of eczema. J Allergy Clin Immunol, 116, 1067–72.

Lachapelle JM (1995). Histopathological and immunohistopathological features of irritant and allergic contact dermatitis. In: Rycroft RJG, Menne T, Frosch PJ (eds) Textbook of contact dermatitis, 3rd edition, pp. 91–102. Springer-Verlag, Berlin.

Lintu P, et al. (2001). Systemic ketoconazole is an effective treatment of atopic dermatitis with IgE-mediated hypersensitivity to yeasts. Allergy, 56, 512–17.

Meding B (1990). Epidemiology of hand eczema in an industrial city. Acta Derm Venereol Suppl (Stockh), 153, 1–43.

Miles EA, et al. (1996). Peripheral blood mononuclear cell proliferative responses in the first year of life in babies born to allergic parents. Clin Exp Allergy, 26, 780–8.

Mudde GC, Bheekha R, Bruijnzeel-Koomen CA (1995). Consequences of IgE/CD23-mediated antigen presentation in allergy. Immunol Today, 16, 380–3.

Ohmen JD, et al. (1995). Overexpression of IL-l0 in atopic dermatitis. Contrasting cytokine patterns with delayed-type hypersensitivity reactions. J Immunol, 154, 1956–63.

Oosting AJ, et al. (2002). Effect of mattress encasings on atopic dermatitis outcome measures in a double-blind, placebo-controlled study: the Dutch mite avoidance study. J Allergy Clin Immunol, 110, 500–6.

Palmer CN, et al. (2006). Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet, 38, 441–6. 

Patrick E, Maibach HI (1995). Predictive assays: animal and man, and in vitro and in vivo. In: Rycroft RJG, Menne T, Frosch P (eds) Textbook of contact dermatitis, 3rd edition, pp. 705–747. Springer-Verlag, Berlin.

Raghupathy R (2001). Pregnancy: success and failure within the Th1/Th2/Th3 paradigm. Semin Immunol, 13, 219–27.

Schultz Larsen FV (1993). The epidemiology of atopic dermatitis. Monogr Allergy, 31, 9–28.

Strachan DP (1989). Hay fever, hygiene, and household size. BMJ, 299, 1259–60.

Tan BB, et al. (1996). Double-blind controlled trial of effect of housedust-mite allergen avoidance on atopic dermatitis. Lancet, 347, 15–18.

Warner JA, et al. (1996). Prenatal sensitisation. Pediatr Allergy Immunol, 7, 98–101.

Willis CM, Stephens CJM, Wilkinson JD (1993). Differential patterns of epidermal leukocyte infiltration in patch test reactions to structurally unrelated chemical irritants. J Invest Dermatol, 101, 364–70.