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Hand Dermatitis: A Review of Clinical Features, Prevention

and Treatment
Dimitar Antonov; Sibylle Schliemann; Peter Elsner
Am J Clin Dermatol. 2015;16(4):257-270.

Abstract and Introduction

Abstract

Hand dermatitis is a socially significant health problem. This review provides a discussion on the clinical
features and patterns as well as the differential diagnosis of hand dermatitis, because these are essential for
proper diagnosis in clinical practice. Themorphology, however, is poorly related to the etiology in chronic cases.
In all cases of chronic hand dermatitis, a full diagnostic examination should be undertaken and the etiology
should be clarified and addressed in the treatment concept, instead of just moving directly from a morphological
diagnosis to therapy. Preventive measures should be included in the treatment concept according to etiology. A
stepwise approach for escalating therapy is advised, including basic topical therapy, topical corticosteroids,
calcineurin inhibitors, as well as phototherapy and systemic therapy with corticosteroids, alitretinoin,
cyclosporine, methotrexate, azathioprine, and others.
Introduction

Hand dermatitis is a socially significant disease because of its high prevalence, morbidity and the associated
lost working time due to sick leave. Its 1-year prevalence is estimated to be about 10 % in the general
population, but only approximately half of the patients seek professional dermatological care. [1,2] The prevalence
is much higher (up to 30 %) in particular risk occupations such as hairdressers, cleaners, healthcare workers
and others.[3]
This narrative review is based on literature searches of the online PubMed database (pubmed.gov) with 'hand
dermatitis', 'hand eczema', 'dermatitis prevention' and the individual treatments as search terms. Key articles
were identified, including systematic reviews and recent guidelines from different societies. For some key
articles, a search through the references and of the cited articles using the ISI database 'Web of Science Core
Collection Indexes' was performed to identify further relevant articles.
The terms 'eczema' and 'dermatitis' are used as synonyms and are interchangeable in this text.

Clinical Features
Hand dermatitis is a heterogeneous entity and this review focuses on the clinical features of its various types.
Hand dermatitis is considered chronic if it lasts more than 3 months or relapses two or more times per year.[2,
4]
The longer the hand eczema persists, the stronger its tendency to become chronic, even after the causative
agents have been withdrawn.[3] Other definitions suggest a duration longer than 6 months for chronic eczema. [5]
The identifiable etiologic factors are given in , but in real life these factors are often concomitantly present and
in approximately 20 % of cases no etiologic factors can be found. [6]

Table 1. Classification of hand dermatitis

Types of hand dermatitis

Duration

Acute (<3 months)

Chronic (>3 months or 2 relapses per year)

Etiologic factors

External factors
Irritant contact dermatitis
Allergic contact dermatitis
Protein contact dermatitis
Atopic dermatitis

There are no reliable morphologic features that would allow distinction between irritant and allergic chronic
eczema. In all cases of chronic hand dermatitis and not just in cases with suspected contact sensitization, a
patch testing should be performed with the relevant standard series or patient substances. [2,7]
In acute irritant contact dermatitis, lesions vary according to the intensity of the provoking agent from mild
irritation to deep chemical burns, graded similarly to thermal burns. There is usually a single or a limited
number of short contacts with caustic or physical irritants and the lesions are limited to the contact area and
accompanied by a burning or stinging sensation rather than itching, with a variable degree of redness,
exudation or oozing, formation of vesicles or bullae and swelling.
Acute allergic contact dermatitis is caused by one or more type IV sensitizations. It spreads beyond the contact
area, with more swelling, more infiltration, and more itching than acute irritant contact dermatitis.
Most patients searching for dermatological help for hand dermatitis have a chronic condition. [8]
For the irritant type of chronic eczema, the most common mechanism is the cumulative irritant one, where
subclinical insults to the skin barrier are not strong enough to induce an acute reaction, but lead to cumulative
damage over a longer period of time. The development of clinically apparent lesions is only the tip of the
iceberg of the functional derangement of the skin barrier.[9,10] Typical risk factors are exposures to wet work,
detergents, wearing occlusive glove material, and frequent hand washings per day (up to 2030 times daily).
After prolonged contact with mild irritants and/or prolonged wet work, redness, dryness and some
desquamation of the affected skin develop, starting in the finger webs or on the back of the hand. These
lesions progress to form fissured, infiltrated and desquamative and not very sharply demarcated plaques (Fig.
1). The eczematous changes are initially limited to the exposed areas, with the palms usually becoming
involved later in the process.

Figure 1.

Cumulative irritant (chronic) contact dermatitis of the hand. Indistinctly demarcated erythematous plaques with
desquamation and fissures on the back of the hands and on the fingers
In patients with chronic hand dermatitis, there is often a mixture of constitutional atopy and irritant factors,
sometimes with an additional contact sensitization, and a sharp distinction between an allergic or irritant
pathogenesis is not always possible. Itching as a symptom is unreliable in distinguishing between allergic and
irritant causation in the chronic phase. A recent study of itching in chronic hand dermatitis unresponsive to
topical therapy found an association of itching with atopy and disease severity among other factors. [11]
A very rare variant of hand dermatitis, protein contact dermatitis, develops morphologically as an initial contact
urticaria, followed by eczema. It is usually caused by a type I IgE-mediated sensitization against proteins, but
non-immunological forms of contact urticaria leading to eczema exist as well. [2] The urticarial stage is, however,
only rarely recognized clinically.

Endogenous hand eczema is a manifestation of atopic skin diathesis. Skin barrier dysfunction, such as the one
caused by filaggrin mutations, plays a role. The diagnosis might be difficult if hand dermatitis remains the only
manifestation, and exogenous causes have to be ruled out to confirm the diagnosis. Finding atopic stigmata or
typical lesions of atopic dermatitis elsewhere on the body, e.g. flexural areas, helps establish the diagnosis.
Personal and family history of, for example, flexural eczema in childhood, asthma or pollinosis might be helpful;
the atopy score is a useful instrument as well.[2] Involvement of the ventral wrists with lichenification is very
typical. The hands and feet might be simultaneously involved. Other common signs are the involvement of the
tips of the fingers (pulpitis sicca) or of the anatomic 'snuff box'. [2] The morphology is diverse and a recent study
found no statistically significant association between atopy and a defined morphological pattern of hand
dermatitis.[12]
There is no internationally accepted classification of hand dermatitis, [4] because different etiologies usually act
concurrently or sequentially, and a combination of clinical patterns may be seen. An international classification
based on the etiology has been proposed in order to provide uniformity in clinical studies and clinical work.
[13]
The cases without identifiable etiology in this study were classified morphologically into vesicular or
hyperkeratotic.[13] Further elaborating on this classification, a newer diagnostic algorithm and classification has
been developed.[14]
It is advisable to use an etiologic diagnosis in clinical practice and in clinical studies, [12,13] rather than just
describing the morphological pattern. For example, atopic hand dermatitis may present any of the discussed
morphological patterns, but defining it as atopic hand dermatitis has implications for treatment and prevention
and is therefore preferable as a diagnosis to, for example, vesicular hand dermatitis. Practically, this means
that a full diagnostic examination should be undertaken and the etiology should be clarified and addressed in
the treatment concept, instead of just moving directly from a morphological diagnosis to therapy.
It is generally considered that clinical morphology is poorly related to etiology.[4,1214] Molin et al.[14] found that
patients with chronic irritant dermatitis more often had a hyperkeratotic rhagadiform and rarely a vesicular
morphology; in allergic contact dermatitis, a mixed pattern of vesicular and hyperkeratotic lesions
predominated. Similar results were reported from Johansen et al., [12] who showed that irritant contact dermatitis
was the most frequent etiology in the dry fissured variety and allergic contact dermatitis in the vesicular types.
In the last study,[12] the most frequent clinical patterns were hyperkeratotic rhagadiform (dry fissured, 36 %), and
vesicular (31.8 %). All other types (nummular, pulpitis sicca, hyperkeratotic) were each observed in<10 % of the
study population.

Dyshidrosiform/vesicular eczema or pompholyx: this type begins with deep-seated vesicles on the
palm and/or palmar aspects and the sides of the fingers and is usually very itchy (Figs. 2, 3). The
vesicles resolve spontaneously with desquamation, but new attacks of new vesicles usually recur. The
term dyshidrotic originates from the belief that the vesicles develop from the sweat glands, because
this eczema is usually aggravated by sweating, hot weather and occlusion. It has been shown in
histological studies that the dyshidrotic vesicles are the result of progressive spongiosis, just as in
other types of eczema.[15,16] The distinct morphology is attributed to the thicker stratum corneum of the
volar skin of the hands and feet. Nevertheless, the term dyshidrosiform is still widely used and some
therapies against sweating, such as tap water iontophoresis and botulinum toxin, may be effective in
some patients. This type is considered generally more difficult to treat than the other types of hand
dermatitis. The palmoplantar pustulosis is the most important differential diagnosis. An id reaction on
the hands to tinea pedis may have a dyshidrosiform morphology as well.

Hyperkeratotic rhagadiform: in this form, the development of erythematous infiltrated plaques with
oozing followed by dry hyperkeratosis and cracking is the typical feature. Usually the palms and the
volar aspects of the fingers are involved, sometimes the plantar aspects of the feet as well. The loss of
skin elasticity and the hyperkeratosis lead to painful fissures in the folds, which is another typical
feature. Such eczema is also called tylotic eczema, when a strong dry hyperkeratosis predominates
the clinical picture. In some patients, little or no inflammation is evident, just hyperkeratotic thickening
of the skin. The differentiation from a variety of disorders, such as hyperkeratotic tinea manus,
psoriasis, genetically determined palmoplantar hyperkeratosis, or pityriasis rubra pilaris, may be
difficult.

Figure 2.

Vesicular (dyshidrosiform) eczema or Pompholyx

Figure 3.

Vesicular (dyshidrosiform) eczema

The following are other distinct patterns of hand eczema, but these do not exhaust the variety of clinical
presentations of hand dermatitis:

Nummular eczema: in this pattern of hand dermatitis, discoid or nummular (coin shaped) plaques
develop on the back of the hands and possibly on the backs and sides of the fingers or the backs of
the feet. These plaques might be scaly or with tiny vesicles on the periphery. The nummular plaques
could be limited to the hands but are usually part of a generalized eruption on the body and limbs.

Fingertip eczema or pulpitis sicca: in this specific pattern, redness and dryness with desquamation
develop on the tips of all or most of the fingers. This leads to little but very painful fissures on the
fingertips. Vesicles may also be seen. The condition is usually worse in the winter and is a part of
atopic eczema. Allergic or occupational variants are also known; a clue in this direction could be the
involvement of just the fingers participating in an occupational activity. One well known example of the

latter is allergic contact dermatitis to handling of dental material, such as acrylates, in dental
technicians. Spread from the tips to the whole fingers or the palms may occur.

Interdigital eczema or finger web eczema develops in the interdigital spaces and on the back of the
fingers with redness, chapping and desquamation. Ring eczema is a condition with a similar
morphology, starting from the skin under a ring where detergents of allergens are more difficult to rinse
off, leading to occlusion. Mechanical rubbing may also play a role.

Differential Diagnosis
There are various conditions that can mimic the morphology of chronic hand dermatitis. A common one is the id
reaction, where eczematous lesions on the hands of variable morphology develop as a reaction to tinea,
usually on the feet. Additionally, tinea on the hands may itself mimic hand eczema. A clue for this differential
diagnosis may be scaling within the palmar hand lines and unilateral involvement, together with involvement of
the feet, the socalled 'one hand two feet syndrome' (Fig. 4). Therefore, in every patient with hand dermatitis,
the feet should be inspected, too. Another typical clinical situation is the differentiation of psoriasis pustulosa
(Fig. 5) and vesicular eczema, especially if impetiginized, which may even be difficult by histological means.
Other dermatoses, such as psoriasis (Fig. 6), pityriasis rubra pilaris and mycosis fungoides, may spread to the
hands and feet and mimic eczema. In such cases, the distinction from an extensive vesicular or hyperkeratotic
dermatitis may be difficult. Lesions on other body parts or on the typical locations for these conditions help
establish the diagnosis. In such cases, a skin specimen for histology is preferably taken from a clinically typical
lesion on a typical location and not from the hands or feet, if possible. When another skin disease is
predominantly located on the hands and feet however, the situation becomes more difficult. For example, there
are published rare cases of limited mycosis fungoides, such as the mycosis fungoides palmaris et plantaris,
[17]
which may have a vesiculobullous or a scaly erythematous morphology, mimicking hand dermatitis. [18] It is
more commonly the case, however, that lesions similar to hand and/or foot eczema develop later in the course
of mycosis fungoides progression or in Sezary Syndrome, when typical plaques on other body parts help to
easily establish the diagnosis. A list of the differential diagnoses of chronic hand dermatitis is given in . [2,19]
Table 2. Differential diagnoses of chronic hand eczema [2, 19, 96]

Psoriasis vulgaris
Psoriasis pustulosa
Tinea manuum, dyshidrotic tinea and id reactions to mycotic
infections with dyshidrotic morphology
Scabies
Bullous impetigo
Erythema multiforme
Herpes infection
Fixed drug eruption
Friction blisters
Lichen planus

Pityriasis rubra pilaris

Mycosis fungoides (vesicular, palmoplantar)
Chemotherapy-associated handfoot syndrome
Porphyria cutanea tarda
Palmoplantar keratodermas
Bowen's disease, radiodermatitis
Acrokeratosis paraneoplastica (Bazex syndrome)

Figure 4.

Tinea manustwo feet one hand syndrome

Figure 5.

Pustular psoriasis of the palms

Figure 6.

Non-pustular psoriasis (psoriasis vulgaris) of the palms

Prevention
Prevention is generally divided into primary, secondary and tertiary prevention.
Primary prevention aims to decrease the incidence of disease by limiting the exposure to its risk factors. The
purpose of secondary prevention is to decrease the prevalence of disease by prompt diagnosis and adequate
treatment. Hand dermatitis should be treated quickly and stepwise progressively in order to prevent it from
becoming chronic. Additional measures include investigations to establish clinically relevant irritant or allergic

triggers, which might frequently be occupational. Tertiary prevention aims to reduce impairment and disability of
established disease. In hand dermatitis, tertiary prevention includes treatment of chronic cases and
rehabilitation measures to return the patient to his environment and prevent job loss.
The avoidance/protection measures can be individual or collective and directed at the occupational or
home/recreational environment. Occupational exposure to wet work carries increased risk for hand dermatitis.
Therefore, preventive programmes have been developed for such occupations and validated in randomized
trials.[2024] These programmes usually include education measures that encourage:

the use of gloves for short intervals in order not to soil the hands and to reduce the frequency of
washing;

the use of gloves for as short a time as possible;

hand washing only when the hands are visibly soiled;

the use of disinfectants instead of washing whenever the hands are not visibly soiled;

the use of cotton gloves under the occlusive gloves for longer intervals of wet work;

application of protective creams and emollients within the 3-step model of skin protection (see below);

no rings or jewellery (irritants or allergens could be trapped beneath);

thorough rinsing after washing;

good drying of the hands before gloves are put on;

organizational measures to share the cleaning and the wet work equally;

organizational measures so that tasks can be completed with minimal exposure to wet work.

The recommendations for the use of alcohol solutions instead of detergents is based on studies which show
that they are less of an irritant than detergents[21,25] and they do not enhance the irritant effects of detergents. [25,26]
The so called '3-step skin protection concept' describing skin protection in the workplace consists of preexposure barrier or protective creams (PCs), mild skin cleansers and post-exposure skincare products such as
emollients or moisturizers. While PCs are designed to prevent skin damage due to irritant contact, skin cleaning
should remove aggressive substances from the skin, and skincare is intended to enhance the epidermal
barrier.
PCs cannot be definitely distinguished from moisturizers or emollients and in some articles they are together
referred to as moisturizers.[27] It may be argued that topical preparations influence mainly the regenerative,
rather than protective functions of the skin and therefore the use of a barrier cream is of no further benefit than
a simple moisturizer. Some published guidelines consider that the PCs by themselves are of ''questionable
value'', while emollients ''appear to confer some degree of protection''. [28] As the pre- and post-exposure
formulations are designed to pursue different objectives, however, certain ingredients may be inappropriate for
either the pre- or the post-exposure preparations.

The benefit of PCs in a real occupational setting has been demonstrated in a large randomized controlled trial
(RCT),[29] where 1020 workers from 19 factories in Germany were randomized to receive both pre- and
afterwork creams, only a protective (pre-work) cream, only a skincare (after-work) cream, or no
recommendations for skin protection (control group). All intervention groups showed statistically significant
differences compared with the control group, but the largest improvement was seen in the group with both skin
protection and after-work skincare creams, followed by skin protection alone. [29] The highest compliance was
also observed in the group with all the components together. It is generally agreed that the best results are
achieved when all the elements of the 3-step skin protection model are used together. Similar observations,
that the 3-step model is best accepted by the workers, have also been made earlier and the 3-step model is
recommended as the standard in current guidelines.[30]

Therapy of Hand Dermatitis

Many treatment modalities are available for the treatment of hand dermatitis; most of them are traditional and
few are studied extensively in quality RCTs.[2,31] The history of previous treatments may help to assess the
patient's compliance and motivation and reveal anxieties towards certain treatment modalities, most commonly
corticosteroids.
Acute or mild contact dermatitis should be treated thoroughly and effectively in order to prevent chronicity.
Sufficient time without contact to irritants and allergens should be designated to allow restoration of the skin
barrier and normal reactivity. If an acute contact dermatitis persists with the tendency to become subacute or
chronic, special attention is required to rule out additional irritants or allergens that could be present in the
home, recreational or occupational environment. A change in environment, such as hospital admission, can be
helpful. The patient's compliance and the possibility of sensitization to treatment modalities (topical
corticosteroids, topical antihistamines or other ingredients of emollients and topical medicinal products) should
be considered.
Basic Topical Therapy

Basic topical therapy helps reduce inflammation and itching, has corticosteroid-sparing effects and promotes
recovery. It has been shown to help heal irritant and allergic contact dermatitis, without any other treatment.
[32,33]
The basic topical therapy should be adjusted according to disease severity, acuteness and stage of
evolution. The general principles of dermatological therapy, such as 'moist on moist' should be observed ( ).
[2]
Basic topical therapy may be underestimated by patients and physicians as 'bland' and without active
ingredients. The result from such an attitude may be reduced compliance or application that is inadequate or in
insufficient quantity, ultimately compromising treatment.[34] Emollients should be continued even after the visible
signs of dermatitis have subsided, because the functional derangements, including barrier dysfunction, take
longer to heal.
Table 3. General principles and effects of basic topical therapy in contact dermatitis, based on disease
acuteness and morphology [2]

Type

Desired effect

Topical therapy

Acute

Drying, astringent,
antibacterial

'Moist on moist', hand baths and soaks,

moisturising or moist dressings; wet dressings with
saline, tannin-based synthetic agents; alcoholbased tinctures
Topical antiseptics in case of superinfection

When hand dermatitis is combined with

hyperhidrosis, aluminum chloride hexahydrate,
tap-water ionophoresis, Botulinum toxin type A
Anti-inflammatory,
Subacute antipruritic,
moisturizing

Chronic

Keratolytic, antiproliferative,
moisturizing

Tar and ichthyol preparations

Polidocanol and urea-based preparations,
moisturizing water-in-oil and oil-in-water emulsions
Keratolytic ointments (salicylic acid up to 20 %,
urea 1020 %)
Lipid-rich ointments, including water-in-oil and oilin-water emulsions; glycerin-based creams
Tar and ichthyol preparations Fissures:
hydrocolloid dressing, silver nitrate,
cyanoacrylates (superglues)

Antihistamines are preferably given as systemic, not topical therapy, to avoid sensitization. In severe pruritus,
sedative antihistamines and sometimes short-term hypnotics are indicated.
For acute dermatitis, hand baths, wet dressings and soaks with solutions that have astringent and drying
effects are recommended. Synthetic tannins are cosmetically more acceptable than the outdated staining
solutions such as Burrow or potassium permanganate.[35] Apart from reducing exudation, these wet dressings
and soaks help soften and remove dried crusts and scales. Bullae should be drained, without removing the
roof. Topical antiseptics are used in cases with superinfection or when bacterial colonization may be an
aggravating factor. Because of the risk of sensitization and bacterial resistance, preference is given to
antiseptic solutions over topical antibacterials. Additional options include chlorhexidine, octenidine, clioquinol,
etc. In cases of clinical signs of infection, systemic antibacterials are indicated. In patients with atopic and nonatopic hand eczema without clinical signs of pyoderma, corticosteroids alone reduced or eliminated
colonization with Staphylococcus aureus.[36] When hand dermatitis is combined with hyperhidrosis, aluminium
chloride hexahydrate and tap-water ionophoresis are recommended, and there are reports of a beneficial effect
of botulinum toxin type A (reviewed in[19]).
In subacute dermatitis, the topical therapy should possess anti-inflammatory, antipruritic and moisturising
effects. Urea- and polidocanol-based topical therapies are recommended. Contact allergy to polidocanol has
been reported, especially in elderly patients with lower-leg dermatitis. [37,38] Ichthyol and tar preparations have
additional antiproliferative effects. However, tar preparations contain pyrenes with established animal
carcinogenicity. In addition to their cutaneous effects, increased systemic exposure correlates with the total
amount applied and body area treated, rather than the barrier impairment. [39]
In chronic dermatitis, rich moisturizing ointments are indicated. Keratolytic ointments are used in cases with
hyperkeratosis, such as tylotic hand eczema. The antiproliferative effects of the tar preparations make them
useful here as well. Fissures frequently form in chronic dermatitis. They are painful, heal slowly and can be
entry points for infection. Softening the epidermis and sealing the fissures improve pain and recovery.
Specific Therapies

The variety of specific therapies is presented in Fig. 7. A stepwise approach is advised, with more potent and
systemic therapies reserved for more severe, more widespread, recalcitrant or chronic cases. [2]

Figure 7.

Treatment options for hand dermatitis, proportionate to disease severity

Topical Corticosteroids. Topical corticosteroids are the primary treatment and are widely used for both
allergic and irritant contact dermatitis, although their application in irritant contact dermatitis has been subject to
debate. The choice of a particular topical steroid should balance the potency with the undesirable effects, such
as skin atrophy. To help such choices, a therapeutic index (TIX) has been developed and made available
online.[40,41] Usually, preparations with the higher ratio of potency to undesirable effects should be chosen.
However, in acute and severe episodes it is advisable to use sufficiently potent topical corticosteroids to quickly
suppress the inflammation, even though they have a higher tendency to induce atrophy. They should be given
for short periods and tapered quickly or replaced with corticosteroids with a more favourable ratio of potency to
undesirable effects. Additionally, in chronic dermatitis with lichenification and hyperkeratosis, such as tylotic
hand eczema, treatment with the most potent corticosteroids is also indicated, because of their antiproliferative
effects and presumed lower penetration.[2] Interval and intermittent dosing regimens help reduce the
corticosteroid load and undesirable effects. For chronic hand eczema, regimens such as administration of
potent corticosteroids only on the weekends or every other day are shown to be safe for long-term
maintenance (up to 36 weeks).[42] Combining topical corticosteroids with other treatment modalities may also
shorten the period of application and reduce corticosteroid load.

Topical corticosteroids are available in different vehicles, and the choice should be guided by the acuteness
and morphology of lesions, as in basic topical therapy. It should be kept in mind that the same corticosteroid
active ingredients may have different potency in different vehicles.
In addition to the well known side effects of topical corticosteroids, they also induce atrophy and impair
skinbarrier regeneration. This makes them inappropriate in conditions where the contact with irritants cannot be
completely excluded. Emollients may help decrease the negative effects of corticosteroids on skin-barrier
repair.[43] The palmar and plantar skin is, however, relatively insensitive to steroid-induced atrophy. Another
drawback is tachyphylaxis, where patients grow less responsive to topical steroids.
Contact sensitization to corticosteroids or to other ingredients of topical therapy should be considered if the
disease worsens or persists (reviewed in[44]). Patients with eczema on the lower legs are more frequently
affected. It is not easy to suspect sensitization because of the anti-inflammatory effect of the corticosteroid, but
it may lead to chronicity.[44,45] Patch testing may require late readings, up to 7 days. [46] Topical corticosteroids are
divided into four groups, so that cross-reactivity is low between the groups and high within. [44]
Topical Calcineurin Inhibitors (TCIs). The topical calcineurin inhibitors (TCIs) provide a needed alternative to
corticosteroids in atopic dermatitis and other conditions. [47] Their most valuable advantage is their safety over
long-term usage, without the induction of atrophy or interference with barrier repair. Their anti-inflammatory
potency has been approximated to that of lower mid-strength corticosteroids, such as 0.1 % hydrocortisone
butyrate or 0.1 % betamethasone-17-valerate. [48,49] There are several studies in chronic hand
eczema[48,50] (reviewed in[51]) where TCIs showed good therapeutic effects worthy of further study in large RCTs.
As TCIs may not penetrate well through hyperkeratosis, in some of the studies they were applied under
occlusion; for example, twice daily with overnight occlusion. [52] In psoriasis, a TCI has been applied with 6 %
salicylic acid to enhance penetration and potency.[47]
TCIs are topical immunomodulators and should not be used when skin infections are present. Additionally, a
small fraction of chronic hand eczema patients experience burning or stinging, erythema, or worsening under
treatment.[48] Concerns over potential photo-carcinogenicity have been raised because of established effects in
systemic therapy in organ transplant recipients and animal data on topical preparations. An expert review
concluded that such concerns are not corroborated by the available data from animal and human studies.
[51]
They also concluded that a combination of TCI and UV therapy is acceptable and may be useful. A recent
cohort study with 7457 children and 25,000 person-years of follow-up found no increased risk of malignancy
with pimecrolimus use.[53] Nevertheless, the warning against skin exposure to UV during TCI treatment,
including UV and PUVA therapy, has not been amended in the official prescribing information and is still valid.
UV protection, such as sunscreens and appropriate clothing, should be advised in patients undergoing TCI
treatment.[51]
The concept of 'proactive' therapy with tacrolimus is well established in the treatment of atopic dermatitis [54] and
may be used in the treatment of chronic hand dermatitis as well. The topical preparations are used twice
weekly to postpone and reduce the intensity of the seemingly inevitable relapse. It is similar to the maintenance
therapy with potent steroids discussed above. [42] A study by Bauer et al.[55] could not demonstrate a benefit of
pimecrolimus versus vehicle twice daily in atopic hand dermatitis, but the study was small with only 36 patients.
Encouraging results were observed in the subgroup with moderate severity.[55]
UV Therapy. Different phototherapy modalities are traditionally used in chronic hand eczema, but of the many
published studies, few are well controlled and usually the number of patients is small. Broad- and narrow-band
UVB, PUVA and UVA1 therapies have shown good results in chronic hand eczema. Phototherapy has a

favourable effect on skin-barrier function. There is accumulated clinical experience with broadband UVB and
PUVA. UVA1 and narrow-band UVB are insufficiently studied. [56]
Currently, PUVA with topical psoralens is mostly used (cream, gel, bath, soaks [57] or paint PUVA), with the
advantage that only a small part of the body is subjected to psoralens and UV irradiation, with no systemic
symptoms or systemic phototoxicity. Different protocols are employed and guidelines are available online; [58] for
example, soaking of patients' hands in a psoralen solution for 15 minutes followed by UVA four times per week,
starting with 0.5 J/cm2 and increasing by 0.51.0 J/cm2 every third procedure until slight erythema.[59] Under
such a regimen, 93 % of the patients with vesicular and 86 % of the patients with hyperkeratotic eczema
achieved excellent or very good results.[59] Hyperkeratotic eczema took more procedures to clear (mean 14.5,
range 825 vs. mean 12.4, range 725) and a higher cumulative UV dosage (mean 27.9 vs. 21.4 J/cm 2). In
another study with three or four procedures weekly for 8 weeks, half of the patients with vesicular hand
dermatitis showed complete remission.[60] Remissions have different durations, some report 6 months mean.
[59]
Good results are also reported with cream PUVA. [61]
Both UVB and PUVA regimens are potentially carcinogenic in the long run and long-term application should be
avoided. Usage as maintenance therapy might be justified in exceptional recalcitrant cases. Topical PUVA is
plausibly less carcinogenic than oral PUVA. Some patients may develop irregular patchy blistering or sunburn
reactions and consecutive hyper-pigmentations in the treated areas. This is related to the method of psoralen
application (bath PUVA gives a more uniform psoralen distribution than paint PUVA). Erythema in PUVA
appears later than in UVB regimens and reaches its peak 7296 h after exposure; thus, frequent PUVA
regimens, such as daily regimens, may lead to severe cumulative phototoxicity.[58]
UVA1 is considered to be less carcinogenic than PUVA and UVB, [62] but as the long-term safety is unknown,
only two treatment cycles per year are recommended. [63] Good results with long remissions are reported with
midand high-dose regimens. For example, 40 J/cm2 five times per week for 3 weeks (~600 J/cm2 per treatment
cycle),[62,64] or five times per week for 3 weeks with increasing dosages, cumulative 1720 J/cm 2.[63]
Phototherapy can be combined with other treatments; for example, topical corticosteroids or systemic retinoids,
to speed up the effect and lower the total UV dosage.[65] Combinations with systemic immunosuppressants are
not recommended because of increased carcinogenicity. As a precaution against possible similar effects,
combinations with TCIs are warned against in the TCIs' official prescribing information. A common drawback for
phototherapies is that special facilities are required and these are not always available, even more so for UVA1
therapy. Patients find it problematic to schedule regular visits within normal working hours and to travel to the
facilities. PUVA with portable home-UVA devices[66] and phototherapy with portable UVB devices[67] have been
described, but are not recommended as a general practice due to concerns that uncontrolled use may be
associated with an increased risk of carcinogenicity.[58]
Ionizing Radiation Therapy. Two modalities of radiotherapy, Grenz rays and superficial X-rays, have
historically been reported as effective treatment of refractory chronic hand eczema, and less frequently for
plantar eczema[68] (reviewed in[69, 70]). It is generally considered that with the availability of other treatment
options, nowadays radiotherapy is justifiable only in exceptional cases and in older patients. [56] However, it is
used more widely in some countries and less or not at all in others and the opinions vary. Radiation therapy for
this indication is regarded as obsolete by some, but according to others the Grenz rays modality is simple,
affordable, effective and ultimately still a valid option.[71]
Of the two radiotherapy modalities, Grenz rays were preferably used over superficial X-ray, because they are
safer (they do not penetrate deeper than the skin). In a double-blind study with 25 patients, superficial X-rays
were found to be more effective than Grenz rays, probably because of their deeper penetration (half value layer

of 13 mm in tissue vs. 0.4 mm for Grenz rays).[72] Different protocols are reported from different studies, with the
greatest clinical improvement being most evident usually several weeks after therapy commencement. The
major disadvantage of radiotherapy is the carcinogenic risk. Other adverse events are erythema and
hyperpigmentation. More severe local adverse events could be induced in the event of overdosage.
Additionally, radiotherapy requires specially licensed facilities and personnel.
Retinoids. Alitretinoin (9-cis-retinoic acid) is a retinoid with a distinct clinical profile. [73] It has proven efficacy for
the treatment of severe chronic hand eczema unresponsive to standard therapy. With more than 2000 patients
included in different controlled trials, it is the therapy for chronic hand eczema with the highest level of
evidence.[2] It has a characteristic receptor-binding profile[73] interacting with high affinity to all RAR and RXR
receptor types.[74] Alitretinoin has anti-inflammatory and immunomodulatory effects and, similarly to other
retinoids, inhibits proliferation and enhances differentiation, but, in contrast to them, has minimal drying effect.
In the largest clinical trial with 1032 patients, alitretinoin 30 mg given once daily after breakfast for 24 weeks led
to a 'clear' or 'almost clear' outcome in 48 % of patients with severe eczema unresponsive to standard therapy,
and 17 % in the placebo group.[75] Partial response was achieved by 62 % of patients. The curve of patients
achieving the 'clear' or 'almost clear' response did not reach a plateau for 200 days, showing that continued
therapy brings further benefit. The remission was sustained, with 65 % being free of recurrence at 6 months.
Median time to relapse was 5.5 months. The most frequent adverse effect was headache (20 %), leading to 4
% withdrawal. Headache was reported in the first 10 days and resolved without alitretinoin discontinuation.
[2]
Additional class effects were mucocutaneous effects and dryness (noted at lower incidence than with other
retinoids), decreased thyroid- stimulating hormone (TSH) levels and hyperlipemia. [75] Patients with high blood
lipids should be given the lower dose of 10 mg. Alitretinoin is teratogenic and the necessary precautions are the
same as with the other retinoids. Contraception is required up to 1 month after therapy cessation.
Topical bexarotene, oral acitretin and etretinate [76] have also been tried in chronic hand eczema with less
success. A study concluded that topical bexarotene had potential use in severe chronic hand dermatitits. A high
rate of treatment-related irritation was reported (29 %).[77] Oral acitretin led to 50 % average improvement in the
clinical score in patients with tylotic eczema for 4 weeks, with no additional improvement with longer treatment.
It might be studied in combination therapy.[78]
Systemic Corticosteroids and Immunosuppressive Agents. Systemic corticosteroids may be required in
extensive or severe hand dermatitis and exacerbations of chronic disease, usually short-term (generally a
treatment course within 3 weeks) 0.51 mg/kg/day prednisolone equivalent with quick tapering. Long-term or
frequent use is not indicated due to well known side effects. [4]
There is accumulated clinical experience in dermatology with immunosuppressives such as cyclosporine,
azathioprine, methotrexate, and others. They are traditionally used for a variety of indications either alone or as
corticosteroidsparing agents. There is limited evidence for their effectiveness in hand dermatitis.
Cyclosporine is reported to be beneficial in chronic hand eczema. [79,80] In a double-blind study with 41 patients,
cyclosporine 3 mg/kg/day for 6 weeks was as effective as topical betamethasone dipropionate, leading to a 57
% reduction in disease severity score.[80] More experience is available with atopic dermatitis and guidelines for
the use of cyclosporine in dermatology have been developed. [81,82] Therapy with cyclosporine should be
conducted for up to 6 months at the minimum effective dose, followed by 3 months' tapering. In some patients,
longer therapy may be required, whereas with good responders earlier discontinuation is advisable. If no
clinical response is observed for 8 weeks, cyclosporine should be withdrawn. In some studies on atopic
dermatitis, higher initial doses (45 mg/kg/day) were used to achieve faster response, but after satisfactory
improvement the dosage should be reduced to the individual minimum effective dose. [82] Gastrointestinal

symptoms, infections, paraesthesia and headaches are most frequently reported. These, along with elevated
blood pressure and reversibly elevated serum creatinine, are dose-related, usually in doses higher than 3
mg/kg/day.[82]
Increased cancer risk is well known with long-term use and higher dosages of cyclosporine, such as with organ
transplant recipients. It is also documented for patients with previous exposure to carcinogens, such as PUVA
or methotrexate.[83]Cyclosporine should not be combined with UV therapy and should not be used in patients
who have significant cumulative life-long UV exposure (the data is insufficient to back up specific threshold
recommendations). The cyclosporine-related risk of malignancies might be expected to be low for
dermatological patients treated with shorter courses and lower doses, and without previous significant UV or
other carcinogenic exposures. However, not enough long-term data are available to allow such conclusions. [84]
Azathioprine is used alone or as corticosteroid-sparing agent. There is efficacy evidence from small RCTs in
airborne contact dermatitis and chronic actinic dermatosis, but no studies in chronic hand dermatitis to our
knowledge. Parthenium dermatitis is the most common airborne contact dermatitis in India. [85] Azathioprine 100
mg daily was as effective as a systemic corticosteroid (betamethasone 2 mg daily) over a period of 6 months in
a doubleblind RCT with 41 patients. Azathioprine had fewer adverse effects and an improved (but not
statistically significant) relapse rate 6 months after treatment. A dose regimen of 300 mg once-weekly pulses
has also been proposed in this indication.[86] There are also anecdotal reports of good results in pompholyx.
The late onset of clinical effect, after 48 weeks, is one of the main drawbacks of azathioprine. The bone
marrow and hepatotoxicity are the most important side effects. The effectiveness and toxicity of azathioprine
are related to the activity of the enzyme thiopurine methyltransferase (TPMT), one of the three inactivation
pathways. The current guidelines recommend its measurement before treatment initiation. [87,88] Due to genetic
polymorphisms, 11 % of the population have intermediate TPMT activity and are predisposed to toxic effects,
and 1 in 300 people has low or no activity and is susceptible to life-threatening pancytopenia, but other
frequencies are also reported.[88] Patients with low activity should not receive azathioprine, those with
intermediate activity can be given 1 mg/kg/day with careful monitoring and those with normal activity (88 % of
population) can receive 2 mg/kg/day. There are those with higher than normal activity; they are likely to be nonresponders and require more aggressive dosing.[87] Other dosage recommendations are also available.
[88]
Inhibition of the other inactivation pathways, which may be caused either by drugs such as xanthine oxidase
inhibitors (allopurinol) and others, or by genetic variability, can lead to azathioprine toxicity as in the
intermediate group. Therefore, dosage based on TPMT pre-treatment activity does not exclude the possibility of
myelosuppression and regular monitoring is necessary.[88] The risk of malignancy in non-transplant patients is
low, but may increase with longer azathioprine application, especially in patients with significant UV exposure. [87]
Due to limited data on the use of methotrexate, mycophenolate mofetil, and other immunosuppressive agents
in contact dermatitis, they cannot be viewed as standard therapy and should be reserved for special cases.
Methotrexate is well established in the clinical practice of dermatology. It has been reported in case series of
patients with unresponsive hand dermatitis[89] and other types of recalcitrant eczema.[90] Good results were
achieved with a range of initiation doses between 5 and 20 mg weekly after 12 months of therapy. Longer
maintenance therapy with the lowest effective doses, such as 2.5 or 5 mg weekly, is advised in one of the
reports.[90] The general safety precautions with methotrexate therapy should be observed, such as monitoring
the serum liver enzymes and complete blood count, as well as the cumulative dosage. Mycophenolate mofetil
is reported to be effective in an individual case of vesicular hand eczema. [91]
Other Treatment Approaches. For the management of cases where complete avoidance of a relevant
allergen is impossible, hyposensitization has been attempted, but the published studies have produced

conflicting results and it is not a standard therapy. There are published examples with nickel
hyposensitization[69,92] and plant dermatitis.[93] Elimination diets have been tried with nickel, but are not routine
clinical practice.[69,94]

Restore the Skin Barrier

The treatment of contact dermatitis is incomplete without measures to restore the skin barrier. The barrier
function of the skin is severely impaired during an episode of irritant or allergic contact dermatitis. Its recovery
may take a long period of time and this should be addressed in the treatment strategy. Additionally, when
allowed to persist, the disruption of the skin barrier induces chronic increase in inflammatory cytokines, leading
to inflammation and epidermal proliferation.[95] It has been demonstrated in early experiments that even after the
skin visually returns to normal, subclinical irritation may persist, resulting in augmented reactivity to rechallenge with irritants.[10]

Conclusion
Knowledge of the different morphological patterns of hand dermatitis is essential for proper diagnosis in clinical
practice. The clinical patterns, however, are poorly related to the etiology in the case of chronic hand dermatitis.
As much as possible, the etiology should be clarified and respective preventive measures should be included in
the treatment concept. A stepwise approach for escalating therapy is advised.

Sidebar
Key Points

The morphology in chronic hand dermatitis is poorly related to the etiology.

Preventive measures should be included in the treatment concept according to etiology.

A stepwise approach for escalating therapy is advised.

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