Hand Dermatitis: A Comprehensive Review with Special Emphasis on COVID-19 Pandemic.

Hand dermatitis (HD) is a chronic, relapsing, and remitting inflammatory condition that adversely affects the quality of life of the individual and gravely impacts the mental and socioeconomic well-being by causing professional hindrance and often leading to loss of wages. Despite being one of the most common skin conditions seen by dermatologists, it is often underreported. With the coronavirus pandemic ongoing, there is an emphasis on hand hygiene-being a widely publicized and important preventive measure to control the spread of the Coronavirus disease (COVID-19) virus. Emphasis on hand hygiene has led to a surge in HD, and the presence of HD, in turn, leads to compromised hand hygiene practices and this breach in the skin barrier contributes to another portal of entry of infective agents. We undertook a comprehensive English literature search across multiple databases such as PubMed, SCOPUS, EMBASE, MEDLINE, and Cochrane using keywords and MeSH items to obtain and review several relevant articles. Thus, this review focuses on various clinical, diagnostic as well as therapeutic aspects of this much prevalent and debilitating skin condition which deserves more attention especially during the times of the COVID-19 pandemic where the utmost emphasis is being given to handwashing leading to a vicious cycle of a surge in the cases of HD and compromised skin barrier causing increased susceptibility to the COVID-19 infection. Copyright:

Introduction

Hand dermatitis (HD) is an inflammatory condition which may be exogenous, endogenous, or both and may clinically present as acute, chronic, or recurrent inflammation characterized by redness, infiltration of the skin, scaling, edema, vesicles, hyperkeratosis, fissures, and erosions.[1] It is a common condition affecting people globally and is often underreported.

This review focuses on this otherwise common but debilitating condition that adversely affects the Dermatology Life Quality Index (DLQI) of patients often leading to occupational hindrance and loss of wages. Due to the chronicity and extensive physical, mental, and socioeconomic impact of this condition, it deserves more attention especially during the times of the COVID-19 pandemic where the utmost emphasis is being given to handwashing leading to a vicious cycle of a surge in cases of HD and compromised skin barrier causing increased susceptibility to the COVID-19 infection.

Methods

We undertook a comprehensive English literature search across multiple databases such as the PubMed, SCOPUS, EMBASE, MEDLINE, and Cochrane using keywords (alone and in combination) and MeSH items such as “hand dermatitis” AND “hand eczema” OR “treatment” OR “COVID-19” to obtain several relevant articles, priority being given to prospective randomized controlled trials. We scanned all the relevant articles in English literature and summarized them to obtain the latest information to prepare the current review article. The references of the selected articles were scanned for more relevant articles. Articles in other languages were excluded from our search.

Epidemiology

HD is a common dermatological condition. The exact numbers are difficult to determine, first, because it is not a reportable disease, second, many who are affected do not seek medical attention, and third, most studies fail to show the true prevalence of HD as they are often conducted on clinical population instead of the general population. It is estimated that 2–10% of the general population is affected by HD at some point in life and it constitutes 20–35% of all diseases affecting the hands.[2] Moreover, HD is by far the commonest form of occupational skin disease (OSD) commonly seen in industrial workers, masons, farmers, healthcare workers, and homemakers because of exposure to various chemicals.[3]

Females are more frequently affected compared to males (2:1).[45] A possible explanation for this could be the increased exposure to wet work and household chemicals.[4]

The mean age of onset of HD is usually in the third decade.[36] HD is rarely seen in patients younger than 20 years and older than 60 years, probably because of the apparent hypo-responsiveness of children due to limited exposure and due to various defects in the elicitation of allergic contact dermatitis (ACD) in older individuals.[6]

Classification

HD can be broadly classified etiologically into

Endogenous HD

Exogenous HD

This can be further classified into various types depending on the etiology and morphology. While the exact prevalence of each condition varies according to the particular population under study, the three most common are irritant, allergic, and atopic dermatitis (AD).[7]

Etiologic Classification

Irritant contact dermatitis (ICD): Repeated exposure to irritants in sufficient concentration and over a prolonged period may cause an inflammatory response of the skin, compromising the skin's barrier function and making it susceptible to the development of contact allergy.

Atopic HD: Patients usually have a positive personal or family history of atopy.

ACD: This is a T-lymphocyte-mediated delayed-type contact allergy to various allergens like chromate (e.g., cement), rubber additives (e.g., in gloves), nickel (e.g., jewelry), and fragrance mix (e.g., soaps, detergent, cosmetics)[7]

Hybrid hand eczema: Clinically a combination of ICD, atopic HD, and ACD.

Protein contact dermatitis: A type of ACD frequently occurring in people involved with food processing. Initially, the reaction to proteins is urticarial (contact urticaria), but eczema may develop. Patch tests are usually negative, and the gold standard for diagnosis is skin prick testing with fresh material or commercial reagents.

Unclassified: In chronic hand eczema, when the original causative factor becomes irrelevant and obscure, it is known as unclassified HD.[1]

Morphologic Classification

Pompholyx: These present as deep-seated vesicles on the palms and rarely soles that tend to recur. The name dyshidrotic eczema is a misnomer since the condition is not related to the sweat glands [Figures 1 and 2].

Figure 1

Pompholyx

Figure 2

Pompholyx

Hyperkeratotic hand eczema: This presents as sharply demarcated areas of thick scaling and painful fissures on the palms (and frequently on the soles) commonly seen in middle-aged or elderly males. The vesicles are absent. (It mimics psoriasis but typical scaling, erythema, and nail changes are absent) [Figure 3].

Figure 3

Hyperkeratotic hand eczema due to frequent hand washing and use of hand sanitizers

Chronic fingertip dermatitis or pulpitis: This condition is characterized by dry, fissured, scaling dermatitis of the fingertips, with occasional episodes of vesiculation. The cause is unknown.

Nummular hand eczema: It is characterized by round, coin-sized eczematous patches that commonly appear over the extensor aspects on the lower limbs and rarely hands.

Chronic relapsing vesiculosquamous dermatitis: It is a common pattern of palmar and finger dermatitis, in which episodes of acute vesicular dermatitis are followed by chronic scaling and fissuring.

Housewives' eczema: It is due to repeated exposure to different household allergens, the most common allergens being nickel, potassium dichromate, fragrance mix, and chlorocresol. Vegetables have been considered as common sensitizers in women in India. The wet form of housewife's HD involves the back of the hand, the fingers, and the palms. The dry form starts at the tips of the first three fingers.

Apron eczema: It is a type of HD that involves the proximal palmar aspect of two or more adjacent fingers and the contiguous palmar skin over the metacarpophalangeal joints, thus resembling an apron.

Gut/slaughterhouse eczema: It is seen as a transient vesicular eczema which begins from the webs of the fingers and spreads to the sides. This specifically affects workers engaged in the evisceration of carcasses of animals in slaughterhouses.

Chronic acral dermatitis: This is a distinctive syndrome affecting middle-aged patients and is characterized by pruritic, hyperkeratotic papulovesicular eczema of the hands and the feet. It is associated with grossly elevated immunoglobulin (Ig) E levels without any personal or family history of atopy.

Ring eczema: This condition is characterized by a patch of eczema which develops under a ring and spreads to involve the adjacent side of the middle finger and the adjacent area of the palm. There is usually no contact sensitivity to metals, instead, it is due to the accumulation of soap and detergent beneath rings.

Unspecified eczemas: These cannot be classified into any morphological types.[146]

Risk factors contributing to hand dermatitis

Various exogenous and endogenous factors contribute to the development and exacerbation of HD Some of them are wet work, frequent hand washing, occlusive gloves for a prolonged duration, exposure to detergents, alkalis, organic solvents, atopy, genetic factors, smoking, etc.[8]

Genetics

The genetics of HD is not completely understood. However, several studies suggest that various genes may be involved as summarized in Table 1.[9]

Table 1

Genes associated with hand dermatitis[9]

Gene	Mutation	Effect
Filaggrin (FLG) gene	Loss of function mutations	Heterozygous status for FLG loss of function mutations in combination with atopy has unfavorable effects on the disease course of hand dermatitis
Tumor necrosis factor (TNF) α gene	Single nucleotide polymorphism	TNF α-238-A allele: Protective against ICD
		TNF α-308-A allele: Risk factor for ICD
Late cornified envelope gene LCE3B and LCE3C	Deletion	Significant association with chronic ACD
SPINK5 gene	Single nucleotide polymorphism	Significant association with non-atopic hand dermatitis
Interleukin (IL) 1A gene	Single nucleotide polymorphism	Significant protective effects with regard to ICD

Of the various genes associated with HD, filaggrin (FLG) mutation has been found to be of significance. FLG mutation may increase the risk of hand eczema irrespective of the atopic status, as it leads to impaired barrier function which in turn increases the penetration of environmental noxious agents, and thus, increase the risk of contact eczema including that of the hands.[10]

In a study by De Jongh et al.,[11] it was seen that patients with FLG mutation (R501X and 2282del4) are at an increased risk of chronic ICD of the hands or the forearms compared with controls. Thyssen et al.[12] reported that FLG null mutations were significantly associated with hand eczema (<12 months) in subjects with AD. Combined AD and filaggrin null mutation status was strongly associated with early onset of hand eczema and hand eczema persistence.

Hand dermatitis and smoking

Numerous studies have been conducted to date to study the association of smoking with HD but the results are quite conflicting. The recent studies by Lai et. al and Zimmer et. al identified smoking as an important risk factor for HD.[1314] Smoking may lead to the onset or exacerbation of hand eczema by disrupting the healing process or via proinflammatory cytokines and oxidative stress. Serum cotinine levels (an alkaloid found in tobacco and a metabolite of nicotine with a long half-life) serve as a useful biomarker to study the association of smoking and HD.

Hand dermatitis and stress

Stress has recently been implicated as a contributing factor in the etiopathogenesis of HD.[5] However, data regarding this association are limited and need further research.

Management

HD being a relapsing and remitting condition with an adverse impact on DLQI and the psychosocial aspects, its management is of utmost importance. The management may be discussed under the following headings:

Assessment of severity

Diagnostic considerations (history and investigations)

Preventive and protective measures

Treatment

A. Assessment of Severity

The severity of hand eczema can be assessed by various scoring methods:

Osnabrück hand eczema severity index (OHSI)

The OHSI employs six morphological signs (erythema, scaling, papules, vesicles, infiltration, and fissuring) scored from 0 to 3 according to the extent, except for fissures, which were classified according to the degree of severity. The total score (0–18) was obtained by adding the affected area score and the severity grade score.[15]

Manu score

This involves semiquantitative assessment of the following three subscales: surface area, minor clinical morphological signs (erythema, scaling, papules / infiltration, vesicles, hyperkeratosis, lichenification, erosions, pustules), and major clinical morphological signs (fissures, oozing, itching). The total score ranges from 0 to a maximum of 6,480 points.[15]

Hand eczema severity index (HECSI)

Each hand is divided into five areas: Fingertips, fingers (except the tips), palms, back of hands, and wrists. For each of these areas, the intensity of erythema, induration, papulation, vesicles, fissuring, scaling, and edema is graded (0: no skin changes; 1: mild disease; 2: moderate; and 3: severe). For each location (total of both hands) the affected area is given a score from 0 to 4 (0: 0%; 1: 1–25%; 2: 26–50%; 3: 51–75%; and 4: 76–100%) for the extent of clinical symptoms. The score given for the extent at each location is multiplied by the total sum of the intensity of each clinical feature, and the total sum called the HECSI score is calculated, varying from 0 to 360 points.[16]

Hand eczema score for occupational screenings (HEROS)

The HEROS comprised both morphological patterns and physiological abnormalities and assesses their extent and severity. This scoring is important for early screening for hand eczema. The maximum score possible is 2,260.[17]

DLQI

The DLQI questionnaire is designed for use in patients over the age of 16 years. It comprises 10 self-explanatory questions and is usually completed in 1 or 2 min. The DLQI is between 0 and 30, the higher the score, the more the quality of life is impaired.

Physician Global Assessment (PGA)

Clinical Photo Guide

It is used for severity assessment based on the comparisons of the hand eczema of the patient with four rows of photographs showing the increasing intensity of eczema.[18]

B. Diagnosis

The diagnosis of HD is mostly clinical based on history and examination. But it may often be confused with other common inflammatory disorders affecting the hands [Table 2]. In such cases, further investigations like a skin biopsy, patch testing for allergens, and skin scrapings in potassium hydroxide mount for hyphae along with fungal and bacterial cultures for the correct diagnosis.

Table 2

Diagnostic features and differential diagnosis of hand dermatitis

Type of Hand Dermatitis	Diagnostic Features
Irritant contact dermatitis	Burning, itching, and tenderness at the site of exposure to an irritant
	Typically involves the finger webs with extension to the dorsal and ventral surfaces
Atopic hand dermatitis	Young age
	Dry and pruritic skin during the patient’s adult life
	Involves dorsum of hands and fingers and may extend to the wrist
Allergic contact dermatitis	Commonly affects the fingertips, nailfolds, and dorsal hands
Nummular dermatitis	Well-defined circular lesions involving dorsum of hands and lower extremities
	Size of lesions usually does not change
Pompholyx	Sago-grain-like vesicles usually on the lateral aspect of the fingers
	May also involve the soles
Psoriasis	Well demarcated thick erythematous plaques with silvery scales and fissuring. It usually spares the pressure areas and involves the center of the palm. Lesions may be present on other extensor surfaces or scalp
Infections	Fungal infections of hands are extremely pruritic, usually unilateral and involve the nails
	Herpes simplex presents as localized recurrent attacks of clustered vesicles, which are very painful but not itchy
Lichen planus	Sharply demarcated hyperkeratotic violaceous lesions are present usually sparing the fingertips
Pityriasis rubra pilaris	Waxy palmoplantar keratoderma with orangish or yellowish hue. The cardinal features are variable degrees of red-orange papules and plaques, hyperkeratotic follicular papules with island of sparing
Dermatomyositis	Mechanic’s hands are frequently seen in such patients. It is roughening and cracking of the skin of the tips and sides of the fingers, resulting in irregular, dirty-appearing lines that resemble those of a mechanic or manual laborer

Patch tests (delayed hypersensitivity) should ideally always be performed in patients with chronic hand eczema, and if done, should be with Indian standard series, after a thorough history and examination. A patch test gives an important clue toward allergens that may be the cause of HD and the identification of allergens helps in the management immensely. In a study by Vigneshkarthik et al.,[19] nickel was the most common allergen followed by para-phenylenediamine (PPD), moreover, they also reported that a discoid form of HD was common among patients with potassium dichromate allergy. Although not a major cause of HD, ACD due to nickel remains a common cause.[19] A prick test detects immediate hypersensitivity and should be a part of routine investigations in patients with HD with suspected occupational contact urticaria especially if there is a history of atopy and are involved in high-risk occupations. Normally, specific allergens from the workplace or home should be used for the same, like fresh food, to diagnose protein contact dermatitis.

C. Preventive and Protective measures

Prevention, identification, reduction, and elimination of causative factors are the cornerstone of the management of HD. The skin protection may be achieved by

Pre-exposure barrier/protective creams to be used before and during work. They are also useful under occlusive gloves to reduce skin maceration.

Using mild skin cleansers to cleanse during and after work with potential irritants.

Post-exposure skin care after work with emollients, moisturizers, humectants (glycerol, sorbitol, urea), lipids (complex mixtures of ceramide, fatty acid, cholesterol).[3]

Alcohol-based disinfectants with or without glycerin are less irritant than soap and water.[20]

Ethanol tends to be less irritant than isopropyl alcohol without compromising its efficacy and should be preferred. Glycerol can also be added to alcohol-based hand rubs to make it moisturizing.[20]

Gloves provide effective protection against most irritants but they should be selected carefully as a wrong selection of gloves may lead to the aggravation of dermatitis. A newer variety of gloves are available like semi-permeable gloves which have selective semi-permeable membranes allowing the transport of water from inside to outside but prevent the penetration of water from outside. They do not provide any protection against chemicals so should be used in wet work where no chemicals are involved. In the metal industry where gloves are not permitted to be worn due to the risk from rotating machinery, rip-up gloves which are easy to tear may be used. For those who are allergic to the standard glove, “hypoallergenic” gloves are now available which are free from vulcanization accelerators.

D. Treatment

A variety of therapeutic options available for HD have been summarized in Table 3.

Table 3

Therapeutic options in hand dermatitis[341516]

	Level of evidence	Grade of recommendation
Topical
Barrier repair	1	A
Corticosteroids	1c	A
Calcineurin inhibitors	2b	B
Calcipotriol	4	C
Coal tar, pine tar and sulfonated shale oil preparations	4	C
Systemic
Corticosteroids	1c	A
Alitretinoin	1b	A
Acitretin	2b	B
Cyclosporine	2b	B
Azathioprine	4	C
Methotrexate	4	C
Oral iron	5	D
Biologics
Dupilumab	4	C
JAK inhibitors (Delgocitinib)	4	C
Phototherapy
Systemic PUVA	1c	A
Topical PUVA
Narrow band UVB
Miscellaneous
Radiotherapy	4	C
Botulinum toxin	4	C
Iontophoresis	4	C

Topical therapy

1. Barrier repair

Topical therapy with emollients or moisturizers is a key component in the treatment of any kind of eczema and should be continued even after visible signs of eczema have resolved. The basic topical therapy helps to reduce inflammation and itching, promotes epidermal barrier recovery, and thereby, exerts corticosteroid-sparing effects.[21]

For acute hand eczema, the basic topical therapy should have drying, astringent, and antibacterial effects which are achieved by Condy's baths and soaks whereas, in subacute hand eczema, the basic topical therapy should have anti-inflammatory, antipruritic, and moisturizing effects; this may be achieved by moisturizing water-in-oil and oil-in-water emulsions. In chronic hyperkeratotic hand eczema, keratolytic, anti-proliferative, and moisturizing effects are needed with keratolytic ointments (salicylic acid, urea) and lipid-rich ointments, including water-in-oil and oil-in-water emulsions. Level of evidence: 1. Strength of recommendation: A.

2. Corticosteroids

Topical corticosteroids (TCS) have been the mainstay of the topical treatment of hand eczema and the European Society of Contact Dermatitis (ESCD) guidelines recommend them as first-line treatment in the management.[2122] Usually, high-potency steroids (clobetasol propionate, betamethasone dipropionate) are used. Their use should be limited to 2–4 weeks to prevent the side effects like atrophy, dryness, and erythema.

They are pregnancy category C drugs. Level of evidence: 1c

Strength of recommendation: A.

3. Calcineurin inhibitors

Tacrolimus and pimecrolimus are calcineurin inhibitors that inhibit the transcription of inflammatory cytokines like IL2 released from the T-cells. The current ESCD guidelines suggest considering topical calcineurin inhibitors for hand eczema patients with a need for long-term treatment.[22]

The advantage of these compounds is their safety over long-term usage, without the induction of atrophy or interference with barrier repair. However, they are only licensed for the treatment of AD, their use in the other types of HD not involving atopy is off-label. The most common side effect of topical calcineurin inhibitors is local skin irritation (burning, pruritus, and erythema). They are pregnancy category C drugs. Level of evidence: 2b.

Strength of recommendation: B.

4. Topical calcipotriol

Its use for HD is off-label. There is anecdotal evidence to suggest its use in hyperkeratotic hand eczema that mimics palmar psoriasis. The exact mechanism of action is still unknown, however, calcipotriol has been shown to inhibit cell growth and development without any evidence of harmful effects to the cell itself. The side effects reported are localized burning, itching, rash, irritation, erythema, or peeling.[21] It is a pregnancy category B drug. Level of evidence: 4.

Strength of recommendation: C.

5. Coal tar, pine tar, and sulfonated shale oil preparations

Topical tar preparations have been used widely in the treatment of psoriasis. Its use in HD is limited due to the possible risk of the tar being carcinogenic. The risk in pregnancy is unknown but the drug is probably not absorbed through the skin.

Sulfonated shale oil preparations seem to have a better safety profile but future studies on their efficacy and safety in HD are needed.[21]

Level of evidence: 4. Strength of recommendation: C.

Systemic therapy

In the systemic treatment of HD, the benefit-risk ratio of the available therapies should be analyzed considering the chronic and recurrent nature of the disease.

1. Systemic corticosteroids

Systemic corticosteroids are usually indicated in severe acute hand eczema and exacerbations of the chronic disease. They exert an anti-inflammatory action by decreasing proinflammatory cytokines. Usually, prednisolone or its equivalent is used in a dose of 0.5–1 mg/kg/day for a short term. Their long-term or frequent use is not indicated in hand eczema due to side effects like osteoporosis, glaucoma, cataracts, hypothalamic-pituitary-adrenal axis suppression, hyperglycemia, and hypertension.[2122] Level of evidence: 1c. Strength of recommendation: A.

2. Alitretinoin

Alitretinoin is a vitamin A derivative that binds with high affinity in a saturable manner to all six known retinoid receptors. It is the only approved systemic treatment licensed specifically for hand eczema.[22] The ESCD guidelines recommend the use of alitretinoin for treating severe, chronic hand eczema that does not respond or responds inadequately to TCS.[21]

Keratinocytes show a significant reduction of chemokine expression after stimulation with alitretinoin whereas it inhibits the upregulation of the maturation marker on dendritic cells leading to impaired T-cell-activating properties.

The recommended dose for alitretinoin is 10 or 30 mg once daily. It has a few dose-dependent adverse effects like headache, mucocutaneous lesions, and hyperlipidemia. It is teratogenic and requires strict pregnancy prevention 1 month before, during, and for 1 month after the cessation of the treatment.[21]

Level of evidence: 1b. Strength of recommendation: A.

3. Acitretin

Acitretin is not approved for the treatment of hand eczema, but has some efficacy, especially in the management of hyperkeratotic HD. It works by targeting specific receptors (retinoid receptors such as RXR and RAR) in the skin which help normalize the growth cycle of skin cells.

It is used at a dose of 25–50 mg orally once a day. It is a pregnancy category X drug. The side effects include dry mouth, dry eyes, xerosis, pain in the abdomen, muscle and joint pain, and headaches.[21]

Level of evidence: 2b. Strength of recommendation: B.

4. Cyclosporine

Cyclosporine inhibits the transcription of interleukin 2 and several other cytokines leading to the inhibition of the activation of T-cells. Cyclosporine is not approved for the systemic treatment of HD and its use in the management of HD is limited to cases of atopic hand dermatitis.

The recommended dose for cyclosporine is 2.5–5 mg/kg daily.

According to the ESCD guidelines, cyclosporine may be considered for hand eczema patients with a long-term need for treatment if the first- and second-line therapies have been insufficient or contraindicated. It is pregnancy category C. The therapy is associated with the risk of hypertension and nephrotoxicity.[21]

Level of evidence: 2b. Strength of recommendation: B.

5. Azathioprine

Azathioprine inhibits purine synthesis and is used off-label for a variety of conditions including HD. The recommended daily dose is 1–2 mg/kg. Caution should be exercised when used in patients with thiopurine methyltransferase deficiency.

Although the efficacy of azathioprine in the management of HD seems to be rather limited, atopic HD and HD seen with parthenium dermatitis respond well to azathioprine. It is a pregnancy category D drug.[21]

Level of evidence: 4. Strength of recommendation: B.

6. Methotrexate

The evidence for the use of methotrexate in hand eczema is limited. Methotrexate is a folate antagonist which inhibits the dihydrofolate reductase enzyme. This leads to anti-proliferative and anti-inflammatory effects.

The recommended daily dose is 7.5–25 mg/week orally, IM, IV, or subcutaneously.

The ESCD guidelines mention the lack of evidence for the efficacy of methotrexate for the treatment of hand eczema. However, it has been used over the years with good efficacy and may be considered if the first- and second-line therapies have been insufficient or contraindicated. It is a pregnancy category X drug. Nausea and vomiting are the most common side effects; others include headache, fatigue, mucositis, and hepatic fibrosis.

Level of evidence: 4. Strength of recommendation: C.

7. Iron therapy

A few studies have shown the effect of oral iron to reduce nickel absorption from the diet. A low nickel diet (onion and garlic, mustard oil, salt, sugar, turmeric powder in moderation) and oral iron could bring a faster reduction in the severity of clinical symptoms of chronic vesicular hand eczema in a nickel-sensitive individual.[23]

Level of evidence: 5. Strength of recommendation: D.

Biologics

Dupilumab

Dupilumab is a fully human monoclonal antibody directed against the interleukin IL-4Ra subunit inhibiting the signaling of the type 2 cytokines IL-4 and IL-13 and is approved for use in the treatment of adult patients with moderate-to-severe AD since 2017. The use of biologics in AD suggests that they may also have a role in the management of hand eczema.

Thus, dupilumab seems to have the potential to control hand eczema in a significant proportion of patients with concomitant AD, but further studies are needed to assess its use in patients with other etiologies of hand eczema.[23]

Level of evidence: 4. Strength of recommendation: C.

JAK inhibitors

Since they are small molecules, they may penetrate the epidermal barrier, thus, being of potential not only for systemic but also for topical use in hand eczema.[21]

Delgocitinib is a novel, pan-JAK inhibitor specific for JAK1, JAK2, JAK3, and TYK2 kinases. It blocks several cytokine-mediated signaling cascades, thereby, inhibiting inflammation and may be a suitable therapeutic agent for topical use in hand eczema.[21]

Level of evidence: 4. Strength of recommendation: C.

Phototherapy

This includes systemic psoralen and ultraviolet A radiation (PUVA), topical PUVA, and narrowband Ultraviolet B (UVB). The mechanism of action includes alteration of cytokine profile, induction of apoptosis, and immunosuppression.

The current ESCD guidelines suggest phototherapy of the hands in adult patients with chronic hand eczema refractory to first-line treatment with TCS. However long-term use of phototherapy carries with it the increased risk of skin malignancy.[21] Narrowband ultraviolet B phototherapy (NB-UVB) is generally accepted as safe in pregnancy. Psoralen has a theoretical risk of teratogenic and mutagenic effects due to the inhibition of DNA synthesis and cell division, and hence, is contraindicated during pregnancy, with an advisable 'washout' period of 3–6 months.

Level of evidence: 1c. Strength of recommendation: A.

Miscellaneous

1. Radiotherapy

Low-dose electromagnetic radiation therapy, in the form of Grenz rays or superficial X-rays, is a potential therapeutic option for recalcitrant hand eczema. Low kilovoltage electromagnetic waves are directed toward the target tissue at fractioned intervals to exert anti-inflammatory effects. As a result of their low penetrative power, the reticular dermis of the skin is relatively spared and the side effects are minimized. The carcinogenic risk, although low, must be considered when recommending this treatment. Further research into the long-term effects, and in particular, cumulative dosing should be undertaken to validate this modality of treatment.[24] Level of evidence: 4. Strength of recommendation: C.

2. Botulinum toxin

Botulinum toxin A (BTXA) is a potent inhibitor of acetylcholine release and inhibits sweating, therefore, it is beneficial in dyshidrotic hand eczema. BTXA is antipruritic as well suggesting that it does not only interact with acetylcholine release but substance P as well.[25]

Level of evidence: 4. Strength of recommendation: C.

3. Iontophoresis

Iontophoresis is a procedure in which an electrical current is passed through the skin soaked in tap water, normal saline (0.9%), or a solution containing an anticholinergic medication, which allows ionized (charged) particles to cross the normal skin barrier. It reduces sweating and is safe, effective, and inexpensive.

The efficacy of tap water iontophoresis in treating palmoplantar hyperhidrosis has been sufficiently documented and has led to its extensive use in clinical practice.[26]

Level of evidence: 4. Strength of recommendation: C.

For better understanding, an algorithmic approach to the treatment of HD has been outlined in Flowchart 1.

Flowchart 1

Algorithmic approach to the management of a patient with hand dermatitis.

Hand dermatitis in special population

Children: Hand eczema is a fairly common condition in children. The most common cause is atopic HD, although cases of ACD and ICD manifesting as hand eczema are not uncommon.[27]

Elderly: The skin becomes xerotic as the lipid content decreases with age. This results in increased transepidermal water loss and reduced barrier function, leading to an increase in susceptibility to develop eczematous changes, including HD.

Pregnancy: Eczema has a fluctuating course in most patients and is influenced by environmental and internal triggers. However, pregnancy does seem to have an effect on eczema in most women with the condition—approximately 25% improve, and more than 50% experience a deterioration.[28] If management mandates systemic therapy, then the effect of various drugs on the fetus must be kept in mind.

Hand dermatitis and the COVID-19 Pandemic

The World Health Organization (WHO) and the Center for Disease Control (CDC) recommends strict hand hygiene practices like frequent handwashing with soap for at least 20 s to mechanically removes the pathogens and curb transmission of COVID-19.[20] This much-needed emphasis on hand hygiene has set up a vicious cycle leading to HD and impaired skin barrier making the individual susceptible to infections.

The hand hygiene measures include frequent handwashing with soap and water for 20 s or using a hand sanitizer containing at least 60% alcohol.[20] The higher frequency of handwashing in contrast to the lower frequency of moisturizer application and other cumulative factors like cold weather, occlusion under personal protective equipment and gloves, atopic predisposition, friction, etc., predispose to an increased risk of HD, especially ICD.[29]

Chernyshov et al.[30] in their study found a high prevalence of hand skin problems in nurses and doctors consistent with the results of other studies on skin complications in health care workers during the COVID-19 pandemic. Frequent handwashing implies a prolonged exposure to water and other chemical or physical agents and may induce several pathophysiologic changes, such as epidermal barrier disruption, impairment of keratinocytes, the subsequent release of proinflammatory cytokines, activation of the skin immune system, and delayed-type hypersensitivity reactions. The alcohol-based hand sanitizers (containing ethanol or isopropyl alcohol) solubilize the components of intercellular lipids, which leads to the disruption of the epidermal barrier.[31] Adverse dermatologic effects, such as excessive skin dryness or even contact dermatitis (particularly the irritant subtype and, to a lesser extent, the allergic subtype), can occur, especially in individuals with a history of AD.[32] Simonsen et al.[33] found that following the implemented hygiene regimen, a high proportion of young children rapidly developed hand eczema.

Skin barrier damage, due to overzealous hand hygiene, has been suggested as a potential route of entry for the SARS-CoV-2 virus based on the mechanism of viral entry into the cells that is mediated by receptor-binding domain located in the viral spike protein (S protein) and the cellular angiotensin-converting enzyme 2 receptors (ACE2) in the basal layer of the epidermis, hair follicle, eccrine gland, and smooth muscle surrounding the sebaceous glands.[34] Caveolins are cytoplasmic proteins which have a definite role in the cellular processes crucial for normal skin function like lipid transport, wound healing, signal transduction, cell migration, and proliferation.[35] COVID-19 orf3A protein is capable of interacting with caveolin, thus, the caveolin receptors may have a pathogenetic role in the coronavirus infection.[36] Thus, there is a theoretical possibility that a compromise in the skin barrier in HD due to overzealous hand hygiene could contribute to the direct contact transmission of SARS-CoV-2.

To avoid the above, it is important to educate the masses regarding the use of proper hand hygiene measures and products. The following recommendations suggested by the American Contact Dermatitis Society may be considered[37]:

A) Handwashing

Lukewarm or cool water should be used. Very hot or cold water should be avoided.

The hands must be patted dry and not rubbed.

The products with antibacterial ingredients are not necessary for proper hand hygiene, instead soaps or synthetic detergents that are devoid of allergenic surfactants, preservatives, fragrances, or dyes but with added moisturizers should be used.

B) Sanitizers

Hand sanitizers with 60% alcohol devoid of allergenic surfactants, preservatives, fragrances, or dyes but with added moisturizers should be used.

C) Moisturizers

Moisturizers should be used immediately after handwashing or hand sanitization.

Avoid moisturizers in jars to prevent double-dipping into and potentially contaminating the product.

For those with HD, the soak and smear method (soak the hands in plain water for 20 min and immediately apply moisturizer of choice to the damp skin) may be used at night for 2 weeks. Loose cotton or plastic gloves can be used post-moisturization to create an occlusive barrier.

For the health care workers, a moisturizer under gloves can also be effective. Moisturizers with a water base are safe under all gloves; however, oil-based moisturizers can break down the latex and rubber by making the material swell or brittle.

D) Gloves

Apply moisturizer after washing hands and before wearing gloves.

Consider a cotton glove liner or loose plastic gloves (e.g., plastic clear, disposable food gloves).

Latex, vinyl, and nitrile gloves are resistant to break down from ethanol or isopropyl alcohol. So, accelerator and rubber-free gloves like neoprene and nitrile are advised.

Individuals with suspected hand ACD should be patch tested.

Conclusion

HD is a very common and fairly recurrent inflammatory condition. Although a range of treatment options are available, this condition is notorious for its relapsing and remitting course, thus having a grave impact on the Quality of life (QOL) and psychosocial aspect including loss of wages. The ongoing COVID-19 pandemic has led to an increased focus on hand hygiene as an effective measure to prevent disease transmission. The vicious cycle of COVID-19 and HD is quite concerning given the disease burden. Further studies are needed to better understand the pathogenesis of the COVID-19 virus and its correlation with HD. However, with newer modalities of protective measures, treatments, and with a variety of drugs in the dermatologists' armamentarium, breaking this cycle is a possibility.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.