Review question
We reviewed evidence on the effects of topical and systemic (oral or injected medicines that work throughout the entire body) treatments for hand eczema when compared against placebo (an identical but inactive treatment), no treatment, vehicle (inactive ingredients that help deliver an active treatment), or another treatment. We included 60 randomised trials (5469 participants) published up to April 2018.
Background
Hand eczema is an inflammation of the skin of the hands that can be caused by contact allergens (i.e. substances that cause an allergic reaction) such as rubber chemicals, but other external factors (e.g. irritants such as water or detergents) and atopic predisposition are often important triggers. Hand eczema can cause a reduction in quality of life leading to many work-related problems. Various types of hand eczema exist, and different topical (creams, ointments, or lotions) and systemic treatments with unknown effectiveness can be used.
Study characteristics
Most participants were hospital outpatients over 18 years of age with mild to severe chronic hand eczema. Treatment was usually given for up to four months, and outcomes were mainly assessed after treatment. A large variety of treatments were studied and compared to no treatment, variants of the same medication, placebo, or vehicle. Twenty-two studies were funded by pharmaceutical companies.
Key results
Limited data are available to support the best way of managing hand eczema due to varying study quality and inability to pool data from studies with similar interventions. Corticosteroid creams/ointments and phototherapy (irradiation with UV light) are the major treatment options, although comparisons between these options are lacking. Below, we present results for the main comparisons of interest.
Corticosteroid creams/ointments: clobetasol propionate foam probably increases participant-rated good/excellent control of hand eczema when compared to vehicle (516 versus 222 per 1000), but the difference between groups was less clear for investigator-rated control, and more adverse events were reported with clobetasol propionate (178 versus 79 per 1000) (all based on moderate-certainty evidence).
Mometasone furoate cream used thrice weekly may slightly improve investigator-rated good/excellent control compared to twice weekly treatment, and participant-rated control was not measured. Mild skin thinning occurred in both groups, but cases were few (all based on low-certainty evidence).
Irradiation with UV light: various types of irradiation (i.e. exposure to radiation) were compared. Local PUVA may improve investigator-rated good/excellent control compared to narrow-band UVB (400 versus 200 per 1000); however, we are uncertain of this finding because results also show that local PUVA may make little or no difference. Participant-rated symptoms were not measured. Nine out of 30 participants in the narrow-band UVB group reported adverse events (mainly redness) compared to none in the PUVA group (all based on moderate-certainty evidence).
Topical calcineurin inhibitors: people receiving tacrolimus are probably more likely to achieve improved investigator-rated good/excellent symptom control compared to those given vehicle (14/14 participants with tacrolimus compared to none with vehicle), but participant-rated control of symptoms was not measured. Four of 14 people in the tacrolimus group versus zero in the vehicle group had well-tolerated application site burning/itching. One small study compared tacrolimus to mometasone furoate, which were both well tolerated, but did not measure investigator- or participant-rated control (all based on moderate-certainty evidence).
Oral interventions: oral immunosuppressant (a drug that hinders the immune response) cyclosporin probably slightly improves investigator- or participant-rated control of good/excellent symptoms compared to topical betamethasone cream (a corticosteroid). The risk of adverse events such as dizziness was similar between groups (all based on moderate-certainty evidence).
The oral vitamin A derivative (retinoid) alitretinoin (10 mg) achieved investigator-rated good/excellent symptom control in 307 compared to 194 participants per 1000 with placebo, and alitretinoin 30 mg achieved investigator-rated control in 432 compared to 157 participants per 1000 with placebo. Similar results were shown for participant-rated control (high-certainty evidence). When the dosage of alitretinoin was increased to 30 mg, risk of headache was higher compared to placebo (74 versus 251 per 1000; high-certainty evidence), but this probably does not differ between alitretinoin 10 mg and placebo (based on moderate-certainty evidence).
Quality of the evidence
The quality of evidence was mainly moderate, with most analyses based on single studies that had small sample sizes; therefore, some results should be interpreted with care.
Most findings were from single studies with low precision, so they should be interpreted with caution. Topical corticosteroids and UV phototherapy were two of the major standard treatments, but evidence is insufficient to support one specific treatment over another. The effect of topical calcineurin inhibitors is not certain. Alitretinoin is more effective than placebo in controlling symptoms, but advantages over other treatments need evaluating.
Well-designed and well-reported, long-term (more than three months), head-to-head studies comparing different treatments are needed. Consensus is required regarding the definition of hand eczema and its subtypes, and a standard severity scale should be established.
The main limitation was heterogeneity between studies. Small sample size impacted our ability to detect differences between treatments.
Hand eczema is an inflammation of the skin of the hands that tends to run a chronic, relapsing course. This common condition is often associated with itch, social stigma, and impairment in employment. Many different interventions of unknown effectiveness are used to treat hand eczema.
To assess the effects of topical and systemic interventions for hand eczema in adults and children.
We searched the following up to April 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, AMED, LILACS, GREAT, and four trials registries. We checked the reference lists of included studies for further references to relevant trials.
We included randomised controlled trials (RCTs) that compared interventions for hand eczema, regardless of hand eczema type and other affected sites, versus no treatment, placebo, vehicle, or active treatments.
We used standard methodological procedures expected by Cochrane. Primary outcomes were participant- and investigator-rated good/excellent control of symptoms, and adverse events.
We included 60 RCTs, conducted in secondary care (5469 participants with mild to severe chronic hand eczema). Most participants were over 18 years old. The duration of treatment was short, generally up to four months. Only 24 studies included a follow-up period. Clinical heterogeneity in treatments and outcome measures was evident. Few studies performed head-to-head comparisons of different interventions. Risk of bias varied considerably, with only five studies at low risk in all domains. Twenty-two studies were industry-funded.
Eighteen trials studied topical corticosteroids or calcineurin inhibitors; 10 studies, phototherapy; three studies, systemic immunosuppressives; and five studies, oral retinoids. Most studies compared an active intervention against no treatment, variants of the same medication, or placebo (or vehicle). Below, we present results from the main comparisons.
Corticosteroid creams/ointments: when assessed 15 days after the start of treatment, clobetasol propionate 0.05% foam probably improves participant-rated control of symptoms compared to vehicle (risk ratio (RR) 2.32, 95% confidence interval (CI) 1.38 to 3.91; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 8; 1 study, 125 participants); the effect of clobetasol compared to vehicle for investigator-rated improvement is less clear (RR 1.43, 95% CI 0.86 to 2.40). More participants had at least one adverse event with clobetasol (11/62 versus 5/63; RR 2.24, 95% CI 0.82 to 6.06), including application site burning/pruritus. This evidence was rated as moderate certainty.
When assessed 36 weeks after the start of treatment, mometasone furoate cream used thrice weekly may slightly improve investigator-rated symptom control compared to twice weekly (RR 1.23, 95% CI 0.94 to 1.61; 1 study, 72 participants) after remission is reached. Participant-rated symptoms were not measured. Some mild atrophy was reported in both groups (RR 1.76, 95% CI 0.45 to 6.83; 5/35 versus 3/37). This evidence was rated as low certainty.
Irradiation with ultraviolet (UV) light: local combination ultraviolet light therapy (PUVA) may lead to improvement in investigator-rated symptom control when compared to local narrow-band UVB after 12 weeks of treatment (RR 0.50, 95% CI 0.22 to 1.16; 1 study, 60 participants). However, the 95% CI indicates that PUVA might make little or no difference. Participant-rated symptoms were not measured. Adverse events (mainly erythema) were reported by 9/30 participants in the narrow-band UVB group versus none in the PUVA group. This evidence was rated as moderate certainty.
Topical calcineurin inhibitors: tacrolimus 0.1% over two weeks probably improves investigator-rated symptom control measured after three weeks compared to vehicle (14/14 tacrolimus versus 0/14 vehicle; 1 study). Participant-rated symptoms were not measured. Four of 14 people in the tacrolimus group versus zero in the vehicle group had well-tolerated application site burning/itching.
A within-participant study in 16 participants compared 0.1% tacrolimus to 0.1% mometasone furoate but did not measure investigator- or participant-rated symptoms. Both treatments were well tolerated when assessed at two weeks during four weeks of treatment.
Evidence from these studies was rated as moderate certainty.
Oral interventions: oral cyclosporin 3 mg/kg/d probably slightly improves investigator-rated (RR 1.88, 95% CI 0.88 to 3.99; 1 study, 34 participants) or participant-rated (RR 1.25, 95% CI 0.69 to 2.27) control of symptoms compared to topical betamethasone dipropionate 0.05% after six weeks of treatment. The risk of adverse events such as dizziness was similar between groups (up to 36 weeks; RR 1.22, 95% CI 0.80 to 1.86, n = 55; 15/27 betamethasone versus 19/28 cyclosporin). The evidence was rated as moderate certainty.
Alitretinoin 10 mg improves investigator-rated symptom control compared with placebo (RR 1.58, 95% CI 1.20 to 2.07; NNTB 11, 95% CI 6.3 to 26.5; 2 studies, n = 781) and alitretinoin 30 mg also improves this outcome compared with placebo (RR 2.75, 95% CI 2.20 to 3.43; NNTB 4, 95% CI 3 to 5; 2 studies, n = 1210). Similar results were found for participant-rated symptom control: alitretinoin 10 mg RR 1.73 (95% CI 1.25 to 2.40) and 30 mg RR 2.75 (95% CI 2.18 to 3.48). Evidence was rated as high certainty. The number of adverse events (including headache) probably did not differ between alitretinoin 10 mg and placebo (RR 1.01, 95% CI 0.66 to 1.55; 1 study, n = 158; moderate-certainty evidence), but the risk of headache increased with alitretinoin 30 mg (RR 3.43, 95% CI 2.45 to 4.81; 2 studies, n = 1210; high-certainty evidence). Outcomes were assessed between 48 and 72 weeks.