We conducted a descriptive, observational, exploratory, cross-sectional study consisting of a chart review of patients with CHE treated with alitretinoin within the Spanish public health system between July and September 2012.

At the time of the study, alitretinoin was only available through hospitals, specialized dermatology units, and hospital pharmacies following authorization from the AEMPS. All patients treated with alitretinoin during the study period were identified from medical records. We included patients aged over 18 years with a diagnosis of CHE who had been treated with alitretinoin and whose medical records contained information pertaining to at least 1 follow-up visit at the time of data collection. We excluded patients with a diagnosis other than CHE involving skin infections or other skin disorders, of any etiology, that could interfere with the evaluation of response to alitretinoin. The patients were selected and included in the study sequentially, not randomly.

Twenty-one public hospitals were invited to participate in the study.

Using a purpose-designed case report form, we recorded various sociodemographic variables (age, sex, job status and sector, and contact with substances associated with CHE) and the following clinical variables: associated concomitant diseases (e.g., atopic dermatitis, allergy, asthma, and rhinoconjunctivitis); personal history of disease (diabetes, thyroid disease, liver failure, kidney failure, hypercholesterolemia, hypertriglyceridemia, hypervitaminosis A, hypertension, obesity, and other dermatologic or systemic diseases); date of diagnosis and diagnostic tests performed; type, location, and severity of CHE; associated signs and symptoms; dose, frequency, and duration of alitretinoin treatment; previous treatments for CHE; concomitant treatments unrelated to CHE and concomitant treatments for CHE; occurrence and severity of adverse events; treatment response assessments by the treating physician (including Physician Global Assessment, Patient Global Assessment, and modified Total Lesion Symptom Score18); treatment response; laboratory tests ordered during diagnosis and follow-up; results of these tests; and pregnancy prevention plan where relevant.

To evaluate physician satisfaction with response to treatment, coinciding with the data collection phase of the study, the participating physicians were asked to complete a purpose-designed questionnaire (available as supplementary material) regarding their satisfaction with the use of alitretinoin in the study population, the type of clinical response obtained, and the level of treatment adherence and compliance. The questionnaire also contained items related to satisfaction with prescribing conditions and adherence to recommendations for the use of alitretinoin. The questions were answered using a 5-point Likert-type scale (1=not at all satisfied, 2=not very satisfied, 3=satisfied, 4=quite satisfied, and 5=very satisfied).

The retrospective design of the study required the participating hospitals to have a policy in place that met the conditions of confidentiality and nontraceability under the Spanish Data Protection Law. The study protocol was approved by the clinical research ethics committee at Hospital Puerta de Hierro, in Madrid, Spain.

Of the 21 hospitals approached, 13 agreed to participate in the study; they were located in 5 of Spain's autonomous communities: Andalusia (n=2), Aragon (n=1), Castilla-la-Mancha (n=2), Catalonia (n=2), and Madrid (n=7). Seventy-two relevant medical records were identified, and 62 (86%) of these met the inclusion criteria. The reasons for exclusion were a change in diagnosis from CHE to psoriasis during treatment (n=1), treatment for psoriasis (n=1), diagnosis of chronic eczema with foot involvement only (n=2), no clinical history (n=1), and no clinical follow-up (n=5).

Table 1 summarizes the patients’ sociodemographic characteristics and employment situation. The mean (SD) age of the patients was 53 (13) years, and there was a similar proportion of men (46.8%) and women (53.2%). Approximately 40.3% of patients (n=25) were in employment at the time of the study; 9.7% were homemakers, 9.7% were pensioners, and 1.6% were unemployed. Most patients were working in the textile, chemical, or plastics industries (11.3%), followed by the domestic work sector (9.7%), the construction sector (8.1%), and the hotel and catering industry (8.1%). Two patients mentioned that CHE had been a determining factor for changing employment, and 6 mentioned it as a reason for temporarily not being able to work.

Tests were used to diagnose CHE in 75.8% of patients (n=47). The mean (SD) number of tests was 1.7 (0.6) and the most common tests were patch tests (66.1%; n=41) and biopsy (29.0%; n=18).

The most common subtype of CHE was hyperkeratotic fissured hand eczema (29.0%; n=18). Eight patients (12.9%) had more than 1 subtype. CHE was observed most frequently on the palms and backs of the hands (69.35%, n=43 and 16.13%, n=10, respectively). Just over two-thirds of patients (n=42) had hand involvement only, but 19.35% (n=12) and 11.29% (n=7) had involvement of 2 and 3 sites, respectively. Figure 1 shows the additional sites affected.

Figure 1.

Distribution of Sample According to Sites of Chronic Hand Eczema Other Than the Hands.

(0.11MB).

At least 1 symptom was recorded for 62.9% of patients (n=39). Symptoms included pruritus (61.3%), pain (16.1%), and burning (3.2%). Pruritus was mild in 2 cases, moderate in 3, and intense in 17. Severity of involvement was not specified in the remaining 16 cases. Pain, in turn, was moderate in 2 cases (16.1%), intense in 4, and not specified in another 4. Finally, burning was described as moderate in 2 patients (3.2%). In total, 90.3% of patients (n=56) had clinical manifestations of CHE, namely reddening, flaking, vesicles, edema, and cracks. The most common signs were flaking (62.9%, n=39), reddening (45.2%, n=28), and cracks (38.7%, n=24).

Severity of CHE at the time of diagnosis was noted for 69.3% of patients. The intensity of the eczema was recorded using different terms (e.g., severe, intense, considerable), which were considered equivalent for our analysis. Nine patients were reported to have severe CHE, while 21 were considered to have moderate CHE (identified by the terms outbreak, moderate, and moderate to intense).

There was mention of nonresponse to potent topical corticosteroids in 87.1% of the medical records (n=54). This lack of response was identified by terms such as no response (69.4%, n=43) and corticosteroid-dependent (9.7%, n=6). Impact on quality of life was mentioned, together with treatment resistance, in 5 cases (8.1%). There was no mention of the use of recommended tools to evaluate these characteristics of CHE.

Over half of the patients’ records (58.1%; n=36) mentioned 1 or more concomitant diseases associated with CHE. The most common ones were atopic dermatitis (22.6%, n=14), allergy (16.1%, n=10), and rhinitis (9.7%, n=6).

The patients in our series received a mean (SD) of 3 (1.6) medications before being prescribed alitretinoin. Topical treatments included corticosteroids (83.9%, n=52), immunomodulators (33.9%, n=21), and topical retinoids (25.8%, n=16). Phototherapy was used in 16.1% of cases (n=10).

Over half of the patients (56.4%, n=35) received systemic treatment for CHE at some point of their disease. Systemic therapies included oral corticosteroids (43.5%, n=27), immunosuppressants (33.9%, n=21), analgesics, and antibiotics (1.6%, n=1). Antihistamines had been prescribed to 14 patients (22.6%) and antigout agents (e.g., colchicine) and antimalarials had each been prescribed to 3 patients (4.8%).

Of the 62 patients included in the study, 83.9% (n=52) received a single cycle of alitretinoin, 14.5% (n=9) received 2 cycles, and just 1.6% (n=1) received 3 cycles.

The mean (SD) time between treatment cycles was 6.7 (8.9) months for the first and second cycle and 16 months for the second and third cycle. Alitretinoin 30mg/d was used in 83.8% of patients (n=52) during the first cycle and in 66.7% of patients (n=6) during the second one. The patient who received a third cycle was also prescribed alitretinoin 30mg/d for this last cycle. The initial dose of 30mg was reduced to 10mg in 1 patient (1.6%) due to headache, and in another patient, an initial dose of 10mg was increased to 30mg on day 20. During the second cycle, the approved dose was changed to a 30-mg dose every 48hours in 2 patients (22.2%). The median duration of treatment was 15.9 weeks (range, 2-82 weeks) for the first cycle and 8.3 weeks (range, 4-65 weeks) for the second cycle. Duration of treatment in the only third cycle administered was 65 days.

The median time from onset of alitretinoin treatment to the first evaluation of response was 35 days (range, 0-607 days) for the first cycle and 42 days (range, 0-61 days) for the second cycle. Time to evaluation was 90 days for the patient who received the third treatment cycle.

Use of a recommended tool for assessing treatment response was recorded in 35.5% of cases. Table 2 summarizes the results per cycle. In most cases, response to treatment (clear or almost clear hands) was based on the physician's clinical assessment.

Considering the data recorded for treatment response, an improvement in CHE was reported for 49 patients (79%) (10 of whom achieved clear or almost clear hands), while no response was reported for 9 (14.5%). There was no mention of response in 4 cases (6.4%). Improvement was observed in 4 (44.4%) of the 9 patients who received a second cycle of treatment. For this cycle, there was 1 nonresponder (11.1%) and no mention of response in 4 cases (44.4%). Clinical improvement was observed at the first follow-up visit for the patient who underwent the third cycle of alitretinoin.

Approximately 43.5% of patients (n=27) were prescribed a concomitant topical treatment, namely emollients (22.6%, n=14), high-potent corticosteroids (19.4%, n=12), and potent corticosteroids (3.2%, n=2). Four patients (6.5%) were coadministered systemic corticosteroids.

Almost all of the patients’ medical records (98.4%) included information on laboratory tests used to monitor the safety of alitretinoin treatment. A median of 2 tests (range, 0-13 tests) was performed per patient. Most patients (93.4%) showed biochemical alterations during the different treatment cycles. The most common alterations were lipid profile alterations (hypercholesterolemia, 32.3%; hypertriglyceridemia, 3.2%; and hypercholesterolemia and hypertriglyceridemia, 6.5%), followed by changes in white blood cell count (3.2%), elevated thyroid stimulating hormone levels (3.2%), and hyperglycemia (1.6%). None of these alterations led to an interruption of treatment.

Of the 33 women studied, 20 (60.6%) were of reproductive age and therefore should have been following a pregnancy prevention plan during alitretinoin treatment. There was, however, no mention of contraceptive methods in the records of 70.0% (n=14) of these patients. Of the remaining 6 women, 4 had been advised to take oral contraceptives. The other 2 did not require a pregnancy prevention plan, as 1 had had a hysterectomy and the other was with a partner who had undergone a vasectomy.

There was no mention of adverse events in 18 (29%) of the 62 patients studied. Seventeen patients (27.4%) did not experience any adverse effects, and 27 (43.5%) experienced at least 1 adverse effect associated with alitretinoin. The most common effect was headache (25.8%), followed by xerophthalmia and xerosis (4.8% in both cases).

Alitretinoin treatment was interrupted in 19 patients. The reasons for interruption were a loss of response (n=5), worsening of CHE (n=2), and adverse effects (headache and swelling at night) (n=2).

All the dermatologists surveyed were satisfied with treatment effectiveness and duration, type of response and duration, and safety and tolerability. They all mentioned that they would recommend alitretinoin for the treatment of CHE.

Almost all of the dermatologists (91.7%) were satisfied, quite satisfied, or very satisfied with the percentage of responders observed in their practice. The same proportion also noted that treatment adherence or compliance (defined as “the extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen”19) was better with alitretinoin than with other treatments prescribed for CHE. In addition, 83.3% observed better adherence to alitretinoin treatment than with the most common treatments used in CHE. Seventy-five percent of dermatologists considered that patients treated with alitretinoin had been able to return to work sooner than if they had received other treatments. Two-thirds of the dermatologists surveyed stated that they were not satisfied with the dispensing and prescribing conditions in place at the time of the study (compassionate use).

The authors declare that no tests were carried out in humans or animals for the purpose of this study.

The authors declare that no private patient data appear in this article.

The authors declare that no private patient data appear in this article.