Hyperkeratotic Hand Eczema Research Articles

Dupilumab for Chronic Hand Eczema: A Systematic Review and Meta-Analysis.

Chronic hand eczema (CHE) is a distressing and pervasive dermatologic condition, and effective treatment can be challenging. The novel IL-4/13 inhibitor dupilumab has shown clinical efficacy for atopic dermatitis (AD) and is being studied for CHE. PubMed database was searched for terms dupilumab and chronic hand eczema/dermatitis, including CHE subtypes (dyshidrotic, hyperkeratotic, allergic, contact, atopic, occupational, vesicular). Twenty-two study publications met inclusion and exclusion criteria for evaluation. Two multicenter prospective studies, one randomized controlled trial, two prospective observational studies, one retrospective study, nine case series, and seven case reports were included in the analysis with 374 total patients. Any partial response or complete resolution of CHE occurred in 80.3% of patients treated with dupilumab within 4-16 weeks of treatment. The patient response tended to increase throughout the duration of these studies for a significant percentage of patients, and for many it lasted beyond the study duration. Significant improvement in hand eczema severity scores and quality-of-life scores were noted. Efficacy was reported in over half of the cases of hyperkeratotic hand eczema; however, efficacy was decreased compared with relatively high consistent efficacy in other CHE subtypes such as dyshidrotic, vesicular, atopic, and contact CHE. Patients with current or previous AD had increased improvement scores compared to those without. The most common adverse effects were conjunctivitis (9.9%), herpes viral infection (1.4%), and facial erythema/dermatitis (1.3%). Dupilumab shows therapeutic efficacy in treating CHE. Further randomized controlled studies of dupilumab use in CHE subtypes are needed.

Hand eczema: a review of clinical, dermoscopic and histological features.

Hand eczema (HE) is a prevalent inflammatory skin condition, impacting 15-20% of individuals, with a notable incidence rate of approximately 7.3 cases per 1000 person/years. This condition exhibits significant gender-based variability, with a higher prevalence in females. The clinical presentation of HE is characterized by pruritic erythematous, edematous, weeping plaques, vesicles, and/or bullae, showcasing considerable heterogeneity. A literature search was conducted across multiple databases, including Medline, Pubmed, Scopus, and the Cochrane Library. The search was conducted using the following key words and medical subject heading (MeSH) terms: "hand," "eczema," "dermatitis," "dermoscopy," and "histology," employing the Boolean term "AND" to combine the research terms for optimal search precision. PRISMA algorithm has been used for article screening. The search scope included manuscripts published up to October 1, 2023. Up to 50% of HE cases are associated with atopic dermatitis, emphasizing the complex interplay between various dermatological conditions. Common subtypes of HE include irritant contact dermatitis (ICD), allergic contact dermatitis (ACD), atopic hand eczema (AHE), and protein contact dermatitis/contact urticaria (PCD). The chronic nature of HE presents a substantial management challenge, often underestimated, leading to delayed treatment and potential progression to chronic hand eczema (CHE). Beyond individual health implications, HE exerts a profound impact on occupational, domestic, social, and psychological aspects, establishing itself as the most prevalent occupation-related skin disease. This paper seeks to establish a comprehensive classification system for HE, integrating clinical, dermoscopic, and histological elements. Dermoscopy, specifically, proves instrumental in distinguishing HE from palmar psoriasis, revealing characteristic features such as yellow scales and irregular vessels. Histopathological findings underscore the dynamic changes observed from acute to chronic stages, while challenges in differentiating hyperkeratotic HE from psoriasis underscore the necessity for a holistic diagnostic approach. Accurate diagnosis and effective management of HE necessitate a holistic perspective that recognizes the inherent complexities of this inflammatory skin disease. By providing a multidimensional classification system, incorporating clinical, dermoscopic, and histological parameters, this paper aimed to contribute to a more nuanced understanding of HE and facilitate improved approaches to its diagnosis and treatment.

Efficacy of apremilast in hyperkeratotic hand and foot dermatitis: results from a randomized observer-blinded comparative study.

Hyperkeratotic hand and foot dermatitis significantly affects quality of life. Some patients respond suboptimally to topical corticosteroids and have multiple recurrences. Our aim was to compare the efficacy and safety profile of apremilast and topical corticosteroid versus corticosteroid alone in hyperkeratotic hand and foot dermatitis. This randomized controlled study involved 77 patients treated for 3 months. GroupA (39 patients) received mometasone furoate 0.1% cream with oral apremilast 30 mg twice daily, and Group B (38 patients) received mometasone alone. They were assessed monthly using the Hand Eczema Clinical Severity Index (HECSI) and Visual Analogue Scale (VAS) scores for pruritus. Investigator Global Assessment (IGA) and Quality of Life in Hand Eczema Questionnaire (QOLHEQ) were conducted at the end of 3 months. The HECSI, VAS score, and QOLHEQ showed a significant decrease in both groups from baseline to the third month. Intergroup comparisons of HECSI failed to reach the significance level. When compared, patients receiving apremilast had significantly better improvement in the third month according to the Patient Global Assessment (PGA) and Investigator Global Assessment (IGA). They also had a smaller number of flares. Adding apremilast to topical corticosteroid leads to better patient and physician-perceived improvement and reduces the number of flares in hyperkeratotic hand eczema.

Immunohistochemical differentiation of keratins and involucrin between palmar psoriasis, chronic hand eczema and hyperkeratotic hand eczema.

Common hyperkeratotic palmar skin lesions include chronic hand eczema (CHE), hyperkeratotic hand eczema (HHE), palmar psoriasis (PP). However, clinically differentiating these disorders is often challenging. To compare the expressions of keratin (K) 5, K9, K14 and involucrin in palmar hyperkeratotic lesions (HHE, CHE and PP). Immunohistochemical staining was performed on skin biopsy specimens obtained from the palms of patients clinically diagnosed with CHE, HHE and PP (n = 21, 24 and 18, respectively). K5 and K14 expression levels were higher in the spinous and granular layers of PP and HHE compared to CHE. Involucrin was expressed in the basal layer of PP and HHE but not in CHE. K9 expression was decreased in PP and HHE compared to CHE. Keratin and involucrin expression in the epidermis are markers of keratinocyte differentiation. Expression levels of keratin and involucrin were similar between the HHE and PP groups, suggesting that HHE shares pathogenesis with PP rather than CHE.

Skin Barrier Dysfunction in Hand Eczema

Hand eczema (HE) is a common chronic inflammatory skin disease of the hand, the occurrence and development of which are related to the dysfunction of the topical skin barrier. Causes of topical skin barrier dysfunction include dysregulation of gene/protein expression, permeability barrier abnormalities, flora imbalance in the microbial barrier, and abnormalities of antimicrobial peptides in the immune barrier. Because the incidence rate of HE is high and the disease is likely to recur, we wrote this review to identify pathogenic factors through skin barrier analysis of HE and to explore more favorable treatment methods. Previous studies have shown that the mutation of the filaggrin gene, a medical history of atopic dermatitis, and the hyperproliferation of Staphylococcus aureus in lesions are related to the prolongation of HE. Moreover, high pH value, increased transepidermal water loss, and damaged integrity of the stratum corneum are closely related to the activity and severity of chronic HE with or without atopic dermatitis. The S100 family of antimicrobial peptides, including S100A7A, S100A7, S100A8/A9, and S100A11, has also been shown to be highly expressed in vesicular and hyperkeratotic HE.

A Clinico-Epidemiological Study of Hyperkeratotic Palmoplantar Lesions and Its Correlation With Dermoscopy and Histopathology in a Tertiary Care Center.

Introduction Hyperkeratotic lesions on the palms and soles are one of the most frequent clinical presentations encountered in dermatological practice, with a myriad of underlying etiologies that closely resemble one another and are clinically indistinguishable. Histopathological examination is the tool used by dermatologists to arrive at a final diagnosis, butit is invasive and not feasible under all circumstances. Dermoscopy is a new age, increasingly popular, noninvasive diagnostic technique of great value that is used to diagnose underlying etiology by acting as a bridge between clinical and histopathological pictures. This study aimed to evaluate the various etiologies underlying palmoplantar hyperkeratosis and the role of dermoscopy in the diagnosis of each disease along with its ability to delineate a close differential diagnosis and ensure appropriate treatment. Materials and methods This was a hospital-based observational cross-sectional studyconducted from July 1to December 31, 2022. Consenting patients with hyperkeratotic palmoplantar lesions on clinical examinationattending the dermatology outpatient department at our tertiary care hospital were included after institutional ethical clearance was obtained. Patients with HIV, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) infection, or a history of hyperkeratotic lesions since birth, i.e., inherited palmoplantar keratodermas, were excluded from the study. A total of 60 patients aged between 18 and 60 years who met the above criteria were included. A complete history was taken; a thoroughexaminationwas performed. Routine investigationsand tissue histology were done. Potassium hydroxide (KOH) mount and patch testing were done as and when required. Dermoscopywith DermLite DL4was performed in all cases on lesional areas, and the findings were noted. Results Palmoplantar psoriasis has been found to be the most common cause of hyperkeratosis in our study with 24 (40%) out of 60 cases, followed bychronic hand-foot eczema found in 19 (31%) cases. Dermoscopic findings that help in differentiating various etiologies arevascular findings and scaling types. Vascular findings, mainlyregularly arranged dots and globules, were more prominent in palmoplantar psoriasis. Yellow white scaling was frequently observed in hyperkeratotic hand eczema.Most of the cases corresponded with their provisional diagnoses on histopathology, butfour out of 19 histopathologically confirmed cases ofeczema showed clinical resemblance to palmoplantar psoriasis, along with dermoscopic features of psoriasis. Two out of four cases of histopathologically confirmed palmoplantar LP were clinically considered palmoplantar psoriasis and hyperkeratotic hand-foot eczema. Conclusion Although hyperkeratoses of palms and soles are a common clinical entity, the similarity between the clinical features of the underlying conditions causes a diagnostic dilemma for treating dermatologists. Dermoscopy is a noninvasive, quick, reproducible, supportive investigation in the diagnosis of these conditions that certainly aids in reaching closer to a differential diagnosis and for better delineation, but it does not avert the need for a skin biopsy. Further confirmation with histopathological examination is advisable, especially in these conditions as they show close morphological similarity. A combination of all these investigations and clinical examinations gives better diagnoses and appropriate treatment.

114 Insight into the pathogenesis of vesicular and hyperkeratotic hand eczema

Hand eczema (HE) is a common inflammatory skin disorder whose pathogenesis is largely unknown. Among the clinical subtypes of HE, vesicular HE (VHE) and hyperkeratotic HE (HHE) are the most well described. We aimed to profile the transcriptome of lesional palmar skin of VHE compared to non-lesional VHE and healthy control palmar skin. After RNA-sequencing, gene expression was validated by RT-qPCR, and protein expression was studied using immunohistochemistry. High expression of genes/proteins involved in keratinocyte host defense and inflammation in lesional palmar skin was observed. Genes involved in epidermal differentiation were either up- or downregulated, while immune signaling genes were upregulated. No significant differences were found between non-lesional VHE and healthy palmar skin. A large overlap between the lesional VHE skin transcriptome and earlier reported atopic dermatitis (AD) transcriptome was found. In addition, expression of keratins, epidermal barrier proteins, and adhesion molecules in HHE were investigated. Immunofluorescence staining showed an upregulation of keratins involved in hyperproliferation and hyperkeratosis, and a downregulation of keratins involved in terminal differentiation and mechanical integrity of palmar epidermis in lesional HHE skin compared to non-lesional and healthy palmar skin. No decreased expressions of skin barrier-associated proteins were found, suggesting that skin barrier dysfunction plays a less significant role in the pathogenesis of HHE. Future studies should focus on transcriptome analysis of other subtypes of HE as this can provide insight into specific pathways, which may lead to new therapeutic targets.

Hyperkeratotic hand eczema: Eczema or not?

BackgroundHyperkeratotic hand eczema (HHE) is a typical clinical hand eczema subtype with a largely unknown pathophysiology.ObjectiveTo investigate histopathology, expression of keratins (K), epidermal barrier proteins, and adhesion molecules in HHE.MethodsPalmar skin biopsies (lesional and perilesional) were obtained from seven HHE patients and two healthy controls. Moreover, 135 candidate genes associated with palmoplantar keratoderma were screened for mutations.ResultsImmunofluorescence staining showed a significant reduction of K9 and K14 in lesional skin. Upregulation was found for K5, K6, K16, and K17 in lesional skin compared with perilesional and healthy palmar skin. Further, upregulation of involucrin and alternating loricrin staining, both in an extracellular staining pattern, was found. Filaggrin expression was similar in lesional, perilesional, and control skin. No monogenetic mutations were found.ConclusionCurrently, the phenotype of HHE is included in the hand eczema classification system; however, it can be argued whether this is justified. The evident expression of filaggrin and involucrin in lesional skin does not support a pathogenesis of atopic eczema. The upregulation of K6, K16, and K17 and reduction of K9 and K14 might contribute to the underlying pathogenesis. Unfortunately, comparison with hand eczema studies is not possible yet, because similar protein expression studies are lacking.

Efficacy and Safety of Oral Alitretinoin in Hand Eczema and Palmoplantar Pustulosis in Korean Patients.

BackgroundPrevious studies have demonstrated efficacy and safety of oral alitretinoin in hand eczema (HE) whereas in palmoplantar pustulosis (PPP), which can be difficult to distinguish from HE, efficacy of alitretinoin is still controversial.ObjectiveThis study aimed to investigate the efficacy and safety of oral alitretinoin in HE and PPP and factors that affect the response of these disorders to alitretinoin.MethodsWe retrospectively analyzed Korean adult patients with moderate-to-severe HE and PPP treated with oral alitretinoin, 46 patients for efficacy assessment and 55 patients for safety assessment.ResultsAmong 46 patients who were treated with alitretinoin for at least 1 month, 29 patients (61.1% in HE and 40.0% in PPP) showed response to alitretinoin in the median 14 weeks after treatment. Hyperkeratotic HE showed higher response rate than either vesicular HE or PPP (p=0.026 and p=0.026, respectively). However, PPP with hyperkeratotic features showed as much response as hyperkeratotic HE (p=0.554). When responders and non-responders in total patients were compared, morphology, not diagnosis or initial severity, was the only significantly different factor between the two groups. After alitretinoin discontinuation in responders, relapse rate was 63.6% (7/11) and median time to relapse was 150 days (range, 76~730 days). Adverse events occurred in 47.3% (26/55); however, there were no serious adverse events.ConclusionIn HE or PPP, lesions with hyperkeratotic morphology can be predicted to respond well to alitretinoin regardless of diagnosis.

Treatment of severe, chronic hand eczema: results from a UK-wide survey.

Treatment of severe hand eczema (HE) that is resistant to topical potent corticosteroid treatment is challenging. In 2013, we surveyed 194 UK dermatologists to obtain information about their usual treatment pathways to inform the choice of the comparator in a trial of alitretinoin in severe HE (ALPHA trial); the results indicated that the treatment approaches favoured by UK dermatologists differ. Psoralen combined with ultraviolet A (PUVA) and alitretinoin were identified as the most frequent first-line treatment options for hyperkeratotic HE, whereas oral corticosteroids were identified as the most frequent first-line treatment for vesicular HE, followed by PUVA and alitretinoin. In terms of potential adverse effects of long-term or repeated use, oral steroids and ciclosporin A were reported to cause most concern. There is uncertainty about which treatment gives the best short and long-term outcomes, because of a lack of definitive randomised controlled trials evaluating the effectiveness of different treatment pathways in severe HE.

Factors associated with combined hand and foot eczema.

As for hand eczema, the aetiology of foot eczema is multifactorial and not very well understood. The aim of the present study was to identify factors associated with foot eczema in a cohort of hand eczema patients being classified into different subgroups. Associations between foot and hand eczema were studied in a cross-sectional design in a cohort of hand eczema patients. Consecutive patients were recruited from nine different European Centres during the period October 2011-September 2012. Data on demographic factors, presence of foot eczema, hand eczema duration and severity, and whether the hand eczema was work-related or not were available, as well as patch-test results. Of a total of 427 hand eczema patients identified, information on foot eczema was available in 419 patients who were included in the present study. A total of 125 patients (29.8%) had concomitant foot and hand eczema. It was found more often in association with hyperkeratotic hand eczema (P = 0.007) and was less often associated with irritant hand eczema (P < 0.001). However, foot eczema was nevertheless found in 18% of patient with irritant hand eczema and in 25% of patients with occupational hand eczema. Combined foot and hand eczema was associated with more severe and long-standing hand eczema (P < 0.001 and P = 0.004, respectively). Contact allergy was found in 51.8% with no difference between patients with combined foot and hand eczema and patients with hand eczema only. Occurrence of combined foot and hand eczema is a common finding and not restricted to endogenous hand eczema.

Alitretinoin and acitretin in severe chronic hand eczema; results from a retrospective daily practice study

Acitretin has been used off-label for years to treat chronic hand eczema, but acitretin is less often prescribed as alitretinoïne was approved. This study evaluates both retinoids in a daily practice cohort of patients with severe chronic hand eczema in terms of drug survival and reasons for discontinuation. Patients using alitretinoin or acitretin between 01-01-1994 and 01-08-2015 were included in this retrospective daily practice study and analyzed by Kaplan-Meier drug survival curves. Potential determinants were analyzed by Cox regression analyses. Ninety-five patients were treated with alitretinoin and 109 patients with acitretin. The main reasons for discontinuation were adverse events and cleared hand eczema, 29.5 and 27.4% in alitretinoin versus 43.1 and 23.9% in acitretin. Patients with hyperkeratotic hand eczema had most often a good effect of treatment: 68.3% in alitretinoin and 50.7% in acitretin treatment. The drug survival rates of alitretinoin and acitretin after 12, 24, 36, and 52 weeks were 69.3, 45.1, 19.6, 7.0% and 74.3, 45.5, 33.8, 23.2%, respectively. Alitretinoin and acitretin are effective treatment options for patients with hand eczema. However, both treatments were more effective in patients with hyperkeratotic hand eczema. Fewer patients discontinued alitretinoin compared with acitretin due to adverse events.

Patch Test as a Diagnostic Tool in Hand Eczema.

Allergic contact dermatitis is an important cause of hand eczema. Patch testing is the only investigation available to prove the diagnosis of allergic contact dermatitis. Exposures to allergens differ according to geographical, occupational, economic and social factors. Accordingly, patterns of allergic contact dermatitis differ in different parts of the world and different regions of the same country. To study the causes of allergic contact dermatitis in adult patients with hand eczema with the help of patch testing. This was a cross-sectional study involving 54 hand eczema patients conducted between October 2013 and June 2015, at a tertiary care centre in Southern India. After a detailed history including history of occupational exposure and detailed examination, patch test was done on these patients with Indian standard series. The patches were removed after 48 hours. Another reading was taken after 72 hours. The readings were interpreted according to International Contact Dermatitis Research Group criteria and noted down. The data were summarized using mean and standard deviation for continuous variables and percentages for categorical and dichotomous variables. The test of association was done with Fisher's-exact test. Hyperkeratotic hand eczema was the commonest morphological type (29%), followed by discoid eczema. Pompholyx was significantly more common among patients with history of atopy. A total of 20 patients (37%) showed patch test positivity to a total of 25 allergens. Nickel was the most common allergen (11.11%) followed by para-phenylenediamine (PPD) (7.4%). Nickel (6 patients) and cobalt (3 patients) were the common allergens among women, while potassium dichromate (3 patients) and parthenium (2 patients) were the common allergens among men. Potassium dichromate allergy was significantly more common among masons and PPD allergy was significantly more common among hair dye users. Discoid pattern of hand eczema was common among patients with allergy to potassium dichromate. Majority of the cases of hand eczema are not due to allergic contact dermatitis. History of atopy is common among patients with pompholyx. Allergic contact dermatitis due to nickel remains a common cause of hand eczema.

Clinical patterns and associated factors in patients with hand eczema of primarily occupational origin.

Hand eczema (HE) is the most common skin disease acquired at work. It presents in different clinical patterns. To classify different types of HE according to their clinical pattern and associated factors in patients taking part in a tertiary individual prevention programme (TIP) for occupational skin diseases. In a retrospective cohort study, the medical records of 843 patients taking part in the TIP were evaluated. HE was classified into three clinical subtypes: vesicular HE, hyperkeratotic HE and HE with erythema and desquamation. About 723 patients (85.8%) suffered from HE. Female TIP patients with HE were significantly younger (OR 0.97, 95% CI 0.96-0.99) and had a higher prevalence of flexural eczema (OR 1.60, 95% CI 1.15-2.23) and an atopic HE component (OR 1.84, 95% CI 1.36-2.48) than men. Vesicular HE was more common in women (OR 1.44, 95% CI 1.07-1.94) and significantly associated with hyperhidrosis (OR 1.69, 95% CI 1.23-2.33), flexural eczema (OR 1.37, 95% CI 0.99-1.89) and an atopic HE component (OR 1.93, 95% CI 1.44-2.61). Hyperkeratotic HE was more frequent in men (OR 3.70, 95% CI 2.27-6.25) and associated with older age (OR 1.04, 95% CI 1.02-1.06). The cohort of patients with HE characterized by erythema and desquamation was very heterogeneous. Vesicular HE was significantly associated with tobacco smoking (OR 1.94, 95% CI 1.40-2.68), while hyperkeratotic HE was significantly less common in smokers (OR 0.38, 95% CI 0.22-0.65). Environmental and individual factors are associated with different clinical patterns of HE in patients taking part in the TIP. They may influence the prognosis and should be considered in the individual management of disease. Tobacco smoking may be in particular a risk factor for vesicular HE.

Hand eczema and stratum corneum ceramides.

Hand eczema (HE) is a multifactorial disease, comprising different aetiological conditions and different morphologies. There are two aetiologically distinct groups of HE recognised: exogenous, such as contact dermatitis (allergic and/or irritant HE) and endogenous, such as the classic hyperkeratotic HE. Differences in the skin barrier properties of these two conditions could theoretically be expected. To examine whether differences exist in the lipid profile and the susceptibility of the stratum corneum (SC) in patients with allergic/irritant HE and those with hyperkeratotic HE. Using cyanoacrylate, SC samples were taken from 23 patients with allergic/irritant HE and 15 with hyperkeratotic HE for lipid analysis by high-performance thin-layer chromatography (HPTLC). Samples were also taken from adjacent, unaffected skin. Severity of HE was assessed by the Hand Eczema Severity Index (HECSI), and skin barrier susceptibility was assessed by measuring transepidermal water loss (TEWL) after a 24-hour patch test with sodium lauryl sulfate (SLS). No statistically significant difference was found between groups for the lipid analysis or for skin susceptibility to SLS. We found a significantly higher HECSI score for hyperkeratotic HE compared with irritant or allergic HE (P=0.02). There appears to be no difference in skin barrier between allergic/irritant HE (exogenous eczema) and hyperkeratotic HE (endogenous eczema) with regard to SC lipids or susceptibility to SLS.

Alitretinoin for the treatment of chronic hand eczema: clinical rationale

Chronic hand eczema (CHE), an inflammatory skin disease, places heavy psychosocial and economic burden on the affected individual and society as a whole. Patch testing is recommended to identify potential causative allergens in each patient. Efficacy of traditional topical treatments render the management of CHE challenging. Oral alitretinoin (9-cis-retinoic acid) is a new drug for the treatment of severe, refractory CHE. This review summarizes the advances on oral alitretinoin for the treatment of severe CHE, with emphasis on its particular benefit for hyperkeratotic hand eczema, and discusses pharmacodynamics and pharmacokinetics, clinical trials and knowledge gaps.

The single‐dose pharmacokinetics of alitretinoin and its metabolites are not significantly altered in patients with cirrhosis

Alitretinoin (9-cis-retinoic acid, Toctino(®) ) has been marketed recently for oral therapy for chronic hyperkeratotic hand eczema. As alitretinoin is highly lipophilic and metabolized mainly in the liver, it is currently considered to be contraindicated in patients with liver disease. However, the pharmacokinetics and metabolism of alitretinoin have not been studied in these patients. To study the single-dose pharmacokinetics and metabolism of alitretinoin and its metabolites in patients with cirrhosis following oral administration. Eight patients with cirrhosis and eight matched volunteer healthy controls were given a single 30-mg oral dose of alitretinoin. Blood and urine samples were collected during the following 24-h study period. Samples were analysed for alitretinoin and for known metabolites using reverse-phase high-performance liquid chromatography. The pharmacokinetics were then evaluated using standard noncompartmental models. No significant differences were found between healthy controls and patients with cirrhosis when analysing the pharmacokinetic parameters of alitretinoin and its metabolites. Thus, the mean half-lives of alitretinoin were 5·3 and 5·6 h (P = 0.733) and the oral clearances were 1·92 and 1·39 L h(-1) kg(-1) (P = 0·243) in the patient group and the healthy control group, respectively. The metabolism and pharmacokinetics of alitretinoin following oral administration of the recommended dose of 30 mg for the treatment of severe hand eczema were similar in patients with cirrhosis and in healthy controls. If indicated, alitretinoin can be used in these patients with careful and close monitoring.

Hyperkeratotic Hand Eczema due to Use of Rubber Gloves While Driving.

Dear Editor: Hyperkeratotic hand eczema (HHE) is defined as a lesion of hand dermatitis that shows thick hyperkeratotic plaques with or without deep fissures. This diagnosis was established in 2%~5% of patients with hand dermatitis1,2. HHE is considered to have multiple causes, such as exposure to repetitive irritation, atopy, contact allergy, and friction3. Previous studies have revealed that contact sensitization is less common in HHE2. Here, we report a case of chronic HHE associated with contact sensitization to black rubber mix and thiuram mix. A 50-year-old nonatopic male patient presented with chronic HHE that had been refractory to previous treatments for the last 2 years. Physical examination revealed relatively well-demarcated erythematous scaly plaques on the palmar sides of both hands (Fig. 1A). He was a salesman who had always driven a car to his meetings. For 3 years, he had been wearing his work gloves, which had rubber on the palmar side, to prevent his hand from sliding off the steering wheel while driving because of his palmar hyperhidrosis (Fig. 2A). He had received eczema treatment with potent topical corticosteroid creams and moisturizer at local clinics; however, his symptoms did not improve. Then, he was referred to our hospital. We performed patch tests with a thin-layer rapid use epicutaneous (TRUE) test kit (Mekos Laboratories AS, Hillerod, Denmark). There were positive reactions to thiuram mix(++) and black rubber mix(++) at 48 h, and additional positive reactions to p-tertbutylphenol formaldehyde resin(+) and p-phenylenediamine(+) at 96 h (Fig. 2B). He was advised to apply a topical steroid with medium potency and to drive without wearing gloves, and his symptoms improved 2 weeks later (Fig. 1B). Thereafter, he underwent use tests with the work gloves, which worsened his symptoms. Fig. 1 (A) Localized scaly yellowish plaques on the palmar sides of both hands. (B) Two weeks after avoiding exposure to the offending allergen. Fig. 2 (A) Blue rubber dotted work gloves. (B) Positive patch test reactions to thiuram mix(++), black rubber mix(++), p-tertbutylphenol formaldehyde resin(+), and p-phenylenediamine(+) at 96 h. A hyperkeratotic morphology is known to be less frequently associated with contact sensitization, irritant exposure, and atopic dermatitis1. Thus, strongly positive reactions to more than two materials during the patch test have clinical implications. We made a diagnosis of HHE due to repetitive use of the work gloves on the basis of the patient's history, patch tests, and use tests. Thiurams are accelerants that are commonly used to manufacture natural rubber latex products. These mixes are present in natural or synthetic rubber products making up materials that are used either at work or at home4. Many tire workers are sensitized to black rubber mix. Concerning nonoccupational exposure, it has been shown that black rubber footgear and the rubber tips of walking sticks can also cause contact dermatitis5. Positive reaction to p-tertbutylphenol formaldehyde resin is related to contact with waterproof glue, bonded leather, and construction materials, whereas that to p-phenylenediamine is related to contact with permanent or semipermanent hair dyes, dyed textiles, and cosmetics; however, these are less relevant compared with our case. In conclusion, this report suggests that patients with HHE should be comprehensively evaluated through history taking and correctly treated by avoiding the suspicious material.

Psoralen plus ultraviolet A (PUVA) soaks and UVB TL01 treatment for chronic hand dermatoses.

Chronic eczematous hand dermatoses with and without contact allergies are complex diseases, which makes it a challenge to select the best treatment and obtain an optimal patient experience and a satisfactory treatment result. The aim of this study was to evaluate retrospectively the clinical effect and patient experience of local treatment with psoralen plus ultraviolet A (PUVA) soaks and TL01 phototherapy for severe chronic hand dermatoses, and also to evaluate the quality of life for the subgroup of patients with allergic contact dermatitis including Compositae allergy. A retrospective evaluation of results for 94 consecutive patients having received a total of 121 treatment courses with local PUVA soaks or TL01 phototherapy for one of the following diagnoses (n=number of treatment courses): psoriasis (n=19), hyperk-eratotic hand eczema (n=27), Pustulosis Palmoplantaris (PPP) (n=22), vesicular eczema (n=16), Compositae dermatitis (n=24), and allergic contact dermatitis (n=13). Moreover, semi-structured interviews with 6 selected patients having multiple contact allergies including Compositae allergy were used to evaluate quality of life. As a result, we found that PUVA soaks has good effect in patients with psoriasis and hyperkeratotic hand eczema and local phototherapy for chronic hand dermatoses is a useful treatment option in selected cases.

THE ROLE OF KERATINOCYTES IN THE PATHOPHYSIOLOGY OF CONTACT DERMATITIS

Industrialization has greatly increased exposure to chemicals, pollutants, and noxious substances, both at home and in the workplace. This trend of increasing chemical exposure continues as reliance on technology deepens. The initial barrier against these substances is the skin. In the majority of individuals, this defense is sufficient and acts without adverse effects. As exposure to chemicals becomes more widespread and frequent, the incidence of pathologic responses to this exposure in the population has increased dramatically. In 1990, the National Center for Health Statistics reported that eczematous dermatitis was one of the most common specific dermatoses encountered in the outpatient setting. 1 It is estimated that dermatitis as a result of incidental or inadvertent exposure to occupational hazards accounts for 30% of all occupational disease. More than 90% of cases described are due to irritant contact dermatitis (ICD) or allergic contact dermatitis (ACD). 85 In a study done in Denmark, hyperkeratotic hand eczema alone was estimated to affect 2.5% of Danish workers on permanent disability at a national cost of $15 million per year. 89 A direct extrapolation to the United States, based on population alone, would imply an impact of nearly $750 million per year solely for hand eczema. Thus, contact dermatitis is a disorder of significant economic dimension. This article seeks to outline the various contact dermatitides, then compare the features of ICD and ACD, and lastly to outline the immune mechanisms of contact dermatitis, with special emphasis on the role of keratinocytes.