Contact dermatitis to topical acne drugs: a review of the literature

Acne vulgaris is a chronic dermatological disorder that affects the majority of teenagers in the Western world. Topical therapy is widely used to treat mild‐moderate acne and is known as well‐tolerated thanks to its low systemic toxicity, although associated to skin adverse effects. Acne seems to be associated also to an intrinsic alteration of the epidermal barrier, regarding both the upper and the follicular stratum corneum that promotes the onset of such local side effects. The commonest one is irritant contact dermatitis, an event of frequent observation occurring with erythema, burning, dryness, scaling, and itching, usually characterized by low severity and limited duration. Among topical acne drugs, retinoids are the most irritating ones. Another side effect is allergic contact dermatitis: it is rare and mainly associated to benzoyl peroxide.     

Photoallergic contact dermatitis from topical diclofenac in Solaraze gel

Solaraze gel (Shire Deutschland GmbH & Co. KG, Cologne, Germany) containing 3% diclofenac has been licensed in 2001 as a topical treatment for actinic keratoses. It is commonly used in dermatological practice. Undesirable effects are believed to be rare but include pruritus, paresthesia and application-site reactions (dry skin, rash, erythema, contact dermatitis and vesicobullous eruptions). Recently, a few cases of contact dermatitis due to three different allergens including diclofenac have been reported (1,2).     

Positive lymphocyte transformation test in a patient with allergic contact dermatitis of the scalp after short-term use of topical minoxidil solution

Topical 2,4-diamino-6-piperidinopyrimidine-3-oxide (minoxidil) solution has been widely used for the treatment of androgenetic alopecia for over 15 years now and the substance is currently approved for this indication in 2% and 5% formulation. Typical side effects of this topical treatment include irritative dermatitis going along with pruritus, erythema, scaling and dryness, which occur especially at the onset of the therapy. In some cases, allergic contact dermatitis or exacerbation of seborrheic dermatitis has been reported. While most of the patients with allergic contact dermatitis described in the literature showed a positive sensitization to the vehicle substance propylene glycol evaluated by patch testing, reactions to the active ingredient minoxidil are rare. Here, we report a case of allergic sensitization to minoxidil, which we evaluated and differentiated from an irritative reaction by a combination of patch testing and lymphocyte transformation test. The differentiation of allergic and irritative adverse effects and the identification of the causative allergen are of major relevance for the proceeding and adjustment of the therapy. Patients with sensitizations against propylene glycol are candidates for preparations with alternative solvents but can proceed treatment with minoxidil. In contrast, patients with allergies to the active ingredient itself are no longer candidates for treatment with minoxidil and should undergo alternative therapeutic options.     

Pimecrolimus cream 1% vs. betamethasone 17-valerate 0.1% cream in the treatment of seborrhoeic dermatitis. A randomized open-label clinical trial

BACKGROUND: Seborrhoeic dermatitis is a chronic inflammatory disease with remissions and exacerbations, characterized by erythema, scaling and pruritus primarily on the face, scalp and chest. Corticosteroids and antifungals are the mainstay of therapy. However, chronic use of corticosteroids is associated with side-effects such as skin atrophy and telangiectasia. Pimecrolimus, an inhibitor of calcineurin, has been used successfully in one patient with seborrhoeic dermatitis. OBJECTIVES: The objective of this randomized open-label clinical trial was to compare the efficacy and tolerability of pimecrolimus in comparison with a potent corticosteroid (betamethasone 17-valerate) in the treatment of seborrhoeic dermatitis. METHODS: Twenty patients with seborrhoeic dermatitis were included in this study, 11 patients in the pimecrolimus 1% cream group and nine patients in the betamethasone 17-valerate 0.1% cream group. Patients were instructed to use a thin layer of the study products twice daily at the lesional area and to discontinue treatment as soon as symptoms were absent. Clinical measures assessed were erythema, scaling and pruritus which were evaluated using a four-point scale (0-3). RESULTS: Both pimecrolimus and betamethasone were highly effective in the treatment of seborrhoeic dermatitis. Betamethasone reduced all three parameters, erythema, scaling and pruritus, faster than pimecrolimus, but the differences in reduction were not statistically significant. Relapses were observed more frequently and were more severe with betamethasone than with pimecrolimus. Moreover, pruritus was not observed after discontinuation of treatment from day 15 and beyond in the pimecrolimus group, whereas it was reported in most patients of the betamethasone group. This difference was statistically significant. CONCLUSIONS: It appears that pimecrolimus, a nonsteroidal topical treatment, may be an excellent alternative therapeutic modality for treating seborrhoeic dermatitis.     

Still elusive relationship between atopic dermatitis and allergic contact dermatitis

The relationship between atopic dermatitis (AD) and allergic contact dermatitis (ACD) has long been and continues to be an unsolved and frequently discussed issue. Whereas AD patients have traditionally been considered to have a decreased frequency of ACD, recent studies revealed that these individuals are more or equally likely to develop ACD. The aim of the present review was to determine whether the results of recent experimental studies and theoretical considerations might lead to a parallel shift in our concept on the causal relationship between AD and ACD. It has been shown that Th2 and Th1-type immune responses are not mutually exclusive, and that at least in AD a mixture of both Th2 and Th1 occurs and the interactions between them account for the clinical characteristics of the disease. This new concept on the immunopathomechanism of AD challenges our previous belief that the cytokine pattern of the affected skin is unsuitable for the development of delayed-type hypersensitivity. Since we do not know the exact quantitative balance between Th1 and Th2 reactions along a time axis, we cannot predict whether the cytokine pattern of AD patients favors or inhibits the development of ACD. What we do know with a greater degree of certainty, is that when the eczematous excoriated skin of AD patients, with its defective epidermal barrier (enhancing the penetration of many antigenic substances) is chronically exposed to skin care products and various sensitizing topical medications, it is more likely to develop a superimposed ACD.     

Beneficial effects of a skin tolerance-tested moisturizing cream on the barrier function in experimentally-elicited irritant and allergic contact dermatitis

In experimentally-induced irritant (ICD) and allergic (ACD) contact dermatitis, an oil-in-water (o/w) cream was applied to investigate its effects on a disturbed barrier function compared to untreated physiological barrier repair. Transepidermal water loss (TEWL) measurements were performed. Before the start of the experiments, the skin tolerance of the cream was examined, revealing the non-irritating characteristics of the ingredients and the absence of any contact allergic patch test reaction. In the ICD study, sodium lauryl sulfate (SLS) patches were applied to the forearms of young female volunteers. Consequently, it was observed that repeated cream application (14 days, 2x/day) significantly improved the TEWL of SLS-damaged skin, leading to a complete recovery on day 15. In the ACD study, disruption of skin barrier function was obtained by a nickel-mediated contact allergy patch (CAP) test. The cream was then applied 2x/day for 4 consecutive days. Assessment of TEWL clearly showed that recovery of the disrupted skin significantly improved after cream application in comparison to untreated barrier repair.     

Adhesion molecule profiles in atopic dermatitis vs. allergic contact dermatitis: pharmacological modulation by cetirizine

BACKGROUND: Experimental data suggest that there is an imbalance between Th1 and Th2 cells in atopic dermatitis (AD) skin compared to allergic contact dermatitis (ACD). This imbalance (Th2 and Th1 predominance, respectively) implies the production of different cytokines in these two conditions leading to different expression of adhesion molecules on skin endothelial cells. OBJECTIVE: The expression of VCAM-1 (IL-4/Th2-dependent) and ICAM-1 (INF-gamma/IL-1) on dermal vessels was compared in six patients with AD and six patients with ACD. The effect of cetirizine, a highly selective H1-receptor antagonist on the expressions was studied. METHODS: Six patients with AD were challenged with Dermatophagoides pteronyssimus (DPT patch tests applied to clinically normal skin) and six patients with ACD challenged in the same way with allergens of the European standard series. Skin biopsies at challenged sites were performed before and 6, 24 and 48 h after challenge. The experiment was carried out under double-blind cross-over conditions during a 4-day treatment with a placebo and cetirizine. RESULTS: In AD patients, the scores for both VCAM-1 and ICAM-1 were high before and after challenge. In ACD patients, the ICAM-1 score was high at each experimental time, but the VCAM-1 score, which was significantly lower before challenge, increased at 6, 24 and 48 h after challenge. The administration of cetirizine significantly reduced the VCAM-1 expression in AD patients at each experimental time. CONCLUSION: It is concluded that the increased VCAM-1 expression in AD patients compared to ACD may reflect greater IL-4 and/or IL-13 production in situ. The study also confirms the existence of a modulating effect of cetirizine in vivo on adhesion molecule expression.     

Guidelines for management of atopic dermatitis

Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease characterized by pruritus and inflammation and accompanied by cutaneous physiological dysfunction (dry and barrier-disrupted skin). Most of the patients have atopic diathesis. A standard guideline for the management (diagnosis, severity classification and therapy) of AD has been established. In our guideline, the necessity of dermatological training is emphasized in order to assure diagnostic skill and to enable evaluation of the severity of AD. The definitive diagnosis of AD requires the presence of all three features: (i) pruritus; (ii) typical morphology and distribution; and (iii) chronic and chronically relapsing course. For the severity classification of AD, three elements of eruption (erythema/acute papules, exudation/crusts and chronic papules/nodules/lichenification) are evaluated in the most severely affected part of each of the five body regions (head/neck, anterior trunk, posterior trunk, upper limbs and lower limbs). The areas of eruption on the five body regions are also evaluated, and both scores are totaled (maximum 60 points). The present standard therapies for AD consist of the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation, topical application of emollients to treat the cutaneous physiological dysfunction, systemic antihistamines and anti-allergic drugs as adjunctive treatments for pruritus, avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. Tacrolimus ointment (0.1%) and its low-density ointment (0.03%) are available for adult patients and 2–15-year-old patients, respectively. The importance of the correct selection of topical corticosteroids according to the severity of the eruption is also emphasized. Furthermore, deliberate use of oral cyclosporine for severe recalcitrant adult AD is referred.     

Effect of the lactic acid bacterium Streptococcus thermophilus on stratum corneum ceramide levels and signs and symptoms of atopic dermatitis patients

A reduced amount of total ceramides could be responsible for functional abnormalities of the skin of atopic dermatitis (AD) patients. The ability of an experimental cream containing sonicated Streptococcus thermophilus to increase skin ceramide levels in healthy subjects has been previously reported. The aim of the present work was to investigate the effects of the topical administration of a S. thermophilus-containing cream on ceramide levels of stratum corneum from AD patients. A 2-week application of the cream, containing a sonicated preparation of the lactic acid bacterium S. thermophilus, in the forearm skin of 11 patients led to a significant and relevant increase of skin ceramide amounts, which could have resulted from the sphingomyelin hydrolysis through the bacterial sphingomyelinase. Moreover, in all patients the topical application of our experimental cream also resulted in the improvement of the signs and symptoms characteristic of AD skin (i.e. erythema, scaling, pruritus).     

Interleukin-4 and the interleukin-4 receptor in allergic contact dermatitis

Cutaneous immune responses involving T helper (TH) type 1 (TH1) and type 2 (TH2) T cells, characterised by secretion of interferon-γ (Ifn-γ) and interleukin-4 (IL-4), respectively, have both been reported in allergic contact dermatitis (ACD). We used immunohistochemistry to localize expression of IL-4 in ACD lesions and unaffected skin. Atopic dermatitis (AD) and psoriasis biopsies provided positive and negative IL-4 immunoreactivity controls. To investigate the rôle of IL-4 in ACD, we investigated expression of IL-4 receptors in ACD, AD and psoriatic skin. IL-4 immunoreactivity was found in cells in the dermal infiltrate in 3 out of 7 ACD lesions, but not in unaffected skin from these patients. IL-4 immunoreactivity was found in the dermal infiltrate of all lesional and unaffected AD biopsies, but in none of the psoriatic biopsies. IL-4 receptor α chain immunoreactivity, associated with dermal mast cells, was found in all patients. Local expression of IL-4 in ACD indicates either TH2 or TH0 immunoregulation in some allergic contact dermatitis lesions. Our findings do not support exclusive TH1 or TH2 cutaneous immune responses in ACD. Expression of IL-4 receptors by cutaneous mast cells provides a route through which local effects of IL-4 might be mediated.     

Allergic contact dermatitis

Contact dermatitis is an inflammatory skin condition induced by exposure to an environmental agent. Eczema and dermatitis are used synonymously to denote a polymorphous pattern of skin inflammation characterized at least in its acute phase by erythema, vesiculation and pruritus. Substances responsible for contact dermatitis after single or multiple exposures are non protein chemicals, i.e. haptens, that induce skin inflammation through activation of innate skin immunity (irritant contact dermatitis) or both innate and acquired specific immunity (allergic contact dermatitis). The present review will focus on allergic contact dermatitis, a delayed-type hypersensitivity reaction, which is mediated by hapten-specific T cells. Recent advances in the pathophysiology of ACD have shown that the occurrence of ACD, as well as its magnitude and duration, is controlled by the opposite functions of CD8 effector T cells and CD4 regulatory T cells. From these studies ACD can be considered as a breakdown of cutaneous immune tolerance to haptens.     

Prognosis of contact dermatitis in epoxy resin workers

Between January 1993 and February 2002, 40 of 1354 (3%) workers who attended a tertiary referral occupational dermatology clinic were diagnosed with allergic contact dermatitis (ACD) from epoxy resin systems (ER). 20 of these patients were followed up at least 2 years post-diagnosis to establish prognosis. Characteristics collected at diagnosis, including age, atopic status and severity, were compared between the follow-up and not followed-up groups. No significant differences were observed. A clinician contacted patients and administered a telephone questionnaire based on variables identified from the literature, which were considered of importance for prognosis. All patients reported improvement of their skin condition since diagnosis. 12 of the 20 {60%[95% confidence interval (CI) 56-94%]} patients had applied for workers' compensation; all of these claims were successful. 16 had ceased working with ER. Of these, 9 [56% (95% CI 29-80%)] reported complete healing and 7 [44% (95% CI 19-70%)] reported ongoing dermatitis. Although no conclusions could be drawn because of the small sample size, factors that may be associated with a poor prognosis were age, atopy, duration of symptoms and severity at diagnosis. The prognosis of ACD from ER is not always favourable, even if a worker ceases exposure.     

Detection of contact hypersensitivity to corticosteroids in allergic contact dermatitis patients who do not respond to topical corticosteroids

The delayed hypersensitivity development against topical corticosteroids which are used in allergic contact dermatitis (ACD) treatment is an important clinical problem. In our study, 41 ACD patients who did not show any response to topical corticosteroid treatment were patch tested with corticosteroid series and the commercial preparations of corticosteroids and their vehicles. In corticosteroid series, there were budesonide, bethametasone-17-valerate, triamcinolone acetonide, tixocortol pivalate, alclomethasone-17-21-dipropionate, clobetasole-17-propionate, dexamethasone-21-phosphate disodium and hydrocortisone-17-butyrate. We detected positive reaction to corticosteroids in 9 of our cases (22%) (5 single and 4 multiple). The sensitivity was mostly produced by tixocortol pivalate (6 patients). This was followed by triamcinolone acetonide (2 patients) budesonide (2 patients), alclomethasone dipropionate (2 patients), dexamethasone 21 phosphate disodium (2 patients) and betamethasone-17-valerate (1 patient). As a result, it should not be forgotten that the corticosteroids used to treat ACD patients may cause ACD themselves. In ACD patients who did not respond to corticosteroid treatment, routinely applying patch test with corticosteroids should be helpful in directing the treatment.     

Relation between diagnoses on severity, sick leave and loss of job among patients with occupational hand eczema

BACKGROUND: Epidemiological studies indicate that occupational hand eczema (OHE) often is associated with persistent dermatitis and prolonged sick leave, which may lead to unemployment. Previous studies suggest that OHE caused by allergic contact dermatitis and atopic dermatitis (AD) carries the worst prognosis. OBJECTIVES: To evaluate and compare the severity and consequences of recognized OHE in different diagnostic and subdiagnostic groups. METHODS: Between October 2001 and November 2002, all new cases of recognized OHE were identified from the Danish National Board of Industrial Injuries Registry (758 cases). Severity was graded from 0 to 2 depending on the intensity of skin response and the frequency of relapse. To supplement the information from the Registry, we surveyed the study population using a postal questionnaire which included questions about disease duration, sick leave, current occupation and loss of job. RESULTS: The overall response rate to the questionnaire was 82%. We observed substantially greater severity among those with occupational irritant contact dermatitis (ICD) and AD than for any other diagnoses. Age above 50 years was also associated with increased severity of OHE. Prolonged sick leave due to OHE was reported by 19.9% and was associated with AD and severe OHE. We found a higher proportion of prolonged sick leave among those in food-related occupations (27.2%) compared with those in wet occupations (20.1%) and other occupations (16.5%). Twenty-three per cent reported that they had lost their job at least once during the past 12 months due to OHE. The only strong association with loss of job was food-related occupations. CONCLUSIONS: Occupational ICD and AD appear to be strongly associated with severity of OHE. AD and severity of OHE were independently associated with prolonged sick leave. Having a food-related occupation appears to be associated with increased risk of loss of job.     

Emollients in a propanol-based hand rub can significantly decrease irritant contact dermatitis

The objective of this study is to determine the effect of emollients in a propanol-based hand rub on skin dryness and erythema. In this prospective, randomized, controlled, double-blind trial, 35 subjects participated; of them approximately half were atopic (modified Erlanger atopy score > or =8). 2 propanol-based formulations were tested in a repeated open application test, 1 contained a mixture of emollients (0.81%, w/w). 2 aliquots of 0.7 ml of each formulation were applied twice per day over 2 weeks to the cubital fossa of each subject after random assignment of the preparations. Treatment areas were assessed before each application and 3 days postfinal application by visual inspection for erythema and dryness according to a standard scale. The sum score over all assessment time-points served as primary parameter. The mean sum score for erythema and dryness was significantly lower for the hand rub with emollients (0.8 +/- 2.4) in comparison with that for the hand rub without emollients (1.5 +/- 3.5; P = 0.022; Wilcoxon signed rank test). A comparison of the atopic and non-atopic subjects revealed no significant difference for any of the products (P > 0.05; Mann-Whitney U-test). It is concluded that the addition of emollients to a propanol-based hand rub can significantly decrease irritant contact dermatitis under frequent-use conditions.     

Skin contact irritation conditions the development and severity of allergic contact dermatitis

Irritant contact dermatitis (ICD) is a frequent inflammatory skin disease induced by skin contact with low molecular weight chemicals such as haptens endowed with proinflammatory properties. Allergic contact dermatitis (ACD) is a frequent complication of ICD and is mediated by hapten-specific T cells primed in lymph nodes by skin emigrating dendritic cells. The aim of this study was to analyze the relationship between ICD and ACD to 2,4-dinitrofluorobenezene (DNFB) in C57BL/6 and BALB/C mice, which develop a severe and a moderate skin inflammation, respectively. Upon a single skin painting with DNFB, C57BL/6 developed within hours a more severe dose-dependent ICD response as compared to BALB/C mice, which was associated with enhanced upregulation of IL-1beta, IL-6, and IL-10. Skin exposure to a low dose of DNFB resulted, in both strains, in a low ICD that resolved in a few hours. Alternatively, skin painting with either an intermediate or a high DNFB concentration induced an ICD that subsequently gave rise to an ACD reaction whose intensity was proportional to the magnitude of the ICD response and was more severe in C57BL/6 mice than in BALB/C mice. In conclusion, the hapten-induced skin contact irritation conditions the development and the severity of ACD.     

Efficacy of topical corticosteroids on irritant skin reactions

Topical corticosteroids are frequently used in the treatment of irritant contact dermatitis (ICD). The efficacy of this treatment has, however, not been thoroughly established, and experimental studies on the topic have provided conflicting results. The aim of the present study was to evaluate the effect of potent topical corticosteroids on experimentally-induced irritant skin reactions in a double-blind, vehicle-controlled study. 16 healthy volunteers had sodium lauryl sulfate patch tests symmetrically applied to the upper arms. After removal of patch tests, a potent topical cortico-steroid (betamethasone-17-valerate) was applied to the irritant skin reaction on one arm, while the corresponding vehicle was applied to the irritant skin reaction on the opposite arm 2 × daily for 7 days. Reactions were evaluated by measurement of transepidermal water loss (TEWL) and erythema. After 7 days, statistically significant lower values of TEWL and erythema were found in corticosteroid-treated, compared to the vehicle-treated, skin reactions. The results indicate that topical corticosteroids improve healing of ICD.     

In vivo nickel allergic contact dermatitis: human model for topical therapeutics

Techniques to determine efficacy of topical agents on allergic contact dermatitis (ACD) may benefit from refinement. The aim of this study was to develop an in vivo human model system for the bioengineering and visual quantification of the effect of topical agents on nickel ACD, and to correlate ACD parameters. 14 nickel patch-test-positive subjects were included in a placebo-controlled, double-blind study after a pre-screening procedure with a standard diagnostic patch test with nickel sulfate in 54 healthy human volunteers. 5% nickel sulfate in petrolatum in a Finn Chamber was applied on forearm skin for 48 h to create a standardized dermatitis. Thereafter, the dermatitis was treated with a model topical agent and a placebo control while recording endpoint parameters daily for 10 days. Resolution was quantified with 4 parameters: visual scoring (VS), transepidermal water loss (TEWL) (Tewameter), skin blood flow volume (BFV) (laser Doppler flowmeter), and skin color (a* value) (Colorimeter). The model agent reduced cutaneous allergic reactions, especially on day 8 to 10, in comparison with the placebo control. A highly significant linear relationship exists among all parameters, except between a* and BFV. This model may provide robust biometrics for determining the efficacy of topical therapeutics on experimentally induced ACD.     

Influence of tumour necrosis factor‐α polymorphism −308 and atopy on irritant contact dermatitis in healthcare workers*

Background. Chronic irritant hand dermatitis is an issue for healthcare workers and may negatively impact infection control. Objectives. We examined the effects of a G to A transition at position ?308 on the tumour necrosis factor‐α (TNF‐α) gene on chronically damaged skin of healthcare workers during exposure and recovery from repetitive hand hygiene, after intensive treatment, and on the irritant response in normal skin. Patients/Materials/Methods. In 68 healthcare workers with irritant hand dermatitis, we genotyped TNF‐α?308 and measured the epidermal response via quantitative digital imaging, erythema, dryness, and barrier integrity. Results. Excess hand erythema decreased with hand hygiene exposure and increased during time off for AA/GA genotypes, but had opposite effects for GG. AA/GA had smaller reductions in dryness with lotion treatment and larger reductions in excess erythema than GG. The atopic diathesis and heightened neurosensory irritation resulting from water and lactic acid significantly influenced the responses. Repeated exposure to water and sodium lauryl sulfate (0.05, 0.1%) produced higher erythema in normal skin for AA/GA than for GG. Conclusions. This study provides evidence that the TNF‐α polymorphism at ?308 and an atopic history impact the severity of irritation and recovery from exposure and response to treatment for common hand skin products in both chronic irritant hand dermatitis and normal skin.     

Occupational contact dermatitis in bakers, confectioners and cooks

A population-based study was performed to investigate incidence rates of occupational skin disease (OSD) in bakers, confectioners and cooks, as well as the rôle of endogenous and exogenous risk factors. In North Bavaria, all closed cases of OSD were recorded systematically in a 3-year period and the total number of employees in the food industry was known over the same period of time, Incidence rates of OSD and relative risks of atopic skin diathesis (AD) and respiratory atopy (RA) were calculated. The overall incidence rate (I) of OSD (in 3 years per 10,000 employees) was 67 (95% CI 58:76) in these occupations. Bakers had a higher risk of OSD, with an incidence of 191 (95% CI 156:226) compared to confectioners with I=84 (95% CI 55;113) and cooks I=34 (95% CI 28;40). Incidence rates were sex-and age-related. Females developed OSD with an incidence rate of 74 (95% CI 64:84) compared to males with I= 58 (95% CI 48:70). OSD occurred mostly between the ages of 15 and 24 years. Irritant contact dermatitis (ICD) was the main type of OSD. 36% of the bakers had an occupationally relevant Type I allergy, while Type I allergies were less frequent in confectioners (16%) and cooks (9%). Assuming a prevalence of 10% of AD in the general population the relative risk (RR) of developing OSD in bakers, confectioners and cooks with AD was 9.7. 10.5 and 5.2, respectively. There were only small differences in calculating sex-related RR of AD. The etiologic fraction of AD was nearly 50% in bakers and confectioners, whereas cooks had a smaller proportion of AD (30%). Respiratory atopy proved to be relevant in bakers (RR-4.0). Preexistence of RA is important in bakers, since Type I reactions seem to be triggered. This is the first population-based study which demonstrates clear differences between OSD in 3 occupations in the food industry, using incidence rate as a parameter. Females have a considerably higher risk of developing OSD. Since AD or RA do not explain sex differences in OSD, different skin sensitivity or different exposure between males and females may be important factors in the development of OSD. ICD is more important than allergic contact dermatitis (ACD). The role of AD and of RA is different in the 3 occupations.