Hand eczema classification: a cross-sectional, multicentre study of the aetiology and morphology of hand eczema.

BACKGROUND: Hand eczema is a long-lasting disease with a high prevalence in the background population. The disease has severe, negative effects on quality of life and sometimes on social status. Epidemiological studies have identified risk factors for onset and prognosis, but treatment of the disease is rarely evidence based, and a classification system for different subdiagnoses of hand eczema is not agreed upon. Randomized controlled trials investigating the treatment of hand eczema are called for. For this, as well as for clinical purposes, a generally accepted classification system for hand eczema is needed. OBJECTIVES: The present study attempts to characterize subdiagnoses of hand eczema with respect to basic demographics, medical history and morphology. METHODS: Clinical data from 416 patients with hand eczema from 10 European patch test clinics were assessed. RESULTS: A classification system for hand eczema is proposed. CONCLUSIONS: It is suggested that this classification be used in clinical work and in clinical trials.

Notification of occupational skin diseases by dermatologists in The Netherlands.

BACKGROUND: A voluntary surveillance scheme of occupational skin diseases (OSDs) in The Netherlands starting in 2001 aimed to improve insight in the incidence of OSD especially occupational contact dermatitis (OCD), risk professions and causal agents. This paper presents the results of this scheme during 2001-05. METHODS: Reports of new cases of OSD received from the participating dermatologists on a monthly basis were analysed. Data evaluated included information on diagnosis, sex, age, sickness, absenteeism, profession and causal agents. Relative differences in incidence rates between industries or branches were estimated by calculating incidence rate ratios. RESULTS: About 80% of the notifications concerned OCD. The highest number of notifications was recorded in the first year of the scheme. This was probably due to reporting of a mixture of incident and prevalent cases. During the following 5 years, the number of yearly notifications of OSD declined. Hairdressers, nurses, metalworkers, mechanics and cleaners were the most commonly affected professions. Wet work and irritating substances were the most frequently reported causal agents. Most patients with OCD were not absent from work. CONCLUSIONS: A voluntary surveillance scheme with dermatologists provides valuable data about the distribution of OCD in risk professions and the causal agents. However, it has certain limitations in assessing trends in incidence. Active medical surveillance in populations at risk should be encouraged not only to improve secondary prevention but also to obtain more reliable information about the incidence of OCD.

CXCL8 secretion by dendritic cells predicts contact allergens from irritants.

Monocyte-derived dendritic cell functions have been explored for identification of contact allergens in vitro. Current methods, including measurement of changes in cell surface marker expression (e.g. CD83, CD86) do not provide a sensitive method for detecting the sensitising potential of a chemical. In this study, we investigated whether chemokine production by monocyte-derived dendritic cells is increased upon maturation and whether chemokine production can provide methodology for the detection of allergens. Monocyte-derived dendritic cells were exposed to allergens (nickel sulphate, cobalt chloride, palladium chloride, copper sulphate, chrome-(III)-chloride, potassium dichromate, p-phenylenediamine and dinitrochlorobenzene) and irritants (sodium dodecyl sulphate, dimethylsulphoxide, benzalkoniumchloride and propane-1-ol). CD83 and CD86 expression was analysed by flow cytometry and chemokine production (CXCL8, CCL5, CCL17, CCL18, CCL19, CCL20, CCL22) was determined by ELISA. Significant up regulation of CD83 and CD86 expression could only be induced by three out of seven and five out of seven allergens, respectively. In contrast, CXCL8 production was significantly increased after stimulation with all allergens tested, whereas irritant exposure led to decreased CXCL8 production. All other chemokines tested, failed in identifying contact allergens. In conclusion, CXCL8 production, next to CD83 and CD86 up regulation, by monocyte-derived dendritic cells provides a promising in vitro tool for discrimination between allergens and irritants.

[Insulin allergy: background, diagnosis and treatment]. / Insulineallergie; achtergrond, diagnostiek en behandeling.

An allergic reaction develops in 2.4% of patients that use insulin. This ranges in severity from erythema and pruritus to life-threatening anaphylaxis. llergic reactions to insulin usually occur within a few hours after an injection and are usually due to a local or systemic type I IgE-mediated hypersensitivity reaction. Despite considerable research into the immunogenicity of insulin, this has not yet been clarified completely and allergic reactions to insulin still occur. A systematic diagnostic approach is essential for an adequate treatment plan. A blood test for anti-insulin antibodies and intradermal skin tests are of great importance. There are many options available for the treatment of insulin allergy and each patient must therefore be evaluated individually.

The CXCR3 activating chemokines IP-10, Mig, and IP-9 are expressed in allergic but not in irritant patch test reactions.

Differentiation between allergic and irritant contact dermatitis reactions is difficult, as both inflammatory diseases are clinically, histologically, and immunohistologically very similar. Previous studies in mice revealed that the chemokine IP-10 is exclusively expressed in allergic contact dermatitis reactions. In the present study, we investigated whether the mRNA expression of IP-10 and the related CXCR3 activating chemokines, Mig and IP-9 are also differentially expressed in human allergic contact dermatitis and irritant contact dermatitis reactions. Skin biopsies from allergic (13 cases) and sodium lauryl sulfate-induced irritant patch test reactions (13 cases), obtained 1-72 h after patch testing, were studied by means of an in situ hybridization technique. Results of chemokine mRNA expression were correlated with clinical scoring, histology, and immunohistochemical data including the proportion of inflammatory cells expressing CXCR3, the receptor for IP-10, Mig, and IP-9, and ICAM-1 and HLA-DR expression on keratinocytes. IP-10, Mig, and IP-9 mRNA were detected in seven of nine allergic contact dermatitis reactions after 24-72 h, but not in sodium lauryl sulfate-induced irritant contact dermatitis reactions. ICAM-1 expression by keratinocytes was only found in allergic contact dermatitis reactions and correlated with chemokine expression. Moreover, up to 50% of the infiltrating cells in allergic contact dermatitis expressed CXCR3, in contrast to only 20% in irritant contact dermatitis reactions. In conclusion, we have demonstrated differences in chemokine expression between allergic contact dermatitis and irritant contact dermatitis reactions, which might reflect different regulatory mechanisms operating in these diseases and may be an important clue for differentiation between allergic contact dermatitis and irritant contact dermatitis reactions.

In vitro studies in nickel allergy: diagnostic value of a dual parameter analysis.

A comparison was made between the diagnostic value of assaying nickel-induced lymphocyte proliferation (lymphocyte transformation test, LTT) and migration inhibition factor (MIF) production in nickel contact sensitivity. Although lymphocyte proliferation was significantly increased in the group of patients with skin test reactivity to nickel, positive LTT were also frequently found in skin test-negative subjects: in 63% of subjects with and in 30% of subjects without a history of metal allergy. This would limit the value of the LTT as an in vitro correlate of skin test reactivity. However, in certain patients positive lymphocyte transformation may reveal nickel sensitization at a time of undetectable skin reactivity. Data obtained with the macrophage migration inhibition test (MMIT) showed a good correlation with nickel patch test reactions. Accurate determination of MIF became feasible by using cells from the human monocytoid cell line U937 as target cells in a microdroplet agarose assay. Using this MMIT, positive reactions occurred in 13% of the healthy controls and false-negative reactions were found in 26% of patients with positive skin test reactivity to nickel. As LTT and MMIT data appeared to be only weakly correlated in the individuals tested, a dual parameter analysis was performed. An excellent correlation [p = 1.8 (10(-8]] was found between skin test and in vitro reactivity for individuals with matching in vitro results (60% of all individuals tested). In those individuals with discordant in vitro data, skin testing will remain indispensable for diagnosing nickel allergy.

Excited skin syndrome (angry back).

The excited skin syndrome, a state of skin hyperirritability often induced by a concomitant dermatitis, is responsible for numerous nonreproducible test results in battery patch testing. We analyzed the mechanisms and circumstances involved in its induction, as well as its clinical importance and frequency. Finally, we provide suggestions about how to deal with patients suspected of having the syndrome.

The effect of occlusion of the skin with transdermal therapeutic system on Langerhans' cells and the induction of skin irritation.

Sensitization to drugs in transdermal therapeutic systems is a common unwanted event. We investigated whether prolonged occlusion of the skin causes skin irritation, and in this way might play a role in the possible induction of sensitization to drugs from these systems. Occlusion was effected with a placebo transdermal therapeutic system and silver-patch test in a time span ranging from eight hours to seven days in five groups of five volunteers. Skin irritation was judged on clinical aspects, histopathologic and immunofluorescence findings, and changes in the Langerhans' cell systems. The results indicate that occlusion with the systems used in this experiment provokes only slight or no skin irritation.

The allergens in cosmetics.

The ingredients responsible for allergy to cosmetics were determined in 119 patients suffering from cosmetic-related contact dermatitis. Most reactions (56.3%) were caused by skin care products, followed by nail cosmetics (13.4%), perfumes (8.4%), and hair cosmetics (5.9%). Preservatives were most frequently implicated (32.0%), followed by fragrances (26.5%) and emulsifiers (14.3%). By far the most important cosmetic allergen was Kathon CG, (a preservative system containing, as active ingredients, a mixture of methylisothiazolinone and methyl chloroisothiazolinone) reacting in 33 patients (27.7%). Other frequent causes of cosmetic-related contact allergic reactions were toluenesulfonamide/formaldehyde resin in nail hardener and/or nail lacquer (15 patients [12.6%]), and oleamidopropyl dimethylamine, an emulsifier in baby body lotion (13 patients [10.9%]).

Allergic reactions, "spillover' reactions, and T-cell subsets.

A strong positive, allergic patch-test reaction was elicited in 15 patients with an established allergy for a particular allergen. Patches with a marginally irritating concentration of sodium lauryl sulfate (SLS) were applied at fixed distances. The SLS patch situated adjacent to the allergic reaction was significantly enhanced in 12 of 15 patients (P less than 0.01) compared to more distant SLS reactions ("spillover'). Only quantitative differences were observed in the histologic pictures of the different types of reaction. The infiltrate consisted of lymphocytes and histiocytes, mainly located perivascular in the upper dermis. T-cell subsets were assessed with monoclonal antibodies using an immunoperoxidase technique. The distribution of the different T cells was the same for both reaction types. T cells located outside the perivascular infiltrates (e.g., in the epidermal vesicles) were OKT-8-positive (cytotoxic/suppressor T lymphocytes). Immunofluorescence examination did not show different patterns for the allergic or "enhanced toxic' reactions with regard to the presence of immunoglobulins and complement. The "spillover' phenomenon may cause false-positive patch-test reactions.

Compression stockings and rubber floor mats: do they benefit workers with chronic venous insufficiency and a standing profession?

Chronic venous insufficiency (CVI) is a burden to many workers, especially to those with a standing profession. Preventive measures are seldom taken. A quasirandomized parallel group trial was performed in 114 male workers with CVI and a standing profession. For 3 months, class II compression stockings or rubber floor mats were used vs controls. Outcome measures were diurnal volume changes (leg swelling) and complaints of the lower legs. With the stockings, a significant decrease in complaints was found, as well as a significant decrease in leg swelling. Rubber mats were often not suitable for hygienic and safety reasons. The decrease in complaints in the group using rubber mats was less pronounced, and leg swelling did not differ from that of the control group. Compression stockings appeared to be superior to rubber mats with regard to applicability, diminishing subjective complaints, and decrease of diurnal leg swelling.

Patch tests with some spices.

Experience is necessary to use commercially available spices and seasonings for patch testing. This experience is easily obtained by composing your own series of locally important flavorings and by using this series to assess the irritant potency. In our patients, not many strong irritation reactions were elicited. Only 100 per cent garlic powder was obviously too irritant, whereas 25 per cent in petrolatum might be too low to detect allergy. Positive reactions to unknown spices need to be checked in controls; this is important when patch tests are done with spices brought in by the patient. A positive patch-test reaction to a fragrance or perfume indicator in housewives, cooks, and confectioners with hand eczema is an indication to perform patch tests with spices because of the relation between spices and fragrances.

Investigation of an unexplained skin disorder in a prison clinic in the Netherlands in 2002.

An unexplained outbreak of skin disorder with itching papules or pustules occurred among drugs body packers in a detention clinic in the Netherlands in October-November 2002. The descriptive cohort study suggests this outbreak could be associated with an expired batch of disposable linens, with an overall attack rate of 30% in the study population (n=118). No additionnal cases have been noted since this expired batch was replaced.

[Cutaneous reactions to drugs]. / Huidreacties door geneesmiddelen.

Exact data concerning the incidence of cutaneous drug eruptions are lacking due to underreporting. Diagnostics of cutaneous drug eruptions is hampered by the fact that one drug may induce different eruptions while the same cutaneous eruption can be caused by several drugs. Important steps in the diagnostics of cutaneous drug eruptions are: suspicion of the drugs as cause of the eruption, precise history-taking with emphasis on medication use and a complete physical examination. The 'golden standard' in the diagnostics of a drug eruption is the dechallenge-rechallenge procedure, but in severe cutaneous reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis and vasculitis, this procedure can cause severe, sometimes life-threatening reactions. Reporting suspected adverse drug reactions to pharmaco-vigilance centres is important to identify rare drug reactions.

[Contact allergy for corticosteroids]. / Contactallergie voor corticosteroïden.

Contact allergy to corticosteroids is not rare. In some studies prevalence rates up to 6% have been observed among patients suspected of allergic contact dermatitis. Hypersensitivity occurs especially in individuals who have been suffering for years from atopic dermatitis, contact dermatitis of the hands and feet, or stasis dermatitis caused by chronic venous insufficiency. The clinical picture is rarely that of acute allergic contact dermatitis, because the reaction is mitigated by the anti-inflammatory properties of the corticosteroid itself; the diagnosis must be suspected when eczema does not improve or spreads during topical corticosteroid therapy. Application to the mucous membranes less frequently leads to sensitisation. Most such cases are caused by nasal sprays containing tixocortol pivalate or budesonide. Oral or parenteral administration of corticosteroids to sensitive individuals causes exacerbation of pre-existing contact dermatitis or widespread allergic cutaneous drug reactions. Allergological investigation with corticosteroids presents some specific problems, the most important being occurrence of false-negative reactions. Nevertheless, most sensitive patients can be identified by testing the 'indicator' allergens, budesonide and tixocortol pivalate, which should be added to the routine series of contact allergens. Cross-reactions to other corticosteroids occur frequently. This should be taken into account when prescribing alternative corticosteroid preparations.

[Contact allergy to eyedrops containing beta-blockers]. / Contactallergie voor oogdruppels met beta-blokkers.

In six patients (4 women aged 80, 62, 43 and 52 years and 2 men aged 58 and 51 years), who used eyedrops containing beta-blockers for the treatment of glaucoma, allergic contact dermatitis of the eyelids was diagnosed. Three were allergic to metipranolol, 2 to levobunolol and 1 to timolol. In literature, less than 50 cases of hypersensitivity to beta-blockers in eye medication have been reported. There are, however, reasons to assume that sensitization is more frequent: (a) not all patients are referred by the ophthalmologist to the dermatologist; (b) false-negative reactions to patch tests with the commercial preparations and with beta-blockers are not infrequent; (c) they are not routinely tested because beta-blockers are difficult to obtain in pure form; (d) cross-reactions with other beta-blockers are infrequent, and changing to another preparation therefore usually solves the clinical problem. Nevertheless it is advisable to test a battery of beta-blockers (befunolol, levobunolol, metipranolol, timolol) in allergic patients. A test preparation of 2% in water or 3%-10% in petrolatum may be suitable. Control testing in non-exposed individuals is necessary to exclude irritation reactions.

[Allergic contact eczema due to 'tea tree' oil]. / Allergisch contacteczeem voor 'tea tree'-olie.

In four patients, three women aged 45, 29 and 52 years and a man aged 45 years, allergic contact dermatitis due to 'tea tree' oil was diagnosed. The case of the man was published before. 'Tea tree' oils are essential oils distilled from the leaves of myrtaceous trees and shrubs occurring in Australia and South-East Asia. The 'tea tree' oil available in the Netherlands is distilled from the Melaleuca alternifolia and mainly contains eucalyptol. Eucalyptol is probably the most important allergen.

[Contact allergy in and around the mouth]. / Contactallergie in en rond de mond.

Contact allergic reactions in and around the mouth are not frequent, but they can have very unpleasant consequences. Discussed are the most important materials that can cause reactions in patients and dental personnel. Particulary the enormous increase in the use of latex gloves has caused a rise in latex allergy and contact dermatitis by rubber additives. Acrylates are also important contact sensitizers; they can cause the dentist serious trouble.