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Nowadays, for modern electrotherapy of cardiac arrhythmias different pacemaker systems are used. Antibradycardia pacing systems (e. g. single-chamber, two-chamber, three-chamber systems, frequency-adapted pacemaker) can be distinguished from antitachycardia pacing systems like implantable or portable cardioverter defibrillators and combined antibradycardia/antitachycardia systems. Cutaneous reactions overlying a pacemaker or defibrillator are often termed "pacemaker dermatitis". In terms of the differential diagnostic workup, these cutaneous reactions can have various causes. After exclusion of infection by analyzing clinical and laboratory-chemical results, "pressure dermatitis" or the often clinically asymptomatic "reticular telangiectatic erythema" (synonym "postimplantation erythema") must be considered. Histological examination of the affected skin can contribute to the diagnosis. In case of suspected contact hypersensitivity to implant material, allergological exploration should be realized. In addition to patch testing with commercially available contact allergens, product-related material metal alloy discs are often available from the pacemaker manufacturer for epicutaneous testing. Due to the lack of additional benefit compared to standardized patch testing, a clear recommendation for such metal alloy discs cannot be given. In selected cases of suspected hypersensitivity reaction, sensitization can eventually be analyzed by the lymphocyte transformation test. Positive reactions must always be critically interpreted taking into consideration the corresponding clinical signs. Depending on the cause, cutaneous reactions are occasionally self-limiting. In many cases, however, removal of the pacemaker is inevitable.

Only a few cases of contact allergic gastritis in patients with nickel allergy have been reported in the literature. We report a case of probable contact-allergic gastritis in a 46-year-old woman. Clinical examination revealed lichenoid mucosal lesions of the gums adjacent to a bridge and crowns that had been implanted several weeks previously. Since implantation, the patient suffered from gastrointestinal complaints including stomach pain. Gastroscopy and histological investigation of stomach biopsies showed eosinophilic gastritis. Patch testing done under the diagnosis of contact allergic stomatitis showed positive reactions to gold sodium thiosulphate, manganese (II) chloride, nickel (II) sulphate, palladium chloride, vanadium (III) chloride, zirconium (IV) chloride, and fragrances. The crowns and the bridge contained gold, palladium, and zirconium, hence they were replaced by titan-based dentition. Shortly after replacing the artificial dentition, all gastrointestinal symptoms resolved spontaneously without further treatment. Delayed-type allergy to components in the artificial dentition seem to have caused the gastritis.

Metal implant sensitivity (intolerance) can cause pain, reduced mobility, loosening of the implant and skin rashes. Knowledge of differential diagnoses, histology and appropriate diagnostics are essential for proper diagnosis. To outline typical clinical signs and histology in metal-implant-associated skin lesions we present three exemplary patients from our implant allergy outpatient department and give an overview of the current literature regarding metal implant sensitivity. In patients with a negative patch test the lymphocyte transformation test may reveal metal sensitization. Even "pure" titanium alloys may contain traces of nickel. The histology of implant-associated skin reactions goes from teleangiectatic postimplantation erythema to eczema and vasculitis. Based on the synopsis of history, clinical picture, allergological testing and histology, metal implant sensitivity can be diagnosed more precisely.

A 73-year-old female with sick sinus syndrome and atrial fibrillation was implanted with a ventricular demand inhibit pacemaker. She subsequently developed multiple episodes of skin irritation and necrosis. Skin patch testing revealed sensitivity to almost every component of the pacemaker system. The pacemaker was removed and replaced with a new pacemaker in which the generator was covered with a polytetrafluoroethylene (PTFE) sheet and the lead was covered with PTFE conduit. The patient suffered no further episodes of pacemaker-associated contact dermatitis.

In Europe often no clear distinction is made between deodorant and antiperspirant. Particularly in Germany, the labeling "deo" is used for both. Only antiperspirants are capable of influencing the activity of eccrine sweat glands. In the treatment of focal hyperhidrosis, the use of aluminum chloride solutions represents the first choice. The efficacy is well documented in a variety of studies. Subjective side effects include pruritus and - less often - irritant dermatitis, which can be treated symptomatically and usually does not require discontinuation of the treatment. Rare variants of focal hyperhidrosis like auriculotemporal syndrome, Ross syndrome and nevus sudoriferus also are suitable for treatment with topical aluminum chloride hexahydrate solutions.

Novel drug delivery systems, such as solid lipid nanoparticles (SLN), have been proposed to reduce retinoic acid (RA)-induced skin irritation. However, one question still remains: could it be accomplished without reducing efficacy? To evaluate this question the comedolytic effects and epidermal thickening of RA-loaded SLN were compared to the conventional RA formulations (gel or cream), as well as the potential of these formulations to induce skin irritation. The comedolytic effects and epidermal thickening of these formulations, both containing RA at 0.01 or 0.05%, were investigated in a rhino mouse model, while the studies of RA-induced skin irritation were evaluated through rabbit skin irritation tests and in the rhino mouse model. RA-loaded SLN, as compared to the placebo, produced a comedolytic effect with a significant reduction of the utricle diameter, which proved to be similar to that observed for marketed gels or creams regardless of the RA concentration. RA formulations (SLN or marketed cream) also induced an epidermal proliferation leading to a thickened epidermis in treated animals. In both animals studied (rhino mice and rabbits), the RA-loaded SLN, when compared to conventional formulations, promoted a significant reduction in RA-induced skin irritation (erythema and scaling). Then, RA-loaded SLN represents an interesting alternative to reduce RA-induced skin irritation without reducing efficacy, and constitutes an innovative approach for the topical treatment of acne with RA.

Postinflammatory hyperpigmentation (PIH) is a benign but cosmetically disturbing skin lesion, which is notoriously difficult to treat. Standard treatments include topical application of bleaching creams and gels. In this case report, we show that fractional photothermolysis might be a new successful option in the treatment of PIH. Its efficacy must be confirmed by further studies and balanced against possible side effects, but the initial results are promising.

A 19-year-old woman with known strong contact sensitization to nickel sulfate presented with persistent periumbilical eczema even though she had been careful to avoid exposure to the allergen. She had childhood atopic dermatitis which had been latent but had flared a year previously, presenting as flexural eczema. Double-blind placebo-controlled oral challenge with 5 mg nickel revealed a hematogenous contact dermatitis, accompanied by fever and malaise. It resolved quickly after treatment with systemic steroids and antihistamines. The possibility of hematogenous contact dermatitis should be considered in patients with strong delayed-type hypersensitivity suffering from persistent or relapsing eczema.

Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses; however few studies have sought to identify the active phytochemical(s) in oat that mediate this anti-inflammatory activity. Avenanthramides are phenolic compounds present in oats at approximately 300 parts per million (ppm) and have been reported to exhibit anti-oxidant activity in various cell-types. In the current study we investigated whether these compounds exert anti-inflammatory activity in the skin. We found that avenanthramides at concentrations as low as 1 parts per billion inhibited the degradation of inhibitor of nuclear factor kappa B-alpha (IkappaB-alpha) in keratinocytes which correlated with decreased phosphorylation of p65 subunit of nuclear factor kappa B (NF-kappaB). Furthermore, cells treated with avenanthramides showed a significant inhibition of tumor necrosis factor-alpha (TNF-alpha) induced NF-kappaB luciferase activity and subsequent reduction of interleukin-8 (IL-8) release. Additionally, topical application of 1-3 ppm avenanthramides mitigated inflammation in murine models of contact hypersensitivity and neurogenic inflammation and reduced pruritogen-induced scratching in a murine itch model. Taken together these results demonstrate that avenanthramides are potent anti-inflammatory agents that appear to mediate the anti-irritant effects of oats.

Skin reactions to chemicals used by hair dressers are usually reported as irritative or allergic contact dermatitis of the hands. We describe a 15-year old girl who suffered an unusually severe injury to her scalp with necrosis of the galea aponeurotica as a result of highlighting her hair. Injury resulted in a scaring alopecia, which can only be treated by plastic reconstructive surgery. The cause for this injury might have been a higher than usual concentration of hydrogen peroxide used for highlighting the hair.

Mitomycin C is an alkylating chemotherapeutic agent which is instilled intravesically to prevent recurrence of superficial bladder carcinomas. After several cycles of mitomycin C, our patient developed a pruritic genital dermatitis and palmar desquamation. Following exclusion of a fungal infection, we performed patch tests using the standard series, the major basic ointment ingredients, disinfectants, and mitomycin C in concentrations of 0.001 to 0.1%; the resulting diagnosis was allergic contact dermatitis due to delayed-type hypersensitivity to mitomycin C. The skin rash rapidly resolved with application of topical steroids, and the intravesical chemotherapy was changed to doxorubicin. Eczematous skin reactions are quite common side effects after intravesical instillation of mitomycin C. In the majority of cases, they are caused by delayed-type hypersensitivity reactions, presumably elicited by hematogenous spread of the allergen, and not by irritation. The sensitization most likely occurs via the bladder mucosa. In order to differentiate between allergic and toxic contact dermatitis, patch tests with the above-mentioned mitomycin C concentrations are useful. In cases of mild allergic contact dermatitis the intravesical chemotherapy might be continued with concomitant topical steroids.

Oral ingestion or parenteral administration of certain contact allergens may elicit eczematous skin reactions "from inside" in sensitized individuals; this phenomenon has been termed "systemically-induced eczema" or "hematogenous contact eczema". There is a wide range of clinical features from polyetiological dyshidrotic hand and foot eczema to baboon syndrome. The most important contact allergens known to elicit systemically-induced contact eczema are metal salts, drugs, phytoallergens and balsam of Peru. Diagnosis is based on proof of delayed type hypersensitivity by patch testing and oral challenge. Until more and better data is acquired, special diets (for instance low nickel) should be instituted only in carefully selected patients.

Histamine is released from mast cells in the skin, causing urticaria and itching. However, little is known about the roles of histamine in development of eczematous lesions in contact dermatitis. Effects of histamine on development of eczematous lesions in contact dermatitis were assessed using histamine-deficient mice in which contact dermatitis was developed by repeated application of diphenylcyclopropenone. Development of eczematous lesions in contact dermatitis was suppressed in histamine-deficient mice compared to wild-type mice. H(1) agonist ((6-12-(4-imidazol)ethylamino)-N-(4-trifluoro- methylphenyl)hepatanecarboxamide) promoted development of eczematous lesions in histamine-deficient mice. H(1) receptor antagonist (loratadine) suppressed development of eczematous lesions in wild-type mice, whereas H(2) agonist (dimaprit) and receptor antagonist (cimetidine) were ineffective. These results suggest that histamine facilitates the development of eczematous lesions in a murine model of contact dermatitis via H(1) receptors.

Perianal dermatitis is one of the most common proctological disorders. The anatomy of the anal region provides suitable conditions for the development of dermatitis. In the diagnostic work-up and the management of patients with perianal dermatitis, three types need to be distinguished: irritant contact dermatitis, atopic dermatitis, and allergic contact dermatitis. Each type has its aetiological and pathogenetic factors, which will provide clues to the diagnosis and subsequent management of the condition. In the differential diagnosis of the condition, consideration should be given to inflammatory diseases of the perianal region which may produce eczema-like patterns.

The selection of the most important contact allergens is subject to a continuous change. Several factors may influence the sensitization rates and thus the decision, which substances to include in the standard series of the most frequent allergens. The Information Network of Departments of Dermatology adds substances of interest for a certain time period to the standard series in order to evaluate parameters such as sensitization rate, grade of reaction, and clinical relevance of positive reactions. In 6 testing periods starting in 1996, 13 test substances were evaluated. Due to the results, propolis, compositae mix, and bufexamac were included in the standard series in 1999, while lyral was added in 2002. Sorbitansesquioleat, dispers blue mix, and iodopropynyl butylcarbamate are under further discussion. Substances such as glutaraldehyde and p-aminoazobenzole should be tested in certain risk groups only, whereas the steroids budesonide and tixocortol should be tested when clinically suspected.

JAK/STAT pathways are described as the major mechanisms by which cytokine receptors transduce intracellular signals. The signalling mechanisms in antigen-presenting cells (APC) in the sensitization phase of contact hypersensitivity are poorly understood. The aim of this study was to clarify whether well-established JAK/STAT signalling pathways might be activated directly by contact sensitizers as described previously for tyrosine kinases and some MAP kinases. As a model of epidermal APC, human monocytes and human monocyte-derived dendritic cells were stimulated with the structurally unrelated contact sensitizers MCI/MI, thimerosal, TNCB and formaldehyde. The phosphorylation states of the transcription factors STAT1, STAT3, STAT4, STAT5 and STAT6 were determined by Western blot analysis using phosphospecific antibodies. In contrast to the positive controls performed with the cytokines IFN-gamma, IL-10, IFN-alpha, GM-CSF and IL-4, no significant increase in the phosphorylation of STAT molecules was recognized in hapten-treated cells. These results suggest that contact allergens do not directly activate common JAK/STAT pathways. Therefore the activation of APC in the early sensitization phase of contact hypersensitivity by haptens does not involve signals normally delivered by JAK-associated cytokine receptors.

Burckhardt proposed the alkali resistance method as a means of assessing the integrity of the stratum corneum barrier in 1947. Researchers after Burckhardt largely found the test unreliable and nonreproducible; it therefore fell into disuse worldwide. We have upgraded the procedure by exposing the skin to 1.0 M sodium hydroxide under strictly specified conditions for successive 1-min periods until the emergence of the first erosions, revealed by staining with nitrazine yellow. Histology showed that the erosions were follicular and limited to the epidermis. The test was highly reproducible and repeatable. We demonstrated the usefulness of the test in the following ways: (1) the erosion time increased with aging, correlating with a thickened horny layer; (2) as few as five Scotch tape strippings greatly decreased the erosion time, although transepidermal water loss was only slightly increased; (3) slight damage to the horny layer by a 24-h exposure to 0.01% sodium lauryl sulfate sharply reduced the erosion time; (4) the erosion time decreased after daily open applications for 3 weeks of clobetasol propionate, corresponding to the thinned horny layer; (5) daily applications of petrolatum increased the erosion time. This new version of the alkali resistance test, renamed the sodium hydroxide erosion assay, promises to be a useful tool for studying the horny layer barrier in healthy and diseased skin.

The development of hand eczema is a relatively commonly seem dermatosis in housewives. In 1986 we presented a first survey of potential contact dermatitis sources for a housewife. Now, we present an update in which we analyse the different contact sources in the household and grade them in comparison to the data of 1986. The results are based on the analysis of a large population of 2633 patients with the occupation "housewife" and the diagnosis "eczema" who have been seen in departments of dermatology belonging to the Information Network of Departments of Dermatology (IVDK).

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases which play key roles in extracellular matrix remodeling, connective tissue damage, inflammation and cell proliferation in a variety of tissues. Since MMP inhibitors have been recently shown to decrease proliferation of vascular smooth-muscle cells, and to prevent neutrophil infiltration in response to alkali burns, we sought to determine whether MMPs play a role in the pathogenesis of inflammatory or hyperproliferative skin disorders. The effects of a specific MMP inhibitor and its analogues on phorbol dibutyrate (PdiBu)-induced inflammation and epidermal hyperplasia in murine skin were assessed. Topical GM 6001, a hydroxamic acid analog with potent inhibitory activity against several MMPs, markedly inhibited PdiBu-induced increases in both ear thickness and ear punch-biopsy weight in a dose-dependent manner 30 h after topical application of PdiBu. Maximal inhibition (75%) was obtained at a dose of 100 micrograms/cm2 (P < 0.01). Moreover, histologic analysis revealed that GM 6001 decreased both the inflammatory cellular infiltrates and epidermal hyperplasia induced by PdiBu. Whereas similar results were found for GM 1489, an analog of GM 6001, acetohydroxamic acid, containing the critical metal ligand group but without the amino acid side chains necessary for binding to the MMPs, did not alter the response to PdiBu inflammation/hyperplasia. These results show that the MMP inhibitors, GM 6001 and GM 1489, are effective in reducing both the inflammatory and hyperproliferative responses that occur following topical phorbol ester application, suggesting a potential role for MMPs in cutaneous inflammatory dermatoses. Moreover, the delivery of this class of inhibitors across intact stratum corneum implies that MMP inhibition could provide an approach to the topical treatment of inflammatory dermatoses.

Dermatologic disorders of the stump in patients with a leg amputation may have characteristic pathophysiologic and clinical features. A knowledge of these factors may lead to earlier diagnosis and avoid immobilization. There ist no German language review of this aspect of dermatology. After providing an overview of the problem, including a discussion of prostheses, we review the following problems: mechanically induced blisters, follicular keratoses, epidermoid cysts, stump edema syndrome, acroangiodermatitis (pseudo-kaposi sarcoma) and verrucous hyperplasia.

Juvenile papular dermatosis is characterized by hypopigmented lichenoid flat papules with predilection for the dorsa of the hands, the elbows and the knees. The disease affects children in the summer months. Changes observed in biopsy specimens show hyperkeratosis, a moderate degree of acanthosis and a lymphocytic perivascular infiltrate in the upper dermis. The pathogenetic influence of such rough materials as sand and wool and of photosensitivity in atopic patients is suggested. We report on a 9-year-old boy who developed lesions of juvenile papular dermatitis (especially severe on the face and the back of the knee) and extreme pruritus for the first time in summer 1994.

In the course of a cohort study addressing the importance of constitutional and occupational risk factors for the development of irritant hand eczema, 859 hairdressing apprentices were examined in 14 vocational training schools in autumn 1993, after an average of 8 weeks of professional exposure. In this cross-sectional survey at the start of training, 38.2% were suffering from skin damage, in most cases mild to moderate and only rarely severe; we observed almost exclusively irritant skin damage, mostly localized interdigitally. Logistic regression analysis revealed previous hand eczema, an elevated ¿atopy score¿ (Diepgen) and, particularly, unprotected work for several hours daily with wet hands as significant risk factors for this early onset irritant damage/eczema. The high wet workload is mainly caused by very frequent shampooing and by permanent waving without wearing gloves; however, other tasks are also often performed without appropriate protective gloves. The implications of the considerable inter-observer variability are described and discussed.

Several integrin heterodimers such as alpha 2 beta 1, alpha 6 beta 4 and alpha v beta 5 are expressed on basal keratinocytes of the epidermis. Because overexpression of these integrins as well as induction of the intercellular adhesion molecule-1 (ICAM-1) have been found in inflammatory dermatoses, we sought to determine whether these modulations could be used as markers of skin irritation. In normal epidermis, topical application of 1% sodium dodecyl sulphate (SDS) for 24 h caused an upregulation of alpha 3, beta 1, alpha 6, beta 4, alpha v, beta 5 and to a lesser extent alpha 2 integrin chains as well as an induction of ICAM-1. To investigate whether these parameters could also be used for evaluation of skin irritancy in vitro, SDS was applied for 24 h to reconstructed epidermis on de-epidermized dermis (RE-DED). In RE-DED, integrin overexpression and aberrant alpha 5 expression was seen under normal in vitro culture conditions and topical application of SDS caused only marginal additional upregulation. We could not detect any ICAM-1 reactivity on either normal or irritated RE-DED. Our results demonstrate that the modulation of integrin and ICAM-1 expression can be used as markers of irritation of the epidermis in vivo, but not in vitro.

Healthy volunteers (n = 14, age range 20-31 years, mean 23) were irradiated on the inside of the left forearm on four consecutive days with their individual minimal erythemal dose of ultraviolet B (UVB) prior to sensitization in the same skin area with a 2% solution of diphenylcyclopropenone (DPCP). The reaction patterns were compared with 14 alopecia areata patients (age range 16-69 years, mean 40) starting topical immunotherapy with DPCP, sensitized without prior UVB treatment. Primary allergic reactions occurred in ten volunteers and in four alopecia areata patients. Patch testing on the upper back with serial dilutions of DPCP (1% to 10(-8)%) showed minimal dermatitis-eliciting concentrations ranging from 1 to 10(-4)% (mean 0.19%) in the volunteers as compared with 10(-1) to 10(-8)% (mean 0.025%) in the alopecia areata patients. Two patterns were discernible within the volunteers with respect to the intensity of the primary allergic and elicitation reactions. Ten volunteers reacted in a similar way to the alopecia areata patients, whereas four probands demonstrated very high minimal dermatitis-eliciting concentrations and overall less severe reactions. The DPCP-specific T-cell response using blood macrophages and B lymphocytes as antigen-presenting cells was measured in an in vitro assay in two alopecia areata patients and two volunteers having similar skin reactions as well as in two volunteers with overall less severe skin reactions. B lymphocytes from the alopecia areata patients and the volunteers with similar skin reactions induced a significant DPCP-specific T-cell proliferation exceeding the responses obtained using macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Recently, high-dose UVA-1 therapy (340-400 nm) was introduced as an effective treatment of severe exacerbated atopic dermatitis. Since the target of this type of radiation in the skin is not known we investigated using the mouse model whether surface markers of the antigen-presenting function of epidermal Langerhans cells are affected by UVA-1 radiation. Even repeated high doses of UVA-1 radiation (up to 50 J/cm2) had no detectable effect on surface ATPase activity and Ia antigen expression on Langerhans cells. Also, the contact allergen oxazolone was presented normally in skin treated with UVA-1 radiation. In contrast, if the mice were injected 1 h before irradiation with 8-methoxypsoralen a dramatic reduction in ATPase activity and Ia antigen expression on Langerhans cells was observed and the induction of contact sensitivity was suppressed (PUVA effect). These results show that epidermal Langerhans cells are not impaired either in structure or function and that these cells probably do not represent the primary target of UVA-1 radiation in the skin. No side effects resulting from a diminished Langerhans cell function should result from high-dose UVA-1 therapy.

In spite of some unsolved questions, an influence of orally ingested nickel on some forms of chronic eczema is generally accepted. In cases of chronic relapsing dermatitis with typical location, positive nickel patch test and positive oral nickel challenge, a nickel-restricted diet may be recommended for a limited period of time. Regional nutritional habits should be considered in the design of diets. Indications, practice and evaluation criteria for oral nickel challenge and nickel-reduced diets are described.

In 121 patients, 26 substances of a standard test battery were applied symmetrically on both sides of the upper back. The Finn chamber on Scanpor was the test system used, the final reading being taken on day 3 or 4. Of 166 tests, 131 were positive on both sides. Test substances and patients age had no influence. In comparison with the results in the literature, ours show a good reproducibility of 78.9%. Doubtful reactions (?+) were difficult to evaluate. These reactions deserve future research.

Loss of earning capacity caused by skin diseases frequently has to be assessed by accredited dermatological experts. Assessments must take account of the appropriate legal situation in each case. Each case needs to be carefully and individually evaluated; tabulated estimations can only be used as a basis.

Since alterations of epidermal Langerhans cells (LC) have been observed in humans infected with HIV, we investigated the morphology and function of these cells in murine acquired immunodeficiency syndrome (MAIDS), a murine model closely resembling human AIDS. The number as well as the shape of dendritic MHC class II+ cells from ear skin of C57BL/6 mice were similar in normal and infected animals. In mixed epidermal cell (EC) lymphocyte cultures, EC from infected mice and from normal mice stimulated allogeneic T cell proliferation to the same extent. In contrast to T cells from normal mice, however, T cells from infected mice did not respond to allogeneic spleen cells, confirming the presence of a T-cell defect in MAIDS. Subcutaneous injection of syngeneic mice with trinitrophenyl-modified MAIDS EC resulted in delayed ear swelling responses after challenge that were equivalent to those induced by hapten-modified EC from normal mice, suggesting that the contact sensitivity inducing potential of MAIDS LC was preserved. To investigate antigen presenting and processing function, EC and spleen cells were tested with the ovalbumin-specific IAb-restricted T cell hybridoma BO.17.10 and either ovalbumin 323-339 peptide or intact ovalbumin protein. MAIDS spleen cells had a reduced antigen presenting capacity compared with normal spleen cells, whereas EC from these mice showed the same processing and presenting capacity as normal controls. In summary, our results demonstrate that the frequency, morphology, level of MHC class II antigen expression and ability to process and present antigen is normal for LC from mice with MAIDS whereas the function of splenic T cells and APC from infected mice is significantly impaired.

Preservatives have come under fire due to their possible detrimental properties and the high rate of contact allergies some of them cause. Therefore, the pharmaceutical industry is searching for alternatives that will be effective, safe and economical. The present paper introduces a selection of new or revived biocides (Kathon CG, benzisothiazolinone, Euxyl K 400, Biobans, Grotans, Bronopol, Germall II), and the range of application and the sensitization potency of each are discussed. Test concentrations for patch tests are recommended. Kathon CG is the most commonly used preservative among these biocides, although it has a high sensitization potency and is a frequently encountered contact allergen. To make discovery of a new allergen easier and to reduce the risk of side effects, manufacturers should be required to specify the ingredients of their products on the labels.

A derivation, more rigorous than hitherto, of the Relative Alkylation Index (RAI) as a quantifier of carrier protein haptenation in skin sensitization tests is presented. It is shown that the RAI, which is a composite parameter made up of dose, reactivity and lipophilicity terms, is likely to require a higher weighting for the reactivity term in the case of non-adjuvant tests than in the case of Freund's adjuvant-based tests. Methyl alkane-sulphonates, RSO3Me with R ranging from n-C6H13 to n-C16H33, were found to be skin sensitizers in a mouse ear swelling test, in agreement with published findings in a guinea-pig adjuvant model. A structure-activity relationship consistent with the published RAI model was observed whereby, in tests at fixed molar induction (0.1 mM) and challenge concentrations (0.025 mM), the level of sensitization response at first increased with increasing chain length of R, then showed a reversal of this trend at the highest chain length (R = n-C16H33). That this is a genuine 'over-load effect', as reported for several other series of compounds examined in guinea-pig adjuvant models, is indicated by the finding that on reducing the induction concentration for the R = n-C16H33 compound the sensitization response was increased. Alkyl and alkenyl methane-sulphonates, MeSO3R (R = n-C12H25, n-C18H37 and R = oleyl) did not give significant sensitization in the mouse ear test. Although they are chemically less reactive than methyl alkanesulphonates, these compounds are reported to be strong sensitizers in guinea-pig adjuvant tests and to fit a common quantitative sensitization-structure-dose relationship with the methyl alkanesulphonates.(ABSTRACT TRUNCATED AT 250 WORDS)

Two female patients developed an allergic contact dermatitis after using Dermatop cream and -ointment for several weeks. Patch tests were positive with the reagent prednicarbate itself. No cross reactions to other glucocorticosteroids were observed. Type-IV-sensitization to glucocorticosteroids should be considered if chronic dermatitis does not improve, or even becomes worse, in spite of adequate therapy. With regard to possible cross reactions or multiple sensitization, epicutaneous tests with other glucocorticosteroids are necessary.

The incidence of propolis contact sensitivity was 1.2-3.3% among 7483 hospital patients during the period 1981-1987, while the prevalence among 1,558 healthy volunteers was 0.64%. A group of 26 patients with contact allergy to propolis was challenged with identified substances isolated from propolis. The mixture of 3-methyl-2-butenylester (3M2B) and 3-methyl-3-butenylester (3M3B) from caffeic acid caused a positive reaction in 7 patients, and in 5 of 9 patients there was a positive reaction to the mixture of 3M2B and 3M3B from diacetyl-caffeic acid. Among the 19 patients challenged with the flavonoid group, 3 had positive reactions, and individual derivatives of cinnamic acid caused positive reactions in 3 and 4 patients each. When five components taken from poplar buds were tested, the one that provoked the largest number of positive reactions was the methanol component (15 of 19 patients). The results show that propolis contact allergy is not caused by one main allergen, but by several allergens varying in chemical composition; the presence of these in propolis depends on the nature of the source plant and the place and time of collection by the bees.

The capacity of interferon-gamma (IFN-gamma) to induce class II histocompatibility antigens on different cell types including keratinocytes, is well known, but the impact of IFN-gamma on the immune response is still unclear. Lewis rats sensitized with dinitrofluorobenzene (DNFB) were injected with recombinant rat IFN-gamma (10(5) U) or phosphate-buffered saline (PBS) once daily on 3 successive days at the bases of the ears either before or after they were challenged on the ears. As expected, the PBS-treated animals showed about a 30% increase in ear thickness and there was an induced expression of class II antigens on the keratinocytes as judged by immunohistochemistry 72 h after challenge. Exogenously added IFN-gamma prior to DNFB challenge resulted in a significantly reduced ear swelling at 24 (p less than 0.01) and 48 h (p less than 0.05) after challenge. In this case the keratinocytes expressed class II antigens already at the time of challenge. When IFN-gamma injections were given during the contact allergic reaction there was no significant reduction of ear swelling until 72 h (p less than 0.01). At that time point there was a more pronounced expression of class II antigens on the keratinocytes compared with PBS-injected animals, due to the IFN-gamma treatment. These in vivo data support our previous observations that IFN-gamma may play a self-limiting role in certain immune responses.

To see whether or not IgE-bearing epidermal Langerhans cells are specific to skin lesions of atopic dermatitis (AD), we performed immunohistochemical and immunoelectron microscopic examinations of dinitro-chlorobenzene (DNCB) contact dermatitis lesions provoked in uninvolved skin of eight patients with AD. In all of the eight examined, IgE-positive epidermal Langerhans cells were observed in the DNCB dermatitis lesions. Typical staining of anti-IgE was absent in the epidermis of normal-appearing skin of five patients with AD. Thus, it is likely that IgE positive epidermal Langerhans cells non-specifically occur in different eczematous diseases provoked in patients with AD.

It is known that the topical application of cyclosporin A (CsA) has a significant suppressive effect on allergic contact dermatitis. In this study, we investigated the effect of topical CsA on toxic (non-allergic) contact dermatitis. Topical CsA significantly suppressed the toxic contact reaction to croton oil. This suppressive effect was short-lived and reversible. Significant inhibition of the reaction to croton oil persisted for 3 days after stopping the CsA. The toxic reaction was blocked when CsA was applied within 6 h of the croton oil application, but when application of CsA was delayed until 12 h after the oil application there was no significant suppressive effect. Topical administration of CsA could become a valuable tool for treating toxic and allergic contact dermatitis without producing the adverse reactions caused by systemic therapy.