Serotonin in human allergic contact dermatitis. An immunohistochemical and high-performance liquid chromatographic study

Abstract Allergic contact dermatitis (ACD) is a common clinical condition leading to considerable morbidity. We have recently demonstrated that ketanserin, a serotonin antagonist, significantly inhibits nickel sulphate-induced ACD. Furthermore, serotonin-immunoreactive (IR) cells have previously been demonstrated in normal human cutaneous melanocytes. To further elucidate the role of serotonin in cutaneous contact hypersensitivity, we compared ACD involved skin and uninvolved skin from nickel-allergic patients, and normal skin from healthy volunteers, for the presence of serotonin-like immunoreactive cells using immunohistochemistry. In addition, serotonin concentrations in ACD involved and uninvolved skin were compared by high-performance liquid chromatography (HPLC). In the skin of normal healthy volunteers, the serotonin-IR cells were situated in the basal layer of the epidermis. In uninvolved skin the cells were also situated in the basal layer, but they were more numerous and the immunofluorescence intensity was greater. In involved skin, the IR cells were fewer and they were found higher up in the epidermis. Also, the configuration of these cells was different: they showed enlarged and elongated dendrites as well as dendritic spines. The serotonin antiserum-labelled cells in ACD involved skin were also NKI-beteb positive (the latter is known as a reliable marker of melanocytes). The concentration of serotonin in involved skin was significantly higher than that in uninvolved skin in ACD patients (P < 0.05). Taken together, our previous and present results indicate that serotonin plays an important role in ACD. The basal epidermal serotonin-IR cells are more dendritic in ACD, and are found more superficial in the epidermis, where they might release their content of serotonin, thereby influencing the inflammatory process. Received: 7 July 1997 / Received after revision: 16 December 1998 / Accepted: 22 December 1998     

Methyldibromoglutaronitrile in rinse-off products causes allergic contact dermatitis: an experimental study

BACKGROUND: The frequency of sensitivity to the cosmetic preservative methyldibromoglutaronitrile (MDBGN) has increased significantly in Europe. Most cases of allergic contact dermatitis from MDBGN are caused by leave-on cosmetic products. The risk of developing allergic contact dermatitis from rinse-off products has been less studied. OBJECTIVES: To investigate the allergic response elicited in presensitized individuals from exposure to a rinse-off product preserved with the maximum permitted level of MDBGN. METHODS: Nineteen contact allergic individuals and nine controls participated in a double-blind, randomized repeated open application test (ROAT) using two coded liquid soaps with and without MDBGN. Areas of 50 cm2 on the lower arms were washed with the soaps twice a day for up to 28 days; two of the subjects continued for 34 days. The subjects were also patch tested with a dilution series of MDBGN to determine their patch test threshold values. RESULTS: Seven presensitized individuals (37%) developed allergic contact dermatitis from the soap containing MDBGN. The mean dose of MDBGN per application was 2.2 micro g cm-2 and the reactions appeared between days 6 and 34. All nine controls had negative ROATs. The difference in reactivity between test subjects and controls was significant (one-sided Fisher's exact test, P = 0.04). Patch test threshold values ranged from < 0.001% to 0.2% MDBGN in ethanol/water. CONCLUSIONS: This study shows that the exposure to a rinse-off product containing the maximum permitted level of MDBGN can easily elicit an allergic response in presensitized individuals. Along with reported cases of induction and elicitation caused by MDBGN in rinse-off products the study indicates that the permitted level of MDBGN in rinse-off products is too high. We recommend that this level should be re-evaluated.     

Alcohol dermatitis: allergic contact dermatitis and contact urticaria syndrome

In spite of not knowing the numbers of people exposed and obviously incomplete reporting, the known mechanisms of alcohol cutaneous intolerance and the literature classified according to mechanisms are listed. Testing techniques for delayed- and immediate-types are proposed.     

An immunohistochemical analysis of cytokine expression in allergic and irritant contact dermatitis

The purpose of this study was to investigate whether the specific and non-specific inflammatory responses to allergens and irritants give rise to immuno-histochemical detectable differences in the cytokine profile in the skin. Skin biopsies taken at 0, 6, 24 and 72 h from contact allergic reactions to nickel and from irritant reactions to sodium lauryl sulphate were analysed. The main finding was that the dermal cells expressed similar patterns of cytokines (IL-1alpha, IL-1beta, IL-2, IL-4, IL-6 and IL-10) in both types of contact reaction at 72 h. However, two differences were observed. Staining for the IL-1 receptor antagonist was more prominent in the dermis at the late stages of the allergic reaction compared with the late stage of the irritant reaction. The other difference was an increased interferon-gamma staining of infiltrating mononuclear inflammatory cells in the dermis in the sodium lauryl sulphate group compared with the nickel group. A more rapid general onset of cytokine production was found in the sodium lauryl sulphate group than in the nickel group. The main conclusion of this study was that after 6 h the cytokine patterns did not differ between the specific and the non-specific inflammatory responses in the skin.     

The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study

BACKGROUND: While many studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of atopic dermatitis (AD), only a few have investigated the effects of tacrolimus on inflammatory cells and their cytokine gene expression in patients with AD. OBJECTIVES: To characterize further the immunophenotype of infiltrating cells and the production of certain cytokines before and after treatment with topical tacrolimus and hydrocortisone butyrate. METHODS: Nine adult patients with moderate to severe AD were treated with tacrolimus ointment, while seven control patients were treated with hydrocortisone butyrate ointment. We performed lesional skin biopsies before and after treatment. These were stained immunohistochemically with a panel of monoclonal antibodies including those to CD1a, CD3, CD4, CD8, myeloperoxidase, EG1, EG2, tryptase, interferon-gamma, interleukin (IL)-4, IL-5, IL-12, IL-13, receptors for CXC chemokines (CXCR) 3 and 4, and receptor 3 for CC chemokines. RESULTS: CD3+, CD4+ and CD8+ lymphocytes, and eosinophil and neutrophil granulocytes were significantly reduced in post-treatment tacrolimus specimens, while CD1a+ cells and mast cells were not. The expression of cytokines and chemokine receptors tested, except for CXCR3, was diminished by tacrolimus treatment. Moreover, tacrolimus produced a greater reduction of lymphocytes, eosinophils and most cytokines than that induced by hydrocortisone butyrate. CONCLUSIONS: Tacrolimus not only inhibits T-lymphocyte proliferation and cytokine production, but also plays an important role in the IL-12-induced shift from a T-helper (Th) 2 to a Th1 cytokine profile that characterizes the development of chronic AD. Tacrolimus also demonstrates wider pharmacodynamic effects than hydrocortisone.     

Skin occlusion and irritant and allergic contact dermatitis: an overview

Occlusion, widely used to enhance percutaneous absorption of drugs, also increases penetration of other chemicals and antigens, and hence may exacerbate irritant and allergic contact dermatitis. This overview summarizes the adverse effects of occlusion.     

Occupational allergic contact dermatitis is more prevalent than irritant contact dermatitis: a 5-year study

BACKGROUND: Irritant contact dermatitis is thought to be the leading cause of occupational skin disease in the United States. Recent reports suggest otherwise. OBJECTIVES: The purposes of this study were to determine the prevalence of allergic and irritant forms of occupational contact dermatitis in the population seen at a Midwestern dermatologic referral clinic, report professions commonly affected by occupational skin disease, and indicate which substances are frequent allergens. METHODS: A retrospective analysis of patch test data collected at the University of Kansas between 1994 and 1999 was performed. RESULTS: Of 537 patients who underwent patch testing, 135 (25%) had occupational skin disease. Allergic contact dermatitis affected 81 (60%) patients, and irritant contact dermatitis was found in 46 (34%). Health care professionals, machinists, and construction workers accounted for nearly half of all patients with occupational skin disease. Nickel sulfate, glutaraldehyde, and thiuram mix were the most common allergens. CONCLUSION: Patch tests with a wider array of allergens than those currently available in the United States are needed to prevent misdiagnosis of occupational contact dermatitis.     

Clonidine: irritant and allergic contact dermatitis assays

Clonidine in petrolatum, clonidine transdermal device, and its placebo device were assayed for relative irritancy potential (21-day cumulative irritancy assay) and allergic contact dermatitis potential (Draize repeat insult patch test assay). Both clonidine in petrolatum and the clonidine transdermal device appear to be of minimal irritancy potential. Only the clonidine device demonstrated, in the Draize assay (and in clinical trials), allergic contact dermatitis potential. Its relatively delayed onset of demonstration of allergic contact sensitization in clinical trials requires investigation as to mechanism.     

Occupational allergic contact dermatitis in beauticians

We patch tested 13 beauticians with hand dermatitis between 1982 and 1986. They were all young female novice beauticians or those in training. The onset of their allergic dermatitis was noticed within 1 month to 1 year of their starting this occupation. Definite positive reactions to products were seen from hair dyes (as is, open test) (6/12), cold permanent wave primary solutions (as is, open test) (7/13) and a shampoo (1% aq., closed test) (1/13). Positive reactions to allergens were seen with para-phenylenediamine (1% pet) (12/13), ammonium thioglycolate (5% aq., open test) (3/7), para-toluylenediamine (1% pet) (7/9), para-aminophenol (1% pet) (1/4), ortho-aminophenol (1% pet) (1/4), Quinoline yellow SS (0.5% pet) (1/4), nickel sulfate (2.5% pet) (1/12), cobalt sulfate (2.3% pet) (1/12), thimerosal (0.05% pet) (1/12) and procaine hydrochloride (1% pet) (1/12). Study of the prognosis showed that 5 out of 12 cases could continue their occupation, but 4 cases had persistent hand dermatitis despite protecting their hands from hair dyes with gloves, 7 cases quitted their jobs, and in 5 their hands healed while 2 cases continued to have atopic hand dermatitis. A personal or family history of atopy was frequent among the cases, so we recommend that those who have such a history should not become beauticians.     

Structure-activity relationships in allergic contact dermatitis

Primin (2-methoxy-6-pentyl-1,4-benzoquinone)is a naturally-occurring strong sensitizer from Primula obconica (Primulaceae), To determine the effect of side-chain length on senstizing potency 15 analogues with linear side chains from to from C₁, to C₁₅ and 4 C₆- analogues with branched side chains were prepared synthetically and devoted to experimental sensitization in guinea pigs The results showed an increase of the sensitizing capacity with increasing length of the alkyl side chain from C₁ to C₁₀, reaching a maximum at C₁₁ and C₁₂. On further elongation the senstizing potency decreased beyond C₁₃ reaching values which finally were as low as those of the C₁ and C₃ derivatives. The results mirror finding which finally were as low as those of the C₁ and C₃ derivatives. The results mirror findings which formerly have been obtained with other non-quinonoid compounds like catechols, phenols hydroquinones and gallates. In the plant kingdom. Compound approximating an "ideal allergen" consisting of a quinonoid ring with a 10 or 11 carbon-remarkably strong sensitizer found in Wigandia caracasana (Hydrophyllaceae)