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Inhibition of scratching behaviour caused by contact dermatitis in histidine decarboxylase gene knockout mice.

A neuronal system dedicated to itch consists of primary afferent and spinothalamic projection neurons. Histamine is thought to be one of the main mediators for the transmission of itch sensation. However, there are little available information on the role of histamine in scratching behaviour and sensory transmission of atopic dermatitis and chronic eczema. In the present study, the role of histamine in scratching behaviour and neural conduction of sensation in the chronic eczema model was investigated by using l-histidine decarboxylase (HDC) gene knockout mice lacking histamine. The chronic contact dermatitis was induced with daily application of diphenylcyclopropenone (DCP) on a hind paw of HDC (+/+) and HDC (-/-) mice for 2 months. The observation of scratching behaviour and the hot-plate test were performed in both mice. Histological studies were performed in the skin and spinal cord tissues. Histological examination revealed that both HDC (+/+) and HDC (-/-) mice displayed the similar extent of inflammatory cell infiltration, hyperplastic epidermis and newly spreading of neuronal processes in the skin tissue. Scratching behaviour was exclusively induced in HDC (+/+) mice, whereas it was barely observed in HDC (-/-) mice. The expression of c-Fos was specifically upregulated in HDC (+/+) mice in lamina I of the spinal dorsal horn following repeated DCP application. Scratching behaviour in chronic contact dermatitis in mice was thought mainly mediated with histamine. The afferent pathway of sensation in chronic contact dermatitis model may connect with the central nervous system through lamina I of the spinal dorsal horn.

Animals↗

Superoxide anion in polymorphonuclear leukocytes of hairless rats suffering from magnesium-deficiency dermatitis.

Clinical and histological studies were made on magnesium-deficiency dermatitis produced on a new strain of hairless rats. Superoxide anion generation in polymorphonuclear leukocytes (PMNs) and the inhibitory effect of some antioxidants and anti-inflammatory agents against the elicited dermatitis were also examined. From the detection of increased superoxide production and effective actions of inhibitors including superoxide dismutase, cepharanthine, 4-4'-diamono-diphenylsulphone and 5,4,11,14-eicosatetraynoic acid (ETYA), it is indicated that superoxide anion or related activated oxygen may be responsible for magnesium-deficiency dermatitis as an inflammatory mediator and that the dermatitis may be related to lipoxygenase metabolites derived from arachidonic acid.

Animals↗

A case of contact dermatitis due to sodium bisulfite in an ophthalmic solution.

We report a case of contact dermatitis due to sodium bisulfite in Tathion eye drops. A 72-year-old woman was treated daily with two solutions including Tathion eye drops for senile cataract for two years and three months. She developed edema, swelling, erythema, and vesicles on her eyelids. Because contact dermatitis due to a topical medication was suspected, patch testing was performed after disappearance of her eruption. A positive reaction to sodium bisulfite in Tathion eye drops was confirmed. Therefore, we diagnosed her eruption as contact dermatitis due to sodium bisulfite. The reaction to sodium sulfite in the next patch testing was negative. To the best of our knowledge, this is the first report from Japan about contact dermatitis caused by this medication.

Aged↗

Itch and atopic dermatitis: an overview.

Itching is the hallmark of atopic dermatitis, and a vicious itch-scratch circle is easily established. Itching and scratching are important factors in the maintenance of symptoms and can have a significant impact on the sufferer's quality of life. The pathophysiology of itch in atopic dermatitis is still not understood. Unlike in urticaria, histamine is not considered to be a major pruritogen in atopic dermatitis. In fact, the peripheral pruritogens and their cellular origin(s) still remain to be identified in this disease. Various treatments are used to relieve the skin inflammation, itching, and scratching in patients with atopic dermatitis, but no specific antipruritic therapy is available. However, several nonspecific therapies can effectively break the vicious itch-scratch circle. The use of topical corticosteroids and emollients and the elimination of individual trigger factors are still first-line measures.

Anti-Inflammatory Agents↗

Changes in the seasonal dependence of atopic dermatitis in Japan.

Although it has been generally accepted that seasonal aggravation of skin symptoms is a basic feature of atopic dermatitis, recent studies have suggested a decrease in the seasonal dependence of the dermatosis in European countries over the past several decades. We examined incidence of seasonal deterioration of atopic dermatitis in Japanese subjects. The study population consisted of 682 patients aged 3 to 30 years with atopic dermatitis, who visited our outpatient clinic from August 1998 through July 2000. Of these, 452 (66%) showed a seasonal aggravation of skin symptoms, and 230 (34%) had perennial deterioration. The overall incidences of exacerbation in spring, summer, autumn and winter were 25%, 19%, 11% and 36%, respectively. Further, 358 (52%) showed unpredictable and irregular exacerbations of skin symptoms every few days or weeks. These irregular worsenings were more frequent in patients who showed perennial deterioration than in those with seasonal aggravation. From a comparison of the present results with those reported in the 1960s, it became evident that a real decrease in the incidence of seasonal aggravation of atopic dermatitis has occurred over the past three decades in Japan and that the incidence of summer deterioration has greatly decreased during the same period of time.

Adolescent↗

Role of foods in irregular aggravation of atopic dermatitis.

Although it is well known that patients with atopic dermatitis often show unpredictable, irregular aggravation of skin lesions, there are no previously published studies examining trigger factors for such unpredictable aggravation. We investigated whether foods play a role in the unpredictable, irregular worsening of atopic dermatitis. The patient group included 195 Japanese adult patients with atopic dermatitis who showed unpredictable, irregular aggravation of skin lesions. They were hospitalized and openly challenged with suspected foods. Photographs of representative skin lesion sites were taken at baseline and before and after the challenge. Challenge-positive foods were determined by evaluating the comparable before-after challenge photographs. One to three (average: 1.7) challenge-positive foods were confirmed in 86 (44%) of the 195 patient examined. Predominant offending foods were chocolate, cheese, coffee, yogurt and some Japanese foods such as glutinous rice cake, soy sauce and fermented soybeans. Specific IgE values to the offending foods were mostly negative. Patients were asked to exclude challenge-positive foods from their diets. They were then discharged and followed up for 3 months at our outpatient clinic. Exclusion of the offending foods for 3 months brought about a progressive improvement of the disease. These results suggest that foods play an important role in unpredictable, irregular aggravation of skin lesions in patients with atopic dermatitis.

Adolescent↗

Bicentre experience in the treatment of severe generalised atopic dermatitis with extracorporeal photochemotherapy.

Pilot studies have shown an improvement of atopic dermatitis in approximately 65% of patients during extracorporeal photopheresis (ExP) therapy. The purpose of the present clinical trial was to investigate the response to ExP by controlling clinical and laboratory parameters during short term ExP therapy in patients with severe generalised atopic dermatitis. Thirty-five patients with severe, therapy-resistant atopic dermatitis were treated with ExP in an open clinical trial at two week intervals over a period of 6 to 10 cycles. Disease activity was measured before each cycle by SCORAD index together with a standardized protocol for blood samples. ExP led to a significant decrease (p < 0.05) in SCORAD from 74.4 +/- 15.5 before to 36.8 +/- 16.8 after ExP therapy (mean 10 cycles). Approximately 70% (24/33 patients = responder) of patients had a favourable response to ExP requiring at least 6 cycles. The decrease in SCORAD was accompanied by a significant decrease of eosinophil cationic protein (27%), sE-selectin (37%) and sIL-2R (53%) levels in serum (p < 0.05). No significant correlation between a decrease in these levels and values of blood eosinophils or lymphocytes was found (p > 0.05). In comparison to responders, most non-responders were characterised by very high levels of total IgE before and during therapy (p < 0.05). The present clinical trial confirms that short term ExP is an effective treatment for certain patients with severe atopic dermatitis based on anti-inflammatory mechanisms. Total IgE could be a predictor of outcome in ExP treatment.

Administration, Oral↗

Airborne contact dermatitis from Compsoitae oleoresins simulating photodermatitis.

American ragweed (Ambrosia) dermatitis has an airborne pattern and is caused by lipid soluble oleoresins of pollens. A similar weed dermatitis has been described in India and Australia. The weeds involved were all of the Compositae family and contain sesquiterpene lactones with one common antigenic determinant. This study reports seven Danish patients treated for many years under the diagnosis of photodermatitis, who eventually proved to suffer from Compsoitae oleoresin dermatitis. Probably, Compsitae dermatitis is a world-wide disease, although aften misdiagnosed as has happened in Scandinavia.

Aged↗

Atopic dermatitis and congenital deafness.

In a family with perceptive, non-progressive hearing loss several of the members suffered from atopic dermatitis. The proband had a severe atopic dermatitis and an extremely high IgE value. Some of the family members suffered from atopic dermatitis, others from deafness, and some from both diseases. The co-existence of these two disorders has been previously described in two families. Atopic dermatitis and perceptive, non-progressive congenital deafness might be genetically associated.

Adolescent↗

Dermatitis herpetiformis and Sjögren's syndrome.

Two patients are described with dermatitis herpetiformis and Sjögren's syndrome. The increased incidence of autoantibodies in dermatitis herpetiformis would suggest that this association is significant. Antinuclear antibodies commonly occur in dermatitis herpetiformis (Seah et al,, 1971) yet are rarely associated with autoimmune disease in these patients (Moncada, 1974). This report records two patients with dermatitis herpetiformis and Sjögren's syndrome.

Aged↗

Dermatitis artefacta induced in a patient by one of her multiple personalities.

A young woman suffered for 5 weeks with an inexplicable, severe dermatitis limited to her left arm. During hospitalization it was found that she had multiple personalities, one of whom had been applying the leaves of the poison ivy plant each night to her left arm, using 'his' gloved right hand. The factitial nature of the dermatitis was further documented by the fact that when the 'responsible personality' was cut off from supplies of poison ivy in the hospital, 'he' produced factitious haematomas by trauma to her left hand. Although this appears to be the first report of dermatitis artefacta associated with the multiple personality disorder, it is suggested that psychiatric study of other dermatitis artefacta patients might reveal the presence of unsuspected occult multiple personalities, responsible for skin lesions that patients cannot explain.

Adult↗

The response of seborrhoeic dermatitis to ketoconazole.

A randomized double-blind placebo-controlled cross-over study was made of ketoconazole 200 mg daily in nineteen patients with seborrhoeic dermatitis. All had scalp lesions and sixteen had seborrhoeic dermatitis at other sites. Responses were measured by clinician and patients independently, using a linear analogue scale. Body and scalp lesions and itch regressed considerably and significantly with ketoconazole in all but five patients, three of whom subsequently responded to a higher dose. The patients studied with seborrhoeic dermatitis had been sent by their family doctors in answer to a request for patients with dandruff, and the clinical difference between the two was found to be only of degree. Three patients with dandruff without erythema were studied separately using the same study design: all three responded similarly to those with seborrhoeic eczema. It is concluded that Pityrosporum yeast infection is the immediate cause of seborrhoeic dermatitis and that dandruff is its mildest manifestation.

Adolescent↗

Vitamin A in skin and serum--studies of acne vulgaris, atopic dermatitis, ichthyosis vulgaris and lichen planus.

The concentrations of vitamin A and total carotenoids were measured in serum and skin of 61 patients with acne vulgaris, atopic dermatitis, ichthyosis vulgaris or lichen planus, and compared with those in 37 healthy subjects. The mean serum concentrations of retinol and retinol-binding protein were significantly decreased in patients with acne (P less than 0.01) and slightly increased in those with ichthyosis (P less than 0.05), but were otherwise normal. Serum carotenoid levels did not differ between patients and controls. Superficial shave biopsies from both involved and uninvolved skin were examined for the presence of retinol (vitamin A1), dehydroretinol (vitamin A2) and total carotenoids. The mean retinol concentration was increased in lichen planus lesions (P less than 0.05) and decreased in both acne skin (involved and uninvolved) and in lesions of atopic dermatitis (P less than 0.05). The mean dehydroretinol concentration was markedly increased in lesions of atopic dermatitis and lichen planus (P less than 0.01). No consistent abnormalities were found in skin of patients with ichthyosis vulgaris. The mean carotenoid concentration in the patients' skin did not differ significantly from that in the controls. The reduced retinol level in the skin of acne patients is probably explained by diminished supply of vitamin A from the blood. The abnormal ratio of retinol to dehydroretinol in lesions of lichen planus and atopic dermatitis is possibly due to changes in cutaneous vitamin A metabolism associated with epidermal hyperproliferation and inflammation.

Acne Vulgaris↗

Cyclosporin A in severe, therapy-resistant atopic dermatitis: report of an international workshop, April 1993.

Data on the use of oral cyclosporin A (CyA; Sandimmun) therapy for severe adult atopic dermatitis have accumulated since 1987. Details of over 200 adult patients who have received short-term CyA were presented at an international workshop in April 1993. Eighty-six of these patients had participated in three randomized, double-blind, placebo-controlled studies in which CyA was given for 6-8 weeks. The efficacy and safety of short-term CyA treatment in atopic dermatitis is established, provided that appropriate guidelines are observed. Evidence to date suggests that atopic dermatitis patients are no more prone to toxicity than patients with psoriasis, in whom more detailed and longer-term data are available. Early data also suggest that long-term CyA may be effective in atopic dermatitis, but there is concern regarding long-term safety, as experience is still limited. Careful monitoring of all CyA-treated patients is therefore mandatory. CyA should only be used under the direct and regular supervision of a hospital-based dermatologist who is knowledgeable in the use of cyclosporin A, and experienced in the management of severe skin disease and in the use of potentially toxic drugs.

Adult↗

25 years' experience of a gluten-free diet in the treatment of dermatitis herpetiformis.

Gluten-free diets have been used in the treatment of patients with dermatitis herpetiformis in our department since 1967. Of the 212 patients with dermatitis herpetiformis attending between 1967 and 1992, 133 managed to take the diet, and 78 of these achieved complete control of their rash by diet alone. Of the remaining 55 patients taking a gluten-free diet, all but three were taking partial diets; over half of these patients managed to substantially reduce the dose of medication required. Of the 77 patients taking a normal diet, eight entered spontaneous remission, giving a remission rate of 10%; a further two patients who had been taking gluten-free diets were found to have remitted when they resumed normal diets. Loss of IgA from the skin was observed in 10 of 41 (24%) patients taking strict gluten-free diets. These patients had been taking their diets for an average of 13 years (range 5-24 years), and their rash had been controlled by diet alone for an average of 10 years (range 3-16 years). The advantages of a gluten-free diet in the management of patients with dermatitis herpetiformis are: (i) the need for medication is reduced or abolished; (ii) there is resolution of the enteropathy, and (iii) patients experience a feeling of well-being after commencing the diet. Thus, we propose that a gluten-free diet is the most appropriate treatment for patients with dermatitis herpetiformis.

Adolescent↗

Irritant susceptibility and weal and flare reactions to bioactive agents in atopic dermatitis. I. Influence of disease severity.

The two main pathogenetic characteristics of atopic dermatitis (AD) are: (i) antigen-dependent 'specific' reactivity, and (ii) altered non-immunological 'non-specific' reactivity. Our understanding of the role of non-specific reactivity is hampered by the fact that methods available for its quantification are limited. The aim of the present study was to assess the usefulness of two parameters as quantitative measures of non-specific skin reactivity in AD: (i) susceptibility to repeated epicutaneous exposure to an irritant (sodium lauryl sulphate, SLS), assessed by visual scoring and transepidermal water loss (TEWL) measurement, and (ii) reactivity to intracutaneously injected bioactive agents (codeine, FMLP, histamine, methacholine, substance P, trypsin), assessed by measurement of weal and flare size. These two parameters were tested in a group of AD patients, subdivided according to the severity of their dermatitis, and a control group. The visual score and TEWL after SLS exposure tended to be higher in the AD group than in the control group. Furthermore, visual score and post-exposure TEWL were positively correlated with the dermatitis severity score. Weal size following injection of codeine, histamine and substance P, and flare size following injection of all agents, except methacholine, were significantly lower in the AD group than in the control group. Negative correlations were found between weal and flare sizes and the dermatitis severity score. These findings can be explained by down-regulation of structures involved in weal and flare reactions. In conclusion, we propose that epicutaneous irritant susceptibility and reactivity to intracutaneous bioactive agents may be useful indicators of non-specific skin reactivity in AD.

Adolescent↗

A protocol for recording the sign of flexural dermatitis in children.

The presence of visible flexural dermatitis is a key feature in diagnosing atopic dermatitis. We describe a protocol for recording this sign in population-based studies, which could be used by suitably trained non-dermatologists. The protocol was developed using a standard set of photographs and accompanying instructions, which define the terms 'dermatitis' and 'flexural'. When assessed during a survey of skin disease in primary schoolchildren, there was excellent agreement between a trained nurse and a dermatologist with regard to the presence or absence of this sign in 73 consecutive children, with perfect agreement in 71 children (97%), and a chance corrected agreement index (kappa statistic) of 0.90 (95% confidence interval [CI] 0.77-0.99). Agreement between two nurses on 114 consecutive schoolchildren was not quite as good, with perfect agreement in 102 children (90%), and a kappa value of 0.51 (95% CI 0.26-0.77). The protocol is easy to perform, does not require children to undress, takes < 1 min to carry out, and is highly acceptable to children and staff. This protocol may be useful in standardizing the assessment of atopic dermatitis in population studies of children.

Child↗

Activated immunocompetent cells in human skin lymph derived from irritant contact dermatitis: an immunomorphological study.

By means of microsurgical lymph cannulation, skin lymph was sampled in the course of a sodium lauryl sulphate (SLS)-induced irritant contact dermatitis in human volunteers. The lymph cells were isolated by centrifugation, and then characterized immunocytochemically using different monoclonal antibodies, and in the late phase of the skin reaction also by electron microscopy. Analyses of lymph cells before the induction of the contact dermatitis revealed median values of about 60% T cells (CD4/CD8 ratio about 2:1), 4% Langerhans cells (LCs), and 1% B cells. The remainder were varying proportions of erythrocytes and uncharacterized cells. During the skin reaction, and even after resolution of the clinical signs of dermatitis, a relative and absolute increase of T and B cells, as well as of HLA-DR positive cells, paralleled the previously reported increased of LCs; a high percentage of the T cells were CD4 and CD8 negative. In addition, surface markers such as CD11a, CD25, CD54 and CD58 were detected on lymph cells sampled during the irritant skin reaction. Cell rosettes observed in the lymph throughout the experiment were analysed in the late phase of the skin reaction, and showed a central LC with three to five peripheral, in part activated, T cells, ultrastructurally revealing gap junction-like structures between the two cell types. These data indicate that immunocompetent cells in the skin are activated by a variety of non-immunological stimuli such as operative trauma and irritant contact dermatitis.

Adult↗