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Treatment of atopic dermatitis and psoriasis vulgaris with bupropion-SR: a pilot study.

OBJECTIVE: To determine whether the antidepressant bupropion may be useful in treating atopic dermatitis and psoriasis in nondepressed patients. METHOD: Ten nondepressed subjects with atopic dermatitis and 10 with psoriasis completed a single-track, open-label treatment protocol with bupropion-SR in doses of 150 mg/day and 300 mg/day, administered sequentially for 3 weeks each, followed by a 3-week wash-out. Treatment response was assessed at the end of each 3-week period. RESULTS: Six of the 10 subjects with atopic dermatitis showed a reduction in affected body surface area by the end of 6 weeks of bupropion treatment, with affected area increasing toward the prestudy baseline in all responders following bupropion discontinuation-a highly significant treatment effect (p =.0003). Of the 10 subjects having psoriasis, improvement over baseline after 6 weeks of treatment was seen in eight subjects, with coverage increasing toward the prestudy baseline in the responders following bupropion discontinuation (p =.001). Average reduction in affected area in the responders at week 6 of treatment was approximately 50% in both groups. CONCLUSIONS: The generally good tolerability and relative safety of bupropion-SR makes a trial of this agent worthwhile in patients with atopic dermatitis or psoriasis who have failed treatment with more conventional medications. Normalization by bupropion of potentially causative neuroendocrine, immunologic, or catecholaminergic abnormalities in both of these dermatologic disorders is a possible mechanism of action for the observed salutary effects of this drug on our subjects' skin disease.

Adult↗

Skin barrier function in atopic dermatitis.

PURPOSE OF REVIEW: Whereas much investigation in atopic dermatitis has focused upon the adaptive immune response, new data suggest that allergic sensitization may occur secondary to impairment of skin barrier function. RECENT FINDINGS: Two common loss-of-function mutations in the FLG gene encoding filaggrin (an important component of terminal keratinocyte differentiation) are strongly associated with the development of atopic dermatitis and asthma associated with atopic dermatitis. SUMMARY: Genetic defects in skin barrier function should be recognized as major risk factors for the development of atopic dermatitis and asthma.

Child↗

Monocyte phosphodiesterase abnormalities and dysregulation of lymphocyte function in atopic dermatitis.

The immunologic aberrations associated with atopic dermatitis include the paradox of reduced cell-mediated immune responses in the setting of increased cell-mediated immunity features that resemble allergic contact dermatitis. In this review, we present evidence that abnormalities in monocytes and Langerhans cells alter the function of T-helper-cell subpopulations to cause the immunologic defects associated with atopic dermatitis. Increased monocyte prostaglandin E2 production inhibits Th1 responses, accentuating interleukin (IL)-4 secretion by Th2 cells. Elevated prostaglandin E2 secretion correlates with abnormally increased cyclic adenosine monophosphate-phosphodiesterase activity in monocytes and this, along with other defective inflammatory cell responses, can be normalized in vitro by phosphodiesterase inhibitors. It appears that in addition to prostaglandin E2, IL-10 acts to regulate the balance between Th1 and Th2 functional responses accounting for many atopic features, including increased IL-4, IL-5, and IL-6 production by T cells; increased IgE synthesis; decreased interferon-gamma production; and impaired cell-mediated immune responses. All of these abnormalities can be related to increased phosphodiesterase activity in atopic monocytes, and inhibition of this key enzyme appears to reverse atopic dermatitis inflammatory abnormalities in vitro and in vivo.

Animals↗

Atopic dermatitis: recent trends in pathogenesis and therapy.

Emerging concepts in the areas related to the pathogenesis and treatment of atopic dermatitis are reviewed. In particular, recent findings have revealed several key steps in the maintenance of a vicious circle of spongiotic dermatitis associated with elevated T-lymphocyte activation, hyperstimulatory Langerhans cells, defective cell-mediated immunity, and B-cell IgE overproduction. The discovery of specific IgE-binding structures on Langerhans cells provides a mechanism for Langerhans cells to capture and present IgE-targeted allergens to allergen-specific T cells. Furthermore, certain microbial allergens that tend to preferentially elicit IgE-type responses also elicit a T-cell response dominated by the IgE-inducing lymphokine interleukin 4. Repeated stimulation by activated Langerhans cells appears to induce just such a response. Abnormal biochemical responsiveness and mediator release by AD monocytes, mast cells, and eosinophils also participate in the sustainment or initiation of such a vicious circle, and contribute directly to the dermatitis as well. Developments in the areas of neuropeptides, genetics, microbial superantigens, and cytokine networks in the skin also appear to have promise in providing a rational link between immune defects and the inflammatory events in AD. Conventional therapy remains the mainstay of atopic dermatitis management; however, new therapies based upon the above concepts are being tested in clinical trials. Although the difficulty of objectively grading AD lesional activity and the high placebo response of AD patients hampers the interpretation of many reports, several types of approaches are coming into focus. The effectiveness of cyclosporin A, which targets T-cell activation and antigen presentation, indicates that additional agents with such activity should be effective, and verifies the criticality of these cells in AD pathogenesis. Therapy with biologic response modifiers, such as interferon gamma or thymopentin, is oriented toward normalization of imbalanced immune responsiveness, rather than direct suppression of the immune system. The mechanism of action of and toxicities of Chinese herbal mixtures require further investigation, but may reveal hitherto unconsidered avenues. Other recent therapeutic trials have focused on reduction of trigger factors, such as house dust mite exposure, foods, and the abnormal epidermal lipid barrier to irritation.

Dermatitis, Atopic↗

Eosinophil migration in atopic dermatitis. I: Increased migratory responses to N-formyl-methionyl-leucyl-phenylalanine, neutrophil-activating factor, platelet-activating factor, and platelet factor 4.

Eosinophil granular protein deposits have been demonstrated in lesional atopic dermatitis skin. This suggests active tissue infiltration of eosinophils. To find an explanation for the tissue influx of eosinophils, eosinophil migration was studied in vitro by means of a microchemotaxis assay. Eosinophils from the circulation of patients with atopic dermatitis showed an altered capacity to respond to chemotactic stimuli in vitro compared with eosinophils from healthy donors. Eosinophils from patients with atopic dermatitis had significantly increased migratory responses toward dose ranges of N-formyl-methionyl-leucyl-phenylalanine, neutrophil-activating factor, platelet-activating factor, and platelet factor 4. Eosinophils from normal individuals did not respond to N-formyl-methionyl-leucyl-phenylalanine and neutrophil-activating factor and responded only slightly to platelet factor 4. The migratory responses toward tumor necrosis factor-alpha and complement factor C5a were identical in both groups. Interleukin-5, an eosinophil-selective cytokine, is a strong modulator of the migratory responses to these chemotaxins in eosinophils from normal donors. A migratory response toward N-formyl-methionyl-leucyl-phenylalanine and neutrophil-activating factor was induced by interleukin-5, whereas the migratory response toward platelet-activating factor and platelet factor 4 was markedly potentiated. In contrast, the response to complement fragment C5a was only slightly influenced. Our findings indicate that the increased migratory responsiveness of eosinophils from patients with atopic dermatitis to various chemotaxins reflects in vivo "priming" of eosinophils, presumably by circulating cytokines such as interleukin-5. This in vivo "priming" is not optimal because it can be further potentiated by renewed contact with interleukin-5.

Adolescent↗

The effect of an elemental diet with and without gluten on disease activity in dermatitis herpetiformis.

Elemental diets are reported to decrease activity of patients with dermatitis herpetiformis. We tested the hypothesis that gluten, given in addition to an elemental diet, is responsible for the intestinal abnormalities, cutaneous immunoreactant deposition, and skin disease activity in dermatitis herpetiformis. At entry eight patients with dermatitis herpetiformis, who were consuming unrestricted diets, were stabilized on their suppressive medications at dosage levels that allowed individual lesions to erupt. Six patients were then given an elemental diet plus 30 of gluten for 2 weeks, followed by the elemental diet alone for 2 weeks. Conversely, two patients received an elemental diet alone for 2 weeks followed by an elemental diet plus gluten during the final 2 weeks. Small bowel biopsies, skin biopsies, and clinical assessments were done at 0, 2, and 4 weeks. Suppressive medication dose requirement decreased over the 4 weeks by a mean of 66%. Six of eight subjects significantly improved clinically during the gluten-challenge phase of the elemental diet and all were improved at the end of the study. The amount of IgA in perilesional skin did not change significantly, but the amount of C3 increased in five of seven evaluable subjects after gluten challenge. Circulating anti-gluten and anti-endomysial antibodies were not significantly affected by the diets. All subjects completing evaluable small bowel biopsies (seven of seven) demonstrated worsening of their villus architecture (by scanning electron microscopy and intraepithelial lymphocyte counts) during gluten challenge and improvement (six of six subjects) after 2 weeks of elemental dietary intake. We conclude that 1) there is a significant improvement in clinical disease activity on an elemental diet, independent of gluten administration, 2) small bowel morphology improves rapidly on an elemental diet, and 3) complement deposition but neither IgA deposition nor circulating antibody levels correlate with gluten intake. It seems likely that dietary factors other than gluten are important in the pathogenesis of the skin lesions in dermatitis herpetiformis.

Adult↗

Quantitative microbiology of the scalp in non-dandruff, dandruff, and seborrheic dermatitis.

The composition of the scalp microflora was assessed quantitatively in normal individuals and in patients with dandruff and seborrheic dermatitis, disorders characterized by increasing scaling. Three organisms were constantly found: (1) Pityrosporum, (2) aerobic cocci, and (3) Corynebacterium acnes. Pityrosporum (mainly Pityrosporum ovale) made up 46% of the total microflora in normals, 74% in dandruff, and 83% in seborvheic dermatitis. The geometric mean number of organisms per cm-2 in non-dandruff subjects was 5.04 times 10-5; 9.22 times 10-5 in dandruff subjects; and 6.45 times 10-5 in those with seborrheic dermatitis. The cocci were dominantly Baird-Parker type SII and no quantitative or qualitative change occurred in the scaling disorders. C. acnes comprised 26% of the flora on the normal scalp, 6% in dandruff, and only 1% in seborrheic dermatitis. These results differ significantly from previous reports which describe a much more complex microflora and suggest an etiologic role for microorganisms in dandruff.

Apicomplexa↗

Circulating immune complexes of IgA type in dermatitis herpetiformis.

There is some evidence that dermatitis herpetiformis may be mediated by circulating immune complexes. This study attempts to define the antibody class of these complexes. All patients studied demonstrated granular deposition of IgA in the papillary dermis on direct immunofluorescence. Serum immune complexes were detected using the qualitative Raji cell immunofluorescent assay, as well as the quantitative immunoradiometric assay. A group of 25 dermatitis herpetiformis patients was found to have higher levels of IgA containing complexes compared to a group of normals (p < .01). Higher levels of IgG containing complexes were also noted in dermatitis herpetiformis patients at a low level of statistical significance (p < .1). The relationship of these complexes to the pathogenesis of dermatitis herpetiformis is yet to be determined.

Antigen-Antibody Complex↗

Allergic contact dermatitis in the hamster.

Allergic contact dermatitis to strong, low molecular weight contact allergens can regularly be induced in the hamster. By its clinical course, histopathology and susceptibility to intensification with complete Freund's adjuvant, this hypersensitivity appears congruent with the allergic contact dermatitis observed in other experimental animals and the allergic contact dermatitis seen in humans. Further, in the hamster, we find that pretreatment with cyclophosphamide intensifies the acquisition of allergic contact dermatitis to dinitrochlorobenzene and to oxazolone; the target of cyclophosphamide immunopotentiation has been shown in the mouse and guinea pig to be a regulator suppressor cell. In addition, we have induced in the hamster specific immune tolerance to dinitrochlorobenzene with dinitrobenzene sulfonate; in the mouse and guinea pig it has been demonstrated that the induction of specific immune tolerance to contact allergens by parenteral hapten involves the elaboration of specific suppressor cells. These findings, then, imply the existence of regulatory suppressor cells for T-cell phenomena in the hamster. This contrasts with reports that suppressor cell function in hamsters, as against other rodents, is defective as it relates to the regulation of, for instance, allogeneic reactions, antibody formation and tolerance to contact allergens.

Animals↗

Abnormal suppressor cell function in atopic dermatitis.

A status of suppressor cells in patients with atopic dermatitis was studied. As a group, they showed absent concanavalin A-inducible suppressor cell function as measured by proliferative responses to pokeweed mitogen and decreased function as measured by responses to phytohemagglutinin or concanavalin A. Similarly, preincubation in medium enhanced proliferative responses in normal donors but not in atopic dermatitis patients, suggesting an absence of a short-lived suppressor cell population in the latter group. Suppressor cell function correlated negatively with log10 of serum IgE concentrations. Theophylline-sensitive suppressor cell numbers were significantly decreased in atopic dermatitis patients (p less than 0.01). In vitro preincubation of normal lymphocytes with aminophylline or isoproterenol (10 microgram/ml) enhanced subsequent proliferative responses to pokeweed mitogen. In contrast, actual depression was seen with cells from atopic dermatitis patients, suggesting abnormal immunomodulatory effects of these drugs in the disease.

Adolescent↗

The risk of cancer among patients previously hospitalized for atopic dermatitis.

In treatment of severe atopic dermatitis, drugs with carcinogenic potentials are used to manage the disease. We therefore analyzed whether patients having severe atopic eczema had an increased cancer risk. The study population included all individuals hospitalized in Denmark with a primary diagnosis of atopic dermatitis during 1977-1996. Follow-up was conducted in 1996 in the Danish Cancer Register. A total of 6275 persons were included. Among 2030 adult patients, an increased risk of cancer was observed, standard morbidity ratio (SMR)=1.5 (95% CI: 1.2-1.9). Half the excess cases of cancer was keratinocyte carcinomas of the skin diagnosed within the first 9 y of follow-up, SMR=2.4 (95% CI: 1.4-3.9). For men, SMR=2.7 (95%CI: 1.2-5.4). In conclusion, earlier hospitalized adult atopic dermatitis patients had an increased risk of cancer. Half the excess cases of cancer were keratinocyte carcinomas. This may be a result of a detection bias or due to the carcinogenic potentials of some of the therapies of severe atopic dermatitis.

Adolescent↗

Allergic contact dermatitis due to phenylephrine hydrochloride, with an unusual patch test reaction.

2-day (2-D) closed patch tests are often used in daily clinical practice and useful for evaluating the cause of allergic contact dermatitis. However, even when 2-D closed patch tests at appropriate concentrations are performed for suspected allergic contact dermatitis based on clinical findings, positive reactions are not always obtained. Therefore, although the use of the allergen again induces similar symptoms, a definite diagnosis cannot be made in some cases. We report a case of allergic contact dermatitis due to phenylephrine hydrochloride in eyedrops, with an unusual patch test reaction. Although the results of the routine 2-D closed patch test were negative, a definite diagnosis could be made by closed scratch-patch test. In addition, long-lasting allergic patch test reactions were observed at the positive scratch-patch test site for about 3 months. We speculated that these unusual results on patch testing in our case were associated with the degree of percutaneous absorption of causative agents. Therefore, even when 2-D closed patch tests are negative, scratch-patch tests may be indicated for patients in whom clinical symptoms continue strongly to suggest contact dermatitis.

Aged↗

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.

Administration, Topical↗

Peristomal allergic contact dermatitis--case report and review of the literature.

Allergic contact dermatitis (ACD) is a rare cause of peristomal skin problems. Only 23 cases have previously been reported in the literature. We report the case of a colostomy patient with a severe disabling blistering peristomal dermatitis. Patch testing to a British Contact Dermatitis Society standard series, medicaments and a plastics and glues series was negative. Patch testing to the patient's own products gave a positive reaction (+) at D2 and D4 to Dansac soft paste and Stomahesive paste. Further patch testing to the components of Dansac soft paste showed a positive (+) reaction at D2 and D4 to ester of polymethyl vinyl/maleic acid copolymer (Gantrez-ES) only. This is the first reported case of ACD due to Dansac soft paste. ACD to Gantrez has previously been reported but in different products. We also review the other previously reported cases of ACD causing peristomal dermatitis and stress the importance of patch testing in these cases, in particular to the patient's own products, as avoidance of identified allergens can have a large impact on the quality of life.

Allergens↗

Occupational protein contact dermatitis from shiitake mushroom and demonstration of shiitake-specific immunoglobulin E.

Shiitake are popular edible mushrooms all over the world, and eating raw shiitake may lead to relatively common 'shiitake dermatitis' or toxicodermia. Workers involved in shiitake cultivation and marketing have distinct occupational respiratory and skin diseases unrelated to 'shiitake dermatitis'. There are no previous reports of protein contact dermatitis (PCD) from shiitake, and there is only 1 report of shiitake-specific immunoglobulin (Ig) E. We report 2 shiitake growers who developed work-related eczematous eruption on their hands. Both of the patients had small prick test reactions to fresh shiitake, and specific IgE to shiitake was detected in their sera by immunospot. One of the patients had a large prick test reaction to dry shiitake and also a positive wheal reaction to fresh shiitake in an open application test. Neither of the patients had noticed any symptoms of contact urticaria at work. Both of the patients had immediate IgE-mediated allergy to shiitake, and the diagnosis of occupational PCD was made. There are no commercial in vitro tests for shiitake-specific IgE. Tests for immediate allergy are important when shiitake contact dermatitis is investigated.

Adult↗

DNA damage and TNFalpha cytokine production in hairdressers with contact dermatitis.

The present work was undertaken to study in hairdressers exposed to several irritants and allergens (prevalently hair-dyeing) and affected by hand contact dermatitis the possible correlation between exposure and direct-oxidative DNA damage, production of tumour necrosis factor alpha (TNFalpha) and allergic inflammatory disease. We evaluated in 19 hairdressers with hand contact dermatitis, 14 allergic contact dermatitis (ACD) and 5 irritant contact dermatitis (ICD) and in a selected control group TNFalpha serum levels by ELISA and direct-oxidative DNA damage by Fpg (formamido-pyrimidine-glycosylase)-modified Comet test on blood. Hairdressers were divided on the basis of number of hair-dyeing carried out weekly into 2 groups: low-exposure (<60 hair-dyeing/week) and high-exposure hairdressers (>or=60 hair-dyeing/week) that reflect also the exposure to other allergens and irritants and 2 different tasks (hairdressers and apprentice hairdressers, respectively). Serum levels of TNFalpha in hairdressers with ACD were significantly higher than controls with a correlation to exposure level. Significant DNA damage in ICD hairdressers with higher exposure as compared to controls was found. These findings suggest that occupational exposure can induce in hairdressers, particularly ICD, DNA damage, increase the TNFa levels particularly in ACD and induce allergic sensitization, suggesting a relationship between direct-oxidative DNA damage, TNFalpha production and allergic inflammatory disease.

Adult↗

Systemic contact dermatitis after oral exposure to nickel: a review with a modified meta-analysis.

Systemic contact dermatitis can be elicited experimentally in nickel-sensitive individuals by oral nickel exposure. A crucial point interpreting such experiments has been the relevance of nickel exposure from drinking water and diet. The aim of this meta-analysis study on former nickel-exposure investigations was to provide the best possible estimation of threshold values of nickel doses that may cause systemic contact dermatitis in nickel-sensitive patients. 17 relevant investigations were identified, and statistical analyses were performed in a stepwise procedure. 9 studies were included in the final dose-response analysis, which divided the studies into a homogenous middle group of 5 studies and 2 groups of 2 studies with a higher and lower response frequency, respectively, described by logistic dose-response curves shifted in parallel. On the basis of these curves, calculations were made of the doses that, theoretically, would cause systemic contact dermatitis in exposed nickel-sensitive patients. The results from the 2 most sensitive groups show that 1% of these individuals may react with systemic contact dermatitis at normal daily nickel exposure from drinking water and diet, i.e. 0.22-0.35 mg nickel.

Administration, Oral↗

Dermatitis artefacta in pediatric patients: experience at the national institute of pediatrics.

Dermatitis artefacta is a factitious disorder in which there is deliberate conscious production of skin lesions. There are only a few reports that evaluate instances of dermatitis artefacta in the pediatric population. The aim of this retrospective study was to assess the characteristics of patients with this disorder who were seen at the National Institute of Pediatrics in Mexico City. The records of all patients diagnosed with dermatitis artefacta from January 1980 to December 1999 were analyzed. There were 29 patients (25 females, 4 males). The upper limbs and the face were the most commonly involved areas. Superficial erosions were the most frequent initial event, and residual lesions consisted of scars and crusts. Time taken to diagnosis was on average 10 months. Half of the patients were lost to follow-up. No correlation was found between the length of time from the disease onset to diagnosis, the type of lesions, and the clinical outcome. Twelve patients had an associated systemic disorder. The possible association with chronic disease has not been sufficiently stressed and demonstrates the importance of providing psychological support for these patients. Psychiatric diagnoses were anxiety, depression, and personality disorder. No correlation was found between the psychiatric diagnosis and the outcome of dermatitis artefacta. A young age at presentation, which has been considered important as a favorable prognostic sign, could not be demonstrated in our patients.

Adolescent↗