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The impact of tacrolimus ointment on health-related quality of life of adult and pediatric patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis can have detrimental effects on health-related quality of life (QOL). OBJECTIVE: Our purpose was to examine the QOL impact of tacrolimus ointment in patients with atopic dermatitis. METHODS: The Dermatology Life Quality Index (DLQI), Children's DLQI (CDLQI), and Toddler QOL Survey were used to assess QOL in adults (16 years or older), children (5-15 years), and toddlers (2-4 years) enrolled in 12-week, randomized, double-blind studies comparing two concentrations of tacrolimus ointment (0.03% and 0.1%) versus vehicle ointment for treatment of atopic dermatitis. QOL was assessed at baseline, week 3, and week 12/early discontinuation. RESULTS: Of the 985 patients enrolled, 91.5% had evaluable QOL data. Among adults, both tacrolimus ointment groups experienced improved QOL relative to the vehicle control group for all QOL scales (P<.001). Among children and toddlers, both tacrolimus ointment groups demonstrated significant QOL improvements relative to the vehicle control group (P<.05) for all but the Personal Relationships scale in the 0.03% tacrolimus ointment group among children. CONCLUSION: Tacrolimus ointment is associated with significant QOL benefits in adults, children, and toddlers with atopic dermatitis.

Adolescent↗

Beard dermatitis due to para-phenylenediamine use in Arabic men.

The most common active ingredient in hair coloring is para-phenylenediamine (PPDA), which can produce contact dermatitis, particularly in persons who dye their scalp hair and in hairdressers. We have identified another group of patients also at risk, namely men from Arab countries, who commonly grow beards and dye them. We searched the computerized patient database at the Mayo Clinic for patients with beard dermatitis associated with dye use. Eight Arabic men presented to the Mayo Clinic between 1994 and 1999 with beard dermatitis and a positive patch test to PPDA. The lesions were described as pruritic, erythematous, papular eruptions that developed in the jaw area after each application of beard dye. The symptoms subsided after the patients discontinued use of the PPDA-containing dye and received treatment with topical corticosteroids. Allergic contact dermatitis in the beard area due to PPDA occurs in Arabic men as a result of their propensity to dye their beards.

Arabs↗

Breast-feeding and the onset of atopic dermatitis in childhood: a systematic review and meta-analysis of prospective studies.

BACKGROUND: Despite the numerous studies on the possible protective effect of breast-feeding against the onset of atopic dermatitis during childhood, this issue remains controversial. OBJECTIVE: We conducted a systematic review with meta-analysis of prospective studies that evaluated the association between exclusive breast-feeding during the first 3 months after birth and atopic dermatitis. METHODS: A comprehensive search of the 1966-2000 MEDLINE database and review of the reference lists of relevant articles identified 18 prospective studies that met the predefined inclusion criteria. By means of a standardized approach, 2 of the investigators independently assessed the methodologic quality of the studies, duration and exclusivity of breast-feeding, outcome measures, and control for potential confounding factors. The same approach was applied during data abstraction and evaluation of the estimates of association. Summary measures of association were then calculated. RESULTS: The summary odds ratio (OR) for the protective effect of breast-feeding in the studies analyzed was 0.68 (95% confidence interval [CI], 0.52-0.88). This effect estimate was higher in the group of studies wherein children with a family history of atopy were investigated separately (OR = 0.58; CI, 0.41-0.92) than in those of combined populations (OR = 0.84; CI, 0.59-1.19). A small subset of studies of children without a history of atopy in first-degree relatives showed no association between breast-feeding and the onset of atopic dermatitis (OR = 1.43; CI, 0.72-2.86). CONCLUSION: Exclusive breast-feeding during the first 3 months of life is associated with lower incidence rates of atopic dermatitis during childhood in children with a family history of atopy. This effect is lessened in the general population and negligible in children without first-order atopic relatives. Breast-feeding should be strongly recommended to mothers of infants with a family history of atopy, as a possible means of preventing atopic eczema.

Breast Feeding↗

Interstitial granulomatous dermatitis associated with pulmonary coccidioidomycosis.

BACKGROUND: Coccidioides immitis is a soil-dwelling fungus found in arid regions of the Western Hemisphere. Interstitial granulomatous dermatitis is a histopathologic pattern that may be a reactive manifestation of diverse systemic diseases. OBJECTIVE: Our purpose was to describe clinical and histopathologic findings in 5 patients who presented with interstitial granulomatous dermatitis associated with pulmonary coccidioidomycosis. METHODS: Medical records and skin biopsy slides from 5 patients were retrospectively reviewed. RESULTS: In each patient, edematous papules, nodules, and plaques developed abruptly during the onset of an acute febrile illness. Coccidioidomycosis was confirmed by serology. Skin biopsy specimens revealed interstitial granulomatous dermatitis with neutrophils, leukocytoclasis, and eosinophils. Fungal stains (5/5 cases) and fungal cultures (2/2 cases) revealed no organisms within the skin biopsy specimens. CONCLUSION: Interstitial granulomatous dermatitis may be a presenting feature of pulmonary coccidioidomycosis and may possibly represent a reactive manifestation of the infection.

Adult↗

Allergic contact dermatitis to topical minoxidil solution: etiology and treatment.

After more than a decade of use, topical minoxidil solution has proven to be a safe and effective treatment for androgenetic alopecia. However, some patients present with complaints of pruritus and scaling of the scalp. The most common causes of these symptoms include irritant contact dermatitis, allergic contact dermatitis, or an exacerbation of seborrheic dermatitis. Patients suffering from allergic contact dermatitis may benefit from patch testing to determine the causative allergen. Among the patients we patch tested, propylene glycol was found to be the contactant in a majority of cases, not the minoxidil itself. Many of these patients may be candidates for treatment with alternative formulations using other solvents, such as butylene glycol, polysorbate, or glycerol. Although predictive, patch testing results do not ensure that the compounded preparations will be tolerated. Unfortunately, patients found to be allergic to minoxidil are no longer candidates for topical treatment of their alopecia with any preparations of minoxidil.

Administration, Topical↗

An open pilot study using tacrolimus ointment in the treatment of seborrheic dermatitis.

Seborrheic dermatitis is generally treated with topical steroids, antifungals, or both. This pilot study was undertaken to examine the possibility of tacrolimus as a useful therapy for seborrheic dermatitis. In a single-center, open-label study, 18 consecutive patients with seborrheic dermatitis were treated with 0.1% tacrolimus for a total of 28 days or until complete clearance occurred, if sooner. Of the patients, 11 (61%) showed 100% clearance of their seborrheic dermatitis; the remaining 7 patients showed 70% to 99% clearance. The most common side effects were mild local burning and irritation.

Adult↗

Tacrolimus ointment 0.1% in the treatment of nickel-induced allergic contact dermatitis.

BACKGROUND: Tacrolimus is a macrolactam that prevents the transcription of messenger RNA for various inflammatory cytokines in both helper T cells (types 1 and 2) (T(H)1 and T(H)2). It is currently approved for the treatment of moderate to severe atopic dermatitis, a Th2-mediated disease, in children and adults. OBJECTIVE: We sought to evaluate the safety and efficacy of tacrolimus ointment 0.1% in the treatment of nickel-induced allergic contact dermatitis, a T(H)1-mediated disease. METHODS: This was a double-blind, randomized, vehicle-controlled, bilateral paired comparison study to assess the safety and efficacy of topical tacrolimus (Protopic, Fujisawa Healthcare Inc, Deerfield, Ill) ointment 0.1% in the treatment of allergic contact dermatitis induced by nickel sulfate. Volunteers were individuals with known hypersensitivity to nickel. Reactivity to nickel was graded both as the investigator's global assessment and total signs and symptoms, which consisted of the cumulative grade from 0 to 4 for each of the following parameters: erythema, induration, vesiculation, and pruritus (range of scores: 0-16). Reactivity was assessed in the per-protocol group at 1 and 2 weeks after beginning treatment with study drug and control. Adverse events were assessed in the intent-to-treat population. RESULTS: Of the 19 volunteers who completed the study (per protocol), 18 had an improvement in total signs and symptoms with tacrolimus versus 10 patients with the vehicle. Of patients, 80% had an improvement in the investigator's global assessment score on the tacrolimus-treated site versus 30% of patients on the placebo-treated site. Overall, tacrolimus was more effective than placebo in ameliorating the nickel reaction. Although the tacrolimus treated site was clear or almost clear in a greater number of individuals at week 1, this difference did not become significant until the second week of the study. Other than application site burning in 25% of volunteers, no significant adverse events were noted in the intent-to-treat population. CONCLUSION: Topical tacrolimus (Protopic, Fujisawa Healthcare Inc) ointment 0.1% may be an option for the treatment of allergic contact dermatitis induced by nickel.

Administration, Topical↗

Proliferation of T lymphocytes from atopic dermatitis skin is enhanced upon anti-CD3, reduced upon mitogen and superantigen, and negligible upon tuberculin stimulation.

Knowledge about the nature of lymphocytes infiltrating atopic dermatitis skin is restricted to allergen-specific T cells. We investigated the proliferative capacities of T lymphocytes cultured in an antigen-independent way from biopsies of atopic dermatitis skin. When compared with peripheral blood mononuclear cells (PBMC) from healthy donors or atopic dermatitis patients, the skin-homing lymphocytes proliferated more vigorously in response to stimulation with anti-CD3 antibodies (1 microglml), reflecting their high response capacity. When stimulated with phytohemagglutinin (10 microg/ml) or staphylococcal enterotoxin A (0.1 microg/ml) the skin-homing lymphocytes achieved significantly lower proliferation levels than PBMC. In contrast to normal and atopic PBMC the skin-homing lymphocytes did not respond to tuberculin purified protein derivative (10 microg/ml). In the mixed lymphocyte reaction the skin-homing lymphocytes did not stimulate autologous PBMC to proliferate. We conclude that skin-homing lymphocytes have more pronounced immune deviations than PBMC in patients with atopic dermatitis. They represent a valuable approach for further investigating the pathogenesis of the disease.

Adolescent↗

Longitudinal case analysis in atopic dermatitis.

The current knowledge on atopic dermatitis comes mainly from cross-sectional studies, which are not suited to establish time-courses or causal links in complex diseases. As an alternative approach, the method of longitudinal case analysis by the autoregressive integrated moving average (ARIMA) method has been introduced to investigate the pathogenesis of atopic dermatitis. The method was applied to the investigation of 2 patients suffering from severe and moderate atopic dermatitis. Disease activity, peripheral blood parameters (differential blood count, lymphocyte subpopulations, immunoglobulin E, eosinophilic cationic protein, soluble interleukin-2 receptor), mental stress and environmental factors were determined daily for 50 days. Both patients showed a positive correlation between CD4+ and CD25+ T-cells, a negative correlation between CD16/56+ natural killer cells and CD4+ T-cells, a negative correlation between eosinophils and polymorphonuclear leukocytes, and a time-shifted positive correlation of up to 2 days between scores quantifying mental stress and disease activity. A positive correlation between T-cells and polymorphonuclear leukocytes, CD4+ T-cells and the CD45RA+ subtype, as well as a negative correlation between stress and eosinophils, sports and eosinophils, and sports and disease activity were found only in one patient with more severe atopic dermatitis. In conclusion, longitudinal time-series analysis might represent an interesting and adequate method to generate and test new hypotheses on biomedical problems which cannot be addressed by cross-sectional studies.

Adult↗

Heliotherapy in atopic dermatitis: a prospective study on climatotherapy using the SCORAD index.

The aim of this study was to investigate the suitability and effectiveness of heliotherapy in moderate or severe atopic dermatitis in adults in the Canary Islands. A total of 216 patients participated on 6 different 2- or 3-week heliotherapy trips. Using the Severity Scoring of Atopic Dermatitis Index (SCORAD), the severity of atopic dermatitis was assessed prior to the start of heliotherapy, after 2 weeks and then 3 months after the end of heliotherapy. A quality-of-life questionnaire was later mailed to all participants. The mean SCORAD index was reduced by 70% after 2 weeks of heliotherapy and was still 45% lower 3 months after therapy (P<0.0001). At 3 months, the use of topical steroids was still significantly reduced (P<0.0001), whereas there was no significant (P=0.1166) change in the consumption of emollients. The quality of life of patients was improved and their self-treatment and working capacity was increased. As the longer 3-week period provided no significant additional advantage over a 2-week period, 2 weeks of heliotherapy can be considered optimal. In conclusion, heliotherapy is an effective and valuable therapeutic adjunct, especially in adults with severe atopic dermatitis.

Adolescent↗

Atopy patch tests in young adult patients with atopic dermatitis and controls: dose-response relationship, objective reading, reproducibility and clinical interpretation.

The clinical interpretation and reproducibility of atopy patch tests was studied in 23 selected young adult patients with atopic dermatitis and 25 healthy controls using standard inhalant allergens. Non-invasive measurements were used for objective assessment of test reactions and the participants were retested after 6 weeks. Ten of 19 (53%) evaluable patients with atopic dermatitis had at least one positive atopy patch test. However, there was no clear clinical relevance of the atopy patch test results when related to patient history and distribution of dermatitis. Reproducible and dose-dependent results were obtained with Dermatophagoides pteronyssinus, grass and cat with a reproducibility rate of 0.69 to 0.81 in patients and 0.60-0.96 in controls. A unique finding was a significant positive correlation between a positive atopy patch test, allergen dose and increase in transepidermal water loss and erythema, while measurement of capacitance did not distinguish between positive and negative reactions. The results of the present study do not support the routine use of atopy patch tests in the evaluation of adult patients with atopic dermatitis.

Adolescent↗

Increased levels of serum interleukin-16 in adult type atopic dermatitis.

Interleukin (IL)-16 serves as a natural ligand of CD4 molecules and induces chemotaxis in CD4-expressing cells such as T cells, eosinophils, dendritic cells and monocytes. We examined the serum levels of IL-16 in patients with adult atopic dermatitis when their eruptions were aggravated and in non-atopic healthy controls, and then analysed the possible correlation between these values and the levels of several clinical markers. The serum levels of IL-16 were significantly higher in patients with atopic dermatitis than in the controls--both in exacerbation status and after conventional treatment. Multiple regression analyses showed that serum IL-16 was a predictor of the eosinophil count. Circulating IL-16 levels decreased significantly in patients with atopic dermatitis after topical treatment with corticosteroids or tacrolimus. These findings provide evidence that IL-16 plays a role in the exacerbation of chronic adult atopic dermatitis.

Administration, Cutaneous↗

Are adverse skin reactions to cosmetics underestimated in the clinical assessment of contact dermatitis? A prospective study among 1075 patients attending Swedish patch test clinics.

It is known that cosmetics and skin care products can cause adverse skin reactions. However, the frequency of adverse reactions reported to the Medical Product Agency (MPA) in Sweden is low. The purpose of the present study was to evaluate the occurrence of adverse skin reactions to cosmetics among patients referred for standard patch testing owing to suspected contact dermatitis in general, most frequently hand eczema. Consecutive patients at four patch test clinics in Sweden were invited to participate; 1075 were included. Of these, 47.3% (54.2% women and 30.8% men) reported current or previous adverse skin reactions to cosmetics and skin care products. This group showed significantly more positive patch test reactions, a higher prevalence of atopic dermatitis and the dermatitis was more frequently located in the face and neck region. Our results show that patients referred for standard patch testing have--or have had--a large proportion of self-reported adverse reactions to cosmetics or skin care products. We conclude that among patients with suspected contact dermatitis, adverse reactions to cosmetics can be a more important aetiological and/or complicating factor than is commonly acknowledged and that the reporting of such reactions to the MPA probably can be improved.

Allergens↗

Malassezia sympodialis stimulation differently affects gene expression in dendritic cells from atopic dermatitis patients and healthy individuals.

It is known that 28-84% of patients with atopic dermatitis exhibit IgE and/or T-cell reactivity to the opportunistic yeast Malassezia sympodialis, which can be taken up by immature monocyte-derived dendritic cells (MDDCs), resulting in MDDC maturation. The aim of this study was to investigate whether MDDCs from patients with atopic dermatitis respond differently to M. sympodialis compared to MDDCs from healthy individuals. Immature MDDCs were stimulated with M. sympodialis and the gene expression profiles were analysed with cDNA arrays containing 406 genes. Our results show that M. sympodialis differently affected MDDCs from patients with atopic dermatitis, and more so in severely ill patients, compared with healthy individuals. Six genes were more than fivefold up-regulated in MDDCs from more than one patient with atopic dermatitis, coding for CD54, CD83, IL-8, monocyte-derived chemokine (MDC), BTG1 and IL-1R antagonist. In healthy individuals this was true only for BTG1. Up-regulations of IL-8 and MDC were confirmed at the protein level. Our findings might reflect an increased trafficking and stimulatory capacity in MDDCs from the patients, which is likely to result in a stronger inflammatory response to M. sympodialis.

Adult↗

Expression of CCR2 on monocytes and macrophages in chronically inflamed skin in atopic dermatitis and psoriasis.

Monocytes form a significant component of the inflammatory reaction taking place in the skin of atopic dermatitis and psoriasis. Chemokines are pivotal in mediating the attraction of leucocytes to sites of inflammation. The CC-chemokine, monocyte chemotactic protein 1 (MCP-1/CCL2), is expressed by keratinocytes in both atopic dermatitis and psoriasis. MCP-1 binds to the chemokine receptor CCR2 which is known to be expressed on monocytes and macrophages. We examined the expression of CCR2 on peripheral blood monocytes from patients with psoriasis (n=8) and atopic dermatitis (n=7) and found it to be expressed on approximately 90% of the cells, whereas monocytes from healthy donors had a significantly lower CCR2 expression (p<0.05). Skin biopsies from patients suffering from atopic dermatitis and psoriasis revealed that CCR2-positive cells expressed CD163, a marker for monocytes/macrophages. However, not all CD163-positive cells expressed CCR2, which could be interpreted as a mechanism for retaining the macrophages in the skin. Furthermore, we found that keratinocytes are able to express MCP-1, when stimulated with tumour necrosis factor-alpha and/or interferon-gamma in a dose-dependent manner. Thus MCP-1 and CCR2 interaction is likely of importance for the monocyte/macrophage trafficking of inflammatory skin disorders.

Antigens, CD↗

Density of Demodex folliculorum in perioral dermatitis.

The role of Demodex folliculorum in perioral dermatitis is not satisfactory explained. Our purpose was to assess the density of D. folliculorum in perioral dermatitis and evaluate the relationship of the mite count to previous therapy with topical steroids. A standardized skin surface biopsy of the chin was performed in 82 female patients with perioral dermatitis and in 70 control female subjects. Patients who received previous topical steroid therapy had a significantly higher mite density than the patients who had received no topical steroids (p<0.001). In the latter group of patients, the mite density did not differ significantly from that of the control group (p=0.629). Mite density increased significantly with the length of treatment with topical steroids (p<0.001). Our results suggest that increased density of D. folliculorum in perioral dermatitis is a secondary phenomenon, associated with topical steroid therapy.

Administration, Cutaneous↗

Modulation of cutaneous SP receptors in atopic dermatitis after UVA irradiation.

Atopic dermatitis is a pruritic inflammatory skin disorder, involving immunological and non-immunological factors. Substance P seems to be involved in the pathogenesis of atopic dermatitis. Substance P-containing nerve fibers are increased in the lesional skin of patients with atopic dermatitis and a reduced weal and flare reaction to intradermal injection of substance P has been observed. We investigated the distribution of substance P receptors in the involved skin of patients before and after single or repetitive UVA irradiations. Our results indicate that substance P receptors of the NK-1 subtype are expressed on blood vessels and on epidermal keratinocytes of involved skin of patients with atopic dermatitis. UVA irradiations did not modify the epidermal distribution of substance P receptors but decreased their expression intensity on blood vessels. UVA irradiations seem to decrease skin inflammation through the modulation of NK-1 receptor expression on endothelial cells.

Dermatitis, Atopic↗

Purified Der p1 and p2 patch tests in patients with atopic dermatitis: evidence for both allergenicity and proteolytic irritancy.

Atopic dermatitis has many similarities with allergic contact dermatitis. Previous studies have revealed delayed-type allergic reactions indicating specific cell-mediated immune reactions in subgroups of patients. It has recently been recognized that purified house dust mite major allergens, Der p1 and Der p2 from Dermatophagoides pteronyssinus, exhibit a proteolytic enzyme activity similar to papain and maybe serine proteases (e.g. trypsin), respectively. This opens the possibility that house dust mites apart from an allergic epitope could elicit irritant reactions in atopic skin. We examined cutaneous reactivity to the purified proteins of house dust mite antigens, Der p1 and Der p2, in 36 consecutive patients with atopic dermatitis. We also patch-tested with trypsin and papain, in order to see if these proteolytic enzymes could induce irritant reactions. Twelve patients had type 1 allergy to Der p1 and two of these had type IV reactivity to D. pteronyssinus extract. Positive reactions were observed in another four patients, but they had also irritant reactions to papain and trypsin, indicating that the enzymatic activity may have elicited the reactions. The cutaneous reactivity was not linked to total serum IgE, but the patients with specific allergic patch tests had type I reactions to D. pteronyssinus extract. Our observations indicate that allergic patch tests towards Der p1 and p2 are rare and that irritant reactions from D. pteronyssinus proteolytic activity may be a more common phenomenon when patch-testing atopic dermatitis patients with house dust mite antigen extract.

Adolescent↗