Safety and efficacy of clocortolone pivalate 0.1 percent cream in the treatment of atopic dermatitis, contact dermatitis, and seborrheic dermatitis.
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Ten patients with moderate to severe atopic dermatitis had increased levels of IgE in the blood and a reduced level of T cells with Fc receptors for IgG (T gamma). After pronase and trypsin digestion of Fc receptors, cultured T cells regenerated the Fc receptors, but preserved the difference between patients and controls. Neuraminidase treatment increased the T gamma-cell level in both patients and controls. Serum from patients with atopic dermatitis could not reduce the T gamma-cell expression in the controls. With regard to Fc receptors, no qualitative difference was observed between patients and controls, but a genuine quantitative difference accounts for the observed reduction of T gamma cells in blood.
Atopic dermatitis (AD), often called eczema, is a disease characterized by intense pruritus, erythema, dry skin, and inflammation. Pimecrolimus is a novel steroid-free treatment for AD. Consistently positive results have been found with pimecrolimus treatment in infants, children/adolescents, and adults. Its safety record is excellent, and studies have found no clinically relevant drug-related systemic adverse events. In this article, we first review atopic dermatitis and conventional treatment strategies. We then discuss various aspects of pimecrolimus, including pharmacologic properties, toxicology, short- and long-term studies, and safety and adverse events. Finally, we propose a new steroid-sparing treatment strategy for AD.
The prevalence of symptoms of atopic eczema among Japanese children aged 6-7 years is the second highest in 56 countries. Reasons for such a high prevalence are unknown. This ecological study examined whether the positive association of water hardness with atopic dermatitis among British primary-school children also exists in Japan. Study subjects were 458,284 of 489,725 children, aged 6-12 years, in 1,016 public elementary schools in Osaka Prefecture with 44 municipalities. The study used data on water hardness and chlorine content of the water supply; prevalence of atopic dermatitis diagnosed by physicians and episodes of wheezing reported by the parents; and potential confounding factors by socioeconomic and health care status per municipality. The prevalence of atopic eczema was significantly higher in the highest water hardness category than that in the lowest (24.4% [n=2,288/9,362] and 22.9% [n=77,408/33,8267], respectively; adjusted odds ratio 1.12, 95% confidence interval 1.06-1.18; P<0.0001 for trend). A significant and slightly J-shaped relationship between chlorine content of the water supply and prevalence of atopic dermatitis was observed after adjustment for confounding factors. There were no apparent associations of water hardness and chlorine content of the water supply with prevalence of wheeze. Water hardness may increase the risk of atopic dermatitis among elementary-school children in Japan, as well as in the United Kingdom.
A 31-year-old man had had atopic dermatitis since childhood and developed vitiligo with inflammatory raised borders 5 years prior to presentation. Immunohistochemically, CD4+ T cells infiltrated predominantly in the raised border of vitiligo, while CD8+ T cells were present just outside of the borders, suggesting that CD8+ cells were an antecedent to the CD4+ cells. Despite the presence of atopic dermatitis, the percentage of CXCR3+ CD4+ Th1 cells increased in the patient's peripheral blood, compared with a representative atopic patient showing a high percentage of CCR4+CD4+ Th2 cells. This case suggests that vitiligo with inflammatory raised borders can occur even in patients with atopic dermatitis when Th1 cells are activated and overcome the Th2-dominant state.
Atopic dermatitis (AD), a chronic inflammatory skin disease, is frequently seen in patients with a personal or family history of asthma and allergic rhinitis. Population studies suggest an increasing prevalence of AD in children since World War II, with 10-15% of the population being affected by AD at some time during childhood. In patients with moderate to severe AD, involvement can be life-long, causing significant interference with school, work and social interactions. The term atopic dermatitis was introduced to reflect the close association between AD and respiratory allergy. During the past decade, extraordinary progress has been made in our understanding of the immunopathogenesis of allergic diseases. In particular, this constellation of inherited illnesses has now been demonstrated to be associated with activation of a specific group of cytokine genes encompassing IL-3, IL-4, IL-5, IL-13 and granulocyte-macrophage colony-stimulating factor (GM-CSF). The molecular basis for selective activation of this cytokine gene cluster and the immunological consequences are now being pursued actively by many laboratories. However, it is clear that allergic diseases result from a polygenic inheritance pattern which involves not only cytokine gene activation but also activation of other less well defined gene products. Furthermore, the clinical expression of allergic diseases is highly dependent on a complex interaction between the host and its environment, e.g. allergen exposure. The genetic predisposition to develop allergic responses may be similar in patients with AD and other allergic diseases, such as asthma. However, targeting of the allergic immune response may relate to the organ in which allergen sensitization first occurs; the capacity of immune effector cells, e.g. T lymphocytes, to home preferentially to the skin versus the respiratory mucosa; and the programmed response of resident cells, e.g. epithelial cells, to injury and inflammation. This review examines the cellular and immunological mechanisms that are thought to play an important role in the pathogenesis of chronic AD. An understanding of the immunological basis of AD is likely to have important clinical implications in our approach to the management of this common illness, and the development of immunomodulators for its treatment.
Previous research on the relationship between stress and atopic dermatitis has employed retrospective approaches such as interviews and measurement of life events and daily hassles. These studies have yielded inconsistent results. In the current study, 50 atopic dermatitis sufferers completed a diary for a fortnight, recording their daily emotional states and skin condition. The results of meta-analyses indicated that both interpersonal stress and depression were significantly related to changes in skin condition. Meta-analyses of lag sequential analyses indicated that interpersonal stress on Day X predicted skin condition on Day X + 1 and that this relationship was reciprocal. Depression was predicted by the skin condition of the previous day but this relationship was not reciprocal. These results were integrated and their implications for psychosomatic relationships between stress, depression, and atopic dermatitis were discussed.
PURPOSE: To determine whether cataract in patients with atopic dermatitis is associated with higher levels of aqueous flare or cells. METHODS: In a prospective study, 35 consecutive patients examined during a 6-month period at the atopic dermatitis service in a university hospital underwent standardized ophthalmologic evaluations including the quantitative measurement of aqueous flare and cells by a laser flare-cell meter. RESULTS: Seven patients had bilateral cataract with anterior or posterior subcapsular opacities, or both; one patient had similar cataract in one eye and no cataract in the opposite eye; and 27 patients had no cataract in either eye. Fifteen eyes with cataract showed significantly higher levels of aqueous flare (2.1 to 33.9 photon counts per millisecond with a median of 18.0) compared with 55 eyes without cataract (2.4 to 16.0 photon counts per millisecond with a median of 9.2; Mann-Whitney U test, P = .0008). The association of cataract with higher levels of aqueous flare remained significant when only one eye (the right eye) of each patient was chosen for statistical analysis (P = .0024). CONCLUSION: Higher levels of aqueous flare caused by the breakdown of blood-aqueous barrier may contribute to the formation of cataract in patients with atopic dermatitis.
Atopic dermatitis is a common, potentially debilitating condition that can compromise quality of life. Its most frequent symptom is pruritus. Attempts to relieve the itch by scratching simply worsen the rash, creating a vicious circle. Treatment should be directed at limiting itching, repairing the skin and decreasing inflammation when necessary. Lubricants, antihistamines and topical corticosteroids are the mainstays of therapy. When required, oral corticosteroids can be used. If pruritus does not respond to treatment, other diagnoses, such as bacterial overgrowth or viral infections, should be considered. Treatment options are available for refractory atopic dermatitis, but these measures should be reserved for use in unique situations and typically require consultation with a dermatologist or an allergist.
In a prospective study of 63 patients with long-lasting hand eczema, a diagnosis of atopic dermatitis could be established in 49%. Comparison between patients with atopic dermatitis and those without atopic dermatitis showed that the hand eczema pattern differed very little between the groups. Hyperlinearity was significantly more common in the palms of the patients with atopic dermatitis.
Atopic dermatitis has been characterized as an autoimmune or auto-allergic phenomenon in which environmental allergens resembling human proteins activate auto-reactive T-cells to release pro-inflammatory cytokines of the T-helper 2 (Th2) cytokine profile (IL-4, IL-5, IL-10, and IL-13). Infliximab is a chimeric IgG1 monoclonal antibody that blocks the effects of the inflammatory cytokine tumor necrosis factor (TNF)-alpha. Infliximab has been shown to benefit greatly patients suffering from diseases associated with a Th1 profile (IL-1, TNF-alpha, and IFN-mu), such as psoriasis, Crohn's disease and rheumatoid arthritis. Some researchers have suggested that disrupting the Th1-Th2 balance by downregulating Th1 cytokines may result in manifestations of Th2 disease. Consistent with this hypothesis, we present the cases of three patients who exhibited vivid manifestations of atopic dermatitis after the inception of infliximab induction therapy.
BACKGROUND: Recently, increased IL-4 and decreased interferon-gamma (IFN-gamma) production in peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis have been reported by several groups. They measured the total amount of each cytokine in culture supernatants in their studies. These studies suggested a predominance of type 2 cytokine-producing cells in atopic dermatitis. However, it is still unclear whether the cytokine imbalance is the result of an imbalance of specific T-cell subsets or of dysregulation of the cytokine-producing ability in T-cell subsets. Here, we examined frequencies of IL-4-, IFN-gamma-, or IL-2-producing CD4+ cells and CD8+ cells in PBMCs from patients with atopic dermatitis at a single cell level by using flow cytometry. METHODS: PBMCs from 45 patients with atopic dermatitis and 24 healthy control subjects were stimulated with immobilized anti-CD3 monoclonal antibody for 6 hours in the presence of monensin. Cells were fixed, made permeable, and stained for intracellular cytokines in combination with staining for cell surface markers CD4 and CD8. RESULTS: The frequency of IL-4-producing CD4+ cells and CD8+ cells from patients with atopic dermatitis was significantly higher (p < 0.001) than that from healthy control subjects. In contrast, the frequency of IFN-gamma-producing CD4+ cells and CD8+ cells was significantly decreased (p < 0.01) in the patients with atopic dermatitis. The frequency of IL-2-producing cells from patients with atopic dermatitis was comparable to that from healthy control subjects. CONCLUSION: Our findings indicate that frequencies of type 2 cytokine-producing cells, not only among CD4+ cells but also among CD8+ cells, were significantly higher in patients with atopic dermatitis than in healthy control subjects.
The clinical manifestations of atopic dermatitis comprise a complex mixture of pharmacological, physiological and immunological responses. Circumstantial evidence suggests that atopic disease may arise consequent upon the migration of bone marrow-derived cells into the target tissue of skin or respiratory mucosa. Mediator release from such cells has been shown to be abnormal in atopic dermatitis, and itch, the hallmark of the disease, may be the result of chronic inflammatory mediator release into the skin. Abnormal release of mediators has been shown to correlate with inadequate nucleotide control of cell function. In particular, elevated cyclic AMP-specific PDE activity causing cyclic AMP hyporesponsiveness has been found in peripheral blood mononuclear leucocytes in atopic dermatitis. Investigation of this pathway has led to the discovery of additional abnormalities of other secondary messenger systems, including abnormalities of protein kinase C activity and of inositol activation. The biochemical abnormalities may be a consequence of down-regulation of the second messenger systems because of chronic exposure to low levels of inflammatory mediators, but may themselves subsequently permit further mediator release. They may provide a biochemical mechanism for many of the immunological abnormalities seen in atopic dermatitis. In particular, they offer a biochemical explanation for the paradox of increased type 1-mediated immunity and diminished cell-mediated immunity commonly observed in this complex disease.
Atopic dermatitis is one of the most common chronic diseases of childhood and closely related to other clinical manifestations of allergy. The incidence is high and still increasing. The genetic contribution to disease development is substantial and complex. Only recently genetic research has begun to focus on this phenotype, and specific susceptibility genes remain to be found. To identify candidate regions holding genes for atopic dermatitis we performed a genome-scan in Danish affected sib-pair families containing sib-pairs matching a phenotype definition of both clinical atopic dermatitis and confirmed specific allergy. The scan was undertaken using 446 microsatellite markers and non-parametric linkage results were obtained from the MAPMAKER/SIBS computer program. We found evidence of linkage to three candidate regions in chromosomes 3p (MLS=2.14), 4p (MLS=2.00) and 18q (MLS=2.25), one of which has not been reported previously. Eight additional regions showed weaker but positive results.
The skin and palmar markings were examined in 178 patients with atopic dermatitis, 66 (37%) of whom had ichthyosis vulgaris. Increased palmar markings were found in 49 (28%) patients, while a normal pattern of palmar markings was present in 129 (72%) patients. Increased palmar markings were commonly observed in patients with atopic dermatitis and ichthyosis, while normal palms were found in almost all patients with atopic dermatitis alone. It is suggested that the increased palmar markings often seen in patients with atopic dermatitis are actually a manifestation of concomitant ichthyosis vulgaris.