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PubMed1985

The relevance of inhalant and food allergens to the etiology and management of patients with atopic dermatitis.

Patients with atopic dermatitis have IgE antibodies to common environmental antigens, both foods and inhalants. Such antibodies are probably relevant and exposure to the corresponding antigens can give rise to eczema. Nevertheless, the mechanisms involved and the role of other etiologies, e.g. contact reactions, remain to be elucidated. Patients with atopic dermatitis should have comprehensive evaluations to determine the role of environmental antigens.

Air Pollutants↗

PubMed2005

Treatment of recalcitrant atopic dermatitis with omalizumab.

Atopic dermatitis is a common diagnosis that presents a therapeutic challenge. Although multiple therapeutic modalities exist, there is no single monotherapy that has proven exceptional in ameliorating the symptoms of this disease. Current topical and systemic therapeutic options offer benefit but carry varying degrees of adverse effects that often limit their application. We present 3 patients with severe, recalcitrant atopic dermatitis successfully treated with omalizumab.

Antibodies, Anti-Idiotypic↗

PubMed2006

Emerging therapeutic options for atopic dermatitis: beyond TIMs.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts both patients and their families. Although current therapies provide relief of symptoms for most but not all patients, they do not prevent or eradicate the disease. In this new era of biological therapy, medications that precisely target the molecular mediators of inflammation are being developed at a rapid pace. These biologic agents have proven useful for treating many inflammatory illnesses, as well as providing insight into disease pathogenesis. In atopic dermatitis, these new therapies may prove highly useful to both treat and prevent the disease. In this review article, we briefly review the pathogenesis of AD to discuss current therapies and to introduce potential new treatments.

Anti-Inflammatory Agents↗

PubMed2005

A multicentre, randomized, double-blind, controlled study of long-term treatment with 0.1% tacrolimus ointment in adults with moderate to severe atopic dermatitis.

BACKGROUND: Atopic dermatis (AD) is a chronic disease that often requires long-term treatment. Topical corticosteroids are the usual therapy for patients with AD, but prolonged usage can result in skin atrophy and other side-effects. OBJECTIVES: In a randomized, double-blind, comparative study, to compare the efficacy and safety of a 6-month treatment period with 0.1% tacrolimus ointment vs. a corticosteroid ointment regimen in adults with moderate to severe AD. METHODS: Treatment was applied twice daily for a maximum of 6 months. Patients in the tacrolimus treatment group (n = 487) applied 0.1% tacrolimus ointment to all affected areas over the whole body. The patients treated with the corticosteroid regimen (n = 485) applied 0.1% hydrocortisone butyrate ointment to affected areas on the trunk and extremities and 1% hydrocortisone acetate ointment to affected areas on the face and neck. The study primary endpoint was the response rate, i.e. the proportion of patients with at least 60% improvement in the modified Eczema Area and Severity Index (mEASI) between baseline and month 3. RESULTS: By month 3, more patients in the 0.1% tacrolimus group responded to treatment (72.6% vs. 52.3% in the corticosteroid group, P < 0.001). The patients treated with 0.1% tacrolimus also showed greater improvement in mEASI, EASI, affected body surface area and physician and patient assessments of global response. Patients applying 0.1% tacrolimus ointment experienced more skin burning (52.4% vs. 13.8% in the corticosteroid group; P < 0.001). In most patients, skin burning was mild to moderate in severity and decreased rapidly after the first week of treatment. There was no increase in the incidence of infections or malignancies over time in either treatment group. CONCLUSIONS: Long-term treatment with 0.1% tacrolimus ointment is significantly more efficacious than a corticosteroid ointment regimen in adults with moderate to severe AD.

Adult↗

PubMed1988

Increased prevalence of atopic dermatitis in Kawasaki disease.

Atopic dermatitis is associated with immunoregulatory abnormalities similar to those observed in acute Kawasaki disease. We investigated whether the prevalence of atopic dermatitis is increased among children who acquire Kawasaki disease. In a case-control telephone survey 83 Kawasaki disease patients and 83 children with innocent heart murmurs were matched for age and time between clinic visit and interview. The interviewer was blinded to the hypothesis of the study. Nine (11%) Kawasaki disease patients but only one (1%) unaffected child had atopic dermatitis; the incidence of atopic dermatitis among children with Kawasaki disease was 9 times greater than that of controls (95% confidence limits, 1.6 to 49.4). Serum immunoglobulin E concentrations were significantly higher (P = 0.02, Mann-Whitney) in 44 unselected Kawasaki disease patients (median, 22; range, less than or equal to 4 to 900 IU/ml) studied 6 to 12 months after onset than in 27 children of similar age (median, less than or equal to 4; range, less than or equal to 4 to 164 IU/ml). We observed that there is a strong association between atopic dermatitis and Kawasaki disease.

Child, Preschool↗

PubMed2006

Dissecting the role of infections in atopic dermatitis.

In patients with atopic dermatitis the skin is highly susceptible to infection by bacteria, fungi and viruses. Increasing knowledge about the complex immune network that regulates anti-microbial responses has helped to dissect further the role of infections in atopic dermatitis. Conserved patterns of microbes are recognized by the innate immune system, which mediates microbicidal activity, either directly or through inflammatory responses. New evidence suggests that components of the innate immune system, such as anti-microbial peptides, humoural lectins, nucleotide-binding oligomerization domain-containing (NOD) proteins, and Toll-like receptors not only protect from microbial invasion, but contribute to skin inflammation in atopic dermatitis. In addition, atopic patients tend to develop Th2-dominated immune responses that weaken anti-microbial immunity. This impairment of an appropriate anti-microbial defence compounded by amplified microbe-driven innate and adaptive immune responses leads to the vicious circle of skin inflammation. New microbial management in atopic dermatitis will foster a well-balanced microbial flora, which establishes natural defence mechanisms to maintain immuno-surveillance of the skin. In addition to anti-microbial therapies, other innate immune stimuli may suppress pro-inflammatory signals and help to break the vicious circle of cutaneous inflammation. To elucidate further these different interactions of the skin immune system and microbes in atopic dermatitis, clinical studies and further efforts in basic research are needed.

Animals↗

PubMed1997

[Mycoses in patients with psoriasis or atopic dermatitis].

Both, psoriasis and atopic dermatitis are multifactorial diseases with an unknown pathogenesis. To elucidate the influence of fungal infections in the onset or recurrence of those inflammatory skin disease we determined the frequencies of Candida and dermatophyte infections of the skin and orointestinal tract concomitantly seen in patients with psoriasis or atopic dermatitis. We analyzed the files of more than 40,000 in-patients of the Department of Dermatology, Kiel. Sex- and age-adjusted relative risk were calculated. The results demonstrate that patients with psoriasis (N = 3006) presented with a decreased rate of tinea. This was significant for tinea corporis (RR = 0.13, p < 0.01). Candida infections of the skin were seen more often in psoriasis patients compared to controls. Differentiating between Type I (early onset) and Type II (late onset) psoriasis only Type I psoriasis patients presented with decreased dermatophyte infections and increased Candida colonization of the intestinum. However, patients with Type II psoriasis demonstrated an increased rate of candidosis cutis and candidosis oris as compared to controls. Patients with atopic dermatitis (N = 1808) displayed a decreased overall incidence of tinea and Candida infections. Furthermore, in patients with atopic dermatitis a Candida colonization of the orointestinal tract was found elevated (RR = 1.51, p < 0.01), whereas tinea corporis (RR = 0.24, p < 0.01) and candidosis cutis (RR = 0.30, p < 0.001) was found decreased compared to controls. Our results show that the influence of fungal infections on the two skin diseases investigated is not as strong as often considered. The increased relative risk in patients with atopic dermatitis to present with Candida colonization in the digestive tract or vice versa may contribute to the pathogenesis of atopic dermatitis.

Candidiasis↗

PubMed1984

Basic and clinical aspects of atopic dermatitis.

The history of atopic dermatitis is replete with many disparate theories. The most enduring is the allergic causation theory but definitive, convincing evidence remains elusive. Elevated IgE synthesis is well established and reflects abnormal immune regulation. The basic mechanism for the regulatory defect remains conjectural. Cellular immune functions, including delayed cutaneous hypersensitivity, in vitro lymphocyte transformation and chemotaxis are reduced in atopic dermatitis. However, these abnormalities fluctuate with the clinical condition and may be secondary phenomena. A number of physiologic and pharmacologic abnormalities in atopic dermatitis are not clearly understood. Recent studies of patients leukocytes have shown that the diminished cyclic AMP responses are a consequence of increased catabolism by elevated cyclic AMP-specific phosphodiesterase. This high enzyme activity correlates well with elevated IgE synthesis and histamine release by cultured leukocytes. Both of these functions can be reduced by phosphodiesterase inhibitors in vitro. These new investigations provide fresh insight into the pathogenesis of atopic dermatitis and offer possible new therapeutic approaches. Basic studies of biochemical abnormalities may help define the defective molecular site that accounts for the many immune and physiologic abnormalities that have been described in atopic dermatitis and the other atopic conditions.

Adolescent↗

PubMed2006

Expression pattern of somatostatin receptor subtypes 1-5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitis.

In psoriasis and atopic dermatitis, the inflammatory events have neurogenic components and the neuropeptides modify the functions of immuno-active cells in the skin. Somatostatin is a neuropeptide with several neuroendocrine and immunomodulating properties and mediates its actions by five distinct subtypes of G-protein-coupled receptors (SSTR1-5). This study describes the distribution of SSTR1-5, analysed with immunohistochemistry, in psoriasis, atopic dermatitis and controls. Normal human skin and lesional skin from patients with psoriasis or atopic dermatitis showed many similarities, but also some differences, as regards SSTR expression. SSTR1-3 were strongly expressed in the epidermis of healthy skin, and in the skin of patients with psoriasis or atopic dermatitis. It is noteworthy that SSTR4 and 5 were strongly expressed in the epidermis of psoriasis patients, but weakly expressed in the epidermis of those with atopic dermatitis and normal skin. The intensity of the staining also varied considerably between the different layers of the epidermis, especially in psoriasis patients. In all cases, the dendritic cells, found mostly in the papillary and upper reticular dermis, showed a strong expression of SSTR1-4, but a weak expression of SSTR5. SSTR1-5 were strongly expressed in the sweat glands in all skin biopsies. Hair follicles and sebaceous glands expressed all five subtypes. Striated muscle fibres showed an intense positive expression of SSTR1-4, but a weak or negative expression of SSTR5. The wide distribution and expression pattern of all five SSTRs in human skin suggest that somatostatin is involved in the interactions between the nervous system and the skin.

Adult↗

PubMed1997

Elevated serum levels of soluble CD30 are associated with atopic dermatitis, but not with respiratory atopic disorders and allergic contact dermatitis.

Type 2 helper T-cell immune responses can be demonstrated in the human atopic disorders atopic dermatitis and allergic asthma/rhinoconjunctivitis. The CD30 (Ki-1) antigen, originally described on Hodgkin and Reed-Sternberg cells, has recently been proposed as a marker of T cells with potent B-cell helper activity producing IL-5 and gamma-IFN, as well as on CD4+ and CD8+ T cells with a Th2 cytokine profile. As a soluble form of CD30 (sCD30) is released by CD30+ cells in vivo, we studied its clinical significance in atopic disorders compared with allergic contact dermatitis and healthy controls. Elevated sCD 30 levels were associated with atopic dermatitis (P < 0.0001), but not with respiratory atopic disorders or allergic contact dermatitis. sCD30 levels in patients with atopic-dermatitis were independent of serum IgE. The particular occurrence of serum sCD30 in patients with atopic dermatitis indicates a special regulatory function of CD30+ cells in this disease.

Adolescent↗

PubMed2004

A multicenter trial of the efficacy and safety of 0.03% tacrolimus ointment for atopic dermatitis in Korea.

BACKGROUND: Atopic dermatitis is a chronically relapsing, common inflammatory skin disease, which significantly affects quality of life negatively in many respects. Topical steroids are the mainstay of atopic dermatitis treatment but they carry the risk of local side effects. A topical formulation of tacrolimus, a macrolide calcineurin inhibitor, has recently been developed. OBJECTIVE: To evaluate the efficacy and safety of 0.03% tacrolimus ointment for the treatment of moderate to severe atopic dermatitis in Korea. METHODS: An open, non-comparative, multi-center study with 4 weeks' follow-up was performed. A total of 180 patients (aged 2-57 years old) were enrolled. Tacrolimus ointment (0.03%) was applied to all involved areas twice daily. Efficacy was evaluated by an investigator's global assessment, the eczema area and severity index score, and by the patient's assessment of pruritus and clinical response at baseline, and after weeks 1, 2 and 4. Dermatology life quality index (DLQI), children's DLQI (CDLQI) and toddler's DLQI were assessed at baseline and at week 4. The safety assessment included monitoring all adverse events and clinical laboratory values. RESULTS: All efficacy parameters were improved. The mean EASI (eczema area and severity index) score was 19.7 at baseline and reduced to 8.0 at the end of the study. Moderate improvement was observed by the investigator's global assessment after 4 weeks' treatment. A marked decrease of pruritus was observed, and mild or moderate improvement was observed by patients' global assessments after the treatment period. Significant benefits in terms of quality of life in adults and children with atopic dermatitis were obtained. The most common adverse events associated with tacrolimus treatment were transient skin burning sensation (45.3%) and pruritus (41.6%) at the site of application. CONCLUSION: 0.03% tacrolimus ointment should be considered effective and safe in both Korean children and adults with moderate to severe atopic dermatitis.

Administration, Cutaneous↗

PubMed1999

Atopic dermatitis and HTLV-1-associated myelopathy: associated or coincidental disorders?

Reports from Jamaica have indicated that some patients with infective dermatitis or atopic dermatitis (AD) are seropositive for antibodies to human T-lymphotropic virus type 1 (HTLV-1). We describe a 32-year-old Israeli woman with long-term AD and paresthesia in the distal parts of the extremities. Neurological examination revealed a positive Babinski's sign. HLA typing demonstrated that this patient has the common HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis haplotype for DRB1* DQB1*. The presence of HTLV-1 was demonstrated with polymerase chain reaction; HTLV-1-antibodies were detected by the Western blot method and by inoculation of the patient's peripheral blood mononuclear cells into F344 rats. This study confirms the presence of HTLV-1 antibodies and proviral genome in a patient with AD which later evolved into HAM/TSP. We cannot yet conclude whether these two diseases are associated or coincidental disorders.

Adult↗

PubMed1994

Infra-auricular fissures in atopic dermatitis.

Retro-auricular or auricular dermatitis in atopic dermatitis (AD) is common and important for the diagnosis of AD in infancy and even in adulthood. Particularly, "infra-auricular fissures", acute eczematous changes like fissures at the adhesive junction of ear lobes, seem to be prominent features for the diagnosis of AD. Of 137 patients with AD, 81.8% showed present or past existence of infra-auricular fissures, but only one of the 30 controls. Of the 46 patients with severe AD, 98% had infra-auricular fissures, compared to 74% in those with moderate and mild AD. Our findings suggest that infra-auricular fissures are important for the diagnosis of AD and should be cited in a list of criteria for the diagnosis of AD.

Adolescent↗

PubMed1998

The photosensitivity dermatitis and actinic reticuloid syndrome (chronic actinic dermatitis) occurring in seven young atopic dermatitis patients.

Seven young patients with atopic dermatitis (AD) who presented with a marked photoexposed site dermatitis have been investigated in detail. The results of phototesting, patch testing and other investigations were compatible with the diagnosis of photosensitivity dermatitis/actinic reticuloid syndrome (PD/AR) (chronic actinic dermatitis). It is known that AD patients may have photoaggravation of their dermatitis or exacerbation secondary to a photodermatosis, such as polymorphic light eruption, actinic prurigo or drug-induced phototoxicity. The patients we describe, however, appear to be an uncommon AD subgroup affected by PD/AR. We recommend that all AD patients who have a history of sunlight-induced exacerbation or marked intolerance of PUVA or ultraviolet B phototherapy should have phototesting and patch testing conducted.

Adult↗

PubMed1994

Abnormal skin irritancy in atopic dermatitis and in atopy without dermatitis.

BACKGROUND AND DESIGN: Past observations have shown increased irritancy in patients with "conditioned hyperirritability" due to active dermatitis, including atopic dermatitis (AD). In less active atopic conditions, irritancy levels are less certain. We have utilized 48-hour Finn Chamber testing with graded dilutions of sodium lauryl sulfate to detect irritancy thresholds in well-defined groups of patients with AD, inactive AD, and allergic respiratory disease with no dermatitis and in normal nonatopic subjects. RESULTS: Significantly greater frequency of response to sodium lauryl sulfate in both AD groups and also in patients with allergic rhinitis with no dermatitis was seen. Effective concentrations of sodium lauryl sulfate causing irritation in 50% or more of subjects (ED50) ranged from 0.0625% to 0.31% in all atopic groups, percentages that were significantly lower than the normal ED50 of 0.60%. Response intensity was also significantly greater in each atopic group. CONCLUSIONS: Our results showed significantly greater irritant responses in atopic subjects with no skin disease or in subjects with inactive AD and confirmed past findings that showed greatly increased irritancy in patients with active AD. We hypothesize that abnormal intrinsic hyperreactivity in inflammatory cells, rather than in skin cells, in atopic individuals predisposes to a lowered threshold of irritant responsiveness.

Adolescent↗

PubMed1998

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↗

PubMed2004

Microbial colonization and atopic dermatitis.

PURPOSE OF REVIEW: Atopic dermatitis is a chronic relapsing, pruritic inflammation of the skin, affecting 10-20% of children and 1-3% adults worldwide, with increasing prevalence in highly industrialized countries. Here we review relevant studies, published since June 2002, about immunological triggers in atopic dermatitis, with emphasis on the role of microbial colonization. RECENT FINDINGS: During the past 2 years there has been considerable interest in the mechanisms and trigger factors underlying the increased microbial colonization of atopic skin. Staphylococcus aureus appears to play a significant role as it leads to a worsening of disease severity by producing superantigens that induce a strong proliferation of T cells and favour a T helper type 2-like cytokine profile. In addition, different Malassezia species seem to elicit and maintain skin inflammation after sensitization, but the precise immunological pathway has not yet been described. All these microorganisms are not only perceived as aetiological factors but also as agents responsible either for sustained disease activity or resistance to therapy by modulation of the immune response. SUMMARY: New insights into the important role of microorganisms and their key immunomodulatory pathways in atopic dermatitis may have important implications from a therapeutic point of view because patients with atopic dermatitis may benefit from more than just anti-inflammatory treatment in the future.

Adolescent↗

PubMed1991

Atopic dermatitis: new therapeutic considerations.

Atopic dermatitis is a genetically determined inflammatory condition in which the primary defect is expressed in one or more hematopoietic cells that infiltrate the skin. It is a multifactorial disease with inflammation triggered by a variety of factors. Among these, atopic dermatitis has been experimentally induced and reproduced by emotional-stress interviews and food challenges only. The inflammatory events of atopic dermatitis appear to initiated by mast cells, but eosinophils, monocytes, and T lymphocytes (predominantly CD4) also are present in lesions. The secondary effects of inflammation are a dry, brittle stratum corneum and pruritus, causing excoriation and a lichenified epidermal layer resulting from chronic rubbing. Therapeutic approaches to atopic dermatitis may be directed at several points in the evolution of the disease. Agents including emollients are needed to preserve and restore the stratum corneum barrier, and effective antipruritics are required to reduce the self-inflicted damage to the involved skin. Various other agents may be needed to antagonize mediators or cytokines and to inhibit cytokine expression and release from lesional, immune-effector cells. Likewise, new phosphodiesterase inhibitors, calcium-active agents, and antiallergic drugs may be used to reduce the quantity and pathologic functioning of inflammatory infiltrating cells in the skin.

Dermatitis, Atopic↗