Why does allergic contact dermatitis exist?

The skin immune system’s propensity to produce allergic contact dermatitis (ACD) to harmless chemicals, while otherwise being an efficient defence system, represents a dermatological paradox. We postulate that a major role in signalling in ACD is played by Toll‐like receptor (TLR)2 and TLR4, and arises from their activation by extracellular danger‐associated molecular patterns (DAMPs). Ligand activation of TLR4/2 results in the expression of interleukins (ILs) IL‐1β, IL‐6, IL‐12, IL‐18 and IL‐23, tumour necrosis factor‐α and interferon‐α. These cytokines promote acquisition of sensitization, and facilitate elicitation of contact allergy via multiple mechanisms, including the recruitment of CD4+ Th1 and Th17 cells. As Th1 cells secrete large amounts of DAMPs, a DAMP immune circuit (positive‐feedback loop) is created. This is an important driver of skin sensitization and skin inflammation. Pathogenic extracellular bacteria, but not commensal bacteria, produce pathogen‐associated molecular pattern molecules, which stimulate the expression of Th1‐ and Th17‐promoting cytokines via TLR2 and TLR4. This also induces an immune circuit. The ability of the skin immune system to activate host defence mechanisms and to distinguish between pathogenic bacteria and commensals provides an explanation for why skin sensitization and ACD develop, as they are processes that rely on the same biological pathways. These pathways may also shed light on the pathogenesis of chronic pustular inflammatory dermatoses (e.g. acne vulgaris). The existence of safety signals from commensal bacteria, which prevent initiation of these pathways, may provide opportunities for novel therapeutic approaches to the treatment of inflammatory skin diseases.     

Tγ and theophylline-sensitive T lymphocytes in allergic contact dermatitis

Summary Two lymphocyte subpopulations, T cells bearing a receptor for the Fc fragment of IgG (T) and theophylline-sensitive T cells, were investigated in 49 patients with allergic contact dermatitis (ACD) in the acute phase and compared with a control group. Patients with ACD had markedly reduced relative T and theophylline-sensitive T lymphocyte levels, compared with normals (P<0.0005). The patients also showed reduced absolute T and theophylline-sensitive T cells with respect to the controls (P<0.01).To determine whether decreased levels of T and theophylline-sensitive T cells were related to the activity of ACD, the same T-cell subsets were determined in 10 of 49 patients after the clearing of the contact dermatitis. Both T-cell subpopulations were found within the normal range.     

Atopic dermatitis in adults: does it disappear with age?

There is limited knowledge of the prognosis in adult atopic dermatitis. We previously published a long-term follow-up questionnaire study of adults with atopic dermatitis. This study is a clinical examination of 79 adults (mean age 57 years) recruited 3 years after that study. Most patients (68%) still reported that they had atopic dermatitis and 53% had ongoing eczema at examination, mainly located on the head and neck. Severity was mainly mild to moderate, but 12% had severe atopic dermatitis. IgE antibodies to Malassezia (m70) were more common in patients with ongoing atopic dermatitis, while positive Malassezia culture was seen mainly in patients with no ongoing atopic dermatitis. M. obtusa and M. globosa were the most commonly cultured Malassezia species. In conclusion, considering increased prevalence of atopic dermatitis in children in recent decades and the fact that atopic dermatitis in most adults continues for many years, we should expect to see more adults with atopic dermatitis in the future.     

Atopic dermatitis – Perspectives and unmet medical needs

Atopic dermatitis (AD) is a chronic inflammatory skin disease for which many new insights have been gained in recent years through a better understanding of pathophysiology, concomitant diseases and therapeutics in particular. In this review, new and practice-relevant results from current research are presented. Many studies have been performed on the diagnosis of AD and on different subtypes, yet no diagnostic biomarker or clinical predictor of treatment response has been established. For topical treatment, some agents such as Janus kinase (JAK) inhibitors are in advanced stages of clinical trials or already approved in some countries, which will be available in Europe for the treatment of certain eczema subtypes in the foreseeable future. Current systemic therapies in Europe include two antibodies for inhibition of the interleukin (IL)-4/13 signaling cascades and three oral JAK inhibitors with somewhat different efficacy and safety profiles. Among the antibody therapies for AD already advanced in development, promising new targets include blockade of IL-31, of neurokinin-1 receptor on sensory neurons, and inhibition of the OX40/OX40L axis for cutaneous dendritic cell and T lymphocyte interaction. Primary prevention and modulation of sequential disease progression as well as effects on concomitant diseases by early therapeutic intervention will be important questions in future research on AD.     

Does allergic contact dermatitis from formaldehyde in clothes treated with durable‐press chemical finishes exist in the USA?

Recent US studies have presented case series of patient with allergic contact dermatitis (ACD) allegedly caused by formaldehyde in clothes treated with durable‐press chemical finishes (DPCF), which are known formaldehyde releasers. However, the amounts of formaldehyde released by modern DPCF are thought to be well below the levels previously estimated to be able to elicit ACD. The objectives of this review are (i) to investigate whether clothes sold in the USA may contain enough free formaldehyde to elicit ACD in previously sensitized individuals and (ii) to assess the validity of US reports on ACD from formaldehyde in DPCF treated clothes. Literature was examined using various resources. The threshold level for formaldehyde in clothes that may cause ACD in sensitized individuals is unknown; we present data suggesting that levels < 200 ppm will be safe for most patients and that textiles will rarely contain higher amounts. All US studies presenting patients with ACD from formaldehyde in clothes had some weaknesses and in no report was the diagnosis proven beyond doubt. Currently, there is no definite proof that textile ACD from formaldehyde in DPCF in the USA exists. Future research should be directed at establishing the elicitation threshold and the amounts of formaldehyde present in textiles.     

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. Copyright (R) 2000 S.Karger AG, Basel     

Atopic dermatitis: which are the diagnostic criteria used in medical literature?

INTRODUCTION: Diagnosis of atopic dermatitis currently relies on diagnostic criteria scales developed by Hanifin and Rafka in 1980 and by the "United Kingdom Working party" in 1994. Some authors have proposed: "AEDS" [sM1] and "Atopiform Dermatitis", which has led to the distinction between different sub-populations and the exclusion of certain diseases from the diagnosis of atopic dermatitis. The aim of our study was to collect the criteria retained in the scientific medical literature during the year 2002 for the definition of atopic dermatitis and to try to understand not only the interest but also the questions that the various definitions lead to. METHOD: A PubMed research was launched with the key word "atopic dermatitis" from January to September of 2002. All the scientific articles either in French or in English were studied. RESULTS: Hanifin and Rafka's criteria were selected in 44 p. 100 of the scientific articles, and the "United Kingdom Working Party" criteria in 12 p. 100. Personal definitions were used in 21 p. 100 of the articles; these were based on the level of total and specific IgE or on personal clinical criteria. For twenty-three p. 100 of the authors, the definition of atopic dermatitis was not specified. DISCUSSION: There was not just one definition of atopic dermatitis. This may affect the interpretation of diagnostic or therapeutic papers concerning the disease, because there has been no proof that these definitions cover the same population of patients.     

Atopic dermatitis: The hygiene hypothesis: Prevention through helminth infections?

The prevalence of atopic diseases has steadily increased over the past decades. While genetic predisposition remains an important risk factor, environmental conditions appear to be additional relevant trigger factors, leading to the development of the "hygiene hypothesis". Current data indicates that atopic respiratory diseases seem to occur less frequently following helminth infections. This effect may be due to the induction of anti-inflammatory cytokines during the helminth infection. In contrast, atopic dermatitis seems to represent a separate entity influenced by more than "allergic sensitization". Recent data demonstrate a reduced risk for the development of atopic dermatitis following helminth infections. Further studies are needed to more closely examine the connections between helminth infections and this chronic skin disease, as well as to identify immunologic pathways.     

Eyeglass frame allergic contact dermatitis: does tacrolimus prevent recurrences?

A 35-year-old man developed well-demarcated, oedematous and erosive erythematous lesions on the nasal bridge and retroauricular regions bilaterally. His eyeglass frame was repaired by an optician 2 weeks prior to symptom onset. Patch testing revealed a positive reaction to scrapings of nose pads and temples of the frame in petrolatum. Because the patient did not take our exhortation to change eyeglass frames, we advised him to cover their nose pads and temples with vinyl tape to prevent direct skin contact. Although topical corticosteroid therapy produced clinical resolution temporally, recurrences were not prevented. After starting tacrolimus ointment therapy, recurrence has not occurred for 9 months. Tacrolimus may be effective for allergic contact dermatitis patients who cannot avoid repeated allergen exposure, as it may not only reduce inflammation but inhibit recurrences.