Neutrophil-derived oxidative stress contributes to skin inflammation and scratching in a mouse model of allergic contact dermatitis via triggering pro-inflammatory cytokine and pruritogen production in skin.

Allergic contact dermatitis (ACD) is a common skin disease featured with skin inflammation and a mixed itch/pain sensation. The itch/pain causes the desire to scratch, affecting both physical and psychological aspects of patients. Nevertheless, the mechanisms underlying itch/pain sensation of ACD still remain elusive. Here, we found that oxidative stress and oxidation-related injury were remarkably increased in the inflamed skin of a mouse model of ACD. Reducing oxidative stress significantly attenuated itch/pain-related scratching, allokonesis and skin inflammation. RNA-Sequencing reveals oxidative stress contributes to a series of skin biological processes, including inflammation and immune response. Attenuating oxidative stress reduces overproduction of IL-1ß and IL-33, two critical cytokines involved in inflammation and pain/itch, in the inflamed skin of model mice. Exogenously injecting H2O2 into the neck skin of naïve mice triggered IL-33 overproduction in skin keratinocytes and induced scratching, which was reduced in mice deficient in IL-33 receptor ST2. ACD model mice showed remarkable neutrophil infiltration in the inflamed skin. Blocking neutrophil infiltration reduced oxidative stress and attenuated scratching and skin inflammation. Therefore, our study reveals a critical contribution of neutrophil-derived oxidative stress to skin inflammation and itch/pain-related scratching of ACD model mice via mechanisms involving the triggering of IL-33 overproduction in skin keratinocytes. Targeting skin oxidative stress may represent an effective therapy for ameliorating ACD.

Patients' perspectives on quality of care for chronic hand eczema: A qualitative study.

BACKGROUND: Hand eczema (HE) has a significant impact on patients' quality of life and work-related activities. However, little is known about the patients' perspectives on quality of care for HE. OBJECTIVES: To evaluate the patient perspective of the HE care process in a tertiary referral center. METHODS: Qualitative, semi-structured focus groups were carried out, recorded, transcribed, and analysed using an inductive-deductive thematic approach. RESULTS: Fifteen patients participated in four focus groups. Time and attention, together with being listened to and understood by the health care professional, were the most important aspects of care for HE mentioned by participants. Other aspects of care that were regarded as important were that diagnoses, causes and follow-up of HE were not always clear to the participant; more psychosocial support was needed, and that participants experienced frequent changes in doctors. Information provided by nurses was valuable, but more individualized advice was needed. CONCLUSIONS: To better meet the needs of patients, more explanation should be given about the causes of HE and the final diagnosis. Besides focusing on the treatment, it is also important to focus on its impact on the patient and options for psychosocial and peer support should be discussed. Furthermore, the beneficial role of the specialized nurse as part of integrated care was emphasized.

Effectiveness of Support Groups for Patients With Contact Dermatitis: A Pilot Study.

BACKGROUND: Contact dermatitis can be difficult to manage and overwhelming for patients, often requiring significant lifestyle changes. OBJECTIVE: The aim of the study was to investigate whether a contact dermatitis support group could help patients find community and learn from others who share similar experiences. METHODS: Hour-long, monthly support group meetings facilitated by a social worker, research fellows, and a faculty dermatologist were held for approximately 1.5 years. A 32-question, cross-sectional survey was administered to assess perception of contact dermatitis and overall usefulness of the group. RESULTS: Between 2 and 5 patients attended each group session; 9 participants completed the survey. Most were female (77.8%) and white (77.8%), with an average age of 68.8 years. Eight participants (88.9%) reported that it was important or somewhat important to socialize with others affected by contact dermatitis. Three group members (33.3%) had met with attendees outside of the monthly sessions. The majority (77.8%) reported that the support group had a positive effect on their understanding of contact dermatitis and would recommend the group to others (88.9%). CONCLUSIONS: Support groups may be helpful for patients learning to cope with the challenges associated with contact dermatitis. Although preliminary feedback is promising, further investigation is warranted to determine whether these groups are effective on a larger scale.

Assessment of the quality of life (QoL) of patients with dermatitis and the impact of patch testing on QoL: A study of 519 patients diagnosed with dermatitis.

BACKGROUND: Dermatitis can impair the quality of life (QoL) of patients. Knowledge of the QoL-associated factors and the impact of patch testing on QoL is limited. OBJECTIVES: To identify demographic and clinical factors affecting QoL, and to measure the impact of patch testing on QoL of dermatitis patients. METHODS: The data and Dermatology Life Quality Index (DLQI) questionnaires of 519 dermatitis patients were analyzed. Of these, 107 underwent patch testing and completed the questionnaires two times (once before testing and again 60 days afterward). RESULTS: The overall mean (±standard deviation) DLQI was 9.5 (±6.4). Patients aged 20 to 59 years and those who had more frequent disease exacerbations demonstrated significantly higher DLQIs. For each DLQI question, being female and aged 20 to 59 years were associated with impairments of various aspects of life, whereas the anatomical site of dermatitis impacted each question differently. The DLQI scores of the patients undergoing patch testing decreased significantly, irrespective of whether the test results were positive or negative. CONCLUSIONS: Being of a working age and having more frequent disease exacerbations had negative QoL impacts. In addition, patch testing improved almost every aspect of the DLQI.

Children with vaccination granulomas and aluminum contact allergy: Evaluation of predispositions, avoidance behavior, and quality of life.

BACKGROUND: Aluminum contact allergy is mostly seen in children with vaccination granulomas, following immunization with aluminum-adsorbed childhood vaccines. OBJECTIVES: To characterize a cohort of children with vaccination granulomas and aluminum allergy concerning early life conditions, exacerbating factors, avoidance behavior, treatments, and potential impact on quality of life. METHODS: A questionnaire study was conducted among 177 children aged 0 to 15 years with vaccination granulomas and aluminum allergy, and a reference group of 61 children aged 3 to 14 years with various types of dermatitis undergoing patch testing. RESULTS: All children in the granuloma group were reportedly affected by itch. Infection exacerbated the itch in 59%. Other worsening factors were eating tin-foiled/canned food (31%) and use of aluminum-containing sunscreen (46%). Many parents took precautions to avoid aluminum exposure. Children with granulomas were more likely to be nonadherent to the National Vaccination Program than the reference group (27% vs 2%, P < .001). Parents in the granuloma group reported a decreased life quality for both parents and children compared with the reference group. CONCLUSIONS: Itching vaccination granulomas and aluminum allergy have a considerable negative impact on affected children and their families, causing avoidance behavior, reduced adherence to vaccination programs, and a negative effect on the overall life quality.

Validating Responsiveness of a Quality-of-Life Instrument for Allergic Contact Dermatitis.

BACKGROUND: Although many generic dermatological quality-of-life (QoL) instruments exist, none have been specifically designed for patients with allergic contact dermatitis (ACD). In the preceding publication-Validating a Quality-of-Life Instrument for Allergic Contact Dermatitis-we developed and validated a QoL instrument specific to the ACD population. OBJECTIVE: The aim of this study was to assess whether this ACD-specific QoL instrument appropriately captures change in QoL after patch testing in ACD patients. METHODS: One hundred individuals completed the previously validated 17-item QoL survey plus 2 global questions and the Skindex-29 before patch testing. Two months after patch testing and allergen avoidance, the participants repeated the same questionnaires. We used statistical methods to evaluate the capacity of the ACD questionnaire to measure change in QoL in comparison with the Skindex-29. CONCLUSIONS: The novel ACD-specific questionnaire was more sensitive to change in QoL than the generic Skindex-29. Eleven of the original 17 items were found to capture change in QoL, and of the 3 domains (emotions, symptoms, functioning), the emotional aspect of the disease was most burdensome and responsive to change 2 months after patch testing. Providers can reliably use this index to assess changes in QoL over time.

Validating a Quality-of-Life Instrument for Allergic Contact Dermatitis.

BACKGROUND: Contact dermatitis is a prevalent condition that has a significant impact on quality of life (QoL). Although many generic dermatological QoL instruments exist, none were developed by and for patients with allergic contact dermatitis (ACD). OBJECTIVE: The aim of the study was to create and validate a reliable QoL instrument specific for the ACD population. METHODS: We identified QoL items specific to ACD through a series of qualitative interviews with ACD patients and experts. We created a 17-question survey that queries the patient across the following 3 major domains: symptoms, functioning, and emotions. We used statistical methods to evaluate the reliability and validity of this tool. RESULTS: Ninety patients with relevant positive results on patch testing completed the novel ACD instrument and the Skindex-29. This instrument exhibited reliability and validity in individuals with ACD and was more sensitive than the generic tool Skindex-29. CONCLUSIONS: This novel instrument is the first tool developed specifically to assess the unique impacts of ACD on QoL. Providers can reliably use this index to assess the specific aspects of the disease most problematic for the ACD patient and use this information to more properly inform counseling and management.

The psychosocial burden of hand eczema: Data from a European dermatological multicentre study.

BACKGROUND: The essential physical role, visibility and social importance of the hands place a major psychological burden on patients with hand eczema. OBJECTIVES: The aim of this study was to identify the psychological, social and clinical characteristics of patients with hand eczema, in particular the prevalences of depression, anxiety, suicidal ideation, and comorbidities. MATERIALS AND METHODS: Data on patients with hand eczema were analysed from a large European multicentre study conducted with dermatology outpatients from 13 countries. Groups of patients and controls were compared to analyse the psychological burden of hand eczema. RESULTS: Female patients with hand eczema had higher Hospital Anxiety and Depression Scale (HADS) scores for anxiety (n = 86, median = 7.0) than controls (n = 900, median = 5.0, P = .02), and for depression (median = 4.0) than controls (3.0, P < .001). Patients with high suicidal ideation, with low socioeconomic status and who were widowed or divorced were more likely to fulfil the HADS criteria for anxiety [odds ratio (OR) > 1, P = .038, P < .001, and P < .001, respectively]. The median Dermatology Life Quality Index score was 7.0 (n = 68). DISCUSSION: This study identifies a specific psychological burden experienced by hand eczema patients, highlighting the need for focused psychosocial interventions. Physicians in particular should be aware of the need to identify anxiety and depression in female patients.

Evaluation and Management of Patch Test-Negative Patients With Generalized Dermatitis.

BACKGROUND: Patients with generalized dermatitis are common in dermatology practices. Allergic contact dermatitis is often suspected, and patients frequently undergo patch testing. When the patch testing result is negative, further evaluation and management of these patients are challenging. OBJECTIVE: The purpose of this study was to survey members of the American Contact Dermatitis Society regarding the evaluation and management of patch test-negative patients with generalized dermatitis. RESULTS: Generalized dermatitis was the most common term identified for patch test-negative patients with diffuse dermatitis. After having negative expanded patch testing results, most physicians proceeded with additional testing including skin biopsy, complete blood cell count with differential, and liver and renal function tests. The most commonly used systemic treatment is prednisone, followed by methotrexate. Narrow-band ultraviolet B (UVB) is the most commonly used light source. Antihistamines are frequently prescribed. Food allergy is not felt to be causative. This cohort of patients experiences significant impairment in quality of life, stress on personal relationships, and time off work. CONCLUSIONS: The management of patch test-negative patients with generalized dermatitis is challenging. This study provides insight into management of these complex patients. It also demonstrates practice gaps in the management of these patients, indicating a need for further studies to direct the evaluation and management of this patient population.

Effects of time and recall of patch test results on quality of life (QoL) after testing. Cross-sectional study analyzing QoL in hand eczema patients 1, 5 and 10 years after patch testing.

BACKGROUND: Patch testing can improve health-related quality of life (HRQOL). OBJECTIVES: To study the impact on HRQOL of elapsed time after patch testing (1-10 years), and how the outcome of testing and patients' recall affects HRQOL. PATIENTS/MATERIALS/METHODS: The Dermatology Life Quality Index (DLQI) questionnaire was sent to all patients (aged 18-65 years) who were patch tested for suspected contact allergy in 2009, 2005 and 2000 at the Department of Dermatology in Örebro. RESULTS: The response rate was 51% (n = 256). The DLQI score was significantly lower at 10 years after patch testing (mean DLQI = 5.5) than at 1 year (mean DLQI = 7.7). Work was the most impaired aspect. A binary logistic model showed that only time (10 years after testing) was associated with no effect, a light effect or a moderate effect (DLQI < 10) on HRQOL. No such association was seen for patients with negative or positive test results concerning full recall, partial recall or no recall of diagnosed allergens. CONCLUSIONS: Although there was an improvement in HRQOL over time, the work aspect remained a major problem. The improvement was not affected by the outcome of testing and patients' recall of test results.

Current Quality-of-Life Tools Available for Use in Contact Dermatitis.

Contact dermatitis is a common dermatologic condition that can cause significant impairment in patients' overall quality of life (QoL). This impact is separate and potentially more clinically relevant than one's disease "severity" in contact dermatitis and should be consistently addressed by dermatologists. Despite this, QoL tools specific to contact dermatitis are lacking, and there is little consistency in the literature regarding the tool used to evaluate clinical response to therapies. Measurements currently available to evaluate disease-related QoL in contact dermatitis fit into 1 of the following 3 general types: generic health-related QoL measures, dermatology-related QoL measures, or specific dermatologic disease-related QoL measures. This article reviews the strengths and weaknesses of existing QoL tools used in contact dermatitis including: Short Form Survey 36, Dermatology Life Quality Index, Skindex-29, Skindex-16, Dermatology-Specific Quality of Life, and Fragrance Quality of Life Index.

Allergic Contact Dermatitis: A Model of Inflammatory Itch and Pain in Human and Mouse.

This chapter is an overview of published observations from our laboratory on the psychophysics and neurobiology of the persistent itch and pain of allergic contact dermatitis (ACD). ACD is a clinically significant problem with many features characteristic of other pruritic disorders. Our approach was to produce ACD experimentally in humans and in the mouse. The goal was to use the mouse as an animal model for investigating the peripheral neural mechanisms of itch and pain of ACD in humans. Humans and mice were each sensitized by cutaneous topical application of squaric acid dibutyl ester, a hapten not encountered in the environment. Subsequent challenge at another cutaneous site produced local inflammation ("ACD") with humans reporting persistent itch (lasting up to a week) and mice exhibiting persistent itch- and pain-like behaviors directed toward the ACD site. Enhanced mechanically evoked itch and pain in surrounding skin in humans were reversibly blocked by numbing the ACD site with cold, suggesting dependence on ongoing activity from the site. In mice, in vivo recordings revealed spontaneous activity in a subset of pruriceptive, mechanoheat-sensitive nociceptors with unmyelinated axons innervating the ACD site. These and a larger subpopulation of acutely dissociated small-diameter neurons innervating the ACD site exhibited an upregulation of the receptor CXCR3 and excitatory responses to one of its ligands, the chemokine CXCL10 (IP-10) that contributes to the pathogenesis of ACD. Preliminary findings point to possible therapeutic targets that could be investigated in inflammatory itch disorders in humans.

Clinical profile and quality of life of patients with occupational contact dermatitis from New Delhi, India.

BACKGROUND: Data regarding occupational contact dermatitis (OCD) and its effect on quality of life (QOL) in India are limited. OBJECTIVES/AIMS: To evaluate patients with OCD and record the outcome of treatment. PATIENTS/MATERIALS/METHODS: All patients with OCD were evaluated for severity of disease (by the use of physician global assessment) and its effect on QOL (by use of the Dermatology Life Quality Index) questionnaire) at the first visit and after 3 months of treatment. RESULTS: Among 117 patients with OCD, hand eczema was present in 81.2%. Positive patch test reactions were found in 76%. The most common allergens were Parthenium hysterophorus and potassium dichromate. The most frequent diagnosis was occupational allergic contact dermatitis (OACD) (57%), caused by farming and construction work, followed by occupational irritant contact dermatitis (OICD) (24%), caused by wet work. Severe psychosocial distress was recorded in 62.5% of patients. After 3 months of treatment, 83% improved significantly, and 54% had improvement in QOL. CONCLUSIONS: Farmers were most frequently affected, followed by construction workers and housewives. OACD was found at a higher frequency than OICD. The most frequent allergens were Parthenium hysterophorus in farmers, potassium dichromate in construction workers, and vegetables in housewives. OCD has a significant impact on QOL. Patch testing, in addition to standard treatment, improves the outcome considerably.

Psychophysical measurements of itch and nociceptive sensations in an experimental model of allergic contact dermatitis.

UNLABELLED: Allergic contact dermatitis (ACD) is a common condition that can significantly affect the quality of life. Contact with allergens results in delayed hypersensitivity reactions involving T lymphocytes, with associated skin inflammation and spontaneous itch and nociceptive sensations. However, psychophysical studies of these sensations are lacking. In the present study, we sensitized 8 healthy volunteers to squaric acid dibutyl ester (SADBE). Two weeks later, 1 volar forearm was challenged with SADBE, and the other with acetone vehicle control. Subsequently, participants rated the maximal perceived intensity of spontaneous itch, pricking/stinging, and burning every 6 to 12 hours for 1 week, using the generalized Labeled Magnitude Scale. In the laboratory, they judged stimulus-evoked sensations within and outside the chemically treated area. The SADBE- but not the acetone-treated skin resulted in 1) localized inflammation, with spontaneous itch and nociceptive sensations peaking at 24 to 48 hours after challenge, 2) alloknesis, hyperknesis, and hyperalgesia to mechanical stimuli that were reduced or eliminated by anesthetic cooling of the SADBE-treated area and restored on rewarming, suggesting that sensations and dysesthesias are dependent on ongoing peripheral neural activity, and 3) enhanced itch to intradermal injection of histamine, BAM8-22, or ß-alanine. This experimental model of T-cell-mediated inflammation may prove useful in evaluating potential treatments of itch from ACD. PERSPECTIVE: In a model of allergic contact dermatitis, experimentally applied in humans, psychophysical measurements were obtained of persistent, spontaneous itch and enhanced stimulus-evoked itch and pain sensations. These sensory measurements will be useful in the identification of the neural mechanisms underlying inflammatory itch and pain.

Course of skin symptoms and quality of life in children referred for patch testing--a long-term follow-up study.

Children are patch tested in the same manner as adults, but little has been done to establish whether positive or negative findings influence the course of skin symptoms. To uncover the course of skin symptoms and the impact of persistent eczema on life quality in paediatric patients referred for patch testing, a retrospective questionnaire was sent to children and adolescents referred for patch testing during a 9-year period. Persistent eczema at follow-up was strongly associated to atopic dermatitis, but was not explained by gender, age, contact allergy or time span from patch testing to follow-up. Among patients without atopic dermatitis, 23.5% reported to suffer from chronic eczema. Persistent eczema increased the risk of severe impairment of life quality. Our findings indicate a significant risk of childhood eczema becoming chronic and affecting life quality considerably. Patch testing did not affect the course of eczema, highlighting the difficulties of avoidance behaviour.

[Definition and psychopathology of chronic hand dermatitis]. / Définition et psychopathologie de la dermite chronique des mains.

Psychopathology in patients with DCM is as complex as its clinical forms where the factors are numerous and often intricate. It combines psychophysiological, psychopathological factors, behavioral disorders which can be the cause or the consequence of DCM but also the negative impact on quality of life and the simplest daily activities. DCM affects the quality of life of every patient, regardless of the severity. Women are more affected by the DCM that man older age, male sex, atopy and the existence of a contact sensitization are independent risk factors of severity. Depression may affect up to 10 % of patients, should involve greater attention from dermatologists and general practitioners. Health authorities and all health actors should be aware of interactions between secondary cognitive troubles or inherent to DCM and efforts required in terms of preventive measures. Thus, the presence of psychiatric comorbidity is more common in patients with chronic dermatoses. Today it is considered that the emotional environment, built by the mother - child relationship must be optimal, otherwise the mental stability of body image may be compromised. Diminished self-esteem, affects less well managed and somatic expression of emotional content. Recently, a surprising study showed that most patients with refractory occupational dermatitis were not able to recognize the warning sign of flare or the role of psychological factors in the formation and maintenance of the dermatose. In fact, they rejected their personal responsibility in the occurrence of the new flare. To address this public health problem, health authorities, trainers and caregivers should be aware of the cognitive impact of DCM in these patients and interactions with current means of prevention. The role of obsessive-compulsive washing as part of an anxiety disorder or personality disorder is most likely a contributing or maintaining factor systematically underestimated in the pathogenesis of DCM and in the therapeutic management.

Enhanced scratching elicited by a pruritogen and an algogen in a mouse model of contact hypersensitivity.

Chemical pruritogens and algogens evoke primarily itch and pain, respectively, when administered to the skin of healthy human subjects. However, the dominant sensory quality elicited by an algesic chemical stimulus may change in patients with chronic itch where bradykinin, elicits itch in addition to pain. Here we tested whether normally pruritic and algesic chemicals evoked abnormal itch- or pain-like behaviors in the mouse after the development of contact hypersensitivity (CHS), an animal model of allergic contact dermatitis. Mice previously sensitized to a hapten (squaric acid dibutylester) applied to the abdomen, exhibited spontaneous itch-like scratching and pain-like wiping directed to the site on the cheek of the CHS elicited by a subsequent challenge with the same hapten. In comparison with responses of control mice, CHS mice exhibited a significant increase in the scratching evoked by bovine adrenal medulla 8-22, a peptide that elicits a histamine-independent itch, but did not alter the scratching to histamine. Bradykinin, an algogen that elicited only wiping in control mice, additionally evoked significant scratching in CHS mice. Thus, within an area of CHS, histamine-independent itch is enhanced and chemically evoked pain is accompanied by itch.

Psychological stress with long-standing allergic dermatitis causes psychodermatological conditions in mice.

Psychological factors have long been assumed to be involved in the pathogenesis of allergic skin diseases. The effects of psychological stress on allergic contact dermatitis (ACD) have been experimentally well investigated; however, the effects of ACD on stress responses are largely unknown. Here, we report that preceding chronic ACD dramatically affects the behavioral and physiological stress responses to social isolation (a psychological stressor). In male BALB/c mice, social isolation combined with long-standing (>2 months) ACD by repeated hapten application caused characteristic symptoms, including chronic dermatitis from persistent self-scratching, behavioral changes related to fear/anxiety, and elevated serum IgE levels. The symptoms were maintained by social isolation alone without further hapten application after the onset, and were improved by resocialization. Treatment with topical corticosteroids exacerbated chronic scratch dermatitis, whereas it was effective for chronic ACD. These results show that the symptoms represent a de novo development of a specific disease state and not a mere exacerbation of a preexisting allergic inflammation. With this experimental protocol, similar results were obtained in several other strains of mice. This murine model provides a tool for investigating the pathogenesis and treatment of allergic skin disease with psychodermatological aspects.