Validation of five patient-reported outcomes for atopic dermatitis severity in adults.

BACKGROUND: Structured patient-reported outcomes of atopic dermatitis (AD) severity are not standardized in clinical practice. OBJECTIVES: To determine the construct validity, internal consistency, cross-cultural validity and floor or ceiling effects of multiple AD severity assessments. METHODS: This is a cross-sectional, population-based study of 2893 adults, including 602 adults who met a modified set of U.K. diagnostic criteria for AD. AD severity was assessed using self-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD) and its objective and subjective components, and numerical rating scale (NRS)-itch. Quality of life was assessed using Short-Form (SF)-12 mental and physical health scores, Short-Form Six Dimensions (SF-6D) health utility scores and Dermatology Life Quality Index (DLQI). Mental health was assessed with the Hospital Anxiety and Depression Scale (HADS). RESULTS: PO-SCORAD, PO-SCORAD objective and subjective subscores, NRS-itch and POEM all had moderate-to-strong correlations with each other and DLQI, fair-to-moderate correlations with HADS-anxiety and HADS-depression, and inverse correlations with SF-12 mental component score and SF-6D (Pearson correlations, P < 0·001). All scores showed good criterion validity as judged by anova and receiver operator characteristics. PO-SCORAD, PO-SCORAD objective subscore and POEM had similarly good internal consistency (Cronbach's alpha = 0·84, 0·82 and 0·86); the PO-SCORAD subjective subscore was less internally consistent (alpha = 0·57). All scores showed potentially poor cross-cultural validity as demonstrated by uniform and nonuniform differential item functioning by age, sex and/or race/ethnicity for multiple items. There were floor effects for POEM, but not for the other assessments. CONCLUSIONS: PO-SCORAD, PO-SCORAD objective and subjective subscores, NRS-itch and POEM appear to be valid for assessing AD severity in clinical practice. What's already known about this topic? Few studies have demonstrated the validity of the atopic dermatitis severity assessments Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD), PO-SCORAD subscores, numerical rating scale (NRS)-itch and Patient-Oriented Eczema Measure (POEM). What does this study add? This study demonstrates that PO-SCORAD, PO-SCORAD subscores, NRS-itch and POEM all had good construct validity in the assessment of atopic dermatitis severity in adults. Only POEM demonstrated floor effects. What are the clinical implications of this work? PO-SCORAD, PO-SCORAD subscores, NRS-itch and POEM all appear to have sufficient validity to be used as assessments of atopic dermatitis severity in clinical practice.

Symptoms and diagnosis of anxiety and depression in atopic dermatitis in U.S. adults.

BACKGROUND: The relationship between atopic dermatitis (AD), anxiety and depression in the U.S. adult population is not well established. OBJECTIVES: To determine the relationship of AD and its severity with symptoms and diagnosis of anxiety and depression in U.S. adults. METHODS: A cross-sectional, population-based study of 2893 adults was performed. AD was determined using modified U.K. Diagnostic Criteria. RESULTS: Adults with AD vs. those without AD had higher mean Hospital Anxiety and Depression Scale anxiety (HADS-A) (7·7 vs. 5·6) and depression (HADS-D) (6·0 vs. 4·3) scores and higher prevalences of abnormal (≥ 11) HADS-A (28·6% vs. 15·5%) and HADS-D (13·5% vs. 9·0%) scores. In multivariable linear and logistic regression models controlling for sociodemographics, AD was associated with significantly higher mean HADS-A and HADS-D scores (7·7 and 6·0) and higher odds of abnormal HADS-A [odds ratio (OR) 2·19, 95% confidence interval (CI) 1·65-2·91] and HADS-D scores (OR 1·50, 95% CI 1·04-2·17) (P ≤ 0·03 for all). Mean and abnormal HADS-A and HADS-D scores were increased in moderate and severe/very severe self-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Scoring AD (PO-SCORAD), PO-SCORAD itch and sleep (P < 0·0001 for all). All respondents with severe PO-SCORAD, POEM and PO-SCORAD itch had borderline or abnormal HADS-A and HADS-D scores. Adults with AD vs. those without AD had higher prevalence of self-reported healthcare-diagnosed anxiety or depression in the past year (40·0% vs. 17·5%). Many adults with AD who had borderline and/or abnormal HADS-A or HADS-D scores reported no diagnosis of anxiety or depression. CONCLUSIONS: AD is associated with significantly increased anxiety and depression, which may go undiagnosed. What's already known about this topic? Previous studies found higher rates of anxiety and depression in clinical cohorts of patients with atopic dermatitis. What does this study add? This study found dramatically higher rates of anxiety and depression among adults with atopic dermatitis in the U.S. population, which was primarily driven by atopic dermatitis severity. Anxiety and depression often go undiagnosed in adults with atopic dermatitis.

Distribution of atopic dermatitis lesions in United States adults.

BACKGROUND: The distribution of atopic dermatitis (AD) lesions and its impact on quality of life (QOL) is not well established in the US adult population. OBJECTIVE: To elucidate the distribution of AD lesions and its impact on QOL in US adults with AD. METHODS: A cross-sectional, population-based study of 602 adults was performed. AD was determined using modified UK Diagnostic Criteria, and its lesional distribution was assessed. QOL was assessed using Dermatology Life Quality Index (DLQI). Latent class analysis (LCA) was used to determine distinct phenotypes of AD lesional distribution. Multivariable logistic regression was used to determine the relationship between DLQI and distinct phenotypes. RESULTS: The most common sites of skin lesions were reported to be the popliteal fossae, lower legs, dorsal feet and antecubital fossae. Most persons reported partial (19.0%) or complete (63.0%) symmetry of lesions on the extremities. Lesions on the trunk were significantly more common in blacks and Hispanics. Age ≥ 60 years was associated with significantly lower proportions of active lesions on the face and scalp, and significantly higher proportion of lesions on the buttocks or genitals. LCA identified 5 classes of lesional distribution: 1. lower probabilities of lesions affecting any sites; 2. Higher probability of lesions involving the anterior and posterior neck and trunk; 3. lesions involving the antecubital fossae and upper extremities; 4. lesions involving the arms, posterior hands, genitals and buttocks, and to a lesser extent face, palms and legs; 5. lesions affecting all sites. Class-2 (multivariable logistic regression; adjusted odds ratio [95% confidence interval]: 7.19 [3.21-16.07], class-3 (7.11 [3.20-15.80]), class-4 (6.90 [3.07-15.50]) and class-5 (7.92 [3.54-17.71]) were all significantly associated with higher DLQI scores compared to class 1. CONCLUSION: AD is associated with heterogeneous distribution of AD lesions, and distinct phenotypes that are associated with QOL impact.

Plasma IL-33 in atopic patients correlates with pro-inflammatory cytokines and changes cholesterol transport protein expression: a surprising neutral overall impact on atherogenicity.

OBJECTIVE: Interleukin (IL)-33 has been associated with atopic and inflammatory conditions. IL-33 may be atheroprotective inducing a Th1-to-Th2 immunologic switch. However, the role of IL-33 in cardiovascular disease remains unclear. This study examines the effect of physiological and elevated IL-33 levels in plasma from atopic patients (AP) on cholesterol metabolism in human macrophages as compared to plasma from healthy controls (HC). METHODS: Twenty-five AP and 25 HC were enrolled in this study. Plasma samples were analysed for levels of IL-33, IFN-γ, TNF-α, IL-17α, IL-5 and soluble ST2. THP-1 differentiated macrophages were exposed to HC and AP plasma. Expression of proteins involved in reverse cholesterol transport (ABCA1, ABCG1 and 27-hydroxylase) and scavenger receptors, responsible for uptake of modified lipids (CD36, ScR-A1, CXCL16 and LOX-1), was measured using QRT-PCR and immunoblotting techniques. RESULTS: IL-33 was significantly higher in AP plasma: 106.7 ± 95 pg/mL versus HC plasma (53.4 ± 23 pg/mL). IL-33 concentration strongly correlated with levels of IFN-γ (r = 0.85), TNFα (r = 0.9) and IL-17α (r = 0.94). No significant difference was found in soluble ST2 levels. An important contrast was observed for 27-hydroxylase: normal IL-33 in AP plasma amplified 27-hydroxylase while increased IL-33 suppressed it. Expression of CD36 and SR-A1 was greater in macrophages exposed to plasma with high IL-33, while CXCL16 was higher in cells grown in the presence of plasma with normal IL-33. CONCLUSIONS: Here, we demonstrate that high levels of IL-33 and a high IL-33/soluble ST2 ratio correlates with elevated levels of IFN-γ, TNF-α and IL-17α as well as IL-5, demonstrating that IL-33 has pleiotropic effects. However, elevated IL-33 did not significantly impact lipid accumulation in macrophages overall. Given the wide variety of cellular responses regulated by IL-33, further investigation with a larger sample size will allow us to clarify the threshold concentration of IL-33 that leads to optimal cholesterol balance.

Ocular allergies.

Ocular allergic disease affects not only the conjunctivae but also surrounding structures including the eyelids. Allergic diseases of the eyelid include atopic dermatitis, contact dermatitis, and urticaria/angioedema. They must be differentiated from nonallergic eyelid diseases. Allergic diseases of the conjunctivae comprise a spectrum of disorders from common, non-sight-threatening conditions such as seasonal allergic conjunctivitis, perennial allergic conjunctivitis, and giant papillary conjunctivitis to less common and potentially sight-threatening diseases such as vernal keratoconjunctivitis and atopic keratoconjunctivitis. Each of these conditions is mediated primarily by type I hypersensitivity reactions. The clinical manifestations, differential diagnosis, and treatment of these conditions are reviewed in this article.

Pneumocystis carinii pneumonia in a 15-year-old with chronic mucocutaneous candidiasis.

A 15-y-old male patient with chronic mucocutaneous candidiasis (CMCC) and new onset adrenal insufficiency developed Pneumocystis carinii pneumonia (PCP). The literature on infectious complications of CMCC is reviewed and clinical and laboratory characteristics of the only previously described case of PCP in CMCC are compared with those of the patient reported here.

IL-1, IL-6, and PDGF mRNA expression in alveolar cells following stimulation with a tobacco-derived antigen.

To test the hypothesis that inflammatory cytokine production might be an early event in the development of the disease associated with smoking, we used alveolar cells from healthy nonsmokers stimulated with TGP as a model system. TGP, a phenol-rich glycoprotein which is present in tobacco leaves and cigarette smoke condensate, activates the immune system. It stimulates polyclonal B cell differentiation, induces primarily an IgE response, and activates human leukocytes to produce IL-1. Using in situ nucleic acid hybridization we show that the steady-state levels of IL-1 alpha, IL-1 beta, IL-6, platelet-derived growth factor (PDGF)-A, and PDGF-B mRNAs are consistently elevated in the alveolar cells of all donors following TGP stimulation. The kinetics of mRNA expression suggest that IL-1 alpha and IL-1 beta mRNAs are independently regulated in alveolar cells, while the regulation of PDGF-A and PDGF-B mRNA seems to be similar. The activated cells also synthesize elevated levels of IL-1 and IL-6. These findings lend support to the suggestion that some clinical consequences of smoking might be initiated and enhanced by the production of inflammatory cytokines. Moreover, IL-6 could also activate a polyclonal B cell response, which could lead to the synthesis of autoantibodies and thus cause immune-mediated tissue injury.

Heterogeneity of pemphigus vulgaris antigens.

The immunologic specificity of pemphigus vulgaris (PV) antigens was studied by serologic analysis. Serum samples of 19 patients with PV antibodies were tested for reactivity with seven specimens of normal human skin by indirect immunofluorescence. Some PV antibodies reacted to antigens expressed in all specimens of skin, while others reacted to antigens expressed in only some specimens of skin. This was not due to differences in the titer of PV antibodies among serum samples or to regional variation or individual-to-individual fluctuations in the expression of a single PV antigen. The patterns of cross-reactivity suggest that PV antigens are heterogeneous. Two different groups can be defined serologically: (1) a "major" (PV) antigen expressed in all individuals, antibodies to which are the most common in PV; (2) a family of "minor" PV antigens whose expression varies from individual to individual. Several immunologically distinct PV antigens are expressed concurrently in the same specimen of skin.

Regional variations in antigenic properties of skin. A possible cause for disease-specific distribution of skin lesions.

The possibility that the distribution of skin lesions in some cutaneous diseases is due to variations in the antigenic properties of skin was investigated by mapping the expression of the skin-specific pemphigus vulgaris and bullous pemphigoid antigens in different regions of the body. The expression of both antigens was relatively stable within the same region, but varied between regions in a pattern that was distinct for each antigen. For each antigen there was a correlation between regions of high expression and location of skin lesions in autoimmune diseases involving the antigen. The results indicate that there are marked regional differences in the antigenic properties of skin and suggest this may influence the distribution of cutaneous lesions in some skin diseases.