Are the concepts of induction of remission and treatment of subclinical inflammation in atopic dermatitis clinically useful?

BACKGROUND: Atopic dermatitis (AD) treatment is often initiated by symptoms or visible erythema. The role of induction of remission or treatment of inflammation that is not visible is unclear. OBJECTIVE: We investigated whether (1) the notion of subclinical inflammation is scientifically sound, (2) treatment corrects subclinical inflammation, and (3) different strategies for initial clearance of AD affect long-term disease control. METHODS: We conducted a systematic review based on searching MEDLINE, Embase, the Cochrane register of randomized controlled trials, and the Global Resource of Eczema Trials from inception to the end of October 2012. RESULTS: Twenty of 26 included studies presented evidence of subclinical inflammation, with a continuum of changes in skin barrier dysfunction, the proinflammatory cytokine milieu, and lymphocytic infiltration from normal-appearing skin to posttreatment lesional skin to active skin lesions in patients with AD. Such subclinical inflammation is improved, with proactive treatment aimed at maintaining remission. Failure to achieve control of AD symptoms with initial therapy was associated with a higher risk of relapse in 14 randomized controlled trials (fluticasone: risk ratio, 1.31; 95% CI, 1.02-1.68; tacrolimus: risk ratio, 1.36; 95% CI, 1.12-1.66). Three trials on systemic therapy/phototherapy suggested that induction of remission resulted in long-term remission without maintenance therapy in approximately 15% of patients. CONCLUSION: Induction of remission followed by maintenance therapy might prove to be an integral part of a disease-modifying strategy for treating atopic diseases.

Does "autoreactivity" play a role in atopic dermatitis?

The role of autoimmunity in atopic dermatitis (AD) is unclear. We sought to critically examine the occurrence, correlation with severity, and possible causative role of autoreactivity in patients with AD. Our systematic review of studies identified from MEDLINE included 31 experiments that described autoreactivity in patients with AD. We defined autoreactivity as in vitro or in vivo evidence of immune response to autologous human, generic human, or recombinant human proteins or other tissue/cellular components. Autoreactivity prevalence in patients with AD ranged from 23% to 91% in 14 studies involving 2644 participants, although it did not appear to vary with age, sex, or disease duration. In contrast to studies of AD, IgE autoreactivity was not found in healthy subjects or in those with allergic rhinoconjunctivitis, psoriasis, systemic lupus erythematosus, or other inflammatory diseases (8 studies of 816 participants). Two reports found a positive correlation between autoreactivity and AD severity. We suggest that autoreactivity might be playing a causative role in AD based on the magnitude and specificity of the associations found; plausible mechanisms through IgE autoantibodies, IgG autoantibodies, and T(H)1 autoreactivity; and experimental elicitation of eczematous lesions after provocation. Whether autoantibodies contribute to AD chronicity now needs to be examined in longitudinal studies.

Adiponectin, total antioxidant status, and urine albumin excretion in the low-risk "Golden Years" type 1 diabetes mellitus cohort.

Adiponectin is associated with inflammation and oxidative stress. Levels are reduced in type 2 diabetes mellitus and coronary heart disease. Conversely, levels are elevated in type 1 diabetes mellitus (T1DM) and associated with microalbuminuria and diabetic nephropathy. An explanation may be that elevated adiponectin in T1DM represents a beneficial counterregulatory response to disease. Our aim was to examine adiponectin in relation to urinary albumin excretion and plasma total antioxidant status (TAOS) in subjects with long-standing T1DM. Serum adiponectin and plasma TAOS were measured in 338 samples from the Golden Years cohort. These subjects have T1DM for at least 50 years and are at low risk of complications. Subjects were divided into normoalbuminuria, microalbuminuria, and macroalbuminuria groups. Adiponectin was elevated in women (20.53 ± 5.94 vs 11.8 ± 3.6 mg/L, P < .001); therefore, the samples were sex stratified. Within men, adiponectin was higher in those with macroalbuminuria (normoalbuminuria vs microalbuminuria vs macroalbuminuria: 10.97 ± 3.26 vs 11.55 ± 3.50 vs 23.63 ± 7.07 mg/L, P = .002). In women, no difference was observed (20.48 ± 5.61 vs 20.75 ± 7.04 vs 29.62 ± 7.81 mg/L, respectively; P = .42). Plasma TAOS did not differ by groups. The correlation between adiponectin and TAOS showed a linear increase from normoalbuminuria, microalbuminuria, to macroalbuminuria in men (r = 0.33, P = .001; r = 0.48, P < .001; r = 0.59, P = .04) and women (r = 0.25, P = .01; r = 0.63, P < .001; r = 0.79, P = .08). Adiponectin was higher in women. Within men, levels were significantly higher in the presence of macroalbuminuria. In both sexes, adiponectin and TAOS were correlated, which was most marked with micro-/macroalbuminuria. The increase in adiponectin in the face of an insult may be a compensatory mechanism to reduce oxidative burden.