Background
Atopic dermatitis and psoriasis are common inflammatory diseases, canonically described as involving distinct T-helper polarization and granulocytic infiltration. Acute atopic dermatitis lesions are associated with TH2 and eosinophilic inflammation, while psoriasis lesions are associated with TH1/17 and neutrophilic inflammation. Despite intensive investigation, these pathways remain incompletely understood in vivo in human subjects.
Objective
Using atopic dermatitis and psoriasis lesional skin as exemplar TH2 and TH1/17 diseased tissue, we sought to clarify common and unique molecular and pathophysiologic features in inflamed skin with different types of inflammatory polarization.
Methods
We conducted gene expression microarray analyses to identify distinct and commonly dysregulated expression in atopic dermatitis (by Hanifin & Rajka criteria) and psoriasis lesions. We defined gene sets comprising genes encoding cytokines, chemokines, and growth factors that were uniquely or jointly dysregulated in atopic dermatitis and psoriasis, and calculated aggregate gene set expression scores for lesional skin of these dermatoses and healthy control skin.
Results
The atopic dermatitis gene set score correlated with systemic and local measures of allergic inflammation including serum IgE, blood eosinophil count, and tissue eosinophils. Unexpectedly, genes encoding neutrophil chemoattractants among the common gene set were highly expressed in atopic dermatitis lesional skin. H&E and immunohistochemical analyses showed the numbers of neutrophils in atopic dermatitis lesional skin were comparable to those in psoriasis lesional skin, and both were correlated with the extent of expression of neutrophil chemoattractant genes.
Conclusion
These data are evidence that neutrophilic inflammation is a feature of lesional atopic dermatitis pathology, comorbid with allergic inflammation.
Galectin-3 belongs to a family of -galactoside-bind-proposed that Th2 cells play a key pathogenic role in AD, which is supported by the presence of peripheral blood eosinophilia and enhanced serum IgE levels in a majority of AD patients. In acute lesions of AD, there is a significant increase in the number of cells expressing IL-4, IL-5, and IL-13 mRNA and proteins, suggesting preferential accumulation of Th2 cells. Our current understanding of AD is that there is a predominant Th2 cytokine milieu in the initiating stages or acute lesions of AD and a mixed Th1 and Th2 pattern in chronic lesions.
Lichen sclerosus (LS) and lichen planus (LP) are two conditions frequently affecting genital skin whose clinical and histologic distinction can be difficult. Both diseases can feature solitary genital lesions with bandlike lymphocytic infiltrates. We reviewed 68 cases of vulvar LS to find sections that contained a transition from a lichenoid interface reaction to pathognomonic LS (i.e., marked papillary dermal sclerosis or edema), and in these nine cases we studied routinely and specially stained sections, as well as sections stained with a panel of antisera to lymphoid antigens, and compared the findings with those in six cases of genital LP. We assumed that changes at the periphery of a lesion of LS mirror findings seen in early lesions. The features that we found more commonly in the inflammatory phase of LS included a psoriasiform lichenoid pattern (100% LS, 0% LP), basilar epidermotropism (78% LS, 0% LP), loss of papillary dermal elastic fibers (100% LS, 33% LP), basement membrane thickening (44% LS, 0% LP), and epidermal atrophy (33% LS, 0% LP). Features found more commonly in LP included many cytoid bodies (0% LS, 100% LP), wedge-shaped hypergranulosis (11% LS, 100% LP), basal squamatization (22% LS, 100% LP), and pointed rete ridges (11% LS, 83% LP). We did not detect any significant differences in the immunohistochemical features of the infiltrates. Taken together, these histologic features comprise light microscopic criteria for the diagnosis of early vulvar LS and its differentiation from LP.
This study substantiates a frequent occurrence of DARs at contrast-enhanced CT compared with that in control subjects. Continued growth in the use of contrast-enhanced CT suggests a need for greater awareness and attention to prevention and management.
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