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Atopic dermatitis is a chronic form of allergic contact dermatitis that is closely associated with a compromised epidermal barrier. Immunogenicity of a given electrophilic hapten after penetration of this barrier depends directly on biochemical reactions in the thiol-rich layer in the stratum granulosum. In response to electrophilic hapten, NF-erythroid 2-related factor 2 (NRF2) in keratinocytes efficiently induces the production of antioxidants. In this study, we show that the immunogenicity of a given hapten depends directly on the extent to which it induces antioxidant host defenses within the epidermal tissue. We found that allergic contact dermatitis did not develop in NRF2-deficient mice because of compromise of the epidermal innate immune responses that upregulate IL-1α. We also analyzed epidermal NRF2 in association with congenital disorders with features similar to atopic dermatitis in humans. Epidermal samples from patients with Netherton syndrome and peeling skin syndrome exhibited elevated levels of NRF2 and also elevated levels of its downstream target, small proline-rich protein 2. Taken together, these results suggest that the thiol-mediated biochemical responses in the stratum granulosum provide a critical link between defective epidermal barrier function and the development of atopy. Likewise, our results suggested that NRF2 may have a profound impact on the generation of cutaneous immunological memory., (Copyright © 2020 by The American Association of Immunologists, Inc.)

The clinical differential diagnosis of erythroderma is extensive and includes both benign and malignant causes. The authors present an exceptional case of erythroderma secondary to pre-B-cell lymphoblastic leukemia cutis, with diagnostic findings on biopsy.

Erythroderma may be secondary to a cutaneous T-cell lymphoma (CTCL) and various other erythrodermic inflammatory dermatoses (EID), and their histopathologic distinction is often difficult. The aim of this study was to determine if morphological parameters, namely: the presence of b-catenin, and JunB (previously shown to be expressed by CTCL cells), the epidermal CD8:CD3 ratio, and CD30 expression may help in the histopathologic diagnosis of erythroderma, especially in differentiating CTCL and EID. We retrospectively reviewed a series of 47 skin biopsies from patients with erythroderma (18 CTCL and 29 EID). The diagnosis of each case was established using clinical, biological and histopathologic data. After a blind assessment of the hematoxylin--eosin--safran stained slides, a correct diagnosis of the underlying cause of erythroderma was made only in 31% of cases. A correct differential diagnosis between lymphoma and EID was done with certainty in 57% of cases. Various morphologic and phenotypic parameters were then recorded and we compared their frequency in the CTCL versus the EID group. With the exception of atypical lymphocytes, the moderate to high density of dermal infiltrates and Pautrier microabcesses, only found in CTCL, no morphologic parameter was found to be specific of CTCL, although single lymphocytes epidermotropism, telangiectasias, and slight lymphocytic dermal infiltrate were significantly more frequent in EID. A low (<10%) CD8:CD3 ratio in the epidermal lymphocytic infiltrate and dermal CD30+ lymphocytes were significantly more frequent in CTCL. JunB expression by lymphocytes was specific of CTCL, but was inconstant in our series (17%). We found β-catenin expression in a minority of cases from both the CTCL and EID groups. Among EID, dermal suprapapillary thinning was specific of psoriasis. Neutrophils exocytosis and edema of papillary dermis were significantly more frequent in psoriasis, and spongiosis was more frequent in eczema. In conclusion, few morphological and phenotypical parameters are helpful in making a differential diagnosis between erythrodermic CTCL and EID using paraffin embedded skin biopsies.

Background: Erythrodermas are often life-threatening conditions in infants. Determination of the underlying cause is crucial. Microscopic changes in adult erythroderma lack specificity., Objective: To determine if an early skin biopsy is helpful for the diagnosis of neonatal and infantile erythroderma., Methods: Seventy-two patients admitted for erythroderma in the first year of life were retrospectively included. One hundred and eleven skin biopsies (12-year period) were examined by 3 pathologists blinded to the clinical diagnosis, and classified into atopic dermatitis, immunodeficiency (ID), psoriasis, Netherton syndrome (NS), ichthyosis, other. From year 2000, LEKTI antibody was performed when NS was suspected. Pathological diagnosis was then compared with clinical diagnosis., Results: The final diagnosis was made in 69.3% of the cases. In 57.6%, pathological diagnosis was in accordance, and in 11.7%, it was in accordance, but other diagnosis had also been proposed. For ID, sensitivity and specificity were 58.5 and 98.5%, respectively. Before year 2000, NS was frequently misdiagnosed with psoriasis, but with the use of LEKTI antibody, sensitivity and specificity were 100%., Conclusion: Skin biopsy is helpful for etiologic diagnosis of early erythroderma of infancy, particularly in ID and NS, the most severe diseases. Consequently, these results justify an early systematic skin biopsy for a better and earlier management.

Background: Exfoliative dermatitis (ED) can result in protein loss due to scaling causing a negative nitrogen balance. Freedberg and Baden (J Invest Dermatol 1962; 38: 277-284) estimated the amount of scale lost in ED by collecting it in an occlusive suit. Subsequently, the nitrogen content was determined by the Kjeldahl method. The exact amount of protein supplementation in ED, dependent on scale loss, is not well established. As occlusion and hyperthermia caused by the suit can inhibit scaling, the objectives of the present study were to design an alternative method to measure the amount of scale lost, to estimate the protein content of the scale, and to propose suitable recommendations for protein supplementation., Methods: In 40 patients with ED, the total protein content lost through scaling per day (P) was determined by the following equation: P = TxIxYxX/25x10(4) g, where T is the total body surface area in square meters, I is the percentage area involved in scaling, estimated using computer-aided design (CAD graph), Y is the amount of scale lost per unit area (0.0025 m2) in milligrams, and X is the quantity of protein present in 1 g of scale in milligrams estimated by a spectrophotometer., Results: It was observed that patients with ED secondary to drug reactions, eczema, and psoriasis lost 7.2, 9.6, and 22.6 g of scale with a protein content of 4.2, 5.6, and 12.8 g respectively. The difference in the amount of protein lost in ED secondary to drug reactions and eczema was not statistically significant; however, the protein lost in psoriasis was significant (p < 0.01 to p < 0.05)., Conclusions: ED may increase the daily protein loss by approximately 25-30% in psoriasis and 10-15% in other causes. Standard treatment for ED and protein supplementation based on our recommendations can minimize the adverse effects of a negative nitrogen balance.

The comparative pattern of 3H-thymidine (3H-T) pulse labelling in lesions of psoriatic erythroderma (3 cases) and of psoriasis vulgaris (20 cases) has been studied by means of radioautography. In the epidermis, no difference was noted between the two types of lesions concerning the epidermal 3H-T labelling index (L.I.) and the localization of labelled cells. The 3H-T L.I. of "round" cells infiltrating the dermis was much higher in lesions of psoriatic erythroderma (4.03 +/- 0.56%) than in lesions of psoriasis vulgaris (0.62 +/- 0.21%), and the difference is highly significant (p less than 0.0001). The findings indicate that most of these labelled cells could well be lymphoblasts, suggesting that an immunological process is possibly involved in the pathogenesis of psoriatic erythroderma.