Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria.

Summary: Background. Biomarkers of disease activity/severity and criteria of autoimmune chronic spontaneous urticaria (CSU) are still a matter of debate. Objective. To investigate possible correlations between clinical and biological markers and their associations with: 1) disease activity, 2) resistance to H1-antihistamines, 3) autoimmunity and 4) autologous serum skin test (ASST) in patients with CSU. To also analyze biological parameter modifications in patients with CSU treated with omalizumab. Materials and methods. Disease activity, H1-antihistamines response and presence of concomitant autoimmune disease were prospectively recorded in 95 patients with CSU. For 60 of them, ASST was performed. Broad biological analysis were performed. Results. C-reactive protein (CRP) serum levels were higher in H1-antihistamines unresponders (p less-than 0.0001) and in more active diseases (p = 0.033). D-dimer plasma levels were higher in H1-antihistamines unresponders (p = 0.008) and in patients with autoimmune status (concomitant autoimmune disease and/or with autoantibodies) (p = 0.016). Total immunoglobuline E (IgE) serum level was lower in patients with positive ASST. Blood basophil counts were lower in patients with CSU and especially in H1-antihistamines unresponders (p = 0.023), in patients with more active disease (p = 0.023), with positive ASST (p = 0.001), and with autoimmune status (p = 0.057). Conversely, under omalizumab, a decrease of CRP (p = 0.0038) and D-dimer serum/plasma levels (p = 0.0002) and an increase of blood basophil counts (p = 0.0023) and total IgE serum levels (p = 0.0007) were observed. Conclusions. This study brings additional evidences of interest to investigate IgE, D-dimer serum/plasma levels and basophil blood counts in patients with CSU as they could be correlated to disease activity, response to treatment and/or autoimmunity.

Phenotype and function of circulating memory T cells in human vitiligo.

BACKGROUND: Vitiligo is a chronic inflammatory skin disorder characterized by the loss of melanocytes. While a T helper cell (Th)1/cytotoxic T cell (Tc)1-skewed immune response is now well demonstrated in vitiligo, recent data suggest that the T-cell component could be more complex, involving different combinatorial T-cell subsets. OBJECTIVES: To analyse the phenotype and function of circulating CD4+ and CD8+ memory T-cell subsets in patients with stable and active vitiligo, in comparison with patients with psoriasis and healthy controls. METHODS: This is a monocentric, prospective, descriptive and exploratory study. Multiparametric flow cytometry analyses were performed to evaluate the surface expression of homing and T-cell-subset markers together with intracellular cytokine production in peripheral blood mononuclear cells from 60 patients with vitiligo, 25 patients with psoriasis and 28 healthy donors. RESULTS: Vitiligo peripheral blood circulating effector and central memory T cells expressed similar proportions of skin-homing markers. Decrease in the frequencies of circulating CD4+ and CD8+ Th1/Tc1, Th17/Tc17, and Th1/Th17 or Tc1/Tc17 effector memory T-cell subsets were observed in patients with vitiligo compared with healthy donors. Similar observations were made in psoriasis. In contrast, vitiligo circulating T cells showed a similar capacity for proinflammatory cytokine production compared with those in psoriasis and healthy controls. CONCLUSIONS: The decreased frequencies of circulating Th1/Tc1, Th17/Tc17 and Th1/Th17-Tc1/Tc17 cells suggest a possible migration of these T-cell subsets into the skin of patients with vitiligo. These could be targeted to prevent flares of the disease. What is already known about this topic? Vitiligo is a chronic inflammatory skin disorder associated with the loss of melanocytes. Vitiligo is characterized by a T helper cell (Th)1/cytotoxic T cell (Tc)1-skewed immune response in the skin. What does this study add? A thorough analysis of the phenotype and function of circulating memory T cells suggests the migration of Th1/Tc1, Th17/Tc17 and Th1/Th17-Tc1/Tc17 cell subsets in the skin. What is the translational message? A better understanding of the different immune T-cell subsets involved in vitiligo could lead to better therapeutic options. Linked Comment: Matos. Br J Dermatol 2020; 183:803.

Traitements topiques et photothérapie dans la dermatite atopique: Topical treatments and phototherapy in atopic dermatitis.

Atopic dermatitis is a chronic disease with an alteration of the skin barrier and an abnormal immune response. The European guidelines for treatment of atopic dermatitis in children and adults recommend basic hygiene rules including daily use of emollient. Then in the first therapeutic line, for mild or acute atopic dermatitis, the prescription of local care by topical corticosteroids or topical calcineurin inhibitors is recommended. A proactive treatment is now recommended. If the atopic dermatitis is moderate or recurrent, the use of phototherapy in addition to topical treatment is recommended. Each therapeutic step can be added to improve the lesions and reduce the burden of the disease on the patient's daily life. © 2019 Elsevier Masson SAS. All rights reserved.

Allergic contact reaction to antiseptics in very young children.

BACKGROUND: Contact dermatitis from topical antiseptic use has been reported mostly in adults, but rare cases of chlorhexidine contact dermatitis have also been described in young children. OBJECTIVE: To evaluate contact allergic dermatitis to antiseptics in young children. METHODS: The children mostly referred for a misdiagnose (cellulitis) were patch tested with a selection of the European baseline series, an antiseptics series and the personal topical products used. RESULTS: Fourteen children (8 boys, 6 girls) received a diagnosis of contact dermatitis to antiseptics between May 2010 and December 2017. The mean age at diagnosis was 38 months (8 months to 8 years); three children only had a personal history of atopy. Chlorhexidine gluconate was positive in seven cases, and benzalkonium chloride in eight cases, and in four cases, both allergens were positive. CONCLUSION: These small case series confirm that both chlorhexidine and benzalkonium chloride are implicated in contact dermatitis from antiseptic use in the paediatric population. We emphasize the initial misdiagnose of these patients, the very young age of the children and the allergenic potential of common antiseptics in non-atopic children. We hypothesize that the systematic use of antiseptics for umbilical cord care could be responsible for the sensitization in newborns.

Heat shock protein 70 potentiates interferon alpha production by plasmacytoid dendritic cells: relevance for cutaneous lupus and vitiligo pathogenesis.

BACKGROUND: Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells specialized in the production of type I interferon (IFN-α/ß) and involved in various cutaneous inflammatory and autoimmune disorders, such as cutaneous lupus erythematosus (CLE) and vitiligo. Heat shock proteins (HSPs) are molecular chaperones essential for maintaining cellular functions, but they can act as a danger signal during inflammation. OBJECTIVES: To decipher the role of HSP70 in the production of IFN-α by pDCs in CLE and vitiligo. METHODS: Expression of HSP70 and CD123+ pDCs was analysed by immunohistochemistry or immunofluorescence in CLE and vitiligo skin samples. Flow cytometry was performed to analyse expression of HSP70 receptors, activation markers on pDCs and DNA uptake by pDCs in the presence of HSP70. The impact of HSP70 on DNA-induced IFN-α secretion by pDCs was evaluated by enzyme-linked immunosorbent assay (ELISA). The effect of IFN-α on chemokine (C-X-C motif) ligand 9 (CXCL9)/10 gene and protein expression by keratinocytes was determined by real-time polymerase chain reaction and ELISA. RESULTS: Infiltration of pDCs in CLE and progressive vitiligo was primarily located in the epidermis, close to keratinocytes expressing HSP70. In vitro experiments revealed that the pDCs expressing HSP70 receptor Lox-1 (lectin-like oxidized low-density lipoprotein-receptor-1) were able to aggregate HSP70. Exogenous HSP70 induced activation of pDCs and increased the uptake of exogenous DNA. Furthermore, HSP70 potentiated DNA-induced IFN-α production by pDCs. Finally, IFN-α induced expression of CXCL9 and CXCL10 by keratinocytes. CONCLUSIONS: These data demonstrate that interaction between HSP70 and pDCs in CLE and vitiligo is a prerequisite for the enhancement of IFN-α production, and could be an interesting target.