BackgroundAtopic dermatitis (AD) is a common chronic eczematous skin disease with severe pruritus. Several new therapeutic agents for AD such as dupilumab, an anti–IL-4Rα antibody, have been developed in recent years. We need to predict which agent is the best choice for each patient, but this remains difficult.ObjectiveOur aim was to examine clinical background factors and baseline biomarkers that could predict the achievement of improved clinical outcomes in patients with AD treated with dupilumab.MethodsA multicenter, prospective observational study was conducted on 110 patients with AD. The Eczema Area and Severity Index was used as an objective assessment, and the Patient-Oriented Eczema Measure and Numerical Rating Scale for Pruritus were used as patient-reported outcomes. In addition, some clinical background factors were evaluated.ResultsThe achievement of an absolute Eczema Area and Severity Index of 7 or less was negatively associated with current comorbidity of food allergy and baseline serum lactate dehydrogenase (LDH) levels. There were negative associations between achievement of a Patient-Oriented Eczema Measure score of 7 or less and duration of severe AD and between achievement of an itching Numerical Rating Scale for Pruritus score of 1 or less and current comorbidity of allergic conjunctivitis or baseline serum periostin level. Furthermore, signal detection analysis showed that a baseline serum LDH level less than 328 U/L could potentially be used as a cutoff value for predicting the efficacy of dupilumab.ConclusionBaseline biomarkers such as LDH and periostin and clinical background factors such as current comorbidity of food allergy and a long period of severe disease may be useful indicators when choosing dupilumab for systemic treatment for AD, as they can predict the efficacy of dupilumab.
Acquired circumscribed hyperpigmented patches and plaques have various differential diagnoses, including post-inflammatory hyperpigmentation and mycosis fungoides (MF). Leukomelanoderma is an uncommon cutaneous condition in which the pathogenesis is not fully elucidated. It has been reported that leukomelanoderma occurs after allergic contact dermatitis from hydroquinone or acute cutaneous graft-versus-host disease (1,2). Hyperpigmented MF is a cutaneous T-cell lymphoma with a frequent CD8+ phenotype (3). Herein, we report a case of leukomelanoderma clinically and histologically resembling hyperpigmented MF. A 55-year-old Japanese woman was referred to our department for evaluation of reticulate pigmentation with pruritic erythema on the face. She had used commercially available depigmenting cosmetic reagents for 20 years and ointment containing 10% hydroquinone for 3 months. Physical examination revealed diffuse hyperpigmentation and demarcated hypopigmented macules on the face and neck (Figure 1, a). Dermoscopy showed depigmented spots and reticulated plus dotted hyperpigmentation; it presented a pseudo-pigment network (Figure 1, b). Histological examination of a tissue specimen biopsied from the lesion showed superficial band-like lymphocytic infiltration in dermis accompanying single cells or small clusters in epidermis (Figure 1, c). Interface changes were observed together with melanophages in the dermis. Melan-A-positive melanocytes were absent. Immunohistochemical analysis demonstrated that the epidermotropic lymphocytes were CD3+CD7-, and they had predominance of CD8+ cells (Figure 1, d). These immunohistochemical results mimicked MF. However, PCR analysis of the T-cell receptor g-gene rearrangement was negative. Closed patch test result with hydroquinone (5% pet.) was graded D2 (+?) and D3 (+). Ten months after discontinuing cosmetic reagents and hydroquinone, the pigmentary changes showed improvement. The pathomechanism of leukomelanoderma is unclear. Although post-inflammatory pigmentation due to allergic or contact dermatitis together with direct depigmenting effects from hydroquinone use has been suggested (1), the immunophenotype of T-cells has not been examined. As observed in our patient, interface changes with melanophages, in addition to frequent CD8+ phenotype of the epidermotropism and dermal infiltrate of lymphocytes, were characteristic for hyperpigmented MF (3). Moreover, minimal CD7 expression was a specific finding for MF (4). T-cell receptor clonality was negative in our patient, but the clonality appears to be detected by PCR in up to 50% of the patients with early MF (3). In contrast, the closed patch test was positive for hydroquinone in our patient, and it is reported that CD8+ T-cells are recruited to the interphase between the epidermis and the dermis of the patients with allergic contact dermatitis (5). CD8+ T-cells might contribute to acute cutaneous graft-versus-host disease-like interface changes and destroy melanocytes in the leukomelanoderma lesion. Allergic contact dermatitis presenting as leukomelanoderma was thus suggested in our patient. However, further reports and studies are required to support this issue. Therefore, we considered it necessary to follow the patient, since MF was not absolutely eliminated.
To develop precision medicine for atopic dermatitis (AD), it is critical to establish relevant biomarkers. However, the characteristics of various biomarkers have not been fully understood. We previously carried out the Biomarkers to Predict Clinical Improvement of AD in Patients Treated with Dupilumab (B-PAD) study, a comprehensive nationwide study in Japan, to explore biomarkers for AD.The aim of this study is to find biomarkers associated with objective and subjective clinical findings in patients with moderate-to-severe AD based on the B-PAD study and to identify biomarkers sensitive enough to assess the severity of AD.We performed the B-PAD study as a consortium composed of 19 medical facilities in Japan, enrolling 110 patients with moderate-to-severe AD. We evaluated the Eczema Area and Severity Index (EASI) for objective assessment as well as the Patient-Oriented Eczema Measure (POEM) and a numeric rating scale for pruritus (pruritis-NRS) for subjective assessment, measuring 19 biomarkers at baseline.We found that 12, 6, and 7 biomarkers showed significant and positive associations with the EASI, POEM, and pruritis-NRS, respectively. Most of the biomarkers associated with either the POEM or the pruritis-NRS were included among the biomarkers associated with EASI. Of the biomarkers examined, CCL26/eotaxin-3 and SCCA2 were the most capable of assessing severity for EASI, as shown by the 2 kinds of receiver operating characteristic analyses, respectively, whereas lactate dehydrogenase was the best for both the POEM and pruritis-NRS, again using the 2 analyses.We found biomarkers associated with the EASI, POEM, and pruritis-NRS, respectively, based on the B-PAD study. Moreover, we identified CCL26/eotaxin-3 and/or SCCA2 as the biomarkers having the greatest ability to assess severity in the EASI; lactate dehydrogenase did the same for the POEM and pruritis-NRS. These findings will be useful in treating patients with moderate-to-severe AD.
Cette etude a pour objectif d'examiner les evolutions stylistiques des chansons realistes, qui sont en vogue sous la Troisieme Republique. La problematique est la suivante : comment le mot « realiste» evolue-t-il? ; quels sont les themes principaux, pourquoi et comment sont-ils traites? ; comment la situation sociale du moment influence-t-elle les oeuvres produites? ; comment la performance des artistes concourt-elle a la creation de l'univers realiste ? ; quelle est la relation entre chanteur/chanteuse realiste et la chanson realiste ? Sur ces bases, j'analyse le processus de la popularisation du genre realiste, tout en examinant la carriere d'Aristide Bruant et ses chansons stereotypees selon le determinisme naturaliste. L’assistance semble attendre de lui et de ses œuvres, censees representer la vie des marginaux, l'illusion de l'encanaillement. Suite a la demolition des furtifications, le genre realiste se cree d'autres decors plus lointains tels les ports et la Legion etrangere, qui augmentent le fantasme des spectateurs sur les milieux marginaux. J'accorde une importance particuliere aux effets des interpretes qui s'identifient aux personnages des chansons, car ils compensent ainsi l'absence du sens de la realite du public. Pour finir, j'argumente, sur la negation de l'univers pseudo-realiste au travers de l'etude des contre-courants du genre realiste et je montre comment le genre decline progressivement avec les transformations de la societe francaise.
Most natural objects have a texture on their surface, so the segregation between shading and texture is crucial for the robust perception of three-dimensional structure: The visual system has to decide whether shading or texture evoked the luminance change. We found that the contextual pop-out that results from shading was not suppressed, but was even facilitated, when random texture was added to the luminance of the entire stimulus, indicating the functional segregation and facilitative interaction between shading and texture cues. The local contrast evoked by random texture within a figure or at a boundary was a major factor in the facilitation, suggesting the crucial role of early vision in the interaction between the cues.
