The skin is the largest organ of the body, whose main function is to protect the body against the loss of physiologically important components as well as harmful environmental insults. From the inside to the outside, the skin comprises three major structural layers: the hypodermis, the dermis and the epidermis. The epidermis contains four different sublayers, the stratum corneum (SC), stratum granulosum, stratum spinosum and stratum basale, where the barrier function of the skin mainly lies in the outermost layer of the epidermis, the SC. The SC contains corneocytes that are embedded in a lipid matrix existing in the form of lipid bilayers. The lipid bilayers are formed mainly from ceramides, free fatty acids and cholesterol, constitute the only continuous pathway across the SC and are responsible for the barrier function of the skin. However, the depletion or disturbance of SC lipids in the SC leads to a perturbation of the barrier function of the skin, and, conversely, several skin diseases such as psoriasis and atopic dermatitis are associated with the depletion of these SC lipids. Therefore, it is of paramount importance to understand the interrelationship between the depletion of SC lipids and skin diseases as well as factors that affect the composition and organization of SC lipids in order to assess the potential benefit of a direct replacement of the missing SC lipids as a means of treating affected, aged or diseased skin. i 2014 S. Karger AG, Basel

Hidradenitis suppurativa (acne inversa) is a chronic suppurative and scarring inflammatory disease with predilection in the apocrine gland-bearing areas. Histological investigations in the 1990s showed keratotic occlusion of the terminal follicle structure to be the initial cause. Our investigations describe and reproduce the morphology and try to figure out very early lesions of HS. A total of 262 operative specimens from 60 patients were investigated by routine histology and 11 operative specimens by immunohistochemistry: HS is dominated by a heterogeneous histological image. 82% of the surgical specimens showed mild or pronounced follicular hyperkeratosis, whereas an isotopic hyperplasia of follicular epithelium was evident in 77%. Pronounced perifolliculitis was seen in 68% and rupture of the follicle structure in 28%. Features which had not so far been described in detail were: epidermal psoriasiform hyperplasia (43%) and subepidermal interfollicular inflammatory infiltrate (78%). In all 11 specimens, immunohistochemical investigations showed a perifollicular and subepidermal inflammation of CD-3-, CD-4-, CD-68-, CD-79- and CD-8-cells, the latter with a striking selective epitheliotropism. To conclude, we could show follicular hyperkeratosis and lymphocytic perifollicular inflammation as early patterns in pathogenesis, whereas rupture of the follicle structure takes place later. Finally, it seems that there are two hot spots of inflammatory events (perifollicular and subepidermal) composed of a comparable inflammatory cell mixture. The CD-8 cell epitheliotropism (follicular and epidermal) described here and its influence in follicular hyperkeratosis, in hyperplasia of follicular epithelium and in epidermal psoriasiform hyperplasia will be of further interest, for instance, concerning early pharmacological intervention.

Infundibular hyperkeratosis, hyperplasia of the follicular epithelium and perifolliculitis are major histopathological characteristics of hidradenitis suppurativa/acne inversa. These apparently precede rupture of the follicle. In particular, hyperplasia of the follicular epithelium probably marks the beginning of sinus formation, which usually spreads horizontally. Psoriasiform hyperplasia of the interfollicular epidermis with subepidermal inflammatory infiltrate might be interpreted as an inflammation-driven process basically identical to that which is evident at the terminal follicle. However, it does not lead to harmful and progressive sequelae like those (rupture, sinus tracts) seen at the terminal follicles.

ObjectiveTo identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6‐month period in patients with systemic sclerosis (SSc).MethodsIn this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses.ResultsOf the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow‐up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681–0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510–0.756).ConclusionThis international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs.

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