Yakun Wang

Psoriasis is associated with increased levels of serum leptin

SIR, Leptin, the product of the obesity gene (ob gene), is a 16-kDa peptide hormone synthesized and secreted by adipocytes. Circulating leptin levels show a marked sexual dimorphism, being two to three times higher in females than in males. Leptin affects many physiological and metabolic pathways, including the regulation of body weight, energy expenditure, endocrine functions, reproduction and immunity. Psoriasis is considered to be a T-cell-mediated inflammatory skin disease, with a preponderance of type 1 cytokines. Because leptin promotes type 1 cytokine synthesis and suppresses type 2 cytokine production, we speculate that leptin might play a role in the pathogenesis of psoriasis. Thus far no studies have been reported on the association of serum leptin with psoriasis. A total of 144 psoriatic patients and 54 healthy nonpsoriatic blood donors were recruited in the study (Table 1). Exclusion criteria included age outside the range 16–69 years, use of systemic medications and systemic diseases. Body mass index (BMI) and psoriasis area and severity index (PASI) scores were calculated as previous described. Table 2 shows that there was a significant difference in the serum leptin levels between male and female controls (P < 0Æ01). A significant increase of serum leptin in female patients with psoriasis (10Æ2 ± 4Æ8) vs. male patients (5Æ5 ± 3Æ1) was also detected (P < 0Æ01). As sex appeared to be an important factor in relation to the level of serum leptin, all the comparisons were made among sex-stratified populations. The serum leptin levels in male (5Æ5 ± 3Æ1) and female (10Æ2 ± 4Æ8) psoriatic patients were significantly higher than those in male (3Æ5 ± 1Æ5) and female (6Æ9 ± 2Æ9) controls (P < 0Æ01). The leptin levels in male psoriasis vulgaris (PV) (5Æ4 ± 2Æ8) and erythrodermic psoriasis (EP) (5Æ2 ± 3Æ3) patients were all significantly higher than those in male controls (3Æ5 ± 1Æ5) (P < 0Æ01 and 0Æ05, respectively). The serum leptin levels in female patients with PV (10Æ1 ± 4Æ6) and palmoplantar pustulosis (PPP) (9Æ9 ± 5Æ3) were also significantly higher than those in female controls (6Æ9 ± 2Æ9) (P < 0Æ01). In addition, compared with their corresponding controls, generalized pustular psoriasis (GPP) in females (13Æ7 ± 5Æ5) and arthropathic psoriasis (AP) in males (7Æ2 ± 4Æ6) also showed a statistically significant difference (P < 0Æ01). As there were only a few cases of male GPP, male PPP, female AP and female EP, the respective differences were not regarded as significant. The serum leptin levels were all significantly higher in male PV patients with or without a family history (P < 0Æ01), and in female PV patients with a family history (P < 0Æ05) or without a family history (P < 0Æ01). In both male and female patients with PV, the difference between serum leptin levels of patients with a family history and those without a family history was not statistically significant (P > 0Æ05). The serum leptin levels in patients with psoriasis showed positive correlation with BMI (male: q = 0Æ51, female: q = 0Æ35, P < 0Æ01), but not with patient’s age (P > 0Æ05). The serum leptin levels in normal controls also showed positive correlation with BMI (male: q = 0Æ49, female: q = 0Æ59, P < 0Æ01), but not with their age (P > 0Æ05). PASI scores in PV patients showed no correlation with serum leptin levels.

Localization of haptoglobin in normal human skin and some skin diseases.

Background  Haptoglobin (Hp) is an acute‐phase reactant, known to be produced mainly in the liver. Haptoglobin can also be detected in the cytoplasm of normal epidermal Langerhans cells (LCs), and can prevent their functional maturation. The synthesis of Hp in skin cells has not been well studied.

Antioxidants add protection to a broad-spectrum sunscreen.

Background.  Exposure of human skin to ultraviolet radiation (UVR) results in erythema, pigment darkening, skin cancer and photoageing. In addition to conventional organochemical and the physical–mineral type sunscreens (SS), other non‐SS protective strategies have been investigated, including antioxidants (AOx) and topical DNA repair enzymes.

Childhood bullous pemphigoid treated by i.v. immunoglobulin.

Bullous pemphigoid is an acquired autoimmune subepidermal blistering disorder mostly seen in the elderly. Childhood bullous pemphigoid is very rare. For the first time we report a case of childhood bullous pemphigoid associated with infantile eczema. Two weeks after a routine vaccination, a 3.5‐month‐old boy with infantile eczema developed a generalized blistering disorder. Histopathology revealed a subepidermal blister. Direct immunofluorescence showed linear depositions of C3 along the basement membrane zone. Indirect immunofluorescence studies demonstrated the presence of circulating immunoglobulin G antibodies directed against the epidermal side of salt‐split skin. Enzyme‐linked immunosorbent assay demonstrated serum level of anti‐BP180 antibody elevated. The patient was successfully treated by high‐dose i.v. immunoglobulin.

Lichen planus pemphigoides associated with Chinese herbs

We report a 62‐year‐old Chinese woman with a 2‐year history of lichen planus presenting with extensive violaceous maculopapules and plaques 1 week after taking an oral preparation of Chinese herbs. The patient developed vesiculobullous skin lesions 7 weeks later. Histopathological examination showed subepidermal blisters and adjacent bandlike lymphocytic infiltration. Direct immunofluorescence revealed linear deposits of IgG and C3 along the basement membrane zone. Indirect immunofluorescence showed IgG antibody deposition along the epidermal side of salt‐split human skin. Circulating anti‐bullous pemphigoid 180 antibodies were detected by ELISA. Lichen planus pemphigoides (LPP) was diagnosed. To our knowledge, this is the first report of LPP associated with oral Chinese herbs.

Expression of haptoglobin in human keratinocytes and Langerhans cells

Background  Epidermal Langerhans cells (LCs) play an important role in cutaneous immunological reactions. Freshly obtained or intraepidermal LCs are incapable of activating autologous naive T cells. However, when they are cultured for 2–3 days, LCs are able to activate autologous T cells. It has been proposed that haptoglobin (Hp) is the inhibitor that prevents LC functional transformation in the skin. Abundant Hp has been found in the cytoplasm of epidermal LCs. However, the source of Hp in LCs has not been addressed.

Protective Effects of Cyclooxygenase‐2 Inhibitors on Narrow‐band Ultraviolet B‐irradiated Epidermal Ia+ Langerhans Cells and Thy‐1+ Dendritic Epidermal T Cells in Mice

Cyclooxygenase (COX)‐2 inhibitors are known to be used as chemopreventative agents against certain malignancies. Thus far, there has been very limited information on whether COX‐2 inhibitors protect against chronic narrow‐band UVB (NB‐UVB)‐induced immunosuppression. The present study investigated the effect of nonselective and specific COX‐2 inhibitors, indomethacin and celecoxib, on epidermal Ia+ Langerhans cells (LCs) and Thy‐1+ dendritic epidermal T cells (DETCs) in mice irradiated with NB‐UVB. Sixty female BALB/c mice were divided randomly into the control group (sham) and the experimental groups (irradiated with NB‐UVB for 17 weeks, further divided into five groups according to the diets containing different concentrations of either COX‐2 inhibitors). Alterations in the density and morphology of epidermal Ia+ LCs and Thy‐1+ DETCs in mice were documented using fluorescence microscopy. Chronic NB‐UVB irradiation substantially decreased the density and altered the morphology of the epidermal Ia+ LCs and Thy‐1+ DETCs in control mice. The dietary supplementation of both COX‐2 inhibitors displayed a dosage‐dependent protective effect on the murine dendritic cells irradiated by NB‐UVB. In conclusion, COX‐2 inhibitors protected against chronic NB–UVB‐induced density and morphologic changes in epidermal Ia+ LCs and Thy‐1+ DETCs in mice.

A Case of Kaposi's Sarcoma Associated with Pemphigoid Nodularis

Pemphigoid nodularis is a rare variant of bullous pemphigoid. Bullous pemphigoid complicated by internal malignancy has been well documented. There have been only a few reported cases of bullous pemphigoid associated with Kaposis sarcoma. We described a case of pemphigoid nodularis who later developed Kaposis sarcoma that might be related to immunosupressive therapy, a situation that has not been reported previously.

Morphological relationship between nerve fibers and Langerhans cells in the epidermis of psoriasis vulgaris and lichen simplex chronicus

represent a founder effect [6]. Exons 5, 11, and 15 are clustered with HPS1 mutations [4]. Different clinical HPS1 phenotypes were associated with different HPS1 frameshifts, which suggested that differentially truncated HPS1 polypeptides may have different effects on the cellular function [3]. The c.1932delC mutation leads to a longer HPS1 protein that a novel 79-residue peptide replaces the wild-type 56-residue peptide after the mutation site at D644 (Fig. 1D). Although the predicted protein keeps most of the sequence of wild-type HPS1, the presence of oculocutaneous albinism suggests the loss-of-function effect on melanocytes and renders the functional importance of the C-terminal 56 residues of HPS1 protein. Similarly, the p.L668P missense mutation, located at the C-terminus of HPS1, abolishes its assembly into BLOC-3, indicating the functional importance of the HPS1 C-terminus [6]. This mutation may cause the unique clinical features as neither prolonged bleeding time nor bleeding tendency was observed in this patient. Further studies on the function of the C-terminus of HPS1 will reveal the underlying mechanism. Follow-up observations are warranted to document the severity of the symptoms in her adulthood. Our success in the identification of the HPS1 mutation in the OCA patients suggests the necessary of the mutational screening of the HPS genes in the unidentified patients without mutations in TYR, OCA2, TYRP1, and SLC45A2. The identification of HPS1 patient in the OCA population implicates the underestimation of HPS frequency in Chinese ethnicity.