Clinical Efficacy and Safety of Naltrexone Combination Therapy in Older Patients with Severe Pruritus.

BACKGROUND: Severe pruritus is a challenging condition, and it is more difficult to deal with in older patients due to their limitations in taking oral medication because of underlying diseases, possible interaction with concurrent medications, and poor general condition. OBJECTIVE: We evaluated the efficacy and safety of naltrexone (Revia®), an opioid antagonist, in elderly patients with severe pruritus that was not easily controlled with conventional antipruritics. METHODS: Eighteen patients were enrolled, with a mean age of 73 years. They additionally received 50 mg of naltrexone per day for an average of 2 months. RESULTS: Using the visual analogue scale, 13 (72.2%) of 18 patients showed a "much improved" condition, reporting more than a 50% decrease in pruritus intensity. Sixteen (88.9%) showed symptomatic improvement, and only 2 (11.1%) had persistent pruritus. Five patients reported side effects including insomnia, fatigue, constipation, and anorexia. However, reactions were either limited to the first 2 weeks or well managed. CONCLUSION: Naltrexone could be an effective and safe alternative treatment option to control severe pruritus in older patients.

Retrospective Analysis on the Effects of House Dust Mite Specific Immunotherapy for More Than 3 Years in Atopic Dermatitis.

PURPOSE: In extrinsic atopic dermatitis (AD), house dust mites (HDM) play a role in eliciting or aggravating allergic lesions. The nature of skin inflammation in AD has raised a growing interest in allergen-specific immunotherapy (SIT). Thus, we assessed clinical improvement and laboratory parameters for evaluation of the benefit of long-term SIT. MATERIALS AND METHODS: A total of 217 AD patients who were treated with SIT for at least 3 years were retrospectively assessed, by using their investigator global assessment, pruritus scores, loss of sleep (LOS), total serum IgE, and eosinophil counts collected. Patients were additionally classified into subgroups according to age, initial AD severity and mono- or multi-sensitization to include different individual factors in the evaluation of SIT efficacy. Lastly, we compared laboratory data of good responders to SIT with that of poor responders to SIT. RESULTS: Improvement after SIT therapy was observed in 192 out of 217 patients (88.4%). Among these patients, 138 (63.5%) achieved excellent, near-complete or complete clinical remission. Significant reduction of pruritus, LOS, and the mean value of total serum IgE were observed (p<0.01). Better outcome was found in patients younger than 12 years of age (p=0.024). Patients with moderate to severe AD showed better treatment outcomes (p=0.036). Patients sensitized only to HDM had the better response to treatment, but SIT was also effective in multi-sensitized groups (p=1.051). No significant differences in baseline laboratory results were observed between good and poor responders (p>0.05). CONCLUSION: We emphasize the usefulness of long-term HDM SIT as a disease-modifying therapy for AD.

DAMP molecules S100A9 and S100A8 activated by IL-17A and house-dust mites are increased in atopic dermatitis.

S100A9 and S100A8 are called damage-associated molecular pattern (DAMP) molecules because of their pro-inflammatory properties. Few studies have evaluated S100A9 and S100A8 function as DAMP molecules in atopic dermatitis (AD). We investigated how house-dust mites affect S100A9 and S100A8 expression in Th2 cytokine- and Th17 cytokine-treated keratinocytes, and how secretion of these molecules affects keratinocyte-derived cytokines. Finally, we evaluated expression of these DAMP molecules in AD patients. S100A9 expression and S100A8 expression were strongly induced in IL-17A- and Dermatophagoides (D.) farinae-treated keratinocytes, respectively. Furthermore, co-treatment with D. farinae and IL-17A strongly increased expression of S100A9 and S100A8 compared with D. farinae-Th2 cytokine co-treatment. The IL-33 mRNA level increased in a dose-dependent manner in S100A9-treated keratinocytes, but TSLP expression did not change. S100A8/A9 levels were also higher in the lesional skin and serum of AD patients, and correlated with disease severity. Taken together, S100A9 and S100A8 may be involved in inducing DAMP-mediated inflammation in AD triggered by IL-17A and house-dust mites.

Comparison of the psychological impacts of asymptomatic and symptomatic cutaneous diseases: vitiligo and atopic dermatitis.

BACKGROUND: Vitiligo and atopic dermatitis (AD) are common dermatological disorders which may cause significant psychological and social distress leading to impaired quality of life (QoL) in patients. OBJECTIVE: We evaluated the degree of psychological stress and impairment of QoL in vitiligo patients as compared with AD patients and normal controls (NCs). METHODS: A total of 60 patients from each group and 60 NCs were enrolled. Five questionnaires on depression (Beck depression inventory, BDI), state anxiety (SA) and trait anxiety (TA), interaction anxiousness (IAS), private body consciousness (PBC) and dermatologic QoL were used. RESULTS: The vitiligo patients had a significantly higher level of TA (p<0.01), PBC (p<0.001) and impaired QoL (p<0.001) than NCs, but not BDI, SA and IAS. The AD patients had significantly higher scores for all five questionnaire items compared with NCs. In the comparison between the AD and vitiligo groups, all of the indexes except body consciousness were higher in AD patients than in vitiligo patients: BDI (p<0.01), SA (p<0.05), TA (p<0.001), IAS (p<0.01) and impaired QoL (p<0.001). Exposure of vitiligo lesions was not a significant variable in the analysis of the contribution of clinical variables of vitiligo on psychological stress and QoL. CONCLUSION: Vitiligo, which is not accompanied by any symptoms, involves less psychological impact than AD, which is accompanied by itching. Compared to NCs, however, the elevated general anxiety and body consciousness in patients with vitiligo suggests that they may be more concerned with the aggravation of hypopigmented patches than difficulties in social interactions.

Insight into newly discovered innate immune modulation in atopic dermatitis.

Atopic dermatitis (AD) is a highly pruritic, chronic relapsing inflammatory skin disease characterized by innate and adaptive immune reactions. In AD, innate immune mechanisms such as pattern recognition receptors and antimicrobial peptides have been investigated in detail, but recently, epidermis-derived cytokines, namely thymic stromal lymphopoietin (TSLP), IL-25 and IL-33, were shown to participate in innate immune reactions independently of adaptive immunity. In addition to conventional innate cells, such as mast cells, basophils and eosinophils, Th2 cytokine-producing invariant natural killer T (iNKT) cells, innate lymphoid cells (ILCs) and Th17/Th22 cytokine-producing innate cells - iNKT cells and natural killer (NK)-like cells - can participate in innate immune modulation in AD. Accordingly, early control of innate immune responses in AD before activation of adaptive immune responses by conventional T and B cells that perpetuate chronic skin inflammation may adequately alleviate acute exacerbations of AD. Therefore, we hypothesized that select immune modulators targeting the innate immune response could potentially be used for individualized treatment of AD.

Knockdown of paraoxonase 1 expression influences the ageing of human dermal microvascular endothelial cells.

Skin is one of the most commonly studied tissues for microcirculation research owing to its close correlation of cutaneous vascular function, ageing and age-related cardiovascular events. To elucidate proteins that determine this correlation between endothelial cell function and ageing in the vascular environment of the skin, we performed a proteomic analysis of plasma samples from six donors in their 20s (young) and six donors in their 60s (old). Among identified proteins, paraoxonase 1 (PON1) was selected in this study. To elucidate the role of PON1 on skin ageing and determine how it controls cellular senescence, the characteristics of PON1 in human dermal microvascular endothelial cells (HDMECs) were determined. When the expression of endogenous PON1 was knocked-down by small interfering RNA (siRNA) targeting PON1, HDMECs showed characteristic features of cellular senescence such as increases in senescence-associated ß-galactosidase stained cells and enlarged and flattened cell morphology. At 48 h post-transfection, the protein expression of p16 in PON1 siRNA-treated HDMECs was higher than that in scrambled siRNA-treated HDMECs. In addition, the expressions of moesin and rho GTP dissociation inhibitor, additional age-related candidate biomarkers, were decreased by PON1 knock-down in HDMECs. In conclusion, these results suggest that PON1 functions as an ageing-related protein and plays an important role in the cellular senescence of HDMECs.

Corticotropin-releasing hormone downregulates IL-10 production by adaptive forkhead box protein 3-negative regulatory T cells in patients with atopic dermatitis.

BACKGROUND: Corticotropin-releasing hormone (CRH) is the central regulating hormone of the hypothalamic-pituitary-adrenal axis. CRH also has diverse functional effects in the periphery and is related to the aggravation of several cutaneous diseases; however, the effect of CRH on T cells in patients with atopic dermatitis (AD) has not been well evaluated. OBJECTIVE: We investigated whether CRH directly affects peripheral T(H)1, T(H)2, and regulatory T (Treg) cells in patients with AD. METHODS: We assessed whether T cells express the CRH receptor protein and mRNA by using flow cytometry, Western blotting, immunofluorescence, immunohistochemistry, and RT-PCR. We evaluated cytokine expression using ELISA after treating the T cells extracted from patients with AD and healthy control subjects (HCs) with CRH. Flow cytometry was then used to evaluate any direct effects of CRH on T(H)1, T(H)2, and Treg cells from patients with AD and HCs. RESULTS: T cells from patients with AD expressed significantly lower CRH receptor 1/2 mRNA levels than T cells from HCs. T cells from HCs reacted with different IL-4 and IFN-γ secretions to CRH treatment, whereas T cells from patients with AD did not. IL-10 production was significantly decreased in the supernatants from both the HCs and patients with AD after CRH treatment. CRH upregulated IL-4 production by T(H)2 cells and downregulated IFN-γ production by T(H)1 cells in HCs. CRH also suppressed the production of IL-10 by forkhead box protein 3-negative Treg cells in both groups, but the difference was only significant in patients with AD. CONCLUSIONS: CRH-mediated suppression of IL-10 secretion from Treg cells might explain stress-related exacerbations in patients with AD.

Progressive muscle relaxation therapy for atopic dermatitis: objective assessment of efficacy.

The aims of this study were to validate the efficacy of progressive muscle relaxation (PMR) in patients with atopic dermatitis and to evaluate the serological parameters that may serve as objective measures of the efficacy of PMR. A total of 25 patients with atopic dermatitis were randomly assigned to either a PMR group (n = 15) or a control group (n = 10). Serum levels of nerve growth, neuropeptide Y, and Th2 cytokines (IL-4, IL-5, and IL-13) were measured at baseline and after one month. At baseline, only anxiety was positively correlated with pruritus score (state anxiety: R = 0.496, p = 0.014; trait anxiety: R = 0.423, p = 0.04). Serum levels of neuropeptide Y were inversely related to the State-Trait Anxiety Inventory (STAI) (state anxiety: R = -0.475, p = 0.019; trait anxiety: R = -0.418, p = 0.042) and pruritus scores (R = -0.451, p = 0.035). After one month of PMR therapy, the degree of pruritus and loss of sleep was significantly decreased in the PMR group (p < 0.001), but not among controls. State anxiety scores showed significant improvement after treatment only in the PMR group (p = 0.005). There were no significant changes in the serological parameters in either group. Reductions in Eczema Area and Severity Index (EASI) scores were significant, but similar, in both groups. PMR may be a useful adjunctive modality for the management of atopic dermatitis through the reduction of anxiety. No change was found in biological parameters, but it was observed that neuropeptide Y may be related to high levels of anxiety in atopic dermatitis at baseline.

Folliculosebaceous cystic hamartoma in a patient with neurofibromatosis type I.

Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma composed of dilated folliculosebaceous units and mesenchymal elements. It presents as a papule or nodule usually on the face and scalp, rarely on the genital or trunk area. Histologically, FSCH shares several similar features to sebaceous trichofolliculoma. We report one case of FSCH misdiagnosed as a neurofibroma. He was a 38-year-old man with a neurofibromatosis type I and a nodule on his left earlobe was excised under the impression of neurofibroma. Pathological examination revealed FSCH. Although FSCH is clinically not distinctive, awareness of the lesion is important to differentiate papulonodular or cyst-like cutaneous lesions.

Cutaneous schwannoma presented as a pedunculated protruding mass.

Schwannoma is a benign neoplasm of the nerve sheath origin. It arises from the nerve sheath of large peripheral or cranial nerves and occurs at the level of the subcutaneous fat layer or deeper layer. Cutaneous schwannoma occurs more superficially and usually presents as a solitary dermal or subcutaneous nodule. We describe a case of cutaneous schwannoma that presented as an erythematous pedunculated protruding mass on the left flank of a 19-year-old female. It was clinically diagnosed as a granuloma pyogenicum. Shaving biopsy was conducted and histological examination revealed an encapsulated tumor mass containing dense, spindle-shaped cells whose nuclei are arranged back to back representing Verocay body, and a diagnosis of schwannoma was made. This is an unusual case of cutaneous schwannoma that presented as a pedunculated protruding mass.

Treatment of syringoma using an ablative 10,600-nm carbon dioxide fractional laser: a prospective analysis of 35 patients.

BACKGROUND: Treatment of syringoma aims to destroy the dermal tumor using methods that can include surgical excision, electrodessication, cryosurgery, chemical peeling, and laser ablation, but complete removal of syringomas is often unsuccessful, and recurrence occurs frequently. OBJECTIVE: To investigate the therapeutic efficacy of an ablative 10,600-nm carbon dioxide fractional laser system (CO(2) FS) for the treatment of periorbital syringomas. METHODS: Thirty-five patients with periorbital syringomas were treated with two sessions of CO(2) FS at 1-month intervals. Laser fluences were delivered in two or three passes over the lower eyelids, using a pulse energy of 100 mJ and a density of 100 spots/cm(2) . Clinical improvement was assessed by comparing pre- and post-treatment clinical photographs and patient satisfaction rates. We examined the histological features of human periorbital syringomas treated with CO(2) FS. RESULTS: Evaluation of clinical results 2 months after treatment showed that 15 of the 35 patients (42.9%) demonstrated marked (51-75%) clinical improvement, 12 (34.3%) had moderate (26-50%) clinical improvement, five (14.3%) showed minimal (0-25%) improvement, and three (8.6%) showed near total (≥75%) improvement. Clinical improvement scores were less 4 months after the second CO(2) FS treatment (not statistically significant). The mean maximal depth of the necrotic column was 1,236.3 µm. A specimen obtained from the infraorbital area immediately after treatment showed formation of necrotic columns on the interfollicular skin. CONCLUSION: The use of CO(2) FS can have a positive therapeutic effect on periorbital syringomas.

Risk of postinflammatory hyperpigmentation with Fern pattern technique in injecting hyaluronic acid gel.

Fern pattern technique refers to a novel technique to inject acids gels in the dermis for optimal correction of dynamic facial lines. Although it has been proposed to show good results in correcting dynamic facial lines, it may result in higher risk of postinflammatory hyperpigmentation (PIH) since this technique requires multiple needle puncture for injection. We present a patient who showed PIH after injection of hyaluronic acid gel with this technique which made the facial lines more visibly apparent.