Effects of Kakato-tsurutsuru socks on dry heels in healthy volunteer subjects.

Kakato-tsurutsuru (Kt) socks have been selling for almost 30 years in Japan. Wearers claim they improve heel dryness despite no scientific evidence. We investigated the effects of Kt socks on heel dryness by questionnaire, clinical scores and non-invasive skin measurements. In a double-blind, randomized cross-over study, 10 healthy volunteers wore control or Kt socks over 2 weeks in sequence for 4 weeks. Skin hydration and evaporation of the medial and dorsal heel were measured before and every week during the trial. Clinical evaluations of desquamation and cracked skin were scored by a dermatologist. A visual analog scale (VAS) questionnaire of comfort, sock climate humidity and skin dryness was conducted. The VAS of comfort was significantly higher in Kt than controls. Average Δskin dryness in control and Kt groups was -1.63 and 2.22, respectively, showing a significant improvement. In the clinical findings of the dorsal side of the heel, Δdesquamation and Δcracked skin scores were significantly decreased and Δstratum corneum hydration significantly increased in Kt compared with controls. Kt socks may retain evaporated sweat with components of natural moisturizing factors, supporting the water-holding ability of the heel stratum corneum. These findings suggest that Kt socks may improve heel skin dryness.

Efficacy of an emollient containing diethylene glycol/dilinoleic acid copolymer for the treatment of dry skin and pruritus in patients with senile xerosis.

BACKGROUND AND AIMS: Pruritus frequently reduces quality of life (QOL) in patients with senile xerosis. This study investigated the moisturizing and antipruritic effects of a topical emollient containing a diethylene glycol/dilinoleic acid copolymer (D/DC) in patients with pruritic senile xerosis. METHODS: This single-blind study involved 50 subjects, aged 50-75 years. Patients were randomized to self-applied treatment of the lower legs with 10% (n = 20) or 20% (n = 20) D/DC-containing cream, white petrolatum (n = 5), or no treatment (n = 5) thrice daily for four weeks. Clinical scores of skin dryness and scratch marks, skin conductance, and Skindex-16 were evaluated before and after treatment. The degree of pruritus was evaluated by visual analog scale (VAS) score once a week. RESULTS: Patients treated with 10% and 20% D/DC showed significant improvements in skin dryness and scratch mark scores, as well as increased skin conductance, compared with the untreated group, whereas white petrolatum treatment improved only skin dryness scores. Moreover, patients treated with 20% D/DC showed significant improvements in skin dryness scores and skin conductance compared with white petrolatum treatment. The VAS scores in the D/DC-treated and white petrolatum-treated groups were significantly lower than in the untreated group, being particularly lower after one week of treatment with 20% D/DC. CONCLUSION: Topical application of an emollient containing D/DC is effective in improving skin dryness and pruritus in patients with senile xerosis.

Successful treatment of three cases of generalized pustular psoriasis with granulocyte and monocyte adsorption apheresis.

Generalized pustular psoriasis (GPP) is a rare form of psoriasis characterized by the presence of variable numbers of sterile pustules appearing in erythematous and scaly lesions, which are associated with moderate to severe constitutional symptoms. It can be life-threatening especially in the elderly; therefore, medical care must be performed in rapid succession of treatment especially in refractory cases. We have performed granulocyte and monocyte adsorption apheresis (GCAP) on three GPP cases associated with several systemic and laboratory findings. As a result, the edema, erythema and numbers of sterile pustules on the skin lesions were reduced dramatically in all three patients after the first sessions of GCAP therapy. The sizes of the psoriatic lesions were reduced in all three patients following a weekly GCAP treatment for 5 consecutive weeks. Psoriasis area and severity index on discharge had improved in all three patients. No serious adverse effects were observed for up to at least 8 months after treatment. We therefore considered GCAP as one effective alternative to currently existing therapies, especially for recalcitrant cases of GPP.

Biophysical evaluation of fractional laser skin resurfacing with an Er:YSGG laser device in Japanese skin.

BACKGROUND: Ablative fractional laser skin resurfacing (FLSR) has recently been used for the amelioration of acne scars, and previous studies have shown clinical effectiveness. Despite its extensive use, few studies have focused on the associated changes in biophysical properties of the epidermis. Herein, we evaluate transepidermal water loss, sebum levels, skin hydration, and skin elasticity, following FLSR treatments with an Er:YSGG laser device (Pearl FractionalTM, Cutera Inc., Brisbane, CA), employing non-invasive measurements. METHODS: Five Japanese patients with facial acne scars underwent one FLSR session. Some acne scars appeared to become less obvious as a consequence of the treatment. All patients were aware of a feeling of skin tightness in treated areas. RESULTS: Objective measurements on the lower lateral angle of the eye and on the inner cheeks were evaluated at baseline and at 3 days, 1 week, and 4 weeks after FLSR. Transepidermal water loss showed a significant two-fold (100%) increase at day 3, but had returned to almost the baseline level at week 4 in both areas. Sebum secretion showed a 50% increase at day 3, but had returned to the baseline level after day 7. Skin hydration showed a significant decrease at day 3, but had returned to the baseline level by day 7, and showed significant improvement at the end of the study. Skin elasticity (R2) was still at baseline on day 3, but showed some improvement--an increase of at least 30%--at the end of the study. CONCLUSIONS: Based on our findings, we believe that FLSR should be performed no more than once a month to allow sufficient time for the damaged skin to recover its barrier function in most areas of the face.

Topically applied semaphorin 3A ointment inhibits scratching behavior and improves skin inflammation in NC/Nga mice with atopic dermatitis.

BACKGROUND: Epidermal hyperinnervation in atopic dermatitis (AD) is activated directly by various external stimuli, causing enhanced itching. Nerve density is regulated by the nerve repulsion factor semaphorin 3A (Sema3A), along with nerve elongation factors. OBJECTIVE: To investigate the effects of Sema3A ointment in the NC/Nga mouse model of AD. METHODS: An AD-like phenotype was induced by repeated application of Dermatophagoides farinae body (Dfb) ointment to the dorsal skin of NC/Nga mice. Vaseline, heparinoid, betamethasone, tacrolimus and recombinant Sema3A ointments were applied to the lesional skin once a day for 4 days. Transepidermal water loss (TEWL) was measured before and after each treatment. We also scored the degree of dermatitis and recorded videos to observe scratching behavior. Subsequently, we collected skin samples from these mice for histological analyses. RESULTS: Topical application of Sema3A, betamethasone and tacrolimus ointments significantly inhibited scratching behavior and improved dermatitis scores in Dfb-treated mice compared with control mice, whereas vaseline and heparinoid had no effects. A significant improvement of TEWL was observed only in Sema3A ointment-treated mice. Moreover, Sema3A ointment reduced the densities of PGP9.5- and substance P-immunoreactive nerve fibers in the epidermis and the numbers of inflammatory cells, such as CD4 immunoreactive T cells and eosinophils, and improved acanthosis in the Dfb-treated mice compared with controls. CONCLUSION: Sem3A ointment may have therapeutic efficacy in patients with pruritus and dermatitis of AD.

Evaluation of epidermal nerve density and opioid receptor levels in psoriatic itch.

BACKGROUND: Psoriasis is a complex, multifactorial inflammatory skin disease with genetic and environmental interactions. Patients with psoriasis exhibit erythematous plaques with itch, but the mechanisms of psoriatic itch are poorly understood. OBJECTIVES: This study was performed to investigate epidermal nerve density and opioid receptor levels in psoriatic skin with or without itch. METHODS: Twenty-four patients with psoriasis aged between 39 and 82 years were included in this study. The number of epidermal nerve fibres, the levels of semaphorin 3A (Sema3A) and the expression patterns of µ- and κ-opioid systems were examined immunohistologically in skin biopsies from psoriatic patients with or without itch and healthy volunteers as controls. RESULTS: The number of epidermal nerve fibres tended to increase in approximately 40% of psoriatic patients with itch compared with healthy controls, while such intraepidermal nerves were not observed in other itchy patients. In comparison with healthy controls, Sema3A levels also tended to decrease in the epidermis of psoriatic patients with itch. However, no relationship was found between nerve density and Sema3A levels in the epidermis of psoriatic patients with itch. The levels of µ-opioid receptor and ß-endorphin in the epidermis were the same in healthy controls and psoriatic patients with or without itch. The levels of κ-opioid receptor and dynorphin A were significantly decreased in the epidermis of psoriatic patients with itch compared with healthy controls. CONCLUSIONS: Based on Sema3A levels in the epidermis, epidermal opioid systems, rather than hyperinnervation, may be involved in the pathogenesis of psoriatic itch.

Keratinocyte-derived anosmin-1, an extracellular glycoprotein encoded by the X-linked Kallmann syndrome gene, is involved in modulation of epidermal nerve density in atopic dermatitis.

BACKGROUND: Epidermal nerve density is increased in atopic dermatitis (AD), suggesting that the hyperinnervation is partly responsible for abnormal itch perception. It is probably controlled by axonal guidance molecules produced by keratinocytes. An extracellular matrix glycoprotein anosmin-1 encoded by KAL1 has chemoattractive or chemorepulsive effects on different neuronal types. OBJECTIVE: This study was performed to investigate the roles of anosmin-1 in skin innervation. METHODS: Rat dorsal root ganglion (DRG) neurones were cultured in conditioned medium from control or KAL1-overexpressing cells for neurite outgrowth assay. KAL1 expression in cultured epidermal keratinocytes or human skin was examined by quantitative RT-PCR (qRT-PCR). Anosmin-1 distribution in normal and atopic skin was examined immunohistochemically. The effects of calcium concentrations and cytokines on KAL1 expression in cultured normal human epidermal keratinocytes (NHEK) were analysed by qRT-PCR. RESULTS: Neurite outgrowth in cultured DRG neurones was inhibited by conditioned medium from KAL1-overexpressing cells, while it was rescued by addition of recombinant fibroblast growth factor receptor 1 for capturing anosmin-1. KAL1 transcripts were expressed in cultured keratinocytes or in normal skin. Anosmin-1 was strongly expressed in the basal cell layer of normal skin, but decreased in atopic skin, concomitant with increases of epidermal nerve fibres. KAL1 expression was downregulated during keratinocyte differentiation. The expression was also upregulated by interleukin-4 (IL-4), IL-13 or transforming growth factor (TGF)-beta1. TGF-beta1 acted synergistically with IL-13 to enhance KAL1 expression, while interferon-gamma inhibited its expression. CONCLUSION: Anosmin-1 produced by epidermal keratinocytes in response to calcium concentrations or cytokines may modulate epidermal nerve density in AD.