Immunomodulatory Effects of Deokgu Thermomineral Water Balneotherapy on Oxazolone-Induced Atopic Dermatitis Murine Model

BACKGROUND: Although the therapeutic mechanism of balneotherapy for atopic dermatitis has not been clarified, many atopic patients who visit thermomineral springs have shown clinical improvements. OBJECTIVE: This study was aimed to evaluate the immunomodulatory effect of thermomineral water balneotherapy on the atopic dermatitis murine model. METHODS: The oxazolone-induced atopic dermatitis murine model was used to evaluate the therapeutic effect of balneotherapy with Deokgu thermomineral water compared with distilled water. Histologic evaluation and confocal microscopic imaging were performed to analyze the lesional expression of cluster-of-differentiation (CD)4 and forkhead box p3 (Foxp3). Lesional mRNA expression of interleukin (IL) 33, thymic stromal lymphopoietin (TSLP), and Foxp3 was evaluated by real-time reverse transcription polymerase chain reaction. RESULTS: Compared with the distilled water bath group, confocal microscopic evaluation of CD4 and Foxp3 merged images showed increased expression of regulatory T cells in the thermomineral balneotherapy group. The lesional mRNA level of IL-33 showed a reduced trend in the thermomineral balneotherapy group, whereas the level of mRNA of Foxp3 was increased. TSLP showed a decreased trend in both distilled water and thermomineral water bath groups. There was a trend of reduced expression in lesional IL-33 mRNA but increased cell count of CD4+ Foxp3+ regulatory T cells in thermomineral balneotherapy compared with distilled water bath. CONCLUSION: Therefore, thermomineral balneotherapy can be an effective and safe adjuvant therapeutic option for atopic dermatitis.

Immunoinflammatory Regulation Effects of Korean Hot Spring Water / 日本温泉気候物理医学会雑誌

Background: The beneficial clinical effects of Korean hot spring spa therapy, as well as their underlying mechanisms are still poorly understood. We performed a series of clinical and laboratory investigations for better understanding of the clinical effects as well as possible mechanisms of their beneficial effects. Methods: HaCaT cells were prepared and treated with TLR agonist in the presence or absence of HS water for quantification of IL-6, IL-8, GM-CSF, and TNF-α levels. The serum levels of IFN-ɤ, IL-4, IL-5, and IgE were measured. CD4+ naïve cells were allowed to polarize into Th1, Th2, Th17, and Treg cells, and CD4+ and CFSE+ cells were measured for the degree of proliferation. Total RNA from the lesional skin was transcribed into cDNA using a reverse transcription system, and RT-PCR was performed subsequently. Confocal microscopy and RT-PCR were utilized to evaluate the target skin localization of Th cell subsets and associated inflammatory cytokine milieu. Results: Treatment with agonists of TLR 1 through 6 induced attenuation of cytokine production in the exposure to HS water. HS water suppressed the proliferation of Th1, Th2, and Th17 cells with anti-CD3 stimulation, while proliferation and differentiation to Treg cells were promoted under HS water treatment. On RT-PCR of the lesional skin, thymic stromal lymphopoietin (TSLP) mRNA decreased dramatically after bathing with HS. IL-33 mRNA decreased markedly in HS water group as compared to control group. Foxp3 mRNA expression, same as in confocal microscopic finding, showed tendency to increase more in HS. Conclusions: HS water suppressed the proliferation of Th1, Th2, and Th17 cells. In contrast, proliferation and differentiation to Treg cells were promoted under HS water treatment. These results indicate that HS water may affect the distribution of the helper T cells in the immune response, by suppressing the polarization of the Th1, Th2, and Th17 cells. Also, APC induced TNF-α and IL-6 levels were reduced in the presence of HS water. These results showed that TLR-triggered inflammatory responses in APCs might also be modulated under HS water treatment. Overall, our findings suggest that HS spa therapy could be an effective and safe modality for the management of adult AD.

Immunoinflammatory Regulation Effects of Korean Hot Spring Water / 日本温泉気候物理医学会雑誌

<b>Background: </b>The beneficial clinical effects of Korean hot spring spa therapy, as well as their underlying mechanisms are still poorly understood. We performed a series of clinical and laboratory investigations for better understanding of the clinical effects as well as possible mechanisms of their beneficial effects.<BR><b>Methods:</b> HaCaT cells were prepared and treated with TLR agonist in the presence or absence of HS water for quantification of IL-6, IL-8, GM-CSF, and TNF-<i>α</i> levels. The serum levels of IFN-ɤ, IL-4, IL-5, and IgE were measured. CD4⁺ naïve cells were allowed to polarize into Th1, Th2, Th17, and Treg cells, and CD4⁺ and CFSE⁺ cells were measured for the degree of proliferation. Total RNA from the lesional skin was transcribed into cDNA using a reverse transcription system, and RT-PCR was performed subsequently. Confocal microscopy and RT-PCR were utilized to evaluate the target skin localization of Th cell subsets and associated inflammatory cytokine milieu.<BR><b>Results: </b>Treatment with agonists of TLR 1 through 6 induced attenuation of cytokine production in the exposure to HS water. HS water suppressed the proliferation of Th1, Th2, and Th17 cells with anti-CD3 stimulation, while proliferation and differentiation to Treg cells were promoted under HS water treatment. On RT-PCR of the lesional skin, thymic stromal lymphopoietin (TSLP) mRNA decreased dramatically after bathing with HS. IL-33 mRNA decreased markedly in HS water group as compared to control group. Foxp3 mRNA expression, same as in confocal microscopic finding, showed tendency to increase more in HS.<BR><b>Conclusions:</b> HS water suppressed the proliferation of Th1, Th2, and Th17 cells. In contrast, proliferation and differentiation to Treg cells were promoted under HS water treatment. These results indicate that HS water may affect the distribution of the helper T cells in the immune response, by suppressing the polarization of the Th1, Th2, and Th17 cells. Also, APC induced TNF-<i>α</i> and IL-6 levels were reduced in the presence of HS water. These results showed that TLR-triggered inflammatory responses in APCs might also be modulated under HS water treatment. Overall, our findings suggest that HS spa therapy could be an effective and safe modality for the management of adult AD.

Immunomodulatory Effects of Balneotherapy with Hae-Un-Dae Thermal Water on Imiquimod-Induced Psoriasis-Like Murine Model

BACKGROUND: Balneotherapy, although not a well-established dermatological treatment, is thought to have therapeutic properties for psoriasis and is used as an alternative treatment modality throughout the world. OBJECTIVE: To evaluate the mechanism underlying the therapeutic immunologic effects of thermomineral water. METHODS: A murine model of imiquimod-induced psoriasis-like skin inflammation was used for evaluating the therapeutic effects of balneotherapy with Hae-Un-Dae hot spring mineral water. The clinical improvements were evaluated by a dermatologist. Lesional cytokines, including interleukin (IL)-17A, IL-23, and IL-22, were quantitatively measured by real-time reverse transcriptase polymerase chain reaction. Serum levels of interferon-gamma, IL-4, IL-5, and IL-17A were measured by enzyme-linked immunosorbent assay. T cell proportions in the spleen were evaluated by flow cytometry, and histopathological evaluation of the skin was also performed. RESULTS: The mineral water balneotherapy group showed faster improvement in skin erythema and scales than the distilled water bathing group. A substantial reduction was observed in the lesional mRNA levels of IL-17A and IL-23 in the mineral water group. Serum levels of IL-4 and IL-5 were significantly decreased in the mineral water group but not in the distilled water group. Normalized T cell proportions were observed after bathing. CONCLUSION: Balneotherapy showed immunomodulatory effects in a psoriasis-like murine model. Balneotherapy suppressed lesional IL-23 and IL-17A, which are important cytokines in the pathogenesis of psoriasis. These results suggest that balneotherapy can be used as an effective and safe treatment for psoriasis.

Therapeutic Effects and Immunomodulation of Suanbo Mineral Water Therapy in a Murine Model of Atopic Dermatitis

BACKGROUND: Balneotherapy is widely used as an alternative treatment modality for AD. Although the clinical benefit of some mineral waters has been established, their mechanisms of action in alleviating AD are only partly understood. OBJECTIVE: The clinical modification and immunomodulatory or anti-inflammatory effects of mineral water from the Suanbo hot springs on the differentiation and cytokine production of Th1, Th2, and regulatory T cells (Treg) were investigated using spleen, skin tissue, and serum from NC/Nga mice. METHODS: The therapeutic effects of bathing in mineral water in a Dermatophagoides farinae body extract ointment (Dfb ointment)-induced AD mouse model were assessed by measuring the modified Scoring atopic dermatitis (SCORAD) index scores, transepidermal water loss (TEWL), histological and immunohistochemical changes of the skin lesion, serum levels of interferon (IFN)-gamma, interleukin (IL)-4, IL-5 and immunoglobulin E, mRNA expression of IFN-gamma, IL-4 and IL-5 of dorsal skin, and helper T cell differentiation in the spleen. RESULTS: Bathing in mineral water significantly reduced the modified SCORAD index scores, TEWL, epidermal hyperplasia, and inflammatory cell infiltration. IL-4 production and Th2 cell differentiation showed a decreasing tendency with mineral water bathing, but the Th1 cells did not. On the contrary, differentiation to Treg cells was promoted with mineral water bathing. CONCLUSION: Balneotherapy not only has anti-inflammatory activity, but also shows positive effects on cutaneous barrier homeostasis. These results suggest that the favorable effects of balneotherapy may be mediated by modifying the Th2 response, and possibly in part by inducing Treg cell differentiation.

Effect of Spa Spring Water on Cytokine Expression in Human Keratinocyte HaCaT Cells and on Differentiation of CD4+ T Cells

BACKGROUND: Skin acts as the first line of defense against any foreign materials outside of our body. In inflammatory skin disease, the pathogenesis is due to an immune reaction in the keratinocytes, immune cells and soluble mediators. Balneotherapy is widely used for the treatment of inflammatory skin disease, but the mechanisms are only partly understood by immune regulation. Balneotherapy in dermatologic disease can affect the secretion of pro-inflammatory cytokines, IL-1alpha and tumor necrosis factor from keratinocytes, and possibly affect the T cell differentiation. OBJECTIVE: In this study, we evaluated the effect of spa spring water from Yong-gung oncheon on the cells, and investigated the skin immune reaction. METHODS: We investigated the immunomodulatory or anti-inflammatory effect of thermal spring water on the expression of pro-inflammatory cytokines in the HaCaT cells under Toll-like receptor (TLR) stimulation, as well as the effect on the differentiation of CD4+ T cells under spring water. RESULTS: The treatment of spa spring water from Yong-gung oncheon decreased the expression of proinflammatory cytokines under TLR stimulation to the HaCaT cells and antigen presenting cells. In addition, spa spring water attenuated the differentiation process of subsets of CD4+ T cells, i.e., Th1, Th2 and Th17 cells. All these immune parameters can be used to evaluate the efficacy of spa spring water in Korea, in terms of the immune modulatory effect. CONCLUSION: Spa spring water treatment suppressed the inflammatory cytokines production and also modulated the differentiation of CD4+ T cells into Th1, Th2, and Th17 cells, but not the Tregs cells.

Botulinum Toxin Type A for Facial Wrinkles and Benign Masseter Hypertrophy in Korean Patients / 대한피부과학회지

BACKGROUND: The utilization of botulinum toxin has rapidly expanded into various aesthetic applications. Achieving success with the aesthetic use of neurotoxins depends on several factors, including an understanding of the anatomy, the methods of dilution and the injection technique. Any guidelines representing a consensus for aesthetic treatments using botulinum toxin type A (BTA) have not been published in Korea. OBJECTIVE: We wanted to provide consensus recommendations on the treatment of facial wrinkles and benign masseter hypertrophy using BTA in Korean patients. METHODS: A panel of experienced Korean dermatologists was convened to develop a clinical consensus. The clinical consensus was comprised of the recommendations of the panel and the guidelines on general issues, such as the reconstitution and handling of the BTA, the procedural considerations, the dosing and injection-site standardizations, and the prevention and treatment of unwanted effects. Specific recommendations were provided according to the area of treatment, including glabellar lines, horizontal forehead lines, lateral periorbital wrinkles and benign masseter hypertrophy. RESULTS: The recommended final concentration of BTA was 50 units/ml (5 units/0.1 ml) after reconstitution with physiologic saline. For glabellar lines, the members recommend three injection points (a total of 8 units). For forehead wrinkles, the members recommend nine injections in two rows into the frontalis with 1 unit/point. For crow's feet, the members recommend three injections per side (7 units/side) at the lateral part of the orbicularis oculi. For benign masseter hypertrophy, three injections per side (24~30 units/side) were recommended. CONCLUSION: These consensus recommendations will provide a framework for Korean dermatologists who wish to perform safe and efficacious injection of BTA for facial rejuvenation.

The Use of Medical Devices for Medical Skin Care and the Legal Issues / 대한피부과학회지

BACKGROUND: Medical skin care is essential for the treatment of skin diseases all over the world. Medical skin care is also part of medical practice and this must be differentiated from the simple skin care that is given for normal healthy skin. OBJECTIVE: We wanted to discuss medical skin care and the related medical devices and legal issues. METHODS: We reviewed the related laws and regulations, we consulted experts and associations and we analyzed the result of the survey. RESULTS: Legally, medical skin care and simple skin care are well classified. However, many illegal procedures are still performed by non-medical personnel and many adverse effects have been reported as a result. Furthermore, there are no legal restrictions for the performer based on the grade of each medical skin care procedure. CONCLUSION: For the best results and safe procedures, medical skin care must be performed by approved medical equipment under the supervision of a physician or medical personnel. Continuous control and guidance by the government is strongly needed.

Tick Bites / 대한피부과학회지

Tick bites are dermatoses not commonly encountered in Korea. Identification of causative ticks as well as recognition of clinical signs and histopathologic findings are important in making a diagnosis in tick-related dermatoses. Hard ticks which belong to the Family Ixodidae are responsible for most tick-related diseases. Since the first human case of tick bite in Korea was reported in 1982, seventeen cases have been reported up to the present. All the inflicted ticks belonged to the genus Ixodes except a case by Haemaphysalis flava. Among 16 ticks, collected from 16 cases of tick bites caused by the genus Ixodes, nine I. nipponenses, an I. ovatus and I. persulcatus were identified. Recently we experienced 8 cases of tick bites, 6 of them were caused by the genus Ixodes including 4 I. nipponenses. One of them, whose essential complaint was fever and chills, showed the clinical course of tick bite pyrexia which had not been reported in Korea. The clinical and epidemiological findings of tick bites reported in Korea were reviewed, including these 8 cases.

Multicenter Prospective Clinico-Epidemiologic Study on the Abuse, Misuse and Adverse Effects of Drugs in Dermatological Field / 대한피부과학회지

BACKGROUND: The abuse, misuse, and resultant adverse reactions of various drugs have been widespread due to lack of division of work of medicine and pharmacy in Korea. OBJECTIVE: This study was conducted to bring people to an awareness of the seriousness of drug abuse and misuse. METHODS: A multicenter, prospective, clinico-epidemiologic evaluation was made from patients with adverse drug reactions who visited 126 dermatologic departments in university hospitals(21) or private clinics(105) nationwide from July 1st to July 31st, 1999. RESULTS: The prevalence of adverse drug reaction was 10.4%, among them 47.9% of the patients had adverse cutaneous effects from external use of topical steroids and 24.1% of the patients had contact dermatitis from external use of various topical agents. The rate(66.3%) of misuse of topical steroids was higher than that(33.7%) of abuse of the drugs. 79.8% of patients had obtained drugs without an accurate diagnosis and prescription from their doctors. Regarding the potency of topical steroids, it was revealed that the lowest potency drugs also caused adverse effects. CONCLUSION: The strict grouping of drugs as prescription drugs or over-the-counter drugs based on drug safety is the key factor to avoid the abuse and misuse of drugs, and to protect the public health from harmful drug effects.

Study of cutaneous hydration effect according to the vehicles of moisturizers / 대한피부과학회지

We investigated on how the nature of vehicles influenced on the efficacy of mo isturizer s, cutaneous hydrat,ion, physical property and roughness. Hydration was measured with corneometer, physical property with fermometer, and mughness with image analyser. Used vehicles were as follows : hydrous gel, vater in oil(W/0) emulsion, oil in water(0/W) emulsion. I.Jsed moisturizers were as follows . glycerine, polypeptide and sodium lactat,e, hyaluronic acid-triethanolamine, sodium lactate, pvopylene glycol, The results are summarized as follows : 1. The increment of the hydration effect according to vehicles was in this order. C/ W emulsion, W/0 emulsion, hydrous gel(After 2 hours). 2. The increment of extensibility as physical property was correlated to the in crcment, of hydration effcet(r=0.924). 3. It was shown that, the roughness was decreased after treatment of all mo isturizers except propylene glycol but, there was not significant st.atistically and alsa was no meaningful difference among the vehicles. 4. Among t,he moisturizers, glycerine was superior to other moisturizers on the hydration effect and extensihility. We conclude that 0/W emulsion was suitable vehicle on cutaneous hydration effect and hydration effect is proportion to the increment of flexibility.

A study of the abnormal cutaneous vascular response in atopic dermatitis / 대한피부과학회지

The delayed blanch is one of the most discussed but undecided facets of atopic dermatitis as yet. At present, they favor the theory that delayed blanch is due to vasoconstriction, but it is not obvious whether this is due to "true" vasoconstriction or to the blood vessels being narrowed by the surrounding exudative edema, resulted from vasodilatation and increased capillary per meability. We compared cutaneous response of severe atopic dermatitis with that of age matched non-atopic individuals after intradermal injection of acetylcholine by means of naked eye and laser Doppler flowmeter examination, control group showed flare and wheals while at,opy group resulted in delayed blanch in addition to flare and whealing. The results of laser Doppler flowmeter examination revealed that, as compared to baseline, atopy group showed statistically significantly increase in spite of delayed blanch. We suggested that the delayed blanch may be not due ta va.soconstriction but due to the vasadilatation and aceumulation of edema fluid.

Allergic contact dermatitis due to topical medicaments in Korea / 대한피부과학회지

No abstract available.

An Immunolhistochemical Study of Extramammary Paget's Disease: Adenokeration , Carcinoembryonic Antigen and Involucrin Expression in Extramammary Paget's Disease / 대한피부과학회지

The origin of Paget cells in extramammary Pagets disease is uncertain, however, some ultrastructural surveys revealed differentistion of Paget cells toward sweat gland apparatus. This is supported by recent immunohistochemical studies that Paget cells are irnmunohistochemically shown to react with antikeratin monoclonal antibodies specific to simple epithelia. In this siudy, seven cases of extramammary Pagets disease were immunohistochemically investigated with adenokeratin, carcinoembryonic antigen(CEA), involucrin by peroxidase-antiperoxidase(PAP) techniques. The results were as follow : l. Epidermis, hair follicies and sebaceous glands revealed negative immunoreacativity for adenokeratin in all cases. Sweat glands(6/7), Paget cells(6/7) and underlying adenocarcinoma revealed positive immunoreactivity for adenokeratin. 2. Epidermis, hair follicles and sebaceous glands(6/7) revealed negative immunoreactivity for CEA. Sweat glands, Paget cells and underlying adenocarcinoma revealed positive immunoreactivity for CEA in all cases. 3. Lower epidermis, sweat glands(6/7), Paget cells and underlying adenocarcinorna revealed negative irnmunoreactivity for involucrin. Upper epidermis, hair follicles and sebaceous glands(5/7) revealed positive immunoreactivity far involucrin. Based on these results, Paget cells of extramammary Pagets disease are considered to be derived from the sweat glands.

A Case of Lymphocytic Infiltration of the Skin ( Jessner ) / 대한피부과학회지

Lymphocytic infiltration of the skin(LIS), first described in 1953 by Jessner and Kanot is relatively uncommon disorder, characterized clinicaily by the presence of erythemat.ous peripherally enlarging papules or plaques which may show central clearing. Histologically, the lesions show patch, perivascular and periadnexal lymphocytic infiltrates. We have experienced a case of 30-year old male who had multiple erythematous nodules and plaques on the face and dorsum of the right wrist with 5 years history. He had first noted erythematous plaques on the cheek and these lesions were gradually increasing in size and spreading to the forehead and forearm. He had transiently improved by medication at the drug store, but recurred after discontinuation.

Three Cases of Extramammary Paget's Disease / 대한피부과학회지

We have experienced three cases of extrarnsmmary Pagets disease. The first case was a 77-year-old female who showed 8x10cm sized, erythematous plaque on the suprspubic area of one year's duration. The second case was a 60-year-old male who showed erythematous, oozing, crusted, well circumscribed patches on the right scrotum and the pubic area of 8 years' duration. Third case was a 79-year-old male who showed erythernstous to gray, eczemstoid plaques with marginal elevation on the right side of the scrotum, penile root and pubic area of 3 years duration. On histologic exarnination, the third case showed swest gland adenocarcinoma in the dermis.

A Case of Impetigo Herpetiformis Treated with Retinoid / 대한피부과학회지

We present a case of impetigo herpetiformis occurring in a 20-year-old primigravida who developed severe cutsneous lesion which was characterized by groups of small, sterile pustules on an inflamed base and was associated with fever, chill, and malaise. Histopathologic findings showed acute inflammatory reaction with spongiform pustule of Kogoj in the upper epidermis and microabscess within the horny layer, Antibiotics and steroids treatment even aggravated the disease. After delivery, she was given oral retinoid(Tigason ), and consequently the skin lesions cleared in (i weeks.

Lichen Sclerosus et Atrophicus

A 48-year-old male patient had white to ivory colored patches on brown colored bases over the right side of his back for 8 years without accompanying pruritus or pain. Six months prior to the onset of his skin eruption, he received acupuncture for the relief of right sided back pain for 1 month. Histopathologic examination of the white patches showed follicular plugging, epidermal atrophy, focal hydropic degeneration of basal cells, lymphedema of papillary dermis, thickened homogenization of collagen fibers; consistent with findings previously reported in lichen sclerosus et atrophicus. We report this case to document the occurence in an acupuncture site and stress the unusual clinical manifestation of a zosteriform distribution.

Pigmented Eccrine Poroma on the Scalp

Eccrine poromas mainly involve the non-hairy surfaces of the skin, however, have also been found on hair bearing areas. Pigmentation in the tumor cells is rare but has been mentioned in a few papers. The following case documents an example of a pigmented eccrine poroma which occurred in an unusual location; the posterior scalp.

Lichen Planopilaris

A 26-year-old Korean woman had a 5 month history of pruritic, keratotic papules on the scalp, trunk, and pubic area, which were accompanied by diffuse hair loss from the scalp, eyebrows and pubic area. She also had flat-topped violaceous papules on the scalp and pubic area, and white lace-like striae on the oral mucous and hard palate. Histopathologic study of the progressive stages of the disease revealed dilated follicles filled with horny material, hyperkeratosis, hypergranulosis and hydropic degeneration of the basal cell layer. Throughout the entire subepidermal region, there was an intense bandlike infiltration of mononuclear cells, which were most prominent at the lower pole of the hair follicles. The late stage of the disorder showed atrophy of the epidermis and atrophy of the hair follicles with fibrotic tracts, and mild mononuclear infiltrate at the sites of the former hair follicles. This is the first recorded case, to the best of cur knowledge, in Korea.