Steroid-induced dermal atrophy. Investigations on discontinuous application

In this study several schedules of discontinuous application (DA) were tested, using various weak and strong topical corticosteroids (CS). The purpose of this study was to measure the influence of corticosteroids on skin thickness by means of a mechanical method. In a first experiment, betamethasone 17,21-dipropionate (Bet) and fluprednidene 21-acetate (Flu) were applied to the skin of the volar side of the forearm at a rhythm of 1:1 (1 day CS, 1-day interval) and 1:2 under occlusive dressing. The investigation period was 8 weeks. For comparison, Bet and Flu were applied continuously (CA) for 3 weeks. Flu thinned the skin to a lesser extent than Bet. With DA the skin was thinned to the same extent as with CA. In a second experiment, hydrocortisone 17-butyrate, betamethasone 17-valerate, desoxymethasone and hydrocortisone were tested. Here the treatment regimen was 5:9. The CS preparations were tested for 3 months on the volar side of the forearms under occlusive dressing. Skin thinning occurred during the 5 days of CS action and, in the beginning, receded again in the CS-free interval. However, this regressive process became weaker each time. At the end of the experiment the skin thinning persisted. With the exception of hydrocortisone, all CS tested produced statistically significant skin thinning after DA. The results of the investigation presented here show that thinning of the skin must also be expected with discontinuous application of topical CS.     

The hairless mouse as a model for study of local and systemic atrophogenic effects following topical application of corticosteroids.

The hairless mouse has been used as a model to distinguish between local and systemic atrophogenic effects of topical steroids. Hydrocortisone-17-butyrate, betamethasone-17-valerate, budesonide and clobetasol-17-propionate were applied topically daily for 21 days. Skinfold thickness and dermal DNA synthesis of treated and untreated skin were evaluated as parameters of local and systemic atrophogenicity. Further, body weight gain and thymus weight were assessed as markers of systemic activity. With respect to local effects, skin thickness and dermal DNA synthesis both proved to be good parameters. Of the systemic parameters, thymic involution and body weight gain paralleled quite well the skin thinning on the untreated side. The results confirmed the potency differences of the steroids. Furthermore, they emphasize the usefulness of the hairless mouse to assess the relative safety with respect to local and systemic side effects of chronically applied topical corticosteroids.     

Steroid-induced dermal thinning: discontinuous application of clobetasol-17-propionate ointment.

The skin thinning effect of discontinuous topical clobetasol-17-propionate applications was tested in human volunteers. Application frequencies were daily (1/0), every third day (1/2), every fifth day (1/4), every seventh day (1/6) and every ninth day (1/8). Clobetasol-17-propionate was administered topically under occlusion for 1 h. The treatment period was 41 days. There were no differences of the skin thinning effect of daily and 1/2 administration. The skin thinning effect of 1/4, 1/6 and 1/8 was smaller but also significant compared to controls. The curves demonstrating skin thinning effects initially were dropping off and reached a plateau within about 2 weeks. After finishing application, skin thickness normalized within 2 weeks. Because of these findings, a treatment interval of 3 days is discussed as therapeutically efficient.     

阿达木单抗联合糖皮质激素治疗儿童Stevens-Johnson综合征一例并文献复习

报道阿达木单抗联合糖皮质激素成功治疗一例儿童Stevens-Johnson综合征,并进行文献复习。患者,女,6岁。全身散在红斑、水疱伴发热4天。入院后第一天开始给予甲泼尼龙40 mg/d、人免疫球蛋白（10 g/d×5）治疗,一周后皮损改善不明显,入院第7天、第14天分别给予阿达木单抗40 mg、20 mg治疗,皮损逐渐消退。     

Suppression of contact sensitivity by local hyperthermia treatment due to reduced Langerhans cell population in mice

The effects of local hyperthermia treatment on contact sensitivity (CS) and on the number of Langerhans cells (LCs) were studied in mice. CS was significantly suppressed when mice were sensitized in the hyperthermia treated skin I, 2 or 4 days after treatment (43 degrees C for 45 min). This suppressive effect was not observed 7 or 14 days after the treatment. CS was also suppressed when mice were sensitized in non-treated skin I day after the treatment. The density of LCs detected as ATPase-positive cells also decreased significantly 1, 2, 4 and 7 days after the treatment. There appeared to be a positive correlation between the number of LCs and the extent of CS when mice were sensitized at hyperthermia treated skin. It was observed that this suppressive effect on CS was dose- and temperature-dependent. It could be transferred by spleen cells from the hyperthermia treated and DNFB-sensitized donors, and was antigen specific when spleen cells were transferred before sensitization of the recipient mice. This indicated it was, in part, associated with the induction of suppressor cells. These findings suggest that local hyperthermia treatment reduces the number of LCs with subsequent suppression of the induction phase of delayed-type hypersensitivity by the generation of antigen-specific suppressor cells.     

The new topical ascomycin derivative SDZ ASM 981 does not induce skin atrophy when applied to normal skin for 4 weeks: a randomized, double-blind controlled study

BACKGROUND: SDZ ASM 981 is a selective inhibitor of inflammatory cytokines released from T lymphocytes and mast cells, which has been developed for the treatment of inflammatory skin diseases. OBJECTIVES: In the present study, the atrophogenic potential of SDZ ASM 981 1% cream in humans was compared with that of medium and highly potent topical steroids, and vehicle. METHODS: Four different preparations, SDZ ASM 981 1% cream, the corresponding vehicle of SDZ ASM 981 1% cream, betamethasone-17-valerate 0.1% cream and triamcinolone acetonide 0.1% cream, were applied to the volar aspect of the forearms of 16 healthy volunteers, twice daily, 6 days a week, for 4 weeks. Skin thickness was evaluated by ultrasound examination, clinical signs of atrophy by stereomicroscopy, and epidermal thickness was assessed by histology. RESULTS: Both topical corticosteroids induced a significant reduction in skin thickness, as compared with SDZ ASM 981 1% cream and vehicle, which were shown to be equivalent. The difference in skin thickness (measured by ultrasound examination) between patients treated with SDZ ASM 981 1% cream and those receiving either of the two topical steroids was significant from day 8 onwards. Histological analysis performed at day 29 showed significant epidermal thinning with topical steroids compared with SDZ ASM 981 1% cream or the vehicle. Conclusion The lack of atrophogenic properties of SDZ ASM 981 1% cream in this short-term study demonstrates its potential as long-term treatment for inflammatory skin diseases, thus overcoming a major drawback of topical steroids. This may also be important for the treatment of children, and sensitive areas of skin, such as the face and skin-folds.     

Recovery of human skin collagen synthesis after short-term topical corticosteroid treatment and comparison between young and old subjects

Summary In the present study, the recovery of the collagen synthesis rate after topical potent glucocorticoid treatment in the human skin in vivo was investigated. In the first experiment, two age groups were compared: young subjects with an age range of 21–26 years (mean 23), and old subjects, aged 55–70 years (mean 64). Twenty healthy male volunteers applied betamethasone-17-valerate to their abdominal skin for 3 days twice a day. Suction blisters were induced on the treated areas, and on the opposite side (healthy non-treated skin), of the abdominal skin on the day following the discontinuation of the treatment, and on the second and seventh day. In another experiment, suction blisters were induced after the treatment and 2 weeks later on the treated area and on healthy skin, in eight male volunteers. In both experiments, the aminoterminal propeptides of type I and III collagens (PINP and PIIINP, respectively) were measured radioimmunologically from the suction blister fluid. Corticosteroid treatment decreased the collagen synthesis in both age groups after a 3-day treatment period, and essentially no recovery in the collagen synthesis could be seen during a 1-week corticoid-free period. The inhibition and downregulation of collagen synthesis in the corticoid-treated skin was similar in both young and old subjects, up to 7 days after the treatment. During the 2-week corticoid-free period, collagen synthesis was recovered to about 50% of the level seen in the non-treated skin. Indicating that collagen synthesis is not completely normalized in the human skin even during a 2-week corticoid-free period.     

Optimized interval treatment of eczema with fluprednidene. A multicenter double-blind study

In a multicenter double-blind study, 44 patients suffering from eczema were bilaterally treated with 0.1% fluprednidene-21-acetate over 21 days. Continuous application twice a day was compared with intermittent therapy, i.e. 1 day intermission (15 patients), 2 days intermission (16 patients) and 3 days intermission (13 patients) using the cream base. Final evaluation was based on 11 criteria. All regimens, continuous and intermittent, proved effective (at least 90% reduction of the lesions). Treatment with 3 days intermission showed the same favorable results as continuous application, although the amount of glucocorticoids applied was 75% less. Measurements of the skin fold thickness (SFT) in healthy controls did not indicate any atrophy after treatment with fluprednidene under the same conditions as the eczema patients or under occlusion for up to 21 days. Clobetasol-17-propionate, in contrast, significantly reduced the SFT already after application of only 1 week.     

Objective assessment of photoageing effects using high-frequency ultrasound in PUVA-treated psoriasis patients

BACKGROUND: Skin ageing can be differentiated into intrinsic (chronological) ageing, and photoageing due to chronic sun exposure. Photoageing is the superimposition of photodamage on the ageing process. OBJECTIVES: The aim of the study was to investigate possible differences between the skin of photochemotherapy (PUVA)-treated psoriasis patients and of untreated normal subjects using a high-frequency ultrasound system. METHODS: A total of 124 volunteers (aged 21-88 years, median 52 years, 62 female, 62 male), 62 psoriasis patients who had received PUVA therapy and 62 healthy controls, were investigated. Skin thickness and a subepidermal low-echogenic band (SLEB), a parameter for photodamage, were measured in 12 different areas. RESULTS: Female skin is thinner than male skin. The skin thickness values of PUVA patients were more markedly decreased than those of the controls for the older patients. There was a clear dependence of the occurrence of SLEB on PUVA therapy in psoriasis patients. CONCLUSIONS: Long-term PUVA treatment in psoriasis patients accelerates thinning of the skin in comparison to age-matched controls. The results show that ultrasonography is a sensitive method to investigate the effects of PUVA-induced skin ageing.     

Radiographic measurement of topical corticosteroid-induced atrophy.

Soft tissue x-ray techniques were used to measure skin thickness as influenced by the chronic usage of topical corticosteroids. In a double-blind study commercial preparations of 1% hydrocortisone (HC), 0.1% triamcinolone acetonide (TA), and a placebo cream were compared for their ability to produce atrophy in normal human forearm skin. After 8 weeks of topical application of the creams, only TA produced clinically apparent atrophy. The average percent decreases in skin thickness measured after 8 weeks of treatment with placebo, HC, or TA were 6.0%, 6.0%, and 17.1%, respectively. During the first week after cessation of treatment the clinical appearance of the skin began to improve and by 1 month all treated skin areas had essentially returned to pretreatment thickness.     

Evaluation of the atrophogenic potential of hydrocortisone 1% cream and pimecrolimus 1% cream in uninvolved forehead skin of patients with atopic dermatitis using optical coherence tomography

Topical corticosteroids are widely used to treat atopic dermatitis (AD), but their anti‐inflammatory mode of action can be accompanied by several unwanted side effects including skin atrophy and telangiectasia. In this 8‐week, investigator‐blinded, intraindividual right‐left comparison study with patients with mild‐to‐moderate AD, hydrocortisone 1% cream (HCT) was applied twice daily for 4 weeks on one side of forehead skin without clinical signs of AD and pimecrolimus 1% cream (PIM) on the other. Epidermal and dermal thickness were assessed by optical coherence tomography (OCT) and high‐frequency ultrasound, respectively. Skin atrophy and telangiectasia were assessed by contact dermatoscopic photography (Dermaphot^®). Treatment with HCT leads to a significant decrease in epidermal thickness after only 2 weeks of treatment, while the decrease in PIM‐treated sites was less pronounced and was not statistically significant. By 4 weeks after the end of treatment, epidermal thickness returned to baseline values. No dermal thinning or development of telangiectasia could be observed by means of ultrasound or Dermaphot^®, respectively. In summary, this study indicates that a 2‐week single course of topical treatment with a mildly potent steroid can cause transient epidermal thinning, an effect not seen in the PIM group. The slight decrease with PIM – although not significant – could be due to normalization of the increased skin thickness caused by a subclinical inflammation in AD. This study suggests that PIM may be safer for treatment of AD in sensitive skin areas like the face, especially when repeated application is required.     

Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm)

Patients with atopic skin show a defective barrier function both in rough and in clinically normal skin, with an increasing risk of developing contact dermatitis. Moisturizing creams are often used in the treatment of dry skin. The purpose of this study was to investigate the influence of treatment with a urea-containing moisturizer on the barrier properties of atopic skin. Fifteen patients with atopic dermatitis treated one of their forearms twice daily for 20 days with a moisturizing cream. Skin capacitance and transepidermal water loss (TEWL) were measured at the start of the study and after 10 and 20 days. On day 21 the skin was exposed to sodium lauryl sulphate (SLS) and on day 22 the irritant reaction was measured non-invasively. Skin capacitance was significantly increased by the treatment, indicating increased skin hydration. The water barrier function, as reflected by TEWL values, tended to improve (P = 0.07), and the skin susceptibility to SLS was significantly reduced, as measured by TEWL and superficial skin blood flow (P < 0.05). Thus, it seems that certain moisturizers could improve skin barrier function in atopics and reduce skin susceptibility to irritants. The mechanism and the clinical relevance need further investigation.     

Clinical and histopathological results following TriPollar™ radiofrequency skin treatments

Introduction: Skin laxity, wrinkles and cellulite are common aesthetic problems associated with the aging process. These symptoms are due to the weakening and thinning of dermal connective tissue and the enlargement of hypodermal fat cells. The aim of this study was to evaluate the safety and efficacy of the TriPollar RF technology in reducing fat and collagen regeneration. Methods: Twelve healthy patients underwent weekly treatments on different body sites using the TriPollar technology. Treatment areas were photographed and measured and patient satisfaction was monitored. One abdominal patient consented to a series of TriPollar treatments prior to her scheduled abdominoplasty. A controlled histopathology analysis was performed on skin samples taken during the abdominoplasty procedure. Results: Histopatho-logical examination revealed marked differences between treated and non-treated abdominal skin areas. An increase of 49% in dermal thickness, focal thickening of collagen fibers and focal shrinkage of fat cells was shown following TriPollar treatments. Average patient satisfaction indicated clear satisfaction with the clinical results achieved. Conclusion: The TriPollar is a safe and effective non-invasive technology leading to skin tightening and body shaping. Histology results indicate changes at the dermal and fat layers following TriPollar treatments resulting in increased collagen regeneration and stimulated fat metabolism.     

Effect of a new topical cyclosporin formulation on human allergic contact dermatitis

We studied the effect of a new topical cyclosporin (CS) formulation on the suppression of allergic contact dermatitis. 4 test sites were outlined on the back of healthy male volunteers. For 7 consecutive days, the test sites were treated as follows: #1: CS formulation (10%), #2: placebo formulation, #3: flumethasone pivalate (FP) formulation (0.02%; #4: no treatment. On day 8, we challenged all test sites in the diphenylcyclopropenone (DCP) sensitized individuals. Photographic and clinical documentation was performed daily. 24 h after the DCP skin challenge, a marked redness accompanied by severe itching and slight pain occurred in the test sites pretreated with CS (#1) and placebo (#2). A considerably milder reaction was noted in the untreated test site (#4) and only a faint redness was noted in the test site pretreated with FP (#3). After 36 h, a further increase in the cutaneous reaction was documented in CS and placebo pretreated test sites (#1, 2). In agreement with other workers, topical CS did not suppress experimentally-induced allergic contact dermatitis in man. On the contrary, in CS and placebo pretreated areas (#1, 2), an increased cutaneous reaction was observed. This observation may be explained by the extensive pretreatment with the topical formulation of CS and placebo, which possibly caused a profound perturbation of the stratum corneum, enabling excessive allergen penetration compared to the untreated area with intact stratum corneum.     

Effects of mechanical massage,manual lymphatic drainage and connective tissue manipulation techniques on fat mass in women with cellulite

Objective To evaluate and compare the effectiveness of three different noninvasive treatment techniques onfat mass and regional fat thickness of the patients with cellulites. Methods Sixty subjects were randomized into three groups. Group 1 (n= 20) treated with mechanical massage (MM), group 2 (n= 20) treated with manual lymphatic drainage (MLD) and group 3 (n= 20) treated with connective tissue manipulation (CTM) techniques. Subjects were evaluated by using standardized photographs, body composition analyzer (TBF 300) (body weight (BW), body mass index (BMI), fat %, fat mass (FM), fat free mass (FFM), total body water (TBW)), circumference measurement from thigh, waist‐hip ratio (WHR), fat thickness measurements from abdomen, suprailium and thigh regions with skin fold caliper. Results All groups had an improvement in thinning of the subcutaneous fat after the treatment (P < 0.05). Thigh circumference decreased by an average of 0.5 cm in all groups and thigh fat thickness decreased 1.66 mm in Group 1, 2.21 mm in Group 2 and 3.03 mm in Group 3. Abdomen and suprailium fat thicknesses decreased 2.4 and 2.58 mm in Group 1, 1.78 and 2 mm in Group 2 and 1.23 and 0.64 mm in Group 3, respectively. The mean difference in waist‐hip ratio was 0.1 cm in all groups. Conclusion All the treatment techniques are effective in decreasing the regional fat values of the patients with cellulites.     

Domoprednate (Stermonid), a topical D-homocorticosteroid, skin atrophy and telangiectasia. A double-blind, randomized comparison with hydrocortisone butyrate, betamethasone valerate, clobetasole propionate and placebo

Five corticosteroid ointments and placebo were compared in 17 volunteers with regard to their influence on normal skin under occlusive conditions. Each volunteer had six simultaneous applications on the forearms and six on the back. The trial was double-blind and lasted 4 weeks. The ointments were placed in randomized order. The treatments were 0.1 and 0.03% domoprednate, 0.1% hydrocortisone butyrate, 0.1% betamethasone valerate, 0.05% clobetasole propionate and placebo. Skin thickness was measured on days 0, 7, 14, 21 and 28, transepidermal water loss on days 0, 14 and 28, while blood flow and telangiectasias were evaluated only on day 28 at termination of the trial. The skin thickness became significantly reduced on all corticosteroids, but not on placebo; 0.03% domoprednate, however, tended to have an intermediate position between placebo and the other ointments. The transepidermal water loss did not change. Rating of telangiectasia under stereomicroscope showed a significantly lower score after 0.03% domoprednate and placebo as compared to the other ointments. Assessment of telangiectasia by laser-Doppler flowmetry showed a similar tendency. It is concluded that 0.1% domoprednate is comparable to other topical corticosteroids with respect to atrophogeneity and formation of telangiectasia, but the 0.03% concentration seems to result in fewer side effects.     

Analyses of a mouse model of the dermatitis caused by 2,4,6-trinitro-1-chlorobenzene (TNCB)-repeated application

BACKGROUND: The model of chronic dermatitis caused by repeated application of hapten is frequently used as a tool for assessment of the efficacy of a compound or the elucidation of chronic dermatitis. OBJECTIVE: The purpose of this study is to provide more detailed analysis of the model of chronic dermatitis caused by repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB). METHODS: BALB/c mice were sensitized with TNCB on day -7 to the ear, and then TNCB was repeatedly applied to the same ear three times per week, through days 0-21. RESULTS: The repeated application of TNCB induced an increase of ear thickness, and a relatively steep increment of ear thickness from days 7 to 9 was observed. This increment reached almost a plateau at day 9. The peaks of ear swelling on days 7, 14 and 21 were approximately two times higher than that on day 0. Regarding cytokines in the ear, the highest production of IL-1 beta, 4, 6 and 18 were observed on day 7. The peak production of IL-1 beta, 4 and 6 on day 7 was found within 24 h after the challenge, while that of IL-18 was found at 0 h. The inflammatory cell infiltration into epidermis and dermis was observed and increased in day 7, then reached almost a plateau on day 9. CONCLUSION: The indices such as thickness, swelling and inflammatory cell infiltration in the lesional skin was increased and maintained by repeated application, however, the protein levels of some cytokines were not always consistent with the reactions.     

透明质酸对BALB/c小鼠激光损伤后皮肤屏障功能修复的研究

【摘要】 目的 探讨透明质酸敷料促进BALB/c小鼠皮肤激光损伤后皮肤屏障修复的作用。 方法 36只清洁级雌性BALB/c小鼠均分为3组,每只小鼠用脱毛膏两侧背部脱毛后,用Q开关1064激光机,频率5 Hz,光斑3 mm,能量6 J的激光照射脱毛区后,每组分别外用基质、基质 + 胶原蛋白、基质 + 透明质酸于小鼠一侧背部,另一侧不做处理（阴性对照）。分别于6 h,24 h,7 d,21 d测试每只小鼠背部皮肤生理功能,并取每组3只小鼠皮损处皮肤做增殖细胞核抗原染色。 结果 与基质组和阴性对照比较,于第7天,基质 + 胶原蛋白组,基质 + 透明质酸组经表皮失水量值差异有统计学意义（P ＜ 0.05）,角质层含水量差异有统计学意义（P ＜ 0.05）,增殖细胞核抗原表达较强（P ＜ 0.05）。24 h、1 d、21 d组间经表皮失水量、角质层含水量及增殖细胞核抗原表达强度差异无统计学意义（P ＞ 0.05）,第21天各组与造模前比较,差异无统计学意义（P ＞ 0.05）。各组小鼠皮肤屏障功能恢复正常。 结论 透明质酸敷料能促进BALB/c小鼠激光术后皮肤屏障功能修复,与胶原蛋白敷料作用相当。     

Effects of p-coumaric acid on erythema and pigmentation of human skin exposed to ultraviolet radiation

Background. It has been recently recognized that p‐coumaric acid (PCA) is a strong inhibitor of cellular melanogenesis. Aim. To evaluate the erythema‐suppressive and skin‐lightening effects of PCA after topical application to human skin. Methods. The control and PCA cream products were applied twice daily to the skin of the forearm of 21 subjects before and after ultraviolet (UV) irradiation to determine whether they could prevent erythema formation and pigmentation. The cream products were also applied to different areas only after the induction of erythema or pigmentation to determine whether they could have a depigmenting effect. Results. A 7‐day application of control and PCA cream products before UV irradiation decreased UV‐induced erythema formation by 31% and 77%, respectively, compared with untreated skin. When the PCA cream was applied after UV irradiation, its effects on skin colour or pigmentation were less remarkable. However, the melanin index was significantly decreased at the sites treated with PCA cream for 70 days compared with control sites, and the Individual Typology Angle (ITA°) value was increased significantly. Of the 21 subjects, 2 had mild adverse skin reactions to both the PCA and control creams. Conclusion. These results suggest that PCA cream can reduce UV‐induced erythema formation and subsequent pigmentation in human skin.