Complications of topical hydrocortisone

Chronic and uninterrupted application of 1% hydrocortisone was followed by complications in six patients. Three developed a rosacea-like eruption for the first time and one also had perioral dermatitis. All of these responded to treatment and remained clear. Another patient had a severe exacerbation of rosacea following use and withdrawal of 1% hydrocortisone cream. Two female adults developed atrophy and telangiectasia of the eyelids following long-term application of 1% hydrocortisone cream. The severity of the complications reported was generally less than that found following use of more potent topical corticosteroids. However, the complications experienced by these patients would suggest that therapy with any effective topical corticosteroid should be intermittent. Particular care should be used in susceptible individuals and in vulnerable areas such as the eyelids.     

Quantifying systemic absorption of topical hydrocortisone in erythroderma

The systemic absorption of topical hydrocortisone (HC) was quantified in seven patients with erythroderma, using the ratio of the areas under the curves for plasma concentration vs. time, following topical and intravenous administration. Over a period of 24 h. 19–93 mg of HC was absorbed systemically, corresponding to 4–19% of the total topical dose of 500 mg. Thus, topical HC therapy of erythroderma is accompanied by a pharmacologically significant systemic dose.     

Percutaneous absorption of hydrocortisone and testosterone on the vulva and forearm: effect of the menopause and site

Summary The percutaneous absorption of hydrocortisone and testosterone was studied following their application to the vulvar and ventral forearm regions of pre- and post-menopausal women. Percutaneous absorption of hydrocortisone was significantly greater in vulvar skin than forearm skin in both pre- and post-menopausal women (P <0·05. respectively), whereas the percutaneous absorption of testosterone was significantly increased (P<0·01) on the vulva compared with the arm only in post-menopausal women.
The effect of age on the percutaneous absorption of hydrocortisone and testosterone was evaluated by using the menopause as a biological chronometric end point. It is a common misconception that older skin has a diminished barrier capacity, and that percutaneous absorption is therefore greater. Our studies showed that absorption of hydrocortisone vulval skin of pre-menopatisal women was significantly greater (P<0·01) than in post-menopausal women. The ventral forearm skin of pre-menopausal women tended to show increased absorption compared with post-menopausal women, but statistical significance was not reached. No significant differences (P > 0· 05) in the percutaneous absorption of testosterone in vulval or forearm skin were observed between the two age groups.     

A comparison of once-daily application of mometasone furoate 0.1% cream compared with twice-daily hydrocortisone valerate 0.2% cream in pediatric atopic dermatitis patients who failed to respond to hydrocortisone

Two hundred and nineteen patients completed this multicenter, randomized, evaluator-blind, parallel-group study evaluating the efficacy and safety of once-daily application of mometasone furoate 0.1% cream compared with twice-daily hydrocortisone valerate 0.2% cream in children with moderate to severe atopic dermatitis. Enrolled patients were between 2 and 12 years of age and had failed to respond to at least 7 consecutive days of treatment with a topical hydrocortisone preparation, with the last application of hydrocortisone occurring within a week before enrolling in the current study. Patients were randomized to treatment from 10 centers in the USA with either mometasone furoate 0.1% cream (n = 109) or hydrocortisone valerate 0.2% cream (n = 110) for up to 3 weeks. At enrollment, a target area of dermatitis (not the face or forehead) of at least 20 cm² was selected by the investigator for specific evaluation of the effects of treatment on disease signs and symptoms. Additionally, patients had to present with at least 15% total body surface involvement, excluding the face and forehead, with the current exacerbation of atopic dermatitis. The severity of erythema, induration/lichenification, scaling/crusting, exudation, excoriation, and pruritus was graded on the following scale: 0 = none; 1 = mild; 2 = moderate; 3 = severe. A total sign/symptom severity score (sum of six individual sign/symptom severity scores) of ≥ 8 was required in the target area (maximum = 18), with a severity score of ≥ 2 required for erythema and for one other sign. Patients were examined on return visits on days 4, 8, 15, and 22 of treatment and the severity of the signs and symptoms present in the target area was rated by the investigator at each visit. Areas outside the target area were also treated with the study medications and evaluated by the investigator in the global response to treatment. The criteria for global clinical response compared to baseline were as follows: cleared (100% improvement); excellent (75–99% improvement); good (50–74% improvement); fair (25–49% improvement); poor (< 25% improvement); exacerbation (a flare-up at a treatment site). No other therapies for atopic dermatitis were permitted.     

Photocontact dermatitis to hydrocortisone

A patient was found to have a delayed positive patch test to hydrocortisone on multiple testing. This proved to be due to a photoallergy with an action spectrum in the UV-A range. The patient coincidently had a polymorphous light eruption in the UV-B range.     

Enzyme inhibition in human skin homogenates by hydrocortisone,hydrocortisone acetate and hydrocortisone butyrate

Summary In fresh human skin homogenates, the activities of four enzymes, lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), acid phosphatase (AcP), and leucine aminopeptidase (LAP) were assayed following an incubation with hydrocortisone, hydrocortisone acetate, or hydrocortisone-17-butyrate, respectively. Concentration of the three compounds measured 2.75 mMol/l. Hydrocortison butyrate inhibited LDH-, G-6-PDH-, and AcP-activities. Hydrocortisone and hydrocortisone acetate exerted a significant inhibitory action only in the case of G-6-PDH-activity.—On pure G-6-PDH from yeast, the inhibition exerted by hydrocortisone butyrate was significantly stronger than the inhibition exerted by the two other steroids. Time/action diagrams revealed the fact that hydrocortisone butyrate is superior to the other two compounds from the beginning of the incubation period.—The data sustain the assumption that hydrocortisone butyrate exerts biochemical-pharmacological actions of its own and that it may not be considered just as an esterified transport form of hydrocortisone.

---

Zusammenfassung In Homogenaten frischer menschlicher Haut wurden die Aktivitäten der Laktatdehydrogenase (LDH), der Glukose-6-phosphat-Dehydrogenase (G-6-PDH), der sauren Phosphatase (AcP) und der Leucinaminopeptidase (LAP) nach Inkubation mit Hydrocortison, Hydrocortison-acetat oder Hydrocortison-17-butyrat bestimmt. Die Konzentration des Steroids betrug in allen drei Fällen 2,75 mMol/l. Hydrocortison-butyrat bewirkte eine signifikante Hemmung der LDH-, G-6-PDH- und AcP-Aktivitäten. Hydrocortison und Hydrocortison-acetat zeigten nur bei der G-6-PDH-Aktivität eine signifikante Hemmwirkung. — An reiner G-6-PDH aus Hefe war die Hemmwirkung von Hydrocortison-butyrat signifikant stärker als die Hemmwirkung von Hydrocortison und Hydrocortison-acetat. Zeit-Wirkungs-Diagramme zeigten, daß Hydrocortison-butyrat vom Beginn der Inkubation an wirksam ist (keine Esterspaltung). — Die Ergebnisse unterstützen die Annahme, daß Hydrocortison-butyrat eigene biochemische-pharmakologische Effekte besitzt und daß es nicht nur als veresterte Transportform von Hydrocortison angesehen werden darf.

     

Contact allergy to hydrocortisone 17-butyrate

Two female patients with stasis dermatitis developed allergic contact dermatitis to hydrocortisone 17-butyrate cream. Patch tests with hydrocortisone 17-butyrate were positive, but not with the vehicle. One patient was also allergic to two other commerical corticosteroids, but patch tests revealed positive reactions only to ingredients of the vehicles. Attention is drawn to the frequency of contact allergy to corticosteroids in patients with stasis dermatitis.     

In vitro evidence of delayed-type hypersensitivity to hydrocortisone

Hypersensitivity to topical hydrocortisone is becoming increasingly recognized. We present further evidence that this is mediated via a delayed-type hypersensitivity reaction. A hydrocortisone: albumin complex was able to induce a proliferative response in the peripheral blood mononuclear cells of patients allergic to hydrocortisone. Protein binding of hydrocortisone or a degradation product may be important in the development of corticosteroid allergy.     

Reactions to other corticosteroids in patients with allergic contact dermatitis from hydrocortisone

It has been proposed that corticosteroid cross-reactions occur more frequently within structurally well-defined groups. To test this hypothesis we have compared the patch-test reactions to other corticosteroids in 96 patients allergic to hydrocortisone. We found that our data did not agree with the previously proposed classification. The presence of a substitution at the C₆ or C₉ position was the most important factor in determining whether a patient would be allergic to another corticosteroid. This information should facilitate the choice of an alternative corticosteroid in patients allergic to hydrocortisone, if facilities for patch testing to other corticosteroids are not available.     

A clinical trial with hydrocortisone butyrate cream in eczema

In a double blind trial 0·1% hydrocortisone butyrate cream gave after a week a significantly better therapeutic response in eczema than 0·1% triamcinolone acetonide (P<0·05) and hydrocortisone acetate. The methods for clinical trials are discussed.     

Randomized,double‐blind,split‐side comparison study of moisturizer containing licochalcone vs. 1% hydrocortisone in the treatment of infantile seborrhoeic dermatitis

Background Infantile seborrhoeic dermatitis (ISD) is a common skin lesion in infants. There may be differences in recommendation for treatment of ISD. Objective To compare the efficacy of moisturizer containing licochalcone vs. 1% hydrocortisone for the treatment of ISD. Methods This was a randomized, prospective, split‐side, double‐blind study that was conducted in 75 infants between the age of 2 weeks and 1 year. Patients with a clinical diagnosis of ISD were treated twice daily, simultaneously with either moisturizer containing 0.025% licochalcone or 1% hydrocortisone on opposite sides of the lesion. The scoring system was used to assess the severity of the rash by the presence of erythema, scale and crusts. The lesions on each side were evaluated on day 0, 3–4, 6–7 and 14. Results A total of 72 patients completed the study. The moisturizer containing licochalcone group had a higher clearing rate (42%) compared to 1% hydrocortisone group (32%) (P = 0.03) on day 3–4. Both products were equally effective in the treatment at day 6–7 and 14 (P = 0.45 and 1, respectively). By the end of the second week, the cure rate of the moisturizer containing 0.025% licochalcone and 1% hydrocortisone group was 90% and 92%, respectively. Limitations The small sample size was a study limitation. Conclusion Moisturizer containing 0.025% licochalcone had higher cure rate compared to 1% hydrocortisone for the treatment of ISD at day 3–4. However, by the end of the first week, this difference was no longer significant.     

Allergy to systemic and intralesional corticosteroids

In this study, allergic reactions to systemic or intralesional corticosteroids were characterized, and skin tests utilized in the diagnosis of corticosteroid allergy. Five patients who had developed a rash when treated with systemic or intralesional hydrocortisone, methylprednisolone, prednisolone or betamethasone, were challenged with oral or intra-articular corticosteroid preparations, and skin tested. Upon provocation the patients reacted with diffuse erythema principally on the trunk or on the face. The erythema appeared within a period ranging from a few hours to 24 h and faded in 1–3 days. On patch testing, one patient reacted to prednisolone and methylprednisolone, which induced a positive response upon provocation, and two patients were positive to Pivalone®. Patients who were sensitive to hydrocortisone or methylprednisolone, as judged by anamnestic data and provocations, reacted to these corticosteroids in the intradermal tests. Allergy to betamethasone could not be verified by intradermal or patch tests. A combination of intradermal and patch tests is recommended when allergy to systemic or intralesional corticosteroids is suspected. If these skin tests remain negative, provocation is the method of choice.     

Hydrolysis of hydrocortisone 17-butyrate 21-propionate by cultured human keratinocytes

Hydrolysis of 17-butyrate 21-propionate (HBP) by human keratinocytes was studied using an in vitro system. In the culture of human keratinocytes 1.308 nmole/ml of hydrocortisone 17-butyrate (de-esterified HBP at the position of 21) was found at 1 h after the addition of 10 nmole/ml HBP. At 6 h most of HBP was de-esterified to become HB17 and a small amount of hydrocortisone 21-propionate (de-esterified HBP at the position of 17) was detected. Hydrocortisone (HC) was not detectable. These results indicate that when HBP is applied on the skin, it is hydrolyzed at the position of 21, and reaches the dermis where it finds the way to get into the systemic circulation. The intracellular concentration of HBP was estimated to be more than 5 times its extracellular concentration and its accumulation was higher than HC. These results were discussed in relation to the potentiation of local antiinflammatory action and the reduction of systemic effects of topical glucocorticoid.     

An evaluation of topical 3% salicylic acid and 1% hydrocortisone in the maintenance of scalp pruritus

Background Scalp pruritus is a common condition causing dermatologic distress. The presence of skin scale on clothing is cosmetically undesirable and scalp scratching in public is socially embarrassing. Scratching can also result in removal of the cuticle and premature hair shaft fracture. Objective To demonstrate the efficacy of 3% salicylic acid in combination with 1% hydrocortisone in the treatment of scalp pruritus. Methods Sixty subjects with moderate scalp scaling and scalp pruritus were enrolled in a three‐arm double blind 2‐week study. The 20 subjects in arm 1 applied a topical 1% hydrocortisone product twice daily. The 20 subjects in arm 2 applied a topical 3% salicylic acid product twice daily. Lastly, the 20 subjects in arm 3 applied a topical 3% salicylic acid product in the morning and a topical 1% hydrocortisone product in the evening. Evaluations were performed at baseline, after 1 week of treatment, and after 2 weeks of treatment. The study investigator evaluated the subjects for scalp scale, erythema, excoriation, and overall assessment. In addition, scalp scale scrapings were collected and analyzed to gain further insight into scalp scale morphology. Subject assessments and scalp photography was also performed. Results The investigator assessments revealed less excoriation in the hydrocortisone twice daily arm over the salicylic acid twice daily arm (P = 0.03), which might be expected because of its anti‐inflammatory effect. The morning salicylic acid application and evening hydrocortisone application arm performed better than the salicylic acid twice daily group at week 2 in terms of erythema (P = 0.02), excoriation (P = 0.03), and overall assessment (P = 0.01). Scalp scale scrapings revealed the least amount of retained skin scale in the combination salicylic acid/hydrocortisone group. Conclusion The combination of a 3% salicylic acid keratolytic combined with a 1% hydrocortisone anti‐inflammatory provides the best relief of scalp pruritus.     

Percutaneous absorption of hydrocortisone during exacerbation and remission of atopic dermatitis in adults

Percutaneous absorption of hydrocortisone was studied in 18 young adults during and after the acute phase of atopic dermatitis using the direct hydrocortisone absorption test. In the acute phase the post-application increase in serum cortisol concentration ranged between 18 and 711 nmol/l (median 125 nmol/l). In remission the increase in serum cortisol ranged between 0 and 114 nmol/l (median 16 nmol/l), which was significantly lower than the rise in the acute phase. In the acute phase of dermatitis, topical hydrocortisone treatment has both a local and a systemic effect, due to percutaneous absorption.     

Proprietary hydrocortisone creams

Six proprietary hydrocortisone creams were evaluated for vasoconstrictor activities and bio-availabilities using an occluded blanching test. Statistical analysis showed a significant difference between the formulations. Dioderm, containing 0.1% hydrocortisone, was significantly more active than the 1% hydrocortisone creams—Alphaderm, Calmurid HC, Efcortelan and Vioform-Hydrocortisone. There was no significant difference between Dioderm and Dioderm C. Unlike creams containing more potent corticosteroids the hydrocortisone formulations apparently failed to produce steroid reservoirs in the stratum corneum as assessed by the blanching response.     

胶原贴敷料联合丁酸氢化可的松乳膏治疗面部过敏性皮肤病65例临床观察

目的观察胶原贴敷料联合丁酸氢化可的松乳膏治疗面部过敏性皮肤病的疗效。方法观察组和对照组均口服盐酸左西替利嗪片5mg,1次/d,同时外用丁酸氢化可的松乳膏,2次/d,连用10天;此外观察组每天用胶原贴敷料敷面1次,连用10天,比较两组患者的疗效。结果观察组治愈率为68.33%,有效率为80.00%;对照组分别为38.33%和53.33%,两组治愈率与有效率比较,差异均有统计学意义(P均<0.05)。结论胶原贴敷料作为面部过敏性皮肤病的辅助疗法,效果明确,值得临床应用。     

The effect of liposomal incorporation of topically applied hydrocortisone on its serum concentration and urinary excretion

We demonstrated previously, that hydrocortisone incorporated in the phospholipid bilayer of liposomes (liposomal hydrocortisone) shows an improved concentration-time profile in the different skin layers after external application when compared with a conventional ointment. In the present work, it was investigated under in vivo conditions, whether or not the liposomal formulation also enhances the percutaneous absorption rate. The results obtained in guinea pigs clearly demonstrate a decrease in serum concentration and urinary excretion. Thus, hydrocortisone-loaded liposomes, when applied topically, act as a selective drug delivery system or "drug localizer" increasing the therapeutic efficacy and, simultaneously, decreasing adverse systemic effects. The significance of liposomal attenuative and potent glucocorticoids in topical treatment is discussed.     

Comparison of desoximetasone and hydrocortisone butyrate in psoriasis.

Thirty psoriatics were treated for 2 weeks on a double-blind controlled basis with desoximetasone (0.25%) and with hydrocortisone butyrate (0.1%). It was a randomised left-right comparative trial. Thirteen out of 27 patients preferred desoximetasone, 3 patients preferred hydrocortisone butyrate. There was also a significantly better effect of desoximetasone as judged by the observer after the second week of treatment.     

皮肤瘙痒症血清P物质的检测及辣椒碱软膏的疗效观察

目的检测P物质在瘙痒症患者中的水平,观察辣椒碱软膏对皮肤瘙痒症的疗效及对P物质的影响。方法选取门诊确诊瘙痒症患者120例,随机分为两组,分别外用辣椒碱和丁酸氢化可的松治疗3周,观察瘙痒的缓解程度及不良反应。治疗前后ELISA法检测血清P物质浓度。结果瘙痒症患者血清P物质显著高于正常人(P<0.0001);治疗前后两组血清P物质差异均有统计学意义(P<0.0001);治疗后辣椒碱组血清P物质浓度显著低于丁酸氢化可的松组(P<0.05)。辣椒碱组和丁酸氢化可的松组的有效率分别为86.67%和70.00%,差异有统计学意义(P<0.05);丁酸氢化可的松组缓解瘙痒的平均起效时间(4.5±1.5)d较辣椒碱组(5.1±1.4)d明显缩短(P<0.05)。结论 P物质在瘙痒症的致痒中起重要作用,辣椒碱能有效降低血清中P物质,对治疗皮肤瘙痒症安全有效。