Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score.

It is important to determine the severity of atopic dermatitis (AD) for evaluation of disease improvement after and during therapy. Scoring of the severity of AD is demanded in clinical trials. The European Task Force on Atopic Dermatitis (ETFAD) has developed the SCORAD (SCORing AD) index to create a consensus on assessment methods for AD, so that study results of different trials can be compared. However, modification of the SCORAD index has led on several occasions to wrong and incorrect use of the system. To measure the extent of AD, the rule of nines is applied on a front/back drawing of the patient's inflammatory lesions. The extent can be graded 0-100. The intensity part of the SCORAD index consists of six items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness. Each item can be graded on a scale 0-3. The subjective items include daily pruritus and sleeplessness. Both subjective items can be graded on a 10-cm visual analogue scale. The maximum subjective score is 20. All items should be filled out in the SCORAD evaluation form. The SCORAD index formula is: A/5 + 7B/2 + C. In this formula A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The maximum SCORAD score is 103. Based on training sessions by the ETFAD, the SCORAD index was modified by excluding the subjective symptoms (objective SCORAD). The objective SCORAD consists of just the extent and intensity items, the formula being A/5 + 7B/2. The maximum objective SCORAD score is 83 (plus an additional 10 bonus points). Bonus points are given for severe disfiguring eczema (on face and hands). The three-item severity (TIS) score involves the scoring of erythema (redness), oedema and excoriations (scratches) in one representative lesion, marked as R-O-S. The TIS score corresponds well with the more detailed objective SCORAD and can be used as a prescreening system or as a quick system in studies and is excellent for epidemiological studies.

Left-right comparison study of the combination of fluticasone propionate and UV-A vs. either fluticasone propionate or UV-A alone for the long-term treatment of vitiligo.

OBJECTIVE: To compare the efficacy and safety of using a combination of fluticasone propionate (FP) and UV-A with that of either drug used alone in the long-term treatment of vitiligo. DESIGN: Prospective, randomized, controlled, left-right comparison study. Repigmentation was judged by a single dermatologist (L.N.-K.) and skin thickness was scored by a pathologist (using biopsy samples), a dermatologist (L.N.-K.) (visually), and patients (using a standard questionnaire). SETTING: Netherlands Institute for Pigmentary Disorders, Amsterdam. PATIENTS: Patients with lesions on arms, legs, and trunk were treated on 2 symmetrical lesions for 9 months with FP alone and a combination of FP and UV-A (FP group) or with UV-A alone and a combination of FP and UV-A (UV-A group). Fluticasone propionate cream was applied once daily at about bedtime, and UV-A (10 J/cm2) exposure was twice a week. Patients attended the clinic at 3-month intervals. RESULTS: One hundred thirty-five patients were included, 96 of whom were evaluable after 9 months. Patients not reaching the end point withdrew because of insufficient repigmentation (n = 23), decreased motivation (n = 11), or protocol violations (n = 5). No patient (irrespective of whether they withdrew) experienced any adverse effects. The FP and UV-A groups were comparable with respect to sex, age, and location of lesions. On average, combination treatment was 3 times more effective than either UV-A or FP treatment alone. In the FP group, no atrophy was seen after 9 months with either treatment. In the UV-A group, a little atrophy was detected twice: as well during UV-A treatment alone as during combination treatment. CONCLUSIONS: Combination treatment with FP and UV-A is much more effective in reaching complete repigmentation than are FP and UV-A used alone, but large inter-individual differences occur. Fluticasone propionate, UV-A, and a combination of FP and UV-A seem to be safe for long-term treatment of vitiligo.

Scoring the severity of atopic dermatitis: three item severity score as a rough system for daily practice and as a pre-screening tool for studies.

Different scoring systems have been developed to determine the severity of atopic dermatitis. The SCORAD (SCORing Atopic Dermatitis), one of the best validated systems, is suited for clinical trials, but is too complicated and time consuming for routine clinical use. The TIS score (Three Item Severity score), a simplified system, is based on the evaluation of erythema, oedema/papulation and excoriation on a scale from 0 to 3. In order to determine the value of the TIS score we conducted a prospective study in 126 children with mild to severe atopic dermatitis. Both the TIS score and the SCORAD were assessed by trained investigators. Interobserver agreement was investigated in 20 children by comparing the independently performed scores of three investigators. A positive correlation was found between the TIS score and the SCORAD (Rank Spearman r(s)=0.86; p<0.0005). The item which correlated best with the SCORAD was excoriation (r(s)=0.72; p<0.0005) followed by oedema/papulations (r(s)=0.66; p<0.0005). Interobserver agreement which was calculated by Cohen's kappa (kappa) was "excellent" for SCORAD (kappa=0.82; p<0.001) and "fair" for TIS score (kappa=0.58; p<0.01). We conclude that the TIS score is a rough, though reliable and simple system for scoring atopic dermatitis. It is particularly suitable in general practice, for routine clinical use and for screening purposes in clinical trials. For research purposes, the objective SCORAD offers a more detailed and comprehensive assessment.

The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate. The Netherlands Adult Atopic DermatitisStudy Group.

This study was designed to investigate a long-term therapeutic strategy for the management of recurring atopic dermatitis (AD) in adults using fluticasone propionate (FP) ointment (CutivateTM) whereby FP could help to prevent a relapse of AD once symptoms were under control. Adult patients with chronic, moderate to severe AD entered this multicentre study. All patients were initially treated with FP 0.005% (g/g) ointment in two different regimens. Patients whose AD had been completely healed by these treatments then entered a long-term treatment phase applying FP or placebo ointment once daily, two times per week for 16 weeks to 'known' healed lesions. By the end of the initial treatment period, mean SCORAD values had significantly (P < 0.0005) improved from baseline. Patients who entered the maintenance phase and were treated with intermittent FP for up to 16 weeks, demonstrated its superior efficacy (P = 0.018) over placebo, maintaining the improvements achieved after the initial treatment phase, reducing risk of relapse and delaying time to relapse (P = 0.013). No significant changes were detected in either treatment group in serum cortisol levels or in skin thickness measurements. Intermittent FP applied two times per week maintained a significant level of control, and delayed relapse of AD by comparison with placebo.

Fluticasone propionate 0.05% cream once daily versus clobetasone butyrate 0.05% cream twice daily in children with atopic dermatitis.

BACKGROUND: Fluticasone propionate is a novel and potent corticosteroid. It seems to have an improved therapeutic index on the basis of studies on skin thinning and suppression of hypothalamic-pituitary-adrenal axis. OBJECTIVE: We assessed the efficacy and safety of fluticasone propionate (FP) 0.05% cream once daily as compared with clobetasone butyrate (CB) 0.05% cream twice daily in children with atopic dermatitis (AD). METHODS: Twenty-two children (3 to 8 years old) with moderately active AD received either FP once daily or CB twice daily. Severity of AD was scored weekly by means of the modified Scoring of Atopic Dermatitis system (SCORAD) and treatment was either stopped when skin lesions were almost cleared (SCORAD < 9) or after 4 weeks. Cortisol excretion was determined by means of 24-hour urine before and after treatment. RESULTS: Twenty-one children completed the study. After 1 week of treatment, mean SCORAD significantly decreased in both treatment groups. After 2, 3, and 4 weeks cumulatively, 8, 12, and 16 children, respectively, were clinically healed (SCORAD < 9). No significant differences in efficacy were observed between the two treatments. Urinary cortisol excretion was not altered by either of the treatments. Two weeks after discontinuation of active treatment, mean SCORAD had increased to 22, but still was significantly lower than that at the beginning of the study. CONCLUSION: Once-daily treatment with FP is as safe and effective as twice-daily treatment with CB in children with AD. All children experienced an exacerbation of AD within 2 weeks after treatment was withdrawn, indicating the need for long-term "intermittent" treatment.

Inhibition of glutathione efflux in the recirculating rat liver perfusion by cysteine but not by oxothiazolidine carboxylate, an intracellular cysteine precursor.

In the recirculating rat liver perfusion a continuous release of glutathione into the perfusion medium is observed. Addition of L-cysteine to the perfusion medium immediately arrested this glutathione efflux. The cysteine precursor oxothiazolidine carboxylate did not block the glutathione efflux in spite of the fact that it generated more L-cysteine inside the liver cells than L-cysteine itself; L-cysteine is rapidly oxidized to cystine, that is no longer taken up by the liver. The results suggest that the inhibition of glutathione efflux results from the presence of cystine in the perfusion medium.

D-cysteine as a selective precursor for inorganic sulfate in the rat in vivo. Effect of D-cysteine on the sulfation of harmol.

D-Cysteine, the unphysiological isomer of the sulfur containing amino acid L-cysteine, is not utilized for protein synthesis, glutathione synthesis or taurine production; it was tested as a selective precursor for inorganic sulfate, required for sulfation of xenobiotics. Both cysteine isomers were injected intravenously in the rat, in order to investigate their sulfoxidation to inorganic sulfate. The rates of sulfoxidation were very similar, so that stereospecificity for the amino acid seemed not to play a role. When the rats were fed a low-protein diet (LP-diet; containing only 8% casein as source of amino acids) the serum sulfate concentration decreased to about 20% of control. Under these circumstances the rate of sulfoxidation of both isomers was decreased to the same extent. In order to confirm that both cysteine isomers were equally efficient in providing inorganic sulfate for sulfation of xenobiotics, a constant infusion of harmol (a substrate for sulfation) was given to rats fed the LP-diet. Administration of L- or D-cysteine yielded similar increases in sulfation of harmol under these conditions. These results show that D-cysteine can be used to selectively enhance sulfate availability.

Effects of variation in the dietary supply of cysteine and methionine on liver concentration of glutathione and "active sulfate" (PAPS) and serum levels of sulfate, cystine, methionine and taurine: relation to the metabolism of acetaminophen.

Amounts of the sulfur-containing amino acids methionine and cysteine in synthetic diets were decreased from 22.8 mmol methionine (= 100 Met) and 26.4 mmol cysteine (= 100 Cys) per kilogram diet in the control group to (Met/Cys) 100:0, 75:0, 50:0, 25:0 and 25:25, respectively, in experimental diet groups, in order to evaluate effects of limiting sulfur supply on the availability of cosubstrates for conjugation. Below a Met level of 22.8 mmol/kg growth rates decreased. Urinary excretion of inorganic sulfate decreased to 10-20% of control values in all groups. Feeding diets 100:0 and 75:0 for 14 days resulted in a decrease of the concentration of inorganic sulfate in serum; on diets 25:25 and 25:0 an increase was found. A decreased content of methionine/cysteine resulted in an increase in cystine, a decrease in taurine and no change in methionine concentration in serum. In all experimental groups the glutathione concentration in the liver diminished to about 20% of control values, and the hepatic concentration of "active sulfate" (PAPS: adenosine 3'-phosphate 5'-phosphosulfate) decreased in most rats. At the lowest methionine supply, sulfate conjugation of acetaminophen decreased to 50% of control. The formation of the acetaminophen glutathione conjugate remained unaffected, in spite of a decreased hepatic glutathione availability.

The oxidation of L- and D-cysteine to inorganic sulfate and taurine in the rat.

Oral administration of L-cysteine to rats (8 mmol/kg body wt.) caused a rapid increase of the concentration of cystine in serum, from less than 5 micro M in controls to about 200 micro M. Concomitantly, the serum concentration of inorganic sulfate increased, reaching a peak 2 h after L-cysteine administration; this level, twice the control level, was maintained for 4 h. Serum sulfate returned to control concentration 23 h after L-cysteine administration. The urinary excretion of inorganic sulfate during the 24 h after administration increased considerably, and 33% of the dose of L-cysteine was recovered as inorganic sulfate in urine. Consumption of comparable amounts of L-cysteine via the food caused the same increase in urinary excretion of sulfate, but did not increase the concentration of sulfate in serum. After oral administration of D-cysteine (8 mmol/kg body wt.), very high cystine levels were reached in serum (mean concentration about 1500 microM); the sulfate concentration was already maximal 30 min after administration. The increase in urinary excretion of sulfate after D-cysteine was also higher than after L-cysteine administration: 55% of the dose. Possible routes for the rapid degradation of D-cysteine to inorganic sulfate are discussed. The administration of L-cysteine also caused an increase the serum concentration of taurine, while methionine was not influenced. D-Cysteine did not increase the serum concentration of taurine, indicating that it is probably not or only slowly converted to taurine.