Clinical characteristics and outcome measures in hidradenitis suppurativa research

Introduction:  Outcome measures for medical treatment of HS are needed.
Patients and methods:  One hundred and sixty-four consecutive patients were prospectively evaluated. A new score was evaluated: HSPAIN = pain intensity on a visual analog scale (VAS 1-10) × number of painful days/month.
Results:  Mean age was 34 years (± 11), sex ratio F/M 2.8:1. Forty-two per cent were over weighted; 82% were smokers, 30% had a family history of HS. Age at onset was 23 years. Hurley's class was I = 72%; II = 25 %; III = 3%. Mean Sartorius' score ( 1 ) was 22 (range: 3–72). Pain on VAS was 4.1 for lower localizations, and its duration was >15 days/month for 25% of patients. Patients with a Sartorius' score > median were older ( P  = 0.003), more frequently overweighted (0.02). The mean HSPAIN scored 7.9 (0–30). It was highly correlated to Sartorius' score ( P  < 10-3). This new score has been used in therapeutic trials of dalacine – rifadin combination and of zinc gluconate. Quality of life study of 61 patients emphasizes the strong impact of HS compared with other dermatological diseases; patients with an early onset, long duration and continuous evolution are particularly affected.
Conclusion:  Surgery is not the only treatment for HS; we need outcome measures that are more adapted to medical treatment, i.e. integrating pain which is the major burden of this disease.     

Evaluation of the efficacy and safety of infliximab on psoriatic nails: an unblinded, nonrandomized, open-label study

Background  Despite advances in the treatment of skin psoriasis during the last years, therapy of psoriatic nails remains a challenge.
Objectives  The objective of this unblended, nonrandomized, open-label study was to evaluate the efficacy and safety of infliximab on nail psoriasis.
Patients/Methods  Eighteen psoriatic patients with nail involvement, consecutively selected among patients scheduled to start infliximab infusions were included in the study. Thirteen of these patients had psoriatic arthritis and five had severe plaque type psoriasis. Outcome measures were assessed at baseline and at weeks 14, 22, 30 and 38 using the nail psoriasis severity index (NAPSI). Patients also filled in a Greek translation of the international onychomycosis-specific questionnaire to assess improvement in quality of life after improvement of psoriatic nail signs.
Results  All 18 patients completed the study. Significant improvement was noted in most patients after the third infusion as shown by the reduction of mean NAPSI (NAPSIm) from 55·8 at baseline to 29·8 at week 14. Evaluation after six infusions, at week 38, showed an almost complete resolution of psoriatic nail involvement (NAPSIm: 3·3). No adverse event was observed. All patients reported satisfaction with the results and significant improvement in their quality of life with reduction of the score of the international quality of life questionnaire from 66·3 at baseline to 19·1 at week 38.
Conclusions  Αlthough there is no control group, this data suggests that infliximab is effective for psoriatic nail disease in the context of severe skin and joint involvement.     

Long-term maintenance treatment of moderate-to-severe plaque psoriasis with infliximab in combination with methotrexate or azathioprine in a retrospective cohort

Background  Effective, fast-acting and safe therapies are needed for long-term maintenance treatment of psoriasis. In October 2005, infliximab was approved for the treatment of moderate-to-severe plaque psoriasis, but long-term data are limited.
Objective  To evaluate the effectiveness of infliximab, used in combination with methotrexate or azathioprine, in maintaining clinical benefit in patients with moderate-to-severe psoriasis.
Methods  The medical charts of 23 patients treated with infliximab from August 2001 to February 2007 were retrospectively reviewed. Most patients received either infliximab 3 mg/kg (17 of 23) or 5 mg/kg (1 of 23) in combination with methotrexate, while 5 of 23 patients received infliximab 5 mg/kg in combination with azathioprine. Psoriasis Area Severity Index (PASI) score and adverse events were recorded at every infliximab infusion visit at the hospital.
Results  Patient data were available for a minimum of 4 weeks and up to 5 years and 5 months. At week 14, 91.3% achieved PASI 50, 69.6% achieved PASI 75, and 39.1% achieved PASI 90. Only two patients discontinued therapy due to loss of response: one after 15 months and one after 3 years. All other patients displayed a good clinical response (≥ PASI 50) and were still receiving this regimen at last observation. Combination regimens of infliximab with methotrexate or azathioprine were well tolerated, and only one patient discontinued therapy because of an adverse event (lung embolism) after two infusions with infliximab.
Conclusions  Long-term (> 1 year) maintenance therapy of infliximab combined with methotrexate or azathioprine is effective and well tolerated for moderate-to-severe plaque-type psoriasis.

Conflicts of interest

None declared     

Platelet-rich fibrin matrix for improvement of deep nasolabial folds

Background  Dermal augmentation continues to grow as an aesthetic facial procedure. Many exogenous filler materials rely on an autologous fibrotic response for volume augmentation.
Aims  To evaluate the efficacy of a single injection of autologous platelet-rich fibrin matrix (PRFM) for the correction of deep nasolabial folds (NLFs).
Patients/methods  Whole blood was obtained from 15 adults, and an activated autologous PRFM produced using a proprietary system (Selphyl^®; Aesthetic Factors, Inc., Wayne, NJ, USA) was then injected into the dermis and immediate subdermis below the NLFs. Subjects were photographed before and after treatment; NLFs were rated by the treating physician before and after treatment using the Wrinkle Assessment Scale (WAS) and patients rated their appearance at each post-treatment visit using the Global Aesthetic Improvement Scale. Patients were evaluated at 1, 2, 6, and 12 weeks after treatment.
Results  All patients were treated to maximal (no over-) correction, with a mean reduction in WAS score of 2.12 ± 0.56. At 1 week after treatment, this difference was 0.65 ± 0.68, but rose to 0.97 ± 0.75, 1.08 ± 0.59, and 1.13 ± 0.72 at 2, 6, and 12 weeks after treatment, respectively ( P  < 0.001). No patient noted any fibrosis, irregularity, hardness, restricted movement, or lumpiness.
Conclusions  PRFM can provide significant long-term diminution of deep NLFs without the use of foreign materials. PRFM holds significant potential for stimulated dermal augmentation.     

Efficacy of oral naltrexone on pruritus in atopic eczema: a double-blind, placebo-controlled study

Aim  The intent of our study was to determine the efficacy of oral naltrexone, an opiod antagonist, in the treatment of pruritus in patients with chronic eczema.
Methods  This double-blind, placebo-controlled study recruited 38 patients with eczema complaining from pruritus. Pruritus scores were evaluated. Patients were given placebo ( n  = 20) or naltrexone 50 mg ( n  = 18) for 2 weeks period. During the study, pruritus scores based on visual analogue scale system (VAS) were assessed three times: at the start of study, after 1 week, and after 2 weeks.
Results  In both groups, decreased VAS scores were observed, but naltrexone showed to be significantly more effective than placebo in decreasing VAS score after 1 week ( P <  0.005) and 2 weeks ( P <  0.001).
Conclusion  Naltrexone is more effective than placebo in the treatment of pruritus in patient with eczema. Naltrexone might be considered as an adjunct treatment in the treatment of pruritus. However, further studies in this aspect are highly fostered.

Conflicts of interest

This study and the authors were not supported by any company with a vested interest in the product being studied and the project was funded by Skin Research Center.     

Infliximab improves health-related quality of life in the presence of comorbidities among patients with moderate-to-severe psoriasis

Background  Psoriasis affects patients both physically and psychologically.
Objectives  To investigate the effect of comorbidities on health-related quality of life (HRQoL) and to determine whether infliximab improved HRQoL in the presence of these conditions.
Methods  In this multicentre, double-blind study, 835 patients with moderate-to-severe plaque psoriasis were randomized to receive infliximab 3 or 5 mg kg⁻¹ or placebo at weeks 0, 2 and 6. Infliximab-treated patients were re-randomized at week 14 to receive the same treatment every 8 weeks or as needed through week 46; placebo patients crossed over to infliximab 5 mg kg⁻¹ at week 16. Disease severity (Psoriasis Area and Severity Index, PASI) and HRQoL (Dermatology Life Quality Index, DLQI; 36-item Short-Form Health Survey, SF-36) were measured at various time points. The effect of patient comorbidities on baseline HRQoL was assessed using multiple regression models. The impact of key comorbidities on infliximab treatment effect was also assessed.
Results  Disease severity (PASI), depression and psoriatic arthritis (PsA) were predictors of poor baseline HRQoL. At week 10, infliximab 3 and 5 mg kg⁻¹ significantly improved physical and mental health dimensions of the SF-36 and the DLQI (all P  < 0·001). Consistent improvement in HRQoL with infliximab treatment was observed regardless of baseline patient characteristics or comorbidities. Through week 50, HRQoL and PASI scores were most improved with infliximab 5 mg kg⁻¹ administered every 8 weeks.
Conclusions  Disease severity, depression and PsA were significant predictors of poor HRQoL. Infliximab significantly improved HRQoL, regardless of these characteristics.     

Hidradenitis suppurativa responding to treatment with infliximab

A series of four cases of severe recalcitrant hidradenitis suppurativa treated with infliximab is presented. All patients had failed to respond to prior medical and surgical management. Baseline Quantiferon‐TB Gold and chest radiograph were carried out before commencement of treatment. No patients had associated Crohn's disease. All patients received induction infusions of infliximab 5 mg/kg at weeks 0, 2 and 6, followed by eight weekly maintenance infusions. The total number of infusions varied between 4 and 6. Skin photography with Sartorius scoring was used to evaluate response to treatment. All patients experienced marked improvement in their disease activity, with a mean 48% improvement in Sartorius score after one infusion (week 2, P < 0.01), and 70% improvement after three infusions (week 14, P < 0.01). Time to relapse following cessation of therapy ranged from 6 weeks to 4 months. Further studies examining the efficacy of infliximab and its effect on the course of the disease, particularly relating to long‐term management, are required.     

英夫利西单抗长疗程治疗关节病型银屑病的临床疗效分析

目的：评价长疗程应用英夫利西单抗治疗关节病型银屑病的临床疗效。方法：随访分析2016年11月至2018年11月就诊于中国人民解放军总医院皮肤科接受英夫利西单抗治疗的关节病型银屑病患者。观察第2周、6周以及此后每间隔8周用药后的关节症状及皮损改善情况以及肿瘤坏死因子-α(TNF-α)等指标的变化。结果：8例患者用药疗程满30周,纳入数据分析, 其中5例满46周。LSD法显示,治疗后患者肿胀关节数（0周VS 30周：t=6.939,P<0.001;0周VS 46周：t=3.822,P=0.019)、压痛关节数（0周VS 30周：t=5.353,P=0.001;0周VS 46周：t=3.132,P=0.035)明显减少,PASI值在第30周时下降最明显（0周VS 30周：t=3.742,P=0.007）, TNF-α水平在第22周最高（0周VS 22周：t=3.569,P=0.009）,超过22周后逐渐降低（30周VS 46周：t=4.104,P=0.009）。 结论：英夫利西单抗能够显著改善关节病型银屑病患者的关节症状和皮损,但长疗程应用时疗效呈降低趋势。     

Treatment of palmoplantar psoriasis with infliximab: a randomized,double‐blind placebo‐controlled study

Background Palmoplantar psoriasis is a difficult to treat variant of plaque psoriasis. Objective To study the safety and efficacy of infliximab in non‐pustular palmoplantar psoriasis. Methods Patients with non‐pustular palmoplantar psoriasis affecting at least 10% of their palms and soles and with a modified palmoplantar psoriasis area and severity index (m‐PPPASI) of at least eight were recruited. Patients were randomized (1:1) to receive infliximab 5 mg/kg or placebo at weeks 0, 2 and 6. Patients initially randomized to placebo received infliximab at weeks 14, 16 and 20 whereas patients randomized to infliximab received additional infliximab infusions every 8 weeks until week 22. Results Twenty four (24) patients were randomized in this study. At week 14, 33.3% and 66.7% of patients treated with infliximab achieved m‐PPPASI 75 and m‐PPPASI 50 respectively compared to 8.3% for both m‐PPPASI 75 (P = 0.317) and m‐PPPASI 50 (P = 0.009) for patients randomized to placebo. A reduction of 50.3% in the mean surface area of palms and soles affected with psoriasis was seen at week 14 in patients randomized to infliximab as compared to an increase of 14.9% in patients randomized to placebo (P = 0.009). Conclusions This pilot study did not reach its primary endpoint of m‐PPPASI 75 at week 14. However, infliximab was observed to be more efficacious than placebo in improving PPSA and with respect to the percentage of patients reaching m‐PPPASI 50 at week 14. Larger and longer term studies are needed for severe patients to better assess the efficacy of infliximab in palmoplantar psoriasis.     

Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1)

Background Infliximab is indicated for treatment of moderate‐to‐severe plaque psoriasis in adults whose disease cannot be controlled with other systemic therapies, including methotrexate (MTX). To date, no studies have directly compared the efficacy and safety of infliximab and MTX. Objectives To compare the efficacy and safety of infliximab vs. MTX in adults with moderate‐to‐severe plaque psoriasis. Methods MTX‐naïve patients (n = 868) were randomized 3 : 1 to receive infliximab 5 mg kg^?1 at weeks 0, 2, 6, 14 and 22 or MTX 15 mg weekly with a dose increase to 20 mg weekly at week 6 if the Psoriasis Area and Severity Index (PASI) response was < 25%. At week 16, patients with < PASI 50 response could switch treatment groups. The primary efficacy endpoint was PASI 75 response at week 16. Major secondary efficacy endpoints were PASI 75 response at week 26, and the proportion of patients achieving a Physician’s Global Assessment (PGA) score of cleared (0) or minimal (1) at weeks 16 and 26. Others included Dermatology Life Quality Index, 36‐Item Short Form Health Survey, and PGA, PASI 50, PASI 75 and PASI 90 responses over time. Results The primary endpoint was achieved by a significantly greater proportion of infliximab‐treated patients (508/653, 78%) than MTX‐treated patients (90/215, 42%; P < 0·001). Key secondary endpoints also were achieved by a greater proportion of infliximab‐treated patients. Similar responses were observed at week 26 in patients who switched from MTX to infliximab at week 16. Overall adverse event (AE) incidence was comparable between groups, but incidence of serious and severe AEs was slightly higher in the infliximab group. Conclusions Infliximab was well tolerated and more efficacious than MTX in patients with moderate‐to‐severe plaque psoriasis. Infliximab also was efficacious in patients who failed MTX and switched to infliximab.     

Vitamin D production in psoriasis patients increases less with narrowband than with broadband ultraviolet B phototherapy

Background: Phototherapy of psoriasis is an effective treatment. In addition to standard broadband ultraviolet radiation B (UVB), (280–320 nm), narrowband phototherapy (NBUVB) (monochromatic UV between 311 and 312 nm) has become an important treatment for psoriasis. The same wavelength range of UVB (290–315 nm) induces synthesis of vitamin D. The aim was to compare the effect of broadband with NBUVB therapy on vitamin D synthesis in patients with psoriasis.
Methods: Sixty-eight Caucasian patients (17 women and 51 men) mean age 54.1 ± 16.0 years, with active plaque psoriasis, were treated with broadband UVB ( n =26) or NBUVB ( n =42) two to three times/week for 8–12 weeks. The serum concentrations of 25-hydroxyvitamin D (25(OH)D3), 1,25-dihydroxyvitamin D (1,25(OH)₂D3), intact parathyroid hormone (PTH), calcium and creatinine were measured before the first exposure and after the last dose of radiation.
Results: In broadband UVB treated patients, 25(OH)D3 increased from 37.9 ± 16.9 to 69.4 ± 19.7 ng/ml ( P <0.0001) and in patients treated with NBUVB from 34.8 ± 11.9 to 55.3 ± 17.6 ng/ml ( P <0.0001) and P =0.008 between the treatment groups. PTH decreased on broadband UVB ( P <0.05). The serum concentrations of 1,25(OH)₂D3, calcium or creatinine remained unaltered.
Conclusion: Serum 25(OH)D3 in psoriasis patients increased less with NBUVB than with broadband UVB phototherapy. Psoriasis improved on both regimens.     

001 UVA-1 for the treatment of chronic hand dermatitis

Endogenous levels of protoporphyrin IX (PpIX) are known to be elevated in psoriatic plaques. Activation of PpIX by visible light after topical application of aminolevulinic acid has been shown to improve psoriasis. This study was designed to determine whether multiple exposures to blue light alone could improve psoriasis in patients exhibiting elevated endogenous PpIX levels.
Patients and methods: Seventeen patients with at least two psoriatic plaques of 4 × 4 cm exhibiting elevated endogenous PpIX levels (as detected by in vivo fluorescence spectroscopy) were included in the study. Patients were required to discontinue all topical therapies for at least 2 weeks and systemic therapy for at least 8 weeks before treatment. One of the two plaques on each patient was exposed to 10 J/cm² Of blue light from a fluorescence panel three times per week for 4 consecutive weeks. The other plaque was used as a non-exposed control. Blinded clinical evaluations were performed at baseline and every week during the 4-week treatment period as well as at 1 and 3 weeks after the last exposure. Psoriasis severity was assessed by evaluating on a scale of 0–4 the presence of erythema, induration, and desquamation. PpIX levels were measured before and after light exposure by in vivo fluorescence spectroscopy at week 1 and 4.
Results: All patients completed the study without presenting treatment related side-effects. In vivo fluorescence spectroscopy demonstrated an almost complete photobleaching of PpIX in exposed plaques immediately after light exposure ( P  = 0.005). There was no significant difference between the mean psoriasis severity score of the exposed or control plaques before and after 12 exposures to blue light.
Conclusion: Under the current conditions multiple exposures to blue light did not improve psoriasis.     

Efficacy of infliximab for severe recalcitrant psoriasis after 6 weeks of treatment

Infliximab treatment has been shown to be effective for moderate-to-severe psoriasis in several large clinical trials. Nonetheless, experience with this new treatment is still needed to evaluate its efficacy and tolerance in everyday practice. In this follow-up study, we report our experience with infliximab for recalcitrant psoriasis. Nineteen patients with recalcitrant psoriasis were treated between July 2004 and December 2006 with 5 mg/kg infliximab i.v. at weeks 0, 2 and 6 followed by maintenance every 8 weeks. In three patients resistant to treatment, methotrexate was added at a 15-25 mg dose weekly after the sixth week of infliximab therapy. Pretreatment evaluations included chest X-ray, tuberculin test (5 units), full blood count, kidney and liver function tests, antinuclear antibodies and patient weight. Response to treatment, using the Psoriasis Area and Severity Index (PASI) score, and adverse effects were prospectively assessed at weeks 0, 6 and 22. At week 6, after only two infusions, 78.9% (15/19) of patients showed at least 75% improvement in baseline PASI (PASI 75). At week 22, 73.6% (14/19) patients had reached PASI 75. Three patients had a relapse. Four developed adverse effects that required suspension of infliximab therapy. No tuberculosis or lymphoproliferative disease was observed. Four patients (21%) showed apparition of positive antinuclear antibody during the course of treatment and 57.8% (11/19) of patients showed an increase in weight at week 22. Our experience shows that infliximab is a very rapidly effective treatment of severe, treatment-resistant psoriasis as soon as the sixth week of treatment.     

Infliximab treatment improves productivity among patients with moderate-to-severe psoriasis

This study examined the impact of infliximab maintenance therapy on productivity in patients with moderate-to-severe psoriasis. Patients from the multicentre, double-blind, placebo-controlled EXPRESS study (n = 378) were randomised to receive infusions of placebo or infliximab 5 mg/kg at weeks 0, 2, and 6 and every 8 weeks through week 46, with placebo crossover to infliximab at week 24. Main outcome measures were a 10-cm productivity visual analog scale (VAS), role-physical and role-emotional domain scores of the Short Form 36-Item questionnaire (SF-36), and Dermatology Life Quality Index (DLQI) scores. The productivity VAS score was 5.9 cm at baseline. Mean change through week 10 with infliximab was significantly greater than that with placebo (2.7 cm vs. - 0.1 cm) and was sustained through week 24. Similar trends were observed for SF-36 scores. The proportion of patients whose skin condition prevented them from working and/or studying per DLQI scores decreased through week 10 with infliximab (12.1% and 1.4%, respectively), but increased slightly with placebo (9.1% and 11.6%, respectively). At week 50, improvements in productivity and SF-36 scores were sustained with infliximab. In placebo patients who crossed over to infliximab, these scores improved and approached those seen with infliximab at week 50. Infliximab significantly improved productivity and ability to work in psoriasis patients.     

Long-term efficacy of a single course of infliximab in hidradenitis suppurativa

BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory skin disease characterized by abscess formation, predominantly in the axillae and groins. The disease is difficult to treat and has a severe impact on quality of life. Recently, several case reports have been published describing successful treatment of hidradenitis suppurativa with infliximab and other tumour necrosis factor alpha inhibitors. OBJECTIVES: To evaluate the long-term efficacy of a single course of infliximab. METHODS: Ten patients with severe, recalcitrant hidradenitis were treated with infliximab (three infusions of 5 mg kg(-1) at weeks 0, 2 and 6) and followed up for at least 1 year. The disease activity was measured using laboratory parameters and a recently developed acne score. The patients rated the efficacy of infliximab on a 10-point scale at regular intervals. Quality of life was measured before and after treatment using the Dermatology Quality of Life Index (DQLI). RESULTS: All patients improved within 2-6 weeks. The average acne score diminished from 164+/-50 (mean+/-SD) before treatment to 89+/-49 after 1 year (P=0.002). The mean CRP (C-reactive protein) was reduced from 31.7 mg mL(-1) to 5.5 mg mL(-1) after 1 month (P=0.015). Patients judged the efficacy with a score of 7.9. The mean DQLI was reduced from 18.4+/-7.9 before treatment to 9.3+/-9.1 after 1 year (P=0.007). In three patients long-lasting improvement was observed, with no recurrence of lesions in a 2-year follow-up period. The other patients showed recurrence of lesions after 8.5 months (range 4.3-13.4 months). CONCLUSIONS: Infliximab is an effective treatment in severe hidradenitis suppurativa, leading to reduction of symptoms for a prolonged period.     

Effect of dosing frequency on the safety and efficacy of imiquimod 5% cream for treatment of actinic keratosis on the forearms and hands: a phase II, randomized placebo-controlled trial

Background  Clinical studies in cutaneous conditions other than actinic keratosis (AK) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency.
Objectives  To evaluate dosing frequency response of imiquimod 5% for treatment of AK.
Methods  This was a phase II, multicentre, randomized, double-blind, placebo-controlled study. Adults with ≥ 10 but ≤ 50 clinical AKs, one of which was histologically confirmed, were randomized (4 : 1) to 2–6 packets of imiquimod or placebo cream applied to the dorsum of the forearms and hands once daily 2, 3, 5 or 7 times per week for 8 weeks. The primary endpoint was complete clearance of AKs in the treatment area at 8 weeks post-treatment.
Results  One hundred and forty-nine (94 men and 54 women) white subjects, with a mean ± SD age of 71 ± 10·2 years, were enrolled. Twenty-eight subjects (18·8%) discontinued from study: 0%, 3·1%, 6·9%, 30·0% and 33·3% withdrew for local skin reactions or adverse events in the combined placebo, and in the imiquimod 2, 3, 5 or 7 times per week groups, respectively. Seven serious adverse events occurred; none was related to the study drug. Median baseline lesions ranged from 38 to 40 for the treatment groups. Complete clearance was achieved in 0%, 3·2%, 6·9%, 3·3% and 6·7% of subjects, and partial clearance (≥ 75% lesion reduction) in 0%, 22·6%, 24·1%, 20·0% and 36·7% of subjects for the placebo and imiquimod 2, 3, 5 or 7 times per week regimens, respectively.
Conclusions  Imiquimod 5% applied more frequently than 3 times per week to AKs was not well tolerated. Complete clearance rates were low; however, partial clearance rates increased with increased dosing frequency ( P  =   0·002).     

Serum levels of the pro-inflammatory cytokine interleukin-12 and the anti-inflammatory cytokine interleukin-10 in patients with psoriasis treated by the Goeckerman regimen

Background  The Goeckerman regimen (GR) involves the dermal application of a crude coal tar (polycyclic aromatic hydrocarbon, PAH) and exposure to ultraviolet (UV) radiation. Both PAH and UV radiation exhibit immunosuppressive activity. This study describes the changes in the serum levels of the pro-inflammatory cytokine interleukin-12 (IL-12) and the anti-inflammatory cytokine IL-10 in patients with psoriasis ( n  = 55) treated with GR.
Methods  The serum levels of IL-12 and IL-10 were compared before and after GR. In addition, the IL-12 and IL-10 levels in psoriatic patients were compared with those in a control group of healthy blood donors ( n  = 47). The Psoriasis Area and Severity Index (PASI) was used to evaluate the efficacy of GR.
Results  When compared with the control group, both IL-12 and IL-10 were significantly higher in psoriatic patients in all cases ( P  < 0.001). When compared before and after GR, the IL-12 and IL-10 levels ( P  < 0.01) and PASI value ( P  < 0.001) were significantly lower after GR. The decrease in the serum level of IL-12 and IL-10 after GR was related to the entry value before GR (IL-12, r  = 0.60, P  < 0.001; IL-10, r  = 0.36, P  < 0.01). There was a significant correlation between the IL-10 level before GR and the PASI value after GR ( r  = –0.39; P  < 0.01).
Conclusions  The results indicate a strong pro-inflammatory effect of IL-12 in the immunopathogenesis of psoriasis, and confirm the immunosuppressive and anti-inflammatory effect of GR. IL-10 seems to be a promising individual marker for a positive effect of GR therapy.     

Effects of oral administration of ciclosporin A on skin carcinogenesis: a study using the two-stage carcinogenesis protocol in mice

Background.  Development of malignant skin neoplasms in patients receiving ciclosporin A (CsA) has been reported. The relationship between the pathogenesis of skin carcinogenesis and the dose of CsA is still unclear.
Aim.  To clarify the effect of oral administration of CsA, especially its dose, on skin carcinogenesis.
Methods.  Hr-1 hairless mice were assigned to the following four groups: (i) control group ( n  = 8), given vehicle intragastrically six times/week and acetone applied to the skin of the back; (ii) chemical-alone ( n  = 11), given vehicle intragastrically + application of 7,12-dimethylbenz[a]anthracene (DMBA) once week and 12- O -tetradecanoyl-phorbol-13-acetate (TPA) twice week to the back; (iii) CsA-alone group ( n  = 8), given CsA intragastrically (10 mg/kg) six times/week and vehicle applied to the back twice week; and (iv) CsA + chemical group ( n  = 8), given 10 mg/kg CsA intragastrically + topical DMBA and TPA. The number of papules > 3 mm in diameter that had developed on the back after 15 weeks was counted. The mean epidermal thickness and number of dermal infiltrates were determined. The same experiments were performed using CsA at doses of 5 and 20 mg/kg.
Results.  Oral administration of either 10 or 20 mg/kg CsA significantly enhanced the formation of papillomas by DMBA and TPA, but no enhancement was observed when 5 mg/kg CsA was administered. The mean epidermal thickness and number of dermal infiltrates were significantly greater in the CsA + chemical group than in the chemical-alone group.
Conclusion.  These data suggest that oral administration of CsA in excess of a certain dose can accelerate tumour development in mice.     

Loss-of-function polymorphisms in the filaggrin gene are associated with an increased susceptibility to chronic irritant contact dermatitis: a case-control study

Background  Polymorphisms in the filaggrin (FLG) gene, which result in loss of filaggrin production, may alter the skin barrier and are a well-known predisposing factor for atopic dermatitis.
Objectives  As a compromised skin barrier and atopic dermatitis are risk factors for chronic irritant contact dermatitis (CICD), our objective was to determine whether polymorphisms in the FLG gene contribute towards susceptibility to occupational CICD.
Methods  In a case–control study, the FLG polymorphisms R501X and 2282del4 were determined in 296 patients with CICD. Two hundred and seventeen apprentices in vocational training for high-risk occupations for CICD were chosen as controls. Data on skin diseases and conditions were collected by dermatologists from patients and by means of questionnaires from controls.
Results  Heterozygotes for R501X and 2282del4, FLG null alleles, were more frequent among patients with CICD (12·5%) compared with controls (6·9%), resulting in an odds ratio of 1·91 (95% confidence interval 1·02–3·59). Among patients who were carriers of a FLG null allele, we found a higher lifetime prevalence of flexural eczema (62% vs. 46%; P  = 0·04) and a higher atopy score (13 vs. 10 points; P  = 0·05) compared with noncarriers. In the apprentice group, signs of dermatitis before the start of the vocational training were four times more prevalent in carriers (43%) than in noncarriers (10%; P  < 0·001).
Conclusions  Our study shows that FLG null alleles are associated with increased susceptibility to CICD; whether or not the FLG null allele is an independent risk factor needs further study.