Reduction of relapses of atopic dermatitis with methylprednisolone aceponate cream twice weekly in addition to maintenance treatment with emollient: a multicentre, randomized, double-blind, controlled study

Background The relapsing nature of atopic dermatitis (AD) presents a challenge for its long‐term treatment. Efficacy and safety of corticosteroids have been proven in the acute treatment of active AD, but their long‐term efficacy and potential to reduce or prevent relapses have only partially been addressed. Objectives To investigate long‐term management (16 weeks) of AD with methylprednisolone aceponate (MPA) 0·1% cream twice weekly in addition to an emollient (Advabase^®) after stabilization of an acute severe or very severe flare of AD with MPA cream. Methods Patients ≥ 12 years of age with a ≥ 2‐year history of moderate to severe AD were eligible for this multicentre, randomized, double‐blind, controlled study if they presented with an acute flare of severe or very severe AD [Investigator’s Global Assessment (IGA) score ≥ 4]. After successful treatment of the flare in an acute phase (AP), patients received either MPA twice weekly plus emollient or emollient alone over a 16‐week maintenance phase (MP). The primary study endpoint was time to relapse of AD. Secondary endpoints included relapse rate and disease status, the patient’s assessment of intensity of itch, the Eczema Area and Severity Index, the IGA score, affected body surface area, Dermatology Life Quality Index (DLQI) and children’s DLQI (CDLQI), patient’s and investigator’s global assessment of response and patient’s assessment of quality of sleep. Results Two hundred and forty‐nine patients entered the AP and 221 continued into the MP. Time to relapse was longer in the MPA group than in the emollient group. The probability of remaining free from relapse after 16 weeks was 87·1% in the MPA group compared with 65·8% for the emollient. Patients treated with MPA twice weekly had a 3·5‐fold lower risk of experiencing a relapse than patients treated with emollient alone (hazard ratio 3·5, 95% confidence interval 1·9–6·4; P < 0·0001). MPA was also superior to emollient for all other efficacy endpoints. Therapy with both treatments was well tolerated. Conclusions MPA twice weekly plus an emollient provides an effective maintenance treatment regimen to control AD. Once stabilized, treatment with MPA significantly reduces the risk of relapse and the intensity of itching, and improves the overall patient status.     

Thalidomide in the treatment of refractory cutaneous lupus erythematosus: prognostic factors of clinical outcome

Background Although thalidomide has been shown to be effective in patients with refractory cutaneous lupus erythematosus (CLE), its use is still hampered by its potential severe side‐effects and the current restricted availability. Objectives To evaluate prospectively the clinical efficacy and safety of low‐dose thalidomide in an observational study and to establish prognostic factors of clinical outcome. Methods Sixty consecutive patients with refractory CLE were treated with thalidomide (100 mg daily). Clinical response was assessed by the CLE Disease Area and Severity Index (CLASI). Clinical and immunological parameters were evaluated during treatment. Results Patients were followed for up to 8 years (range 2–18). One patient discontinued treatment because of side‐effects. Of the 59 remaining patients, 58 (98%) achieved clinical response, already noticeable at 2 weeks following treatment. Complete response occurred in 50 patients (85%). Clinical relapse was frequent (70%) and usually occurred 5 months after withdrawal or reduction of thalidomide. Subacute CLE (SCLE) was the predicting factor of long‐term remission after therapy discontinuation [odds ratio (OR) 30, 95% confidence interval (CI) 5·82–154·63], whereas discoid lupus erythematosus (DLE) was predictive of relapse (OR 5·71, 95% CI 1·36–24·06). Eleven patients (18%) reported paraesthesia; in five of the 11, nerve conduction studies confirmed a sensory polyneuropathy. Neurological symptoms resolved in 12 months (range 6–18) after thalidomide withdrawal. Two patients, heavy smokers and without antiphospholipid antibodies, had a cerebral ischaemic event. Conclusions Low‐dose thalidomide is an effective treatment for refractory CLE, but its benefits need to be balanced against the potential adverse effects. Whereas DLE forms tended to relapse and required a long‐term maintenance dose of thalidomide, SCLE forms showed a sustained remission after withdrawal.     

5‐Methoxypsoralen plus ultraviolet (UV) A is superior to medium‐dose UVA1 in the treatment of severe atopic dermatitis: a randomized crossover trial

Background Ultraviolet (UV) A1 and psoralen plus UVA (PUVA) are effective treatment options for severe atopic dermatitis (AD); however, their relative efficacy has not yet been determined in a head‐to‐head study. Objectives To compare UVA1 and oral 5‐methoxypsoralen (5‐MOP) plus UVA with respect to efficacy, tolerability and duration of response in patients with severe generalized AD. Methods Forty patients were included in this randomized observer‐blinded crossover trial. The patients received either 15 exposures to medium‐dose UVA1 as the first treatment and, in cases of relapse, another 15 exposures to 5‐MOP plus UVA as the second treatment, or vice versa. All patients were followed until 12 months after discontinuation of the last treatment. The SCORAD score was determined by a blinded investigator at baseline, after 10 and 15 treatments each and during the follow‐up period. In addition, all adverse events were recorded during the whole study period. Results Twenty‐three patients completed the crossover treatment. Both phototherapies resulted in clinical improvement; however, PUVA reduced the baseline SCORAD score to a significantly greater extent than UVA1 (mean ± SD 54·3 ± 25·7% vs. 37·7 ± 22·8%; P = 0·041). The median length of remission was 4 weeks (interquartile range 4–12) after UVA1 and 12 weeks (interquartile range 4–26) after PUVA therapy (P = 0·012). Conclusions PUVA provides a better short‐ and long‐term response than medium‐dose UVA1 in patients with severe AD.     

Practical experience of ustekinumab in the treatment of psoriasis: experience from a multicentre, retrospective case cohort study across the U.K. and Ireland

Background There are limited data on the use of ustekinumab outside of clinical trials. Objectives To assess the efficacy and safety of ustekinumab in patients with severe psoriasis attending 10 dermatology centres in the U.K. and Ireland. Methods A retrospective case‐note review of 129 patients with psoriasis treated with ustekinumab. Results Baseline Psoriasis Area and Severity Index (PASI) was 22·9 ± 10·1 (mean ± SD). After 16 weeks of treatment with ustekinumab PASI 75 (75% reduction in PASI) was observed in 63·0% (n = 80/127) of patients, although four patients required concomitant therapy at the 16‐week time point. Previous biologic use did show a small, non‐significant trend towards treatment failure. A PASI 75 response was seen in 29·4% (n = 5/17) of individuals weighing 90–100 kg and treated with the standard 45 mg ustekinumab dose compared with PASI 75 of 70·3%, 71·4%, 75·0% and 55·6% for weight groups < 80, 80–90, 100–110 and > 110 kg, respectively (P = 0·024). Ustekinumab therapy was well tolerated; serious adverse events were observed in 2·3% (n = 3/129) of patients. Conclusions Ustekinumab is a novel biologic agent for psoriasis. When used in everyday clinical practice it demonstrates high levels of short‐term therapeutic efficacy with an acceptable short‐term safety profile.     

Treatment of severe pemphigus with a combination of immunoadsorption, rituximab, pulsed dexamethasone and azathioprine/mycophenolate mofetil: a pilot study of 23 patients

Background It has been previously shown in a relatively small group of patients that a combination of immunoadsorption (IA) and rituximab with daily use of high‐dose oral corticosteroids and azathioprine/mycophenolate mofetil may induce a rapid and durable remission in severe, treatment‐resistant pemphigus. Objectives To achieve a more rapid reduction of serum autoantibody levels by a more frequent use of IA in the initial phase of treatment and to reduce the number of severe adverse events of continuous oral corticosteroid therapy by switching to pulsed intravenous applications. Methods Twenty‐three consecutive patients with severe pemphigus were included. IA was performed at initially 3‐ and later 4‐week intervals until lesions healed by 90%; 1000 mg rituximab was given at weeks 1 and 3, and intravenous dexamethasone pulses were administered at first every 3 weeks and then at increasing intervals in addition to daily azathioprine/mycophenolate mofetil. Results Along with a fast and durable decline of circulating autoantibody levels, all patients showed improvement of pemphigus lesions within the first weeks of therapy and long‐term complete remission was induced in 19 (83%) patients. In the remaining four patients, one (4%) minimal disease and three (13%) partial remissions were observed. Over the long‐term follow‐up of 11–43 (mean 29) months, six (26%) patients had a recurrence and in two (9%) patients, severe adverse events occurred. Conclusions This novel protocol treatment induces a fast and long‐term remission in severe pemphigus and seems to offer an improved side‐effect profile compared with daily use of corticosteroids.     

Patients with delusional infestation (delusional parasitosis) often require prolonged treatment as recurrence of symptoms after cessation of treatment is common: an observational study

Background Delusional infestation (DI) is an uncommon psychiatric disorder in which patients present with the false and fixed belief of infestation. Numerous studies have demonstrated improvement with pharmacological treatment; however, recurrence rates on cessation of treatment remain unknown. Objectives To assess the clinical response and recurrence rates following treatment for DI. Methods All patients with DI seen in our combined dermatology/psychiatry clinic to date (n = 73) were offered pharmacological therapy. Patients were contacted to complete a telephone questionnaire to assess clinical outcomes, including remission and recurrence rates following treatment. Results Fifty‐nine of 73 (81%) patients with DI received treatment, of whom 40/59 (68%) reported improvement or resolution of symptoms, and the remaining 19/59 (32%) failed to respond. Fifteen of 40 patients with DI completed a course of treatment, 12/40 patients are still undergoing treatment, and outcomes are unknown for 13/40. Of those who completed treatment, 11/15 (73%) reported total remission for at least 9 months after discontinuing treatment (range 9 months–2·5 years). Recurrence of symptoms occurred in 4/15 (27%) within 4 months of stopping treatment. Conclusions Pharmacological treatment of DI can be effective, particularly in a combined dermatology/psychiatry clinic. Most treated patients have a good prognosis, and a remission period can be expected. However, more than 25% of patients may relapse on stopping treatment, with the greatest risk being within the first few months of discontinuation. These patients may require longer treatment courses, or long‐term maintenance therapy for symptom control, although further studies are needed to provide recommended guidelines on drug and dosing regimen.     

A 4-year follow-up study of atopic dermatitis therapy with 0.1% tacrolimus ointment in children and adult patients

Background For the treatment of a chronic disease like atopic dermatitis, sustained tolerability and efficacy of the applied medication are essential. Objectives The present open‐label, noncomparative study was conducted to obtain information on the long‐term safety and efficacy of 0·1% tacrolimus ointment. Methods Patients aged 2 years or older with an affected body surface area of more than 5%, who previously participated in a clinical trial on tacrolimus ointment, were eligible for this study. The treatment area was defined by the investigator at study entry. Both children and adults applied continuously or intermittently 0·1% tacrolimus ointment twice daily during episodes of active disease plus an additional week after remission over a follow‐up period of up to 4 years. Results The intent‐to‐treat population comprised 782 patients, with a median age of 22 years (range 2–72). Patients remained in the study for up to 4 years. Approximately half of the patients discontinued the study prematurely; the median follow‐up was 1422 days. Median tacrolimus ointment use was 31·2 g during the first week; ointment use decreased during the first year and then remained stable for the remainder of the study. The median cumulative tacrolimus use was 271·5 g at month 6, 462·5 g at month 12, 739·9 g at month 24, 1029·3 g at month 36 and 1320·8 g at month 48. Altogether 51·8% of patients discontinued the study prematurely; the main reasons were withdrawal of consent (13·3%), loss to follow‐up (11·3%) and lack of efficacy (9·4%). Adverse events led to study discontinuation in 3·7% of the patients. The most frequent application site events were skin burning and pruritus. These events were most often reported in adult patients during the initial treatment period; prevalence decreased after the first week and remained at a low level throughout the study. Nonapplication site events occurred with stable incidences throughout the study period. In general, calculated daily hazard rates did not indicate an increased risk of adverse events with prolonged treatment. The total affected body surface area decreased substantially upon onset of treatment and efficacy of treatment was maintained until the end of the study with smaller but continuous improvements throughout the follow‐up period. Overall, 75% of the patients and 76% of the investigators rated their satisfaction with the treatment as excellent, very good or good at the end of the study or at the time of premature discontinuation. Conclusions The safety profile of intermittent or continuous long‐term application of 0·1% tacrolimus ointment for up to 4 years was consistent with that which has been established from shorter studies and gave no reason for concern. In addition, 0·1% tacrolimus ointment demonstrated sustained efficacy as reflected by the expression of high satisfaction with treatment by both patients and investigators.     

Treatment of refractory adult‐onset pityriasis rubra pilaris with TNF‐alpha antagonists: a case series

Background Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long‐term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long‐term follow‐up or comparison between different biological agents. Objectives To assess the long‐term efficacy and safety of TNF‐alpha antagonist, infliximab and etanercept, either in monotherapy or in combination therapy of severe, refractory adult‐onset PRP. Methods Seven patients of adult‐onset PRP, six newly diagnosed type‐I and 1 type‐II, which were resistant or ineligible to conventional systemic treatment, received a single course of infliximab or etanercept therapy, alone or in combination with low‐dose acitretin (>0.25 mg/kg/daily). After complete remission and treatment discontinuation, a follow‐up period of 12 months was evaluated for relapses. Results Six patients obtained complete remission after a single course of anti‐TNF‐alpha therapy: mean therapy duration was 19.3 weeks (range 6–48 weeks). All patients obtained significant clearing (>75% of body surface area) of skin lesions at week 12. Two patients with marked keratoderma developed localized disease recurrence during treatment. During follow‐up, only a single patient, affected by type II PRP, had disease relapse. Conclusions Both TNF‐alpha antagonists proved successful for the treatment of refractory, adult‐onset PRP, yielding complete and persistent clinical responses in type‐I PRP. Infliximab was associated with a more rapid onset of action, while treatment duration was comparable with etanercept. PRP type II warranted long‐term therapy and showed relapse after drug discontinuation.     

Etanercept plus narrowband ultraviolet B phototherapy of psoriasis is more effective than etanercept monotherapy at 6 weeks

Background A substantial portion of patients with psoriasis does not achieve a satisfactory response under antitumour necrosis factor (TNF)‐α biological therapies. Objectives We aimed to evaluate whether etanercept plus narrowband ultraviolet B (NB‐UVB) phototherapy is superior to etanercept monotherapy in the management of psoriasis. Methods In this prospective study, patients with psoriasis were treated with etanercept 25 mg twice weekly. Two marker lesions were selected for determination of the modified Psoriasis Area and Severity Index (M‐PASI). NB‐UVB was administered thrice weekly whereby one marker lesion was covered as nonirradiated control. Skin biopsies for histology and immunohistochemistry were performed in both marker lesions after a 6‐week treatment course. Results After 6 weeks of therapy, the relative M‐PASI reduction (mean ± SD) in etanercept‐treated sites (53·7 ± 36·9%) was significantly lower than the reduction in etanercept plus NB‐UVB‐treated lesions (64 ± 27·8%; P = 0·011). At the end of treatment, histology scores of etanercept‐treated psoriatic plaques were significantly higher than scores of etanercept plus NB‐UVB‐treated sites (4·6 ± 2·7 vs. 3·7 ± 2·4; P = 0·045). Epidermal immunoreactivity for CD1a, CD4 and CD8 was significantly lower in etanercept plus NB‐UVB‐treated lesions when compared with etanercept monotherapy. Conclusions Etanercept combined with NB‐UVB is more effective than etanercept monotherapy at 6 weeks as demonstrated at a clinical, histological and immunohistological level. However, as there is an increased risk for malignancy by treatment with TNF‐α blockers alone or in combination with phototherapy, we recommend to restrict this highly effective combination to short periods of time, for instance to obtain a quicker response, and to avoid long‐term treatment.     

Short‐term efficacy and safety of new biological agents targeting the interleukin‐23–T helper 17 pathway for moderate‐to‐severe plaque psoriasis: a systematic review and network meta‐analysis

A new generation of biologics targeting the interleukin‐23–T helper 17 pathway has been developed. This study aimed to assess the short‐term effectiveness and safety of these new agents using a network meta‐analysis. Twenty‐seven randomized clinical trials (10 629 patients) were identified by a comprehensive systematic literature review (PROSPERO 2015: CRD42015025472). Quality of evidence was assessed following Cochrane‐compliant rules and the Grading of Recommendations, Assessment, Development and Evaluations approach. Efficacy and safety outcomes at weeks 10–16 were compared using a random‐effects network meta‐analysis within a frequentist framework to estimate pooled odds ratios (ORs) of direct and indirect comparisons among the therapeutic options. There were six direct drug‐to‐drug comparisons in the network, with a high degree of consistency between the direct and indirect evidence. From the available evidence, infliximab 5 mg kg⁻¹ every 8 weeks [OR 118·89, 95% confidence interval (CI) 60·91–232·04] and secukinumab 300 mg every 4 weeks (OR 87·07, 95% CI 55·01–137·82) are shown to be among the most effective short‐term treatments, but are ranked as the biologics most likely to produce any adverse event or an infectious adverse event, respectively. Ustekinumab 90 mg every 12 weeks, the third most efficacious treatment (OR 73·67, 95% CI 46·97–115·56), was the only agent that did not show increased risk of adverse events compared with placebo. Treatment recommendations should also consider long‐term outcomes and costs.     

Successful ultraviolet A1 phototherapy in the treatment of localized scleroderma: a retrospective and prospective study

Background Ultraviolet (UV) A1 phototherapy is an effective anti‐inflammatory treatment modality that influences fibroblast functions. Objectives To document the effects of UVA1 treatment in patients with localized scleroderma (LS) in a retrospective study (at least 6 months after UVA1 treatment) and in a prospective study before and immediately after medium‐dose UVA1 irradiation. Methods In total, 30 patients (retrospective study n = 17, prospective study n = 13) with LS receiving UVA1 phototherapy five times weekly (for 3–6 weeks) were investigated. Improvement was documented using standardized questionnaires and clinical evaluation (using modified Rodnan skin score, Cutometer and 7·5‐MHz ultrasound measurements). Levels of collagen I and collagen III metabolites were measured in serum and urine. Results In the retrospective study, medium‐dose UVA1 phototherapy had been performed 6 months–3 years earlier (cumulative dose 750–1400 J cm^?2; mean ± SD number of irradiations 19·3 ± 3·8). Fourteen of 17 patients (82%) reported an improvement in symptoms following UVA1 therapy. In the prospective study, skin elasticity increased in 77% of the patients following medium‐dose UVA1 phototherapy (cumulative dose 750–1250 J cm^?2; mean ± SD number of irradiations 20·8 ± 4·0). 7·5‐MHz ultrasound measurements showed a mean reduction of lesional skin thickness of 13% compared with skin thickness before UVA1 phototherapy. The ratio of deoxypyridinoline to creatinine was significantly elevated in about two‐thirds of the patients. Conclusions This open study showed a positive short‐ and long‐term efficacy of UVA1 phototherapy in patients with LS, with a reduction in sclerotic plaques, an increase in skin elasticity and a reduction of lesional skin thickness. UVA1 phototherapy had a significant effect on collagen metabolism. UVA1 phototherapy can be regarded as a safe treatment modality for patients with LS.     

Short- and medium-term efficacy of specific hydrotherapy in inherited ichthyosis

Background Management of inherited ichthyoses is symptomatic. Despite treatment, skin symptoms have a major impact on patients’ quality of life (QoL). Objectives To assess the short‐ and medium‐term efficacy of hydrotherapy on QoL and clinical symptoms of patients with inherited ichthyosis. Methods In this 9‐month prospective, open‐label, multicentre study, 20 children and 24 adults with ichthyosis were enrolled in several French reference and competence centres, 2 months before undergoing a 3‐week treatment with specific hydrotherapeutic management at Avène Hydrotherapy Centre. At baseline (2 months before hydrotherapy), beginning (D0) and end of hydrotherapy (D18), and 3 and 6 months later at the reference and competence centres, patients self‐assessed QoL using the Dermatology Life Quality Index (DLQI) or its paediatric version (Children’s DLQI), and investigators evaluated ichthyosis severity using a specific clinical ichthyosis score. Results The DLQI scores were significantly improved not only at the end of the hydrotherapy treatment (?56% vs. baseline; mean ± SD 3·59 ± 4·30 at D18 vs. 8·35 ± 5·71 at D0; P < 0·0001), but also at 3 months (?28% vs. baseline; P = 0·01) and 6 months after hydrotherapy (?26% vs. baseline; mean ± SD 5·21 ± 5·11 vs. 6·89 ± 5·38; P = 0·03) (primary criterion). Clinical symptoms were also significantly improved at all post‐treatment visits, with a decrease of the mean clinical ichthyosis score by ?38% between D0 and D18, by ?30% at 3 months and by ?31% at 6 months vs. baseline. Conclusions A 3‐week treatment at Avène Hydrotherapy Centre provided significant and persisting improvement of QoL and clinical symptoms in patients with inherited ichthyoses.     

Long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo: effect of disease activity

Background Punch grafting is a simple and frequently used technique for the treatment of stable vitiligo, resistant to medical therapy. However, studies reporting long‐term results are exceptional. Objectives To evaluate the long‐term results of 2‐mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo. Methods We studied a prospective cohort study involving 61 patients (25 male, 36 female) with vitiligo vulgaris and nine patients (all male) with segmental vitiligo who underwent 2‐mm punch grafting more than 3 years ago. The main outcome measure was the degree of repigmentation of a single transplanted lesion as measured with a digital image analysis system with a mean follow‐up of 5·2 years. Results In patients with vitiligo vulgaris, 17 lesions (28%) showed excellent, 14 lesions (23%) showed good, 14 lesions (23%) showed fair and 16 lesions (26%) showed poor repigmentation. In patients with segmental vitiligo, seven of nine lesions (78%) showed excellent repigmentation. A cobblestone‐like effect was observed in 19 of 70 patients (27%). Disease activity after punch grafting was reported in 94% of patients with poor repigmentation but in only 18% of patients with excellent repigmentation (χ² test, P < 0·0005). Patients who reported disease activity after transplantation had a lower mean repigmentation than those who did not report disease activity (77% vs. 39%, P < 0·05). Conclusions Two‐millimetre punch grafting in vitiligo is an effective surgical procedure with long‐lasting effect. To prevent a cobblestone‐like effect, we advise the use of smaller grafts (1–1·2 mm). Disease activity after grafting, localization and type of vitiligo, prior ultraviolet B treatment and a Koebnerized donor site influence the long‐term outcome of punch grafting and should be taken into account in the selection of patients eligible for this treatment.     

Tumescent liposuction in lipoedema yields good long-term results

Background Lipoedema is a painful disease in women with circumscribed increased subcutaneous fatty tissue, oedema, pain and bruising. Whereas conservative methods with combined decongestive therapy (manual lymphatic drainage, compression garments) have been well established over the past 50 years, surgical therapy with tumescent liposuction has only been used for about 10 years and long‐term results are unknown. Objectives To determine the efficacy of liposuction concerning appearance (body shape) and associated complaints after a long‐term period. Methods A total of 164 patients who had undergone conservative therapy over a period of years, were treated by liposuction under tumescent local anaesthesia with vibrating microcannulas. In a monocentric study, 112 could be re‐evaluated with a standardized questionnaire after a mean of 3 years and 8 months (range 1 year and 1 month to 7 years and 4 months) following the initial surgery and a mean of 2 years and 11 months (8 months to 6 years and 10 months) following the last surgery. Results All patients showed a distinct reduction of subcutaneous fatty tissue (average 9846 mL per person) with improvement of shape and normalization of body proportions. Additionally, they reported either a marked improvement or a complete disappearance of spontaneous pain, sensitivity to pressure, oedema, bruising, restriction of movement and cosmetic impairment, resulting in a tremendous increase in quality of life; all these complaints were reduced significantly (P < 0·001). Patients with lipoedema stage II and III showed better improvement compared with patients with stage I. Physical decongestive therapy could be either omitted (22·4% of cases) or continued to a much lower degree. No serious complications (wound infection rate 1·4%, bleeding rate 0·3%) were observed following surgery. Conclusions Tumescent liposuction is a highly effective treatment for lipoedema with good morphological and functional long‐term results.     

Topical preparations for the treatment of psoriasis: a systematic review

Summary Background There is clinical uncertainty about the appropriate use of first‐line topical treatments for psoriasis. Objectives To assess the relative effectiveness and tolerability of topical treatments for psoriasis suitable for use both in primary and secondary care. Methods All major medical databases of published literature were searched electronically; references of trial reports and recent reviews were searched; authors and companies were contacted for missing data from published reports. The study selection comprised: (1) randomized placebo‐controlled trials of topical treatments for psoriasis; and (2) randomized head‐to‐head studies of the new vitamin D3 derivative treatments for psoriasis that reported clinical outcome using a Total Severity Score (TSS), Psoriasis Area Severity Index or Investigator Assessment of Global Improvement. Eligibility and validity were assessed and data extracted independently by two authors. Clinical outcomes were pooled using a random effect standardized weighted mean difference (SWMD) metric, including 3380 patients randomized in 41 placebo (vehicle)‐controlled trials and 4898 patients randomized in 28 head‐to‐head studies. Results There was a significant benefit in favour of active treatments against vehicle, SWMD: ?1·06 (95% confidence interval [CI]: ?1·26 to ?0·86), approximately a 2‐point improvement on a 12‐point TSS after 6–8 weeks of treatment. The only significantly different benefit was for very potent corticosteroids: SWMD: ?1·51 (95% CI: ?1·76 to ?1·25), approximately a 3‐point improvement on a 12‐point TSS. Head‐to‐head studies support these findings, except that calcipotriol was estimated to be more effective than dithranol, coal tar and other vitamin D₃ derivatives. Polytherapy, using a potent steroid and calcipotriol, was more effective than calcipotriol alone: SWMD 0·42 (95% CI: 0·12–0·72) approximately a 0·8‐point improvement on a 12‐point TSS. No important differences in withdrawal or reporting of adverse events were identified. Conclusions Trials of short duration neither adequately inform the management of chronic disease nor describe the sequelae of treatment. The evidence base for long‐term care, reflecting the disease pathway, should be improved. Combination therapy with topical vitamin D analogues and steroids, and maintenance therapy following treatment response merit further investigation.     

Conradi–Hünermann–Happle syndrome with abnormal lamellar granule contents

Background Long‐term maintenance treatment with 0·1% tacrolimus ointment for the prevention of flares has been demonstrated to be well tolerated and effective in adults for the treatment of atopic dermatitis (AD) but its impact on health‐related utility has not been reported. Objectives The purpose of this study was to estimate utility changes associated with the use of tacrolimus ointment in the maintenance treatment of adults with AD. Methods Data were collected from a clinical trial investigating long‐term maintenance treatment with 0·1% tacrolimus ointment in adults with AD. All patients were treated with twice‐daily tacrolimus ointment during an open‐label period (OLP) of up to 6 weeks, with subsequent randomization to a double‐blind disease‐control period (DCP) of 12 months comparing tacrolimus ointment, used twice weekly as maintenance treatment, vs. the emollient vehicle as standard treatment. Health‐related utility (EQ‐5D_index) was estimated by Monte Carlo simulation from SF‐12 responses by application of a published response mapping algorithm and the U.K. tariff for EQ‐5D responses and SF‐6D responses, respectively. Results Evaluable data were available for 257 patients stratified into mild, moderate or severe AD with a median age at screening of 28 years [interquartile range (IQR) 22–38] and 40% male. At screening the median EQ‐5D_index across the strata was 0·848 units (IQR 0·704–0·882) for mild cases, 0·796 (0·737–0·876) for moderate cases, and 0·760 (0·661–0·823, P < 0·001) for those with severe disease. At the end of the OLP, mean utility improvement across all strata was 0·027 [95% confidence interval (CI) −0·011 to 0·065, P = 0·165] for mild cases, 0·046 (95% CI 0·015–0·064, P = 0·002) for moderate cases and 0·076 (95% CI 0·035–0·118, P < 0·001) for those with severe disease. At the end of the blinded DCP, repeated measures analysis showed an age‐ and sex‐adjusted mean change of 0·045 units (P < 0·001) for subjects treated with tacrolimus ointment over those treated with emollient vehicle. Conclusions Patients with AD of all severities showed considerable decrements in health‐related utility. However, treatment with 0·1% tacrolimus ointment was associated with clinically significant improvement in health‐related utility for patients with moderate and severe AD, which was sustained over a 12‐month maintenance period compared with those using standard treatment with an emollient vehicle.     

Effectiveness, side-effects and period of remission after treatment with methotrexate in localized scleroderma and related sclerotic skin diseases: an inception cohort study

Background  Detailed information is lacking on effectiveness of methotrexate (MTX) in sclerotic skin diseases, side-effects, and duration of remission after discontinuation.
Objectives  To determine effectiveness, side-effects and period of remission gained by use of MTX in sclerotic skin diseases.
Methods  All patients with a sclerotic skin disease who were treated with MTX (group A) or MTX with corticosteroids (CS) (group B) between 1995 and 2007 were evaluated. Detailed information was collected on dosage and duration of MTX treatment, concomitant immunosuppressive medication and CS treatment, effectiveness, side-effects, duration of the remission period, and time until restart.
Results  Fifty-eight patients (A, n  =   47; B, n  =   11) were evaluated. Clinical assessment revealed that 38 patients (81%) treated with MTX and 11 patients (100%) treated with MTX + CS showed improvement of sclerotic skin. After one treatment course 51% of the patients treated with MTX and 73% treated with MTX + CS reached remission status with a median follow-up time of 55 and 58 months. Patients showing relapse still responded to a second and even to a third course of MTX. Patients who showed a relapse had received a lower cumulative dose, due to a shorter period of treatment with MTX in the first course. Serious side-effects were seen in six patients (10%).
Conclusions  MTX was an effective treatment for various sclerotic skin diseases with a long period of remission and relatively low toxicity. Patients showing relapse still responded to a second and third course of MTX.     

Comparison of immunological parameters in patients with pemphigus vulgaris following rituximab and IVIG therapy

Background Information on certain immunological parameters in patients with pemphigus vulgaris (PV) treated with rituximab (RTX) and intravenous immunoglobulin (IVIG) therapy is limited. Objective Comparing immunological parameters in patients who achieved long‐term clinical remission (LTR) with those who relapsed. Methods Retrospective analysis of 19 patients treated at a single centre using the same protocol. Comparisons were made between patients who went into LTR and those who relapsed following completion of the protocol. Treatments prior to IVIG and RTX included prednisone with or without an immunosuppressive agent. The immunological parameters measured included peripheral blood B cells (CD19+), serum quantitative immunoglobulin levels, and levels of antibodies to desmogleins (Dsg) 1 and 3. Results Eleven patients achieved LTR. Eight patients developed 15 relapses. The mean follow‐up time for the LTR group was 29·6 ± 11·2 months, and for the relapse group, 40·0 ± 7·0 months. There were no significant differences in times to B‐cell depletion, repopulation, or recovery to pretreatment levels between the patients who achieved LTR and those who relapsed. Recurrences usually occurred after B‐cell repopulation. Repeated treatments did not influence the time to B‐cell repopulation. IgM levels were decreased after therapy and remained decreased. A consistent increase in anti‐Dsg1 antibody levels occurred at the time of relapse in patients with mucocutaneous disease. Conclusions The majority of patients treated with rituximab and IVIG therapy achieved LTR. Retreatment of relapses can induce LTR. Decreased serum IgM levels persisted following treatment. Increases in anti‐Dsg1 antibodies during therapy in patients with mucocutaneous disease suggests a close follow‐up for a potential relapse is required.     

The pulsed‐dye laser as an adjuvant treatment modality in acne vulgaris: a randomized controlled single‐blinded trial

Background Acne vulgaris is the most common skin disease and can pose a substantial therapeutic challenge. Recently, several phototherapeutic modalities, most notably pulsed‐dye laser (PDL) treatment, have been introduced, but the published results – albeit promising – are controversial. Objectives To assess the efficacy of an adjuvant PDL treatment when combined with a proven topical treatment [fixed‐combination clindamycin 1%–benzoyl peroxide 5% hydrating gel (C/BPO)]. Methods Eighty patients (38 males and 42 females, mean ± SD age 19·7 ± 5·9 years) were randomized in a 1 : 2 ratio to receive C/BPO alone or in combination with PDL treatment (wavelength 585 nm, energy fluence 3 J cm⁻², pulse duration 0·35 ms, spot size 7 mm). Patients were evaluated at baseline and at 2 and 4 weeks after initial treatment. The primary end points were the Investigator’s Static Global Assessment (ISGA) score and lesion count; the secondary end point was the Dermatology Life Quality Index (DLQI). Results Both groups showed a significant improvement during observation [ISGA 27·1% (C/BPO) and 24·6% (C/BPO + laser), total lesion count 9·2% and 9·0%, inflammatory lesion count 36·3% and 36·9%, DLQI 54·5% and 42·5%], but there was no significant or otherwise appreciable difference between treatment modalities as far as the extent of improvement was concerned. Patients with more severe findings at baseline had a greater benefit from either therapy regimen. Conclusions Our findings do not support the concept of a substantial benefit of PDL treatment in acne vulgaris.     

Efficacy of mycophenolate mofetil in severe mucocutaneous lichen planus: a retrospective review of 10 patients

Summary Background Ulcerative lichen planus is an uncommon and severe subtype of lichen planus primarily affecting the oral mucosal surfaces. It may be associated with significant morbidity and often requires immunosuppressive therapy to achieve disease control. There have been no previous reports in which objective outcome measures have been used to assess the efficacy of mycophenolate mofetil (MMF) in severe ulcerative lichen planus. Objective To evaluate the clinical responses of patients with severe ulcerative oral lichen planus who were treated with MMF at a tertiary oral medicine/dermatology centre. Methods This was a retrospective review of oral disease severity scores performed in 10 patients with recalcitrant ulcerative oral lichen planus (vulvovaginal–gingival, n = 8; penogingival, n = 1; oral, n = 1) before and after treatment with MMF therapy. The results were analysed using the Wilcoxon matched pairs signed‐rank test. Results The mean duration of MMF treatment was 3·7 (SD ± 2·4) years with a mean follow‐up of 4·2 (SD ± 2·7) years. The mean baseline oral disease severity scores (39·1 ± 11·9) improved by 40% after 12–15 months (24·3 ± 11·9, n = 8, P = 0·01) and by 43% after 21–24 months of MMF treatment (22·2 ± 10·4, n = 9, P = 0·01). Of the 10 patients, six achieved remission, one had well‐controlled disease and three had partially controlled disease. Two patients who achieved remission successfully discontinued treatment. MMF was well tolerated in all patients. Conclusion Our case series demonstrates the efficacy and favourable side‐effect profile of MMF in the treatment of severe ulcerative lichen planus.