Efficacy of fixed low-dose isotretinoin (20 mg, alternate days) with topical clindamycin gel in moderately severe acne vulgaris

Background  In view of the potentially serious side-effects of standard isotretinoin (0.5–1.0 mg/kg per day) therapy for acne, we studied the safety and efficacy of low-fixed dose isotretinoin plus topical 1%clindamycin gel in the treatment of moderate grade of acne.
Methods  In this prospective, non-comparative study, 320 adult patients, with moderately severe acne were enrolled and treated with fixed-dose isotretinoin at 20 mg every alternate day (approximately 0.15 mg/kg/day to 0.28 mg/kg/day) for 6 months along with topical clindamycin gel. All female patients were assessed for polycystic ovarian disease. Patients were followed up for 6 months.
Results  A total of 305 patients completed the study. Overall, patients received a mean of 38.4 mg/kg cumulative dose of isotretinoin, and very good results were observed in 208 (68.20%), while good response was seen in 59 (19.34%) of patients. Failure of the treatment occurred in 38 (12.46%), while relapses occurred in 50 (16.39%) of patients. Relapses were commoner in females, and 37 of 43 (86.04%) patients had polycystic ovarian disease. Though mild chelitis (91%) and xerosis (43%) were common, laboratory abnormalities in the form of elevated hepatic enzymes (5%) and elevated serum lipids (6%) were rare.
Conclusion  Six months of treatment with fixed-dose, alternate-day isotretinoin (20 mg) plus topical 1%clindamycin gel was found to be effective in the treatment of moderate acne in adult patients, with a low incidence of side-effects.

Conflicts of interest

None declared     

Epidermolysis bullosa acquisita: a retrospective clinical analysis of 30 cases

Epidermolysis bullosa acquisita (EBA) is an acquired, autoimmune blistering disorder caused by autoantibody production against type VII collagen. The aim of this study was to examine the clinical types, treatments, and outcomes of 30 patients with EBA. In our cohort, the median age of onset was 44.0 years, with a similar incidence for both genders (46.7% male, 53.3% female). The majority of patients had classic type (36.7%) and bullous pemphigoid (BP)-like type (46.7%) EBA. The remaining patients had mucous membrane pemphigoid-like (6.7%), Brunsting-Perry pemphigoid-like (6.7%), and linear IgA bullous dermatosis-like type (3.3%) EBA. All patients were treated initially with a combination of methylprednisolone, dapsone and colchicine. No significant differences in time to remission were identified between patients with classic vs. BP-like EBA. In a second subset analysis of 19 patients, a group treated with high-dose (>?8 mg) methylprednisolone achieved remission earlier (median time to remission: 3 months) than a group treated with low-dose (≤?8 mg) methylprednisolone (median time to remission: 12 months), irrespective of clinical type (p?=?0.003).     

Adjuvant treatment of recalcitrant bullous pemphigoid with immunoadsorption

Elimination of pathogenic autoantibodies by immunoadsorption (IA) has been described as an effective adjuvant treatment in severe bullous autoimmune diseases, especially in pemphigus. There is much less experience in the treatment of bullous pemphigoid (BP). BP was diagnosed in a 62-year-old Caucasian woman presenting a pruritic rash with multiple tense blisters. Standard treatments with topical and oral corticosteroids, steroid-sparing agents including dapsone, azathioprine, mycophenolate mofetil (MMF) and intravenous immunoglobulins were ineffective or had to be discontinued due to adverse events. An immediate clinical response could be achieved by two treatment cycles of adjuvant protein A immunoadsorption (PA-IA) in addition to continued treatment with MMF (2 g/day) and prednisolone (1 mg/kg/day). Tolerance was excellent. Clinical improvement remained stable after discontinuation of IA and went along with sustained reduction of circulating autoantibodies. Our data demonstrate that PA-IA might be a safe and effective adjuvant treatment in severe and recalcitrant BP.     

A systematic review of treatments for bullous pemphigoid

OBJECTIVE: To assess the effectiveness of treatments for bullous pemphigoid. METHODS: The Cochrane Library search strategy was used to identify randomized controlled trials from MEDLINE and EMBASE, from their inception to September 30, 2001. All randomized controlled trials on interventions for bullous pemphigoid, confirmed by immunofluorescence studies, were included. RESULTS: We found 6 randomized controlled trials with a total of 293 patients. Two trials, one comparing prednisolone, 0.75 mg/kg per day, with prednisolone, 1.25 mg/kg per day, and the other comparing methylprednisolone with prednisolone, did not find any significant difference in effectiveness. The higher dose of prednisolone, however, was associated with more severe adverse effects. Combination treatments of prednisone with azathioprine in one trial and of prednisolone with plasma exchange in another were useful in halving the corticosteroid dose required (mean +/- SD, 0.52 +/- 0.28 mg/kg in the plasma exchange-treated group vs 0.97 +/- 0.33 mg/kg in the prednisolone only-treated group). However, a fifth trial, including all 3 treatment groups (prednisolone alone, prednisolone and azathioprine, and prednisolone and plasma exchange), failed to confirm the benefit of combination treatment over prednisolone alone. A trial of 20 patients, comparing prednisone with tetracycline and niacinamide, found no statistically significant difference in response between the 2 groups, but the prednisone-treated group had more serious adverse effects. CONCLUSIONS: There is inadequate evidence for a recommendation of a specific treatment for bullous pemphigoid, and there is a need for larger randomized controlled trials with adequate power. Starting doses of prednisolone greater than 0.75 mg/kg per day do not seem to give additional benefit, and it seems that lower doses may be adequate for disease control. The effectiveness of the addition of plasma exchange or azathioprine to corticosteroids has not been established. Combination treatment with tetracycline and niacinamide seems useful, although this needs further validation.     

Analysis of side-effects of medium- and low-dose cyclosporin maintenance therapy in psoriasis

The side-effects of long-term cyclosporin A (CyA) treatment in 26 patients with severe psoriasis were evaluated. These patients had a mean PASI score of 30.2 and were treated with CyA for between 7 and 37 months (mean 19.5 months). There were three groups according to the dose of CyA, less than 2 mg/kg per day, 2-3 mg/kg per day and greater than 3 mg/kg per day. In all three groups, CyA was found to be equally effective. Treatment with CyA was discontinued in 12 of the 26 patients because of nephrotoxicity and/or development of hypertension. One was in the less than 2 mg/kg per day group, three were in the 2-3 mg/kg per day group and eight in the greater than 3 mg/kg per day group. There was no hepatotoxicity with CyA treatment. One patient developed two squamous cell carcinomas of the skin.     

儿童头皮深在性红斑狼疮五例

目的 探讨儿童头皮深在性红斑狼疮（LEP）临床及病理学特征。 方法 回顾性分析5例LEP患儿临床、组织病理特点及治疗和预后情况。 结果 5例儿童头皮LEP,男2例,女3例;中位发病年龄5个月（范围2 ～ 38个月）;中位病程15个月（范围4 ～ 72个月）。皮损为头部弧形或环形紫红色萎缩性斑块伴脱发,枕部及颞部最常受累。1例患儿抗核抗体（ANA）1 ∶ 100,4例患儿ANA抗Ro/SSA、La/SSB抗体检查均为阴性。组织病理学改变主要为脂肪透明变性,黏蛋白沉积及脂肪小叶淋巴细胞灶状聚集。2例口服泼尼松（1.5 ~ 2） mg·kg-1·d-1, 1例口服羟氯喹5 mg·kg-1·d-1,1例口服泼尼松1.5 mg·kg-1·d-1并联合羟氯喹5 mg·kg-1·d-1;1例患儿仅外用卤米松乳膏及0.03%他克莫司软膏。患儿皮损于治疗后2 ~ 3月均获得缓解,6个月消退,新发生长,随访1.5年未见病情反复。 结论 头皮LEP对泼尼松及羟氯喹治疗反应良好,患儿可选用强效糖皮质激素及钙调磷酸酶抑制剂外用治疗。     

Rifampicin and dapsone in superficial pustular folliculitis

Fifty male patients diagnosed to have superficial pustular folliculitis (SPF) were included in an open trial to study the effects of rifampicin vs dapsone. Rifampicin, in a dose of 10mg/kg body weight for a period of 8 weeks was given for 25 patients in phase I and the drug cleared the lesions in 72%. Dapsone in a dose of 100 mg/day produced moderate response in 20% only. 17 patients who did not clear with dapsone were started on rifampicin (phase II) and 7/17 showed marked improvement. Remissions with rifampicin ranged from 3-9 months or longer. In patients who relapsed, a second course of the drug was effective.     

Diagnosis and treatment of patients with autoimmune bullous disorders in Germany

In Germany, more than 2000 new patients per year have been calculated to be diagnosed with autoimmune blistering diseases. In a recent survey, the most frequently applied treatment regimens for bullous pemphigoid were class IV topical corticosteroids and oral prednisolone 0.5 mg or 1.0 mg/kg/d plus dapsone or azathioprine. For pemphigus, two-thirds of the clinics applied oral prednisolone at doses of 1.0 mg or 1.5 mg/kg/d and in more than 80% of departments, azathioprine was chosen as concomitant immunosuppressant. High-dose intravenous immunoglobulin, rituximab, and immunoadsorption are increasingly used for refractory patients. Treatment and diagnostic costs are covered by the health insurances when applied according to published expert recommendations.     

Dapsone treatment of folliculitis decalvans

BACKGROUND: Folliculitis decalvans consists of recurrent patchy painful folliculitis of the scalp causing scarring alopecia. The physiopathology of this condition is still unclear, but is likely a manifestation of chronic neutrophilic bacterial folliculitis. Numerous topical and systemic treatments (corticosteroids, antistaphylococcal antibiotics) have been used with variable results. Based on the dapsone antimicrobial activity and its anti-inflammatory action especially directed to the neutrophil metabolism, we treated two patients with severe folliculitis decalvans with this drug. CASE REPORTS: The patients were treated with dapsone at a daily dose of 75 and 100 mg, respectively for 4 to 6 months. After 1 and 2 months, pustular folliculitis progressively cleared, leaving a residual non inflammatory cicatricial alopecia. When maintaining a dapsone dosage at 25 mg/day no relapse occurred during 3 years and 1 year, respectively. No important adverse effect to dapsone was evidenced. After dapsone withdrawal, a moderate relapse of the disease with pruritus and folliculitis occurred after a few weeks in both cases. The disease relapse rapidly cleared after dapsone reintroduction at a daily dose of 25 mg. COMMENTS: Dapsone at moderate dosage was well tolerated and rapidly effective in treating the two cases of folliculitis decalvans. A long term and low dose (25 mg daily) maintenance treatment avoided disease relapses.     

Clinical usefulness of a supplementary cyclosporin administration with a topical application of maxacalcitol ointment for patients with moderate psoriasis vulgaris

In this study, we aimed at confirming the clinical usefulness of a supplementary additional cyclosporin microemulsion preconcentrate (CyA MEPC) administration in 15 patients with psoriasis vulgaris whose disease activity had been unchanged or exacerbated with topical maxacalcitol treatment. Each patient took a supplementary CyA MEPC administration, 2.5 mg/kg per day in addition to maxacalcitol ointment therapy. When the Psoriasis Area and Severity Index (PASI) score revealed over a 75% decrease against the initial value, the administration of CyA MEPC was tapered off, and a topical application of maxacalcitol ointment was continued for the maintenance phase. All patients could obtain improvement within 12 weeks. In 12 patients whose PASI score reduced over 75%, CyA MEPC was tapered off. Of those, five patients remained in remission by maxacalcitol ointment for over 12 months and three patients for 6 months. In conclusion, this preliminary study may suggest that supplementary therapy of short-term CyA MEPC administration in combination with topical vitamin D3 treatment may be worth trying for patients with moderate psoriasis vulgaris.     

Evaluation of five treatment regimens, using either dapsone monotherapy or several doses of rifampicin in the treatment of paucibacillary leprosy

The objective of the present study was to define short-course treatment regimens for PB leprosy and to compare them with the 'classical' dapsone treatment and the WHO-PB regimen. Five treatment regimens were studied and evaluated by the histologic evolution. The regimens were: (1) dapsone 100 mg daily, non-supervised for 3 years; (2) RMP 900 mg supervised, once weekly, 8 doses; (3) idem 12 doses; (4) RMP 600 mg, once monthly, supervised, 6 doses and during this treatment dapsone 100 mg daily unsupervised; (5) RMP 600 mg together with dapsone 100 mg daily, supervised for 6 days. For each of these regimens there were between 114 and 195 person-years of follow-up. Results are comparable for the 5 treatment regimens, and reach 65-75% cure rates at 36 months and 80-90% at 48 months after the start of therapy. The relapse rate for all groups is about 0.5% per year. The difficulty for the diagnosis of relapse in PB leprosy is discussed. It is concluded that treatment of PB leprosy can be relatively simple but that a relatively long time is needed to evaluate its effect.     

Evaluation of mycophenolate mofetil as a steroid‐sparing agent in pemphigus: a randomized,prospective study

Background Mycophenolate mofetil (MMF) has been lately proposed as one of the most promising steroid‐sparing agent in pemphigus. Objective To compare effectiveness and adverse events of two different therapeutic protocols for pemphigus: methylprednisolone alone vs. the combination of methylprednisolone and Mycophenolate mofetil. Methods A randomized prospective non‐blinded trial was performed in a tertiary care medical centre. Forty‐seven of 52 initially evaluated patients with newly diagnosed pemphigus vulgaris or pemphigus foliaceous that had not previously been treated with systemic corticosteroids or immunosuppressive drugs were randomly assigned to treatment with either methylprednisolone (prednisone equivalent, 1 mg/kg) or methylprednisolone plus mycophenolate mofetil (3 g/day, 1.5 g twice daily). Patients were followed up for clinical outcome based on time required until the achievement of control of disease activity, induction of partial and complete remissions on or off minimal therapy, total amount of corticosteroids administered, frequency of relapses and development of side‐effects and complications. Results The two groups were similar in terms of demographics and baseline disease characteristics. There was no difference between groups in any of the variables used to measure response to treatment or total amount of corticosteroids administered. Side‐effects did not differ significantly. Conclusion Combination treatment with corticosteroids and mycophenolate mofetil, 3 g/day, offers no advantage over monotherapy treatment with corticosteroids in patients with pemphigus.     

Investigations into the haemolytic effects of dapsone therapy in leprosy patients

Investigations into the haemolytic effects of dapsone therapy were carried out in forty four leprosy patients admitted to the Sacred Heart Leprosy Centre, Kumbakonam. They received weight based dapsone dosages varying from 1.3-3.3 mg/kg body weight. Blood levels and urinary Dapsone/creatinine ratio were assessed at 1 day, 7 days and 30 days of Dapsone treatment. At the same points of time, haematological observations were also carried out. Serum bilirubin as well as blood mathaemoglobin were also examined. The findings showed a reduction in Hb levels at 30 days observation in a good proportion of cases on 100 mg. In one case (child) weighing 15 kg and receiving 50 mg dapsone increased mathaemoglobin was observed. It is suggested that dapsone dosage be regulated to body weight and preferably not to exceed 1.5 mg/kg body weight.     

Double-blind placebo-controlled study of long-term low-dose cyclosporin in the treatment of palmoplantar pustulosis

We previously showed in a double-blind, placebo-controlled study that cyclosporin at a dose of 2.5 mg/kg per day is an effective treatment for palmoplantar pustulosis (PPP). In the present randomized, double-blind, placebo-controlled multicentre study we treated 58 PPP patients with placebo or cyclosporin at an initial dose of 1 mg/kg per day. Disease activity was calculated from the number of fresh pustules. Treatment success was defined as the number of fresh pustules not exceeding 50% of the patients' own baseline pustule number. In cases of treatment success the dose of the test medication was not increased and the treatment was kept blinded for a maximum of 12 months. Blinding was broken only on treatment failure of the initial test medication dose. The mean blinded treatment time was 5.1 months for the patients receiving cyclosporin and 2.1 months for placebo (P < 0.01). Treatment was kept blinded for 12 months for seven patients in the cyclosporin and two in the placebo group (P < 0.05). Patients whose treatment code was broken continued in an open dose-finding part of the study with dose adjustments of cyclosporin every second month. In cases of treatment failure the dose of cyclosporin was increased in steps of 1 mg/kg per day; in cases of treatment success the cyclosporin dose was decreased by 1 mg/kg per day. The minimum and maximum doses were 1 and 4 mg/kg per day, respectively. The mean effective dose during the dose-finding part was between 1.2 and 1.7 mg/kg per day. Two patients did not respond to the highest dose of 4 mg/kg per day. In two patients serum creatinine levels increased by > 30% of their own baseline. The other main adverse events were hypertension (seven patients) and hypertrichosis (six patients). After stopping cyclosporin treatment the mean number of fresh pustules showed a maximum after 2 weeks with a continuous decline after that. Twelve months after completing the treatment the mean number of pustules was reduced to 20.0 compared with 63.6 at baseline (P < 0.001); 11 patients were free from pustules and two of these were totally cleared. We conclude that cyclosporin at 1–2 mg/kg per day is an effective and well tolerated treatment for PPP in most patients.     

Eosinophilic Pustular Folliculitis

Eosinophilic pustular folliculitis (EPF), also known as Ofuji disease, is a disease that manifests with follicular papules or pustules. Its variants include a classic type that occurs most commonly in Japan, an HIV-associated type, an infantile type, a type that occurs on the palms and soles, a rare medication-associated variant, and a rare neoplasia-associated variant.A wide range of medications has been used to treat EPF. Topical corticosteroids are the first-line treatment option for EPF. Topical tacrolimus seems to be useful initial therapy as well. Oral indometacin (50-75 mg/day) is an effective treatment of classic EPF although it can induce peptic ulcers. For treatment of HIV-associated EPF when topical corticosteroids and indometacin do not work, various other treatments should be considered. These treatment options include cetirizine 20-40 mg/day, metronidazole 250 mg three times a day, itraconazole starting at a dosage of 200 mg/day and increasing to 300-400 mg/day, and topical permethrin. If these treatments do not work phototherapy with UVB is the 'gold standard' of treatment and is often curative. Treatments with less certain risk-benefit ratios but with some efficacy include PUVA (psoralen + UVA) photochemotherapy, oral corticosteroids, synthetic retinoids (i.e. isotretinoin 1 mg/kg/day), and acitretin (0.5 mg/kg/day), oral cyclosporine (ciclosporine) 5 mg/kg/day, interferon (IFN)-alpha-2b, and IFNgamma. Minocycline 100mg twice daily and dapsone 50-100mg twice daily have been used with some effect. The use of highly active antiretroviral therapy for HIV has resulted in the amelioration of EPF as CD4 cell counts rise above 250/mm(3). The diversity of clinical presentations and affected populations make it seem that EPF is a reaction pattern as much as a disease and that therapy should be tailored to the variant of EPF and the underlying etiology.     

Sulphamethoxypyridazine for dermatitis herpetiformis, linear IgA disease and cicatricial pemphigoid

One-hundred and sixty-eight cases of dermatitis herpetiformis were reviewed to compare the clinical response to and incidence of side-effects from dapsone and sulphamethoxypyridazine. Thirty-seven received sulphamethoxypyridazine (0.25-1.5 g/day) as a single agent therapy at some stage during their care and 161 had dapsone only (50-450 mg/day). Thirty of these patients received both drugs, but at different times. Both were highly effective in controlling the skin disease in 97% of patients on dapsone and 89% on sulphamethoxypyridazine. While 36 (22%) of dapsone-treated subjects had intolerable side effects warranting a change in therapy, this occurred in only five (13.5%) of those treated with sulphamethoxypyridazine. Sulphamethoxypyridazine was also effective as a single agent in three patients with linear IgA disease who had suffered adverse effects from dapsone, and in 10 out of 15 patients with oral and cutaneous lesions of cicatricial pemphigoid.     

糖皮质激素治疗进展期白癜风疗效分析

目的:评价糖皮质激素治疗进展期白癜风的疗效及不良反应。方法:甲泼尼龙组进展期白癜风185例(VIDA评分4分,皮损面积1%),予甲泼尼龙片0.48 mg/kg·d口服3日,后0.24 mg/kg·d口服27日,第2个月减为0.12 mg/kg·d,第3个月减为0.12 mg/kg·d;复方倍他米松注射液组107例(VIDA评分3分或4分,皮损面积1%),成人予复方倍他米松注射液1.0 m L,儿童予0.015 m L/kg肌肉注射,1次/月,连用3次。结果:治疗3个月后,甲泼尼龙组和复方倍他米松注射液组有效率分别为93.0%和82.3%(P0.05)。甲泼尼龙组不良反应发生率为82.7%,显著高于复方倍他米松注射液组62.6%(P0.05)。结论:系统使用甲泼尼龙治疗进展期白癜风疗效优于复方倍他米松肌肉注射,但不良反应发生率相应增高。     

Cicatricial Pemphigoid in a 6-Year-Old Child: Report of a Case and Review of the Literature

Cicatricial pemphigoid has been documented previously in only four patients under the age of 20 years. We report a 6-year-old male who had erosions of the oral and genital mucosa, conjunctivitis, hoarseness, dysphagia, recurrent vomiting, and weight loss. Upper airway obstruction due to a chronically inflamed and scarred epiglottis necessitated tracheostomy. Biopsy of tissue from a solitary cutaneous lesion demonstrated a subepidermal bulla. Direct and indirect immunofluorescence confirmed a diagnosis of cicatricial pemphigoid. Therapy was begun consisting of prednisone, 2 mg per kg per day, in combination with dapsone, 2 mg per kg per day. He did not improve until the prednisone dosage was increased to 4 mg per kg per day.     

Generalized pustular psoriasis responsive to PUVA and oral cyclosporin therapy

A patient with acute generalized pustular psoriasis was successfully treated with a combination of oral cyclosporin (6 mg/kg per day) and photochemotherapy (PUVA). Although early inpatient treatment with weak topical steroids and PUVA produced initial improvement, the patient's clinical condition fluctuated, with the subsequent development of erythroderma. The addition of oral cyclosporin produced dramatic improvement within 1 week of its commencement. The patient remained in remission 12 months following cessation of therapy.     

Dermatitis herpetiformis intolerant to dapsone in Aids

A 35-year-old man with AIDS and pulmonary tuberculosis presented with lesions suggestive of dermatitis herpetiformis and intolerance to dapsone. He was managed successfully with a combination of nicotinamide 200 mg/day and indomethacin 75 mg/day, topical steroids and gluten free diet.