Thirty‐two Japanese cases of infantile hemangiomas treated with oral propranolol

Infantile hemangiomas undergo rapid growth during early infancy followed by gradual involution. Infantile hemangiomas sometimes impair vital functions or cause disfigurement. Thirty‐two Japanese patients between the ages of 1 and 4 months with proliferating infantile hemangiomas received oral propranolol on an outpatient basis. The success rate (complete or nearly complete resolution) at week 25 was 56% (18/32). Two patients dropped out because of a personal reason and moving out. Recurrence after termination of treatment was seen in six patients. Adverse events occurred in 16 patients. There were no adverse events on day 1 (initiation of treatment at a dose of 1 mg/kg per day) and day 8 (dose increase to 2 mg/kg per day). One patient was hospitalized due to pneumonia, and suspended propranolol for 26 days. Oral propranolol at 2 mg/kg per day is effective and safe in Japanese patients with infantile hemangiomas.     

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.     

An appraisal of acitretin therapy in children with inherited disorders of keratinization

Retinoid therapy represents the treatment of choice for severe inherited disorders of keratinization. This paper reviews our experience of acitretin, compares acitretin with etretinate and defines guidelines for treatment. Forty-six children have received acitretin since 1992 in our hospital: 29 children had either lamellar ichthyosis (nine), non-bullous ichthyosiform erythroderma (five), bullous ichthyosiform erythroderma (four), Sjögren-Larsson syndrome (three) or another rare condition (eight). The other 17 children who had psoriasis (16) and extensive viral warts (one), were excluded. Data on efficacy and tolerability of retinoid therapy were available for all but one patient. The cumulative follow-up was 472 months for acitretin. The mean (± standard deviation) optimal dosage for acitretin was 0-47 ± O17mg/kg per day, and this did not significantly differ between disorders. The overall improvement was considerable, with only three patients responding poorly. Mild to moderate mucocutaneous dryness was frequent. Minor abnormalities of liver function tests (four patients) and triglycerides (one patient) never led to changes of therapy. Irreversible side-effects did not occur. Acitretin therapy for children with inherited keratinization disorders is best started at 0-5 mg/kg per day. It represents a safe and effective treatment, provided that the minimal effective dose is maintained and that side-effects are carefully monitored. When switching from etretinate to acitretin, a 20% reduction is recommended if the etretinate dose is over 0-75 mg/kg per day or if side-effects are dose limiting. Otherwise the same dose can be used.     

9-cis-retinoic acid capsules in the treatment of AIDS-related Kaposi sarcoma: results of a phase 2 multicenter clinical trial

OBJECTIVE: To evaluate the safety, dose tolerance, and anti-tumor effects of 9-cis-retinoic acid in the treatment of Kaposi sarcoma (KS) related to acquired immunodeficiency syndrome (AIDS). DESIGN: Phase 2, open-label clinical trial of oral doses of 9-cis-retinoic acid increasing in 40-mg increments every 2 weeks from 60 mg/m(2) per day to a maximum of 140 mg/m( 2) per day. SETTING: Five hospital or health maintenance organization outpatient clinics. PATIENTS: Fifty-seven adult male patients with human immunodeficiency virus and biopsy-proven KS. MAIN OUTCOMES MEASURES: Safety was evaluated by adverse events, physical examination, laboratory test abnormalities, treatment-limiting toxic effects, and reasons for early withdrawal. Response (>/=50% improvement) was evaluated by an overall KS response and by the area and height from 6 index lesions selected at baseline. RESULTS: Patients tolerated 60 and 100 mg/m(2) per day. Most patients found 140 mg/m(2) per day intolerable owing to headache. Common treatment-related adverse events were headache, xerosis, rash, alopecia, and hyperlipemia. The patient response rate for the overall KS disease was 19% (11/57), including 1 patient with clinically complete response. The response rate assessed by measuring 6 index lesions during treatment was 39% (22/57). Sixteen responding patients (73%) were refractory to at least 1 previous anti-KS therapy. Patients with CD4( +) counts of 150 cells/ micro L or lower were as likely to respond as patients with counts of higher than 150 cells/ micro L. The median time to response was 8.5 weeks (range, 4.0-21.1 weeks). The median duration of treatment was 15.1 weeks (range, 0.14 to >/=62 weeks). CONCLUSION: 9-cis-retinoic acid capsules have moderate activity and provide durable responses, but substantial toxic effects at higher doses limit its suitability as an anti-KS therapy.     

Results of cyclosporin treatment of severe, chronic psoriasis vulgaris

Controlled double-blind studies have demonstrated the efficacy of 14 mg/kg per day cyclosporin A (CsA) in patients with severe psoriasis. Recently a placebo-controlled double-blind randomized study confirmed that CsA therapy (mean dose 5.5 mg/kg/day improves psoriasis significantly. We have carried out a placebo-controlled, double-blind, randomized trial involving 12 patients suffering from severe psoriasis resistant to local therapy. Within 4 weeks, 5 mg/kg per day CsA resulted in 6 patients in a mean reduction of 72.5% of the PASI score, which differed significantly from the mean reduction of 18.1% in 6 patients receiving placebo. The most important side-effect was reversible hypertension in 1 patient. The preliminary results of a dose-finding study that started recently indicate that 1-3 mg/kg per day CsA results in a significant improvement in the patient's condition.     

Cyclosporin A in the treatment of chronic dermatitis of the hands

Summary The efficacy of cyclosporin A (CyA) treatment was studied in seven patients with chronic dermatitis of the hands. CyA was started at a daily dose of 2·5 mg/kg in five patients, and 1·25 mg/kg in two patients. In patients who responded to the treatment at 2·5 mg/kg/day, the daily CyA dose was reduced stepwise, to the lowest maintenance dose of 1·25 mg/kg. In patients who did not respond, the dose was increased, to a maximum of 5 mg/kg/day. The patients were treated for 2–16 weeks. In six of the seven patients the dermatitis responded to CyA treatment within a few weeks. No response was seen with a starting dose of 1·25 mg/kg/day. In three of the five patients with a starting dose of 2·5 mg/kg/day, the daily CyA dose could be reduced to 1·25–2 mg/kg/day. After stopping CyA treatment, the dermatitis recurred during follow-up in three patients, three remained in remission, and one patient was not available for study. Treatment-related side-effects occurred in three patients. CyA treatment had to be stopped in one patient due to headache. The present study suggests that CyA could be a useful treatment for chronic dermatitis of the hands not responding to conventional therapy.     

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.     

Doubled dose of oral terbinafine is required for Microsporum canis tinea capitis

Fourteen children, ages 1-15 years, with Microsporum canis tinea capitis were given oral terbinafine for 4 weeks at the recommended daily dose according to their weight: 10-20 kg, 62.5 mg; 20-40 kg, 125 mg; > 40 kg, 250 mg. Because none of the patients had clinically responded to treatment by week 4 the dose of terbinafine was doubled (up to 250 mg) for an additional 4-8 weeks in six patients, and continued at the original dose in six patients. Two patients dropped out of the study. On final evaluation, four patients were cured after 8-12 weeks of treatment. All cured patients received the doubled dose of terbinafine, except for one who was on the usual adult dose of 250 mg from the onset. Oral terbinafine was well tolerated by all but one patient, who experienced gastrointestinal disturbance and slightly raised transaminase levels during the first 4 weeks of treatment. Terbinafine side effects were not correlated with dosage or duration of treatment. We conclude that oral terbinafine should be dosed for M. canis tinea capitis at a revised schedule according to body weight: 10-25 kg, 125 mg/day and > 25 kg, 250 mg/day. The appropriate duration of terbinafine treatment remains to be determined.     

胺碘酮治疗老年心力衰竭合并快速心律失常的疗效和安全性

目的观察胺碘酮治疗老年慢性心力衰竭合并快速心律失常的疗效和安全性。方法124例快速心律失常患者,年龄（79±6．3）（70-93）岁,首剂静注胺碘酮150mg,10min注入,随后1mg/min维持静滴6h,0．5mg/min维持静滴至24～48h。首剂静注后若心律控制不满意,可间隔30min,再静注胺碘酮150mg追加负荷量2-3次,24h之内总量600-1200mg。根据病情部分患者24h后重叠口服胺碘酮600mg,d,1周后减为400mg/d,2周后减至200mg／d维持。结果有效率89．52％,副反应12．10％。结论胺碘酮治疗老年慢性心力衰竭合并快速心律失常安全有效。     

Epidermolysis bullosa acquisita — successful treatment with colchicine

The treatment of epidermolysis bullosa acquisita (EBA) is difficult and often disappointing. We report on the successful treatment of two EBA patients with colchicine. The drug was administered orally at an initial dose of 2 mg/day. After 2 weeks of therapy a dramatic improvement was observed. Most of the cutaneous and buccal mucosal lesions had healed and both of the patients were able to go about their normal daily activities. In the first patient the disease was refractory to dapsone alone or combined with steroids. In the second patient no other treatment was tried. After 6 months a maintenance dose of 1 mg/day colchicine was given. The disease had remained stable in both patients at the time of writing for more than 8 months. No side effects were observed. We suggest that colchicine may be a helpful and safe drug for patients with EBA.     

Treatment of pyoderma gangrenosum with cyclosporin A

Two patients with recalcitrant pyoderma gangrenosum were treated with oral cyclosporin A (5 mg/kg body-weight/day). Healing of the lesions was achieved in Patient 1 within 1 month of starting treatment, but new areas of ulceration appeared when the dose was reduced to 3 mg/kg body-weight/day. The ulcers showed marked improvement by 3 weeks after the start of treatment in Patient 2 and remained inactive at a maintenance dosage of 100 mg/day, but there was no change in the associated seronegative arthritis. A steroid-sparing effect of CyA was evident in both patients. It is suggested that a lower dose of cyclosporin A than doses used previously in the treatment of pyoderma gangrenosum may be equally effective.     

Safety and efficacy of a fixed-dose cyclosporin microemulsion (100 mg) for the treatment of psoriasis

Cyclosporin is a second-line modality for the treatment of psoriasis. The long-term efficacy of cyclosporin and potential adverse side-effects, however, are a concern to patients. Therefore, a cyclosporin microemulsion (Neoral), which is steadily absorbed at an ultra-low dosage (1-2 mg/kg per day) or low dosage (2-3 mg/kg per day), is currently recommended. The dose must be calculated based on patient bodyweight and the blood concentration monitored regularly, which is time-consuming. Furthermore, the concentration is related to the safety profile, but not to efficacy. We examined whether a fixed-dose cyclosporin microemulsion (100 mg/day) is effective for treating psoriasis. Enrolled patients (n = 40) were given either 100 mg cyclosporin emulsion once daily (group A) or 50 mg twice daily (group B), regardless of patient weight and condition, before meals in a randomized controlled study. Patient bodyweight ranged 50-80 kg. We assessed the serum cyclosporin concentration 1 h after administrating the medicine (C1 score), Psoriasis Area and Severity Index (PASI) score, quality of life, and the results of regular blood examinations. The improvement rate was 69.4 ± 4.8% in group A and 73.4 ± 4.3% in group B. PASI-50 was achieved by 82% in group A and 84% in group B. At 6 weeks, the number of patients with PASI-50 was significantly higher in group A than in group B. PASI-75 and -90 were also achieved in both groups with no significant difference between groups. Administration of a fixed-dose cyclosporin microemulsion (100 mg/day) is practical for second-line psoriasis treatment.     

CLINICAL EVALUATION OF A NEW ORAL RETINOID R010 9359 IN THE TREATMENT OF DARIER'S DISEASE*

Eleven patients with moderate to severe Darier's disease were treated with an oral aromatic retinoid, R010 9359 in a dose of 1 mg/kg/day for six weeks. Three patients were clear after six weeks, seven patients showed marked improvement and one patient showed moderate improvement. Pruritus, palmo-plantar desquamation and hair loss proved troublesome in some patients but this was reversed by reduction of the dose or cessation of treatment. One patient showed moderate elevation of liver transaminases, thought to be significant. It is felt that maintenance therapy is necessary in most patients and should be limited to 0.5 mg/kg/day if possible.     

Incidence and risk factors for thalidomide neuropathy: a prospective study of 135 dermatologic patients

Thalidomide is effective in several cutaneous diseases. Peripheral neuropathy is the most important adverse event limiting its use. Its incidence rate and its relation to thalidomide doses remain unclear. We prospectively monitored 135 patients treated with thalidomide for various dermatologic diseases for 2 y in order to estimate the annual incidence rate and risk factors for neuropathy. Patients underwent standardized neurologic examination and nerve conduction studies prior to, and regularly during treatment. Risk factors for neuropathy were assessed using a Cox proportional-hazards model. Clinical and electrophysiologic evidence of a thalidomide-induced neuropathy were present in 25.2% of the patients; however, when considering all potential cases, this rate reached 55.6%. The incidence rate was maximal during the first year of treatment (20%). The risk of neuropathy was related to the daily dose whatever the duration of treatment (p<10-3). Considering a daily dose < or =50 mg per day as reference, the relative risk for thalidomide neuropathy was 8.2 for a daily dose comprised between 50 and 75 mg per day and 20.2 for a daily dose >75 mg per day (p<10-3). No neuropathy occurred for daily doses < or =25 mg per day. The neuropathy was subclinical in nearly a quarter of patients with such an adverse event. These data confirm the high rate of thalidomide neuropathy and identify the daily dose as the main risk factor. The risk of neuropathy seems to be negligible for doses less than 25 mg per day, whatever the duration of therapy.     

Low dose azaribine in the treatment of psoriasis

Thirteen patients with severe psoriasis were treated with low dose azaribine (125 mg/kg/day) for 8-week periods. Two patients with generalized pustular psoriasis and four patients with psoriatic arthritis had a good to excellent response. Severe neurotoxicity occurred in four patients, requiring lowering of the dose in three and discontinuance of the drug in one patient. Because of these results, azaribine at 125 mg/kg/day cannot be recommended for plaque-type psoriasis, though it is very effective against generahzed pustular psoriasis and psoriatic arthritis. Of the eleven patients with plaque psoriasis, seven had a good or excellent response initially but subsequently relapsed while on therapy; the other four patients failed to respond to the medication.     

Granuloma anulare disseminatum – erfolgreiche Therapie mit Fumarsäureester

A 64-year old female patient was treated for a therapy-resistant generalized granuloma annulare with fumaric acid esters (Fumaderm initial). One week following begin of therapy with an initial dose of 30 mg per day, the papules had regressed significantly. A 6-week therapy with a final dose of 90 mg Fumaderm initial per day led to a nearly complete healing of the illness.     

Azathioprine as a corticosteroid-sparing agent in air-borne contact dermatitis

Two patients having air-borne contact dermatitis (ABCD) caused by Parthenium hysterophorus.for 10 and 15 years respectively and without having had complete remissions in spite of oral betamethasone in a dose of 2-3 mg per day, experienced complete relief while taking 50-100 mg azathioprine for 5 and 12 weeks without having to take systemic corticosteroids. There were no side effects of azathioprine. With further experience and standardization of the treatment schedule, it may be possible to use azathioprine as a corticosteroid-sparing agent to reduce the side effects of corticosteroids in patients having ABCD.     

Clinical improvement and significant reduction of total serum IgE in patients suffering from severe atopic dermatitis treated with oral azathioprine

Atopic dermatitis (AD) is a common inflammatory skin disease: the incidence is increasing in many countries and treatment can be difficult. The aim of this retrospective case series was to examine the effect of oral azathioprine on the clinical severity and serum IgE levels in 38 patients with severe atopic dermatitis. The AD was well-controlled in nearly 80% (30/38). The maintenance dose required was in the range 25-200 mg per day. Four patients withdrew because of adverse affects, including one case of pancytopenia, and a further four ceased azathioprine after 4 months because of a lack of clinical improvement. Total serum IgE levels were measured before commencing azathioprine and after two years of treatment in 26 patients. IgE levels decreased in almost all patients and this was statistically significant (P = 0.012).     

Photodynamic therapy with meta-tetrahydroxyphenylchlorin for basal cell carcinoma: a phase I/II study

BACKGROUND: Photodynamic therapy (PDT) is a convenient and effective method of treating small superficial tumours. New second-generation photosensitizers offer some advantages over first-generation sensitizers such as haematoporphyrin derivatives. OBJECTIVES: To define the optimal treatment parameters (drug dose, light dose and time interval) using meta-tetrahydroxyphenylchlorin (mTHPC) as a photosensitizer in patients with multiple basal cell carcinomas (BCCs). METHODS: Light of 652 nm (100 mW cm(-2)) was used for illuminating different tumours (n = 187) with light doses of 5--15 J cm(-2). Following an intravenous injection of 0.1 mg kg(-1) mTHPC each patient (n = 5) was illuminated on 4 consecutive days. Each day at least three BCCs per patient were treated with PDT. RESULTS: Response evaluation at 6, 12 and 18 months showed maximum responses for illumination with 10 or 15 J cm(-2) on days 1 or 2 after injection (86% complete responses). Normal tissue reactions (oedema and erythema) around the treatment site were more severe on day 1 than after longer intervals. CONCLUSIONS: mTHPC is a very effective photosensitizer; short illumination times can result in long-term cures with good cosmetic healing and with skin phototoxicity of short duration.     

Intralesional rituximab in the treatment of indolent primary cutaneous B-cell lymphomas: an epidemiological observational multicentre study. The Spanish Working Group on Cutaneous Lymphoma

Summary Background Intravenous rituximab is a safe and effective option for the treatment of systemic non‐Hodgkin B‐cell lymphoma. The effectiveness of intralesional rituximab (ILR) in primary cutaneous B‐cell lymphomas (PCBL) has been described in a small number of patients. Objectives To evaluate the effectiveness, tolerance and adverse effects of ILR in patients with follicle centre (FCL) and marginal zone (MZL) PCBL. Methods This was an epidemiological observational multicentre study of patients with PCBL treated with ILR. Results Seventeen patients with MZL and 18 with FCL PCBL were included. The median number of lesions treated was two per patient. The treatment regimen used in 74% of the patients was a course of three injections in a single week at 1‐month intervals. The dose per lesion and day of treatment was 10 mg in 71% of the patients. The median cumulative dose of rituximab per lesion was 60 mg (range 13–270) and per patient was 150 mg (range 20–360 mg). Complete response (CR) and partial response were achieved in 71% and 23% of patients, respectively. The median time to CR in patients who received 10 mg of ILR per lesion was 8 weeks. Similar response rates were observed in MZL and FCL. Median disease‐free survival was 114·1 weeks. No parameters that significantly predicted CR were identified. Adverse reactions were recorded in 19 patients; the most frequent was localized pain at the injection site. Median follow‐up was 21 months. Conclusions Intralesional rituximab is a well‐tolerated and effective treatment for FCL and MZL PCBL. It should be considered a useful alternative in patients with recurrent lesions and in which the sequelae of radiotherapy or surgery would be significant.