Multi-centre, double blind, randomized trial of three steroid regimens in the treatment of type-1 reactions in leprosy

OBJECTIVE: The objective of this randomized trial was to compare three different steroid regimens in treating type 1 reactions in leprosy in routine clinical practice. DESIGN: The study design was a multicentre, double-blind, randomized, controlled, parallel group trial in patients with acute reversal reactions. The trial was conducted in six leprosy treatment centres in India. A total of 334 participants with acute type 1 reaction were recruited to the trial and randomized to one of three prednisolone regimens: high dose (60 mg per day) or low dose (30 mg per day) both tapered over 20 weeks, and short duration (60 mg per day tapered over 12 weeks). The main outcome measure was the proportion of patients failing to respond to treatment and requiring additional steroids. RESULTS: At the end of 12 months, 46% on the short course required additional steroids compared with 31% on the low dose and 24% on the high dose regimen. CONCLUSIONS: The two 20-week regimens were significantly better than the 12-week regimen. The high dose 20-week regimen was marginally and non-significantly better than the low dose regimen, but the high dose regimen contained 50% more steroid. Reactions in leprosy persist over many months and require long courses of steroids.     

A retrospective review of 20% vs. 10% incremental narrowband UVB regimens to treat psoriasis in skin phototypes III–V Koreans

Background: The optimal incremental dose regimen of narrowband UVB (NBUVB) phototherapy that will provide maximal efficacy and safety has not been determined for patients with brown skin and psoriasis.
Objective: To compare 20% and 10% incremental dose regimens of NBUVB phototherapy with respect to efficacy and safety in Korean patients with brown skin and psoriasis whose Fitzpatrick skin phototypes (SPT) are III–V.
Method: A retrospective study was designed to compare the 20% and 10% incremental dose groups with respect to the number of sessions, duration of treatment, maximum dose, cumulative dose until response, and adverse effects.
Results: The mean number of sessions was significantly lower, the duration of treatment was significantly shorter, and the maximum dose was significantly higher in the 20% incremental dose group. The cumulative dose was not significantly different between the two groups, and there was no statistically significant difference between the groups with respect to the percentage of total adverse effects.
Conclusion: Use of a 20% incremental dose regimen could be advantageous over a 10% incremental dose regimen in patients with brown skin and psoriasis because of a faster treatment response and higher efficacy without a significant increase in the risk of adverse effects.     

A comparative trial of single dose chemotherapy in paucibacillary leprosy patients with two to three skin lesions

A multicentric, double-blind, controlled, clinical trial was carried out to compare the efficacy of a combination of rifampicin 600 mg plus ofloxacin 400 mg plus minocycline 100 mg (ROM) administered as single dose with that of standard WHO/MDT/PB six months regimen. The study subjects were 236 previously untreated, smear-negative patients, without nerve trunk involvement and having only two or three skin lesions. Randomization was done on individual patient basis. Results were analyzed for mean clinical score for improvement, marked clinical improvement and complete clinical cure at the time of release from treatment and at 12 months and 18 months of follow-up. Clinical improvement was seen in most patients in both regimens. Marked improvement (i.e., more than 90% reduction in clinical score) at 18 months was seen in 46.2% and 53.4% of the patients treated with ROM and standard regimens, respectively. But, significant difference in favour of standard PB regimen was seen in patients with three skin lesions and in patients in whom more than one body part was affected. Reversal reaction and adverse drug reactions were minimal in both groups.     

Treating pelvic inflammatory disease with doxycycline and metronidazole or penicillin and metronidazole.

The best way of treating pelvic inflammatory disease (PID) is not known. The clinical response to two treatment regimens (penicillin plus metronidazole v doxycycline plus metronidazole) was studied in 33 patients with PID confirmed by laparoscopy and endometrial biopsy. The overall failure rate, according to the criteria used in this study was five of 11 (45%) women with chlamydial PID, none of six women with gonococcal PID, all of four women with chlamydial gonococcal PID, and three (25%) of 12 women with non-chlamydial non-gonococcal PID. The failure rate with penicillin plus metronidazole treatment was unacceptably high (53%), and significantly higher than that with doxycycline plus metronidazole (19%) (p = 0.038). In most cases the microbiological and histopathological evaluations identified a probable explanation for the poor response to the treatment regimen used.     

Two-day trimethoprim-sulfamethoxazole treatment of pharyngeal gonorrhea

The efficacy of three different regimens of oral medication for pharyngeal gonorrhea was examined in a study of 119 patients. Of 34 patients treated with 1.4 g of pivampicillin plus 1.0 g of probenecid, both taken once a day for five days, 33 (97.1%) were cured. The other two regimens consisted of tablets containing sulfamethoxazole (400 mg) and trimethoprim (80 mg). Of 36 patients treated with a single ten-tablet dose on the first day, two five-tablet doses on the second day, and two three-tablet doses for the next three to five days, 35 (97.2%) were cured. Of 49 patients treated with a single ten-tablet dose on the first day and two five-tablet doses on the second day, 44 (89.8%) were cured. The cure rates for the three regimens were not significantly different (P greater than 0.05). Therefore, we conclude that a two-day trimethoprim-sulfamethoxazole regimen is quick, inexpensive, and reliable in the treatment of pharyngeal gonorrhea.     

Treatment of actinomycetoma foot – our experience with ten patients

Background Mycetoma is a chronic granulomatous inflammation of the subcutaneous tissue and usually results due to traumatic implantation of soil organisms. Mycetoma can be eumycotic or acinomycotic in origin. Actinomycetoma is susceptible to a large number of chemotherapeutic agents, but the response is variable and affected by various factors such as extent of involvement, duration of disease, presence or absence of bony involvement and drugs used for treatment. Aims and objectives To describe our experience of various treatment regimens used for actinomycetoma. Material and methods It was a prospective, open label study of actinomycetoma. Ten patients who were diagnosed clinically as mycetoma were included in this study. All patients were completely evaluated and investigated including skin biopsy, Gram staining of grains and discharge, Ziehl –Nielson stain, KOH preparation, fungal and bacterial cultures and CT scan/Magnetic resonance imaging (MRI), if required. Patients were treated with different treatment regimens, for example, Ramam regimen, modified Ramam regimen, Welsh regimen and its modification. Results Ten patients (eight males, two females) age ranging from 9 to 55 years (mean 29.6 years) were included in this study. Six patients were successfully treated with Ramam regimen, three patients were treated with our modified Welsh regimen (one of these three patients (case 7) initially failed to respond to Ramam regimen), and one patient was treated with modified Ramam regimen. Conclusion Ramam regimen was found to be quite effective in treating patients of actinomycetoma with only minimal bony involvement, while Welsh regimen and its modification should be used in case of severe disease due to amikacin being more sensitive than gentamicin in treating resistant organisms. Intensive phase of Modified Welsh regimen can be extended to five cycles in case of extensive bony involvement.     

MDT-MB therapy in paucibacillary leprosy: a clinicopathological assessment

BACKGROUND: The World Health Organization recommends treatment regimens for paucibacillary (PB) and multibacillary (MB) leprosy, which differ in their duration and components. Hence accurate classification of the disease is required. To overcome difficulties in classification Uniform Multi Drug Therapy (U-MDT) has been recommended. AIM : To evaluate the benefit of adding clofazimine to paucibacillary regimens in leprosy patients by measuring clinical and histological resolution. METHODS: Forty-four paucibacillary patients were included in the study. Twenty-two patients were given MDT-PB regimen and the remaining MDT-MB regimen for six months . Skin biopsies were done before the commencement and at the end of treatment. Clinical and histological resolutions were measured according to the standard criteria a laid down. The results were analyzed using Fishers' test and Crammers' V test. RESULTS: Clinical improvement was observed in 90.9% in the MB group as compared to 27.3% in the PB group. Regression in the nerve swelling was observed in 70% in the MB group and in 37.5% in the PB group while histological resolution was observed in 72.8% and 54.5% respectively. CONCLUSIONS: Addition of clofazimine helps to resolve leprosy lesions both clinically and histologically, thus justifying the concept of Uniform MDT regimen for all patients.     

Chemotherapeutic trials with different regimens containing rifampicin in paucibacillary type of leprosy cases--a preliminary report

Different regimens containing Rifampicin have been tried in treating paucibacillary leprosy patients. In our study we have studied three regimens. Regimen I consists of treating patients with Rifampicin 600 mg once a month for six months combined with Dapsone 100mg daily and treatment is stopped at six months. Regimen II is same as regimen I except that instead of stopping treatment at the end of six months the treatment was continued with dapsone 100 mg daily for another six months and treatment was stopped at one year. Regimen III is the same as recommended by I.A.L. in which treatment is started with Rifampicin 600 mg daily for seven days in the first month to be followed by Rifampicin 600 mg once a month for five more months. This is combined with dapsone 100mg daily for one year. Treatment in this group is also stopped at one year. Eighty one patients in Regimen I, thirty five patients in Regimen II and sixty three patients in Regimen III completed the six month treatment. It was found that the inactivation index in all the three regimens was nearly the same.     

A comparison of twice-weekly MPD-PUVA and three times-weekly skin typing-PUVA regimens for the treatment of psoriasis

The most frequent PUVA treatment regimen in current use is three times weekly, using skin typing to estimate the starting dose. Recently, it was suggested that twice-weekly treatment, using the minimal phototoxic dose (MPD) to calculate suberythemal starting doses of UVA, achieved similar clearance rates with fewer treatments and a lower cumulative UVA dose. We have carried out a trial on 83 patients, comparing twice-weekly MPD-PUVA with three times-weekly skin typing-PUVA, in order to test this hypothesis. Although clearance rates were comparable between the two regimens, there was no overall significant difference in the number of treatments or in the cumulative UVA doses at clearance. However, for patients with skin types I and II the cumulative UVA dose was significantly higher using the twice-weekly MPD regimen (70–0 J/cm² vs. 55–8 J/cm²; P < 005). Our results do not confirm that there is a reduction in cumulative UVA dosage with twice-weekly MPD-PUVA.     

Is weekly azathioprine pulse effective and safe in dermatological conditions?

Azathioprine, a purine synthesis inhibitor is widely used as an effective immunosuppressant in several immune mediated diseases, usually in a dose of 2 to 2.5 mg/kg per day. The pulse dose of azathioprine is an unique once weekly dosing regimen, which has been used as an alternative to daily dose regimen in some immune mediated dermatologic disorders. In this review, we looked at a specific dosing regimen, “weekly azathioprine pulse” with respect to its efficacy and safety in the treatment of dermatologic diseases. We performed a literature search for studies on azathioprine weekly pulse in dermatology in various scientific databases using keywords “azathioprine‐pulse”, “dermatology”, “weekly azathioprine”, and so on. Dosing regimens, indications, efficacy, monitoring, and side effect profile as described in these studies were recorded. Evidence level of the regimens used in various indications was also calculated. We could find six published studies using azathioprine weekly pulse, of which three were randomized comparative clinical trials. Azathioprine pulse was administered in a dose of 300 mg (6 tablets of 50 mg each) every week in all the studies. It has been found to be effective in management of contact dermatitis due to parthenium (IB), chronic plaque psoriasis (IIB), and alopecia areata (IB). Adverse effect profile was found to be almost similar to daily azathioprine. Weekly azathioprine pulse, therefore, appears to be an effective and safe alternative to daily azathioprine in the management of immune mediated disorders in dermatology. Although studies are limited, this regimen seems promising and further studies are warranted.     

8-MOP PUVA for psoriasis: a comparison of a minimal phototoxic dose-based regimen with a skin-type approach

Summary Two ultraviolet A (UVA) regimens for oral S-methoxypsoralen (8-MOP) photochemotherapy (PUVA) for moderate/severe chronic plaque psoriasis using a half body study technique were compared. Each patient received both regimens. A higher-dose regimen based on minimal phototoxic dose (MPD) within percentage incremental increases was given to one-half of the body. The other half received a lower dose regimen based on skin type with fixed incremental UVA increases. Patients were treated twice weekly. Symmetrical plaques were scored to determine the rate of resolution with each regimen. In addition, the number of treatments, cumulative UVA dose and number of days in treatment to achieve overall clearance were recorded. Patients were reviewed monthly for 1 year to record remission data. Thirty-three patients completed the study. Both regimens were effective and well tolerated. With the MPD-based approach, the number of exposures was significantly less for patients with skin types I and II but not III. Although the cumulative UVA dose was higher with the MPU regimen for all skin types studied, the reduced number of exposures required for clearance for skin types I and II but not III, combined with thesecurity of individualized MPD testing, has practical attractions. MPD testing also identified live patients who required an increased psoralen dose and six patients who required a reduction of the initial UVA dose with the skin type regimen. Forty-two per cent were still clear 1 year after treatment and there was no significant difference in the number of days in remission between the regimens for those whose psoriasis had recurred. The reduction in the number of exposures required lor clearance with the MPD-based regimen may be safer and more cost effective in the long term.     

Long-term continuous versus intermittent cyclosporin: therapy for psoriasis

A multicenter randomized controlled study was conducted to assess the long-term efficacy and safety of cyclosporin A therapy for psoriasis using either a continuous or an intermittent regimen. Initially, both regimens consisted of 3-5 mg/kg/day administration of CyA. Once remission was obtained, CyA dose was maintained between 0.5 and 3 mg/kg/day under the continuous regimen, while under the intermittent regimen, CyA dose was tapered off and, when necessary, topical corticosteroids were used until relapse occurred. Thirty-one patients were followed for at least 48 months (mean follow-up period: 55.9+/-4.6 months): 15 received continuous therapy, and 16 received intermittent therapy. With both regimens, the PASI (Psoriasis Area and Severity Index) score was maintained at 5-12 points throughout the follow-up period. The score was decreased by more than 70% from baseline with both regimens: the responses between them were not significantly different. However, overall control of psoriasis, as assessed from the averaged PASI score, was better in the patients receiving continuous therapy. Although the overall frequency of adverse reactions was similar for the two regimens, cancer occurred in two patients on continuous therapy (gastric cancer and hepatocellular carcinoma in one patient each). We could not, however, definitely attribute the cancers in the two patients to continuous therapy itself. There was a significantly higher incidence of renal impairment in elderly patients receiving either regimen when compared with younger patients. In conclusion, CyA administered to psoriasis patients under both regimens exhibited long-term efficacy and tolerability. Despite a lower overall efficacy, it seems proper to conclude that intermittent therapy is more useful than continuous therapy due to the occurrence of malignancies with continuous therapy. Further investigation is required to determine whether intermittent therapy is really safer than continuous therapy, and, if so, how it should be designed to minimize long-term adverse reactions and achieve overall control comparable to that of continuous CyA therapy.     

Large increments in psoralen-ultraviolet A (PUVA) therapy are unsuitable for fair-skinned individuals with psoriasis

The ideal psoralen-ultraviolet A (PUVA) regimen for chronic plaque psoriasis has yet to be established. There are four components to a PUVA regimen: the dose of psoralen, the starting dose of UVA, the frequency of treatment and the incremental UVA dose protocol. Recent studies have been directed at trying to optimize the efficacy of PUVA while minimizing acute side-effects and the risk of cutaneous carcinogenesis, believed to be independently related to the cumulative dose of UVA and the total number of treatments. The British Photodermatology Group recommends two twice-weekly PUVA regimens: one starts with 50% of the minimal phototoxic dose (MPD) and uses weekly increments of 40%, 30%, 25%, 20%, 15%, 10% and 5% of the previous dose to a maximum of 14.5 J/cm2; the other starts with a fixed dose based on skin type and uses weekly dose increments of 40%, decreasing to 20% once erythema develops. We undertook a prospective randomized controlled trial comparing these regimens in 85 Irish patients. The clearance rate with the MPD regimen was lower than with the skin type regimen, 67.5% vs. 95% (P < 0.05). The reasons for treatment failure were grade 3 erythema and severe PUVA itch. There was a trend suggesting that patients with skin types I and II, but not skin type III, required a higher cumulative UVA dose and fewer exposures to clear with the MPD regimen than the skin type regimen, although this did not reach statistical significance. Grades 2 or 3 erythema were very common in both treatment groups (52. 5% of the skin type group and 45% of the MPD group). This is the third study to suggest that patients with skin types I and II receive a higher total UVA dose when the starting dose is 50-70% of the MPD (rather than 0.5 J/cm2 for skin type I and 1.0 J/cm2 for skin type II) and when large dose increments are used. We suggest that smaller dose increments should be used in patients with skin types I and II.     

A controlled therapeutic trial in paucibacillary leprosy comparing a single dose of rifampicin with a single dose of rifampicin followed by one year of daily dapsone. The Collaborative Study Group for the Treatment of Leprosy in Zaire

The cure rates of two treatment regimens in PB leprosy were compared in a prospective randomized trial: treatment U consisting of a single dose of rifampicin 40 mg/K bodyweight, and treatment A of rifampicin 1500 mg in a single dose, followed by one year of daily dapsone 100 mg. In patients with a BI = 0, the cure rates evaluated on the basis of histopathology of skin biopsies, were identical for the two regimens but in patients with a BI = 1, cure and relapse rates were unacceptable. For this reason and particularly the need to separate patients on the basis of the BI in skin biopsies, the single dose regimen does not appear to be suited for wide-scale application.     

Intermittent corticosteroid maintenance treatment of psoriasis: a double-blind multicenter trial of augmented betamethasone dipropionate ointment in a pulse dose treatment regimen.

Ninety psoriasis patients, who were either completely cleared of or manifested only a minimal presence of disease signs following 3-4 weeks of twice daily treatment with augmented betamethasone dipropionate (ABD) ointment 0.05%, were enrolled in this multicenter, double-blind, placebo-controlled study. The study was designed to determine if an intermittent pulse dose regimen of ABD ointment could safely and effectively maintain a remission disease status when treatment was applied in three consecutive applications 12 h apart, once a week for a maximum treatment period of 6 months. The disease of 60% of the patients in the active treatment group was successfully controlled for 6 months, while 80% of the placebo-treated patients experienced exacerbation of disease signs. No serious local or systemic treatment-related adverse experiences were reported. ABD ointment 0.05%, when applied using the intermittent treatment regimen described here, was shown to be a clinically beneficial and well-tolerated method of long-term (up to 6 months) maintenance therapy for psoriasis patients.     

A trial of fludarabine and cyclophosphamide combination chemotherapy in the treatment of advanced refractory primary cutaneous T-cell lymphoma

BACKGROUND: The combination of fludarabine and cyclophosphamide shows synergistic toxicity in vitro and has been used to treat nodal non-Hodgkin's lymphoma and relapsed chronic lymphocytic leukaemia. OBJECTIVES: To test the efficacy of this combination in 12 patients with cutaneous T-cell lymphoma (CTCL). METHODS: Nine patients with erythrodermic CTCL were identified for the study, eight of whom met the criteria for Sézary syndrome (SS), and three with tumour-stage mycosis fungoides (MF). Patients received intravenous fludarabine and cyclophosphamide 3 days monthly for 3-6 months. RESULTS: Six patients tolerated at least three cycles. Five with SS had a response (one had a complete clinical response and four a partial response) and one patient with MF had stable disease. The mean duration of the response was 10 months. Six patients had treatment withdrawn, five due to bone marrow suppression and one due to progressive disease. No difference in pretrial parameters were found in those who had treatment withdrawn and those who tolerated at least three courses. Survival since the trial was similar in both groups at 11 months. CONCLUSIONS: These data indicate that the combination of fludarabine with cyclophosphamide may be of clinical benefit in patients with SS but does not affect patient survival. As with other multiagent chemotherapy regimens, bone marrow toxicity is a common and severe side-effect. These data suggest that this regimen should be considered palliative and should be reserved for patients with refractory disease without bone marrow suppression.     

UVA1 phototherapy for disseminated granuloma annulare

BACKGROUND/PURPOSE: Disseminated granuloma annulare is a benign granulomatous skin disease of unknown etiology. Recently, UVA1 (340-400 nm) phototherapy has been found effective in a small series of four patients. The purpose of this two-center study was to determine the rate and duration of clinical response to UVA1 phototherapy in a larger cohort of 20 patients with disseminated granuloma annulare. METHODS: Twenty patients with long-standing, stable disease (median 42 months, 95% CI 23-105) underwent UVA1 phototherapy. Sixteen patients were treated with a high-dose regimen (median single dose 110 J/cm2, 95% CI 103-121) and four patients with a medium-dose regimen (median single dose 50 J/cm2, CI 50-50). The clinical response was graded on a 5-point scale [0 = none, 1 = poor, 2 = moderate, 3 = substantial, 4 = (near) complete]. After cessation of therapy, patients with a clinical score of 3 or 4 were followed up to evaluate the duration of clinical improvement. RESULTS: At the end of treatment, five patients each had substantial improvement or (near) complete clearance. Another five patients had a moderate response, three patients were considered as poor responders and two patients as treatment failures. Out of the 10 patients with good or excellent response nine were available for follow up. Of these, two patients were still clear after 3 and 6 months, and seven patients relapsed after a median of 3 months (95% CI 1.68-6.46). CONCLUSIONS: UVA1 phototherapy provided good or excellent results in half of our 20 patients with disseminated granuloma annulare. In the majority of patients with a satisfactory response, however, discontinuation of treatment was followed by early recurrence of disease.     

A dose-finding study of azithromycin in the treatment of acne vulgaris

This open, multicenter, comparative, randomized study included 120 subjects with papulopustular stage of acne vulgaris. Subjects were randomized to one of the three treatment groups (A, total dose 4.5 g of azithromycin in 7 weeks; B, total dose 6.0 g in 10 weeks; and C, total dose 7.5 g in 13 weeks). The aim was to identify the optimum azithromycin dose in the treatment of acne vulgaris through monitoring the efficacy and safety of three dosage regimens. Clinical efficacy was assessed upon completion of study therapy and six months of therapy initiation. Post-therapeutic efficacy assessment was available in 104 subjects. The difference between three treatment groups was most pronounced in the "cure" category (36.11% in group A, 58.82% in group B and 55.88% in group C) and "failure" category (8.33% in group A, and no failures in groups B and C). Follow up efficacy assessment was available in 87 subjects. The group percentage of "cure" was lower and group percentage of "treatment failure" higher in group A than in groups B and C. Azithromycin in a total dose of 6.0 g in 10 weeks seems to be a promising agent in the treatment of papulopustular acne vulgaris with few side effects and good patient compliance.     

Clinical response to antibiotic regimens in lower limb cellulitis: a systematic review

There is variation in the treatment of lower limb cellulitis (LLC) with no agreement on the most effective antibiotic regimen. Many patients with cellulitis fail to respond to first‐line antibiotics. This can negatively affect patient care and result in unnecessary hospital admissions. The aim of this systematic review was to determine the clinical response and safety of antibiotic regimens for the management of LLC. A systematic review for randomized controlled trials (RCTs) was conducted using OVID MEDLINE, Ovid Embase and Cochrane Central Register of Controlled Trials in January 2019. Outcomes of interest included the clinical response to antibiotic regimens (type, dose, route, duration) and the safety of antibiotics in LLC. Trial quality was identified using the Cochrane Risk of Bias tool. Four RCTs were included. All included studies showed no significant differences between the clinical response to different antibiotic type, administration route, treatment duration or dose. LLC may be overtreated and shorter courses of oral antibiotics, possibly with lower doses, may be more suitable. There is a lack of published data on the clinical response and safety of antibiotics in LLC. Three studies were high risk for bias overall. Further high‐quality studies may help determine whether less intensive antibiotic regimens can effectively treat LLC.