A comparative clinico-pathological study of single dose ROM in paucibacillary leprosy patients with 1-3 skin lesions

A controlled clinical and histopathological study 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 a single dose with that of standard WHO/MDT-PB six months' regimen with regard to resolution of lesion clinically and histopathologically. Skin biopsy was performed at the intake and at 6 months. The study subjects were 32 previously untreated, smear-negative patients, without nerve trunk involvement and having 1-3 skin lesions. The results were analyzed for mean clinical score for marked, moderate and no improvement and mean histopathological score was graded as active, resolving and complete resolution, according to granuloma fraction at the end of 6 months. Marked clinical improvement was seen in 25% and 12%, moderate improvement in 50% and 56% patients treated with ROM and standard regimens respectively. Histopathologically, activity was seen in 62.5% and 43.7% and resolution of granuloma in 25% and 31.2% in the ROM and standard regimens respectively. Both the regimens were equally efficacious in the reduction of clinical score and granuloma fraction. No adverse drug reactions or reversal reactions were seen during the study period in both the groups.     

Lesional characteristics and histopathology in paucibacillary leprosy patients with 2 or 3 skin lesions: comparison between ROM and PB-MDT regimens

Paucibacillary (PB) patients form a large segment of newly diagnosed leprosy patients and those who present with only two or three skin lesions could have problems with compliance. With prolonged anti-leprosy drug regimens that last over six months. ROM therapy, a one-dose regimen, offers an attractive alternative in treating such patients. We conducted a longitudinal study of 51 such PB patients, placing them in two groups at random: one receiving the standard PB-MDT regimen, and the other the ROM regimen. Patients were followed up for 2 years, with a comprehensive clinical examination done every six months. 14 patients, 7 in each group, also had their skin biopsies evaluated histopathologically at recruitment, at 6 months and at the end of 2 years. There was a consistent improvement of lesions in both the groups over time. The fall in granuloma fraction and the clearance of the initial bacterial index were seen in the histopathology of both groups. Although the PB-MDT regimen is an effective and robust one, the operational convenience and drug compliance with ROM could make it an acceptable, parallel regimen for PB patients when the disease is localized to 2 or 3 skin lesions.     

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.     

Chemotherapy trial in paucibacillary leprosy using clofazimine

In a double blind study, 300 PB patients (smear negative, indeterminate, tuberculoid and borderline tuberculoid) were randomly allotted to two regimens, the control subjects (150 patients) receiving the standard WHO multidrug regimen of six doses of once a month rifampicin with daily dapsone therapy for six months, while the study group (150 patients) receiving 50 mg of clofazimine daily for six months in addition to the WHO regimen. After stoppage of therapy all the patients were followed up on placebo. The regimens were well tolerated. In 7.5% of patients on clofazimine containing regimen, the lesions showed persisting activity at the time of stoppage of therapy, compared with 16% on the control regimen. This activity subsided spontaneously, more rapidly, in the study group (80% compared with 30% in the control group) in six months. Two patients in the control group and one patient in the study group developed late reaction. There were no relapses in the study group, whereas, two patients have relapsed in the control group during a follow-up of 2.5 to 3.5 years.     

Effectiveness of multidrug therapy in multibacillary leprosy: a long-term follow-up of 34 multibacillary leprosy patients treated with multidrug regimens till skin smear negativity

The World Health Organization (WHO) Field Trials of multidrug therapy (MDT) started at Schieffelin Leprosy Research and Training Centre (SLR & IC), Karigiri, India in December 1981. The patients were treated with two MDT regimens. The first (regimen A) consisted of 600mg rifampicin and 300mg of clofazimine given under supervision on 2 consecutive days monthly, 225mg injection of acedapsone bimonthly and dapsone 100mg daily. The second regimen (regimen B) was the conventional MDT (WHO/MDT), rifampicin 600mg and clofazimine 300mg supervised once a month, dapsone 100mg and clofazimine 50mg daily, unsupervised. Both the regimens were administered for a minimum period of 2 years or until skin smear negativity, whichever occurred later. Thirty-four newly detected previously untreated MB patients, 16 of whom received regimen A and 18 regimen B, were reassessed. Both regimens were well accepted and well tolerated by the patients. Clofazimine discolouration was the only adverse effect of MDT seen in these patients. After completion of treatment with MDT, the patients were followed up for a total duration of 466 person-years with a mean of 13.7 +/- 1.4 years per patient. No relapse was seen.     

Once monthly rifampicin (1200 mg) plus daily dapsone (100 mg) and clofazimine (100 mg) in the initial treatment of lepromatous leprosy

The therapeutic effect of rifampicin 1200 mg once monthly and 100 mg clofazimine daily for the first six months of treatment was evaluated in 30 patients of bacteriologically positive lepromatous leprosy patients. Moderate to marked clinical improvement was seen in all the patients and a very rapid bacteriological regression as indicated by the decrease in bacteriological and morphological indices of the skin within one week. Seven patients become MI negative at one month and three months and 13 at the end of nine months. Two patients became MI and BI negative at the end of six months and six at the end of nine months. These observations clearly establish the high therapeutic efficacy and practicability of the three drug regimen. Once monthly rifampicin is highly effective and well tolerated, and has many advantages like low cost, better patient compliance and reliability of the treatment. Addition of clofazimine to rifampicin and dapsone prevents the emergence of E.N.L. reactions which were seen during treatment with once monthly rifampicin and daily dapsone. This regimen is thus ideal for initial, intensive treatment of lepromatous leprosy and may help in preventing the spread of the disease and development of dapsone resistance.     

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.     

Comparison of Bacillary Index on Slit Skin Smear with Bacillary Index of Granuloma in Leprosy and its Relevance to Present Therapeutic Regimens

Background:

As the world moves toward elimination of leprosy, persistence of infective cases in endemic pockets remains a significant problem. The use of clinical criteria to decide the paucibacillary (PB) versus multibacillary (MB) regimens has greatly simplified therapy at the field setting. However, a small but significant risk of under-treatment of so-called “PB” cases which actually have significant bacillary load exists. This study was undertaken to assess this risk and compare two methods of assessment of bacillary load, namely bacillary index on slit skin smear (BIS) versus bacillary index of granuloma (BIG).

Aims:

To compare BIS with BIG on skin biopsy in consecutive untreated cases of leprosy.

Materials and Methods:

This prospective study was conducted over a period of 12 months, wherein new untreated patients with leprosy were consecutively recruited. After a thorough clinical examination, each patient underwent slit skin smear (SSS) where the BIS was calculated. The same patient also underwent a skin biopsy from a clinical lesion where, the BIG was calculated. SSS and skin biopsy for BIS and BIG respectively were repeated for all patients at the end of therapy for comparison. All patients received therapy according to World Health Organization-Multidrug Therapy Guidelines.

Results:

The BIG was positive in all cases where the BIS was positive. Significantly, BIG was positive in three cases of borderline tuberculoid leprosy with <5 lesions who received PB regimen, whereas the BIS was negative in all three cases.

Conclusion:

This study suggests that BIG may be a better indicator of the true bacillary load in leprosy as compared to BIS. Its role in management is significant, at least in tertiary care centers to prevent “under-treatment” of so called PB cases, which may actually warrant MB regimens.     

Paucibacillary leprosy: a comparative study of different schedules of multidrug therapy

The study was undertaken to evaluate the efficacy of various multidrug regimens (MDT). Three groups of 10 cases each of Paucibacillary cases were given different schedule of multidrug therapy. First group (T-0) was administered modified WHO regimen consisting of Rifampicin 600 mg once a month, Clofazimine 100 mg alternate days and Dapsone 100 mg daily for 6 months. In second group (T-1) Rifampicin 600 mg was given daily for 6 weeks and in third group (T-2) Rifampicin 600 mg was given daily for 6 months. In both the latter groups Clofazimine 100 mg on alternate days and Dapsone 100 mg daily was also administered for 6 months. Objective clinical scoring was done at the time of admission, three months and six months after treatment in all three groups. The best results were obtained by T-2 followed by T-1; and least effective was T-0 regimen. Pinkish colour of urine and skin was observed in 26 cases and icthyosis in all the cases. All the patients remain under treatment. The work is in progress and subsequent results will be published later.     

Relapse rate in paucibacillary leprosy patients after multidrug therapy in North Arcot District

Surveillance data from 14,227 paucibacillary (PB) patients who had been released from treatment one year earlier, after completing multidrug therapy (PB regimen) for 6 to 12 months, were analysed to assess relapse rates and the influence of three variables, viz., number of lesions, nerve involvement and duration of treatment. The overall relapse rate at one year of surveillance was acceptably low at 0.34%. Relapse rates were about four times higher when there were many (4-9) lesions, or, when nerve was involved (0.80% cf 0.20%). Extending the duration of treatment beyond 6 months did not reduce the relapse rates significantly in the high risk groups. Detection of PB cases early, before these risk factors become operative, and treating them with MDT would appear to be the best strategy to minimize relapse rates.     

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.     

Erfolgreiche symptomatische Tazarotentherapie der juvenilen Acanthosis nigricans vom familiär adipositasassoziierten Typ bei Insulinresistenz

An 11-year-old boy suffering from morbid obesity since infancy developed at age 9 a progressive brown-black hyperpigmentated and hyperkeratotic eruption in the neck and axillary region with minor involvement of both groins. Based on this clinical picture, and confirmed by histopathology, we diagnosed acanthosis nigricans. Following a thorough endocrinological examination and because the patient's obese mother showed similar skin lesions, the disease was subclassified as a familial obesity-associated type of acanthosis nigricans associated with insulin resistance. In a right-left-comparison the affected skin of one body side was treated with tazarotene 0.05% versus urea 10%, once daily each. A great benefit for the tazarotene-treated over the opposite side could already be seen after three weeks which was also verified by dermatohistopathology. Three months after topical tazarotene treatment had been extended to both sides, the residual lesions were significantly improved. The highly satisfying, good result has been maintained up to now by a continuous topical retinoid treatment over 18 months, usually with an interval application regimen, i.e., 3× per week.     

Evaluation of leprosy patients with 1 to 5 skin lesions with relevance to their grouping into paucibacillary or multibacillary disease

BACKGROUND: Patients with 1 to 5 skin lesions are arbitrarily categorized as belonging to the paucibacillary (PB) group for treatment purposes. With the decreasing prevalence of leprosy in India and modifications in leprosy program, the relevance of this grouping needs further study. AIMS: To study a group of leprosy patients with 1 to 5 skin lesions and compare the clinical parameters with histopathological findings and bacteriological status of the skin and nerve to evaluate the relevance of this grouping. METHODS: Seventy seven patients of leprosy with 1 to 5 skin lesions were included in the study. The number of skin lesions was recorded. Slit skin smears (SSS) and skin biopsies were taken in all patients and nerve biopsy was performed in 19 of them. The biopsies were evaluated for the type of pathology and AFB status. RESULTS: In these 77 patients (single skin lesions, 42; two lesions, 18; three lesions, 10; four lesions, 5; and five lesions, 2 patients) the clinical classification was indeterminate leprosy (IL) in 4, tuberculoid leprosy (TT) in 4 patients and borderline tuberculoid leprosy (BT) in 69 patients. Skin smears were positive only in 1 patient. The histological diagnoses in the skin were IL in 13, TT in 3, BT in 48 and borderline lepromatous (BL) in 4 patients. Acid-fast bacilli (AFB) were found in 14 out of 77 skin biopsies. Of the 19 nerve biopsies, 17 showed histological features of BT leprosy; of these, 12 demonstrated AFB on Fite staining. The bacillary index of granuloma (BIG) ranged from 1+ to 2+. The clinico-histopathogical correlation was 63% in the BT group, with 4 patients of this group showing features of BL on histopathology. When the presence of AFB was assessed, the percentage of positivity was 1.3% in SSS, 18% in skin biopsies and 63% in nerve biopsies. CONCLUSION: Our results point to the non-homogeneous nature of this group of leprosy patients with 1 to 5 skin lesions, with varied bacteriological and histopathological features. The significance of MB type findings on histopathology in patients grouped as PB leprosy should be resolved so that these patients may be given the drug therapy and the duration of therapy they warrant.     

Evaluation of two multidrug regimen in hospitalised multibacillary cases

Fifty three multibacillary leprosy cases were treated with two regimens of MDT L1 consisting of Rifampicin, Dapsone and Ethionamide and L2 consisting of Rifampicin, Dapsone and clofazimine. The results were compared at regular intervals and at the end of the study (24 months). Clinical inactivity, bacteriological negativity, ENL reactions, upgrading reactions were seen in L1 group in 65%, 4.54%, 50% and 41% of cases respectively while 65%, 25.8%, 30% and 45% respectively in L2 regimen group. Zero percent morphological Index was achieved in all cases in L1 regimen 90% in L2 regimen cases. No viability was found on mouse foot pad inoculation after 6 months in L1 while after 18 months in L2 cases.     

Clinical, bacteriological and histopathological study of 62 referral relapse cases between Jan 2004 and Dec 2009 at the Foundation for Medical Research, Mumbai

Sixty two patients with relapsed leprosy seen between Jan 2004 and Dec 2009 were studied using clinical, bacteriological and histopathological parameters. The findings thus obtained were correlated to parameters such as trend and source of referral, clinical characteristics at diagnosis, treatment received, other events during or after RFT and duration between cessation of treatment and relapse. FINDINGS: Referrals per year have doubled since 2006. Most patients were referred by NGOs (58%), followed by Govt. hospitals (16%) and then by GPs (25%); 76% had received one of the WHO - MDT regimens including 16 treated with 24 months or more MB - MDT, 23 with 12 months MB - MDT and eight with 6 months PB - MDT. Of the remaining 14 cases, four had received DDS mono-therapy, seven had single dose of Rifampicin, Ofloxacin and Minocycline (ROM) and four Rifampicin and Ofloxacin (RO) daily for 28 days. The average incubation time of relapse, defined as duration between cessation of treatment and relapse was (SD) + 6-4 years. 59% of patients had positive slit skin smears on relapse. Relapse for the second time occurred in six BL cases including five from group 2 and one RO treated patient and 11/23 cases from group 2 conferred to BT-BB leprosy. Clinical features at diagnosis and on relapse were comparable in 47% of cases. CONCLUSION: All leprosy patients, regardless of their type and MDT regime, carry 'risk of relapse'. A shorter treatment duration reduces the incubation time to relapse. In group 2 (treated with 12 months MB-MDT regime) 11/23 were BT-BB cases and 5/23 (21%) were relapse for the second time, which further supports our earlier documented findings and maybe the efficacy of WHO-MDT regime is poor in a small subset of patients.     

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.     

In vivo porphyrin production by P. acnes in untreated acne patients and its modulation by acne treatment

Propionibacterium acnes is often discussed as a contributing pathogenic factor in the aetiology of acne lesions. The aim of this study was to test which porphyrin patterns are synthesized by P. acnes in vivo in untreated acne patients and during standard acne regimens. These photosensitive compounds are potential targets for photo-dynamic therapy of acne and need to be better characterized in the skin. Using high-performance liquid chromatography coproporphyrin III was the main porphyrin identified in all patients. Coproporphyrin I and protoporphyrin were found at considerably lower concentrations. When the porphyrin concentration of individual patients receiving isotretinoin was analysed repeatedly over time, clinical improvement was associated with lowered levels of porphyrins. Statistical analysis demonstrated a significant reduction in the porphyrin fractions only in the isotretinoin group which was associated with clinical improvement 2 months after starting therapy.     

Severe chronic actinic dermatitis treated with cyclosporine: 2 cases

INTRODUCTION: The treatment of the severe forms of photodermatoses often requires potent systemic immunosuppressive drugs. We report two patients suffering from severe photodermatitis successfully treated with oral cyclosporine. CASES REPORT: A 58-year-old man developed severe pruritic eczematous reactions for several years on light-exposed and light-protected skin following each sun exposure. A 66-year-old man showed similar lesions restricted to the head and neck. The clinical presentation and evolution as well as histologic, immunohistologic, allergologic and photobiologic assessments suggested the diagnosis of actinic reticuloid and persistent light reactivity, respectively. The lesions of both patients did not respond to a high dose regimen of systemic corticosteroids (methylprednisolone 1 mg/kg/day) for several weeks. The severity of cutaneous lesions and pruritus required another potent immunosuppressive treatment. Oral cyclosporine at the maximum daily dose of 4 mg/kg was given for three months. A rapid improvement of the pruritus and skin lesions occurred in the two patients, without significant side-effect. The first patient experienced recurrent lesions after termination of cyclosporine treatment during summer time. The other patient did not develop new skin eruption for 3 years after stopping the initial treatment with cyclosporine. DISCUSSION: Low-dose oral cyclosporine is a quick-acting and well tolerated symptomatic treatment of severe photodermatoses resistant to other systemic immunosuppressive drugs. However, therapeutic results do not consistently exhibit long-standing remanent effect.     

Efficacy and safety study of two zinc gluconate regimens in the treatment of inflammatory acne

This double-blind study was conducted on 67 patients with inflammatory acne who received one of two zinc gluconate regimens (Rubozinc) for three months. One was a constant-dose regimen and the other included an initial three-week loading dose, but both regimens provided the same cumulative dose at three months. The primary assessment criteria was the change with respect to baseline in the total number of superficial inflammatory lesions (papules and pustules). The two treatment groups were not statistically significantly different, with respect to this criteria, after three, five, seven or thirteen weeks of treatment. Therefore, the regimen that included a loading-dose provided no additional benefit. The results of this study are in favor of the conventional therapeutic regimen of two capsules daily for three months, as defined in the marketing authorization.     

Effectiveness of ketotifen in the treatment of neurodermatitis in childhood

17 children suffering from neurodermatitis, aged 2 to 14 years, were treated with ketotifen at a dosage of 1 mg twice daily. In 7 children polyvalent therapy was given. Ketotifen therapy produced a pronounced alleviation of the itching within only two weeks and the patients became entirely itching free after 20 days on an average. The improvement of skin lesions appeared after two months of treatment. Patients became entirely skin lesions free between seven and nine months. In three patients the deterioration of skin lesions was triggered with infection. With regard to long-lasting of Ketotifen therapy, the side effects were not observed.