Minocycline successfully treats exaggerated granulomatous hypersensitivity reaction to Mw immunotherapy.

Mycobacterium W (Mw) vaccine has been found to be effective in the treatment of leprosy and warts. Despite increasing use of Mw immunotherapy, data on its safety is limited. We report a series of eight patients who developed persisting injection site granulomatous reaction following Mw immunotherapy and were successfully treated with minocycline. Eight patients with persistent nodular swelling at the site of Mw injections were identified. Seven of them had received Mw immunotherapy for cutaneous warts and one for verrucous epidermal nevus. The lesions were firm, erythematous, succulent, non-tender nodules confined to the sites of Mw vaccine injections. In 6 of these patients nodules also involved the previously injected areas. Skin biopsy from all patients showed eosinophil rich inflammation admixed with histiocytes and lymphocytes. In addition granulomas were seen in all with septal and nodular panniculitis in four patients. Broken and granular acid-fast bacilli were identified in two cases. All patients were treated with oral minocycline 100 mg/day for a mean of 9 weeks and showed good clinical response. Granulomatous reaction is a rare but significant adverse effect of Mw immunotherapy at cosmetically and functionally imperative sites. Oral minocycline appears to be effective therapy in this situation.

Monthly rifampicin, ofloxacin, and minocycline therapy for generalized and localized granuloma annulare.

BACKGROUND: The localized form of granuloma annulare is usually self-limiting, resolving within 2 years. Generalized granuloma annulare, on the other hand, runs a protracted course, with spontaneous resolution being rare. It is also characterized by a later age of onset, an increased incidence of diabetes mellitus, poor response to therapy, and an increased prevalence of HLA Bw35. OBJECTIVE: To assess the efficacy of monthly pulsed rifampicin, ofloxacin, and minocycline (ROM) therapy in the management of granuloma annulare. METHODS: Six biopsy proven patients of granuloma annulare were included in the study, five of the generalized variety, and one localized. Three of these patients were resistant to standard modalities of treatment. All six patients were treated with pulses of once monthly ROM till complete resolution of all lesions. Results were analyzed in terms of complete resolution of lesions and side effects. Presence of comorbid conditions was noted. RESULT: All six patients were successfully treated with 4-8 pulses of monthly ROM. None of the patients reported any adverse effects. LIMITATIONS: Small sample size and the lack of a control group are limitations. CONCLUSION: Treatment with pulses of once monthly ROM caused complete resolution of lesions in both localized and generalized granuloma annulare, even in cases recalcitrant to conventional therapy. There were no side effects in any of the patients. Larger trials are needed to substantiate the efficacy of monthly ROM in granuloma annulare.

Randomized controlled study to evaluate the effectiveness of dexamethasone oral minipulse therapy versus oral minocycline in patients with active vitiligo vulgaris.

BACKGROUND: Oral minocycline has been recently shown to halt disease progression in active vitiligo. AIMS: The present study was planned to compare the efficacy and tolerability of oral minocycline with oral mini pulse (OMP) corticosteroids in active vitiligo. METHODS: A total of 50 patients with actively spreading vitiligo were randomized to receive either minocycline 100 mg/day (Group I-25 patients) or OMP 2.5 mg dexamethasone on 2 consecutive days in a week (Group II-25 patients) for 6 months. These were followed-up at every 2 weeks interval. Mean vitiligo disease activity score (VIDA) and mean Vitiligo Area Scoring Index (VASI) were assessed in all patients in addition to the photographic comparison before and after treatment. RESULTS: Both groups showed a significant decrease in VIDA from 4.0 to 1.64±0.86 (P<0.001) in Group I and from 4.0 to 1.68±0.69 (P<0.001) in Group II. However, the difference between the mean VIDA scores in the two groups was not statistically significant (P=0.60) at the end of treatment period. The mean VASI declined from 1.71±1.45 to 1.52±1.43 Group I (P=0.06) and from 1.39±1.31 to 1.17±1.34 in Group II (P=0.05). The difference between VASI in Group I and II was not significant at the end of 24 weeks of treatment (P=0.11). CONCLUSION: Both dexamethasone OMP and oral minocycline are effective drugs for managing the arrest of disease activity in vitiligo.

A case of Hansen Disease presenting as tinea versicolor.

Hansen Disease (leprosy) is an infectious disease that targets macrophages and Schwann cells, caused by the acid fast intracellular organism, Mycobacterium leprae. Clinically, it presents with a spectrum of findings that may include hypopigmented macules, erythematous plaques and nodules, and thickened or tender peripheral nerves. The most feared complication is mutilating damage to facial structures or digits resulting from loss of sensation in affected skin. In non-endemic areas, the diagnosis of leprosy is frequently delayed because it may mimic other more common skin conditions. We present a case of borderline/lepromatous leprosy in an otherwise healthy young Brazilian man that was initially diagnosed as tinea versicolor, but did not respond to appropriate treatment. This case highlights the importance of having a high index of suspicion for leprosy in patients from endemic areas who present with lesions that could be consistent with this disease.

Adverse effects of alternative therapy (minocycline, ofloxacin, and clofazimine) in multibacillary leprosy patients in a recognized health care unit in Manaus, Amazonas, Brazil.

BACKGROUND: After the introduction of the multidrug therapy, there was a decline in the coefficients of prevalence and detection of new cases of leprosy. However, the records of drug resistance and relapses are threatening factors in leprosy control. Hence, new alternative schemes and monitoring of adverse effects to avoid treatment abandonment are important considerations. OBJECTIVE: Describe the side effects of a multidrug regimen containing minocycline, ofloxacin, and clofazimine in multibacillary leprosy patients. METHODS: We conducted a prospective, descriptive, and observational study with multibacillary patients, including cases of intolerance to standard MDT and relapses. The study was carried out at Fundação Alfredo da Matta (Alfredo da Matta Foundation), in Manaus, Amazonas, from April 2010 to January 2012. The patients received alternative therapy, which consisted of daily self-administered doses of 100mg of minocycline, 400 mg of ofloxacin, and 50mg of clofazimine and a supervised monthly dose of 300mg of clofazimine for six months, followed by eighteen months of daily doses of ofloxacin 400mg, clofazimine 50mg, and a supervised monthly dose of clofazimine 300mg. RESULTS: Twenty-one cases were included. Mild and transitory side effects occurred in 33.3% of patients. Of the total episodes, 45.9% were attributed to ofloxacin and they included abdominal pain, nausea, vomiting, headache, and insomnia; 21.6% were due to clofazimine, with 100% of patients presenting skin pigmentation. The mean time for the development of adverse effects after beginning the therapy was 15.2 days. CONCLUSION: All patients tolerated the drugs well, and compliance was satisfactory, with no serious events. Unlike other standard MDT studies had shown, no treatment was stopped due to side effects. Nevertheless, patient follow-up and studies with bigger samples are necessary to guarantee the efficacy and safety of the alternative regimen as a second-line scheme in multi-drug therapy.

Adverse effects of alternative therapy (minocycline, ofloxacin, and clofazimine) in multibacillary leprosy patients in a recognized health care unit in Manaus, Amazonas, Brazil / Efeitos adversos das drogas (minociclina, ofloxacina e clofazimina) utilizadas no esquema alternativo para pacientes com hanseníase multibacilar, em unidade de referência, Manaus, Amazonas, Brasil

BACKGROUND: After the introduction of the multidrug therapy, there was a decline in the coefficients of prevalence and detection of new cases of leprosy. However, the records of drug resistance and relapses are threatening factors in leprosy control. Hence, new alternative schemes and monitoring of adverse effects to avoid treatment abandonment are important considerations. OBJECTIVE: Describe the side effects of a multidrug regimen containing minocycline, ofloxacin, and clofazimine in multibacillary leprosy patients. METHODS: We conducted a prospective, descriptive, and observational study with multibacillary patients, including cases of intolerance to standard MDT and relapses. The study was carried out at Fundação Alfredo da Matta (Alfredo da Matta Foundation), in Manaus, Amazonas, from April 2010 to January 2012. The patients received alternative therapy, which consisted of daily self-administered doses of 100mg of minocycline, 400 mg of ofloxacin, and 50mg of clofazimine and a supervised monthly dose of 300mg of clofazimine for six months, followed by eighteen months of daily doses of ofloxacin 400mg, clofazimine 50mg, and a supervised monthly dose of clofazimine 300mg. Results: Twenty-one cases were included. Mild and transitory side effects occurred in 33.3% of patients. Of the total episodes, 45.9% were attributed to ofloxacin and they included abdominal pain, nausea, vomiting, headache, and insomnia; 21.6% were due to clofazimine, with 100% of patients presenting skin pigmentation. The mean time for the development of adverse effects after beginning the therapy was 15.2 days. CONCLUSION: All patients tolerated the drugs well, and compliance was satisfactory, with no serious events. Unlike other standard MDT studies ...

FUNDAMENTOS: Após introdução do esquema poliquimioterápico padrão, houve declínio nos coeficientes de prevalência e detecção de casos novos; entretanto, os registros de resistência medicamentosa e recidivas representam ameaça para o controle da hanseníase. Dessa forma, a proposição de novos esquemas alternativos e a necessidade de monitorar efeitos adversos são importantes para evitar o abandono do tratamento. OBJETIVO: Descrever efeitos adversos do esquema alternativo contendo clofazimina, ofloxacina e minociclina em pacientes com hanseníase multibacilar. MÉTODOS: Estudo prospectivo, descritivo e observacional de casos multibacilares, incluindo recidivas ou intolerância à poliquimioterapia padrão, realizado na Fundação Alfredo da Matta, Manaus, Amazonas, de abril de 2010 a janeiro de 2012. Os indivíduos receberam a terapia composta de doses diárias auto-administradas de 100mg de minociclina, 400mg de ofloxacina e 50mg de clofazimina e mensais supervisionadas de 300mg de clofazimina por seis meses, seguidas de 18 meses de doses diárias de ofloxacina 400mg, clofazimina 50 mg e supervisionadas mensais de clofazimina 300mg. Resultados: 21 pacientes foram incluídos. Efeitos adversos leves e transitórios foram observados em 33,3% dos pacientes; 45,9% foram atribuídos à ofloxacina, como dor abdominal, náuseas, vômitos, cefaléia e insônia; 21,6% foram associados à clofazimina, com relatos e observação em 100% dos pacientes de hiperpigmentação cutânea. O tempo médio de desenvolvimento das reações adversas a partir do início do esquema foi de 15,2 dias. ...

Histoid leprosy: case report.

Histoid leprosy is a rare but well-defined entity with specific clinical, histopathologic, and bacteriologic features. We present a case of histoid leprosy in an 84-year-old Egyptian male in view of the rarity of this condition. The patient presented with erythematous itchy discrete and coalescent papules that were distributed bilaterally and symmetrically on the front and back of the trunk. Before approaching us, he was initially misdiagnosed as a case of pityriasis rosea. There was no mucosal or facial affection and the patient's general examination was normal. Routine hematologic investigations, urine analysis, liver and renal function tests were all normal. Slit skin smear revealed acid-fast bacilli of BI - 6+ and MI - 50-60%. Histopathologic examination of hematoxylin and eosin-stained section revealed atrophic epidermis with flattened rete ridges and dermal infiltration by nodular granulomata formed of spindle shaped histiocytes with pyknotic nuclei oriented in a storiform pattern. Fite's stain for lepra bacilli showed plenty of acid fast bacilli. So, the diagnosis of histoid leprosy was made. Therefore, ROM therapy (rifampicin 600 mg, ofloxacin 400 mg, minocycline 200 mg) was started and followed by multi-drug therapy for 2 years.

Efficacy of single-dose chemotherapy (rifampicin, ofloxacin and minocycline-ROM) in PB leprosy patients with 2 to 5 skin lesions, India: randomised double-blind trial.

UNLABELLED: We conducted randomized double-blind trial for single-dose of Rifampicin, Ofloxacin and Minocycline (ROM) compared to WHO-PB-MDT among paucibacillary (PB) leprosy patients with 2-5 skin lesions. We enrolled 1526 patients from five centres (ROM=762; WHO-PB-MDT=764) and followed them for 36 months posttreatment during 1998-2003. We generated information on clearance of skin lesions and relapse rates per 100 person-years (PY) for all the five centres. At base-line, the patients in the two arms were comparable. Complete clearance of skin lesions was similar (72% vs. 72.1%; p=0.95) in both the arms. Clinical scores declined steadily and equally. Difference in relapse rates was statistically highly significant (ROM=1.13 and WHO-PB-MDT=0.35 per 100 PY; mid-p exact=0.001016). Twenty eight of 38 of these relapses occurred within 18 months. In all, 10 suspected adverse drug reactions were.observed (ROM=2; WHO-PB-MDT=8). We extended the follow-up to 48 months for 1082 of 1526 patients from two programme-based centres. No further relapses occurred. Decline in clinical score was not dependent on age, gender, number of lesions or affected body parts. Single dose ROM, though less effective than the standard WHO-PB-MDT regimen conceptually offers an alternative treatment regimen for PB leprosy patients with 2-5 lesions only when careful follow-up for relapse is possible. Registered at the Clinical Trials Registry of India; REGISTRATION NUMBER: CTRI/2012/05/002645

Is there a role for rifampicin, ofloxacin and minocycline (ROM) therapy in the treatment of leprosy? Systematic review and meta-analysis.

BACKGROUND: A combination of rifampicin, ofloxacin and minocycline (ROM) is one of the newer recommendations for treatment of leprosy. We performed a systematic review and a meta-analysis of studies that had evaluated the efficacy of ROM therapy in treatment of paucibacillary and multibacillary leprosy patients. METHODS: Studies were identified by searching the PubMed, Embase, LILACS and Cochrane databases. Data were abstracted from all relevant studies, and fixed effects models were used to calculate the summary estimate of effect in paucibacillary and multibacillary leprosy patients. RESULTS: Six studies comparing ROM therapy to multidrug therapy and eight studies that evaluated the effect of ROM therapy alone (no comparison group) were included in the review and meta-analysis. The combined estimate for single dose ROM vs. multidrug therapy in paucibacillary leprosy patients suggested that ROM was less effective than multidrug therapy in these patients [relative risk: 0.91, 95% confidence intervals (CI): 0.86-0.97]. However, the combined estimate for multiple doses of ROM vs. multidrug therapy in multibacillary leprosy patients suggested that ROM was as effective as multidrug therapy in reducing bacillary indices in these patients (proportion change: -4%, 95% CI -31% to 23%). No major side effects were reported in either the ROM or the multidrug treatment groups. CONCLUSIONS: Single-dose ROM therapy was less effective than multidrug therapy in paucibacillary patients. However, there are insufficient data to come to a valid conclusion on the efficacy of multidose ROM therapy in multibacillary leprosy, and additional studies with ROM therapy in multibacillary leprosy are needed. Furthermore, multiple doses may be considered as another alternative even for paucibacillary patients, and randomised controlled trials of this therapy may be useful to understand its contribution in the treatment and control of leprosy.

[Evaluation years in leprosy patients treated with single dose alternative scheme ROM (rifampin, ofloxacin, minocycline), after seven to nine]. / Avaliação de hansenianos tratados com esquema alternativo dose única ROM (rifampicina, ofloxacina e minociclina), após sete a nove anos.

INTRODUCTION: In 1997, after obtaining a combined multi-state double-blind randomly controlled clinical trial study from nine Indian centers involved in the treatment of Hansen's Disease, the Ministry of Health adapted the single dose ROM Therapy approach in those cases involving the treatment of a single skin lesion, paucibacillary leprosy without evidence of peripheral nerve trunk involvement and indication of negative baciloscope, in the Referral Centers in Brazil. The study aimed to evaluate the effectiveness of the single dose ROM Therapy approach in those patients who were treated from the period of 1997 to 1999 in the Ambulatory Dermatologic Unit in the Hospital in Vitória, ES. METHODS: Fifty-four patients with tuberculoid and indeterminate leprosy were selected and treated with the single dose ROM Therapy approach. These patients were contacted from March 2006 up and until October 2006 for further clinical reevaluation. RESULTS: From the studies conducted, the following results were found to exist: 29 patients (85,2%; 95%CI: 70-100,4) were cured, 5 patients (14,7%; 95%CI: 7,4-22,0) relapsed, and 20 patients didn't return; however, there are no additional records of any notification of other treatment(s) in the State Department of Health's informational data banks. CONCLUSIONS: The study demonstrated a rate of cure of 90.8% and a rate of relapse of 9.2% after a period of seven to nine years using the single dose ROM Therapy approach. Additionally, this alternative treatment further demonstrated a better effectiveness for a single skin lesion smaller than four centimeters and with an appearance in less than five years.

Avaliação de hansenianos tratados com esquema alternativo dose única ROM (rifampicina, ofloxacina e minociclina), após sete a nove anos / Evaluation years in leprosy patients treated with single dose alternative scheme ROM (rifampin, ofloxacin, minocycline), after seven to nine

INTRODUÇÃO: Em 1997, após a realização de estudo multicêntrico, duplo cego e randomizado, em nove centros de tratamento de hanseníase na Índia, o Ministério da Saúde adotou o esquema alternativo dose única ROM para casos de lesão única, paucibacilar, sem nervo periférico afetado, índice baciloscópico negativo, em Centros de Referência da doença no Brasil. O estudo se propôs a avaliar a efetividade do esquema ROM em pacientes tratados no período de 1997 a 1999 no Serviço de Dermatologia da Santa Casa de Vitória. MÉTODOS: Foram selecionados e tratados com o esquema ROM, 54 pacientes das formas indeterminada e tuberculóide. Estes pacientes foram convocados de março a outubro de 2006 para reavaliação clínica. RESULTADOS: Vinte e nove pacientes avaliados (85,2 por cento; IC95 por cento: 70-100,4) estavam curados, cinco (14,7 por cento; IC95 por cento: 7,4-22,0) recidivaram e 20 pacientes não retornaram; porém, não havia outra notificação de reingresso ao tratamento no banco de dados da Secretaria Estadual de Saúde. CONCLUSÕES: O estudo evidenciou taxa de cura de 90,8 por cento e taxa bruta de recidiva de 9,2 por cento, após período de sete a nove anos da dose ROM. O tratamento alternativo ROM demonstrou melhor efetividade para lesão única menor que quatro centímetros e aparecimento há menos de cinco anos.

INTRODUCTION: In 1997, after obtaining a combined multi-state double-blind randomly controlled clinical trial study from nine Indian centers involved in the treatment of Hansen's Disease, the Ministry of Health adapted the single dose ROM Therapy approach in those cases involving the treatment of a single skin lesion, paucibacillary leprosy without evidence of peripheral nerve trunk involvement and indication of negative baciloscope, in the Referral Centers in Brazil. The study aimed to evaluate the effectiveness of the single dose ROM Therapy approach in those patients who were treated from the period of 1997 to 1999 in the Ambulatory Dermatologic Unit in the Hospital in Vitória, ES. METHODS: Fifty-four patients with tuberculoid and indeterminate leprosy were selected and treated with the single dose ROM Therapy approach. These patients were contacted from March 2006 up and until October 2006 for further clinical reevaluation. RESULTS: From the studies conducted, the following results were found to exist: 29 patients (85,2 percent; 95 percentCI: 70-100,4) were cured, 5 patients (14,7 percent; 95 percentCI: 7,4-22,0) relapsed, and 20 patients didn't return; however, there are no additional records of any notification of other treatment(s) in the State Department of Health's informational data banks. CONCLUSIONS: The study demonstrated a rate of cure of 90.8 percent and a rate of relapse of 9.2 percent after a period of seven to nine years using the single dose ROM Therapy approach. Additionally, this alternative treatment further demonstrated a better effectiveness for a single skin lesion smaller than four centimeters and with an appearance in less than five years.

Granuloma annulare treated with rifampin, ofloxacin, and minocycline combination therapy.

BACKGROUND: Granuloma annulare (GA) is a benign, usually self-limiting, dermatosis, that typically presents as asymptomatic, flesh-colored or erythematous papules, frequently arranged in an annular or arciform pattern on the distal extremities. Although localized GA is most commonly observed, a generalized or disseminated form can occur. The etiology of GA is unknown; however, multiple inciting factors have been proposed. Histologically, GA is characterized by foci of degenerative collagen associated with palisading, sometimes infiltrating granulomatous inflammation. OBSERVATIONS: We report 6 cases with biopsy-proved GA, resistant to the standard modalities of treatment that resolved after 3 months with monthly rifampin (600 mg), ofloxacin (400 mg), and minocycline hydrochloride (100 mg) combination therapy. Rifampin, ofloxacin, and minocycline combination therapy has been successfully used to treat patients with paucibacillary leprosy. Given reports that prolonged antibiotic agents are a useful treatment for GA, rifampin (600 mg), ofloxacin (400 mg), and minocycline hydrochloride (100 mg) combination therapy was initiated in these patients. Complete clearance of the plaques was achieved 3 to 5 months after the initiation of treatment. Some patients experienced postinflammatory hyperpigmentation. CONCLUSION: Although our treatment was effective, further studies may be needed to confirm the success of this therapeutic option for patients with recalcitrant lesions of GA.

Serological response to chemoprophylaxis in extended contacts in leprosy--a randomized controlled trial.

Chemoprophylaxis was carried out on high risk group of extended contacts of new leprosy cases in Nyaungdon Township, Ayeyarwaddy Division, Myanmar and serological response was followed up for two years. In September 2003, blood samples were collected from 829 contacts after getting informed consent and sera were tested for immunoglobulin M antibodies using NTP-BSA ELISA test. These 300 seropositives were randomized to treated and non-treated groups. In each group 102 each were enrolled in adults and 48 each in children. A single dose of ROM (rifampicin, ofloxacin and minocycline) and RMP (rifampicin) by body weight was administered to treated group of above 15 years and those below 15 years respectively. The vitamins were administered to non-treated group. The blood samples of all contacts were collected again in September 2004 and September 2005 and ELISA was carried out on paired samples on one plate. The mean optical density (OD) titers before vs after chemoprophylaxis were 0.24 vs 0.10 and 0.20 vs 0.09 in treated and non-treated group respectively in adults and 0.25 vs 0.11 and 0.22 vs 0.11 respectively in children after one year. These were 0.24 vs 0.17 and 0.20 vs 0.19 respectively in adults and 0.25 vs 0.19 and 0.22 vs 0.20 respectively in children after two years. The difference of mean antibody titers before and after chemoprophylaxis in treated group was significantly reduced compared to non-treated group in adults but was not significant in children. The findings show that there is a significant role of chemoprophylaxis on serological response in the form of decreasing antibody titer among the adult group of extended contacts.

[Long-term follow-up of ofloxacin-combined therapy for leprosy patients].

This reports a long-term follow-up study on clinical effects of ofloxacin (OFLX)-combined therapy to 14 leprosy patients with various types and stages. Combined drugs were diaminodiphenyl sulfone (DDS), rifampicin (RFP) and clofazimine. Clinical evaluation of the treatment after OFLX-combined therapy was remarkable improvement 10 cases, improvement 3 and re-exacerbated after improvement 1 to whom clofazimine and minocycline were prescribed. The evaluation during the follow-up was remarkable improvement 10, improvement 1; three cases died of traffic accident or complications not related to chemotherapy and none of them showed relapse of leprosy. Bacterial negativity after onset of OFLX-combined therapy was achieved in about the same periods as RFP-combined therapy. OFLX-combined therapy was effective and safe. This follow-up study supports the efficacy of clinical guideline for the use of new quinolones published by Japanese leprosy Association.

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.