Regression and relapse

Immediately after leprosy treatment initiation, changes in leprosy lesions also commence. The histopathological and bacilloscopic characeristics of the regressing lesions undergo continuous changes over years of decades. It is important to recognize these changes as they allow for the assessment od whether a particular lesion is in regression or if there are signs of disease reactivation. Interpretation of the findings will depend on a close correlation among histopathological patterns, bacilloscopic characteristics, and clinical data. This chapter discusses the main factors that allow the recognition of the histopathological characteristics of regressive phenomena from initial phases to late or residual phases, the changes typical in effectiveness, the reaction phenomena triggered after treatment initiation on regressing lesions, and the evaluation of leprosy recurrence. Further, this chapter includes a discussion on the main differential diagnoses of leprosy regression and relapse.

Report on an unusual case of leprosy from Germany: just an exception of the rule?

CASE PRESENTATION: We report on a German leprosy patient originating from Pakistan who had a relapse more than 5 years after completion of multi-drug therapy (MDT) of his first episode of multibacillary (MB) leprosy. State-of-the-art laboratory techniques (histopathology, PGL-I serology, microscopy and DNA/RNA qPCR) were applied for laboratory confirmation and monitoring of treatment outcome. Serology indicated the relapse long before the presence of unambiguous clinical signs. At the time of diagnosis of the relapse the patient had a remarkably high bacterial load suggesting increased risk for a second relapse. Furthermore, unexpectedly prolonged excretion of viable bacilli through the upper respiratory tract for more than 3 months after onset of MDT was shown. Therefore, MDT was administered for 2 years. DISCUSSION AND CONCLUSIONS: The clinical course of the patient, as well as the prolonged excretion of viable bacilli, underlines the usefulness of laboratory assessment. Laboratory tools including up-to-date molecular assays facilitate rapid diagnosis, timely MDT, identification of individuals excreting viable bacilli and patients at risk for relapses, monitoring of treatment outcome and respective adaptation of treatment where appropriate.

Determining the best percent-predicted equation for estimated VO2 peak by a 1-km moderate perceptually-regulated treadmill walk to predict mortality in outpatients with cardiovascular disease.

OBJECTIVES: To determine the prognostic ability of established percent-predicted equations of peak oxygen consumption (%PRED) estimated by a moderate submaximal walking test in a large cohort of outpatients with cardiovascular disease (CVD). DESIGN: Population-based prospective study. METHODS: A total of 1442 male patients aged 25-85 years at baseline, underwent a moderate perceptually-regulated (11-13 on the 6-20 Borg scale) treadmill walk (1k-TWT) for peak oxygen consumption estimation (VO2 peak). %PRED was derived from ACSM, Ades et al, Morris et al, and the Wasserman/Hansen equations, and their prognostic performance was assessed. Overall mortality was the end point. Participants were divided into quartiles of %PRED, and mortality risk was estimated using a Cox regression model. RESULTS: During a median 8.2year follow-up, 167 all-cause deaths occurred. The Wasserman/Hansen equation provided the highest prognostic value. Mortality rate was lower across increasing quartiles of %PRED. Compared to the first quartile, after adjustment for confounders, the mortality risk decreased for the second, third, and fourth quartiles, with HRs of 0.75 (95% CI 0.44-1.29, p=0.29), 0.67 (95% CI 0.38-1.18, p=0.17), and 0.37 (95% CI 0.10-0.78, p=0.009), respectively (p for trend <0.0001). Each 1% increase in %PRED conferred a 4% improvement in survival. CONCLUSIONS: The percent-predicted VO2 peak determined by Wasserman/Hansen equations applied to the 1k-TWT is inversely and significantly related to survival in cardiac outpatients. The 1k-TWT is a simple and useful tool for stratifying mortality risk in patients participating in secondary prevention programs.

Perfil clínico e laboratorial de pacientes hansenianos atendidos no ILSL / Clinical findings of leprosy patients attended in ILSL

A partir do perfil clínico e laboratorial de pacientes hansenianos avaliados no Instituto Lauro de Souza Lima, entre 2004 e 2008, verificamos a concordância entre a classificação operacional baseada em número de lesões e uma classificação alternativa baseada no resultado de exames laboratoriais (índice baciloscópico (IB) do raspado intradérmico (RI) e presença de anticorpos anti-PGL-I). Foram avaliados 94 pacientes, a maioria do sexo masculino, com idades entre 5 e 80 anos, sendo a maior parte com as formas clínicas mais bacilíferas da hanseníase. O perfil clínico e laboratorial foi semelhante entre homens e mulheres, exceto com relação ao grau de incapacidade que foi maior entre os homens. Os IBs da biópsia e RI tiveram correlação positiva com o número de lesões. Os níveis de anticorpos anti-PGL-I foram maiores em pacientes que apresentavam nódulos, pápulas ou infiltração difusa e tiveram correlação positiva com IB RI, IB Biópsia, porcentagem de pontos positivos na baciloscopia e número de sítios acometidos por lesões. Houve correlação negativa entre os níveis de anti-PGL-I e a resposta ao antígeno de Mitsuda. Dentre os pacientes com cinco ou menos lesões cutâneas (PB) 7 apresentaram resultados positivos para IB RI e/ou anti-PGL-I, enquanto nos pacientes classificados como multibacilares 10 tinham resultados de IB RI e anti-PGL-I negativos. O nível de concordância entre as classificações foi moderado, (índice kappa = 0,54; IC = 0,35 - 0,74). Pela complexidade da hanseníase, todos os critérios possíveis devem ser observados antes da classificação clínica e inicio do tratamento. Este trabalho resgata conhecimentos, que estão sendo perdidos por conta da simplificação do diagnóstico e classificação clínica da doença. A junção de exames clínicos (lesões) e laboratoriais (PGL-I e IB) pode ser útil para orientar a terapêutica da hanseníase e prevenir a ocorrência de recidivas devidas a tratamentos inadequados.

Práticas e limitações de clientes com Hanseníase no cuidar das lesões cutâneas / Practices and limitations of users with Hansen's disease in care of skin lesions

Objetivo: conhecer a prática dos clientes com hanseníase quanto aos cuidados inerentes às lesões primárias e secundárias (úlceras plantares e palmares). Método: estudo exploratório-descritivo com abordagem quantitativa, realizado com 20 clientes que responderam a um questionário em um centro de referência para o tratamento de doenças infectocontagiosas, na cidade de João Pessoa/PB/Nordeste do Brasil. As respostas foram analisadas pela estatística descritiva, apresentados em tabelas e discutidos à luz da literatura. O projeto foi aprovado pelo Comitê de Ética e Pesquisa, CAAE nº 011040000126-11. Resultados: destacaram-se os casos multibacilares, e presença de ulcerações em apenas 15% da amostra. Número considerável da amostra não referiu cuidados com as mãos, realização de compressas de forma incorreta, além de não executarem cuidados adequados na presença de calos, fissuras e rachaduras. Conclusão: verificou-se necessidade de melhores estratégias de prevenção das úlceras e dos cuidados com as mãos e os pés.(AU)

Ingrown toenails.

Onychocryptosis or ingrown toenail is a very common pathology of the toenail unit, chiefly affecting adolescents and young adults. The ingrown toenail is responsible for disabling complaints like pain and difficulty in walking. It is associated with significant morbidity, hampering the quality of life as it interferes with sporting activities, school, or work. It principally occurs in the hallux. It is ascribed to poor trimming of the nails in combination with local pressure due to ill-fitting footwear, hyperhidrosis, poor foot hygiene and nail abnormalities. Pain, swelling and discharge are the main clinical features. Four stages of the condition have been described. Diagnosis is usually evident, but it should be differentiated from subungual exostosis and tumors of the nail bed. The current standard of care focuses on conservative treatment like the gutter splint technique in the initial stages, and in cases that are resistant to medical management or recurrent, surgical correction is the treatment of choice. There are various surgical techniques that are described in literature. Although there is no ideal technique, lateral nail plate avulsion with lateral matricectomy by phenol is commonly used and reported to be more effective in reducing recurrences. The aim of this review article is to focus on this common pathology of the nail, the various techniques employed in management and aid in the selection of treatment according to the stage and severity of the disease.

Relapses in multibacillary leprosy patients: a retrospective cohort of 11 years in Colombia.

OBJECTIVES: To determine the frequency and factors associated with relapse in multibacillary leprosy. DESIGN: We performed a retrospective cohort study on multibacillary leprosy patients treated at Centro Dermatologico Federico Lleras Acosta between January 1994 and December 2004. By survival analysis we studied the incidence density for recurrence and bacillary index conversion. The assessment of risk factors associated with the occurrence of relapse was constructed using a Cox regression model. RESULTS: We included 299 cases of which 243 received WHO-MB MDT on a regular basis, and followed them up to assess the frequency of relapses. We obtained 490 person-years of follow-up and an incidence density of 6.70 relapses/100 patient-years that was higher than most of the data reported in the literature. The relapse rate was 9.80 per 100 person-years when the initial bacillary index was > or = 2.0 and 5.60 relapses/100 patient-years when it was < 2 (P = 0.03). The relapse rate increased to 7.70/100 patient-years among those treated with WHO-MB 24 month fixed-dose, and it reduced to 5.70/100 patient-years when treated until smear negative. The variables that showed association with relapse were: initial bacillary index > or = 2.0, antireactional treatment and clinical classification of lepromatous leprosy. For each variable, the risk was four to five times more likely to present relapse. We also found that 21 patients' BI became negative per 100 treated for 1 year with WHO-MB MDT. CONCLUSIONS: We found a high relapse rate associated with initial high bacillary index in the Colombian population. Among the patients who received MDT on a regular basis 33 out of 165 (20%) relapsed.

OFLOXACIN multicentre trial in MB leprosy FUAM-Manaus and ILSL-Bauru, Brazil.

UNLABELLED: Recently antimicrobials of the fluoroquinolone class (pefloxacin and ofloxacin) were found far more effective against Mycobacterium leprae in studies with both mice and patients than dapsone and clofazimine. As multicentre trial participants, we evaluated the therapeutic efficacy, in terms of rate of relapse, of two new multidrug regimens containing ofloxacin, comparing them to 1 year and 2 years of standard WHO-MDT regimen in multibacillary (MB) leprosy patients. A total of 198MB patients were recruited to participate in a randomized, double-blind trial. Among those, 53 patients were treated with 1 year of WHO-MDT (a regimen including dapsone, clofazimine, and rifampin), 55 patients received 1 year of WHO-MDT plus an initial 1 month of daily ofloxacin, 63 patients were treated with 1 month of daily rifampin and daily ofloxacin, whereas 27 were treated with 2 years of WHO-MDT. Patients were regularly monitored for signs of relapse, in at least 7 years follow-up after being released from treatment. RESULTS: Relapse occurred in those treated with 1-month regimen alone at a significant higher rate (P < 0.001): 388%, whereas in the other three regimens that included WHO-MDT it ranged from 0 to 5%. This study found that a short-course treatment for MB patients with rifampicin-ofloxacin combination had a higher failure rate. The addition of one month of daily ofloxacin to 12 months MB WHO-MDT did not increase its efficacy.

Assessing and improving adherence with multidrug therapy.

INTRODUCTION: Adherence with multidrug therapy (MDT) in the treatment of leprosy is important to minimise the risk of relapse and avoid the emergence of drug resistance. Adherence is defined as the extent to which the patient's behaviour matches recommendations from the prescriber. This paper reviews the methods for assessing adherence with MDT in leprosy, and community approaches to improving adherence based on evidence from the treatment of tuberculosis (TB) and HIV, as well as leprosy. METHODS: To identify and summarise the available literature regarding the assessment of treatment regularity in leprosy, a literature search of MEDLINE was conducted using the following search terms: 'leprosy' AND ('adherence' OR 'compliance' OR 'concordance'). To identify evidence for interventions that have involved community members in HIV, TB or leprosy adherence support, a literature search was conducted using the key terms and medical subject headings 'treatment or adherence' 'community,' 'HIV, TB or Leprosy' and 'low and middle income countries' combined using Boolean operators. RESULTS: Leprosy programmes routinely use defaulting and treatment completion as proxy measures of adherence as recommended by the WHO global strategy. However, a number of other methods have been used to assess adherence including questionnaires, pill counts, as well as direct measures based on testing urine for the presence of dapsone. Direct methods were extensively used during the dapsone mono-therapy era but there is little evidence of their use in MDT. Use of multiple methods of assessing adherence improves the accuracy and reliability of the results. Community activities in TB and HIV such as variants of treatment observation, and/or wider programmes of counselling or direct support to the patient or their family or to increase community or social support were shown to improve treatment outcomes. Outcomes evaluated included treatment default and completion, clinical indicators, and adherence (pill-count, self report). CONCLUSIONS: Adherence is very important in leprosy and regular assessment of medication adherence together with constructive feedback and counselling of patients is likely to be beneficial. Leprosy programme can learn from adherence support interventions developed by both TB and HIV programmes.

Evaluation of multi-drug therapy for leprosy in the United States using daily rifampin.

OBJECTIVES: To evaluate the occurrence of relapse of multibacillary leprosy after multi-drug treatment including daily rifampin. METHODS: A retrospective review was performed utilizing data from the National Hansen's Disease Program (NHDP) on patients with leprosy treated and followed from 1988-1997 who received multi-drug therapy including daily rifampin. The occurrence of relapse in this cohort was measured, and demographic data and various clinical variables were also gathered. RESULTS: Ultimately, 158 cases fulfilled the eligibility criteria. 77% of cases were multibacillary patients and were treated with 2 or 3 drug protocols at rates of 36% and 35% before and after 1992, respectively. Only one case of relapse was found, and this patient underwent 2-drug therapy versus 3-drug therapy. CONCLUSION: These data are remarkable for the absence of relapse with daily rifampin, as contrasted with the published experience using the WHO protocol with monthly rifampin.

Leprosy beyond MDT: study of follow-up of 100 released from treatment cases.

Appearance of new skin and/or nerve lesions during or after fixed duration of multidrug therapy (MDT), in leprosy, is not uncommon. It could be a lesion due to leprosy reaction or relapse. Differentiation is easy in classical reactions both clinically and histopathologically. But, difficult in other situations especially when the relapse cases present with features of reaction at the onset. A study was done to find the reasons for released from treatment (RFT) cases to come to clinic and to follow in terms of clinical and neurological activity, leprosy reactions and deformity progression. Out of them, 14 cases and 86 cases had received paucibacillary (PB) and multibacillary (MB) multidrug therapy respectively. Skin lesions either old or new were noticed in 74% cases which might be due to inactivity or activity were noticed in 74% cases which might be due to inactivity or activity in forms of relapse and reaction. Relapse was seen in 26 cases. Out of these, 10 and 16 cases were previously diagnosed as PB and MB cases respectively. PB cases relapsed into MB cases while MB cases relapsed into MB cases. 46 cases presented with either type 1 or type 2 reaction. After declared as RFT, parasthesia in 34 cases, weakness in 18 cases, paresis and paralytic deformity in 6 cases were seen. So, all the RFT cases need regular follow-up, IEC and physiotherapy to prevent deformity and to diagnose relapse and reactions at the earliest.

Does circumcision influence recurrences in herpes genitalis?

BACKGROUND AND AIMS: The effect of therapeutic circumcision in men for preventing recurrences of herpes genitalis remains largely unelucidated despite its well documented albeit conflicting role in reducing the risk of acquiring sexually transmitted infections, including genital herpes. METHODS: Twenty volunteer adult males with a history of recurrent herpes genitalis were included in the study after informed consent and circumcision was carried out. Twenty more adult males having recurrent herpes genitalis and registered in the clinic during the same period were selected as controls. All patients and controls were followed-up for recurrences of herpes genitalis. RESULTS AND CONCLUSIONS: Six patients and six controls did not follow-up. Seven patients reported no recurrences during 3-18 years, seven patients had two to six recurrences during 11-27 years of postcircumcision follow-up, 0.0080 (average) recurrences per person per year as compared with 0.20 (average) recurrences per person per year recorded before the circumcision. Two patients had first recurrence 11 years after the circumcision. In comparison, 14 controls had 0.17 (average) recurrences per person per year, comparable with the number of recurrences in uncircumcised patients, and frequently at shorter intervals. Despite being a small study, the circumcision appears to reduce the number of recurrences on an average and evidently prolongs the disease-free period in between two recurrences.

Relapse in leprosy.

Leprosy is unique in terms of the nature of the causative organism (Mycobacterium leprae), the chronicity of the disease, its prolonged treatment and the definitions of "cure" and "relapse." The principal mode of assessing the efficacy of therapeutic regimens in leprosy is the "relapse rate." There are wide variations in estimates of relapse rates after the World Health Organization (WHO) multidrug therapy in different regions. The important predisposing factors for relapse include the presence of "persister" bacilli, monotherapy, inadequate/irregular therapy, presence of multiple skin lesions/thickened nerves and lepromin negativity. The conventional methods of confirming activity or relapse in an infectious disease (demonstration and/or culture of the etiologic agent) have limited utility in leprosy because of the difficulty in demonstrating bacilli in paucibacillary (PB) cases and absence of a method of in vitro cultivation of M. leprae. Bacteriological parameters are useful in multibacillary (MB) leprosy, whereas in PB leprosy, the criteria for relapse depend primarily on clinical features. Although there are no widely available serologic tests for leprosy other than in a research setting, various immunological tests may be useful for monitoring patients on chemotherapy as well as for confirming suspected cases of relapse. The main differential diagnoses for relapse are reversal reactions, erythema nodosum leprosum and reactivation/resistance/reinfection. The most reliable criteria for making an accurate diagnosis of relapse include clinical, bacteriological and therapeutic criteria. Additional ones that may be used, depending on the setting, are histopathological and serologic criteria. Relapsed cases of leprosy should be identified and put back on chemotherapy as soon as possible to prevent further disability and transmission of infection. Factors that should be considered in choosing an appropriate regimen are the type of leprosy (PB or MB), previous treatment and drug resistance. Occasionally, clinicians may need to use their judgement to modify the standard WHO treatment regimens according to the scenario in each patient.

Relapse of leprosy presenting as nodular lymph node swelling.

Lymphadenopathy is known to be associated with lepromatous leprosy and has also been observed as a feature of type-2 lepra reaction. However, nodular lymph node enlargement is not commonly reported in leprosy patients or as a feature of relapse. We herewith are presenting a case of bacteriological relapse in a patient of lepromatous leprosy treated 22 years before till smear negativity with WHO multidrug therapy (MDT) multibacillary type (MB). She presented with prominent nodular swelling of the cervical group of lymph nodes along with generalized lymphadenopathy, which was mistakenly treated as tubercular lymphadenopathy. A diagnosis of late bacteriological relapse of lepromatous leprosy presenting with prominent lymphadenopathy and ENL was made after relevant investigations. The patient was started on treatment with WHO MDT MB (daily dapsone and clofazimine and monthly rifampicin) and thalidomide (200 mg/day). Nerve pain regressed within 2 weeks of therapy. The lymph nodal swelling regressed within 3 months of starting treatment.

An 8-12 year follow-up of highly bacillated Indian leprosy patients treated with WHO multi-drug therapy.

OBJECTIVES: To follow up highly bacillated leprosy patients for a long period after release from treatment (RFT) and to look out for possibility of relapses. RESULTS: 660 patients with an initial bacterial positivity of 4 +, 5 + or 6 + who had undergone WHO multi-drug therapy and released from treatment, were followed up. The regularity of their treatment was kept high by close monitoring with home visits. They were reviewed twice, once 4 to 9 years after RFT and again 7 to 12 years after RFT. 516 patients were available in the second review. As per WHO definition, 5 patients were found to have relapsed, giving a relapse rate of 0.103 per 100 person years. This low relapse rate could be due to high regularity of treatment. CONCLUSION: With well supervised MDT and high regularity of treatment and proper consumption of drugs, relapse rate is very low.

Relapses in multibacillary leprosy patients after multidrug therapy.

OBJECTIVES: To determine the magnitude of relapses in multibacillary leprosy patients after multi-drug therapy and to determine the factors influencing the relapse. DESIGN: A retrospective study pertaining to multibacillary leprosy patients treated with MBMDT as per WHO guidelines was carried out. The study included 300 MB patients who had successfully completed treatment during 1986-2002, of whom 163 patients were available for follow-up. Patients were examined clinically and bacteriologically to asses the present status of disease. RESULTS: A total of three cases relapsed at 2, 4 and 11 years after being released from treatment which gives a crude cumulative relapse rate of 1.84% for the 18 year period of follow-up with mean duration of follow-up 7.13 +/- 1.25 years. It also gives the total follow-up period of 1163 person-years with the relapse rate of 0.26/100 person-years of follow-up (95% confidence interval is 0.235-0.285). CONCLUSION: Relapse rate after WHO recommended MDT leprosy is low. High bacterial load before initiation of therapy is an important factor which determines the relapse.

Hemicrania continua-like headache with leprosy: casual or causal association?

Hemicrania continua is a strictly unilateral, moderate to severe, continuous, indomethacin-responsive primary headache disorder with ipsilateral autonomic cranial symptoms at the time of exacerbations. We describe a 30-year-old woman with a 4-month history of indomethacin-responsive hemicrania continua-like headache and one-month history of mononeuritis multiplex due to leprosy. Indomethacin was successfully weaned off after completion of antileprotic therapy.