A clinical prediction rule for nerve function impairment in leprosy patients-revisited after 5 years of follow-up

Nerve function impairment (NFI) commonly occurs during or after chemotherapy in leprosy. We previously described a clinical prediction rule to estimate the risk of NFI occurring within 2 years of diagnosis, based on 2510 patients who are followed up in the Bangladesh Acute Nerve Damage Study (BANDS). This prediction rule assigns new leprosy patients to one of three risk groups based on leprosy group and the presence or absence of NFI at registration. Updated data with up to 5 years of follow-up showed that 95% of all NFI occurred within 2 years. This study confirms the validity of the rule and supports the conclusion that there is little value for the detection of NFI in extending follow-up beyond 2 years.     

Minocycline for the treatment of cutaneous silicone granulomas: A case report

Silicone oil injections are often used for soft tissue augmentation and local and general adverse effects occurring from a few months to 15 years after injection have been reported. Here, we present a case of delayed granuloma formation due to liquid injectable silicone with large extent of involvement, which precluded surgical removal. Our patient was successfully treated with minocycline, considering its anti-inflammatory, immunomodulating and antigranulomatous properties. This case presents minocycline monotherapy as a useful treatment option for the management of severe granuloma induced by silicone use when surgical excision is not possible.     

The treatment of acute nerve function impairment in leprosy: results from a prospective cohort study in Bangladesh

In this paper, the outcome of 132 patients having acute nerve function impairment (NFI) is reported at 4 and 12 months after the start of prednisolone treatment. In all, 68% of sensory nerves and 67% of motor nerves showed improvement at 12 months, with no statistical difference in responsiveness of various nerves to prednisolone. Duration and severity of impairment were not found significant predictors of treatment outcome. A core of 32% of impaired nerves did not respond to prednisolone, and 12% of impaired nerves had functional deterioration despite treatment. The mean eye-hand-foot (EHF) score improved from 2.02 to 1.33 in the treatment group (median score improved from 2 to 1). Approximately one-third of all patients requiring prednisolone treatment did not receive it, an important reason being that some patients developed new NFI against a background of chronic impairment, and were thus overlooked. The 'unjustly untreated' group of patients had a spontaneous sensory nerve function improvement rate of 62% and a motor nerve function improvement rate of 33% at 12 months from onset of NFI. The EHF score showed no statistically significant improvement.     

Lymphocytic Thrombophilic Arteritis: A Possible Association with Minocycline

We describe a case of lymphocytic thrombophilic arteritis in a 15‐year‐old girl who had previously taken minocycline for a year. Cutaneous polyarteritis nodosa and lymphocytic thrombophilic arteritis share many features and may both be triggered by minocycline. There may be a long latency between drug exposure to minocycline and development of disease.     

Treatment with corticosteroids of long-standing nerve function impairment in leprosy: a randomized controlled trial (TRIPOD 3)

Some leprosy patients with long-standing nerve function impairment (NFI) appear to have responded favourably to treatment with corticosteroids. This study investigated whether patients with untreated NFI between 6 and 24 months duration and who are given standard regimen corticosteroid therapy, will have a better treatment outcome than a placebo group. A multicentre, randomized, double-blind placebo-controlled trial was conducted in Nepal and Bangladesh. Subjects were randomised to either prednisolone treatment starting at 40 mg/day, tapered by 5 mg every 2 weeks, and completed after 16 weeks, or placebo. Outcome assessments were at 4, 6, 9, and 12 months from the start of treatment. 92 MB patients on MDT were recruited, of whom 40 (45%) received prednisolone and 52 (55%) placebo treatment. No demonstrable additional improvement in nerve function, or in preventing further leprosy reaction events was seen in the prednisolone group. Overall, improvement of nerve function at 12 months was seen in about 50% of patients in both groups. Analysis of subgroups according to nerve (ulnar and posterior tibial), duration of NFI, and sensory and motor function, also did not reveal any differences between the treatment and placebo groups. There was however, indication of less deterioration of nerve function in the prednisolone group. Finally, there was no difference in the occurrence of adverse events between both groups. The trial confirms current practice not to treat long-standing NFI with prednisolone. Spontaneous recovery of nerve function appears to be a common phenomenon in leprosy. Leprosy reactions and new NFI occurred in a third of the study group, emphasizing the need to keep patients under regular surveillance during MDT, and, where possible, after completion of MDT.     

Adverse events of standardized regimens of corticosteroids for prophylaxis and treatment of nerve function impairment in leprosy: results from the 'TRIPOD' trials

Reactions in leprosy causing nerve function impairment (NFI) are increasingly treated with standardized regimens of corticosteroids, often under field conditions. Safety concerns led to an assessment of adverse events of corticosteroids, based on data of three trials studying prevention of NFI (the TRIPOD study). A multicentre, randomized, double-blind placebo-controlled trial was conducted in leprosy control programmes in Nepal and Bangladesh. Treatment was with prednisolone according to fixed schedules for 16 weeks, starting in one trial with 20 mg/day (prophylactic regimen: total dosage 1.96 g) and in the other two trials with 40 mg/day (therapeutic regimen: total dosage 2.52 g). Minor adverse events were defined as moon face, fungal infections, acne, and gastric pain requiring antacid. Major adverse events were defined as psychosis, peptic ulcer, glaucoma, cataract, diabetes and hypertension. Also, the occurrence of infected plantar, palmar, and corneal ulceration was monitored, together with occurrence of TB. Considering all three trials together, minor adverse events were observed in 130/815 patients (16%). Of these, 51/414 (12%) were in the placebo group and 79/401 (20%) in the prednisolone group. The relative risk for minor adverse events in the prednisolone group was 1.6 (P = 0.004). Adverse events with a significantly increased risk were acne, fungal infections and gastric pain. Major adverse events were observed in 15/815 patients (2%); 7/414 (2%) in the placebo group and 8/401 (2%) in the prednisolone group. No major adverse events had a significantly increased risk in the prednisolone arm of the trials. No cases of TB were observed in 300 patients who could be followed-up for 24 months. Standardized regimens of corticosteroids for both prophylaxis and treatment of reactions and NFI in leprosy under field conditions in developing countries are safe when a standard pre-treatment examination is performed, treatment for minor conditions can be carried out by field staff, referral for specialized medical care is possible, and sufficient follow-up is done during and after treatment.     

Clinical and electrophysiological evaluation of nerve function impairment following cessation of multidrug therapy in leprosy.

Seventeen multibacillary (MB) and 15 paucibacillary (PB) cases of leprosy who had had regular and adequate multidrug therapy (MDT) were examined clinically and electrophysiologically at periodic intervals for 1 year following cessation of MDT. All the major nerves were assessed for nerve function impairment (NFI). Overall, two MB (13.3%) and three PB (20%) cases showed signs of deterioration clinically and/or electrophysiologically. The nerve conduction (NC) follow-up studies revealed no significant improvement in the sensory conduction in both the MB and PB groups of nerves, whilst motor conduction showed a significant improvement at the first 6-monthly follow-up among the MB group of nerves. At the study onset, sensory impairment (MB = 62%, PB = 25%) predominated over motor in terms of both severity and frequency. The lower extremity was more frequently and severely affected than the upper in both groups of patients. As an individual test, NC measurement proved to be more sensitive in detecting NFI, but the combination of physical palpatation for nerve thickening and graded nylon test (GNT) was closely comparable to measurement of nerve conduction.     

Unexplained delayed nerve impairment in leprosy after treatment

The objective of this study was to examine the clinical signs, symptoms and course of neuropathies in patients with leprosy who after treatment developed nerve impairment, not explained by relapse or reversal reactions. We searched the case-records of leprosy patients, seen between 1985 and 2002 at the department of dermatology at our centre. Included in the study were patients who had developed nerve impairment after treatment of leprosy in the absence of relapse, erythema nodosum leprosum, or reversal reactions, and who were referred to a neurologist. In these patients, we recorded age, onset of leprosy, type of leprosy, treatment of leprosy, signs and symptoms of delayed nerve impairment, results of electrophysiological studies, responses to treatment and course. Included were 14 patients, of whom eight had a (sub)acute multiple mononeuropathy (group I); and six had a slowly progressive multiple mononeuropathy (group II). Patients in group I had limited improvement of nerve impairment after treatment with corticosteroids, and recurrence of symptoms and signs (usually of the motor nerves) when corticosteroids were tapered off. Patients in group II had slowly progressive predominantly sensory nerve impairment. Initially, they had only subjective symptoms, after at least 3 years objective signs became detectable. These patients were not treated with immunosuppressants. Two groups of patients with unexplained delayed nerve impairment could be distinguished. One group had a multiple mononeuropathy resembling reversal reactions with insufficient response to corticosteroids. In these patients, more aggressive and prolonged immunosuppressive treatment should be considered. The aetiology for the neuropathy in the other group remains unclear and further investigations are needed to understand the pathogenesis before treatment recommendations can be given.     

Minocycline hydrochloride treatment for atypical acid-fast infection.

Atypical acid-fast infections are not infrequent in the Gulf Coastal region. The development of erythematous papules within three or four weeks after aquatic exposure deserves such consideration. Deeper tissues may also become involved. This should signal a caution when considering the use of corticosteroid injections in such a suspicious lesion. Inasmuch as hypertrophic scar formation at a site of trauma must be considered in the differential diagnosis, it is important to secure histopathologic examination prior to treatment. While a surgical approach has been required for the most part, oral administration of minocycline hydrochloride has brought about healing in the patients reported herein. This article deals with only three cases. However, response was complete and without recurrence in each. Such therapy is recommended prior to the use of more drastic procedures.     

Minocycline is a useful adjuvant therapy for pemphigus

Pemphigus is an autoimmune blistering disease with high mortality if untreated. The cases of 10 patients who had minocycline 100 mg daily added as adjuvant therapy are reported. Prior to the use of minocycline, all patients had active disease, nine were on prednisolone (10–40 mg) and five were on azathioprine (100–200 mg). The response was assessed on clinical improvement and reduction of immunosuppressive (IS) drugs. It was graded into four categories: major, minor, equivocal and no significant response. A major response was seen in four patients, minor in two, equivocal in one and no improvement in three patients. The prednisolone dose in the six responders was reduced to 0–6 mg (0 mg in three patients), with an average decrease of 21 mg. The average time to respond was 8 months. Of the six responders, three were on azathioprine, which was ceased in two patients and reduced by two-thirds in the other patient. No patient ceased minocycline because of side effects. In conclusion, minocycline 100 mg daily is a simple, safe and well tolerated treatment that should be tried in patients with pemphigus to reduce disease activity and/or the dose of potent IS agents.     

Incidence rates of acute nerve function impairment in leprosy: a prospective cohort analysis after 24 months (The Bangladesh Acute Nerve Damage Study)

In this paper, the incidence rates and cumulative incidence of nerve function impairment (NFI) and leprosy reactions over 24 months follow-up of the prospective cohort of 2664 new leprosy cases are presented. Graphs showing the cumulative incidence of NFI relative to time since registration are presented. Hazard ratios (HRs) for the development of NFI for four variables are given. The majority of patients who developed NFI after registration did so in the first year (67% of multibacillary (MB) patients, and 91% of paucibacillary (PB) patients who developed NFI). Thirty-three percent of all MB patients who developed NFI after registration did so in the second year of follow-up. No PB patients developed NFI for the first time in the last 6 months of follow-up. However, seven NFI events occurred amongst PB patients in that period, amongst those who had already had one NFI event. The incidence rate (IR) of NFI amongst MB patients was 24/100 person-years at risk (PYAR), and amongst PB patients was 1.3/100 PYAR. The HR for the development of NFI amongst MB patients compared with PB patients was 16 using univariate analysis. Amongst patients who had long-standing NFI present at registration, the IR was 27/100 PYAR compared with 1.7/100 PYAR amongst those who did not have long-standing NFI. The HR for developing acute NFI amongst those with long-standing NFI present at registration compared with those without was 14 using univariate analysis. When multivariate regression analysis is applied, the apparently significant univariate HRs for sex and age disappeared. The resultant multivariate HR for leprosy group is 8.8, and 6.1 for the presence/absence of long-standing NFI at registration. In all, 142/166 (86%) of all new NFI events were silent, underlining the need for regular nerve function testing. IRs are presented for the four 6-month periods of the 24-month follow-up. They show a clear stepwise reduction over the total period. The IRs amongst MB patients and those with long-standing NFI present at registration are very high at 34 and 41/100 PYAR, respectively, for the first 6 months of follow-up. Even during the final 6-month period, the IR is maintained at a moderately high level (18 and 15/100 PYAR, respectively).     

641例麻风患者上肢神经损害的分析

为了解麻风患者上肢神经损害的状况，选择兴化市存活的麻风治愈者及现症患者1575人为调查对象。结果显示麻风患者上肢神经损害的发生率为40．7％，单侧损害（23．17％）高于双侧（17．52％），现症及复发病人（69．23％）高于治愈者（40．46％），多菌型（55．94％）高于少菌型（38．46％）。尺神经损害为36．63％，正中神经为16．95％，桡神经为2．35％，爪形指继发关节强直为73．03％，神经损害与麻风反应有关的为43．37％。兴化市麻风上肢神经损害多见于现症及复发病人以单侧损害为主，尺神经损害第一，其次为正中神经、桡神经，2／3的神经损害是不可逆的。因麻风诊断的延迟、麻风反应及麻风型别的不同，上肢神经损害的差异非常明显。     

Monitoring motor nerve function in leprosy patients

Manual muscle strength testing has an important function in the management of leprosy patients. Its importance was first recognized in the 1960s, especially when following patients who were started on steroid treatment to monitor the nerve function and the effect of treatment. In those days, and still in many centres today, many or all muscles were tested that are innervated by the nerves that can be at risk in leprosy. The author argues that not all muscles innervated by the nerves at risk need to be tested and also that many muscles cannot be tested in isolation. A muscle charting form is presented which is suitable for screening purposes, and that also allows for more detail when motor function is impaired.     

Minocycline hyperpigmentation: model for in situ phagocytic activity of factor XIIIa positive dermal dendrocytes

Pigmentary disorders resulting from the prolonged use of the semisynthetic tetracycline derivative antibiotic, minocycline, are rare but well recognized sequelae of ingestion of this drug. We present two cases of women with bullous pemphigoid who developed blue-black pigmentation in areas of scarring on the legs after oral minocycline therapy. On histologic examination, the deposited pigment was localized within dendritic cells limited to the upper dermis. Immunohistochemical analysis revealed these cells to be factor XIIIa positive dermal dendrocytes which was confirmed by transmission electron microscopy. We believe these cases demonstrate, in-situ, the phagocytic capabilities of this recently described cell population.