Evaluation of altered patterns of tactile sensation in the diagnosis and monitoring of leprosy using the Semmes-Weinstein monofilaments.

BACKGROUND: Leprosy neuropathy is the most common peripheral neuropathy of infectious etiology worldwide; it is characterized as asymmetric and focal multiple mononeuropathy. Semmes-Weinstein monofilament (SWM) test is a simple method to assess sensory nerve function. METHODS AND FINDINGS: In this prospective cohort study, a dermatologist carried out hands and feet tactile sensation test with SWM in 107 multibacillary leprosy patients at diagnosis and in 76 patients at the end of treatment from 2016 to 2019. At diagnosis, 81/107 (75.7%) patients had some degree of functional disability, and 46 (43%) of them had altered SWM-test in the hands and 94 (87.9%) of them in the feet. After one year of multibacillary multidrug therapy, the disability decreasing to 44/76 patients (57.9%) and decreasing of the percentual of patients with altered SWM-test to 18% for the hands, and to 28.7% for the feet. At the end of treatment, the number of SMW-test points presented improvement in the hands of 22 (28.9%) patients, and in the feet of 47 (61.8%). In the hands, by SWM-test, only the radial nerve point demonstrated a significant asymmetry, while in the feet, the difference between the sum of altered SWM-test points showed significant asymmetry between both sides, highlighting the tibial nerve for the establishment of asymmetric leprosy neuropathy. In Spearman's correlation analysis, a positive correlation with statistical significance was observed between the number of hands and feet SWM altered points at diagnosis and the degree of disability at diagnosis (0.69) and at the end of the treatment (0.80). CONCLUSION: The patterns of hands and feet tactile sensation at diagnosis and their consequent modifications with the anti-leprosy drugs define the bacterial etiology of neuropathy, an important tool for the clinical diagnosis and follow up of the disease, highlighting the tibial nerve findings, the most affected nerve among leprosy patients by SWM-test, with significant asymmetry and focality impairments.

Primary neural leprosy: clinical, neurophysiological and pathological presentation and progression.

Disability in leprosy is a direct consequence of damage to the peripheral nervous system which is usually worse in patients with no skin manifestations, an underdiagnosed subtype of leprosy known as primary neural leprosy. We evaluated clinical, neurophysiological and laboratory findings of 164 patients with definite and probable primary neural leprosy diagnoses. To better understand the disease progression and to improve primary neural leprosy clinical recognition we compared the characteristics of patients with short (≤12 months) and long (>12 months) disease duration. Positive and negative symptoms mediated by small-fibres were frequent at presentation (∼95%), and symptoms tend to manifest first in the upper limbs (∼68%). There is a consistent phenotypic variability between the aforementioned groups. Deep sensory modalities were spared in patients evaluated within the first 12 months of the disease, and were only affected in patients with longer disease duration (∼12%). Deep tendon reflexes abnormalities were most frequent in patients with longer disease duration (P < 0.001), as well as motor deficits (P = 0.002). Damage to large fibres (sensory and motor) is a latter event in primary neural leprosy. Grade-2 disability and nerve thickening was also more frequent in cases with long disease duration (P < 0.001). Primary neural leprosy progresses over time and there is a marked difference in clinical phenotype between patients with short and long disease duration. Patients assessed within the first 12 months of symptom onset had a non-length-dependent predominant small-fibre sensory neuropathy, whilst patients with chronic disease presented an asymmetrical all diameter sensory-motor neuropathy and patchily decreased/absent deep tendon reflexes.

Treatment and Evaluation Advances in Leprosy Neuropathy.

Neuropathy and related disabilities are the major medical consequences of leprosy, which remains a global medical concern. Despite major advances in understanding the mechanisms of M. leprae entry into peripheral nerves, most aspects of the pathogenesis of leprosy neuropathy remain poorly understood. Sensory loss is characteristic of leprosy, but neuropathic pain is sometimes observed. Effective anti-microbial therapy is available, but neuropathy remains a problem especially if diagnosis and treatment are delayed. Currently there is intense interest in post-exposure prophylaxis with single-dose rifampin in endemic areas, as well as with enhanced prophylactic regimens in some situations. Some degree of nerve involvement is seen in all cases and neuritis may occur in the absence of leprosy reactions, but acute neuritis commonly accompanies both Type 1 and Type 2 leprosy reactions and may be difficult to manage. A variety of established as well as new methods for the early diagnosis and assessment of leprosy neuropathy are reviewed. Corticosteroids offer the primary treatment for neuritis and for subclinical neuropathy in leprosy, but success is limited if nerve function impairment is present at the time of diagnosis. A candidate vaccine has shown apparent benefit in preventing nerve injury in the armadillo model. The development of new therapeutics for leprosy neuropathy is greatly needed.

Semmes-Weinstein monofilament: A tool to quantify skin sensation in macular lesions for leprosy diagnosis.

INTRODUCTION: Hypochromatic macules with altered sensitivity are the first manifestations of skin leprosy. Validation of this sensory loss assists in the confirmation of the clinical diagnosis. AIMS: The aim of the study was to quantify the loss of sensation in leprosy lesions using the Semmes-Weinstein monofilament to strengthen the clinical diagnosis mainly of macular forms. METHODS: Seventy-four hypochromatic macules in the macular leprosy subgroup, 27 typical borderline leprosy subgroup lesions and 49 macules of other macular dermatoses (non-leprosy group) were evaluated using the 0.05 g force Semmes-Weinstein monofilament to quantify the alteration of sensitivity within and outside of the lesions. The esthesiometric change index was established as the total number of points with altered sensation divided by the total number of tested points within the lesions to calculate the internal esthesiometric change index and outside the lesions to calculate the peripheral esthesiometric change index; these indexes were calculated for all groups. The difference (Δ) between the esthesiometric change indices of the lesional area and the adjacent skin was calculated for the leprosy and nonleprosy groups. RESULTS: The percentage of points with touch sensitivity alterations within the macular and typical borderline leprosy lesions was higher in leprosy than in the non-leprosy group. The borderline and macular leprosy presented higher esthesiometric change index within injured areas than outside injured areas or in the nonleprosy group (P < 0.005). When internal esthesiometric change index values in the macular and borderline leprosy groups were higher than 0.53 and 0.5, respectively, the receiver operating characteristic curve showed 98% sensitivity and approximately 99% specificity for both groups (P < 0.0001). Regarding the difference between indices, borderline and macular leprosy had values that were higher and closer to one than in the nonleprosy group (P < 0.0001), with 100% sensitivity and 96.5% specificity for leprosy diagnosis when ΔLG was higher than 0.34. A limitation was the inability to perform a double-blind study. CONCLUSION: Semmes-Weinstein esthesiometry is a simple, useful and low-cost tool to quantify the focal alteration of cutaneous sensitivity to improve clinical leprosy diagnosis, especially for macular lesions.

Comparison between nerve conduction study anf high-resolution ultrasonography with color doppler in type 1 and type 2 leprosy

Objective: To analyze the role of high-resolution ultrasonography with color Doppler (HRUS with CD) to diagnose inflammatory activity (IA) in nerves of leprosy patients under type 1 (RT1) and 2 (RT2) reactions compared to Nerve Conduction Studies (NCS). Methods: Leprosy patients with signs or symptoms suggestive of neuritis (RT1 and RT2) without corticosteroids use were selected. They were evaluated by NCS and subsequently by HRUS with CD. Subacute segmental demyelination and the presence of blood flow, respectively, were considered signs of IA. The two methods were compared for their ability to diagnose patients with leprosy reactions. Results: A total of 257 nerves from 35 patients were evaluated. NCS and HRUS with CD diagnosed IA in 68% and 74% of patients, respectively. When both methods were used concomitantly, the diagnosis rate was 91.4%. HRUS with CD was particular helpful when there was minimal neurophysiological compromise in NCS or when motor potentials were not detected. Conclusion: HRUS with CD was able to detect leprosy reactions, especially when combined with NCS. It was especially useful in two opposite situations: nerves with only minor changes and those without motor response in NCS. Significance: Our data shows the usefulness of HRUS and CD, similar to NCS, as a tool to diagnose leprosy reactions.

Appropriately Selected Nerve in Suspected Leprous Neuropathy Yields High Positive Results for Mycobacterium leprae DNA by Polymerase Chain Reaction Method.

Identification of Mycobacterium leprae DNA by polymerase chain reaction (PCR) is a reliable and an affordable method to confirm leprosy. DNA from 87 nerve samples (61 from paraffin blocks and 26 fresh samples) was extracted. Mycobacterium leprae DNA was amplified by PCR from 80/87 (92%) specimens. Patients were seen over a period of 11 years (2007-2019), and leprosy was diagnosed based on clinical and characteristic histopathology findings. The clinical diagnostic possibilities were as follows: leprous neuropathy in 73/80 (91.3%), mononeuritis multiplex of unknown etiology in four (5.0%), vasculitic neuropathy in two (2.5%), and distal symmetric sensory motor neuropathy in one (1.3%). The biopsied nerves were as follows: superficial radial = 34 (42.6%), dorsal cutaneous branch of ulnar = 19 (23.8%), sural = 18 (22.5%), and superficial peroneal = 9 (11.3%), and corresponding neurological deficits were recorded in 77 (96.3%) cases. The histopathological diagnoses in total group were as follows: (borderline tuberculoid (BT) = 52, tuberculoid (TT) = 8, borderline lepromatous (BL) = 8, borderline borderline (BB) = 3, nonspecific inflammation = 3, healed/fibrosed = 4, and axonopathy = 2). Acid fast bacilli (AFB) was demonstrated in 11 (13.7%) samples. For comparison, 31 clinically and histopathologically defined non-leprous disease control nerves (inherited neuropathy = 20, vasculitis = 8, and nutritional neuropathy = 3) subjected to PCR were negative for M. leprae DNA. In most instances, there are multiple thickened peripheral nerves in suspected cases of leprosy, but neurological deficits pertaining to the thickened nerve are not as widespread. The current findings emphasize the importance of selecting the most appropriate nerve for biopsy to obtain a positive PCR result. We infer that clinical, histopathological, and PCR tests complement each other to help achieve a definitive diagnosis of leprosy particularly in pure neuritic leprosy and in leprous neuropathy with negative skin smears/biopsy.

Pathological, ultrasonographic, and electrophysiological characterization of clinically diagnosed cases of pure neuritic leprosy.

A subset of neuritic form of leprosy, called pure neuritic leprosy (PNL), seen in a minority of leprosy patients, is characterized by peripheral neuropathy without skin lesions and an absence of acid-fast bacilli on skin smears. Patients with PNL are often started on drug therapy without confirmation of diagnosis. We, therefore, did a prospective study of clinically diagnosed PNL patients with correlation of ultrasonographic and biopsy findings. A total of 100 consecutive patients with PNL, diagnosed according to the consensus case definition, were included in the study. All patients underwent nerve conduction study, peripheral nerve ultrasonography, and sural nerve biopsy. Multiple mononeuropathies were present in 75% of cases, mononeuropathy in 18%, and polyneuropathy in the remaining 7%. Compared to clinical examination, ultrasonographic assessment of the peripheral nerves was not only better at the detection of thickening but also helped in characterization of their fascicular architecture, echogenicity, and vascularity. A total of 32 cases were confirmed on nerve biopsy, out of which 75% had demonstrable lepra bacilli. Cranial nerve involvement, presence of trophic ulcers, and bilateral thickening of the great auricular nerve were significantly associated with the positivity of lepra bacilli. A significant improvement in the disability score happened after multidrug therapy. A comprehensive electrophysiologic, ultrasonographic, and histological evaluation may be helpful in establishing a diagnosis of PNL with greater confidence, while ruling out other non-leprosy diagnoses.

Orthopedic Surgical Foot Management in Hansen Disease.

Hansen disease remains a common problem worldwide with 750,000 new cases diagnosed each year. Nerve injury is a central feature of the pathogenesis because of the unique tendency of Mycobacterium leprae to invade Schwann cells and the peripheral nervous system, that can be permanent and develop into disabilities. The orthopedic surgeon has an important role in the management of neuropathy, performing surgical release of the tibial and common peroneal nerves in potentially constricting areas, thus providing a better environment for nerve function. In cases of permanent loss of nerve function with drop foot, specific tendon transfers can be used.

Peripheral neuropathy and the role of nerve biopsy: A revisit.

BACKGROUND: Nerve biopsy has been widely used to investigate patients with peripheral neuropathy and in many centers, it is still a part of the diagnostic armamentarium. In this study, the histopathological spectrum of the nerve biopsies received is being revisited to analyze the various clinical and pathologic features and also to assess their relevance. MATERIALS AND METHODS: Retrospective analysis of the data retrieved was done for 74 cases of nerve biopsies. RESULTS: On the basis of the data and histopathological features, broad diagnoses were obtained in 52 cases and further categorized into biopsies being supportive for patient management (including acute and chronic axonopathies and demyelinating neuropathies) and biopsies considered essential for patient management (including vasculitic neuropathies, leprous neuropathies, hereditary neuropathies, and chronic inflammatory demyelinating neuropathies). Nine nerve biopsies did not show any abnormal histopathological features, while 13 nerve biopsies were found to be inadequate for diagnosis, both these groups were categorized as noncontributory. CONCLUSION: With advanced nerve conduction studies available, nerve biopsy is losing its relevance. However, in our experience, nerve biopsy did complement the clinical findings and nerve conduction studies, with which a close correlation is required to make the histopathology of nerve biopsy more relevant in terms of guiding further specific workup and management.

Molecular, immunological and neurophysiological evaluations for early diagnosis of neural impairment in seropositive leprosy household contacts.

BACKGROUND: Household contacts constitute the highest risk group for leprosy development, and despite significant progress in the disease control, early diagnosis remains the primary goals for leprosy management programs. METHODS: We have recruited 175 seropositive and 35 seronegative household contacts from 2014 to 2016, who were subjected to an extensive protocol that included clinical, molecular (peripheral blood qPCR, slit-skin smear qPCR, skin biopsy qPCR) and electroneuromyographic evaluations. RESULTS/PRINCIPAL FINDINGS: The positivity of peripheral blood qPCR of seropositive contacts was 40.6% (71/175) whereas only 8.6% (3/35) were qPCR positive in seronegative contacts (p = 0.0003). For the slit-skin smear, only 4% (7/175) of seropositive contacts presented positive bacilloscopy, whereas the qPCR detected 47.4% (83/175) positivity in this group compared with only 17.1% (6/35) in seronegative contacts (p = 0.0009). In the ENMG evaluation of contacts, 31.4% (55/175) of seropositives presented some neural impairment, and 13.3% (4/35) in seronegatives (p = 0.0163). The presence of neural thickening conferred a 2.94-fold higher chance of ENMG abnormality (p = 0.0031). Seropositive contacts presented a 4.04-fold higher chance of neural impairment (p = 0.0206). The peripheral blood qPCR positivity presented odds 2.08-fold higher towards neural impairment (OR, 2.08; p = 0.028). Contrarily, the presence of at least one BCG vaccine scar demonstrated 2.44-fold greater protection against neural impairment (OR = 0.41; p = 0.044). CONCLUSIONS/SIGNIFICANCE: ELISA anti-PGL-I is the most important test in determining the increased chance of neural impairment in asymptomatic leprosy household contacts. The combination of the two assays (ELISA anti-PGL-I and peripheral blood qPCR) and the presence of BCG scar may identify individuals with higher chances of developing leprosy neuropathy, corroborating with the early diagnosis and treatment.

Revisiting primary neural leprosy: Clinical, serological, molecular, and neurophysiological aspects.

BACKGROUND: Leprosy neuropathy is considered the most common peripheral neuropathy of infectious etiology worldwide, representing a public health problem. Clinical diagnosis of primary neural leprosy (PNL) is challenging, since no skin lesions are found and the slit skin smear bacilloscopy is negative. However, there are still controversial concepts regarding the primary-neural versus pure-neural leprosy definition, which will be explored by using multiple clinical-laboratory analyses in this study. METHODOLOGY/PRINCIPAL FINDINGS: Seventy patients diagnosed with primary neural leprosy from 2014 to 2016 underwent clinical, laboratorial and neurophysiological evaluation. All patients presented an asymmetric neural impairment, with nerve thickening in 58.6%. Electroneuromyography showed a pattern of mononeuropathy in 51.4%. Positivity for ELISA anti-PGL1 was 52.9%, while the qPCR of slit skin smear was 78.6%. The qPCR of nerve biopsies was positive in 60.8%. Patients with multiple mononeuropathy patterns showed lower levels of anti-PGL-1 (p = 0.0006), and higher frequency of neural thickening (p = 0.0008) and sensory symptoms (p = 0.01) than those with mononeuropathy. CONCLUSIONS/SIGNIFICANCE: PNL is not a synonym of pure neural leprosy, as this condition may include a generalized immune response and also a skin involvement, documented by molecular findings. Immunological, molecular, and neurophysiological tools must be implemented for diagnosing primary neural leprosy to achieve effective treatment and reduction of its resultant disabilities that still represent a public health problem in several developing nations. Finally, we propose a algorithm and recommendations for the diagnosis of primary neural leprosy based on the combination of the three clinical-laboratorial tools.

Early detection of neuropathy in leprosy: a comparison of five tests for field settings.

BACKGROUND: Early detection and treatment of neuropathy in leprosy is important to prevent disabilities. A recent study showed that the Nerve Conduction Studies (NCS) and Warm Detection Thresholds (WDT) tests can detect leprosy neuropathy the earliest. These two tests are not practical under field conditions, however, because they require climate-controlled rooms and highly trained staff and are expensive. We assessed the usefulness of alternative test methods and their sensitivity and specificity to detect neuropathy at an early stage. METHODS: Through a literature search we identified five alternative devices that appeared user-friendly, more affordable, portable and/or battery-operated: the Neuropad®, Vibratip™, NC-Stat®DPNCheck™, NeuroQuick and the Thermal Sensibility Tester (TST), assessing respectively sweat function, vibration sensation, nerve conduction, cold sensation and warm sensation. In leprosy patients in Bangladesh, the posterior tibial and sural nerves that tested normal for the monofilament test and voluntary muscle test were assessed with the NCS and WDT as reference standard tests. The alternative devices were then tested on 94 nerves with abnormal WDT and/or NCS results and on 94 unaffected nerves. Sensitivity and specificity were the main outcomes. RESULTS: The NeuroQuick and the TST showed very good sensitivity and specificity. On the sural nerve, the NeuroQuick had both a sensitivity and a specificity of 86%. The TST had a sensitivity of 83% and a specificity of 82%. Both the NC-Stat®DPNCheck™ and Vibratip™ had a high specificity (88% and 100%), but a low sensitivity (16% and 0%). On the posterior tibial nerve, the NeuroQuick and the TST also showed good sensitivity, but the sensitivity was lower than for the sural nerve. The Neuropad® had a sensitivity of 56% and a specificity of 61%. CONCLUSIONS: The NeuroQuick and TST are good candidates for further field-testing for reliability and reproducibility. The feasibility of production on a larger scale should be examined.

Nerve Damage in Young Patients with Leprosy Diagnosed in an Endemic Area of the Brazilian Amazon: A Cross-Sectional Study.

OBJECTIVE: To describe nerve damage and its association with clinical and epidemiologic characteristics in young patients with leprosy diagnosed in an endemic area of the Brazilian Amazon. STUDY DESIGN: All 45 patients with leprosy younger than 15 years of age and diagnosed at a health referral unit in northern Brazil were invited to participate in a cross-sectional, descriptive, analytical study. Subjects were submitted to a templated simple neurologic examination of the peripheral nerves and answered a structured questionnaire. RESULTS: Of 41 cases, referral was the mode of detection in 33 participants (80.5%); 19 (46.3%) had been seen by 3 or more physicians to obtain a diagnosis, and 26 (63.4%) had received other diagnoses. The interval between the onset of symptoms and diagnosis was more than 1 year in 30 cases (73.2%). Borderline leprosy was the predominant clinical form (48.8%); 63.4% of the participants had multibacillary leprosy, 31.7% had nerve damage, and 17.1% exhibited disabilities. The following variables showed a statistically significant association (P???.05) with nerve damage at diagnosis: home visit by the community health worker, number of doctors seen, number of skin lesions (>5), and lesions along the path of nerve trunks. CONCLUSION: Centralized healthcare, a low frequency of home visits by community health workers, and the difficulty in diagnosing leprosy in children are factors that contribute to late treatment initiation and an increased risk of peripheral nerve damage. In addition, multiple skin lesions and lesions along the path of nerve trunks require rigorous monitoring.

Minocycline in leprosy patients with recent onset clinical nerve function impairment.

Nerve function impairment (NFI) in leprosy may occur and progress despite multidrug therapy alone or in combination with corticosteroids. We observed improvement in neuritis when minocycline was administered in patients with type 2 lepra reaction. This prompted us to investigate the role of minocycline in recent onset NFI, especially in corticosteroid unresponsive leprosy patients. Leprosy patients with recent onset clinical NFI (<6 months), as determined by Monofilament Test (MFT) and Voluntary Muscle Test (VMT), were recruited. Minocycline 100mg/day was given for 3 months to these patients. The primary outcome was the proportion of patients with 'restored,' 'improved,' 'stabilized,' or 'deteriorated' NFI. Secondary outcomes included any improvement in nerve tenderness and pain. In this pilot study, 11 patients were recruited. The progression of NFI was halted in all; with 9 out of 11 patients (81.82%) showing ?restored? or ?improved? sensory or motor nerve functions, on assessment with MFT and VMT. No serious adverse effects due to minocycline were observed. Our pilot study demonstrates the efficacy and safety of minocycline in recent onset NFI in leprosy patients. However, larger and long term comparative trials are needed to validate the efficacy of minocycline in leprosy neuropathy.

Comprehensive electrophysiology in leprous neuropathy - Is there a clinico-electrophysiological dissociation?

OBJECTIVE: The diagnosis of leprous neuropathy is mostly empirical and electrophysiological studies may not truly represent the clinical findings. This study comprehensively evaluates the neuroelectrophysiology and looks at clinico-electrophysiological dissociation. METHODS: Conventional electrophysiological recording included evaluation of median, ulnar, radial, tibial, and common peroneal nerve; an extended protocol included great auricular, phrenic, and facial nerves, along with sympathetic skin response and blink reflex. Nerve biopsy and slit skin smear were done to aid categorization. RESULTS: Forty-six patients of leprosy were enrolled. Mononeuritis multiplex was the commonest presentation. Sensory loss was commoner than motor deficits. Approximately 60% of all cases were nerve-biopsy proven. Nerve thickening was present in 38.7% (214/552) of nerves examined. Clinico-electrophysiological dissociation between nerve thickening and nerve conduction findings was present in median, ulnar, great auricular, and common peroneal nerves. CONCLUSION: Electrophysiological findings outnumber occurrence of nerve thickening and clinical deficits in leprous neuropathy. From a clinical perspective, enlargement of great auricular, ulnar, and common peroneal nerves may be more sensitive in predicting electrophysiological abnormalities. SIGNIFICANCE: A comprehensive nerve conduction study including great auricular and phrenic nerves, coupled with a sympathetic skin response, may aid in detecting cases with paucity of findings since such a combination is seldom seen in other disorders.

Correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy.

BACKGROUND: In leprosy, sensory function of nerves is evaluated with monofilaments test and the motor function with voluntary muscle test, however electroneuromyography is considered as the gold-standard tool. OBJECTIVES: This study aimed: i) to evaluate the correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy; and ii) to identify the prevalence of leprosy neuropathy and the most compromised peripheral nerves in leprosy. METHODS: We analysed the data from a nested case-control study that identified 166 patients diagnosed with leprosy neuropathy confirmed by electromyography. This study was designed for an analysis of correlation between the diagnostic tests. RESULTS: The most prevalent type of the neural damage was the sensory and motor multiple mononeuropathy, observed in 62 (37.3%) cases. The highest prevalence was the ulnar nerve in 67 (40.3%) cases. Agreement specified by nerves was moderate, ranging from k = 0.58 in the deep peroneal nerve to k = 0.41 in the posterior tibial nerve). Overall agreement between the clinical tests and electroneuromyography was very poor. Monofilaments test with k = 0.02 (95% CI 0.00-0.12) and voluntary muscle test with 0.16 (95% CI 0.04 to 0.28, P = 0.01). CONCLUSIONS: There is a low to moderate correlation between clinical tests (monofilaments and voluntary muscle tests) and the electroneuromyography examination. The most prevalent type of neural impairment was the sensory and motor multiple mononeuropathy, and the most affected nerve was the ulnar.

[Borderline leprosy as a rare differential diagnosis]. / Borderline-Lepra als seltene Differenzialdiagnose.

History and clinical findings | A 42-year-old migrant from Brazil presented with persistent sensory disturbances, skin discolorations and local alopecia in the upper limbs. Decisive for the presentation in our Tropical Medicine Clinic were new occurrences of severe pain and redness and swelling in the area of the lesions that had already been assessed by a number of medical specialists without a clear diagnosis could be made. Investigations and diagnosis | The histological analysis of skin biopsies showed perivascular, perineural, periadnexial lymphocytic and granulomatous dermatitis. In a direct microbiological preparation individual acid fast bacilli could be detected (Ziehl-Neelsen stain). The electroneurographical examination demonstrated a sensitive peripheral-neurogenic damage with emphasis on the right median nerve and the left ulnar and radial nerves. Thermography revealed an increased heating or cooling threshold. The serological investigation by ELISA for IgM antibodies against the phenolic glycolipid (PGL-1) was positive (titer 1 : 1200). In summary, the diagnosis of borderline leprosy (infection with Mycobacterium leprae) with transition to multibacillary leprosy (according to WHO) and leprosy reaction type 1 was made. Treatment and course | We initiated an oral antimycobacterial therapy (multidrug therapy, MDT) with rifampin, clofazimine and dapsone for 12 months (WHO regimen for multibacillary leprosy). Leprosy reaction type 1 was treated with prednisolone and by increasing the dose of clofazimine. Analgesic therapy on demand was carried out with nonsteroidal anti-inflammatory drugs (ibuprofen). MDT and successful management of leprosy reaction lead to a rapid improvement of symptoms. Conclusions | Leprosy is an infectious disease occurring only rarely in Germany (average incidence of 1-2 cases per year) that is diagnosed almost exclusively among migrants. Main symptoms comprise non-itchy, reddish, touch insensitive skin lesions or nerve deficits. The diagnosis is based primarily on the clinical presentation, supplemented by pathogen detection, histology, neurophysiological findings and serology. Standard therapy is a combination of rifampin, clofazimine and dapsone (WHO scheme) for at least 6 months.

Corticosteroids for treating nerve damage in leprosy.

BACKGROUND: Leprosy causes nerve damage that can result in nerve function impairment and disability. Corticosteroids are commonly used for treating nerve damage, although their long-term effect is uncertain. This is an update of a review first published in 2007, and previously updated in 2009 and 2011. OBJECTIVES: To assess the effects of corticosteroids on nerve damage in leprosy. SEARCH METHODS: On 16 June 2015, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, and LILACS. We also checked clinical trials registers and contacted trial authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of corticosteroids for nerve damage in leprosy. The comparators were no treatment, placebo treatment, or a different corticosteroid regimen. DATA COLLECTION AND ANALYSIS: The primary outcome was improvement in nerve function after one year. Secondary outcomes were change in nerve pain, limitations in activities of daily living, limitations in participation, and adverse events. Two review authors independently extracted data and assessed trial quality. When data were lacking, we contacted trial authors for additional information. MAIN RESULTS: We included five RCTs involving 576 people. The trials were largely at low risk of bias, but we considered the quality of the evidence from these trials as moderate to low, largely due to imprecision from small sample sizes. Two out of the five trials reported on improvement in nerve function at one year. These two trials compared prednisolone with placebo. One trial, with 84 participants, treated mild sensory impairment of less than six months' duration, and the other, with 95 participants, treated nerve function impairment of 6 to 24 months' duration. There was no significant difference in nerve function improvement after 12 months between people treated with prednisolone and those treated with placebo. Adverse events were not reported significantly more often with corticosteroids than with placebo. The other three trials did not report on the primary outcome measure. One (334 participants) compared three corticosteroid regimens for severe type 1 reactions. No serious side effects of steroids were reported in any participant during the follow-up period. Another trial (21 participants) compared low-dose prednisone with high-dose prednisone for ulnar neuropathy. Two participants on the higher dose of prednisone reported adverse effects. The last (42 participants) compared intravenous methylprednisolone and oral prednisolone with intravenous normal saline and oral prednisolone. The trial found no significant differences between the groups in the occurrence of adverse events. AUTHORS' CONCLUSIONS: Corticosteroids are used for treating acute nerve damage in leprosy, but moderate-quality evidence from two RCTs treating either longstanding or mild nerve function impairment did not show corticosteroids to have a superior effect to placebo on nerve function improvement. A third trial showed significant benefit from a five-month steroid regimen over a three-month regimen in terms of response to treatment (need for additional corticosteroids). Further RCTs are needed to establish optimal corticosteroid regimens and to examine the efficacy and safety of adjuvant or new therapies for treating nerve damage in leprosy. Future trials should address non-clinical aspects, such as costs and impact on quality of life, which are highly relevant indicators for both policymakers and participants.