Effectiveness of neurolysis as a treatment for complications of leprosy neuritis: a systematic review.

BACKGROUND: Complications of leprosy neuritis are considered serious and apparent, with the potential to disable and/or limit individuals. These complications affect not only a patient's physical functioning, but also their family and social lives, while directly impacting the ability to work and/or maintain financial independence, subsequently interfering with their overall quality of life. The present review, therefore, aimed to analyze the effectiveness of neurolysis as an alternative treatment for the complications associated with leprosy neuritis. METHODS: The present review was performed based on the Joanna Briggs Institute methodology, in an effort to answer the following research question: what is the effectiveness of neurolysis as a treatment for leprosy neuritis complications? This research question was defined using the patient-intervention-outcome (PIO) framework, where leprosy represents 'P', neurolysis for 'I', and neuropathic pain/motor function/sensorial function/physical disability/quality of life for 'O'. Randomized and non-randomized clinical trials and prospective observational cohort studies were included in the present review, with no time or date restrictions. RESULTS: The present review included 1 randomized clinical trial and 10 prospective studies, published between 1976 and 2020. All of the outcomes showed improvement, with relief from neuropathic pain being the primary finding. CONCLUSIONS: The evidence obtained in the present review suggested that neurolysis is an effective alternative for the treatment of physical disabilities, the recovery of sensory and motor function, the restoration of quality of life, and neuropathic pain relief.

Ultrasonography as a diagnostic tool for Neural Pain in Leprosy.

Leprosy is still a prevalent disease in Brazil, representing 93% of all occurrences in the Americas. Leprosy neuropathy is one of the most worrying manifestations of the disease. Acute neuropathy usually occurs during reaction episodes and is called neuritis. Twenty-two leprosy patients were included in this study. These patients had neural pain associated with ulnar sensory neuropathy, with or without adjunct motor involvement. The neurological picture began within thirty days of the clinical evaluation. The patients underwent a nerve conduction study and the demyelinating findings confirmed the diagnosis of neuritis. Ultrasonographic study (US) of the ulnar nerve was performed in all patients by a radiologist who was blinded to the clinical or neurophysiological results. Morphological characteristics of the ulnar nerve were analyzed, such as echogenicity, fascicular pattern, transverse cross-sectional area (CSA), aspect of the epineurium, as well as their anatomical relationships. The volume of selected muscles referring to the ulnar nerve, as well as their echogenicity, was also examined. Based on this analysis, patients with increased ulnar nerve CSA associated with loss of fascicular pattern, epineurium hyperechogenicity and presence of power Doppler flow were classified as neuritis. Therefore, patients initially classified by the clinical-electrophysiological criteria were reclassified by the imaging criteria pre-established in this study as with and without neuritis. Loss of fascicular pattern and flow detection on power Doppler showed to be significant morphological features in the detection of neuritis. In 38.5% of patients without clinical or neurophysiological findings of neuritis, US identified power Doppler flow and loss of fascicular pattern. The US is a method of high resolution and portability, and its low cost means that it could be used as an auxiliary tool in the diagnosis of neuritis and its treatment, especially in basic health units.

Leprosy as immune reconstitution inflammatory syndrome in patients living with HIV: Description of French Guiana's cases over 20 years and systematic review of the literature.

BACKGROUND: HIV infection is highly prevalent in French Guiana, a territory where leprosy is also endemic. Since the introduction of Highly Active Antiretroviral Treatment (HAART) in the management of HIV, leprosy has been reported as part of the immune reconstitution inflammatory syndrome (IRIS). METHODOLOGY/PRINCIPAL FINDINGS: We aimed to present a general description of these forms of leprosy as IRIS, highlighting clinical and therapeutic specificities. A retrospective study was conducted in French Guiana, including patients living with HIV (PLHIV) with advanced infection (CD4 < 200/mm3) and developing leprosy or a leprosy reaction within six months of HAART initiation, from 2000 to 2020. Clinical, histological and biological data were collected for all these patients. Six patients were reported in French Guiana. A systematic review of the literature was conducted, and its results were added to an overall analysis. Overall, seventy-three PLHIV were included. They were mainly men (74%), aged 22-54 years (median 36 years), mainly from Brazil (46.5%) and India (32.8%). Most leprosy cases (56.2%) were borderline tuberculoid (BT). Leprosy reactions were frequent (74%), mainly type 1 reaction (T1R) (68.5%), sometimes intense with ulceration of skin lesions (22%). Neuritis was observed in 30.1% of patients. The outcome was always favorable under multidrug therapy (MDT), continuation of HAART and additional corticosteroid therapy in case of neuritis or ulceration. There was no relapse. CONCLUSION: Leprosy as IRIS in PLHIV mainly presents as a BT leprosy in a T1R state, sometimes with ulcerated skin lesions. Response to MDT is usually good. Systemic corticosteroids are necessary and efficient in case of neuritis.

Dramatic secukinumab-mediated improvements in refractory leprosy-related neuritis via the modulation of T helper 1 (Th1) and T helper 17 (Th17) immune pathways.

A 39-year-old woman was diagnosed with relapsed multibacillary leprosy and refractory neuritis. Here, we describe an evident loss of therapeutic effectiveness after the third pulse of corticosteroids, which may be attributed to tachyphylaxis and the posterior modulation of interferon- γ (IFN-γ), tumor necrosis factor- α (TNF-α,) interleukin-17A (IL-17A), and IL-12/23p40 after the induction phase of secukinumab. In this case, plasma cytokine analysis showed that secukinumab induced a reduction in IL-17 concomitant with impressive clinical improvements in the patient's neural function. Interestingly, secukinumab induced reductions in cytokines related to Th1 responses and earlier stages of the Th17 response, including IL-23/12.

Dramatic secukinumab-mediated improvements in refractory leprosy-related neuritis via the modulation of T helper 1 (Th1) and T helper 17 (Th17) immune pathways

Abstract A 39-year-old woman was diagnosed with relapsed multibacillary leprosy and refractory neuritis. Here, we describe an evident loss of therapeutic effectiveness after the third pulse of corticosteroids, which may be attributed to tachyphylaxis and the posterior modulation of interferon- γ (IFN-γ), tumor necrosis factor- α (TNF-α,) interleukin-17A (IL-17A), and IL-12/23p40 after the induction phase of secukinumab. In this case, plasma cytokine analysis showed that secukinumab induced a reduction in IL-17 concomitant with impressive clinical improvements in the patient's neural function. Interestingly, secukinumab induced reductions in cytokines related to Th1 responses and earlier stages of the Th17 response, including IL-23/12.

Ultrasonography of Leprosy Neuropathy: A Longitudinal Prospective Study.

BACKGROUND: Previous studies have shown that leprosy multi-drug therapy (MDT) does not stop the progression of nerve function impairment. There are no prospective studies investigating the evolution of nerve anatomic abnormalities after treatment. We examined leprosy patients aiming to investigate the evolution of nerve ultrasonography (US) abnormalities and the risk factors for poor outcomes after MDT. METHODOLOGY/PRINCIPAL FINDINGS: We performed bilateral US of the ulnar (U), median (M) and common fibular (CF) nerves in 9 paucibacillary (PB) and 64 multibacillary (MB) patients before and after MDT. Forty-two patients had leprosy reactions (type 1, type 2, acute neuritis) during the study. We analyzed nerve maximum cross-sectional areas (CSA), echogenicity and Doppler signal. Poor outcomes included a post-treatment CSA above normal limits with a reduction of less than 30% (U, M) or 40% (CF) from the baseline, echogenicity abnormalities or intraneural Doppler in the post-treatment study. We found that PB and patients without reactions showed significant increases in CSA at CF, whereas MB and patients with reactions had CSA reduction in some nerves after treatment (p<0.05). Despite this reduction, we observed a greater frequency of poor CSA outcomes in the MB compared to the PB (77.8% and 40.6%; p>0.05) and in the patients with reactions compared to those without (66.7% and 38.7%; p<0.05). There was significantly higher odds ratio (7.75; 95%CI: 1.56-38.45) for poor CSA outcomes only for M nerve in patients with reactions. Poor echogenicity outcomes were more frequent in MB (59.4%) compared to PB (22.2%) (p<0.05). There was significant association between poor Doppler outcomes and neuritis. Gender, disease duration, and leprosy classification were not significant risk factors for poor outcomes in CSA, echogenicity or Doppler. CONCLUSIONS/SIGNIFICANCE: US nerve abnormalities can worsen after treatment despite the leprosy classification or the presence of reactions.

Management of chronic neuritis with a combination regimen of lower doses prednisolone and methotrexate: a brief report.

INTRODUCTION: Recommended fixed duration prednisolone regimen was not found effective in the treatment of chronic neuritis. Alternate effective treatment was being sought to reduce the deformity in the field of leprosy. OBJECTIVE: We wished to see whether a prolonged course of prednisolone and methotrexate could be of any help for them. METHODOLOGY: In 2012-2014, an open pilot clinical study was undertaken where three chronic neuritic patients were treated with lower doses prednisolone and methotrexate for 12 months and a follow up period was delivered for 12 months. The study was undertaken in one of the outdoor clinics of the university. RESULTS: Complete and permanent remission of neuritis was achieved with appreciable functional recovery. Few mild self-limiting side-effects from prednisolone were observed and there was no side-effects from methotrexate. CONCLUSION: Prolonged course of prednisolone and methotrexate was found safe and effective in treating chronic neuritis.

Surgical treatment of type I neuritis in a teenage boy with borderline tuberculoid leprosy.

Exacerbation of the immune response against Mycobacterium leprae can lead to neuritis, which is commonly treated via immunosuppression with corticosteroids. Early neurolysis may be performed concurrently, especially in young patients with a risk of functional sequelae. We report the case of a young patient experienced intense pain in the left elbow one year after the treatment of tuberculoid-tuberculoid leprosy. The pain was associated with paresthesias in the ulnar edge and left ulnar claw. After evaluation, the diagnosis was changed to borderline tuberculoid leprosy accompanied with neuritis of the left ulnar nerve. Early neurolysis resulted in rapid reduction of the pain and recovery of motor function.

Surgical treatment of type I neuritis in a teenage boy with borderline tuberculoid leprosy

Exacerbation of the immune response against Mycobacterium leprae can lead to neuritis, which is commonly treated via immunosuppression with corticosteroids. Early neurolysis may be performed concurrently, especially in young patients with a risk of functional sequelae. We report the case of a young patient experienced intense pain in the left elbow one year after the treatment of tuberculoid-tuberculoid leprosy. The pain was associated with paresthesias in the ulnar edge and left ulnar claw. After evaluation, the diagnosis was changed to borderline tuberculoid leprosy accompanied with neuritis of the left ulnar nerve. Early neurolysis resulted in rapid reduction of the pain and recovery of motor function.

Leprous polyneuritis cranialis mimicking orbital apex syndrome.

Leprosy is one of the most prevalent infections in India, with our country accounting for almost 60 percent of the world's patients. Hence unusual presentations of leprosy should be sought for and treated at the earliest. We report this rare case of polyneuritis cranialis secondary to leprosy. Affection ofa single cranial nerve has been described previously but there is only one report of leprosy presenting like orbital apex syndrome.

Pure neuritic leprosy in patients from a high endemic region of Colombia.

Agua de Dios was a leprosarium for leprosy patients' obligatory isolation (1872-1961). Its leprosy incidence is the highest in Colombia (1.5-7/10000). Relapses are common. Government grant of US$ 200 per month subsidy is available to patients with disabilities. Spontaneous consultation with neural symptoms is frequent and simulation to get the subsidy has to be considered. We studied 36 subjects (2007-2009), with ages from 29-78, 19 of them men, with neural symptoms of 6 months to 20 years evolution. All had clinical examination, bacteriological examination, skin and nerve biopsies, electromyography (EMG), PCR for M. leprae, IgM anti-PGL1, and lepromin A. All but two are household contacts of leprosy patients. Symptoms were hypoesthesia of the hands and feet, and difficulty using hands with loss of muscular strength. None had skin lesions. Three had thickening of ulnar nerve. Lepromin was positive in all; bacteriology and biopsies were negative in all. The speed and amplitude of neural conduction were altered in 34 patients; two women had normal EMG and were considered to be feigning the disease; 21 were diagnosed as PNL by clinical, epidemiological and EMG findings; five of them had a positive PCR and one, high titers for IgM anti PGL1. Nine other subjects had diabetes and six carpal tunnel syndrome (CTS). Slow progression of disease, the lack of neural enlargement and the neural biopsies without inflammation suggest that most of these patients could have spontaneously cured PNL, as happens with other cases of paucibacillary leprosy. Diabetes and CTS are important differential diagnoses of PNL. Patients were treated with MDT and received the state subsidy.

A review of therapeutic nerve decompression for neuropathy in Hansen's disease with research suggestions.

Nerve decompression surgery for leprosy neuritis has a long history and large literature. New understanding of the high frequency of spontaneous recovery from nerve function impairment requires re-evaluation of the value of decompression in acute nerve dysfunction with strong evidence-based protocols. Several reports and theoretical considerations suggest research avenues that might offer hope for prevention of long-term complications and relief of impairment and disabilities.

Neuropatía hanseniana en una adulta joven / Hansenian neuropathy in a young adult

Se presenta el caso de una paciente de 27 años de edad, sin previos antecedentes, que en el período de puerperio comenzó a presentar deterioro neurológico progresivo, dificultad para la marcha, graves trastornos sensitivos, del tipo de las parestesias y artralgias, pérdida de la sensibilidad propioceptiva, al tacto, al dolor, a la temperatura y en zonas dístales de miembros inferiores, además de manchas violáceas en tórax, abdomen y rodillas. En la muestra para biopsia se encontró un patrón inflamatorio compatible con lepra lepromatosa(AU)

The case of a 27 year-old patient without previous history is reported, who in the puerperium began to present with progressive neurological deterioration, difficult walking, serious sensitive conditions such as paresthesia and arthralgia, loss of the proprioceptive sensibility to the tact, pain, temperature and in distal areas of inferior extremities besides violaceuos plaques in thorax, abdomen and knees. In the biopsy sample an inflammatory pattern consistent with lepromatous leprosy was found(AU)

Neuropatía hanseniana en una adulta joven / Hansenian neuropathy in a young adult

Se presenta el caso de una paciente de 27 años de edad, sin previos antecedentes, que en el período de puerperio comenzó a presentar deterioro neurológico progresivo, dificultad para la marcha, graves trastornos sensitivos, del tipo de las parestesias y artralgias, pérdida de la sensibilidad propioceptiva, al tacto, al dolor, a la temperatura y en zonas dístales de miembros inferiores, además de manchas violáceas en tórax, abdomen y rodillas. En la muestra para biopsia se encontró un patrón inflamatorio compatible con lepra lepromatosa.

The case of a 27 year-old patient without previous history is reported, who in the puerperium began to present with progressive neurological deterioration, difficult walking, serious sensitive conditions such as paresthesia and arthralgia, loss of the proprioceptive sensibility to the tact, pain, temperature and in distal areas of inferior extremities besides violaceuos plaques in thorax, abdomen and knees. In the biopsy sample an inflammatory pattern consistent with lepromatous leprosy was found.