scholarly journals Neutrophil NETworking in ENL: Potential as a Putative Biomarker: Future Insights

2021 ◽  
Vol 8 ◽  
Author(s):  
Smrity Sahu ◽  
Keshav Sharma ◽  
Maryada Sharma ◽  
Tarun Narang ◽  
Sunil Dogra ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Point Of Care ◽  
Unmet Need ◽  
Skin Lesions ◽  
Immunosuppressive Drugs ◽  
Lepromatous Leprosy ◽  
Metabolic Reprogramming ◽  
Prolonged Treatment ◽  
Erythema Nodosum Leprosum ◽  
Leprosy Patients

Erythema nodosum leprosum (ENL), also known as type 2 reaction (T2R) is an immune complex mediated (type III hypersensitivity) reactional state encountered in patients with borderline lepromatous and lepromatous leprosy (BL and LL) either before, during, or after the institution of anti-leprosy treatment (ALT). The consequences of ENL may be serious, leading to permanent nerve damage and deformities, constituting a major cause of leprosy-related morbidity. The incidence of ENL is increasing with the increasing number of multibacillary cases. Although the diagnosis of ENL is not difficult to make for physicians involved in the care of leprosy patients, its management continues to be a most challenging aspect of the leprosy eradication program: the chronic and recurrent painful skin lesions, neuritis, and organ involvement necessitates prolonged treatment with prednisolone, thalidomide, and anti-inflammatory and immunosuppressive drugs, which further adds to the existing morbidity. In addition, the use of immunosuppressants like methotrexate, azathioprine, cyclosporine, or biologics carries a risk of reactivation of persisters (Mycobacterium leprae), apart from their own end-organ toxicities. Most ENL therapeutic guidelines are primarily designed for acute episodes and there is scarcity of literature on management of patients with chronic and recurrent ENL. It is difficult to predict which patients will develop chronic or recurrent ENL and plan the treatment accordingly. We need simple point-of-care or ELISA-based tests from blood or skin biopsy samples, which can help us in identifying patients who are likely to require prolonged treatment and also inform us about the prognosis of reactions so that appropriate therapy may be started and continued for better ENL control in such patients. There is a significant unmet need for research for better understanding the immunopathogenesis of, and biomarkers for, ENL to improve clinical stratification and therapeutics. In this review we will discuss the potential of neutrophils (polymorphonuclear granulocytes) as putative diagnostic and prognostic biomarkers by virtue of their universal abundance in human blood, functional versatility, phenotypic heterogeneity, metabolic plasticity, differential hierarchical cytoplasmic granule mobilization, and their ability to form NETs (neutrophil extracellular traps). We will touch upon the various aspects of neutrophil biology relevant to ENL pathophysiology in a step-wise manner. We also hypothesize about an element of metabolic reprogramming of neutrophils by M. leprae that could be investigated and exploited for biomarker discovery. In the end, a potential role for neutrophil derived exosomes as a novel biomarker for ENL will also be explored.

Unusual non-trophic ulcerations in leprosy: A case series of 17 patients

2021 ◽  
pp. 004947552199849
Author(s):  
Prakriti Shukla ◽  
Kiran Preet Malhotra ◽  
Parul Verma ◽  
Swastika Suvirya ◽  
Abir Saraswat ◽  
...  
Keyword(s):  
Erythema Nodosum ◽  
Case Series ◽  
Lepromatous Leprosy ◽  
Sweet Syndrome ◽  
Erythema Nodosum Leprosum ◽  
Leprosy Patients ◽  
Atypical Presentations ◽  
Neuropathic Ulcers

Non-neuropathic ulcers in leprosy patients are infrequently seen, and atypical presentations are prone to misdiagnosis. We evaluated diagnosed cases of leprosy between January 2017 and January 2020 for the presence of cutaneous ulceration, Ridley–Jopling subtype of leprosy, reactions and histologic features of these ulcerations. Treatment was given as WHO recommended multi-bacillary multi-drug therapy. We found 17/386 leprosy patients with non-neuropathic ulcers. We describe three causes – spontaneous cutaneous ulceration in lepromatous leprosy (one nodular and one diffuse), lepra reactions (five patients with type 1; nine with type 2, further categorised into ulcerated Sweet syndrome-like who also had pseudoepitheliomatous hyperplasia, pustulo-necrotic and necrotic erythema nodosum leprosum) and Lucio phenomenon (one patient). Our series draws attention towards the different faces of non-neuropathic ulcers in leprosy, including some atypical and novel presentations.

Bacillary and phagolysosomal changes in skin lesions of multidrug-treated borderline or lepromatous leprosy patients

1989 ◽  
Vol 27 (2) ◽  
pp. 196-197
Author(s):  
J. Boddingius ◽  
H.B.P.M. Dijkman ◽  
E.G. Hendriksen ◽  
E.P. Prens ◽  
J. Muntendam ◽  
...  
Keyword(s):  
Skin Lesions ◽  
Lepromatous Leprosy ◽  
Leprosy Patients

scholarly journals Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients.

1992 ◽  
Vol 175 (6) ◽  
pp. 1729-1737 ◽  
Author(s):  
E P Sampaio ◽  
A L Moreira ◽  
E N Sarno ◽  
A M Malta ◽  
G Kaplan
Keyword(s):  
Interferon Gamma ◽  
Erythema Nodosum ◽  
Lepromatous Leprosy ◽  
Whole Body ◽  
Prolonged Treatment ◽  
Tnf Alpha ◽  
Multiple Drug ◽  
Recombinant Interferon ◽  
Erythema Nodosum Leprosum

10 patients with borderline and lepromatous leprosy were selected for a prolonged trial with recombinant interferon gamma (rIFN-gamma). Patients received 30 micrograms intradermally for six injections over a 9-d period, and then either 100 micrograms intradermally every 1 mo for 10 mo or every 2 wk for 5 mo (total, 1.2 mg). Erythema nodosum leprosum (ENL) was induced in 60% of the patients within 6-7 mo, as compared with an incidence of 15% per year with multiple drug therapy alone. The mean whole-body reduction in bacterial index over the first 6 mo was 0.9 log units. Cutaneous induration at the intradermal injection sites of greater than or equal to 15 mm predicted the development of a subsequent reactional state. Monocytes obtained from patients receiving the lymphokine demonstrated an increased respiratory burst and a 2.5-5.1-fold increase in tumor necrosis factor alpha (TNF-alpha) secretion in response to agonists. Patients in ENL had an even higher release of TNF-alpha from monocytes as well as high levels of TNF-alpha in the plasma (mean, 2,000 pg/ml). Thalidomide therapy was required to treat the systemic manifestations of ENL. Control of toxic symptoms with thalidomide was associated with a 50-80% reduction in agonist-stimulated monocyte TNF-alpha secretion. IFN-gamma enhanced the monocyte release of TNF-alpha by 3-7.5-fold (agonist dependent) when added to patient's cells in vitro, and this could be suppressed by the in vitro addition of 10 micrograms/ml of thalidomide.

scholarly journals Histopathological features of relapse cases in leprosy

2020 ◽  
Vol 8 (11) ◽  
pp. 4099
Author(s):  
Navdeep Kaur
Keyword(s):  
Skin Lesions ◽  
Etiologic Agent ◽  
World Health ◽  
Prolonged Treatment ◽  
Causative Organism ◽  
In Vitro Cultivation ◽  
Erythema Nodosum Leprosum ◽  
Immunological Tests ◽  
Health Organization

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.

scholarly journals Characterization of MicroRNA Expression Profiles and Identification of Potential Biomarkers in Leprosy

2017 ◽  
Vol 55 (5) ◽  
pp. 1516-1525 ◽  
Author(s):  
Karina T. O. S. Jorge ◽  
Renan P. Souza ◽  
Marieta T. A. Assis ◽  
Marcelo G. Araújo ◽  
Massimo Locati ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Principal Component ◽  
Skin Lesions ◽  
Lepromatous Leprosy ◽  
Diagnostic Potential ◽  
Reverse Transcription Quantitative Pcr ◽  
Leprosy Patients ◽  
Healthy Control ◽  
Validation Experiments

ABSTRACT Leprosy is an important cause of disability in the developing world. Early diagnosis is essential to allow for cure and to interrupt transmission of this infection. MicroRNAs (miRNAs) are important factors for host-pathogen interaction and they have been identified as biomarkers for various infectious diseases. The expression profile of 377 microRNAs were analyzed by TaqMan low-density array (TLDA) in skin lesions of tuberculoid and lepromatous leprosy patients as well as skin specimens from healthy controls. In a second step, 16 microRNAs were selected for validation experiments with reverse transcription-quantitative PCR (qRT-PCR) in skin samples from new individuals. Principal-component analysis followed by logistic regression model and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic potential of selected miRNAs. Four patterns of differential expression were identified in the TLDA experiment, suggesting a diagnostic potential of miRNAs in leprosy. After validation experiments, a combination of four miRNAs (miR-101, miR-196b, miR-27b, and miR-29c) was revealed as able to discriminate between healthy control and leprosy patients with 80% sensitivity and 91% specificity. This set of miRNAs was also able to discriminate between lepromatous and tuberculoid patients with a sensitivity of 83% and 80% specificity. In this work, it was possible to identify a set of miRNAs with good diagnostic potential for leprosy.

scholarly journals Dysregulation of IL-4 expression in lepromatous leprosy patients with and without erythema nodosum leprosum

2000 ◽  
Vol 71 ◽  
Author(s):  
I. NATH ◽  
N. VEMURI ◽  
A. L. REDDI ◽  
M. BHARADWAJ ◽  
P. BROOKS ◽  
...  
Keyword(s):  
Erythema Nodosum ◽  
Lepromatous Leprosy ◽  
Erythema Nodosum Leprosum ◽  
Leprosy Patients

scholarly journals Early Detection of Diabetic Peripheral Neuropathy: A Focus on Small Nerve Fibres

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 165
Author(s):  
Jamie Burgess ◽  
Bernhard Frank ◽  
Andrew Marshall ◽  
Rashaad S. Khalil ◽  
Georgios Ponirakis ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Nerve Fibre ◽  
Diabetic Peripheral Neuropathy ◽  
Point Of Care ◽  
Unmet Need ◽  
Screening Tools ◽  
Nerve Fibres ◽  
Diagnostic Laboratory ◽  
Corneal Confocal Microscopy ◽  
Small Nerve

Diabetic peripheral neuropathy (DPN) is the most common complication of both type 1 and 2 diabetes. As a result, neuropathic pain, diabetic foot ulcers and lower-limb amputations impact drastically on quality of life, contributing to the individual, societal, financial and healthcare burden of diabetes. DPN is diagnosed at a late, often pre-ulcerative stage due to a lack of early systematic screening and the endorsement of monofilament testing which identifies advanced neuropathy only. Compared to the success of the diabetic eye and kidney screening programmes there is clearly an unmet need for an objective reliable biomarker for the detection of early DPN. This article critically appraises research and clinical methods for the diagnosis or screening of early DPN. In brief, functional measures are subjective and are difficult to implement due to technical complexity. Moreover, skin biopsy is invasive, expensive and lacks diagnostic laboratory capacity. Indeed, point-of-care nerve conduction tests are convenient and easy to implement however questions are raised regarding their suitability for use in screening due to the lack of small nerve fibre evaluation. Corneal confocal microscopy (CCM) is a rapid, non-invasive, and reproducible technique to quantify small nerve fibre damage and repair which can be conducted alongside retinopathy screening. CCM identifies early sub-clinical DPN, predicts the development and allows staging of DPN severity. Automated quantification of CCM with AI has enabled enhanced unbiased quantification of small nerve fibres and potentially early diagnosis of DPN. Improved screening tools will prevent and reduce the burden of foot ulceration and amputations with the primary aim of reducing the prevalence of this common microvascular complication.

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