Autophagy as a Target for Drug Development Of Skin Infection Caused by Mycobacteria.

Pathogenic mycobacteria species may subvert the innate immune mechanisms and can modulate the activation of cells that cause disease in the skin. Cutaneous mycobacterial infection may present different clinical presentations and it is associated with stigma, deformity, and disability. The understanding of the immunopathogenic mechanisms related to mycobacterial infection in human skin is of pivotal importance to identify targets for new therapeutic strategies. The occurrence of reactional episodes and relapse in leprosy patients, the emergence of resistant mycobacteria strains, and the absence of effective drugs to treat mycobacterial cutaneous infection increased the interest in the development of therapies based on repurposed drugs against mycobacteria. The mechanism of action of many of these therapies evaluated is linked to the activation of autophagy. Autophagy is an evolutionary conserved lysosomal degradation pathway that has been associated with the control of the mycobacterial bacillary load. Here, we review the role of autophagy in the pathogenesis of cutaneous mycobacterial infection and discuss the perspectives of autophagy as a target for drug development and repurposing against cutaneous mycobacterial infection.

Epidemiological aspects of leprosy.

Leprosy is a bacterial infection causing severe disfigurement of the affected individual. It is considered as an ancient disease affecting humanity since thousands of years and also has tremendous stigma associated with it. It is known as a neglected tropical disease. In spite of all the efforts, the disease remains a major healthcare distress in many underdeveloped and developing countries like India and Brazil. Thus, to understand the disease and implement various strategies successfully, one need to understand the epidemiological aspect of the disease along with various operational factors influencing the epidemiological data. Thus, the present paper describes the various epidemiological facts and figures of leprosy along with the suggestions and measures to tackle this global ailment.

Clinicodermoscopic study of histoid leprosy: a case series.

BACKGROUND: Histoid leprosy (HL) is a highly bacilliferous form of leprosy which requires early diagnosis and management. Dermoscopy is a noninvasive diagnostic method for various malignant and nonmalignant disorders. The aim of this study was to describe the dermoscopic patterns of various types of HL lesions over different body parts. METHODS: This was a hospital-based observational study which evaluated the clinical and dermoscopic features of a series of patients with the diagnosis of HL. The diagnosis was confirmed clinically, histologically, and through the demonstration of bacilli. A handheld dermatoscope at 10x magnification in polarized mode was employed to examine multiple lesions over various body sites. RESULTS: A total of four patients (three female, one male) were included. Papules were the most common type of lesion, and limbs were most frequently involved. Linear branching vessels and shiny white structures were present in all cases and in all lesion types. The linear branching vessels frequently presented in the form of crown vessels. Ulcerated lesions and umbilicated lesions also showed prominent vascularity. Follicular plugging was observed in the lesions over limbs. CONCLUSION: Dermoscopy may aid in the diagnosis of HL by showing prominent dermoscopic features such as linear branching vessels and shiny white structures.

Cutaneous atypical mycobacteriosis with sporotrichoid clinical presentation caused by automotive accident

Abstract: Atypical mycobacterial infections are caused by mycobacteria other than those from the M. tuberculosis complex and M. leprae. Its incidence has increased progressively, with considerable increase of scientific publications on the subject. Only 10% of the cases present with cutaneous infections, most of them related to surgical interventions and aesthetic procedures. We present a case of mycobacteriosis due to automotive accident that presented a diagnostic challenge due to its clinical presentation with lesions of sporotrichoid progression in the lymphatic system.

Cutaneous atypical mycobacteriosis with sporotrichoid clinical presentation caused by automotive accident.

Atypical mycobacterial infections are caused by mycobacteria other than those from the M. tuberculosis complex and M. leprae. Its incidence has increased progressively, with considerable increase of scientific publications on the subject. Only 10% of the cases present with cutaneous infections, most of them related to surgical interventions and aesthetic procedures. We present a case of mycobacteriosis due to automotive accident that presented a diagnostic challenge due to its clinical presentation with lesions of sporotrichoid progression in the lymphatic system.

Tuberculoid leprosy presenting as a "racket" lesion.

The "racket" lesion is a rare presentation of tuberculoid leprosy, which consists of a thickened nerve branch emerging from a tuberculoid plaque. It results from centripetal damage to cutaneous nerves caused by granuloma formation. We describe a typical case of tuberculoid leprosy presenting as a "racket" lesion. The lesion persisted after treatment with paucibacillary multidrug therapy.

Leprosy: review of the epidemiological, clinical, and etiopathogenic aspects - part 1.

Leprosy is caused by Mycobacterium leprae and has been known since biblical times. It is still endemic in many regions of the world and a public health problem in Brazil. The prevalence rate in 2011 reached 1.54 cases per 10,000 inhabitants in Brazil. The mechanism of transmission of leprosy consists of prolonged close contact between susceptible and genetically predisposed individuals and untreated multibacillary patients. Transmission occurs through inhalation of bacilli present in upper airway secretion. The nasal mucosa is the main entry or exit route of M. leprae. The deeper understanding of the structural and biological characteristics of M. leprae, the sequencing of its genome, along with the advances in understanding the mechanisms of host immune response against the bacilli, dependent on genetic susceptibility, have contributed to the understanding of the pathogenesis, variations in the clinical characteristics, and progression of the disease. This article aims to update dermatologist on epidemiological, clinical, and etiopathogenic leprosy aspects.

Leprosy: review of the epidemiological, clinical, and etiopathogenic aspects - Part 1

Leprosy is caused by Mycobacterium leprae and has been known since biblical times. It is still endemic in many regions of the world and a public health problem in Brazil. The prevalence rate in 2011 reached 1.54 cases per 10,000 inhabitants in Brazil. The mechanism of transmission of leprosy consists of prolonged close contact between susceptible and genetically predisposed individuals and untreated multibacillary patients. Transmission occurs through inhalation of bacilli present in upper airway secretion. The nasal mucosa is the main entry or exit route of M. leprae. The deeper understanding of the structural and biological characteristics of M. leprae, the sequencing of its genome, along with the advances in understanding the mechanisms of host immune response against the bacilli, dependent on genetic susceptibility, have contributed to the understanding of the pathogenesis, variations in the clinical characteristics, and progression of the disease. This article aims to update dermatologist on epidemiological, clinical, and etiopathogenic leprosy aspects.

Mycobacterium leprae and Mycobacterium haemophilum co-infection in an iatrogenically immunosuppressed patient.

We present the case of a native Texan who was diagnosed with tuberculoid leprosy and later developed a cutaneous infection with M. haemophilum following iatrogenic immunosuppression. To our knowledge, there are no such reports of M. haemophilum and M. leprae infection occurring simultaneously in the same host.

Feline cutaneous mycobacteriosis: a review of clinical, pathological and molecular characterization of one case of Mycobacterium microti skin infection and nine cases of feline leprosy syndrome from France and New Caledonia.

BACKGROUND: Ten cats with skin lesions characteristic of cutaneous mycobacteriosis were included in this retrospective clinical, pathological and molecular study. HYPOTHESIS/OBJECTIVES: The aim of this study was to identify the causative agent and to compare the clinicopathological features of these cases with those of previous studies. METHODS: Cats were from the south east of France (eight cases), central France (one case) and New Caledonia (South Pacific; one case). Criteria for inclusion were histological evidence of granulomatous dermatitis and/or panniculitis, with acid-fast bacilli within macrophages or extracellularly in regions of tissue necrosis. PCR targeting the 16S-23S internal transcribed spacer region and sequence analysis were performed using DNA extracted from formalin-fixed, paraffin-embedded tissues from all cases. RESULTS: All cats were presented with a history of alopecic to ulcerated nodules. Most cases had limited disease, with one to few nodules, while others (three cats) showed a more aggressive clinical course. Lesions from eight cats yielded a sequence consistent with Mycobacterium lepraemurium, while Mycobacterium microti was identified postmortem from the cutaneous lesion in the cat originating from central France and euthanized for its debilitating condition. No PCR product could be amplified from the remaining specimen. CONCLUSIONS AND CLINICAL IMPORTANCE: Based on this geographically restricted case series, feline leprosy in southern France is most likely to be caused by M. lepraemurium and presents as a generally self-limiting disease. Molecular testing is essential to assess zoonotic potential, because M. microti-induced cutaneous mycobacteriosis can resemble feline leprosy syndrome.

One year follow up of a cohort of suspected leprosy cases: findings from a leprosy 'Selective Special Drive' in Gadchiroli district, Maharashtra, India.

OBJECTIVES: The study involves a follow-up visit in 2010, to hyper-endemic Gadchiroli district of Maharashtra, India, to evaluate the current status of those suspected in 2009 of having skin/nerve lesions suggestive of leprosy, and to study the interactions between such people and the State leprosy programme. DESIGN: The study cohort comprised of those confirmed with leprosy (n = 151 and 157/233 absentee 'suspects' who were not examined by the study team in 2009 in 14 of 45 Primary Health Centres (PHCs). At follow-up, the treatment status of the confirmed cases was checked from PHC registers and cross-checked by direct questioning of patients and their views were sought on PHC leprosy services. The 157 absentee 'suspects' were queried about the reasons for their absence. RESULTS: Thirty nine 'absentee suspects' were found to have leprosy. A notable feature of the follow-up visit was that 114 people in the communities, other than those listed as 'suspects' by Community Health Workers (CHWs), voluntarily sought out the team for their opinion on hypopigmented/anaesthetic lesions, which resulted in a further 39 new cases being brought to light. (Total new cases = 78). The follow-up revealed discrepancies (100% vs. 75%) between PHC records and testimonies of the registered patients about regularity of treatment; irregularity of MDT supply was cited by some for dropping out of treatment. Other reasons proffered for irregularity were lepra reaction, fear of stigma, ignorance about leprosy and preference for faith healers. Medical Officers of PHCs were not trained in the management of lepra reactions; that task, along with disability care being entrusted to a paramedical worker of an NGO during periodic visits. CONCLUSIONS: There are remediable lacunae in the recording and dispensing of MDT by the State apparatus, as well as a need for refresher training in leprosy diagnosis for PHC staff, and in lepra reaction management for medical officers. The large number (78) of new cases detected in the follow-up, in part of Gadchiroli district strongly suggests more to-be-discovered cases in the communities.

Anaplastic large cell lymphoma and lepromatous leprosy: a rare coexistence.

Lepromatous leprosy (LL) has been reported in the literature with Non Hodgkin Lymphoma and rarely with Hodgkin Lymphoma. However, an extensive search of the literature shows no case report describing anaplastic large cell lymphoma (ALCL) in association with LL. We report a case of a young male with LL who was found to have ALCL. This is an interesting case of coexistence of an endemic infectious disease and a rare lymphoma involving the same lymph node, with a brief review of the literature.