Macrophage immunophenotypes in Jorge Lobo's disease and lepromatous leprosy- A comparative study.

Jorge Lobo's disease (JLD) and lepromatous leprosy (LL) share several clinical, histological and immunological features, especially a deficiency in the cellular immune response. Macrophages participate in innate and adaptive inflammatory immune responses, as well as in tissue regeneration and repair. Macrophage function deficiency results in maintenance of diseases. M1 macrophages produce pro-inflammatory mediators and M2 produce anti-inflammatory cytokines. To better understand JLD and LL pathogenesis, we studied the immunophenotype profile of macrophage subtypes in 52 JLD skin lesions, in comparison with 16 LL samples, using a panmacrophage (CD68) antibody and selective immunohistochemical markers for M1 (iNOS) and M2 (CD163, CD204) responses, HAM56 (resident/fixed macrophage) and MAC 387 (recently infiltrating macrophage) antibodies. We found no differences between the groups regarding the density of the CD163, CD204, MAC387+ immunostained cells, including iNOS, considered a M1 marker. But HAM56+ cell density was higher in LL samples. By comparing the M2 and M1 immunomarkers in each disease separately, some other differences were found. Our results reinforce a higher M2 response in JLD and LL patients, depicting predominant production of anti-inflammatory cytokines, but also some distinction in degree of macrophage activation. Significant amounts of iNOS + macrophages take part in the immune milieu of both LL and JLD samples, displaying impaired microbicidal activity, like alternatively activated M2 cells.

Trans-epidermal extrusion of lepra bacilli from histoid lesions: a risk of continued transmission.

The current goal of Zero Leprosy focuses on the interruption of the transmission of infection within endemic regions. While the role of the skin in the transmission dynamics of leprosy has not been clearly delineated, recent research on the environmental presence of lepra bacilli brings this aspect back into focus. We present a case of lepromatous leprosy with perforated-appearing histoid lesions on the palms and soles, demonstrating the presence of lepra bacilli throughout the epidermis.

Case Report: Borderline Lepromatous Leprosy Therapy Complicated by Type 1 Leprosy Reaction and Adverse Reactions with Dapsone and Clofazimine.

Leprosy is a global health issue, causing long-term functional morbidity and stigma. Rapid diagnosis and appropriate treatment are important; however, early diagnosis is often challenging, especially in nonendemic areas. Here, we report a case of borderline lepromatous leprosy accompanied by dapsone-induced (neutropenia, anemia, and methemoglobinemia) and clofazimine-induced (skin discoloration and ichthyosis) side effects and type 1 leprosy reactions during administration of the multidrug therapy. The patient completely recovered without developing any deformities or visual impairment. To ensure early diagnosis and a favorable outcome, clinicians should be aware of the diminished sensation of skin lesions as a key physical finding and manage the drug toxicities and leprosy reactions appropriately in patients on multidrug therapy.

Reverse Koebner phenomenon in erythema nodosum leprosum.

BACKGROUND: Erythema nodosum leprosum (ENL) is an immunologically mediated phenomenon complicating the course of leprosy. Reverse Koebner phenomenon is the term used to describe the sparing of previously injured or diseased skin by new skin lesions of the disease. METHODS: A middle-aged woman with a known case of lepromatous leprosy for the past year presented with an eruption of reddish painful nodules over her body. The lesions were found to characteristically spare the sites of previous scars. RESULTS: This sparing phenomenon of previous scar sites has been termed reverse Koebner phenomenon, a site of the body that offers greater resistance than the rest of the body to the onset of the disease, seen in various diseases, but it has never been described in ENL. CONCLUSION: This sparing of scar sites in ENL can be attributed to reverse Koebner phenomenon.

Genomic characterization of Mycobacterium lepromatosis from ENL patients from India.

BACKGROUND: Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis. Both organisms cannot be cultured in vitro. M. lepromatosis was found to be associated mainly with diffuse lepromatous leprosy and with Lucio's phenomena initially. Later, M. lepromatosis was observed in borderline leprosy cases (BL), lepromatous leprosy cases (LL) and leprosy reactional cases (T1R and ENL). Although many cases are being reported with similar clinical features like Lucio phenomenon in India but M. lepromatosis was not isolated from these cases. The aim of this study was to screen MB patients and patients with type 2 reaction for the presence of M. lepromatosis. METHODOLOGY: We recruited a total of 75 multibacillary leprosy cases (45 MB cases without reaction and 30 type 2 reaction (ENL) cases) from TLM hospitals Purulia (West Bengal), Barabanki (Uttar Pradesh), Shahdara (Delhi) and PGIMER (Chandigarh), India. Punch biopsies of 5 mm were collected in 70% ethanol from all the study subjects. DNA was extracted followed by Hemi-nested PCR targeting 16S rRNA gene specific for M. lepromatosis. Further, PCR products were processed for Sanger sequencing for an absolute confirmation of M. lepromatosis. Whole genome sequencing was done to confirm the presence of M. lepromatosis. RESULT: We observed presence of M. lepromatosis in 4 necrotic ENL patients by heminested PCR. There was 100% 16S rRNA sequence similarity with M. lepromatosis FJ924 in one case, 98.96% in two cases and in one case it was 90.9% similarity by nucleotide BLAST (BLASTn) by using the NCBI website. On the basis of Sanger sequencing, we noted presence of M. lepromatosis in 3 necrotic ENL patients as one sample only gave 90.9% similarity by BLASTn. On the basis of de novo assembly and genome obtained, only one sample S4 with a 2.9 mb genome size was qualified for downstream analysis. Sixteen M. lepromatosis- specific proteins were identified in this case and the closest species was M. lepromatosis strain FJ924 based on whole genome level phylogeny. CONCLUSION: These results provide valuable insights into the prevalence of M. lepromatosis in ENL patients in different regions of India and contribute to our understanding of the genetic characteristics of this pathogen in the context of leprosy.

Evidencing leprosy neuronal inflammation by 18-Fluoro-deoxy-glucose.

BACKGROUND: Leprosy is caused by multiple interactions between Mycobacterium leprae (M. leprae) and the host's peripheral nerve cells. M. leprae primarily invades Schwann cells, causing nerve damage and consequent development of disabilities. Despite its long history, the pathophysiological mechanisms of nerve damage in the lepromatous pole of leprosy remain poorly understood. This study used the findings of 18F-FDG PET/CT on the peripheral nerves of eight lepromatous patients to evaluate the degree of glucose uptake by peripheral nerves and compared them with clinical, electrophysiological, and histopathological evaluations. METHODS: Eight patients with lepromatous leprosy were included in this study. Six patients were evaluated up to three months after leprosy diagnosis using neurological examination, nerve conduction study, 18F-FDG PET/CT, and nerve biopsy. Two others were evaluated during an episode of acute neuritis, with clinical, neurophysiological, and PET-CT examinations to compare the images with the first six. RESULTS: Initially, six patients already had signs of peripheral nerve injury, regardless of symptoms; however, they did not present with signs of neuritis, and there was little or no uptake of 18F-FDG in the clinically and electrophysiologically affected nerves. Two patients with signs of acute neuritis had 18F-FDG uptake in the affected nerves. CONCLUSIONS: 18F-FDG uptake correlates with clinical neuritis in lepromatous leprosy patients but not in silent neuritis patients. 18F-FDG PET-CT could be a useful tool to confirm neuritis, especially in cases that are difficult to diagnose, such as for the differential diagnosis between a new episode of neuritis and chronic neuropathy.

Case Report: Lepromatous Leprosy Masquerading as Acute Suppurative Lymphadenitis.

Leprosy is a chronic cutaneous infection. It is usually characterized by thickened nerves and maculo-anesthetic patches. Leprosy often has an unusual presentation, which is a diagnostic challenge. In this case report, we present a case of an elderly male who presented with fever and chronic pus-draining axillary, cervical, and inguinal lymph nodes. He also had a weak left foot for the previous 5 months. During his hospital stay, he developed additional papular lesions over his extremities. We performed fine needle aspiration from the lymph nodes and skin biopsy, which were suggestive of lepromatous leprosy. We initiated him on antileprosy medication. On follow-up, he was responsive to therapy. Although skin and nerve involvement in leprosy is common, this case had an atypical presentation of discharging lymph nodes.

Unusual clinical presentations in leprosy: a case series and review.

Conventionally, leprosy has been divided into various spectra of presentation ranging from the tuberculoid to the lepromatous pole, as well as histoid, pure neuritic leprosy and reactional states. This however is an oversimplification as leprosy can present in unusual clinical forms that may obfuscate the diagnosis. Our objective was to highlight unusual clinical presentations of leprosy occurring across all spectra of the disease. Our case series describes eight uncommon presentations of leprosy seen over a period of 10 y from 2011 to 2021, wherein clinical diagnosis followed by a histopathological confirmation of leprosy was performed. These include rare presentations such as psoriasiform plaques, Lazarine leprosy, verrucous plaques and hypertrophic scarring. Many of these rare presentations remain hitherto unreported, such as primary hypogonadism and annular plaques mimicking erythema annulare centrifugum and erythema gyratum repens. Sarcoidosis and syphilis have been labeled as great mimickers in dermatology. The current case series and review is an attempt to highlight a multitude of unusual presentations of leprosy that need a separate mention to make a correct and timely diagnosis and prevent the debilitating sequelae of this otherwise treatable infectious disease.

Progressive neuropathy in patients with lepromatous leprosy after multidrug therapy.

BACKGROUND: The lepromatous pole is a stigmatising prototype for patients with leprosy. Generally, these patients have little or no symptoms of peripheral nerve involvement at the time of their diagnosis. However, signs of advanced peripheral neuropathy would be visible during the initial neurological evaluation and could worsen during and after multidrug therapy (MDT). Disabilities caused by peripheral nerve injuries greatly affect these patients' lives, and the pathophysiological mechanisms underlying nerve damage remain unclear. OBJECTIVES: To evaluate the outcome of peripheral neuropathy in patients with lepromatous leprosy (LL) and persistent neuropathic symptoms years after completing MDT. METHODS: We evaluated the medical records of 14 patients with LL who underwent nerve biopsies due to worsening neuropathy at least four years after MDT. FINDINGS: Neuropathic pain developed in 64.3% of the patients, and a neurological examination showed that most patients had alterations in the medium- and large-caliber fibers at the beginning of treatment. Neurological symptoms and signs deteriorated despite complete MDT and prednisone or thalidomide use for years. Nerve conduction studies showed that sensory nerves were the most affected. MAIN CONCLUSIONS: Patients with LL can develop progressive peripheral neuropathy, which continues to develop even when they are on long-term anti-inflammatory and immunosuppressive therapy.

Presentation of Hansen's disease as Lucio phenomenon in an Indian male.

Lucio phenomenon is a reactional state described in patients with Lucio leprosy and in a few cases of lepromatous leprosy; it is rarely seen outside Mexico and Central America. We report a case of 35-year old labourer who presented with clinical features classical of Lucio phenomenon without any pre-existing cutaneous nodules or infiltrative lesions of either Lucio or lepromatous leprosy. This case report demonstrates the need to consider Lucio phenomenon in patients presenting with clinical features of medium vessel vasculitis even in areas not endemic for Lucio leprosy.

Leprosy Caused by Mycobacterium lepromatosis.

OBJECTIVES: Leprosy is caused by Mycobacterium leprae or Mycobacterium lepromatosis. This study reviews literature on M lepromatosis and reports on a Mexican family with this infection. METHODS: The review included all primary studies. Family history and surveys were used to uncover the infection cluster. Genome-based differential polymerase chain reactions were designed to detect etiologic agents. RESULTS: Since the discovery of M lepromatosis in 2008, 154 cases of M lepromatosis infection from 11 countries in the Americas and Asia have been reported, with most cases coming from Mexico. These cases included diffuse lepromatous leprosy (DLL) and other leprosy forms. Genomes of M lepromatosis strains have lately been sequenced, revealing 3,271,694 nucleotides and approximately 15% mismatches with M leprae. The Mexican family with leprosy involved the grandfather, mother, and 2 grandsons. The index was the oldest grandson, who manifested DLL and likely contracted the infection from his maternal grandfather approximately 13 years earlier. Family surveys diagnosed DLL in the index patient's mother and borderline leprosy in his brother; both were likely infected by the index patient. M lepromatosis was identified from archived biopsies from the index patient and his mother, while M leprae was excluded. CONCLUSIONS: M lepromatosis is a significant cause of leprosy in Mexico and requires better surveillance and control.

Challenges related to the cases of lepromatous leprosy: a report of two cases.

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae with various clinical symptoms. Even though the incidence of leprosy has diminished in Saudi Arabia, it still has not been eliminated. We present two cases of leprosy from India residing in Saudi Arabia that were successfully managed with multidrug therapy. The first patient was a 33-year-old man with a history of enlarging erythematous patch and nose deformity on his face and upper and lower extremities started two years ago. The second patient was a 25-year-old man who presented with multiple hyperpigmented plaques on the upper and lower extremities in the last two years. The patient was firstly misdiagnosed and treated as tinea corporis without improvement. In both patients, the histological study from cutaneous lesions confirmed lepromatous leprosy. This report aimed to introduce the manifestations of leprosy, emphasizing the nose's involvement in the first case and the misdiagnosis of leprosy in the second case.

Lepromatous leprosy with dermatofibroma features: colonization or morphological variant of histoid leprosy with epidermal induction?

BACKGROUND: Leprosy is one of the main health problems in developing countries. It can show many different clinical presentations. CASE REPORT: A 37-yr-old woman with multiple reddish-brown papules on the lower and upper limbs, including the palms. The initial clinical impression was pityriasis lichenoides chronica. Biopsies were taken. The specimen from the left shin showed classical histological features of lepromatous leprosy. The specimen from the left thigh was similar to lipidized dermatofibroma showing epidermal hyperplasia with basal layer hyperpigmentation, a narrow Grenz zone, and spindle xanthomatous cells among dermal fibers. Fite-Faraco staining revealed many bacilli. DISCUSSION: No matter the clinical presentation, in the presence of lipidized macrophages, Fite-Faraco staining (an inexpensive method available worldwide) should be performed to rule out leprosy, even in nonendemic areas or associated with a tumor.

Necrotic erythema nodosum reaction associated with histological alterations of Lucio's phenomenon.

Patients with lepromatous or borderline leprosy may present two types of vasculonecrotic reactions: Lucio's phenomenon (LP) and necrotic erythema nodosum leprosum (nENL). These are serious conditions, which mostly lead to life-threatening infectious and thrombotic complications. The authors report the case of a patient with leprosy recurrence associated with an atypical type II reaction with LP characteristics on histopathology.

Lucio phenomenon in an adolescent female.

INTRODUCTION: LP is an uncommon reaction characterized by outbreaks of erythematous, painful, slightly infiltrated macules and hemorrhagic bullae that progress to ulceration that occurs in patients with Lucio leprosy and lepromatous leprosy; it can be considered a variant of type 2 or 3 reaction. Death can occur because of blood dyscrasia or sepsis. Precipitating factors include infections, drugs, and pregnancy. CASE REPORT: A 17-year-old female presented with fever, tachycardia, adynamia, extensive hyperchromic and purplish macular lesions, erythematous plaques, multiple blisters with serohematic content, and necrotic exulcerations and ulcers on the lower and upper limbs, ears, nose, palms, and soles. Past medical history included leprosy and a first trimester miscarriage. The patient was diagnosed with borderline lepromatous leprosy in reactional state (ie, LP) and MDT was restarted in association with systemic corticosteroid and pentoxifylline. Local therapy was performed with cleansing solution (0.9% sodium chloride), dressing with silver sulfadiazine ointment, and surgical debridement of the necrotic lesions. CONCLUSION: LP is a rare manifestation that may be fatal because of considerable inflammatory activity and the extent and severity of dermatologic lesions. Pregnancy is strongly associated with exacerbation of symptoms. Debridement is required to excise nonviable tissue and promote wound healing.

Lucio's phenomenon: A systematic literature review of definition, clinical features, histopathogenesis and management.

Leprosy is a chronic disease with clinical presentations according to the immunologic spectrum. Lepromatous form is the most advanced, with the highest transmissibility and risk of causing disabilities. Lucio's phenomenon is a rare manifestation among lepromatous patients with a rapid and severe evolution and high mortality. It is difficult to differentiate from ulcerative/necrotic erythema nodosum leprosum and has no consensus on how it should be treated. This article is a qualitative review of the literature after the introduction of multidrug therapy, aiming to bring consensus related to the clinical, laboratory and histopathological diagnostic criteria of the disease and its management.

Histoid leprosy presenting as a large tumor

Abstract Histoid leprosy is a rare form of multibacillary leprosy, characterized by the presence of papules, plaques, or nodules whose appearance is keloid-like, skin colored, or erythematous. Fusiform cells are the main histopathological feature. Due to the fact that it can simulate other dermatological lesions, for example, dermatofibroma and neurofibroma, it constitutes a diagnostic challenge for clinicians and pathologists. It is a bacilliferous form of leprosy, and it plays an important role in disease transmission. A case of a patient with histoid leprosy living in the Northeast Region of Brazil is reported.

Case Report: Successful Outcome of Primary Infertility with Multidrug Therapy in a Long-Standing Case of Hypogonadism Resulting from Lepromatous Leprosy: Shattering the Dogma of Irreversible Infertility in Leprosy.

We present a case of primary infertility with features of hypogonadism in a male patient with lepromatous leprosy who had remained undiagnosed for 3 years. On investigation, azoospermia and deranged gonadotropin levels with normal serum testosterone were noted and the patient was initiated on multibacillary-multidrug therapy with the primary aim of treating the disease. Although the cutaneous lesions improved within 6 weeks, remarkably infertility was reversed in 2 months-with concomitant normalization of luteinizing hormone, follicle stimulating hormone, and sperm count-an outcome that was unexpected. While reiterating leprosy as a cause of infertility, we discuss the probable mechanism for the efficacy of multidrug therapy in what seemed to be an irreversible outcome of advanced lepromatous leprosy.

Case Report: Rapid Response to Low-Dose Thalidomide in a Case of Severe Steroid Recalcitrant Erythema Nodosum Leprosum.

Erythema nodosum leprosum (ENL), or type 2 lepra reaction, presents with crops of evanescent, tender erythematous nodules accompanied by fever, arthralgia, malaise and organ-specific manifestations and is seen in borderline and lepromatous leprosy. The drugs approved for ENL include nonsteroidal anti-inflammatory drugs, systemic steroids, thalidomide and clofazimine. The management of ENL is challenging because long-term steroid use leads to steroid dependence. The present patient had severe steroid recalcitrant ENL with vesicular and pustular lesions mimicking Sweet's syndrome and was treated effectively with a low-dose thalidomide regimen (100 mg/d) as opposed to high dose (400 mg/d) recommended in literature. We discuss the patho-mechanics and clinical utility of a low-dose thalidomide regimen as an effective treatment option for ENL.