Neural leprosy investigation using electroneuromyography and the ML Flow rapid test: a case report.

Neural leprosy, which is characterized by nerve involvement without visible skin lesions, presents a diagnostic challenge. This case report examined the significance of diverse diagnostic modalities in the identification of pure neural leprosy. A 28-year-old patient with symptoms of edema, pain, paresthesia, and diminished sensitivity in the lower limbs underwent various tests. A stilt skin smear yielded negative results on bacilloscopy, whereas a Fast ML Flow leprosy test and electroneuromyography supported the diagnosis. This discussion highlights the importance of accessible methods for early investigation. This study emphasizes the multidisciplinary approach and value of the Fast ML Flow leprosy test and electroneuromyography for diagnosing neural leprosy.

Half a Century in Hiding: A Unique Case of Tuberculoid Leprosy with an Unprecedented Incubation Period.

BACKGROUND Leprosy, also known as Hansen's disease, is a neglected tropical disease with low prevalence in the United States. The disease's long incubation period can cause delayed presentation, and most affected individuals have a history of travel or work in leprosy-endemic regions. The immune response to Mycobacterium leprae determines the clinical characteristics of leprosy, with tuberculoid leprosy being characterized by well-defined granulomas and involvement of peripheral nerves. The recommended treatment is a combination of dapsone and rifampin for 12 months. CASE REPORT A 78-year-old man with a history of extensive travel to Africa and Asia 50 years ago, presented with a non-tender, non-pruritic, and hypopigmented skin lesion on his left knee. Biopsy results confirmed granulomatous inflammation and the presence of Mycobacterium leprae, leading to a diagnosis of tuberculoid/paucibacillary leprosy. The patient received dapsone and rifampin treatment, which resulted in symptom improvement. CONCLUSIONS The patient's long incubation period of 50 years between exposure and symptom onset is remarkable and possibly one of the longest reported for tuberculoid leprosy. It emphasizes the importance of considering leprosy in cases with an extensive travel history and long incubation periods. Our patient's case presented contradictory staining results, suggesting potential sampling variation or a rare mixed leprosy form. Based on his clinical findings, he was diagnosed with tuberculoid leprosy. Early diagnosis and treatment are crucial to prevent irreversible nerve damage and improve patient outcomes. Healthcare providers should be vigilant in acquiring a detailed travel history to facilitate early diagnosis and appropriate management of leprosy cases.

Cytokines profile in pure neural leprosy.

Introduction: Pure Neural Leprosy (PNL) is a form of this long time known disease that affects only the peripheral nervous system. Since it is a rare form of the disease, its pathophisiology is still poorly understood. Objective: Describe the cytokines profile in patients with PNL. Methods: 30 Patients diagnosed with PNL in the Souza Araujo Outpatient Clinic and with cytokines evaluated were selected. They were evaluated by neurologists and diagnosed after a nerve biopsy. Serum levels of IL-1 ß, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-ϒ, CXCL-10/IP-10 and TGF-ß were evaluates at the moment of the diagnosis. Results: Neural thickening was a common clinical finding in this groups of patients. Small and medium sensitive fibers signs and symptoms were present in 92% of the patients and motor involvement in 53%. 43% of patients presented neuropathic pain and no one had neuritis TGF-beta, IL-17, CCl-2 and IP-10. CCL-2 levels were associated with demyelinating patters and IP-10 and IL-1o were associated with axonal patterns at NCS. Discussion: PNL patients' cytokine profile appears to be different of other clinical forms of leprosy, with the presence of cytokines described in both tuberculoid and lepromatous leprosy. High levels of CCl-2 may be related to the presence of silent neuritis as well as the presence of IL-10. PNL is unique a form of leprosy, therefore, understanding its immunological profiles essential to better understand the disease itself.

Follow-up assessment of patients with Pure Neural Leprosy in a reference center in Rio de Janeiro-Brazil.

INTRODUCTION: Pure Neural Leprosy (PNL) is a rare clinical form of leprosy in which patients do not present with the classical skin lesions but have a high burden of the disability associated with the disease. Clinical characteristics and follow up of patients in PNL are still poorly described in the literature. OBJECTIVE: This paper aims to describe the clinical, electrophysiological and histopathological characteristics of PNL patients, as well as their evolution after multidrug therapy (MDT). METHODS: Fifty-two PNL patients were selected. Clinical, nerve conduction studies (NCS), histopathological and anti-PGL-1serology were evaluated. Patients were also assessed monthly during the MDT. At the end of the MDT, all of the patients had a new neurological examination and 44 were submitted to another NCS. RESULTS: Paresthesia was the complaint most frequently reported by patients, and in the neurological examination the most common pattern observed was impairment in sensory and motor examination and a mononeuropathy multiplex. Painful nerve enlargement, a classical symptom of leprosy neuropathy, was observed in a minority of patients and in the motor NCS axonal injuries, alone or in combination with demyelinating features, were the most commonly observed. 88% of the patients did not present any leprosy reaction during MDT. There was no statistically significant difference between the neurological examinations, nor the NCS pattern, performed before and after the MDT. DISCUSSION: The classical hallmarks of leprosy neuropathy are not always present in PNL making the diagnosis even more challenging. Nerve biopsy is an important tool for PNL diagnosis as it may guide therapeutic decisions. This paper highlights unique characteristics of PNL in the spectrum of leprosy in an attempt to facilitate the diagnosis and management of these patients.

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.

The cellular architecture of the antimicrobial response network in human leprosy granulomas.

Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1ß. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response.

Morphometric analysis of nerve fibers in neural leprosy.

BACKGROUND: The present study assesses the contributions of axonal degeneration and demyelination in leprosy nerve damage. New clinical strategies can emerge from an in-depth understanding of the pathogenesis of neural leprosy (NL). METHODS: Morphometric analysis of myelinated nerve fibers was performed on 44 nerve biopsy samples collected from leprosy patients. Measures of density, diameter distribution, g-ratios, and the counting of axonal ovoids on the myelinated fibers were taken and compared to those in the control group. RESULTS: The proportion of small myelinated fibers increased in the leprosy group while large fiber frequency decreased. Indicative of axonal atrophy, the g-ratio was lower in the leprosy group. The frequency of axonal ovoids was identical to that found in the non-leprosy neuropathies. CONCLUSIONS: Axonal atrophy, Wallerian degeneration, and demyelination coexist in NL. Axonal degeneration predominates over demyelination in the chronic course of the disease; however, this may change during leprosy reactive episodes. This study regards demyelination and axon degeneration as concurrent mechanisms of damage to nerve fibers in leprosy. It also calls into question the view that demyelination is the primary and predominant mechanism in the complex pathogeny of NL.

Immune Complex-Driven Generation of Human Macrophages with Anti-Inflammatory and Growth-Promoting Activity.

To maintain homeostasis, macrophages must be capable of assuming either an inflammatory or an anti-inflammatory phenotype. To better understand the latter, we stimulated human macrophages in vitro with TLR ligands in the presence of high-density immune complexes (IC). This combination of stimuli resulted in a broad suppression of inflammatory mediators and an upregulation of molecules involved in tissue remodeling and angiogenesis. Transcriptomic analysis of TLR stimulation in the presence of IC predicted the downstream activation of AKT and the inhibition of GSK3. Consequently, we pretreated LPS-stimulated human macrophages with small molecule inhibitors of GSK3 to partially phenocopy the regulatory effects of stimulation in the presence of IC. The upregulation of DC-STAMP and matrix metalloproteases was observed on these cells and may represent potential biomarkers for this regulatory activation state. To demonstrate the presence of these anti-inflammatory, growth-promoting macrophages in a human infectious disease, biopsies from patients with leprosy (Hanseniasis) were analyzed. The lepromatous form of this disease is characterized by hypergammaglobulinemia and defective cell-mediated immunity. Lesions in lepromatous leprosy contained macrophages with a regulatory phenotype expressing higher levels of DC-STAMP and lower levels of IL-12, relative to macrophages in tuberculoid leprosy lesions. Therefore, we propose that increased signaling by FcγR cross-linking on TLR-stimulated macrophages can paradoxically promote the resolution of inflammation and initiate processes critical to tissue growth and repair. It can also contribute to infectious disease progression.

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.

[Atypical Localization of a Case of Leprosy in Lomé (Togo)]. / Localisation atypique d'un cas de lèpre à Lomé (Togo).

This was a 50-year-old woman with a selling activity living in Lomé who came for a consultation in March 2016 for a facial flushing that had been going on for 2 months without pain or pruritus. On examination, there was a single, erythemato-squamous closet of the right hemiface. There was no infiltration of the right ear. There was moderate cutaneous heat compared to the left hemiface which was without any lesion. Examination of nails, hair, palms and plants was normal. There was no hypertrophy of the peripheral nerves (superficial cervical plexus, ulnar, median). The face was not fixed. Complementary examinations noted a normal blood count and negative HIV status. Histology performed on a biopsy fragment concluded tuberculoid leprosy. The patient was first put on WHO multidrug therapy during 6 months. But one month after stopping this treatment, the lesions resumed. She was referred to a multibacillary leprosy protocol during one year. She had been seen 4 months after stopping treatment, without recurrence. It is important not to ignore leprosy in case of atypical erythema of the face even in the absence of other evocative signs and to perform a biopsy to the slightest doubt.

Il s'agit d'une femme de 50 ans, revendeuse, résidant à Lomé qui a consulté en mars 2016 pour une rougeur du visage évoluant depuis 2 mois sans douleur, ni prurit. À l'examen, on notait un placard unique érythémato-squameux de l'hémiface droit avec une bordure infiltrée. Il n'y avait pas d'infiltration du pavillon de l'oreille droite. Il y avait une chaleur cutanée modérée par rapport à l'hémiface gauche qui était sans aucune lésion. L'examen des ongles, des cheveux, des paumes et plantes était normal. On notait une absence d'hypertrophie des nerfs périphériques (plexus cervical superficiel, cubital, médiane). Le visage n'était pas figé. Les examens complémentaires notaient un hémogramme normal et une sérologie VIH négative. L'histologie réalisée sur un fragment biopsique a conclu à une lèpre tuberculoïde. La patiente a d'abord été mise sous le protocole de polychimiothérapie de l'OMS pendant 6 mois. Mais un mois après l'arrêt de ce traitement, les lésions ont repris. Elle a été remise sous un protocole de lèpre multibacillaire pour une durée d'un an. Elle a été revue 4 mois après l'arrêt du traitement, sans récidive. Il importe de ne pas méconnaître une lèpre devant un érythème atypique du visage même en l'absence d'autres signes évocateurs et de réaliser une biopsie au moindre doute.

Neuritic Leprosy; An Intriguing Re-visit to a Forbidden Ailment.

Leprosy is a chronic infectious disease that presents with varied manifestations. Pure neuritic leprosy is one of the rarest forms of the disease which is characterized by nerve involvement without the characteristic cutaneous stigmata. Eleven year old, healthy male presented with progressively increasing painful swelling at the medial aspect of the arm near to the right elbow joint with difficulty in extending right ring and little fingers at interphalangeal joint and numbness in the same region for last 1 year with no cutaneous abnormalities. Physical examination revealed 6x3 cm firm, tender lesion 3 cm proximal to the right elbow joint with positive tinel's sign, without signs of inflammation, along with characteristic claw hand deformity of right hand and atrophy of hypothenar and interossei muscle. Electro-diagnostic testing revealed findings consistent with a right ulnar axonal neuropathy above the elbow. Magnetic resonance imaging revealed well defined heterogeneously hyper intense linear lesion along the course of thickened ulnar nerve in the distal arm extending posterior to the medial condyle. It also showed an oval shaped lesion (2.1x1.0 cm) arising from the same segment of the nerve, without any bony or muscular involvement of that area. The patient underwent surgical exploration and ulnar nerve decompression with biopsy. Pathology revealed necrotizing granulomatous inflammatory acid fast bacilli stain negative lesion, which was histologically consistent with caseous abscess caused by tuberculoid leprosy, pathognomonic for Hansen's disease. He has been started on antibiotic therapy and is referred to leprosy center for further course of management. Pure neuritic leprosy, though rare, should be considered as differential diagnosis in cases presenting with peripheral neuropathy at leprosy-endemic areas. Prompt diagnosis and treatment is imperative to prevent permanent neurological injury.

Fibrosis: a distinguishing feature in the pathology of neural leprosy.

BACKGROUND: Fibrosis in the peripheral nerve is the end stage of leprous neuropathy and the cause of the resulting permanent neural function impairments. Preventive measures to avoid this irreversible pathological state are a relief strategy for leprosy sufferers. OBJECTIVES: The present study describes the frequency of fibrosis along with its characterisation and pathogenic development. METHODS: Six-hundred-and-thirteen nerve samples were sorted from 278 neural leprosy (NL) and 335 non-leprosy neuropathy patients (ON). The total number of samples was histologically examined by routine staining methods (haematoxylin-eosin, Wade staining and Gomori's trichrome) and fibrosis was evaluated via semi-quantitative estimation. FINDINGS: Fibrosis was most frequent in the NL group (33% against 0.4% in ON) while fibrosis in association with endoneurial microfasciculation was found in 38 (41.3%) of the NL samples in the examination of semithin sections. Pericytic activation in the perivascular environment was confirmed to be the source of the fibroblasts and perineurial cells delimiting microfascicles. End-stage fibrosis in leprosy displays an arrangement of microfascicles devoid of neural components (i.e., Schwann cells and axons) lined by an intermediate phenotype of fibroblastic-perineurial cells filled with bundles of collagen fibres. MAIN CONCLUSIONS: The present study underscores that fibrosis is frequently the severe end stage of neural leprosy NL pathogeny after analysing the notably distinct development of fibrosis within the neural environment.

Primary Neural Leprosy mimicking rheumatological disorders.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which affects mainly the skin and peripherical nerves. Brasil has not yet achieved its goal of elimination of the number of cases of this disease, ranking second in terms of absolute numbers worldwide, with India occupying the first position. Primary Neural Leprosy is considered to be a challenge in diagnosis, since it affects the peripherical nerve system with the absence of skin lesions, thus mimicking rheumatological disorders, like in the case presented. A male, 31, with no previous comorbidities, five years ago, started feeling severe pain in the left ankle as well as morning hand pain and stiffness. After many years of being submitted to intense rheumatological disease investigation, they all proved to be negative. Upon physical examination, the patient presented no skin lesions, symmetric polyarthritis in metacarpophalangeal joints and thickness of the left sural nerve. Lab exams showed no alterations and bacilloscopy was negative. Ultrasonography was used to investigate the thickness of the left sural nerve. Biopsy showed a minimal amount of perineural lymphocytes and positive AFB testing. Based on the electroneuromyography, the conclusion was multiple mononeuropathy, and multibacillary polychemotherapy was started. Leprosy remains a public health problem in Brasil. Due to the high prevalence of the disease, our medical colleagues must be alert and trained to recognize this clinical presentation of leprosy. Correct referral to Reference Centers accelerates research, contributing to an accurate diagnosis, classification, and treatment, thus preventing irreversible sequelae with severe functional disability.

Dermatoscopy in leprosy and its correlation with clinical spectrum and histopathology: a prospective observational study.

BACKGROUND: Leprosy, a chronic granulomatous infection has varied clinical presentations spanning across different spectrums. The scope of dermatoscopy is vast and has been studied for other granulomatous disorders like sarcoidosis. OBJECTIVES: The objective of this study was to describe the dermatoscopic features of the entire spectrum of leprosy and to correlate with clinical and histopathological findings. METHODS: This was a prospective observational study of treatment naïve leprosy patients over a period of 1 year. The study patients were categorized as per Ridley-Jopling classification based on clinical, slit skin smear and histopathological findings. Most representative lesions were photographed, evaluated by dermatoscopy and were biopsied. RESULTS: A total of 30 patients (21 males and 9 females) were recruited; 2 cases of tuberculoid leprosy, 12 cases of borderline tuberculoid (3 with type 1 reaction), 8 cases of borderline lepromatous, 6 cases of lepromatous leprosy (3 with type 2 reaction) and 2 cases of Histoid leprosy. The dermatoscopic featues consistently seen were yellowish orange areas and vascular structures like linear branching vessels and crown vessels correlating with the presence of dermal granulomas and dilated vessels. Broken pigment network, white chrysalis like areas were seen in addition. Tuberculoid spectrum also had absence of or diminished hair follicles and eccrine duct openings correlating with presence of peri-appendageal granuloma and appendageal destruction. Scaling and follicular plugs were other features in lesions of type 1 reaction. CONCLUSION: Yellowish-orange areas and vascular structures are the common dermatoscopic features of leprosy. Broken pigment network and paucity of appendageal structures are additional specific features.

Second-harmonic generation imaging analysis can help distinguish sarcoidosis from tuberculoid leprosy.

Sarcoidosis and tuberculoid leprosy (TL) are prototypes of granulomatous inflammation in dermatology, which embody one of the histopathology limitations in distinguishing some diseases. Recent advances in the use of nonlinear optical microscopy in skin have enabled techniques, such as second-harmonic generation (SHG), to become powerful tools to study the physical and biochemical properties of skin. We use SHG images to analyze the collagen network, to distinguish differences between sarcoidosis and TL granulomas. SHG images obtained from skin biopsies of 33 patients with TL and 24 with sarcoidosis retrospectively were analyzed using first-order statistics (FOS) and second-order statistics, such as gray-level co-occurrence matrix (GLCM). Among the four parameters evaluated (optical density, entropy, contrast, and second angular moment), only contrast demonstrated statistical significance, being higher in sarcoidosis (p = 0.02; 4908.31 versus 2822.17). The results may indicate insufficient differentiating power for most tested FOS and GLCM parameters in classifying sarcoidosis and TL granulomas, when used individually. But in combination with histopathology (H&E and complementary stains, such as silver and fast acid stains), SHG analysis, like contrast, can contribute to distinguishing between these diseases. This study can provide a way to evaluate collagen distribution in granulomatous diseases.

Immunohistochemical characterization of the M4 macrophage population in leprosy skin lesions.

BACKGROUND: Since macrophages are one of the major cell types involved in the Mycobacterium leprae immune response, roles of the M1 and M2 macrophage subpopulations have been well defined. However, the role of M4 macrophages in leprosy or other infectious diseases caused by mycobacteria has not yet been clearly characterized. This study aimed to investigate the presence and potential role of M4 macrophages in the immunopathology of leprosy. METHODS: We analyzed the presence of M4 macrophage markers (CD68, MRP8, MMP7, IL-6, and TNF-α) in 33 leprosy skin lesion samples from 18 patients with tuberculoid leprosy and 15 with lepromatous leprosy by immunohistochemistry. RESULTS: The M4 phenotype was more strongly expressed in patients with the lepromatous form of the disease, indicating that this subpopulation is less effective in the elimination of the bacillus and consequently is associated with the evolution to one of the multibacillary clinical forms of infection. CONCLUSION: M4 macrophages are one of the cell types involved in the microbial response to M. leprae and probably are less effective in controlling bacillus replication, contributing to the evolution to the lepromatous form of the disease.

Histomorphometric approach to differentiate skin lesions of tuberculoid leprosy from sarcoidosis.

BACKGROUND: More than 200 000 new cases of leprosy are detected worldwide annually. Physicians commonly have difficulty in differentiating tuberculoid form of leprosy (TL) from sarcoidosis' cutaneous manifestation. METHODS: Skin biopsies of 33 patients with TL and 24 with sarcoidosis were reviewed on hematoxylin and eosin- and Gomori-stained sections, in order to find reliable criteria for distinguishing one disease from another. RESULTS: Nine of the 24 features analyzed presented significant predictive value for diagnosis (P < .05). Predominance of tuberculoid granulomas in adnexal and neural distribution, and granulomas replacing the nerves localized within sweat gland glomeruli were predictive to TL diagnosis. For sarcoidosis, dermal fibrosis, back-to-back distribution of the granulomas, presence of atypical giant cells and plasma cells, greater number of conventional giant cells, and spared nerves beside the granuloma were predictive criteria. The median surface density of reticulin fibers was significantly higher in sarcoidosis (3.44) than in TL (2.99). Nonetheless, using logistic regression, this variable did not discriminate between the diseases (P = .096). CONCLUSIONS: Isolated histological features are not fully predictive to differentiate the 2 diseases. However, those with statistical value can assist this distinction in diagnostic practice. Although the results of the analysis of the reticulin fibers density did not tell apart TL from sarcoidosis, they corroborate the idea of fiber fragmentation within tuberculoid leprosy granulomas, reiterating the importance of morphometry in the histological examination.

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.

Perineural and intraneural cutaneous granulomas in granulomatous mycosis fungoides mimicking tuberculoid leprosy.

BACKGROUND: Histological similarities between granulomas and granulomatous mycosis fungoides (GMF) may lead to misdiagnoses of sarcoidosis or leprosy. METHODS: This report presents four patients with GMF in whom skin biopsies showed perineural and intraneural granulomas that were confused with tuberculoid leprosy granulomas. RESULTS: Patient 1 presented with erythematous plaques and bulky nodules. Biopsy findings suggested cutaneous sarcoidosis. Tumor resection showed granulomatous infiltrate extending to the fascia and skeletal muscle. Clinicopathological correlations permitted a diagnosis of GMF. Patient 2 presented with erythematous plaques. Skin biopsies had indicated sarcoidosis. Resection of a thigh nodule excluded leprosy, and GMF was diagnosed. Patient 3 presented with scaly, hyperpigmented plaques. Biopsy showed diffuse granulomatous inflammation with epithelioid and giant cells, abundant lymphocytes, and some eosinophils, and indicated GMF. Patient 4 presented with pruritic, erythematous plaques. Biopsy of an indurated mammary plaque initially indicated sarcoid granulomatous inflammation. Biopsy review suggested GMF. CONCLUSIONS: This study highlights both the diagnosis of GMF, and granulomatous cutaneous nerve injury in GMF and its possible confusion with leprosy granulomas. The histological diagnosis of GMF includes: (i) a granulomatous infiltrate rich in giant cells, emperipolesis, histiocytic cells, and scattered eosinophils, which may reach the fascia and muscle; (ii) the absence of elastic fibers or their phagocytosis by giant cells; and (iii) lymphocytes that may show atypia and epidermotropism. Deep biopsies reveal GMF diagnostic changes and, in conjunction with clinicopathological correlations, exclude a diagnosis of leprosy and support one of GMF, thus facilitating its appropriate management.