Triple Infectious Syndrome: Pulmonary Tuberculosis and HIV in a Case of Pure Neuritic Leprosy With Underlying Diabetes Mellitus.

Pulmonary tuberculosis (PTB), human immunodeficiency virus (HIV), and leprosy are of public health importance, as all three diseases are communicable and contribute to disease burden in society. Co-infection with these three entities is extremely rare but leads to significant mortality and morbidity. We report a case that highlights the diagnostic challenges and therapeutic management of a patient who was diagnosed with pure neuritic leprosy on multibacillary-multidrug therapy (MB-MDT) and subsequently co-diagnosed with PTB and HIV. The patient was started on anti-tubercular therapy and anti-retroviral therapy for treatment under India's national health programs, which play a major role in treating those of low socioeconomic status. The optimization of these therapeutic drugs is quite challenging during treatment due to potential drug interactions and toxicities. High clinical suspicion is required to rule out PTB before initiating rifampicin-containing MB-MDT, which can lead to rifampicin-resistant TB and screening for HIV. As there is a social stigma associated with these patients, they require good psychological support during and after treatment.

Pure neuritic leprosy: Latest advancements and diagnostic modalities: Diagnosis of Pure Neuritic Leprosy.

Pure neuritic leprosy (PNL) is characterized by exclusive peripheral neuropathy without dermatological alterations. Diagnosis is difficult since skin lesions and acid-fast bacilli (AFB) in slit smears are absent. Presently, the gold standard for diagnosis is the histopathological examination of peripheral nerve biopsy. Even then, the detection of bacteria is difficult, and histological findings may be non-specific. Nerve biopsy is an invasive procedure that is possible only in specialized centers and limited to certain sensory nerves. Therefore, the establishment of serological, immunological, and molecular laboratory tests could be more beneficial for diagnosing pure neuritic leprosy to achieve effective treatment and reduction in its consequent disabilities. This review suggests that the presence of Mycobacterium leprae (M.leprae) in PNL cases can be proven by using non-invasive procedures, viz., multiplex polymerase chain reaction (M-PCR), serological findings, immunological profiling, and improved nerve-imaging. Findings also indicate the necessity for improving the sensitivity of PCR and further research on specificity in ruling out other clinical conditions that may mimic PNL.

Unmasking Carpal Tunnel Syndrome by High-Resolution Ultrasonography in Misdiagnosed Pure Neuritic Leprosy: A Case Report.

We present a case of a woman in her 70s who was initially diagnosed with pure neuritic leprosy due to bilateral hand numbness and tingling with associated muscle weakness. However, after undergoing high-resolution ultrasonography (HRUS), it was found that she had bilateral carpal tunnel syndrome (CTS). This case highlights the importance of considering other possible causes of peripheral neuropathy, such as CTS, in patients with suspected Hansen's disease. It also establishes the role of HRUS in the prompt diagnosis of CTS. Appropriate treatment of CTS can prevent unnecessary and potentially harmful treatment for Hansen's disease.

From periphery to center, untold story of pure neuritic leprosy: an electrophysiological study.

BACKGROUND: Pure neuritic leprosy (PNL) is uncommon form of leprosy involving peripheral nerves. Some isolated case reports have shown imaging changes in the central nervous system (CNS) and also impairment in visual evoked potential (VEP), somatosensory evoked potential (SSEP) and brain stem auditory-evoked potentials (BAEPs) parameters in PNL, but there is lack of large study. This prospective observational study evaluates impairment in these central conduction studies among PNL patients. METHODS: We screened patients with leprosy presenting with features of neuropathy and/or thickened nerves. Patients with bacilli-positive nerve biopsies were included in the study and subjected to routine tests along with nerve conduction study (NCS), VEP, tibial SSEP and BAEPs. Parameters of these studies were analyzed based on data from previous studies. RESULTS: Of 76 patients screened for PNL 49 had positive findings in biopsy. Most of patients were male and mean age group was 46.35 ± 15.35 years. Mononeuritis multiplex was most common NCS pattern in 46.93% (23/49) patients. We found abnormal VEP in 13 out of 35 patients (37.14%). Similarly abnormal SSEP and BAEPs among 42.85% and 40% patients respectively. DISCUSSION: This study shows that in PNL significant number of patients have subclinical CNS involvement. Exact pathophysiology of CNS involvement is not known till now but study of VEP, SSEP and BAEPs parameter may help in early diagnosis of PNL.

Rare occurrence of lepra type 1 reaction in pure neuritic leprosy: A case report.

Type 1 reaction in pure neuritic leprosy usually occurs in the form of neuritis. The development of new skin lesion during reaction is rare. Clinicians should be aware about occurrence of type 1 reaction in pure neuritic leprosy.

Cytomorphological Patterns of Nerve Aspirates in Pure Neuritic Leprosy-A Single Centre Cross-Sectional Observational Study.

BACKGROUND: Pure neuritic leprosy (PNL) poses a diagnostic challenge because of absence of skin patches, inconclusive skin biopsies and nerve conduction studies. Nerve biopsy though the diagnostic gold standard, is invasive, requires expertise, and may not be feasible in all cases. Fine needle aspiration cytology (FNAC) of accessible thickened nerves can be utilized as a minimally invasive diagnostic modality in PNL. This study was carried out to describe cytomorphological patterns of nerve aspirates in patients of PNL for diagnosis and classification of leprosy and study its advantage, if any, over skin biopsy. METHODS: Twenty-seven treatment naive clinically diagnosed patients of PNL were included in this cross-sectional study carried out from January 2017 to December 2018 at a tertiary care centre in Western India. FNAC was done from a clinically involved nerve and aspirates were evaluated for cytomorphological characteristics and the presence of Acid-Fast Lepra bacilli. RESULTS: Nerve aspirates were diagnostic in 10 (37%) patients while 17 (63%) aspirates showed non-specific or no inflammation. Of the diagnostic aspirates, six (22.2%) were classified as tuberculoid leprosy, three (11.1%) as lepromatous and one (3.7%) as borderline leprosy. Mycobacterium leprae were demonstrated among three (11.1%) of these aspirates. In comparison, only three (11.1%) skin biopsies were diagnostic of leprosy with features of indeterminate spectrum. Remaining 24 skin biopsies showed normal histology in 20 (74.1%) cases to perivascular lymphocytic infiltrate in four (14.8%) cases. CONCLUSION: Our study demonstrates that FNAC of clinically thickened nerves has a better diagnostic yield than skin biopsy in PNL and shows all spectrums of leprosy. It also offers the advantage of sampling major nerve trunks without the fear of residual neurological deficit. However, most of the smears were paucicellular and a negative aspirate does not rule out leprosy.

Mononeuritis Multiplex as Initial Manifestation of Pure Neuritic Leprosy-A Forgotten Cause: Clinical, Electrodiagnostic and Pathologic Correlations.

Despite being common, polyneuropathy remains a diagnostic challenge for most clinicians. Mononeuritis multiplex (MM) refers to involvement of several or many peripheral nerves at the same or different points in time by a disease process. This report describes a case of an atypical presentation of Hansen's disease (HD) as mononeuritis multiplex in the left lower limb with corresponding radiographic, electrodiagnostic, and histopathological data that confirmed pure neuritic leprosy (PNL). We reiterate that although the incidence of PNL is exceedingly low characterized by nerve involvement without the characteristic cutaneous stigmata, leprosy is still the commonest cause of MM in the Indian sub-continent.This report underscores the crucial need for a heightened multi-disciplinary awareness of this "forgotten and uncommon" presentation of PNL. It is imperative that the treating physician should also understand the various neurological presentations, both mimics and chameleons, of this treatable disease to prevent permanent neuropathic injury and disability.

Pathological, ultrasonographic, and electrophysiological characterization of clinically diagnosed cases of pure neuritic leprosy.

A subset of neuritic form of leprosy, called pure neuritic leprosy (PNL), seen in a minority of leprosy patients, is characterized by peripheral neuropathy without skin lesions and an absence of acid-fast bacilli on skin smears. Patients with PNL are often started on drug therapy without confirmation of diagnosis. We, therefore, did a prospective study of clinically diagnosed PNL patients with correlation of ultrasonographic and biopsy findings. A total of 100 consecutive patients with PNL, diagnosed according to the consensus case definition, were included in the study. All patients underwent nerve conduction study, peripheral nerve ultrasonography, and sural nerve biopsy. Multiple mononeuropathies were present in 75% of cases, mononeuropathy in 18%, and polyneuropathy in the remaining 7%. Compared to clinical examination, ultrasonographic assessment of the peripheral nerves was not only better at the detection of thickening but also helped in characterization of their fascicular architecture, echogenicity, and vascularity. A total of 32 cases were confirmed on nerve biopsy, out of which 75% had demonstrable lepra bacilli. Cranial nerve involvement, presence of trophic ulcers, and bilateral thickening of the great auricular nerve were significantly associated with the positivity of lepra bacilli. A significant improvement in the disability score happened after multidrug therapy. A comprehensive electrophysiologic, ultrasonographic, and histological evaluation may be helpful in establishing a diagnosis of PNL with greater confidence, while ruling out other non-leprosy diagnoses.

The first report of pure neuritic leprosy with involvement of the anterior femoral cutaneous nerve.

We describe the case of a young man, 22 years old, a household contact of leprosy, presenting paresthesia in the right leg and great thickening in the anterior femoral nerve and in the ipsilateral sural nerve. There were no typical dermatological lesions of leprosy. Ultrasonography confirmed the clinical finding. The clinical diagnosis of the disease was established and the patient started multibacillary-multidrug therapy, obtaining improvement of the initial symptomatology.

Mandating nerve biopsy: A step towards personalizing therapy in pure neuritic leprosy.

Pure neuritic leprosy (PNL) accounts for 5% to 10% of leprosy patients who usually present with asymmetrical neuropathy in the absence of lepra bacilli on slit-skin smears. However, nerve biopsies in PNL lack appropriate categorization in current immunologic terms. We aimed to classify nerve biopsies according to the immune spectrum of leprosy and assess the role of histologic classification of nerve biopsies in treating PNL. Patients from two tertiary care referral centres were enrolled in this incident case study. Patients presenting with mononeuropathy and multiple mononeuropathies presumably with leprosy, without skin lesions, underwent nerve biopsy and slit-skin smear examination. Amongst 78 patients with mononeuropathy, 38 were diagnosed with leprosy on nerve biopsy. Leprosy was classified as tuberculoid in 16, lepromatous in 5 and borderline in 17 patients. Lepra bacilli were present in 15 biopsies. On comparing histologic subtypes with number of nerves involved clinically, a significant number of cases with single nerve involvement showed multibacillary (BB, BL or LL) histology and vice versa. Nerve biopsy helps in diagnosing patients presenting with PNL and aids in classifying it to customize the treatment for best results. Current treatment recommendations for PNL from WHO and National Leprosy Eradication Program are based on clinical assessment only, which are likely to result in inconsistent treatment and possibly relapse in cases where histomorphology shows disparity. Inclusion of nerve biopsy to guide therapy in patients with PNL is suggested.

Hansen's Neuritis Revisited - A Clinicopathological Study.

INTRODUCTION: Leprosy affecting the nerve solely or with concomitant skin lesions is not an uncommon condition in clinical practice. It is responsible for extensive morbidity and often poses a diagnostic challenge. This study aims to highlight the clinicopathological features of Hansen's neuritis (HN). MATERIALS AND METHODS: In this retrospective study, cases of histologically diagnosed HN, from January 2010 to July 2017, were reviewed in the light of clinical features, treatment history, and outcome. RESULTS: There were 18 cases of HN which accounted for 3.97% of total nerve biopsy samples (n = 453) and 0.02% of total histopathology samples (n = 81,013). The male: female ratio was 5:1 in the cases of HN. Age range was 20-79 years with a mean age of 42.4 years (standard deviation: ±14.03). Among the HN cases, there were 13 cases of pure neuritic leprosy (61.1%). Mononeuritis multiplex was the most common finding in the nerve conduction study. Six (33.3%) cases exhibited histological features of borderline tuberculoid leprosy, followed by five (27.8%) cases of mid-borderline features, three (16.7%) cases each of borderline lepromatous and burnt-out HN, and one (5.6%) case of polar tuberculoid leprosy. Lepra bacilli were detected on Fite-Faraco stain in 44.4% cases. CONCLUSION: Diagnosis of HN depends on astute search for skin lesions, nerve thickening or tenderness, sensory or motor symptoms, histopathological examination, and demonstration of lepra bacilli.

Evaluation of polymerase chain reaction in nerve biopsy specimens of patients with Hansen's disease.

BACKGROUND: Pure neuritic variety of leprosy (PNL) presents as peripheral neuropathy with absent skin lesions and negative skin smears. Diagnosing PNL is an uphill task as most of these patients have nonspecific changes on nerve biopsy. In such circumstances, additional molecular diagnostic tools like polymerase chain reaction (PCR) has proven to be useful in diagnosing leprosy. The present study was planned to evaluate the role of PCR in nerve biopsy specimens of patients with PNL. METHODS: Patients attending the neuromuscular clinic from January 2013 to June 2014 with mononeuropathy multiplex underwent detailed diagnostic evaluation to ascertain the cause of neuropathy. Patients where this evaluation failed to establish an etiology underwent a nerve biopsy. RESULTS: Nerve biopsy was done in 52 patients, of which 35 were diagnosed as pure neuritic leprosy. Definite leprosy with positive wade fite staining for lepra bacilli was seen in 13 patients and 22 biopsies revealed a probable leprosy without lepra bacilli being identified. PCR for M. leprae was positive in 22 patients (62%). 12 of the 13 cases with definite leprosy on histopathology were PCR positive while in the AFB negative group, PCR was positive in 10 cases. PCR had a sensitivity of 92.3%, specificity of 54.5%. The positive and negative predictive value of PCR was 54.5% and 92.3% respectively. CONCLUSIONS: PCR helps in diagnosing PNL in doubtful cases. A positive PCR increases the sensitivity of detection of M. leprae especially in cases of probable PNL group where AFB cannot be demonstrated on histopathology.

Pure neuritic leprosy: Resolving diagnostic issues in acid fast bacilli (AFB)-negative nerve biopsies: A single centre experience from South India.

BACKGROUND AND PURPOSE: Demonstration of lepra bacilli is essential for definite or unequivocal diagnosis of pure neuritic leprosy (PNL) on nerve biopsy. However, nerves always do not show bacilli owing to the changes of previous therapy or due to low bacillary load in tuberculoid forms. In absence of granuloma or lepra bacilli, other morphologic changes in endoneurium and perineurium can be of help in making a probable diagnosis of PNL and treating the patient with multidrug therapy. MATERIALS AND METHODS: Forty-six biopsies of PNL were retrospectively reviewed and histologic findings were compared with 25 biopsies of non leprosy neuropathies (NLN) including vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP). The distribution of endoneurial infiltrate and fibrosis, perineurial thickening, and myelin abnormalities were compared between PNL and NLN biopsies and analyzed by Chi-square test. RESULTS: Out of 46 PNL casses, 24 (52.17 %) biopsies were negative for acid fast bacilli (AFB). In these cases, the features which favor a diagnosis of AFB-negative PNL were endoneurial infiltrate (51.1%), endoneurial fibrosis (54.2%), perineurial thickening (70.8%), and reduced number of myelinated nerve fibers (75%). INTERPRETATION AND CONCLUSION: Nerve biopsy is an efficient tool to diagnose PNL and differentiate it from other causes of NLN. In absence of AFB, the diagnosis of PNL is challenging. In this article, we have satisfactorily evaluated the various hisopthological features and found that endoneurial inflammation, dense fibrosis, and reduction in the number of myelinated nerve fibers are strong supportive indicators of PNL regardless of AFB positivity.

Isolated tenosynovitis as a sole manifestation: the great mimicker still continues to surprise us.

A middle aged male presented with non-tender cystic swelling over left distal forearm since 1 year. No other cutaneous abnormality could be found except mild paresthesia of the overlying skin and equivocal thickening of the ipsilateral ulnar nerve. Routine investigation was within normal limits. Detailed workup of the patient including MRI of the lesion suggested the diagnosis as tenosynovitis with a soft tissue mass. Fine needle aspiration cytology from the cyst showed foamy macrophages and acid fast bacilli; while PCR of the aspirate confirmed the etiological agent as M. leprae. We, thus, report a unique case of isolated tenosynovitis as a sole manifestation of pure neural leprosy which is extremely rare in world literature.

Fine needle aspiration cytology as an aid to diagnosis, categorization and treatment when pure neuritic leprosy presents as nerve abscess.

BACKGROUND: Pure neuritic leprosy (PNL) usually presents with neurological symptoms without skin involvement. Fine needle aspiration can play an important role in the management of PNL cases presenting as nerve abscesses. AIM: To assess the role of fine needle aspiration cytology (FNAC) in diagnosing and categorizing PNL cases presenting as nerve abscesses in the absence of neurological symptoms. MATERIALS AND METHODS: Five patients with subcutaneous nerve related swellings without clinically evident neurological deficits were subjected to FNAC. As the cytological features were suggestive of nerve abscesses due to leprosy, Fite stain was performed in all cases. As none of the patients had any leprosy skin lesions, they were diagnosed as cases of PNL. Features like cellularity, caseous necrosis, presence or absence of lymphocytes, macrophages, epithelioid cells, granulomas, Langhans giant cells and nerve elements were analyzed with the bacteriological index, to categorize PNL according to the Ridley-Jopling classification. RESULTS: Based on the cytological features and bacteriological indices, 3 cases were cytologically categorized into tuberculoid (TT)/borderline tuberculoid (BT) leprosy and the other two, as BT/borderline lepromatous (BL) and BL leprosy respectively in spite of having similar clinical presentation. Based on the cytological diagnoses, category-specific treatment could be instituted with clinical improvement. CONCLUSIONS: The simple and minimally invasive FNAC procedure allows diagnosis and a reasonably accurate categorization of PNL presenting as nerve abscess and therefore, highly useful in its clinical management.