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.

Modified simple decompression in the treatment of cubital tunnel syndrome: avoiding ulnar nerve subluxation.

OBJECTIVE: In this study, we propose a modification to the simple decompression technique that contains the ulnar nerve in the cubital fossa, thus preventing subluxation during forearm flexion movements. METHODS: Five consecutive patients with leprosy-associated cubital tunnel syndrome underwent surgery with the modified technique between July 2011 and October 2012. RESULTS: The most common symptoms were neuropathic pain and sensory changes (both 60%). On the McGowan scale, three patients maintained their preoperative score and two patients improved by two points, while on the Louisiana State University Health Sciences Center scale, two patients maintained the same scores, two improved by two points, and one improved by one point. Four patients were able to discontinue corticosteroid use. The mean follow-up time was 25.6 months (range 2-48 months). There were no recurrences or subluxations in the long-term. CONCLUSION: This alternative technique resulted in excellent functional results, as well as successful withdrawal from corticosteroids. Furthermore, it resulted in no ulnar nerve subluxations.

Modified simple decompression in the treatment of cubital tunnel syndrome: avoiding ulnar nerve subluxation / Descompressão simples modificada no tratamento da síndrome do túnel cubital: evitando subluxação do nervo ulnar

ABSTRACT Objective In this study, we propose a modification to the simple decompression technique that contains the ulnar nerve in the cubital fossa, thus preventing subluxation during forearm flexion movements. Methods Five consecutive patients with leprosy-associated cubital tunnel syndrome underwent surgery with the modified technique between July 2011 and October 2012. Results The most common symptoms were neuropathic pain and sensory changes (both 60%). On the McGowan scale, three patients maintained their preoperative score and two patients improved by two points, while on the Louisiana State University Health Sciences Center scale, two patients maintained the same scores, two improved by two points, and one improved by one point. Four patients were able to discontinue corticosteroid use. The mean follow-up time was 25.6 months (range 2-48 months). There were no recurrences or subluxations in the long-term. Conclusion This alternative technique resulted in excellent functional results, as well as successful withdrawal from corticosteroids. Furthermore, it resulted in no ulnar nerve subluxations.

RESUMO Objetivo Neste manuscrito apresentamos uma modificação da técnica de descompressão simples do nervo ulnar no túnel cubital que impede a subluxação do nervo em movimentos de flexão do antebraço. Métodos Foram incluídos cinco pacientes consecutivos acometidos por síndrome do túnel cubital (Hanseníase) submetidos à cirurgia entre 2011 e 2012. Resultados Os sintomas mais comuns foram dor neuropática e alterações sensitivas (60%). No pós-operatório, três pacientes mantiveram o mesmo escore e dois melhoraram dois pontos na escala de McGowan, enquanto na escala Louisiana State University Health Sciences Center, dois pacientes mantiveram o mesmo escore, dois melhoraram dois pontos e um melhorou um ponto. Os corticosteróides foram descontinuados em quatro pacientes. O tempo médio de seguimento foi 25,6 meses (variação 2-48 meses). Não foram observadas recorrência ou subluxação no longo prazo. Conclusões A técnica alternativa apresentou excelentes resultados funcionais e foi bem sucedida na retirada dos corticosteróides. Ademais, subluxações do nervo ulnar não foram observadas.

Compound heterozygous CORO1A mutations in siblings with a mucocutaneous-immunodeficiency syndrome of epidermodysplasia verruciformis-HPV, molluscum contagiosum and granulomatous tuberculoid leprosy.

PURPOSE: Coronin-1A deficiency is a recently recognized autosomal recessive primary immunodeficiency caused by mutations in CORO1A (OMIM 605000) that results in T-cell lymphopenia and is classified as T(-)B(+)NK(+)severe combined immunodeficiency (SCID). Only two other CORO1A-kindred are known to date, thus the defining characteristics are not well delineated. We identified a unique CORO1A-kindred. METHODS: We captured a 10-year analysis of the immune-clinical phenotypes in two affected siblings from disease debut of age 7 years. Target-specific genetic studies were pursued but unrevealing. Telomere lengths were also assessed. Whole exome sequencing (WES) uncovered the molecular diagnosis and Western blot validated findings. RESULTS: We found the compound heterozygous CORO1A variants: c.248_249delCT (p.P83RfsX10) and a novel mutation c.1077delC (p.Q360RfsX44) (NM_007074.3) in two affected non-consanguineous siblings that manifested as absent CD4CD45RA(+) (naïve) T and memory B cells, low NK cells and abnormally increased double-negative (DN) ϒδ T-cells. Distinguishing characteristics were late clinical debut with an unusual mucocutaneous syndrome of epidermodysplasia verruciformis-human papilloma virus (EV-HPV), molluscum contagiosum and oral-cutaneous herpetic ulcers; the older female sibling also had a disfiguring granulomatous tuberculoid leprosy. Both had bilateral bronchiectasis and the female died of EBV+ lymphomas at age 16 years. The younger surviving male, without malignancy, had reproducibly very short telomere lengths, not before appreciated in CORO1A mutations. CONCLUSION: We reveal the third CORO1A-mutated kindred, with the immune phenotype of abnormal naïve CD4 and DN T-cells and newfound characteristics of a late/hypomorphic-like SCID of an EV-HPV mucocutaneous syndrome with also B and NK defects and shortened telomeres. Our findings contribute to the elucidation of the CORO1A-SCID-CID spectrum.

Nerve abscess in primary neuritic leprosy.

Nerve abscess is an infrequently reported complication of leprosy. We describe a patient with a pure neuritic type of leprosy with multiple nerve abscesses, who presented with tingling and numbness in the medial aspect of his right forearm and hand. Subsequently he developed pain, redness and swelling over the medial side of his right elbow and the flexor aspect of his right wrist. High-resolution ultrasound showed diffuse thickening of the right ulnar nerve with hypoechoic texture housing a cystic lesion with internal debris suggesting an abscess, at the cubital tunnel. Histopathological examination of the pus and tissue obtained from the abscess revealed presence of granulomas with lepra bacilli. The patient responded to surgery and multidrug therapy. In conclusion, the nerve abscess as the first manifestation of leprosy is uncommon and a high index of suspicion is required to make a correct diagnosis.

[Diagnosis and treatment of leprous neuropathy in practice]. / Diagnostic et traitement de la neuropathie lépreuse en pratique.

Leprosy still affects 240,000 persons every year in the world. It is a particularly common cause of neuropathy and severe disabilities in developing countries. With increasing migration, new cases of leprosy are regularly diagnosed in developed countries, where it still remains rare and so underestimated. Cutaneo-nevritic leprosy is the most frequent form of leprosy. It may be diagnosed by the clinical features and the cutaneous histology and bacteriology. Neuritic leprosy without obvious skin lesions is reported in 5 to 15% of leprosy patients. It must be suspected in persons from areas of endemic disease presenting with nerve thickening and associated nerve deficit. Nerve biopsy is essential for diagnosis. However search for bacilli in cutaneous samples may be of great help and avoid nerve biopsy. Acute and severe neuritis occurs during reactional states, reversal reaction (Type 1) and erythema nodosum leprosum (Type 2). Multidrug therapy is advocated. The treatment of acute neuropathy needs a supplementary medical and sometimes surgical treatment.

Trigeminal trophic syndrome complicating a case of borderline tuberculoid leprosy.

An example of trigeminal trophic syndrome presenting as ulceration of ala nasi in a case of borderline tuberculoid leprosy is reported. To the best of our knowledge, this is only the second case report of this manifestation in leprosy to be documented.

The wide range of clinical manifestations in leprous neuropathy: two case reports.

The present report describes two patients with leprous neuropathy diagnosed in Japan and manifesting with different clinical features. A 78-year-old Japanese man presented with a 3-year history of numbness and weakness affecting the upper and lower extremities. Although he did not have skin eruptions, nerve biopsy revealed acid-fast bacilli. Another patient, a 41-year-old Japanese-Brazilian man, presented with a 1-month history of numbness in the right fourth and fifth fingers and whole-body erythema. These cases highlight the fact that, as a result of worldwide travel and immigration, leprosy should still be considered in the differential diagnosis of neuropathy in developed countries.

Mutilating acral ulcers: the spectrum of differential diagnosis.

Prominent acral mutilating ulcers can be present in sensorimotor neuropathies. Although diabetes mellitus is the most common cause of neuropathic ulcers, these skin lesions may manifest in nondiabetic neuropathies. The dermatologic abnormalities may even precede the onset of typical neuropathic symptoms, leading to diagnostic confusion. Therefore, a broad differential diagnosis of neurological and systemic disorders should be considered when evaluating patients who have acral skin ulcerations. We report 3 cases of mutilating ulcers associated with nondiabetic neuropathies. The first case is a woman with multiple ulcerations on her forearm, hands, and toes. Her nerve biopsy revealed neuropathy with multiple congophilic deposits consistent with amyloid neuropathy. The second case is a woman with necrotic painless ulcer on her heel. Nerve biopsy in this patient revealed features suggestive of vasculitic neuropathy. The third case is a man with multiple ulcers on his extremities. A sural nerve biopsy in this patient was consistent with leprous neuropathy.

Angiogenesis in cutaneous lesions of leprosy: implications for treatment.

OBJECTIVE: To examine the potential role of angiogenesis in leprosy. DESIGN: Immunohistochemical analysis of leprosy lesions. SETTING: Department of Dermatology, Venereology, and Leprology, Kasturba Medical College; Division of Dermatology, University of California at Los Angeles; and Departments of Dermatology and Pathology, Emory University. PATIENTS: Thirty-two cutaneous lesions that represented the spectrum of leprosy were obtained from 32 patients. MAIN OUTCOME MEASURE: CD31 microvessel counts. RESULTS: The mean CD31 microvessel count in borderline tuberculoid, midborderline, and lepromatous leprosy lesions was significantly higher than in indeterminate leprosy lesions. CONCLUSIONS: Increased bacterial load is associated with increased angiogenesis. Angiogenesis inhibitors may be of benefit in the treatment of leprosy.

Leprosy & gangrene: a rare association; role of anti phospholipid antibodies.

BACKGROUND: Leprosy still remains an important public health problem for many parts of the world. An association of gangrene with leprosy is a rare one & can have a number of causative mechanisms. We present a case with Leprosy & gangrene with positive anti phopholipid antibody titers. CASE PRESENTATION: A 50-year-old non-diabetic, non-hypertensive lady presented with 2 months history of progressive gangrene of bilateral toes. She was found to have madarosis & hypopigmented, hypoaesthetic macular lesions on the upper limb & thighs. Bilateral ulnar & popliteal nerves were thickened. A skin biopsy of the lesions revealed borderline tuberculoid leprosy, slit skin smears revealed a bacteriological index of 1+. She did not have any evidence of thromboembolic episode or atherosclerosis. ACLA was positive at presentation & also on another occasion 6 weeks later. ACLAs were of the IgM type on both occasions. Lupus Anticoagulant & beta2 GPI antibody were negative. DOPPLER of the lower limb arteries did not reveal any abnormality. Patient was successfully treated with multi-drug antileprotics & anticoagulants. CONCLUSION: Infectious APLAs should be recognized as a cause of thrombosis in Leprosy. Appropriate anticoagulation can salvage limb function.

The development of cutaneous lesions during follow-up of patients with primary neuritic leprosy.

BACKGROUND: Primary neuritic leprosy (PNL) is a rare form of leprosy where the characteristic skin lesions are absent. Investigations of apparently normal skin from the areas of sensory change have revealed microscopic evidence of nerve involvement. Clinical studies have found that a proportion of patients develop visible skin lesions during follow-up. The aim of the study was to perform a clinical and histological analysis of PNL patients who developed visible skin lesions during treatment and follow-up, to gain insight into the pathogenesis of the disease. METHODS: Twenty-nine individuals in a series of 182 PNL patients developed visible skin lesions during follow-up. Analysis of the number, location, histology and time of onset of the new skin lesions in relation to the type and regularity of the treatment regimen were noted. A biopsy from the new skin lesion when available was compared with the nerve biopsy findings at the time of initial diagnosis. RESULTS: Thirty-eight per cent of patients developed a single patch and 28% developed two patches. Over three-quarters of these were on the lower limb (47%) or the upper limb (29%). Sixty-two per cent of patients developed the lesions within 2 years of the onset of symptoms. Patients on regular treatment developed patches earlier than those on irregular treatment or no treatment. A skin biopsy from the new patch revealed borderline tuberculoid leprosy histology in 47% of the patients. CONCLUSIONS: The findings suggest that leprosy primarily affects the nerve and that a neuritic phase precedes the development of visible cutaneous lesions.

Fine needle aspiration cytology of leprous neuritis.

OBJECTIVE: To document the cytomorphologic features of leprous neuritis and their correlation with bacterial density. STUDY DESIGN: A partly retrospective, partly prospective study of the fine needle aspiration cytology of enlarged nerves in leprosy. Cytomorphologic features of nerve aspirates from 28 patients were studied. May-Grünwald-Geimsa and Ziehl-Neelsen staining methods were employed. RESULTS: Five cytomorphologic patterns were observed in smears of nerve aspirates in 19 group I patients with concurrent skin and nerve lesions: (1) inflammation composed of epithelioid cell granulomas (5), bacillary index (BI) = 0; (2) epithelioid cell granulomas with necrosis (5), BI = 0-1+; (3) acellular necrosis (5), BI = 0-4+; (4) macrophage granuloma (3), BI = 5-6+; and (5) granulation tissue (1), BI = 1+. In 9 group II patients with pure neuritic leprosy, 3 patterns were seen: (1) epithelioid cell granulomas (5), BI 0-6+; (2) epithelioid granulomas with necrosis (1), BI = 0; and (3) acellular necrosis (3), BI = 0-6+. CONCLUSION: The entire spectrum of leprosy is seen in nerve aspirates. Necrosis is often a prominent feature. Recognition of the range of cytomorphologic patterns and their correlation with BI contribute to accurate calibration of the disease in nerves, resulting in appropriate choice of treatment.

Pseudoathetosis in a patient with leprosy.

A 35-year-old man with borderline tuberculoid leprosy developed Type I lepra reaction 12 days after anti-leprosy treatment. There was acute worsening of neuropathic symptoms and skin lesions. He developed severe sensory ataxia and pseudoathetosis resulting in marked disability. His symptoms significantly improved on corticosteroid therapy.