Neuropathic pain and psychological morbidity in patients with treated leprosy: a cross-sectional prevalence study in Mumbai

Background

Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated.

Methodology/Principal Findings

Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity.

Conclusions/Significance

One hundred and one patients were recruited, and 22 (21.8%) had neuropathic pain. The main sensory symptoms were numbness (86.4%), tingling (68.2%), hypoesthesia to touch (81.2%) and pinprick (72.7%). Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity.     

Asymmetric Nerve Enlargement: A Characteristic of Leprosy Neuropathy Demonstrated by Ultrasonography

Background

Neurological involvement occurs throughout the leprosy clinical spectrum and is responsible for the most feared consequences of the disease. Ultrasonography (US) provides objective measurements of nerve thickening and asymmetry. We examined leprosy patients before beginning multi-drug therapy aiming to describe differences in US measurements between classification groups and between patients with and without reactions.

Methodology/Principal Findings

Eleven paucibacillary (PB) and 85 multibacillary (MB) patients underwent nerve US. Twenty-seven patients had leprosy reactions (type 1, type 2 and/or acute neuritis) prior to US. The ulnar (at the cubital tunnel–Ut–and proximal to the tunnel–Upt), median (M) and common fibular (CF) nerves were scanned to measure cross-sectional areas (CSAs) in mm² and to calculate the asymmetry indexes ΔCSA (absolute difference between right and left CSAs) and ΔUtpt (absolute difference between Upt and Ut CSAs). MB patients showed greater (p<0.05) CSAs than PB at Ut (13.88±11.4/9.53±6.14) and M (10.41±5.4/6.36±0.84). ΔCSAs and ΔUtpt were similar between PB and MB. The CSAs, ΔCSAs and ΔUtpt were similar between PB patients with reactions compared to PB patients without reactions. MB patients with reactions showed significantly greater CSAs (Upt, Ut and M), ΔCSAs (Upt and Ut) and ΔUtpt compared to MB patients without reactions. PB and MB showed similar frequencies of abnormal US measurements. Patients with reactions had higher frequency of nerve thickening and similar frequency of asymmetry to those without reactions.

Conclusions/Significance

This is the first study to investigate differences in nerve involvement among leprosy classification groups using US before treatment. The magnitude of thickening was greater in MB and in patients with reactions. Asymmetry indexes were greater in patients with reactions and did not significantly differ between PB and MB, demonstrating that asymmetry is a characteristic of leprosy neuropathy regardless of its classification.     

Sonographic Appearance of Primary Thyroid Lymphoma-Preliminary Experience

Objective

Primary thyroid lymphoma (PTL) is an uncommon thyroid malignancy. Despite the rarity of PTL, it is important to recognize PTL promptly because its management differs from that of all the other thyroid neoplasms. This study was designed to investigate the sonographic features of PTL.

Methods

Twenty-seven pathologically confirmed PTLs were categorized into diffuse and non-diffuse type. Sonographic features including thyroid size, thyroid background echotexture, lesion size, echogenecity, calcification, vascularity, cervical lymphadenopathy of each type were retrospectively analyzed.

Results

All 27 PTLs were diffuse large B-cell lymphomas and were accompanied by diffuse Hashimoto''s thyroiditis. Ten were diffuse type and seventeen were non-diffuse type sonographically. The observations in diffuse group included goiter (10/10, 100.0%), marked echogenesity (10/10, 100.0%), heterogeneous echotexture (10/10, 100.0%), and cervical lymphadenopathy (4/10, 40.0%). The observations in non-diffuse group included marked hypoechogenicity (17/17, 100.0%), heterogeneous background thyroid gland (17/17, 100.0%), goiter (15/17, 88.2%), increased vascularity (8/13, 61.5%), mulifocality (10/17, 58.8%), and cervical lymphadenopathy (7/17, 41.2%).

Conclusions

Although some common features were found, the sonographic appearance of PTL is unspecific, especially for the diffuse type. Therefore, interventional diagnostic procedures should be warranted in the clinical settings when PTL is suspected.     

Early diagnosis of neuropathy in leprosy--comparing diagnostic tests in a large prospective study (the INFIR cohort study)

Background

Leprosy is the most frequent treatable neuromuscular disease. Yet, every year, thousands of patients develop permanent peripheral nerve damage as a result of leprosy. Since early detection and treatment of neuropathy in leprosy has strong preventive potential, we conducted a cohort study to determine which test detects this neuropathy earliest.

Methods and Findings

One hundred and eighty-eight multibacillary (MB) leprosy patients were selected from a cohort of 303 and followed for 2 years after diagnosis. Nerve function was evaluated at each visit using nerve conduction (NC), quantitative thermal sensory testing and vibrometry, dynamometry, monofilament testing (MFT), and voluntary muscle testing (VMT). Study outcomes were sensory and motor impairment detected by MFT or VMT. Seventy-four of 188 patients (39%) had a reaction, neuritis, or new nerve function impairment (NFI) event during a 2-year follow-up. Sub-clinical neuropathy was extensive (20%–50%), even in patients who did not develop an outcome event. Sensory nerve action potential (SNAP) amplitudes, compound motor action potential (CMAP) velocities, and warm detection thresholds (WDT) were most frequently affected, with SNAP impairment frequencies ranging from 30% (median) to 69% (sural). Velocity was impaired in up to 43% of motor nerves. WDTs were more frequently affected than cold detection thresholds (29% versus 13%, ulnar nerve). Impairment of SNC and warm perception often preceded deterioration in MF or VMT scores by 12 weeks or more.

Conclusions

A large proportion of leprosy patients have subclinical neuropathy that was not evident when only MFT and VMT were used. SNC was the most frequently and earliest affected test, closely followed by WDT. They are promising tests for improving early detection of neuropathy, as they often became abnormal 12 weeks or more before an abnormal monofilament test. Changes in MFT and VMT score mirrored changes in neurophysiology, confirming their validity as screening tests.     

Granulomatous reactivation during the course of a leprosy infection: reaction or relapse

Background

Leprosy is a chronic granulomatous infectious disease and is still endemic in many parts of the world. It causes disabilities which are the consequence of nerve damage. This damage is in most cases the result of immunological reactions.

Objectives

To investigate the differences between a type 1 leprosy (reversal) reaction and relapse on using histopathology.

Methods

The histopathological changes in 167 biopsies from 66 leprosy patients were studied. The patients were selected when their sequential biopsies demonstrated either different patterns or maintained the same pattern of granulomatous reaction over more than two years during or after the treatment of leprosy.

Results

In 57 of the patients studied, a reactivation was seen which coincided with a decrease in the bacteriological index (BI), suggesting that this reactivation (reversal reaction or type 1 leprosy reaction) coincides with an effective capacity for bacteriological clearance. In nine patients, an increase of the bacteriologic index (IB) or persistence of solid bacilli occurred during the reactivation, indicating proliferative activity, suggestive of a relapse. The histopathological aspects of the granulomas were similar in both groups.

Conclusion

Bacterioscopy provided the only means to differentiate a reversal reaction from a relapse in patients with granulomatous reactivation. The type 1 leprosy reaction may be considered as a part effective immune reconstitution (reversal, upgrading reaction) or as a mere hypersensitivity reaction (downgrading reaction) in a relapse.     

Viral Co-infection and Leprosy Outcomes: A Cohort Study

Background

The role of the host immunity in determining leprosy clinical forms and complications is well recognized, implying that changes in the immune status may interfere with several aspects of the disease. Therefore, we hypothesized that the presence of viral co-infections and associated immunological changes will have a clinical impact on leprosy outcomes. The aim of our study was to determine the clinical impact of human immunodeficiency virus (HIV), human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection on the development of reactions, neuritis, neuropathy and relapses.

Methodology/Principal Findings

Cohort study in 245 leprosy subjects from Bahia, Brazil. Patients were followed from the time of diagnosis until at least the end of multidrug therapy. Viral co-infection was detected in 36 out of the 245 patients (14.7%). Specific co-infection rates were 10.6% for HBV, 2.9% for HIV, 2.5% for HTLV-1 and 0.8% for HCV. All four groups of co-infected patients had higher rates of neuritis and nerve function impairment compared to non co-infected leprosy subjects. The relapse rate was also higher in the co-infected group (8.3%) versus patients without co-infection (1.9%); relative risk 4.37, 95% confidence interval 1.02–18.74.

Conclusions/Significance

Leprosy patients should be screened for HBV, HCV, HIV and HTLV-1 co-infections. Besides contributing to better health care, this measure will facilitate the early detection of severe complications through targeting of higher risk patients.     

Predicting Neuropathy and Reactions in Leprosy at Diagnosis and Before Incident Events—Results from the INFIR Cohort Study

Background

Leprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions.

Methodology/Principal Findings

The study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event.

Conclusions/Significance

These findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability.     

Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort

Background

Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions.

Methodology/Principal Findings

TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100.

Conclusions/Significance

Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-β with T1R.     

Cost-effectiveness of a chemoprophylactic intervention with single dose rifampicin in contacts of new leprosy patients

Background

With 249,007 new leprosy patients detected globally in 2008, it remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy.

Methods

We conducted a single centre, double blind, cluster randomised, placebo controlled trial in northwest Bangladesh between 2002 and 2007, including 21,711 close contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to close contacts, with follow-up for four years. The main outcome measure was the development of clinical leprosy. We assessed the cost effectiveness by calculating the incremental cost effectiveness ratio (ICER) between the standard multidrug therapy (MDT) program with the additional chemoprophylaxis intervention versus the standard MDT program only. The ICER was expressed in US dollars per prevented leprosy case.

Findings

Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total, $6,009 incremental cost was invested and 38 incremental leprosy cases were prevented, resulting in an ICER of $158 per one additional prevented leprosy case. It was the most cost-effective in neighbours of neighbours and social contacts (ICER $214), slightly less cost-effective in next door neighbours (ICER $497) and least cost-effective among household contacts (ICER $856).

Conclusion

Chemoprophylaxis with single dose rifampicin given to contacts of newly diagnosed leprosy patients is a cost-effective intervention strategy. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world.     

Comparing the clinical and histological diagnosis of leprosy and leprosy reactions in the INFIR cohort of Indian patients with multibacillary leprosy

Background

The ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment in leprosy. The aim was to study correlations between clinical and histological diagnosis of reactions.

Methodology/Principal Findings

Three hundred and three newly diagnosed patients with World Health Organization multibacillary (MB) leprosy from two centres in India were enrolled in the study. Skin biopsies taken at enrolment were assessed using a standardised proforma to collect data on the histological diagnosis of leprosy, leprosy reactions and the certainty level of the diagnosis. The pathologist diagnosed definite or probable Type 1 Reactions (T1R) in 113 of 265 biopsies from patients at risk of developing reactions whereas clinicians diagnosed skin only reactions in 39 patients and 19 with skin and nerve involvement. Patients with Borderline Tuberculoid (BT) leprosy had a clinical diagnosis rate of reactions of 43% and a histological diagnosis rate of 61%; for patients with Borderline Lepromatous (BL) leprosy the clinical and histological diagnosis rates were 53.7% and 46.2% respectively. The sensitivity and specificity of clinical diagnosis for T1R was 53.1% and 61.9% for BT patients and 61.1% and 71.0% for BL patients. Erythema Nodosum Leprosum (ENL) was diagnosed clinically in two patients but histologically in 13 patients. The Ridley-Jopling classification of patients (n = 303) was 42.8% BT, 27.4% BL, 9.4% Lepromatous Leprosy (LL), 13.0% Indeterminate and 7.4% with non-specific inflammation. This data shows that MB classification is very heterogeneous and encompasses patients with no detectable bacteria and high immunological activity through to patients with high bacterial loads.

Conclusions/Significance

Leprosy reactions may be under-diagnosed by clinicians and increasing biopsy rates would help in the diagnosis of reactions. Future studies should look at sub-clinical T1R and ENL and whether they have impact on clinical outcomes.     

Perineural Mast Cells Are Specifically Enriched in Pancreatic Neuritis and Neuropathic Pain in Pancreatic Cancer and Chronic Pancreatitis

Background

Pancreatic neuritis is a histopathological hallmark of pancreatic neuropathy and correlates to abdominal neuropathic pain sensation in pancreatic adenocarcinoma (PCa) and chronic pancreatitis (CP). However, inflammatory cell subtypes that compose pancreatic neuritis and their correlation to the neuropathic pain syndrome in PCa and CP are yet unknown.

Methods

Inflammatory cells within pancreatic neuritis lesions of patients with PCa (n = 20) and CP (n = 20) were immunolabeled and colorimetrically quantified with the pan-leukocyte marker CD45, with CD68 (macrophages), CD8 (cytotoxic T-lymphocytes), CD4 (T-helper cells), CD20 (B-lymphocytes), NCL-PC (plasma cells), neutrophil elastase, PRG2 (eosinophils), anti-mast cell (MC) tryptase and correlated to pain sensation. Perineural mast cell subtypes were analyzed by double immunolabeling with MC chymase. Expression and neural immunoreactivity of protease-activated receptor type 1 (PAR-1) and type 2 (PAR-2) were analyzed in PCa and CP and correlated to pain status of the patients.

Results

In PCa and CP, nerves were predominantly infiltrated by cytotoxic T-lymphocytes (PCa: 35% of all perineural inflammatory cells, CP: 33%), macrophages (PCa: 39%, CP: 33%) and MC (PCa: 21%, CP: 27%). In both entities, neuropathic pain sensation was associated with a specific increase of perineural MC (PCa without pain: 14% vs. PCa with pain: 31%; CP without pain: 19% vs. CP with pain: 34%), not affecting the frequency of other inflammatory cell subtypes. The vast majority of these MC contained MC chymase. PAR-1 and PAR-2 expression did not correlate to the pain sensation of PCa and CP patients.

Conclusion

Pancreatic neuritis in PC and CP is composed of cytotoxic T-lymphocytes, macrophages and MC. The specific enrichment of MC around intrapancreatic nerves in neuropathic pain due to PCa and CP suggests the presence of MC-induced visceral hypersensitivity in the pancreas. Therefore, pancreatic and enteric neuropathies seem to share a similar type of neuro-immune interaction in the generation of visceral pain.     

Preliminary evaluation of the sural nerve using 22-MHz ultrasound: a new approach for evaluation of diabetic cutaneous neuropathy

Background

The application of 22-MHz high-frequency ultrasound allows for visualization of the inner part of the sural nerve. The aim of this study was to evaluate the morphological changes of sural nerves in patients with type 2 diabetes mellitus using ultrasound.

Materials and Methods

The thickness/width (T/W) ratio, the cross-sectional area (CSA) of the sural nerves and the maximum thickness (MT) of the nerve fascicles were measured in 100 patients with type 2 diabetes mellitus and 50 healthy volunteers using 22-MHz ultrasound. Receiver operating characteristic (ROC) curves were plotted to determine the optimal cut-off values as well as the sensitivities and specificities. All parameters were significantly different between the subject and control groups. The ROC curves demonstrated that the MT was the most predictive of diabetic cutaneous neuropathy, with an optimal cut-off value of 0.365 mm that yielded a sensitivity of 90.3% and a specificity of 87.7%.

Conclusions

The results of this study suggest that 22-MHz ultrasound may be a valuable tool for evaluating diabetic cutaneous nerve neuropathy.     

Retinal Nerve Fibre Layer Thinning in Patients with Clinically Isolated Optic Neuritis and Early Treatment with Interferon-Beta

Background

Optic neuritis is associated with neurodegeneration leading to chronic impairment of visual functions.

Objective

This study investigated whether early treatment with interferon beta (IFN-β) slows retinal nerve fibre layer (RNFL) thinning in clinically isolated optic neuritis.

Methods

Twenty patients with optic neuritis and visual acuity decreased to ≤0.5 (decimal system) were included into this prospective, open-label, parallel group 4-month observation. After methylprednisolone pulse therapy, 10 patients received IFN-β from week 2 onwards. This group was compared to 10 patients free of any disease modifying treatment (DMT). The parameter of interest was change in RNFL thickness assessed at baseline and at weeks 4, 8, and 16. Changes in visual acuity, visual field, and visual evoked potentials (VEPs) served as additional outcome parameters.

Results

RNFL thinning did not differ between the groups with a mean reduction of 9.80±2.80 µm in IFN-β-treated patients (±SD) vs. 12.44±5.79 µm in patients who did not receive DMT (baseline non-affected eye minus affected eye at week 16; p = 0.67, t-test, 95% confidence interval: −15.77 to 10.48). Parameters of visual function did not show any differences between the groups either.

Conclusions

In isolated optic neuritis, early IFN-β treatment did not influence RNFL thinning nor had it any effect on recovery of visual functions.     

Venous graft-derived cells participate in peripheral nerve regeneration

Background

Based on growing evidence that some adult multipotent cells necessary for tissue regeneration reside in the walls of blood vessels and the clinical success of vein wrapping for functional repair of nerve damage, we hypothesized that the repair of nerves via vein wrapping is mediated by cells migrating from the implanted venous grafts into the nerve bundle.

Methodology/Principal Findings

To test the hypothesis, severed femoral nerves of rats were grafted with venous grafts from animals of the opposite sex. Nerve regeneration was impaired when decellularized or irradiated venous grafts were used in comparison to untreated grafts, supporting the involvement of venous graft-derived cells in peripheral nerve repair. Donor cells bearing Y chromosomes integrated into the area of the host injured nerve and participated in remyelination and nerve regeneration. The regenerated nerve exhibited proper axonal myelination, and expressed neuronal and glial cell markers.

Conclusions/Significance

These novel findings identify the mechanism by which vein wrapping promotes nerve regeneration.     

Metabolic changes in the visual cortex are linked to retinal nerve fiber layer thinning in multiple sclerosis

Objective

To investigate the damage to the retinal nerve fiber layer as part of the anterior visual pathway as well as an impairment of the neuronal and axonal integrity in the visual cortex as part of the posterior visual pathway with complementary neuroimaging techniques, and to correlate our results to patients'' clinical symptoms concerning the visual pathway.

Design, Subjects and Methods

Survey of 86 patients with relapsing-remitting multiple sclerosis that were subjected to retinal nerve fiber layer thickness (RNFLT) measurement by optical coherence tomography, to a routine MRI scan including the calculation of the brain parenchymal fraction (BPF), and to magnetic resonance spectroscopy at 3 tesla, quantifying N-acetyl aspartate (NAA) concentrations in the visual cortex and normal-appearing white matter.

Results

RNFLT correlated significantly with BPF and visual cortex NAA, but not with normal-appearing white matter NAA. This was connected with the patients'' history of a previous optic neuritis. In a combined model, both BPF and visual cortex NAA were independently associated with RNFLT.

Conclusions

Our data suggest the existence of functional pathway-specific damage patterns exceeding global neurodegeneration. They suggest a strong interrelationship between damage to the anterior and the posterior visual pathway.     

The prevalence of previously undiagnosed leprosy in the general population of northwest bangladesh

Background

The prevalence of previously undiagnosed leprosy (PPUL) in the general population was determined to estimate the background level of leprosy in the population and to compare this with registered prevalence and the known PPUL in different levels of contacts of leprosy patients.

Methodology and Principal Findings

Multistage cluster sampling including 20 clusters of 1,000 persons each in two districts with over 4 million population. Physical examination was performed on all individuals. The number of newly found leprosy cases among 17,862 people above 5 years of age from the cluster sample was 27 (19 SLPB, 8 PB2-5), giving a PPUL rate of 15.1 per 10,000.

Conclusions and Significance

PPUL in the general population is six times higher than the registered prevalence, but three times lower than that in the most distant subgroup of contacts (neighbour of neighbour and social contacts) of leprosy patients in the same area. Full village or neighbourhood surveys may be preferable to contact surveys where leprosy is highly endemic.     

Very different performance of the power Doppler modalities of several ultrasound machines ascertained by a microvessel flow phantom

Introduction

In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To clarify how the PDUS signal differs between machines we created a microvessel flow phantom.

Methods

The flow phantom contained three microvessels (150, 1000, 2000 microns). A syringe pump was used to generate flows. Five US machines were used. Settings were optimised to assess the lowest detectable flow for each US machine.

Results

The minimal detectable flow velocities showed very large differences between the machines. Only two of the machines may be able to detect the very low flows in the capillaries of inflamed joints. There was no clear relation with price. One of the lower-end machines actually performed best in all three vessel sizes.

Conclusions

We created a flow phantom to test the sensitivity of US machines to very low flows in small vessels. The sensitivity of the power Doppler modalities of 5 different machines was very different. The differences found between the machines are probably caused by fundamental differences in processing of the PD signal or internal settings inaccessible to users. Machines considered for PDUS assessment of RA patients should be tested using a flow phantom similar to ours. Within studies, only a single machine type should be used.     

Degree of Skin Denervation and Its Correlation to Objective Thermal Sensory Test in Leprosy Patients

Background

Leprosy is an infectious disease affecting skin and peripheral nerves resulting in increased morbidity and physical deformities. Early diagnosis provides opportune treatment and reduces its complications, relying fundamentally on the demonstration of impaired sensation in suggestive cutaneous lesions. The loss of tactile sensitivity in the lesions is preceded by the loss of thermal sensitivity, stressing the importance of the thermal test in the suspicious lesions approach. The gold-standard method for the assessment of thermal sensitivity is the quantitative sensory test (QST). Morphological study may be an alternative approach to access the thin nerve fibers responsible for thermal sensitivity transduction. The few studies reported in leprosy patients pointed out a rarefaction of thin dermo-epidermal fibers in lesions, but used semi-quantitative evaluation methods.

Methodology/Principal Findings

This work aimed to study the correlation between the degree of thermal sensitivity impairment measured by QST and the degree of denervation in leprosy skin lesions, evaluated by immunohistochemistry anti-PGP 9.5 and morphometry. Twenty-two patients were included. There were significant differences in skin thermal thresholds among lesions and contralateral skin (cold, warm, cold induced pain and heat induced pain). The mean reduction in the density of intraepidermal and subepidermal fibers in lesions was 79.5% (SD = 19.6) and 80.8% (SD = 24.9), respectively.

Conclusions/Significance

We observed a good correlation between intraepidermal and subepidermal fibers deficit, but no correlation between these variables and those accounting for the degree of impairment in thermal thresholds, since the thin fibers rarefaction was homogeneously intense in all patients, regardless of the degree of sensory deficit. We believe that the homogeneously intense denervation in leprosy lesions should be objective of further investigations focused on its diagnostic applicability, particularly in selected cases with only discrete sensory impairment, patients unable to perform the sensory test and especially those with nonspecific histopathological finds.     

Recent food shortage is associated with leprosy disease in Bangladesh: a case-control study

Background

Leprosy is remaining prevalent in the poorest areas of the world. Intensive control programmes with multidrug therapy (MDT) reduced the number of registered cases in these areas, but transmission of Mycobacterium leprae continues in most endemic countries. Socio-economic circumstances are considered to be a major determinant, but uncertainty exists regarding the association between leprosy and poverty. We assessed the association between different socio-economic factors and the risk of acquiring clinical signs of leprosy.

Methods and Findings

We performed a case-control study in two leprosy endemic districts in northwest Bangladesh. Using interviews with structured questionnaires we compared the socio-economic circumstances of recently diagnosed leprosy patients with a control population from a random cluster sample in the same area. Logistic regression was used to compare cases and controls for their wealth score as calculated with an asset index and other socio-economic factors. The study included 90 patients and 199 controls. A recent period of food shortage and not poverty per se was identified as the only socio-economic factor significantly associated with clinical manifestation of leprosy disease (OR 1.79 (1.06–3.02); p = 0.030). A decreasing trend in leprosy prevalence with an increasing socio-economic status as measured with an asset index is apparent, but not statistically significant (test for a trend: OR 0.85 (0.71–1.02); p = 0.083).

Conclusions

Recent food shortage is an important poverty related predictor for the clinical manifestation of leprosy disease. Food shortage is seasonal and poverty related in northwest Bangladesh. Targeted nutritional support for high risk groups should be included in leprosy control programmes in endemic areas to reduce risk of disease.