Neuritic Leprosy Research Articles

Microscopic leprosy skin lesions in primary neuritic leprosy

The histologic diagnosis of primary neuritic leprosy (PNL) remains a public health care concern, especially when nerve biopsies cannot be performed. As such, some authors emphasize the importance of performing a skin biopsy of a hypoesthetic area even without clinically visible lesions. In this study, an attempt was made to define the histologic changes in the sensory altered skin of 42 clinically diagnosed PNL patients. Histologic alterations caused by leprosy were seen in 31% of these patients: 6 were classified as borderline tuberculoid and 7 as indeterminate. In addition, 33% showed mild, non-specific, mononuclear cell infiltrates around the blood vessels within the papillary and reticular dermis that probably reflected an early inflammatory reaction to Mycobacterium leprae infection. Only 36% of those biopsied had no significant lesions. Our results suggested that, while not all PNL patients are similar, histologic skin examination can contribute to early leprosy detection and commencement of adequate treatment.

Leprosy and the peripheral nervous system: basic and clinical aspects.

Leprosy is one of the most common causes of nontraumatic peripheral neuropathy in the developing world. The causative agent, Mycobacterium leprae, has a predilection for Schwann cells, where the organism multiplies unimpeded by organism-specific host immunity, resulting in destruction of myelin, secondary inflammatory changes, and destruction of the nerve architecture. The cardinal diagnostic features of leprosy are anesthetic skin lesions, neuropathy, and positive skin smears for the bacilli. However, patients may rarely present without skin lesions in pure neuritic leprosy. Electrodiagnostic findings early in the disease reveal demyelinating features, such as slowing of conduction velocity and prolongation of latencies, but as the disease progresses secondary axonal damage commonly ensues. Electrodiagnostic studies are also useful to monitor for toxicity secondary to therapy, particularly thalidomide-associated neuropathy. Nerve biopsy of a sensory cutaneous nerve is sometimes essential to confirm a diagnosis of leprosy. Significant advances in understanding of the pathogenesis, mapping of the genome, and other advances in molecular biology may result in better preventive and therapeutic modalities, and the goal of eradicating leprosy as a global problem may yet be realized.

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

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. 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. 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. The findings suggest that leprosy primarily affects the nerve and that a neuritic phase precedes the development of visible cutaneous lesions.

Nerve thickening in leprosy patients and risk of paralytic deformities: a field based study in Agra, India

This paper examines the extent of nerve thickening among leprosy patients detected in the field in Agra district. All the clinically diagnosed leprosy patients were examined in detailed for thickening of local cutaneous nerves and peripheral nerve trunks. In each case all the major nerve trunks in both upper and lower extremities, forehead and neck were examined for thickening. Nerve thickening was found in 94% of multibacillary (MB) patients and among 52% paucibacillary (PB) patients. Nerve thickening was found to be more in males, in prevalent cases than in new (untreated) cases and increased significantly with age and delay in diagnosis (P<0.001). Visible deformities of grade > or =2 were found in 10% (58/573) of the leprosy patients; paralytic deformity accounted for 78% (45/58). Claw hand alone or in combination was seen in 82% (37/45) of patients with paralytic deformities. Risk (odd ratio) for deformities was observed to be high (15-18 times) with increasing number of nerves among patients with neuritic leprosy but correlated with delay in diagnosis of over 5 years. Likewise, deformities were more often seen in those with skin lesions, provided they had > or =3 thickened nerves. Findings suggest that early detection and treatment is useful in preventing deformities.

Posterior tibialis transfer for foot-drop due to leprosy: a case with 40 years follow up

A 56-year-old male was transferred to our centre because of a relapse of leprosy neuritis in the hands. We found that the patient had received a posterior tibialis tendon transfer for correction of his left dropped foot 40 years previously. On examination active dorsiflexion of the left ankle joint was close to 0° with grade 4 power of dorsiflexion, and the plantar flexion was about 35°. Walking gait was almost normal. There were some scars on the plantar surface of the left metatarsal area; but with the continuous use of a soft dressing pad under the middle part of the sole, plantar ulceration has been avoided for many years even with active daily activities of the patient. The patient is very satisfied with the operative results.

A Comparison of Economic Aspects of Hospitalization Versus Ambulatory Care in the Management of Neuritis Occurring in Lepra Reaction

Neuritis is one of the important causes of deformities and disabilities in leprosy. Neuritis has been managed both in the field and in hospital. This study was done to compare the economic aspects of cost of ambulatory vs in-patient management of neuritis in leprosy. The quality of life of the affected patients and the clinical improvement in the 2 groups were also studied. Twenty six patients fulfilling the study criteria were randomized into the ambulatory and in-patient group (13 in each group). The primary outcome examined was cost, in various categories; the secondary outcomes included pre- and post-treatment comparison of Quality of Life (QOL) scores and tests of sensory and motor function. The direct and indirect medical costs incurred by patients in the hospitalized group were higher than those patients in the ambulatory group. The difference in the direct medical costs between the two groups was Rs. 9110.5, and the extra direct non medical costs incurred by patients in the hospitalized group was Rs. 888.50 because of more frequent visits of family members. A greater percentage of ambulatory than in-patients returned to work in </= 15 days (53.8% vs 15.3%), and the mean duration before returning to work was 19.5 days ambulatory patients compared to 66.8 days for in-patients group. The QOL scores and motor and sensory function tests showed no significant difference between groups. Although the sample size was small, these preliminary results suggest that substantial cost minimization by ambulatory care is possible without significantly affecting the quality of life or peripheral nerve function.

Pure neuritic leprosy in India: an appraisal.

Pure neuritic leprosy (PNL) constitutes a significant proportion of all cases in India, however, this form of disease has not been fully recognized and investigated and there is little information in the existing literature. To study the epidemiological characteristics of PNL in India. A retrospective analysis of leprosy clinic records for the period 1993 to 2003 was undertaken. Detailed demographic profiles and clinical findings were noted from the predesigned clinic proforma. A slit-skin smear for acid-fast baclli (AFB) was done in all cases from the area of sensory loss. A skin biopsy was done from the area of sensory impairment to study histopathological changes. Further investigations such as nerve conduction velocity studies (NCV), fine needle aspiration cytology (FNAC), or nerve biopsy (superficial nerve twigs) were done if indicated in patients whenever there was difficulty in clinical diagnosis. Of the total 1542 leprosy patients seen over this period, 65 (4.2%) had PNL. Males were more commonly affected than females (2.6:1.). The majority of patients 40/65(61.5%) were aged between 15 and 35 yrs. Predominant presenting symptoms were paresthesia, pain, sensory/motor deficit, and trophic changes. A majority of the patients 39/65 (60.0%) presented with involvement of 2 or more nerves in the same extremity. Mononeuritis was seen in 26 (40%) patients. The nerves most often involved were the right ulnar nerve in the upper extremity, and the right common peroneal nerve in the lower limb. In general, the nerves of the upper extremity were more commonly involved than in the lower limbs (67 vs. 55). Motor deformities such as claw hand and foot drop were present in 13/75 (20%) and 7/65 (10.8%) patients, respectively. Slit-skin smears were negative in all patients, and skin histopathology from the area of sensory loss revealed non-specific inflammation in the dermis in a majority of patients, with perineural inflammation in a few. All patients were treated with multi-drug therapy (MDT); patients with >/=2 peripheral nerve trunk involvements were treated with WHO MDT MB regimen, while others were administered WHO MDT PB regimen. Follow-up for up to 2 yrs was available in only 32/65 (49.2%) patients, none of whom developed any skin lesions during this period. PNL is a distinct subset of disease frequently seen in India. There is need to pay more attention to this form of leprosy and diagnose and treat patients earlier to prevent deformities and sequelae of nerve damage.

Fine Needle Aspiration Cytology of Leprous Neuritis

To document the cytomorphologic features of leprous neuritis and their correlation with bacterial density. 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. 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+. 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.

Traitement chirurgical de décompression des névrites lépreuses à l’hôpital Bom-Pastor (Amazonie brésilienne)

Purpose. – Only leprosy resource centres undertake surgery for neuritis. Patients’ accessibility to this surgical procedure is poor because these centres are often far from their homes. The aim of our work is to study the feasibility of neuritis surgery in the field. Methods. – A surgeon trained in this surgery was recruited by Bom-Pastor hospital in Brazilian Amazonia, which is located 400 km away from the leprosy resource centre. Patients operated from May 1996 to December 1997 were enrolled in this retrospective study. Results. – A total of 45 operations were carried out during 17 procedures on 13 patients, among which 12 were multibacillary cases. The decompression surgery was performed with a median delay of 1 year after leprosy diagnosis and 3.5 months after the neuritis diagnosis. Among 17 operations, 14 were performed for painful neuritis of recent onset unsuccessfully treated with corticoids or recurring during the month after corticoids were withdrawn. The other three operations were performed for long-standing neuritis with paralysis and deformity. Pain was relieved in all the cases of recent neuritis, except for one patient who suffered from a serious steroid-dependant erythema nodosum leprosum. An improvement of motor function was observed in one out of three patients with long-standing neuritis. Adverse effects were few: a scar infection with a rapid recovery and a keloid scar. Two neurites recurred 2 and 10 months after the surgery. Conclusions. – In an endemic leprosy region, field access to surgery for neuritis appears to prove real progress in the management of leprosy neuritis.

Fine needle aspiration cytology (FNAC) of nerves in leprosy.

Leprosy is primarily a disease of the peripheral nerves and a technique that is simpler than nerve biopsy is required to evaluate nerve involvement, especially in pure neuritic (PN) leprosy. This study was designed to evaluate the role of FNAC of the nerve in the diagnosis and classification of leprosy. A prospective study was carried out on 25 patients with clinically active leprosy and at least one thickened peripheral sensory nerve. Nerve aspirates were evaluated by May-Grunwald-Giemsa and Fite's staining. Lepromin test, slit skin smears (SSS), skin biopsies (except PN cases) and nerve biopsies were performed and compared with FNAC. FNAC of nerve from 23 cases (92%) yielded diagnostic aspirates. Acid fast bacilli were observed in six cases by FNAC. FNAC and nerve pathology were equally comparable with the other parameters evaluated. Based on the results, cytological criteria were developed for interpreting nerve aspirates and the cases were classified as paucibacillary (18), BB (2), BL (2), LL (1) and non-diagnostic (2). All PN cases showed diagnostic paucibacillary type cytology. FNAC of the nerve yields diagnostic aspirates in leprosy comparable with nerve pathology and the proposed cytological criteria may be useful in classification of nerve aspirates.

The diagnosis of leprosy among patients with symptoms of peripheral neuropathy without cutaneous lesions: a follow-up study.

Forty-four patients with neuritic leprosy were individually followed for periods ranging from 4 months to almost 4 years for the purpose of ascertaining the presence and/ or absence of leprosy. The neural symptoms presented were sensory impairment (41), parasthesia (28), nerve enlargement (22), nerve tenderness (20), paresia (20), amyotrophy (8). Leprosy was diagnosed in ten out of the total number of patients studied. Leprosy was confirmed by the appearance of reactional neuritis (4), reversal reaction (2), biopsy of the hypoesthesic area (3) and the appearance of non-reactional cutaneous lesion. We reported an experience in the diagnosis of neuritic leprosy and its most frequent clinical presentation with which clinicians have to be acquainted. We can also state that the clinical follow-up was an effective strategy for the diagnosis of the disease when diagnostic facilities are not available or have not confirmed the diagnosis.

Detection of disease related immune complexes in the serum of leprosy patients: A novel single step method

Mycobacterium leprae antigen and antibody complexes could be detected in the serum of leprosy patients using monoclonal antibody ML34 and anti-BCG antibodies by enzyme-linked immunosorbent assay. This simplified system detects disease related complexes without the need for isolating and purifying them from the serum. Immune complexes captured using monoclonal antibody ML34 revealed positivity in seven out of eight neuritic, two out of nine tuberculoid (TT), five out of ten borderline tuberculoid (BT), four out of ten borderline lepromatous (BL) and four out of ten lepromatous (LL), leprosy cases. One of the controls also showed immune complex of an IgM type. Anti-BCG based IgG immune complexes assay revealed positivity in six out of eight neuritic, one out of nine TT, four out of ten BT, two out of ten BL, four out of ten LL leprosy cases, and two out of 24 healthy controls. IgM type of mycobacterial immune complexes were almost negligible. Capture of complexes using monoclonal antibody ML34 which is against lipoarabinomannan of M. leprae seems to work better than polyclonal anti-BCG antibody. The probable role of immune complexes in nerve damage needs to be evaluated, as very high levels of immune complexes are found in neuritic leprosy by both the assays. The above test would be useful in immunodiagnosis of neuritic leprosy and also in cases where antibody response is not detectable because of the formation of immune complexes.

Histological studies in primary neuritic leprosy: changes in the nasal mucosa.

The nasal mucosae of 39 cases of primary neuritic leprosy (PNL) registered at Karigiri were studied histologically to determine nasal mucosal involvement in PNL and its relevance to the pathogenesis of the disease. Specific changes of leprosy were seen in 20 (51%) biopsies, ranging from macrophage granulomas with acid fast bacilli, to epithelioid granulomas and nerve inflammation. The remaining biopsies revealed chronic inflammatory changes of the mucosa or mild non-specific nerve changes. These findings show that there are widespread effects of the disease even in PNL patients in whom the disease is believed to be confined to the peripheral nerves. The findings also show that early leprosy involvement can be found in the nasal mucosa even before lesions become apparent in the skin or other parts of the body. The nasal mucosa could be one of the sites for the primary lesion in leprosy. Clinical and histological examination of the nasal mucosa may be useful and important in the early diagnosis of leprosy and especially in contacts.

Histological studies in primary neuritic leprosy: changes in the apparently normal skin.

The visually normal skin of 196 patients diagnosed clinically to have primary neuritic leprosy was studied histologically to determine whether there were any specific changes due to the disease in this site. Histological changes due to leprosy were seen in 32.1% of the patients, and included, indeterminate leprosy in 19.4%, borderline tuberculoid leprosy in 6.6% and borderline lepromatous leprosy in 6.1%. The remaining biopsies showed mild non-specific dermal inflammation, mild nerve changes or no significant lesion. The nerve inflammation and/or granulomas were mostly in the deep dermal nerves or neurovascular complexes. This study shows that there is a cutaneous component to primary neuritic leprosy and the disease is not totally confined to nerves. The absence of visible hypopigmented patches in these patients is probably related to the deep location of the dermal inflammation.

Doit-on pratiquer des biopsies de la branche sensitive du nerf radial chez les malades lépreux?: A propos de 112 cas

Biopsies of the superficial sensory branch of the radial nerve are contested. Some authors mention it to be simple and without harm, but others are formally against this procedure. At ILAD, 274 biopsies were made between 1986 to 1992. We present a review of 112 leprosy patients for whom biopsy was done. On 112 reexamined patients, we observed 2 benign neuroma, hence 2%. The comparison of nerve function before biopsy and after, of 63 of the 112 patients, reexamination shows no significant modification of the functional score. Given even the occurrence of benign neuroma in only 2% of the cases, the authors do not recommend the biopsy of the superficial sensory branch of the radial nerve. For research purposes on neuritis in leprosy, as well as to assure diagnosis in primary neuritic leprosy, we propose the biopsy of the sensory branch of the musculo cutaneous nerve at elbow level.

Surgery for neuritis in leprosy: indications for and results of different types of procedures.

From December 1988 to December 1992, 129 surgical procedures were performed on the peripheral nerves of 64 leprosy patients at the Hospital Cardinal Léger de l'Institut Fame Pereo for leprosy control in Haiti. Sixty-four patients totalizing 129 nerves with sufficient clinical data form the basis of this study. Based on the retrospective analysis of the operated cases, a new classification built on macroscopic findings of the involved nerves is presented. Five grades, according to the presenting aspects of these nerves, are set up as guides for different surgical procedures to be performed on the nerves: external decompression for the lesser grades I and II, intraneural neurolysis, interfascicular neurolysis for the higher grades III and IV, cleaning, and debridement for grade V. The final results are discussed. This new macroscopic grading done at surgery helps to minimize the aggressive procedures performed on nerve trunks, decrease the morbidity of surgical action on the nerve vascular structures, and consequently, preserves all possible sensory and motor functions of a nerve.

Temporalis muscle transfer in the correction of lagophthalmos due to leprosy.

In the correction of lagophthalmos due to leprosy neuritis temporalis muscle transfer (TMT) is used to provide a motor to assist in lid closure. This study of TMT in 51 eyes was carried out to assess the effectiveness of TMT in achieving lid closure and corneal protection. The average lid gap preoperatively on light closure was 7.3 mm which was reduced to 3.2 mm on final follow-up. The average lid gap pre-operatively on tight closure was 5.3 mm which was reduced to 0.4 mm at final follow-up. It is possible to train patients with partial or total anesthesia of the cornea in a visual THINK-BLINK reflex. The common complications encountered were ectropion in 6 eyes (12%) and ptosis in 3 eyes (6%).

Practical problems in the management of leprosy.

The categorization of leprosy into paucibacillary or multibacillary depends on the report of slit-skin smears. Unfortunately, in many control programmes the quality of slit smears is below par. Taking the example of India, the main reasons were that the work of laboratory technicians was unrewarding as compared to serving in a general health care system. There was lack of equipment and an unrealistic patient to technician ratio. Future attempts were made by experienced workers to devise a clinical system for classifying leprosy as paucibacillary or multibacillary based on counting the number of lesions. However this method did not prove cost-effective because more paucibacillary patients were classified in the multibacillary group increasing the burden of treatment. A renewed attempt to improve slit-smear performance should be made by modifying the existing methods. This can definitely improve the situation. Patients with multiple macular lesions and those with neuritic leprosy are best treated with the MB-MDT regimen. The treatment for PB leprosy is to continue up to 6 months but in MB leprosy with a high bacterial index a longer duration of MDT may be required. Following completion of MDT many cases with deformity are accumulating and their care forms are a neglected part of many control programmes. In addition to strengthening the infrastructure, simple techniques must be imparted to those with deformities and disabilities. This involves the artful and innovative cooperation of the health worker, patient and the community. The leprosy worker should be motivated to promote such activities.

TIBIALIS POSTERIOR TRANSFER FOR THE CORRECTION OF FOOT DROP IN LEPROSY

A comparison was made of the results produced by the circumtibial and interosseous routes of transfer of tibialis posterior for the correction of foot drop due to leprosy neuritis. The findings in 69 feet, of which 63 also had elongation of tendo Achillis, showed that the interosseous route gave a much lower incidence of recurrent inversion deformity of the foot. The results, in terms of improvement in gait and prevention of trophic changes, were satisfactory.

Tibialis posterior transfer in the correction of footdrop due to leprosy.

In the correction of footdrop due to leprosy neuritis the tibialis posterior muscle is re-routed and used to provide dorsiflexion of the foot. This study of tibialis posterior transfer was carried out to compare the results of the circumtibial and interosseous routes. There is no significant difference in the range of motion between either route through the range of the interosseous route is more functional (better dorsiflexion). The interosseous route is preferable as this results in a significantly lower incidence of recurrent inversion deformity of the foot at long-term follow-up when compared with the circumtibial route.