Clinical guidelines for the management of cutaneous leishmaniasis in British military personnel.
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Animals↗
Biomedical subjects
D N Lockwood
Publications and source records attributed to D N Lockwood.
Borderline tuberculoid leprosy: an immune reconstitution phenomenon in a human immunodeficiency virus-infected person.
Two months after starting highly active antiretroviral treatment (HAART), an individual with human immunodeficiency virus type 1 (HIV-1) infection and profound CD4+ T lymphocytopenia developed several erythematous plaques on his face, which were due to borderline tuberculoid leprosy with reversal reaction. The temporal association between the development of these lesions and changes in blood CD4+ lymphocyte count and plasma HIV-1 load observed during HAART strongly suggests that the presentation of leprosy resulted from immune reconstitution.
AIDS-Related Opportunistic Infections↗
The diagnosis of leprosy is delayed in the United Kingdom.
Diagnostic delay in leprosy can have serious neurological consequences for the patient. We studied the presentation of leprosy patients, focusing on delays in diagnosis, in a retrospective case-note review of 28 patients referred to The Hospital for Tropical Diseases during 1995-1998. The median ages at onset of symptoms and at diagnosis were 25.1 years (range 9-77.7) and 30.1 years (range 9-78.3), respectively. The median time from symptom onset to diagnosis was 1.8 years (0.2-15.2). Prior to referral to a leprologist, patients had seen a dermatologist (20), neurologist (9), orthopaedic surgeon (5) and rheumatologist (2). Delay in diagnosis occurred in 82% of cases. Misdiagnoses as dermatological and neurological conditions were important causes of delay, and 68% of patients had nerve damage resulting in disability. Leprosy can be difficult to diagnose outside endemic areas. Increased awareness amongst general practitioners and hospital specialists would lead to more rapid diagnosis, thus minimizing damage and disability.
Adolescent↗
Immunohistochemical analysis of cellular infiltrate and gamma interferon, interleukin-12, and inducible nitric oxide synthase expression in leprosy type 1 (reversal) reactions before and during prednisolone treatment.
The effects of prednisolone treatment on the cellularity and cytokine (gamma interferon, interleukin-12, and inducible nitric oxide synthase) profiles of leprosy skin type 1 (reversal) reactions were studied using immunohistochemistry. Skin biopsies were taken from 15 patients with leprosy type 1 (reversal) reactions at days 0, 7, 28, and 180 after the start of steroid treatment. Prednisolone treatment had little effect at day 7, but by day 28 significant decreases were found in cytokine levels. Some patients maintained cytokine production at days 28 and 180. These results illustrate the strong Th1 profile of type 1 reactional lesions, the slow response to steroid therapy, and continuing activity at 180 days.
Humans↗
Update on leprosy.
Leprosy, a result of infection by Mycobacterium leprae, is a leading cause of peripheral neuropathy. The World Health Organization aimed to eliminate leprosy as a public health problem by 2000, but this has not been attained. Patients with leprosy continue to present in the UK. The diagnosis of leprosy is frequently not considered, with resultant pathological and psychological problems for patients.
Clofazimine↗
The pattern of leprosy-related neuropathy in the AMFES patients in Ethiopia: definitions, incidence, risk factors and outcome.
The ALERT MDT Field Evaluation Study (AMFES) began in 1988 and followed patients prospectively for up to 10 years after release from treatment (RFT). This paper presents the findings from this cohort with regard to neuropathy and nerve damage. Five hundred and ninety-four new cases of leprosy are included in the study, 300 multibacillary (MB) and 294 paucibacillary (PB) cases. Fifty-five percent of patients had some degree of impairment at diagnosis and a further 73 (12%) developed new nerve function impairment (NFI) after starting multiple drug therapy (MDT). The overall incidence rate for neuropathy was 39 episodes per 100 PYAR in the first year after diagnosis, gradually declining to 12 episodes per 100 PYAR in the sixth year. In those patients without impairment at diagnosis, the incidence rate of neuropathy was 25 episodes per 100 PYAR for MB cases and 11 per 100 PYAR for PB cases in the first year; in 33% of MB cases whose first episode of neuropathy occurred after diagnosis, that first episode took place after the first year, or after the normal period of treatment with MDT. Seventy-three patients with neuropathy developing after diagnosis are reported more fully: 34 (47%) had only one nerve involved and of these 25 (73%) had a single, acute episode of neuropathy. Nine (27%) had further episodes. Thirty-nine (53%) had more than one nerve involved and of these 16 (41%) had a single, acute episode, while 23 (59%) had further episodes. The terms 'chronic' and 'recurrent' neuropathy are defined and used to describe the pattern of neuropathy in those with repeated attacks. In patients with no impairment at the start of the study, treatment with steroids resulted in full recovery in 88% of nerves with acute neuropathy but only 51% of those with chronic or recurrent neuropathy. The median time to full recovery from acute neuropathy was approximately 6 months, but in a few cases recovery occurred gradually over 2-3 years. Severe neuropathy was less likely to be followed by a complete recovery than mild or moderate neuropathy. Forty-two percent of nerves with acute neuropathy that were not treated with steroids also fully recovered. In the group of patients who were thought to have old, permanent impairments at diagnosis, full recovery of nerve function occurred in 87/374 (23%) of the nerves involved. The overall outcome is illustrated by examining the average EHF score for groups of patients. Patients with no new neuropathy after diagnosis show a gradual improvement in their EHF score, while those with any episodes of neuropathy after diagnosis show a gradual deterioration after completion of MDT. Possible explanations for these findings are discussed. Risk factors for neuropathy, for chronic and recurrent neuropathy, and for a poor outcome 5 years after release from treatment, are examined. Impairment at diagnosis was the main risk factor for a poor outcome, accompanied by the occurrence of chronic/recurrent neuropathy or a reversal reaction.
Adult↗
Steroids in leprosy type 1 (reversal) reactions: mechanisms of action and effectiveness.
Steroids are widely used for the treatment of leprosy reactions. The effectiveness of steroid treatment is variable, with only 60% of patients regaining nerve function. Sequential skin biopsy specimens, obtained from 15 patients with type 1 (reversal) reactions, have been studied to document the cytokine profile and cellularity of the lesions. All of the patients were placed on a standard course of steroids after the first biopsy. Subsequent biopsies were performed seven, 28 and 180 days later. The specimens were stained for interferon-gamma (IFN gamma), interleukin-12 (IL-12) and inducible nitric oxide synthase (iNOS). After the first biopsy, all patients were placed on a standard reducing course of steroids beginning at 30 mg daily. By day 7, treatment with prednisolone showed little effect on the cellularity and cytokine profiles. However, by day 28, significant decreases of IFN-gamma, IL-12 and iNOS were found for most patients. Some patients maintained cytokine production at day 28 and even at day 180. These data illustrate the strong Th1 profile of type 1 reactional lesions, the relatively slow response to therapy, and the continuing activity after treatment with steroids for 180 days. The variation of individual responses emphasizes their importance. Additional prospective studies will be required to determine whether patients with high intra-lesional levels of cytokine are at risk of recurrent reactions. The need for studies both of different glucocorticoids and of other non-steroidal immunosuppressants for the treatment of reactions is discussed.
Biopsy, Needle↗
Leprosy--new perspectives on an old disease.
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Humans↗
Specificity and function of immunogenic peptides from the 35-kilodalton protein of Mycobacterium leprae.
We identified a T-cell determinant of the 35-kDa antigen of Mycobacterium leprae which is discriminatory against cross-sensitization by its closely related homologue in Mycobacterium avium. From synthetic peptides covering the entire sequence, those with the highest affinity and permissive binding to purified HLA-DR molecules were evaluated for the stimulation of proliferation of peripheral blood mononuclear cells (PBMCs) from leprosy patients and healthy sensitized controls. Responses to the peptide pair 206-224, differing by four residues between M. leprae and M. avium, involved both species-specific and cross-reactive T cells. Lymph node cell proliferation in HLA-DRB1*01 transgenic mice was reciprocally species specific, but only the response to the M. leprae peptide in the context of DR1 was immunodominant. Of the cytokines in human PBMC cultures, gamma interferon production was negligible, while interleukin 10 (IL-10) responses in both patients and controls were more pronounced. IL-10 was most frequently induced by the shared 241-255 peptide, indicating that environmental cross-sensitization may skew the response toward a potentially pathogenic cytokine phenotype.
Animals↗
Immunohistochemical detection of PGL-1, LAM, 30 kD and 65 kD antigens in leprosy infected paraffin preserved skin and nerve sections.
A panel of lipid, carbohydrate and protein antibodies were optimized for use in detecting M. leprae antigens in paraffin embedded material. Skin and nerve biopsies from 13 patients across the leprosy spectrum were studied. All antibodies detected antigen in tissues with a BI > 1. Phenolic-glycolipid was not detected in bacteriologically negative tissue but lipoarabinomanan (LAM) and protein antigens were detected. Staining with LAM was strongest and gave least background. The transfer of this immunohistochemical technique to paraffin embedded material will allow examination of tissue with better morphology and from clinics without access to tissue freezing facilities.
Antibodies, Monoclonal↗
Leprosy in England and Wales.
This paper reviews cases of leprosy notified in England and Wales to the Central Leprosy Register since its inception in 1951. Leprosy remains a rare condition in England and Wales, with fewer than ten cases notified on average in recent years. No definite case of indigenously acquired leprosy has been reported since the disease became notifiable. Although only a small number of patients present each year, leprosy remains a debilitating disease, and the unfamiliarity of clinicians with this condition can lead to delays in diagnosis and undernotification.
Adult↗
Pregnancy and leprosy: a comprehensive literature review.
The interaction between pregnancy, leprosy and leprosy reactions was examined in a systematic literature review. Several retrospective case series and one retrospective cohort study but only one prospective cohort study were identified in the English literature. Type 1 (reversal) reactions were particularly likely to occur during the post partum. This temporal association was also present for both overt and silent neuritis. Type 2 (erythema nodosum leprosum) reactions occur throughout pregnancy and during lactation, and may be severe and recurrent. No prospective, controlled studies were found that documented the complications of pregnancy in women treated with multidrug therapy regimens. Our study highlights the need for such studies, with appropriate controls, on women throughout pregnancy and lactation so that risk factors for reaction and neuritis during pregnancy can be identified and quantified.
Cohort Studies↗
Kellersberger Memorial Lecture 1998: Nerve Damage in Leprosy: a problem for patients, doctors and scientists.
There are interesting challenges in leprosy right now. The last fifteen years have seen the world-wide implementation of multidrug therapy with tangible benefits for patients and doctors. Paradoxically this success has revealed how much we still need to understand about leprosy nerve damage. For patients it is imperative that nerve damage is detected at an early stage when damage is still reversible. They need effective education to prevent the development of disability and to minimise the social and economic effects of nerve damage. For doctors and paramedical workers nerve damage needs effective treatment. We need to use current treatments effectively and also develop new treatments. This lecture looks critically at the pathology, detection and treatment of nerve damage, reviewing our present knowledge and looking to future developments.
Anti-Inflammatory Agents↗
Immunocytochemical localization of inducible nitric oxide synthase and transforming growth factor-beta (TGF-beta) in leprosy lesions.
Inducible nitric oxide synthase (iNOS) and TGF-beta were localized by immunocytochemistry in skin lesions from patients across the leprosy spectrum, and from patients undergoing reversal reaction. iNOS expression was highest at the tuberculoid pole of the spectrum, and increased during reversal reaction. TGF-beta was observed throughout the leprosy spectrum, but was highest at the lepromatous pole. Levels of TGF-beta decreased during reversal reaction. Reduced levels of TGF-beta may contribute to unregulated inflammatory responses during reactional episodes.
Humans↗
Rifampicin/minocycline and ofloxacin (ROM) for single lesions--what is the evidence?
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Anti-Bacterial Agents↗
The management of erythema nodosum leprosum: current and future options.
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Erythema Nodosum↗
Harnessing the strengths of the leprosy programme to control tuberculosis.
Tuberculosis remains a leading cause of death in Ethiopia but there is no effective national tuberculosis control programme. By contrast, the leprosy control programme has been very successful, with a 10-fold reduction in the number of leprosy cases requiring antibacterial treatment, though patients with nerve damage require continuing care. The paradox of rising numbers of tuberculosis cases and declining numbers of leprosy cases may be solved by joint leprosy-tuberculosis clinics. The strengths of leprosy fieldworkers in control management, case holding, and compliance can be harnessed in developing an effective tuberculosis control programme. Implementing a joint programme in Ethiopia may be beneficial not only for tuberculosis patients but also for leprosy patients, who are thus brought closer to general medical services.
Ethiopia↗