Leprosy Reactions: Experience in the Puerto Rico Hansen's Disease Population.

OBJECTIVE: Hansen's disease (HD) is a chronic granulomatous infection endemic in the tropics. Its main clinical manifestations involve the cutaneous, nervous, and musculoskeletal systems. Leprosy reactions (LR) are systemic inflammatory and immune-mediated complications of HD. These include reversal reactions (RR), erythema nodosum leprosum (ENL), and Lucio phenomenon. These reactions significantly increase disease-related morbidity and disability. We aimed to determine the number and type of LR, their association to hosts' immune responses (Ridley Jopling classification), timing of development, and treatment of HD patients in Puerto Rico. METHODS: A retrospective medical record review was performed on 291 HD patients containing LR status data available from the Dermatology Service at the Hispanic Alliance for Clinical & Translational Research. RESULTS: Our data revealed that 83 (29%) patients developed LR, of which 31% had RR and 69% had ENL. Most LR were observed in patients in the lepromatous border (97%): Borderline lepromatous leprosy (BL) and Lepromatous Leprosy (LL). Most patients with RR and ENL had a single episode (83% and 62%, respectively), and those that received multi-drug therapy (MDT) had a reaction onset occurring most frequently within the first year of MDT and after the first year of MDT, respectively. Prednisone was the first line treatment used to manage both types of LR. CONCLUSION: Most lepromatous reactions occur within the lepromatous border. ENL was the most common LR. Prompt recognition and management of these immunologic reactions is essential to prevent long term nerve function impairment.

Identification, replication, and functional fine-mapping of expression quantitative trait loci in primary human liver tissue.

The discovery of expression quantitative trait loci ("eQTLs") can help to unravel genetic contributions to complex traits. We identified genetic determinants of human liver gene expression variation using two independent collections of primary tissue profiled with Agilent (n = 206) and Illumina (n = 60) expression arrays and Illumina SNP genotyping (550K), and we also incorporated data from a published study (n = 266). We found that ∼30% of SNP-expression correlations in one study failed to replicate in either of the others, even at thresholds yielding high reproducibility in simulations, and we quantified numerous factors affecting reproducibility. Our data suggest that drug exposure, clinical descriptors, and unknown factors associated with tissue ascertainment and analysis have substantial effects on gene expression and that controlling for hidden confounding variables significantly increases replication rate. Furthermore, we found that reproducible eQTL SNPs were heavily enriched near gene starts and ends, and subsequently resequenced the promoters and 3'UTRs for 14 genes and tested the identified haplotypes using luciferase assays. For three genes, significant haplotype-specific in vitro functional differences correlated directly with expression levels, suggesting that many bona fide eQTLs result from functional variants that can be mechanistically isolated in a high-throughput fashion. Finally, given our study design, we were able to discover and validate hundreds of liver eQTLs. Many of these relate directly to complex traits for which liver-specific analyses are likely to be relevant, and we identified dozens of potential connections with disease-associated loci. These included previously characterized eQTL contributors to diabetes, drug response, and lipid levels, and they suggest novel candidates such as a role for NOD2 expression in leprosy risk and C2orf43 in prostate cancer. In general, the work presented here will be valuable for future efforts to precisely identify and functionally characterize genetic contributions to a variety of complex traits.

Leprosy in a Mexican immigrant.

A new diagnosis of borderline lepromatous leprosy was established in a man who had immigrated to Kentucky from Mexico. He was placed on a World Health Organization treatment regimen consisting of dapsone, clofazimine, and rifampin. The biology of leprosy, its diagnosis, treatment, and worldwide impact are reviewed. Because of the potential for highly mobile populations to export endemic diseases, Kentucky physicians must expand their lists of differential diagnoses.

A continuing focus of Hansen's disease in Texas.

To describe epidemiologic and clinical characteristics of Hansen's disease cases in Texas, information was abstracted from records of 810 patients reported from 1973 through 1997. Annually, from 18 to 54 patients were reported. Average annual incidence rates ranged from 1.9 to 2.4 cases per million population. A majority of the patients were male (63%) and white (77%). More than half (53%) of the patients were born in the United States; a majority (83%) of the patients born in the United States were born in Texas. Most (76%) patients were diagnosed with multi-bacillary leprosy. Foreign-born patients were more likely to be younger at onset and have multi-bacillary disease compared with patients born in the United States. Within Texas, an endemic focus of Hansen's disease exists along the Gulf of Mexico coast.

Preventive health care and screening of Latin American immigrants in the United States.

BACKGROUND: The Central and South American immigrant population in the United States is large and growing. A review of the preventive health care needs of this population has not previously been done but would be helpful to clinicians caring for immigrants in this country. METHODS: Using MEDLINE, the literature related to immigrants and their health status was searched, using the key words "immigrant," "refugee," "South/Central/Latin America," "health status," "screening," "nutrition," "parasites," "stomach/gastric cancer," "children," and "psychological." The American Statistics Index and Index to International Statistics were also resources. The available literature was reviewed and led to the recommendations in this article. RESULTS: Screening strategies for Latin American immigrants are discussed for intestinal parasites, tuberculosis, hepatitis B, schistosomiasis, leprosy, American trypanosomiasis (Chagas disease), malaria, human immunodeficiency virus (HIV) infection, cervical and gastric cancer, sickle cell trait, malnutrition, iron-deficiency anemia, incomplete immunizations, dental problems, psychological problems, impairment in the elderly, alcohol use, smoking, physical inactivity, and hypertension. There are not enough data to evaluate fully the screening strategies for most of these conditions, but recommendations are offered based on current knowledge. CONCLUSIONS: Screening is recommended for intestinal parasites and schistosomiasis, tuberculosis, hepatitis B in prenatal patients, leprosy in immigrants from high-risk areas, yearly Papanicolaou smears, malnutrition, iron-deficiency anemia, incomplete immunizations, dental problems, history of violence, and depression. Screening for sickle cell trait in prenatal patients from South America and universal hepatitis B screening are less clearly indicated but could be appropriate. Screening for American trypanosomiasis (Chagas disease), malaria, and gastric cancer is not recommended. Screening for HIV infection, functional impairment in the elderly, alcohol use, cigarette smoking, physical inactivity, and hypertension should be the same as for the general population.

Cancer mortality among patients with Hansen's disease.

For the evaluation of cancer risks associated with immunodeficiencies experienced by patients with Hansen's disease (leprosy) and for the assessment of possible adverse effects of dapsone therapy, a follow-up study was conducted of 1,678 patients admitted to the National Hansen's Disease Center in Carville, La., between 1939 and 1977. Overall, no substantial cancer mortality was observed (standardized mortality ratio = 1.3), nor was there any excess among patients exhibiting defects in cellular immunity by virtue of lepromatous forms of the disease. Notable was the absence of any significant excess of lymphoma (5 observed vs. 2.3 expected), despite the predominance of this tumor in certain other immunodeficiency states. Several cancer sites (oral, bladder, and kidney) occurred excessively, but reasons for the elevations were obscure. Although dapsone has been implicated as a carcinogen in laboratory animals, the use of sulfones, including dapsone, did not appear to affect significantly the risk of any cancers in this population.