Abstract
This population-based study examines the incidence and treatment of patients with Hansen disease residing in the United States.
Although endemic elsewhere, Hansen disease (HD) is a chronic infection caused by Mycobacterium leprae and Mycobacterium lepromatosis that is rarely seen in the United States.1 Few domestic reports offer long-term follow-up of patients with HD, who sometimes develop significant morbidity owing to delayed recognition of their illness.2 The Los Angeles County HD clinic, in operation since 1963, offers an archive that allows the description of the disease courses of a large group of patients with HD.
Methods
A retrospective review was performed on patients in our HD clinic from 1973 to 2018. Medical records were reviewed for demographics, clinical characteristics, treatment course, and outcomes. Two-tailed, unpaired testing using χ2 and analysis of variance were applied; P < .05 was considered significant. This study was approved with waiver of informed consent by the institutional review board of the University of Southern California. Data were deidentified.
Results
The demographics of the 187 patients (130 men [69.5%]) with HD and available records are reported in the Table. Six patients were age 18 years or younger at diagnosis. Most patients were Latino and originated from Mexico. Median delay in diagnosis was more than 3 years.
Table. Demographics, Classifications, and Outcomes of Patients With Hansen Disease.
| Characteristic | Value |
|---|---|
| Demographics | |
| Patients, No. (%) | |
| Total | 312 |
| Excludeda | 125 (40.1) |
| Included | 187 (59.9) |
| Age at diagnosis, mean (SD) [range], y | 35.7 (12) [7-75] |
| Sex, No. (%) | |
| Male | 130 (69.5) |
| Female | 57 (30.5) |
| Race/ethnicity, No. (%) (n = 171) | |
| Latino | 99 (57.9) |
| Asian | 45 (26.3) |
| Pacific Islander | 11 (6.4) |
| Unknown/other | 14 (8.2) |
| White | 2 (1.2) |
| Country of origin, No. (%) (n = 132) | |
| Mexico | 69 (52.3) |
| Vietnam | 14 (10.6) |
| The Philippines | 13 (9.8) |
| India | 8 (6.1) |
| China | 5 (3.8) |
| Cambodia | 5 (3.8) |
| Otherb | 18 (13.6) |
| Delay in diagnosis (n = 23), median [range] | >3 y [4-6 mo to >10 y] |
| Follow-up duration, mean (SD) [range], y | 22.4 (14.0) [1-45] |
| Leprosy Classification, No. (%) | |
| Ridley-Jopling | |
| Polar lepromatous leprosy | 10 (63.5) |
| Borderline lepromatous leprosy | 41 (24.6) |
| Borderline tuberculoid leprosy | 16 (9.6) |
| Polar tuberculoid leprosy | 2 (1.2) |
| Indeterminate leprosy | 1 (0.6) |
| Mid-borderline leprosy | 1 (0.6) |
| WHO (n = 167) | |
| Multibacillary leprosyc | 148 (88.6) |
| Paucibacillary leprosyd | 19 (11.4) |
| Reactional State, No. (%) | |
| Erythema nodosum leprosum (n = 116) | 86 (74.1) |
| Multibacillary leprosy with erythema nodosum leprosum (n = 86) | 86 (100.0) |
| Paucibacillary leprosy with erythema nodosum leprosum (n = 86) | 0 |
| Delayed-type reversal reaction (n = 116) | 27 (23.3) |
| Multibacillary leprosy with delayed-type reversal reaction (n = 27) | 20 (74.1) |
| Paucibacillary leprosy with delayed-type reversal reaction (n = 27) | 7 (25.9) |
| Lucio reaction (n = 116) | 3 (2.6) |
| Multibacillary leprosy with Lucio reaction (n = 3) | 3 (100.0) |
| Paucibacillary leprosy with Lucio reaction (n = 3) | 0 |
| Neuritis (n = 84) | 31 (36.9) |
| Antibiotics Used, No. (%) | |
| Multibacillary leprosy (n = 147) | |
| 1 | 26 (17.7) |
| 2 | 47 (32.0) |
| 3 | 50 (34.0) |
| 4 | 20 (13.6) |
| >5 | 4 (2.7) |
| Paucibacillary leprosy (n = 19) | |
| 1 | 6 (31.6) |
| 2 | 7 (36.8) |
| 3 | 5 (26.3) |
| 4 | 1 (5.3) |
| >5 | 0 |
| Antibiotics Used in WHO Grade 0 Disability, No. (%)e | |
| Multibacillary leprosy (n = 93) | |
| 1 | 26 (28.0) |
| 2 | 33 (35.5) |
| 3 | 24 (25.8) |
| 4 | 8 (8.6) |
| >5 | 2 (2.2) |
| Paucibacillary leprosy (n = 13) | |
| 1 | 3 (23.1) |
| 2 | 6 (46.2) |
| 3 | 3 (23.1) |
| 4 | 1 (7.7) |
| >5 | 0 |
| Patient Outcome | |
| WHO grade 0 disabilitye | 106 (56.7) |
| WHO grade 1 disabilitye | 30 (16.0) |
| WHO grade 2 disabilitye | 49 (26.2) |
| Death related to Hansen disease | 0 |
Abbreviation: WHO, World Health Organization.
Patients were excluded from analysis if they did not have Hansen disease or information was not available in the electronic medical record.
Brazil, Cuba, Colombia, El Salvador, Ethiopia, Indonesia, Laos, Malaysia, Thailand, America Samoa, Sri Lanka, United States.
More than 6 lesions (mid-borderline leprosy, polar lepromatous leprosy, borderline lepromatous leprosy).
One to 5 lesions (indeterminate leprosy, polar tuberculoid leprosy, or borderline tuberculoid leprosy).
Grade 0, no signs or symptoms suggestive of leprosy or disability for more than 1 year; grade 1, loss of protective sensation; grade 2, visible deformity.
Nineteen patients (11.4%) had paucibacillary leprosy (PB) and 148 patients (88.6%) had multibacillary leprosy (MB) (Table).3 Patients with MB were more likely to be younger at diagnosis than were those with PB (polar tuberculoid, 59 years; borderline tuberculoid, 34 years vs polar lepromatous, 35 years; and borderline lepromatous, 38 years; P = .02). Latino patients were more likely than non-Latino patients to have MB (88/134 [65.7%] vs 46/134 [34.3%] patients; P < .001). Patients from Central or South America were more likely than patients from other regions to have MB (70/106 [66.0%] vs 36/106 [34.0%] patients; P < .001).
Multidrug therapy was used in 134 of 166 patients (80.7%) (Table) and 151 of 163 patients (92.6%) received antibiotics for more than 2 years. Patients with MB were more likely than those with PB to be treated with antibiotics for more than 5 years (116/126 [92.1%] vs 10/126 [7.9%]; P < .001). The most common adverse effect of therapy was hyperpigmentation associated with clofazimine and minocycline use.
Immunologic reactions to HD include reversal reaction (type 1 reaction), erythema nodosum leprosum (ENL) (type 2 reaction), Lucio reaction (LR), and neuritis. Reversal reaction is characterized by sudden inflammatory changes of the skin lesions and neuritis, but no systemic symptoms; ENL presents with eruption of painful subcutaneous nodules in addition to systemic symptoms. Lucio reaction is a life-threatening, systemic necrotizing vasculopathy. The most common reactional state in the present sample was ENL, followed by delayed-type reversal reaction and LR; ENL and LR occurred only in patients with MB. Neuritis was identified in 31 patients (36.9%). The median time to onset was 1 to 2 years after HD diagnosis.
In regard to HD-related disabilities, 106 patients (56.7%) had World Health Organization grade 0 disability (no signs or symptoms suggestive of leprosy or disability for >1 year) at the 1-year follow-up; 30 patients (16.0%) had grade 1 disability (loss of protective sensation) and 49 patients (26.2%) had grade 2 disability (visible deformity) at the last follow-up. Fifty of 57 patients (87.7%) did not regain protective sensation following therapy.
Conclusions
To our knowledge, this preliminary study represents one of the largest and longest-term analyses of HD in the United States. Significant morbidity is associated with HD despite standard treatment.4 The skew toward the MB pole in the present sample may involve genetic susceptibilities and infection with mycobacterium lepromatosis, which is endemic to Mexico.5,6 Neuritis associated with HD and reactional states result in loss of sensation that is associated with long-term disability. Adequate care for patients with HD involves early diagnosis and long-term, multidisciplinary follow-up.
References
- 1.Nolen L, Haberling D, Scollard D, et al. ; Centers for Disease Control and Prevention (CDC) . Incidence of Hansen’s Disease—United States, 1994-2011. MMWR Morb Mortal Wkly Rep. 2014;63(43):969-972. [PMC free article] [PubMed] [Google Scholar]
- 2.Kerkeni N, El Fékih N, Fazaa B, Zéglaoui F, Mnif E, Kamoun MR. A delayed diagnosis of lepromatous leprosy: pitfalls and clues to early recognition. Int J Dermatol. 2011;50(11):1383-1386. doi: 10.1111/j.1365-4632.2011.04935.x [DOI] [PubMed] [Google Scholar]
- 3.World Health Organization Guidelines for the diagnosis, treatment and prevention of leprosy. https://www.who.int/lep/resources/9789290226383/en/. Published October 2018. Accessed April 9, 2019.
- 4.Van Brakel WH. Peripheral neuropathy in leprosy and its consequences. Lepr Rev. 2000;71(suppl):S146-S153. [DOI] [PubMed] [Google Scholar]
- 5.Han XY, Seo Y-H, Sizer KC, et al. A new mycobacterium species causing diffuse lepromatous leprosy. Am J Clin Pathol. 2008;130(6):856-864. doi: 10.1309/AJCPP72FJZZRRVMM [DOI] [PubMed] [Google Scholar]
- 6.Shankarkumar U, Ghosh K, Badakere S, Mohanty D. Novel HLA class I alleles associated with Indian leprosy patients. J Biomed Biotechnol. 2003;2003(3):208-211. doi: 10.1155/S1110724303210019 [DOI] [PMC free article] [PubMed] [Google Scholar]