Hansen’s disease (Leprosy) is a chronic infectious disease caused by Mycobacterium leprae, an acid-fast bacillus that cannot be cultured. It primarily affects the skin, nasal and oral mucosa, and peripheral nerves, causing chronic granulomatous inflammation. The eye is also a frequently affected target organ.
In 1874, Hansen of Norway identified M. leprae. This was the first instance of a bacterium being identified as the cause of a human disease. Treatment was not possible until the development of dapsone in the late 1940s.
Epidemiology
Globally, the number of new cases has decreased significantly, but according to WHO reports, there were 210,942 new cases worldwide at the end of 2017, with a prevalence rate of 0.25 per 10,000 population. Major endemic countries include India, Brazil, Indonesia, the Democratic Republic of the Congo, Angola, Bangladesh, and Nigeria. In Japan, there are only a few new patients per year, most of whom are foreign residents. Approximately 1,450 patients (as of April 2018) are living in sanatoriums, and the population is aging.
The optimal growth temperature for M. leprae is around 31°C, so infection of internal organs with higher body temperatures is rare, and it is specifically attracted to superficial facial tissues and the anterior segment of the eye, which have lower temperatures. Because it has an affinity for ectodermal tissues, it commonly occurs in peripheral nerves and the eye.
Route of infection
Droplet infection via aerosols from nasal secretions is the most likely route. M. leprae cannot penetrate intact healthy skin, so contact transmission does not occur. The infectivity is very weak, and almost no one develops the disease except after heavy exposure in infancy. In North America, zoonotic transmission from nine-banded armadillos has been confirmed, and molecular epidemiological studies have shown that single nucleotide polymorphism (SNP) type 3I-2 matches that of armadillos. 1)
QDoes leprosy still occur in Japan today?
A
There are only a few new patients per year, most of whom are foreign residents in Japan. After the repeal of the Leprosy Prevention Law in 1996, leprosy became covered by health insurance as an infectious disease, and most new patients are now seen at university hospitals or general medical facilities. Domestic onset is extremely rare, but imported cases are sporadically reported.
The frequency of ocular lesions varies by disease type. Eyelid and corneal lesions due to facial nerve palsy occur in all types, but keratitis, episcleritis, scleritis, and uveitis are observed only in lepromatous (L) and borderline (B) types.
Lepromatous (L) type · Borderline (B) group
Uveitis: Chronic iridocyclitis is predominant. It presents findings similar to sarcoidosis and recurs repeatedly over a long course.
Iris pearls: Pathognomonic finding. Dead leprosy bacilli gradually enlarge and fuse, becoming pedunculated and stagnating in the anterior chamber. Small spherical white nodules seen at the pupillary margin or angle.
Iris atrophy and miosis: Observed as a result of chronic inflammation or sympathetic nerve damage to the dilator pupillae muscle.
Cataract and secondary glaucoma: Develop due to chronic inflammation.
Corneal hypoesthesia or anesthesia: Caused by damage to the first branch of the trigeminal nerve (ophthalmic nerve). Leads to neurotrophic keratitis.
Madarosis: Loss of eyelashes on the upper and lower eyelids.
Beaded corneal nerves: A characteristic finding visible under slit-lamp microscopy.
Overview of ocular complications
Ocular involvement is estimated to occur in approximately 30–40% of patients (based on recent estimates in new patients). Older reports indicated involvement in 70–80%.
Iris pearls are formed when dead M. leprae gradually enlarge and fuse, becoming pedunculated and stagnating in the anterior chamber. They are a pathognomonic finding in lepromatous uveitis and can be observed as small, white nodules on the iris surface or in the anterior chamber using a slit-lamp microscope.
In lepromatous (L) type patients, bacteria may directly invade the eye via the bloodstream. In tuberculoid (T) type, eye damage occurs indirectly mainly through nerve damage (facial and trigeminal nerves).
The diagnosis recommended by WHO is based on the following major criteria:
Hypopigmented or reddish skin lesions with definite sensory loss
Thickening of peripheral nerves
Confirmation of acid-fast bacilli in skin smears or biopsy specimens
In Japan, diagnosis is made by combining the following four items: (1) skin rash with sensory loss, (2) nerve paralysis, thickening, or motor impairment, (3) detection of M. leprae, and (4) histopathological findings.
Tissue fluid from within the skin lesion is collected, stained for acid-fast bacilli, and examined under a microscope. If all sites are negative, it is classified as paucibacillary; if any site is positive, it is classified as multibacillary.
Special histopathological staining
Histopathological examination using acid-fast staining or S100 staining. In paucibacillary type, epithelioid cell granulomas and giant cells are observed; in multibacillary type, histiocytic granulomas (foamy changes (leproma) and vacuolation) are observed.
PCR and serum anti-PGL-1 antibody test
Used for specific detection of Mycobacterium leprae. In Japan, testing is available at the Leprosy Research Center.
Metagenomic next-generation sequencing has been reported as a new complementary diagnostic tool, particularly improving diagnostic accuracy in difficult cases such as atypical clinical presentations or identification of bacteria in cerebrospinal fluid. 2)
The standard treatment is multidrug therapy (MDT) recommended by the WHO. In Japan, rifampicin, dapsone, and clofazimine are used, with ofloxacin added as needed. These four drugs are covered by insurance.
Standard regimen for multibacillary type (12 months)
Rifampicin 600 mg (once monthly)
Dapsone 100 mg (daily)
Clofazimine 300 mg (once monthly) + 50 mg (daily)
Standard regimen for paucibacillary type (6 months)
Surgical outcomes for lagophthalmos are not satisfactory, and the most commonly used tarsorrhaphy may be insufficient. The need for more effective surgical options has been pointed out.
Differences in the patient’s immune response to Mycobacterium leprae determine the clinical spectrum of the disease.
Relationship between immune response and disease type
Tuberculoid type (T type): Strong cell-mediated immune response (Th1 cytokine dominant). Lesions are localized with few bacilli.
Lepromatous type (L type): Lack of M. leprae-specific cell-mediated immunity (Th2 cytokine dominant). Bacilli proliferate extensively, causing numerous skin lesions and systemic symptoms.
Borderline group (Group B): Immunologically unstable and prone to leprosy reactions.
Leprosy reaction (acute immune complication)
Type 1 reaction (borderline group): Delayed-type hypersensitivity reaction. Causes sudden painful nerve function loss.
Type 2 reaction (erythema nodosum leprosum, ENL): Systemic reaction due to immune complex deposition. Occurs in lepromatous and borderline lepromatous types. Causes fever, painful erythematous skin lesions, and multi-organ involvement (iridocyclitis, glomerulonephritis, hepatitis). 2)
Mechanism of ocular involvement
Direct invasion (L type, Group B): M. leprae hematogenously invades the anterior segment of the eye, which has a lower temperature, directly affecting the iris and cornea.
Pure Neural Leprosy (PNL) is a rare form in which there are no skin lesions and neurological deficits appear only in the peripheral nervous system. Cytokine profile studies have reported that pure neural leprosy shows a unique immunological profile with cytokines of both tuberculoid and lepromatous types (such as CCL-2 and interleukin-10). 3)
7. Latest Research and Future Perspectives (Research-stage Reports)
Naidu et al. (2021) reported a case of lepromatous leprosy in a Canadian-born male (age 50) with no history of armadillo contact. 1) The single nucleotide polymorphism type 3I-2 was of European origin and matched the type found in North American armadillos. This is considered the second case of naturally acquired infection within Canada.
This report highlights the increase in zoonotic infections in North America and the possibility of new transmission routes, underscoring the importance of clinical awareness of leprosy in non-endemic areas.
Application of Metagenomic Next-Generation Sequencing to Diagnosis
Zhao et al. (2024) reported a case where M. leprae infection was definitively diagnosed by metagenomic next-generation sequencing of cerebrospinal fluid. 2) In a 30-year-old woman with systemic lupus erythematosus and Listeria meningitis, a combination of slit skin smear and metagenomic next-generation sequencing confirmed multibacillary leprosy (type 2 reaction: erythema nodosum leprosum). Metagenomic next-generation sequencing is gaining attention as a new tool to complement conventional diagnostic methods.
Naidu P, Sharma R, Kanji JN, Marks V, King A. Autochthonous North American Leprosy: A Second Case in Canada. Infect Dis Rep. 2021;13:917-923.
Zhao C, Liu Z. A case report and literature review: Mycobacterium leprae infection diagnosed by metagenomic next-generation sequencing of cerebrospinal fluid. BMC Infect Dis. 2024;24:666.
Pitta IJR, Angst DBM, Pinheiro RO, et al. Cytokines profile in pure neural leprosy. Front Immunol. 2023;14:1272471.
Copy the article text and paste it into your preferred AI assistant.
Article copied to clipboard
Open an AI assistant below and paste the copied text into the chat box.
