Leprosy

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Article initiated by:

Ana Rita Baptista Couceiro Neto, MD, MS

All contributors:

Brad H. Feldman, M.D., Ghazala D. O'Keefe, MD, Ana Rita Baptista Couceiro Neto, MD, MS, Alan Palestine, MD, Edmund Tsui, MD

Assigned editor:

Olivia Lee, MD

Review:

Assigned status Update Pending

 by Edmund Tsui, MD on September 19, 2023.

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Disease Entity

Leprosy or Hansen’s disease is an infection caused by Mycobacterium leprae that primarily affects the skin, the peripheral nerves and the eyes, causing chronic granulomatous inflammation. The first description of the disease goes back to the VI century BC, but it was only in 1873 that Hansen identified M. leprae as being the causative agent, making it the first identification of a bacteria as causing disease in humans. Treatment for leprosy was only made available in the late 1940s with the development of dapsone and its derivatives.

Although a major decrease in new cases has been noted in past couple decades, by the end of 2017, the World Health Organization (WHO) still reported that there were 210 942 new cases worldwide with a prevalence of 0.25 per 10 000 population, mostly in countries like Angola, Mozambique, India, Brazil, Indonesia, Democratic Republic of Congo, Bangladesh, Nigeria and China, among others. The exact mechanism of disease transmission is not well determined, but it is most likely spread through aerosol of nasal secretions and uptake through nasal or respiratory mucosa. M. leprae cannot be transmitted through intact skin and therefore the infection is not spread by touching.

General Pathology

Depending on the patient’s immune response to M. leprae, Hansen’s disease may show a wide range of clinical manifestations - from tuberculoid leprosy to lepromatous leprosy and borderline forms in between the previous two.

In tuberculoid leprosy, patients experience a robust cellular immune response to the mycobacterium and therefore manifestations of the disease are limited to a few skin lesions or nerve trunks.

In lepromatous leprosy, there is no specific cellular immunity to M. leprae, which gives rise to a wide proliferation of the bacilli, originating numerous skin and nerve trunk lesions and eventually systemic signs.

At the time of diagnosis, patients typically present with skin lesions, muscle weakness or a burn/ulcer in a limb, associated with peripheral neuropathy. Impairment of sensitive and motor nerve functions causes early dysfunction and later limb deformity. Limbs with impaired sensibility are also more prone to injuries and infection. Borderline patients can present with neurogenic pain, sudden paralysis, new skin lesions or fever.

Serious acute immune complications, can precede or appear during anti-bacillary treatment. These constitute an important factor for no compliance with treatment and are classified in to two types:

• Type 1: characterized by delayed hypersensitivity reactions in borderline cases causing sudden painful loss of nerve function
• Type 2: erythema nodosum leprosum, which can occur in lepromatous leprosy and borderline lepromatous leprosy, caused by immune complex deposits resulting in systemic manifestations (fever, painful erythematous skin lesions, multiorgan involvement).

Ocular involvement in leprosy

The eye may be involved in leprosy in several ways, depending on the immune status of the patient. Ocular involvement is more common in lepromatous leprosy, where direct invasion of the globe by M. leprae can occur, probably through the bloodstream.

M. leprae has a known affinity for cooler parts of the body and therefore has a particular attraction to the superficial structures of the face and the anterior segment of the eye. Rarely there is involvement of structures posterior to the equator.

The most frequent ocular manifestation in lepromatous leprosy is uveitis, commonly in the form of chronic low-grade iridocyclitis. In such cases, the presence of iris pearls is pathognomonic, representing dead M. leprae bacillus that progressively enlarged, coalesce, become pedunculated and lodge in the anterior chamber. Inflammation also promotes cataract development and intraocular hypotony. In later stages of the disease large areas of iris atrophy and miotic pupils may be noted, as a result of chronic inflammation and of sympathetic nerve involvement of the pupillary dilator muscle.

Corneal involvement in leprosy can also occur, in the form of visible beaded corneal nerves, interstitial keratitis, avascular keratitis and corneal leproma.

In tuberculoid leprosy, ocular manifestations result from lid closure impairment and reduced corneal sensation, through involvement of the facial nerve and of the ophthalmic division of trigeminal nerve. Corneal opacification resulting from exposure keratopathy and chronic neurotrophic keratitis can cause significant visual impairment. Lacrimal gland involvement can result in dry eye and conjunctival keratinization. Miotic pupils in multibacillary leprosy, combined with cataract can also contribute to low visual acuity.

Scleritis can also happen, as a result of direct infiltration by M. leprae or due to a lepromatous erythema nodosum reaction, although episcleritis is more common than scleritis.

Acute inflammatory reactions affecting the facial nerve, cornea and iris are a feature of Type I and Type 2 reactions and may cause severe damage to the eye either directly or indirectly.

List of possible ocular complications in leprosy:

• Lids: madarosis, blepharochalasis, nodules, ectropion, entropion, lagophthalmos, reduced blinking, trichiasis
• Cornea: thickened corneal nerves , superficial stromal keratitis, corneal anesthesia, pannus, exposure keratopathy, Interstitial keratitis, band shaped keratopathy, corneal leproma.
• Iris: acute iritis (synechiae, secondary glaucoma, secondary cataract, seclusio pupillae), chronic iritis (iris pearls, iris atrophy, miosis, corectopia, polycoria, secondary cataract), iris leproma.
• Ciliary body: loss of accommodation, hypotonia, phthisis.
• Sclera: episcleritis, scleritis, nodules, staphyloma.
• Lens: cataract.
• Fundus: peripheral choroidal lesions, retinal vasculitis, papillitis
• Lacrimal system: acute dacryocystitis, chronic dacryocystitis.

Clinical diagnosis

Diagnosis of leprosy is made through clinical criteria, namely the existence of: hypopigmented or reddish skin lesions with definite sensory loss, with or without thickened peripheral nerves and acid-fast bacilli identified on skin smears or biopsy samples. There is also a classification of disease based on bacteriological criteria, distinguishing between paucibacillary leprosy and multibacillary leprosy and this distinction has implications on which treatment regimen to choose. Regarding skin smears: patients with negative smears at all sites are considered to have paucibacillary leprosy, while those with positive smears at any site are considered to have multibacillary leprosy. However, in practice, clinical criteria are usually used to distinguish between paucibacillary and multibacillary leprosy, since skin smears are not always available. Regarding the number of skin lesions: one to five skin lesions corresponds to paucibacillary leprosy and more than five skin lesions corresponds to multibacillary leprosy. Paucibacillary leprosy includes the tuberculoid form of the disease and the borderline tuberculoid form, while multibacillary leprosy includes the remaining borderline forms and the lepromatous form of the disease.

Management

Treatment of leprosy includes multidrug oral therapy and its duration depends on the type of infection (paucibacillary vs multibacillary). First line drugs are rifampin, dapsone and clofazimine, but minocycline and ofloxacin are occasionally used in cases where only one skin lesion exists.

WHO recommended multidrug treatment regimens are the following:

For Multibacillary leprosy, the standard regimen in adults has a 12 months duration and includes: Rifampin 600 mg once a month, Dapsone 100 mg daily and Clofazimine 300 mg once a month and 50 mg daily. For Paucibacillary leprosy the regimen as a 6 months duration and includes: Rifampin 600 mg once a month and Dapsone 100 mg daily. If only a single skin lesion exists, the regimen includes a single dose of: Rifampin 600 mg, Ofloxacin 400 mg and Minocycline 100 mg.

Management of uveitis requires topical corticosteroids and eventually oral corticosteroids to manage acute exacerbations. Phenylephrine is used to keep pupils mobile, in order to prevent miosis.

Prognosis

Nowadays, the risk of severe visual impairment in patients with recent infection by M. leprae is relatively low, due to timely diagnosis and treatment of infection and associated immune reactions. On the other hand, patients with long-standing disease or patients who have been treated but remained with sequelae have a 2 to 3 times higher prevalence of blindness than the general population. However in 40-50% of cases this is a reversible blindness caused by cataract. These findings highlight the need to invest in surgical treatment of cataract in this particular group of patients, who are already at risk of disability due to other physical consequences of Hansen’s disease. Moreover, these patients require good visual acuity in order to monitor wounds and ulcers in neuropathic limbs.

A 2006 study determined several risk factors which independently relate to a higher risk of blindness in leprosy: longer disease course, treatment provided in later stages of the disease and older age.

Surgical outcomes of lagophthalmos are unsatisfying, particularly the most frequently used tarsorrhaphy technique, raising the need for more effective surgical options.

Risk factors for the severe visual impairment in leprosy patients:

• Multibacillary Leprosy
• Active disease for more than 10 years
• Type 2 immune reactions, with or without iritis
• Facial skin lesion or large facial skin infiltration
• Lagophthalmos
• Corneal hypoesthesia or anesthesia
• Scleritis
• Patients with only one eye or vision severely reduced to begin with
• Coexisting diseases like diabetes or glaucoma