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Hansen Disease

Author: Eva C Kim, MD, Fellow in Ocular Inflammation/Uveitis, Francis I Proctor Foundation for Research in Ophthalmology, Department of Ophthalmology, University of California at San Francisco
Contributor Information and Disclosures

Updated: Jan 27, 2010

Introduction

Background

Leprosy, also known as Hansen disease, is a chronic infectious disease with a wide range of clinical manifestations. It is a chronic granulomatous disease of the skin, mucous membranes, nerves, lymph nodes, eyes, and internal organs such as the liver, spleen, and testicles.

Pathophysiology

Hansen disease is caused by a bacillus, Mycobacterium leprae, first described by G. Amauer Hansen, MD, of Norway in 1874, which multiplies very slowly and mainly affects the skin, nerves, and mucous membranes. They have a predilection for the cooler areas of the body. This acid-fast rod has never been grown on artificial media or tissue culture, but, in 1960, Shepard successfully grew M leprae bacilli in mouse foot pads. Studies have shown that solid staining bacilli were infectious to mice, whereas beaded were not.¹

Incubation in humans ranges from 6 months to 8 years, and the bacilli are believed to enter the body through the skin or mucous membranes of the upper respiratory tract. The extent of involvement and the type of manifestation after infection depend on the immune response of the host and may consist of complete resistance, no disease, incomplete resistance, and the indeterminate, which can progress to the other forms. A classification system is shown in the image below.

The tuberculoid type affects skin and nerves but not internal organs and eye except occasional lagophthalmos. Few if any bacilli are present in the affected tissues. The tuberculoid type derives its name from the characteristic granuloma of tuberculosis consisting of giant cells, epithelioid cells, and lymphocytes. The lepromatous type can affect practically any organ, including skin and nerves. Usually, numerous bacilli are present and are characterized by a foam cell granuloma, often separated from the epidermis by a zone of normal connective tissue.

The Lepromin test developed by Mitsuda 4 consists of an intradermal injection of 0.1 mL of a suspension of killed lepra bacilli. The findings are positive when a papule 6 mm or larger appears after 3 weeks at the injection site. This shows a strong immune response, suggesting the tuberculoid type. A negative test result means a poor or absent immune response, suggesting the lepromatous type. Diagnosis must be established on the basis of clinical and histologic criteria.

Frequency

United States

An estimated 500,000 new Hansen disease cases are identified each year, with 96 new cases reported to the Centers for Disease Control and Prevention (CDC) in the United States in 2002.²

International

Approximately 15 million individuals worldwide, mainly in the equatorial regions/tropical countries of Asia, Africa, and South America, have Hansen disease. Most cases come from 55 countries where the disease continues to be endemic. In 2002, the World Health Organization (WHO) listed those countries reporting the most cases (90%) as Brazil, Madagascar, Mozambique, Tanzania, and Nepal. In 2002, the number of new cases worldwide was 763,917.³ In 2007, Brazil had the highest prevalence rate, with more than 2 cases per 10,000 population.⁴

Mortality/Morbidity

Race

No racial variation has been noted.

Sex

The disease affects males more than females.

Age

Any age can be affected.

Clinical

History

A complete careful eye examination is necessary to establish some of the subtle changes in Hansen disease as described below.

• A typical tuberculoid skin lesion shows asymmetrical either hypopigmented sharply demarcated macules or reddish plaques, which spread in the periphery and heal in the center. The lesions may be circinate or gyrate and can spread to the entire extremity or trunk. Nerve involvement in tuberculoid leprosy occurs early, is unilateral, and can result in muscle atrophy with claw hand or foot drop. Enlarged great auricular nerves frequently are found.
• The skin lesions in lepromatous leprosy are nodules and hypopigmented macules. The papules and nodules are frequently copper colored, sometimes flat topped, and can reach considerable size and imitate skin tumors. Ear nodules and loss of the lateral part of the eyebrows are common.
• A diffuse form of lepromatosis, described by Lucio and frequently seen in the state of Sinaloa, Mexico, with numbness of the extremities is usually the only subjective complaint. The normal-appearing skin on biopsy results shows a mild inflammatory infiltrate in the perivascular location consisting of round cells with acid-fast stain showing numerous acid-fast bacilli cuffing vessels.
• Leprosy is usually a slow chronic process interrupted by reactive phases.
  • In tuberculoid, one finds exacerbation of skin lesions and neuritis, which may be extremely painful.
  • Erythema nodosum leprosum (ENL) is a frequent finding in lepromatous leprosy with lesions that may appear anywhere on the body including the face and are accompanied by fever, arthralgia, lymphadenopathy, and often neuritis. These patients are extremely toxic and can die; to control this reaction, first and second episodes may be treated with aspirin if mild or with short courses (1 wk) of prednisone 40-60 mg/day if significant, in addition to antimicrobials. For recurrent cases, thalidomide 100-400 mg/day is the drug of choice. However, because of its teratogenicity, thalidomide should not be given to women who may become pregnant. Adverse effects are mild constipation, mild leukopenia, and sedation.
  • In diffuse lepromatous reactions, sharply demarcated erythematous lesions ulcerate, and after healing, leave scars. This is called erythema necroticans or Lucio phenomenon.
• A review of 237 patients at the USPHS Hospital San Francisco showed the following findings related to Hansen disease:
  • Ocular lesions - 100%
  • Corneal reduced sensation - 22%
  • Avascular keratitis - 39%
  • Pannus and interstitial keratitis - 20%
  • Corneal facets - 7%
  • Beading or opaque corneal nerves - 47%
  • Conjunctival or episcleral hyperemia - 20%
  • Leproma - 1%
  • Iridocyclitis and synechia - 6%
  • Iris pearls - 4%
  • Glaucoma - 3%
  • Chorioretinal lesions - 6%
  • Adnexal lesions - 100%
  • Loss of eyebrows or cilia - 61%
  • Eyelid and facial lesions
  • Nodules - 11%
  • Erythema nodosum - 11%
  • Erysipeloid reaction - 1%
  • Entropion or ectropion - 6%
  • Lagophthalmos - 6%
  • Tearing - 9%
• See Mortality/Morbidity.

Physical

Leprotic uveal infections

• Incidence of leprotic uveal infections is 6-7% of patients with Hansen disease at the USPHS Hospital, San Francisco.
• Histopathology is completed by corneal, conjunctival, and subcutaneous skin scrapings; anterior chamber or vitreous taps; or skin and tissue biopsy. Findings show multiple acid-fast bacilli with acid-fast stains or Fite-Faraco stain (see Laboratory Studies).
• Manifestations
  • Insidious chronic anterior uveitis (chronic plasmoid iridocyclitis) - Posterior synechia, keratic precipitates, iris pearls, complicated cataract, vitreous opacities, retinal detachment, secondary glaucoma, and phthisis bulbi
  • Diffuse plastic reactions (acute diffuse plasmoid iridocyclitis)
  • Isolated leproma
  • Posterior uveal involvement (rare) - Retinal pearls, uveal effusion
• Diagnosis
  • Typical systemic disease is confirmed by histopathology of corneal conjunctival, subcutaneous skin scrapings, anterior chamber or vitreous taps, or by skin tissue biopsy. Findings show multiple acid-fast bacilli with acid-fast stains or Fite-Faraco stain (see Laboratory Studies) and iris pearls.
  • Leprotic punctate keratitis usually
  • Iris pearls with uveitis (lesions are diagnostic): These represent miliary lepromas. Iris pearls are creamy round spheres usually less than 0.5 mm in diameter located near the papillary border, the chamber angle, or they may migrate and fuse with other pearls. They contain acid-fast material, remains of lepromatous cellular debris, and calcium salts. They form deep in the iris stroma and are extruded to the surface and may persist for months or years.
  • Beading of corneal nerves
    • Beading of corneal nerves (abnormally wide edematous nerves) is probably the earliest detectable ocular findings. These are sometimes difficult to detect and are seen best using slit lamp broad beam, retroillumination, or sclerotic scatter. This opacification and beading is due to the localization and multiplication of bacilli in or adjacent to nerves with or without infiltration of plasma cells, lymphocytes, and epithelioid cells.
    • The corneal stroma reacts, and the cornea becomes covered with milky chalky deposits causing a keratitis pathognomonic of Hansen disease. These avascular punctate subepithelial opacities usually require a slit lamp examination for their detection. The lesions are seen between the epithelium and the Bowman membrane, and they later spread and become confluent. They are lepromas containing acid-fast organisms, lymphocytes, and macrophages, and some become calcified and can destroy the Bowman membrane.
    • With progression of the disease, superficial and deep vascularization develops with reduced vision. In Carville PHS Hospital, 16% of the first ocular lesions noticed were episcleritis, scleritis, or uveitis. This type of episcleritis usually has early pain, tenderness and circumcorneal injection, and lack of exudates or bacteria. Late lepromas may develop in the episcleral area because this is a low temperature area. Bacilli are present in the ciliary body and pass through the sclera, episclera, conjunctiva, cornea, and also into the anterior chamber and iris.
  • Leprous pannus usually develops in the superior limbus and later extends around the entire corneal circumference.
  • The uveitis in Hansen disease may be a severe and prolonged course and with extensive anterior or posterior synechia. After repeated attacks, extensive iris atrophy and intractable glaucoma develop.
  • Uveal effusion in association with conjunctival and episcleral hyperemia as well as retinal pearls rarely may occur.
  • Lagophthalmos or unexplained seventh nerve weakness, associated with skin or neurologic disorders should be considered in the differential diagnosis of Hansen disease. Exposure keratitis and corneal ulceration also may occur and especially with decreased corneal sensation, thickened eyelids and incomplete blinking, decreased mucin and meibomian secretions, and denervation of the lacrimal gland.

Causes

• M leprae causes Hansen disease .

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