Author
Lars Grimm, MD, MHS
House Staff
Department of Internal Medicine
Duke University Medical Center
Durham, North Carolina
Lars Grimm, MD, MHS, has disclosed no relevant financial relationships.
Editor
Ramaratnam Sridharan, MBBS, MD
Head
Department of Neurology
Professor of Neurology
Chennai Neurospeciality and Research Institute
Chennai, India
Ramaratnam Sridharan, MBBS, MD, has disclosed no relevant financial relationships.
Leprosy, or Hansen's disease, is a chronic infection caused by Mycobacterium leprae. It is one of the oldest recorded infections affecting humanity, and despite vigorous eradication efforts still affects people worldwide. The significant disfigurement from skin and nerve damage has led to the stigmatization of people with leprosy throughout history. Image courtesy of Wikimedia Commons.
M leprae was the first bacterial pathogen to be associated with a specific human disease. It was discovered by GH Armauer Hansen in Norway (pictured). Leprosy was a significant medical problem in Norway and Iceland at the end of the 17th century, leading to extensive research efforts. Because of the stigma associated with the name leprosy, an alternative name, Hansen's disease, has been advocated by healthcare groups. Image courtesy of Wikimedia Commons.
Before the development of sulfone drug therapy in the 1940s, treatment for leprosy was supportive only. Because of the fear of contagion, individuals with leprosy were ostracized from society. The Louisiana Leper Home (shown) was established in 1894 to provide "a place of refuge, not reproach; a place of treatment and research, not detention." Image courtesy of the US Department of Health and Human Services.
Leprosy is asymmetrically distributed globally, with the greatest incidence and prevalence in the developing world. Globally, the incidence has fallen by 70% and the prevalence has fallen by 90% since 2000 thanks to aggressive eradication efforts with multidrug treatment regimens. In the United States, fewer than 200 cases are reported yearly, with the majority of cases in California, Louisiana, Massachusetts, New York, and Texas. Most of these cases are in foreign-born individuals. Image courtesy of the World Health Organization.
Mycobacterium leprae is an acid-fast, rod-shaped bacillus. It is an obligate, intracellular organism that preferentially proliferates in tissues with cooler temperatures. The organism exhibits the longest reproduction time among all bacteria, requiring 13 days to double in experimentally infected mice, and with an incubation time of up to 50 years in humans. Transmission is believed to be through prolonged skin contact or respiratory secretions. Fortunately, only 5%-10% of the population is believed to be susceptible to infection. The photomicrograph shown was taken from a leprosy skin lesion. Image courtesy of the Centers for Disease Control.
In the United States, armadillos are a major reservoir of leprosy infection. They are one of the few animals known to become infected and are used in research efforts to study the disease. They have an unusually low body temperature of around 34°C, which is hospitable to M leprae growth. Image courtesy of Wikimedia Commons.
Leprosy is classified between 2 extreme subtypes: tuberculoid (TT) and lepromatous (LL). The TT type occurs in individuals with a more vigorous cellular immune response. Between these ends of the spectrum are the borderline forms, which are subclassified as borderline tuberculoid (BT), midborderline (BB), and boderline lepromatous (BL). The natural history of the disease is not static. Transition toward the TT pole is referred to as upgrading and transition toward the LL pole is referred to as downgrading. These transitions are the result of a shifting in the host-parasitic immunologic balance.
Histologic findings, usually from skin biopsy, vary based on the type of leprosy. TT leprosy is characterized by noncaseating granulomas, destruction of dermal nerves, loss of sweat glands and hair follicles, and absent bacilli. LL leprosy demonstrates a normal epidermis, subepidermal granulomas particularly around blood vessels, nerves, and skin appendages, foamy histiocytes, and many intracellular acid-fast bacilli. The histologic slide of LL leprosy shows large numbers of acid-fast bacilli (in clusters) in histiocytes and within nerves. Image courtesy of Tara Ramachandra and D. Scott Smith, MD.
The clinical manifestations of TT leprosy are mainly cutaneous and neurologic. Skin lesions are circular, ovoid, or serpiginous, sharply demarcated, and often hypopigmented. They may have elevated, erythematous borders and a dry scaly appearance in the center with complete anesthesia. Lesions are commonly found on the extensor surfaces of the limbs, face, or buttocks. Cutaneous nerves may be palpably enlarged and visible. The image shown of tuberculoid leprosy shows an infiltrated, scaly skin patch, with thickening of the cutaneous nerve close to the patch.
The clinical manifestations of LL leprosy are cutaneous, ocular, and neurologic. Skin changes in LL leprosy are more extensive than in TT leprosy. Patients may show extensive, bilaterally symmetric, nonanesthetic skin lesions with macules, nodules, plaques, or papules. Bullous or ulcerated lesions may also be seen. The image shown is of a patient with LL showing multiple skin nodules with diffuse infiltration. Neurologic changes involve diffuse hypesthesia, but function is somewhat preserved until late in the disease course.
Ocular manifestations of leprosy are very diverse, but the most common findings are reduced corneal sensation, avascular keratitis, pannus and interstitial keratitis, beading or opaque corneal nerves, conjunctival or episcleral hyperemia, and loss of eyebrows or cilia. Evaluation by an experienced ophthalmologist is imperative to prevent irreversible changes. A photograph of iris pearl avascular keratitis in a patient with leprosy is shown.
The erythema nodosum leprosum reaction is characterized by acute peripheral nerve damage and may be found in varying degrees in all forms of leprosy. Involved nerves become tender and increase in size. Claw hand (shown) and foot drop are particularly common because of involvement of the ulnar, median, and lateral popliteal nerves.
Leprosy reactions are produced by changes in the body's immunologic response to the infection and often lead to nerve damage. They do not indicate disease progression or treatment failure, and are classified as type 1 or type 2. Type 1 reaction is also called "reversal reaction" and demonstrates increased erythema, induration of preexisting lesions, and appearance of new lesions. Type 2 reaction is also referred to as "erythema nodosum leprosum" and is characterized by new skin nodules, fever, redness of the eyes, and muscle and joint pain. The patient shown has an erythema nodosum leprosum type 2 reaction, which occurred several weeks after initiation of drug therapy. Image courtesy of D. Scott Smith, MD.
Plain film x-rays can demonstrate significant bony changes in patients with long-standing disease. The x-ray of the foot shows absence of the second to fifth toes and distal tapering of the metatarsals secondary to neuropathy, the so-called licked candy stick appearance. The phalanges of the great toe show destruction secondary to osteomyelitis.
On magnetic resonance imaging, bony and soft-tissue changes are readily apparent. The sagittal fat-saturated T2-weighted image shows amputation of the great toe with increased signal intensity in the head of the first metatarsal indicating osteomyelitis (white arrow). A small abscess is noted beneath the head of the first metatarsal (yellow arrow).
Formal diagnosis is made based on the clinical presentation and skin biopsy results. Skin biopsies, along with the paperwork shown, can be sent to the National Hansen's Disease Program Clinical Laboratory for evaluation. Skin biopsy with nerve inflammation is considered diagnostic. A lepromin test, similar to a tuberculin skin test, can be used to indicate host resistance to M leprae. Serology aimed at M leprae-specific phenolic glycolipid antibodies and polymerase chain reaction may also be used but fail to reliably detect early disease. Image courtesy of the US Department of Health and Human Services.
Medical therapy is dictated by the presence or absence of bacilli on smears. For those with negative smears, dapsone and rifampin for one year is the standard of care in the United States. For patients with positive smears, clofazimine is added and treatment is for 2 years, with interval follow-up to assess for relapse. An unfortunate common side effect of clofazimine is increased skin pigmentation (shown). Patients with leprosy reactions may respond to salicylates, chloroquine, nonsteroidal anti-inflammatory drugs, or steroids. Surgery is reserved for nerve decompression, abscess incision and drainage, tenodesis, cosmetic repair, and amputation. Ophthalmology, podiatry, orthopedic surgery, and plastic surgery involvement are based on patient-specific complications. Courtesy of D. Scott Smith, MD.
The World Health Organization is currently implementing a "Final Push" strategy to eliminate leprosy globally. Elimination, as opposed to eradication, is defined as less than 1 case per 10,000 individuals, a rate at which new cases in the community would gradually decrease independently. Efforts are multipronged, focusing on healthcare worker education, the availability of multidrug therapy, and the creation of a positive environment in which individuals with leprosy do not fear coming forward for treatment.
Author
Lars Grimm, MD, MHS
House Staff
Department of Internal Medicine
Duke University Medical Center
Durham, North Carolina
Lars Grimm, MD, MHS, has disclosed no relevant financial relationships.
Editor
Ramaratnam Sridharan, MBBS, MD
Head
Department of Neurology
Professor of Neurology
Chennai Neurospeciality and Research Institute
Chennai, India
Ramaratnam Sridharan, MBBS, MD, has disclosed no relevant financial relationships.
