Leprosy (Hansen’s Disease)

Etiology

Mycobacterium leprae is an obligate intracellular pathogen, first identified in the nodules of lepromatous leprosy patients by Armauer Hansen in 1873. It is a rod-shaped, Gram-positive organism that is acid-fast when stained by the Ziehl–Nielsen or the better Fite methods. Viable organisms stain in a uniform, solid manner. With therapy, most organisms quickly lose their solid staining, appearing beaded or fragmented.

M. leprae has never been successfully grown in artificial media but can be propagated in the mouse footpad and the nine-banded armadillo, which is the only known natural reservoir of the organism. The organism has a long doubling time of 13 days at low temperatures (33-35° C), selectively invading skin macrophages and peripheral nerve Schwann cells. M. leprae does not produce any known toxins, and tissue injury is caused by the host's immune response or by the sheer mass of infecting bacilli.

In 2001, the genome of M. leprae was sequenced. The organism appears to have undergone extensive reductive evolution with considerable downsizing of its genome compared with Mycobacterium tuberculosis . Almost half of the genome is occupied by pseudogenes.

Epidemiology

In 2013, some 215,616 new cases were registered worldwide and reported to the World Health Organization (WHO) by 103 countries. Seven endemic countries reported the most new cases: India, Brazil, Indonesia, Ethiopia, Democratic Republic of the Congo, Nigeria, and Nepal. India reported 59% of the global burden of leprosy.

In the United States, 188 new cases were reported in 2013 by the Centers for Disease Control and Prevention. Immigrants from Mexico, the Philippines, Pacific Islands, and India account for the bulk of new cases. Leprosy has a long incubation period (2-10 years), so patients can present long after leaving endemic areas. However, in recent years 20-25% of new cases have occurred in those who were born in the United States, had not traveled to endemic countries, and were living in Texas, Louisiana, and Florida.

Leprosy affects adult males more than females, with ratios of 1.6 : 1 to 3 : 1 in different countries. In children the ratio is 1 : 1.

The exact mode of disease transmission is unknown. Studies of disease transmission have been hampered by the lack of a culture system, the absence of serologic markers, the latent period of 2-10 years before disease onset, and the high degree of natural immunity in most persons. Tuberculoid leprosy patients shed no demonstrable organisms and are regarded as noncontagious, although this is unproven. Untreated lepromatous patients shed millions of viable-appearing organisms daily, primarily in nasal and oral secretions. Bacilli may also be found in skin scales, sweat, blood, breast milk, and wound exudate. The possibility of animal-to-human transmission is supported by reports of cases in persons handling or consuming armadillos in the Americas.

Transmission is thought to occur mainly through aerosolized nasal droplets, spread when coughing or sneezing takes place. Following contact with an infective dose of M. leprae , most people will develop adequate protective immunity and therefore will not develop any clinically detectable signs or symptoms. Only a small percentage of individuals will develop clinical disease. Some literature suggests transmission via contact with broken skin, blood, or soil, as the mycobacteria are known to survive in the environment for up to 46 days.

Clinical Features

Leprosy may be considered an immunologic disease. Immunity defines susceptibility to leprosy, type of clinical leprosy, pathology, and major clinical complications of leprosy. Classification of the disease is important to determine prognosis, transmission risk, and selection of treatment. There are two systems used to classify leprosy patients.

The Ridley–Jopling system uses clinical and histopathologic features and the bacteriological index ( Fig. 40.1 ). Leprosy manifests in a spectrum of disease forms, ranging from the tuberculoid to the lepromatous.

The WHO classification is a simplified version depending on the number of skin lesions, which can be used in the field when slit skin smears or biopsies are not available. Patients with one to five skin lesions are classified as paucibacillary and those with six or more lesions as multibacillary. Up to 60% of patients classified as multibacillary are smear negative.

Clinical features of leprosy are a continuum between the tuberculoid and lepromatous forms of disease. There is substantial overlap in the appearance of the different forms, and careful assessment of clinical and histologic parameters is needed for accurate diagnosis. Important clinical features include (1) number of skin lesions, (2) size and morphology of skin lesions, (3) presence of neuropathy, and (4) presence of reactional states.

Indeterminate leprosy is the earliest recognizable form of the disease and may be extremely difficult to diagnose. There is typically a single hypopigmented or erythematous macule without abnormal sensation or sweating. There is no nerve enlargement. It is commonly seen in children. Biopsy is nonspecific and shows few or no organisms. Most heal without treatment, but 25% may progress to established leprosy.

Table 40.1 describes the varied clinical manifestations of leprosy. These are determined by the host's response to the leprosy bacillus: tuberculoid (TT) patients have a uniform clinical, histologic, and immunologic response manifesting as limited clinical disease, granuloma formation, and active cell-mediated immunity ( Fig. 40.2 ); lepromatous leprosy (LL) patients have multiple clinical signs, a high bacterial load, and low cell-mediated immunity ( Fig. 40.3 ). Between these two extremes there is a range of variations in host response; these comprise borderline cases (BT, BB, BL) ( Fig. 40.4 ). Immunologically, borderline cases are unstable, while polar tuberculoid and lepromatous cases are stable.

Neural involvement in leprosy is due to selective proliferation of M. leprae in superficial peripheral nerves. Nerve destruction occurs either from inflammation or from infiltration by masses of infecting organisms. Inflammation in the nerves may result in nerve entrapment. Damage to peripheral nerve trunks produces sensory loss and weakness of the muscles supplied by the affected peripheral nerves. Sensory function is the earliest affected in leprosy; sensory impairment can occur alone without motor involvement. Autonomic nerve damage results in dryness of the hands and feet. The ulnar, median, posterior tibial, common peroneal, and radial nerves are most commonly involved. The central nervous system is never involved, and M. leprae does not usually propagate within internal organs due to high human core body temperature.

Diagnosis

A clinical diagnosis of leprosy is made by considering key features associated with the disease (the presence of characteristic skin lesions with anesthesia, and thickening of one or more peripheral nerves), supported by skin smears and biopsy. A patient may present with a macular hypopigmented skin lesion, weakness or pain in the hand due to nerve involvement, facial palsy, acute foot drop, or a painless burn or ulcer in an anesthetic hand or foot. Patients may also present with painful eyes as a first indication of lepromatous leprosy. The diagnosis of leprosy should be considered in anyone from an endemic area who presents with typical skin lesions, neuropathic ulcers, or a peripheral neuropathy. In leprosy-endemic settings, a typical skin lesion that is also anesthetic is said to be 70% sensitive for the diagnosis of leprosy, and has been recommended by the WHO as sufficient for leprosy diagnosis by knowledgeable health providers. Clinicians need to have a high index of suspicion when dealing with patients from endemic areas.

The differential diagnosis of leprosy is wide due to its protean manifestations. Individuals found to have granulomatous pathology on skin or nerve biopsy, peripheral neuropathy, mononeuritis, or mononeuritis multiplex may have leprosy. Examples of other diagnoses that may enter the differential diagnosis depending on the type of leprosy include superficial fungal infections of the skin, such as tinea corporis, pityriasis versicolor, or pityriasis alba; vitiligo; sarcoidosis; secondary and tertiary syphilis; mycosis fungoides; and psoriasis. Other mycobacterial infections such as Mycobacterium tuberculosis and Mycobacterium ulcerans may also cause diagnostic confusion.