Infectious Skin Diseases

Hansen's Disease (HD/Leprosy) is a chronic infectious disease of man, caused by Mycobacterium leprae. It involves primarily the skin and peripheral nerves, and in some cases can affect other organs such as eyes, testicles, bone, nasal mucous membrane, and lymph nodes. In most cultures, HD still carries a strong stigma; sometimes the problems associated with it are more troublesome than the disease itself.

The disease has been known for several thousand years, with the earliest descriptions recorded about 600 BC in India. Prior to 1873, the cause of HD was unknown and there was no effective treatment. Studies were confined to clinical and postmortem observations. In 1873, Hansen in Norway recognized that the disease was caused by M. leprae, and subsequently, improved staining methods and better microscopes made possible a wealth of pathological studies. During this period hydnocarpus oil was used for treatment and appeared to be of some benefit in some cases. Until the sulfones became available in the 1940s, early diagnosis and isolation were the only possible methods of HD control. In 1941 the sulfones were first used to treat HD at Gillis W. Long Hansen's Disease Center, Carville, Louisiana and by 1950 dapsone became the standard treatment for HD. The rapid improvement in patients, brought about by dapsone led to hopes of the eradication of HD. However multiplication of M. leprae had not been obtained either in vitro or in experimental animals.

In 1960, Shepard described the limited multiplication of M. leprae which occurs when small inocula are injected into the foot pads of mice. This made it possible for the first time to screen drugs for anti-leprosy activity and diagnose drug resistant HD other than by clinical methods. Since then, armadillos, nude mice, and immunosuppressed rodents have been used to obtain higher yields of M. leprae. This has greatly increased the availability of M. leprae for study of the bacteriological and immunological aspects of HD. Infected armadillos have been one of the main sources of M. lepra~ antigens for scientific investigations and lepromin skin test material, and have also contributed to the development of potential anti-leprosy vaccines.

The most recent major event in the history of HD was the introduction of Multidrug Therapy (MDT) by the World Health Organization (WHO) in1982. This has had a major impact on the HD endemic areas of the world and has resulted in a significant decrease in estimates of total cases of HD in the world.

In 1985 the Worid Health Organization estimated there were 10-12 million cases of HD with about 5.4 million cases registered. The estimates for 1995 were 1.8 million and 1.3 million respectively. The distribution of HD, though worldwide, is not uniform. There are unexplained differences of prevalence between adjacent countries and within a single country. Approximately 75% of the total cases in the world are within 6 countries India, Brazil, Bangladesh, Indonesia, Myanmar, and Nigeria. In 1993 there were 591,000 new cases reported and in 1994, 561,000 cases. There are also an estimated 1-2 million cases who have completed treatment but who have residual disabilities who are not included in the 1995 totals.

It should be noted that the marked reduction in registered cases is so far largely due to the shortened treatment period and a revised definition of a case of HD and not as a result of a significant decrease in new cases. The current definition of a case, according to WHO, is a patient requiring chemotherapy. Patients who have completed their chemotherapy are not counted as cases. Thus, though the number of cases on treatment has decreased markedly in the last decade, the new case rates have decreased relatively little or not at all in some places.

The median age of onset of HD is somewhere between 20 and 30 years. Whether there are significant differences in susceptibility among different age groups is not clear. It may be that all age groups are equally susceptible and that the pattern of age at onset depends on the opportunity for contact with an infectious case. For example, HD is rarely seen in children under 5 years of age. When it does occur in very young children, there is usually an index case in the child's household. HD in children of any age is rare in the U.S. In countries such as the U.S where the prevalence of HD is low, the first exposure to M. leprae may be late in adult life, and new cases in the elderly are relatively more frequent.

There are an estimated 5,000 to 6,000 cases in the United States, which includes all cases reported to the registry and does not distinguish between active and inactive cases. In the past five years, 200-250 new cases have been reported to the registry each year. Of these, approximately 175 are new cases diagnosed for the first time. The remainder are cases previously diagnosed and treated but not reported to the U.S. registry. The major proportion of new cases in the U.S. are in immigrants, or from immigrant background, especially those with Southeast Asian and Hispanic origins. Of the new cases reported each year, 25-35 are in persons born in the U.S. and are mostly from Texas, Louisiana, and Hawaii. The largest numbers of cases overall are in California, Florida, Hawaii, Louisiana, New York, and Texas; however, almost all states have reported a few cases.

The usual source of infection is patients with untreated lepromatous HID, though contact with such patients cannot be regularly traced. Patients on adequate chemotherapy are not infectious. Untreated lepromatous patients excrete large numbers of viable bacilli from the upper respiratory tract, especially by way of nasal mucous secretions. It has been shown that M. leprae commonly remain viable for 24 hours outside the body, and may survive for a week or more under certain conditions. There is no evidence of sexual transmission.

Mycobacteiium leprae was first described by Armauer Hansen in Norway in 1873. It was the first human pathogenic bacterium to be discovered, preceding by 10 years the identification of M. tuberculosis. The failure to culture M. lWae in artificial media inhibited study for a century until armadillo derived M. leprae became available in large quantities in about 1973.

The Host Response

Hansen's Disease is a disease in which many of the clinical manifestations are due to the immune response of the host to the presence of M. leprae. It is a classical example of a disease which demonstrates a spectrum. Only 3-5 percent of a population appears to be susceptible to clinically detectable infection. This depends on variations in the host's immune response.

The clinical features of HD cover a wide range, from a single hypopigmented skin macule to very generalized disease.

There are three cardinal signs of HD.

• Localized skin lesions which show sensory loss
• Nerve enlargement at the sites of predilection
• The presence of acid-fast bacilli as determined by skin smears and/or biopsy

STT is now the recommended treatment for all newly diagnosed HD patients in the U.S. who can be followed regularly and can have long term follow-up.

Paucibacillary (PB)

PB-1 Dapsone 100 mg daily plus rifampin 600 mg daily for 12 months, and then therapy discontinued.

Multibacillary (MB)

• MB-1 - Dapsone 100 mg daily plus rifampin 600 mg daily both given for 2 years, and therapy then discontinued.
• MB-2 - Dapsone 100 mg daily plus dfampin 600 mg daily plus clofazimine 50 mg daily for 2 years, and therapy then discontinued.
• MB-3 - Dapsone 100 mg daily plus dfampin 600 mg monthly, plus clofazimine 50 mg daily and rAofazimine 300 mg monthly for 2 years, and therapy then discontinued.

Patients diagnosed for the first time in the U.S. generally have little or no disability at the time of diagnosis. Antibacterial treatment is very effective and most patients develop very little or no further nerve damage during treatment. The vast majority continue their activities and occupations with little interTuption. In the U.S. relapses of the disease in patients who have received MDT are very rare. Occasional relapses are seen in patients who have had only dapsone monotherapy.

Disability and deformity in HD are primarily due to nerve damage. Therefore, the primary goal in HD treatment is prevention of nerve damage by early diagnosis and treatment of new cases and the adequate treatment of reactions and neuritis.

Much of the disability and deformity in HD is secondary due to repetitive trauma and infection of insensitive areas. Persons with normal sensation rely on the sense of pain to warn them of possible trauma and are able to prevent serious injury. Those who have lost sensation have to learn other methods to protect insensitive areas from injury.