Leprosy, also known as Hansen disease, is a chronic mycobacterial infection caused by the acid-fast rod Mycobacterium leprae. It is an infectious disease that mainly affects the skin and nerves. Although rare, it is still seen in the United States, with 79.6% of the cases coming from Florida, California, Hawaii, and Texas.1 It is seen more often in a few endemic countries. Since nurse practitioners (NPs) see patients who have lived or traveled overseas in endemic countries, it is important for them to know about this serious, yet uncommon disease. This article will review the epidemiology, clinical manifestation, diagnosis, and treatment of leprosy within the context of a case study of a patient with multibacillary leprosy, seen in a rural mission hospital in Rwanda, Africa.

Epidemiology

The prevalence of leprosy has decreased dramatically over the last 10 years. Two countries listed by the World Health Organization (WHO) as having continued high endemic rates are Tanzania and the Democratic Republic of Congo (DRC); both countries border Rwanda. In the United States, the number of new cases reported in 2010 was 169.2 In Rwanda, the number of new cases was 36, whereas, in neighboring Tanzania, it was 2,349, and in the DRC, 5,049. This was a decrease of (between) 36% to 51% compared with the rate in 2005. In the United States, leprosy is predominantly related to immigration from areas in which the disease is endemic.

There are currently 6,500 cases of leprosy on the National Hansen's Disease Program's Registry, which includes all cases since the registry was initiated, and the patients are still alive. There are 3,300 cases that are considered active and require drug treatment.3

The transmission method of leprosy is unknown, but researchers believe it is related to respiratory droplets. One researcher has also suggested that Mycobacterium leprae may shed via the skin. In this study, 60% of untreated patients with Mycobacterium leprae had acid-fast bacilli noted in their keratin layer.4 When looking at the cases in the United States, the risk factors of infected persons include close contact with people having untreated multibacillary disease, travel or prior residence to/in endemic countries, and armadillo exposure5; armadillos are a known host to Mycobacterium leprae. Truman et al. compared the genetic sequence of armadillos and humans known to have leprosy, and they found a particular genotype that was common between humans and armadillos in a majority of cases. It is not known how the mycobacterium was transmitted from armadillos to humans.5 It is also suggested that there is a hereditary component to leprosy making certain population groups more susceptible.6 The incubation period is 2 to 7 years, which has made containment difficult.7 There are two peak age groups affected: children between the age of 10 and 15 years, and adults between the age of 30 and 60 years.8

Clinical manifestations

Patients with leprosy are classified using the WHO or the Ridley-Jopling systems.9 In the WHO system, a patient is classified as having paucibacillary if they have 5 or fewer hypopigmented macules with distinct borders. The macules are hypopigmented in darker-skinned individuals and copper-colored in lighter-skinned persons. Multibacillary disease is diagnosed when there are 6 or more skin lesions, but they usually have nodules and frequent involvement of the nasal mucosa.10 The Ridley-Jopling system identifies patients as tuberculoid, borderline tuberculoid (equivalent to paucibacillary), or as midborderline, borderline lepromatous, and lepromatous leprosy (equivalent to multibacillary).9,11 The Ridley-Jopling system is most useful for research purposes. In multibacillary disease, leprosy physical findings include a skin lesion as the most common presenting physical complaint. Other signs and symptoms include sensory loss, anhidrosis, neuropathic pain, palpable peripheral nerves, muscle atrophy and weakness, foot drop, claw hands and toes, lagophthalmos, nasoseptal perforation, and collapse of the bridge of the nose.12 Over time, there is thickening of the skin, coarsening of the facial features, and nodular thickening of the ear lobes. Later, there can be thinning of eyebrow hairs and eyelashes. The disease commonly affects the trigeminal nerve; thus, one can have reduced sensation of the cornea and conjunctivae. The facial nerve can be affected causing lagophthalmos. The combination of facial and trigeminal nerve dysfunction puts the patient at risk for corneal trauma. There can also be testicular atrophy with resultant azoospermia and gynecomastia.12

Diagnosis

The diagnosis of multibacillary leprosy is made by doing a punch biopsy or skin smears of skin lesions (most commonly at the ears, elbows, or knees). The skin smear is taken from two sites by following these steps: prep the site (typically the earlobe); squeeze the earlobe to minimize blood flow to the distal aspect of the earlobe; make a 5 mm long and 2 mm deep incision; keep pinching the site to prevent blood oozing (no blood should be at the site) at the incision site; turn the scalpel at 90 degrees, and hold it at a right angle to the incision; scrape inside the cut once or twice to collect tissue; and spread the material collected onto a slide. The slide is then sent to the lab for exam. This process is completed at two sites. If the patient has atrophy but no skin lesions, one can diagnose the disease by doing a biopsy of a peripheral nerve, such as the sural or radial cutaneous nerve. Nerve conduction studies show more severe changes in patients with multibacillary disease; however, nerve conduction studies are not used to diagnose leprosy in nonendemic countries.13 Serology and polymerase chain reaction (PCR) testing for Mycobacterium leprae DNA is not sensitive or specific enough for early diagnosis.14,15

Case study

A 34-year-old male from the DRC crossed the border to come to a rural mission hospital in Rwanda, Africa. He had a chief complaint of multiple facial nodules developing over the past several months. He was given an antibiotic by a local clinic 2 weeks prior with no change in the nodules. He had no fever, chills, or night sweats. He complained of some numbness in the hands and feet. On further questioning, he admitted he had an uncle with similar facial lesions that he lived with for several weeks a year prior. He had not seen the uncle since that time and was not aware of his medical diagnosis. Lab tests conducted included testing for HIV and complete blood count (CBC). The physician working in the ED took a skin smear with acid-fast staining from ear slits and sent them for microscopy. The HIV was negative, and the CBC revealed a white blood cell count of 4,600/cells/mm3; no differential was completed due to lab limitations, and microscopy revealed Mycobacterium leprae. On physical exam, this was an ambulatory male who walked slowly. His blood pressure was 128/74, pulse 84, respiratory rate was 16, and temperature 97.4[degrees] F (37.3[degrees] C) orally. He had multiple flat nodules on his face including the lips, nose, and ears. There was conjunctivitis, and the patient could not shut his eyes completely (see Patient with leprosy and ocular involvement). Since an ophthalmologist was not available, the eye technician did an evaluation and found no scleritis or corneal injury. He was placed on a petroleum-based optic lubricant for eye protection. Upon learning of the positive skin smear, the patient was transferred to the isolation ward. He was treated using the current WHO treatment guidelines: rifampicin (known as rifampin in the United States) 600 mg monthly, dapsone 100 mg daily, and clofazimine 300 mg once a month and 50 mg daily; the duration of treatment was 12 months.16 The patient elected to stay at the hospital to complete his therapy because of the concern of obtaining the medications in the DRC. He was given written information to share with his family and the local health clinic so that other family members could be screened for disease. Upon completion of the course of treatment, the patient had no vision loss, and his facial nodules had completely resolved.

Treatment

The WHO guidelines for treating multibacillary disease were discussed in the case study. In the United States, the current recommendation for multibacillary disease treatment includes dapsone 100 mg daily, rifampin 600 mg daily, and clofazimine 50 mg daily; the duration of treatment is 24 months.17 Clofazimine is considered an investigational drug, and requests need to be directed at the National Hansen Disease Program. The National Hansen's Disease Program is located in Baton Rouge, Louisiana, and is the only agency in the United States that focuses on the diagnosis, treatment, and research of Hansen Disease. The treatment of paucibacillary (tuberculoid or borderline tuberculoid) is dapsone 100 mg daily and rifampin 600 mg daily for 12 months according to the National Hansen's Disease Program.17 The WHO recommends the same dose of dapsone but for only 6 months and 600 mg of rifampin only once each month for 6 months.16 The WHO and U.S. guidelines are the accepted standards, although other treatment regimens have been suggested.18 Since there are many ophthalmologic risks, there should be a prompt referral to an eye care provider to reduce the risk of corneal trauma. The patient should wear custom shoes with a wide toe box because of the risk of ulceration associated with peripheral neuropathy. Although not exhibited by the patient in the case study, persons being treated for leprosy can exhibit worsening of symptoms after initiation of treatment; this is called a leprosy reaction. Leprosy reactions are characterized by inflammatory reactions of the skin, nerves, and other organs. The reactions usually occur shortly after initiating treatment of leprosy but can occur any time (including years after treatment).19 There have also been reports of reversal reactions being noted as part of immune reconstitution inflammatory syndrome in patients with HIV-initiating, antiretroviral treatment.20,21 Leprosy reactions can affect up to 30% to 50% of patients and can cause permanent nerve loss.22 Type 1 or reversal reaction is characterized by swelling, erythema, and tenderness of previously existing lesions; loss of nerve function in the lateral popliteal or ulnar nerve has been seen. This reaction typically occurs within the first two months of treatment.23 It is accompanied by pain or tenderness of one or more nerves. Type 2 or erythema nodosum leprosum (ENL) reactions are characterized by areas of new, tender, subcutaneous nodules; at times, it is associated with fever, arthralgia, neuritis, adenopathy, and occasionally, uveitis, orchitis, or dactylitis (see Typical ENL lesions).19 Type 2 reactions, in contrast to type 1 reactions, occur during the second year of therapy.23 Type 1 reactions are treated with corticosteroids tapered over a 12-week period.24 Type 2 reactions are also treated with corticosteroids, but occasionally, thalidomide is used for severe reactions.25 Thalidomide is a known teratogen that can cause amelia and phocomelia, so it should not be used in women of childbearing age.26 Factors associated with relapse include use of monotherapy, inadequate therapy, and presence of multiple skin lesions.27

Implications for practice

A patient diagnosed with leprosy along with family members should be educated about the risk of transmission and the associated signs and symptoms of the condition. Further education includes informing the family that the patient with leprosy is no longer contagious after 3 days of treatment.3 First- and second-degree relatives should be examined. The exam should include a full-body skin exam accompanied by a history looking for neurologic symptoms (numbness, tingling, or paresthesias). The examiner should use visual inspection and palpation to assess for enlargement of peripheral nerves; if found, the provider proceeds with skin biopsy, slit smears, and nerve conduction velocities. Rifampin has been studied to prevent leprosy in close contacts; it was not efficacious after two years, so it is not recommended.28 Hansen disease is a notifiable condition. The CDC recommends the local health department to fill out the appropriate form (http://www.hrsa.gov/hansensdisease/pdfs/hansenssurveillance.pdf), and forward it to the State health department; they will forward it to the CDC. The current WHO strategy is to examine household contacts of persons with leprosy, and if none are found, to educate the family on early signs and symptoms.29 Education should also include potential adverse medication reactions. Rifampin can cause hepatic and renal dysfunction, agranulocytosis, and thrombocytopenia. Therefore, liver function tests, creatinine, and a CBC should be monitored. Asymptomatic liver enzyme elevation up to three times normal is considered acceptable. Patients should be advised that their urine will turn a reddish-orange color, and the change in color of their tears could cause permanent staining of their contact lenses.30 Dapsone can cause methemoglobinemia and agranulocytosis, and this is most severe in patients with preexisting glucose-6-phosphate dehydrogenase (G6PD) deficiency. Most patients have a decrease in the hemoglobin of 1 to 2 g/dL with dapsone. Clofazimine causes a pink-to-brownish-black pigmentation of the skin in most patients. Ichthyosis and gastrointestinal intolerance occur in about half of the patients receiving this medication. In summary, prior to starting therapy, patients should have the following lab tests performed: CBC, aspartate aminotransferase, alanine aminotransferase, calcium, blood urea nitrogen, creatinine, bilirubin, and G6PD. The CBC should be repeated at 1 month. The CBC and liver function tests should be repeated at 3, 6, 12, 18, and 24 months.17

Moving forward

The goal of the WHO and CDC is to completely eradicate leprosy. There have been strides made toward the elimination of leprosy in the last 10 years. A disease is considered eliminated if there is less than 1 case per 10,000 inhabitants; in a country of 8,000,000 people, less than 800 cases would mean the disease was eradicated. Eradication efforts have included free treatment, close monitoring, and education of family members. Novartis has formed an alliance with the WHO to provide free treatment of multibacillary disease until at least 2015.31 Some of the reasons eradication is difficult is that the disease may not make an appearance until several years after an individual acquires the disease. There is ongoing research to find a way to make an early diagnosis of leprosy using immunological testing.14 In addition, there has been some testing on the use of bacillus Calmette-Guerin vaccination (BCG) to reduce the risk of malaria; however, the WHO is not currently recommending this strategy.32 NPs should have a high index of suspicion for leprosy when a person has new skin lesions, lives in the Southern United States, or has traveled to or emigrated from endemic countries.

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