FIDSSA

Case of the Month

May 2016

Dr Juno Thomas on behalf of the Infection Control Society of South Africa
A 54-year-old female is referred by her general practitioner (GP) to a physician in private practice for assessment and further management. She has been asthmatic since childhood, and was diagnosed with hypertension seven years previously. Her asthma-related symptoms have steadily worsened over the past three months despite numerous changes in therapy.

On her first visit to the physician, the patient reports that apart from the poorly controlled asthma, she is also concerned about a persistent ‘rash’ on her face.

The ‘rash’ began five months before, initially as a single lesion on the right cheek, but a month later a second lesion appeared on her nose. The GP initially thought it was likely to be a drug-related adverse reaction, but as the lesions progressed and enlarged he diagnosed it as Tinea corporis (ringworm). The patient had been applying topical corticosteroid and terbinafine creams for two months with no improvement in the lesions, so the GP prescribed systemic (oral) terbinafine treatment one month previously. The lesions had not improved and the patient reported that they were steadily increasing in size. She also mentioned that her nose sometimes felt numb.

Apart from further investigation and management of her underlying asthma and hypertension, the physician suggested a skin biopsy of the rash. He agreed with the GP’s diagnosis of Tinea corporis, but was concerned that there had been no improvement despite prolonged topical and systemic antifungal therapy.

One week later, the biopsy of both skin lesions was performed. Meanwhile, the topical and oral terbinafine treatment was continued.

The histology report of the biopsies reads as follows:

Skin biopsy left nose

Skin biopsy right cheek

Conclusion

Question 1: Is the patient’s clinical presentation consistent with a diagnosis of leprosy?

Answer to Q2

Yes. Leprosy (also known as Hansen’s disease) is a chronic infectious disease caused by Mycobacterium leprae involving mainly the skin and peripheral nerves. Chronic skin lesion/s that do not respond to standard treatment for more common conditions is a typical early presenting feature of leprosy. Sensory loss within such lesions or in the extremities makes the diagnosis of leprosy highly likely. Leprosy is often mistaken for other skin conditions (including allergic reactions, fungal infections, vitiligo, autoimmune diseases, other mycobacterial infections) or for conditions with peripheral neuropathy (including diabetes and HIV).

The most common presenting features of leprosy include:

Hypopigmented or reddish skin patch/es: usually macular (flat) but may be papular (raised) or maculopapular
Decreased sensation or loss of sensation within skin patch/es
Parasthesiae (tingling or numbness in hands or feet)
Lumps (nodules) or swelling on the earlobes or face
Tender, enlarged peripheral nerves (ulnar nerve at the elbow, median and superficial radial cutaneous nerve at the wrist, great auricular nerve in the neck, common peroneal nerve at the popliteal fossa).

Late complications include weakness of the hands with claw fingers, weakness of the feet with foot drop, facial paralysis, lack of eyebrows and eyelashes, collapsed nose, and perforated septum.

Source: World Health Organization. Guide to eliminate leprosy as a public health problem. First edition, published 2000. Available online at: http://www.who.int/lep/resources/Guide_Int_E.pdf?ua=1

Question 2: How is leprosy diagnosed?

Answer to Q2

The diagnosis of leprosy is most commonly based on the clinical signs and symptoms, especially in endemic areas where there is a high index of suspicion for leprosy. The diagnosis is confirmed when a skin biopsy from the active margin of a skin lesion reveals the presence of acid-fast bacilli. Skin smears (small incisions made on ears, elbows or knees to collect a dermal fluid sample which is examined for the presence of acid-fast bacilli) are still used in some endemic countries, but are inferior to skin biopsy samples.

Unlike other Mycobacterium spp., M. leprae cannot be cultured on artificial media in the laboratory. There are no commercial PCR assays for M. leprae, and the PCR assays currently in use for diagnosing TB and other non-tuberculous mycobacteria (such as those commonly used in South Africa) do not detect M. leprae. Reliable serological tests are not available.

The National Department of Health Guidelines on leprosy control in South Africa (2011) requires that the diagnosis of leprosy should be:

Based on clinical signs and symptoms of leprosy
Confirmed by a punch biopsy or skin smear

Case continued
The patient returned to her physician for a follow-up consultation. The physician was extremely surprised at the histological diagnosis of leprosy. During his training and 30 years of practice as a specialist in South Africa, he had never seen a case of leprosy. He asked the patient if she had ever been in contact with a case of leprosy, where she had grown up and which countries she had travelled to. The patient was born and grew up in the Johannesburg area, had never travelled outside of the country, and had never been in contact with a case of leprosy.

The physician wanted to discuss the case further with the histopathologist and other colleagues, and requested the patient to return a week later.

After consulting the histopathologist, who had experience with the diagnosis of leprosy having worked in an academic pathology laboratory servicing a leprosy management facility, the physician regarded leprosy as the most likely diagnosis.

He then advised all healthcare workers who had been in contact with the patient to take rifampicin prophylaxis, and started a ‘course’ of rifampicin himself.

Question 3: How is leprosy transmitted, and what are the risk factors for leprosy?

Based on clinical signs and symptoms of leprosy
Confirmed by a punch biopsy or skin smear

Case continued

The patient returned to her physician for a follow-up consultation. The physician was extremely surprised at the histological diagnosis of leprosy. During his training and 30 years of practice as a specialist in South Africa, he had never seen a case of leprosy. He asked the patient if she had ever been in contact with a case of leprosy, where she had grown up and which countries she had travelled to. The patient was born and grew up in the Johannesburg area, had never travelled outside of the country, and had never been in contact with a case of leprosy.

The physician wanted to discuss the case further with the histopathologist and other colleagues, and requested the patient to return a week later.

After consulting the histopathologist, who had experience with the diagnosis of leprosy having worked in an academic pathology laboratory servicing a leprosy management facility, the physician regarded leprosy as the most likely diagnosis.

He then advised all healthcare workers who had been in contact with the patient to take rifampicin prophylaxis, and started a ‘course’ of rifampicin himself.

Question 3: How is leprosy transmitted, and what are the risk factors for leprosy?

Answer to Q3

Contrary to widespread cultural beliefs, leprosy is not highly contagious. The exact mechanism of transmission of leprosy is unknown. Previously it was thought that the disease was transmitted strictly by contact (prolonged close association) between cases of leprosy and healthy persons, but there is recent and increasing evidence that transmission by the respiratory route is more likely. The portals of exit for M. leprae are the skin and nasal mucosa. Humans are almost exclusively the reservoir of infection, apart from wild 9-banded armadillos in the Americas – which can also develop leprosy disease, and infrequently transmit leprosy to humans (who have contact from handling, killing or eating armadillos).

Most persons exposed to M. leprae do not develop disease. Risk factors for developing disease include:

Genetic susceptibility – the innate immunologic response to M. leprae affects the likelihood of development of disease. Certain genetic factors (e.g. PARK2/PACRG gene alleles) have been linked to increased risk for developing leprosy. It is thought that about 95% of the world’s population is not genetically susceptible to developing leprosy disease.
Close contact – prolonged close physical distance association increases the risk of leprosy
Type of leprosy – cases of lepromatous leprosy are likely more infectious since they have a greater number of skin lesions and shed greater loads of bacilli in nasal discharge
Age – older individuals appear to be at increased risk for leprosy
Immunosuppression – an increased risk of developing leprosy after exposure has been observed following solid organ transplantation, chemotherapy, use of biologic agents for autoimmune diseases, and also in persons with HIV infection initiating antiretroviral therapy.

The incubation period following exposure to M. leprae is generally about 3-5 years, but can be up to 20 years. Although it is more common in adults, leprosy can affect persons of all ages, including infants and young children.

Question 4: Is chemoprophylaxis indicated for close contacts (household contacts or healthcare workers) of patients diagnosed with leprosy?

Answer to Q4

No. Leprosy is not highly contagious and secondary post-exposure prophylaxis is not indicated. Only household contacts with prolonged close physical contact may be at increased risk for being exposed to M. leprae; such persons should be educated about the disease manifestations and the need to seek immediate attention if skin or neurological changes develop. Ideally, they should also be examined annually for evidence of disease for about 5 years. In addition, the National Department of Health Guidelines on leprosy control in South Africa (2011) advise that household contacts should receive BCG vaccine; BCG vaccination is partially protective for leprosy, and although BCG is administered at birth in South Africa, an additional dose further increases protection and therefore may be beneficial.

Once receiving a few doses of appropriate multi-drug therapy (1-2 days), a person with leprosy is non-infectious. Isolation (at healthcare facilities or in the home) is not indicated.

Case continued
At the follow-up consultation, the physician conducted a targeted physical examination to ascertain whether additional signs of leprosy were present. The following cardinal signs were elicited:

The skin lesions showed loss of sensation to pin prick
Thickened, minimally tender ulnar nerves at both elbows

Question 5: How is leprosy classified (staged)?

Answer to Q5

Leprosy manifests with a spectrum of clinical and pathological features, depending on the strength of the immune response. At one end of the spectrum is a form with robust immune response, few skin lesions, and very few bacilli (tuberculoid or paucibacillary leprosy), and at the other end of the spectrum is a form with the weakest immune response, more skin lesions and many bacilli (lepromatous or multibacillary leprosy).

There are two major classification systems for leprosy:
1. World Health Organization system: based on number of skin lesions present, and skin smears where available.
Two categories:

a. Paucibacillary: ≤5 skin lesions and skin smear negative b. Multibacillary: ≥6 skin lesions; may be skin smear positive2. Ridley-Jopling system: based on cutaneous, neurological and histological findings; the optimal classification system.
Six categories: tuberculoid, borderline tuberculoid, mid-borderline, borderline lepromatous, lepromatous, indeterminate.

Disease classification is important as it guides further management of the patient, dictating the number of drugs used and the duration of the treatment regimen.

The National Department of Health Guidelines on leprosy control in South Africa (2011) requires that patients with leprosy be classified using both WHO and Ridley-Jopling classification systems.

Question 6: What is the management of leprosy in South Africa?

Answer to Q6

Leprosy is a notifiable medical condition in South Africa and any case (whether suspected or confirmed) must be notified to the appropriate Department of Health official and a GW 17/5 form completed.

Leprosy is curable, and the National Department of Health Guidelines on leprosy control in South Africa (2011) treatment regimens align with WHO recommendations – i.e. multi-drug therapy (MDT, a combination of rifampicin and dapsone, with the addition of clofazimine for multibacillary disease ) for variable duration depending on the classification of disease.

MDT leprosy treatment is provided free of charge by the WHO in collaboration with the manufacturers. The Leprosy Mission of Southern Africa partners with the Department of Health in the management and control of leprosy in South Africa, facilitating the supply and provision of leprosy treatment in the country.

A number of provincial facilities in each province are designated as leprosy management facilities, and leprosy management services are supported by the Leprosy Mission of Southern Africa at these sites (including: supervision of leprosy clinics, supervision of leprosy treatment, training of healthcare workers, conducting home visits to leprosy patients and the facilitation of rehabilitation of leprosy patients). The list of provincial facilities and their contact details, as well as contact details for the Leprosy Mission of Southern Africa appear in the National Department of Health Guidelines on leprosy control in South Africa (2011).

Patients with leprosy require close monitoring and prompt management of complications, including:

those arising from peripheral nerve sensorimotor dysfunction and the associated deformities and disability
adverse effects of treatment
leprosy reactions: these are systemic inflammatory episodes that may occur before treatment, during treatment, or months to years after treatment. 30-50% of all patients with leprosy experience leprosy reactions. The inflammation associated with the reactions can lead to severe nerve injury and subsequent paralysis and deformity. There are two types of reactions: type 1 (reversal reaction) and type 2 (erythema nodosum leprosum).

Household contacts should receive BCG vaccination, and must be educated regarding leprosy disease manifestations and the need to seek medical attention promptly.

Question 7: What is the management of leprosy in South Africa?

Discussion
Leprosy is an ancient disease of humankind, with evidence of human infection at least 4 000 years ago, yet is still widely misunderstood with cultural misbeliefs and social stigma still prevalent. Despite being curable, it is still a global health concern and is targeted for elimination by the WHO. The countries reporting the highest number of new cases include India, Brazil, Indonesia, Bangladesh, Democratic Republic of Congo, Nepal, Myanmar, Sri Lanka, Philippines, Sudan, Madagascar, China, Mozambique, Angola and Tanzania.

Leprosy has been a notifiable disease in South Africa since 1921, the WHO elimination target of < 1 case per 10 000 population having already been achieved at a country level at that time. about 50 cases of leprosy have been notified annually in south africa over recent years, so although leprosy has been eliminated, there is still a low prevalence of disease in the country. historically, the distribution of leprosy in the country is heterogeneous with a prominent ‘leprosy belt’ of greater prevalence stretching across mpumalanga province into northern kwazulu-natal province, with a ‘hot spot’ in ermelo and surrounds.

in countries with low prevalence of leprosy, the focus should be on detection of hidden leprosy cases in order to reduce ongoing transmission. unfortunately, many healthcare workers are not aware of the clinical manifestations of leprosy and have no experience identifying suspected cases; there is concern that lack of education regarding the disease and low index of suspicion leads to considerable delay in the diagnosis and treatment of leprosy cases, resulting in increased morbidity in case-patients as well as continued transmission. of note is that neighbouring angola and mozambique are still endemic for leprosy and have reported high numbers of new cases over the past few years.

there is no clear evidence that hiv per se is a risk factor for developing leprosy, and the response to leprosy treatment is not affected by hiv status. however, initiation of haart may unmask ‘subclinical’ leprosy, which then manifests as an immune reconstitution inflammatory syndrome, presenting generally as a type 1 leprosy reaction.

References

1. National Department of Health. Guidelines on leprosy control in South Africa. Published 2011, available online at http://www.health.gov.za/index.php/2014-03-17-09-09-38/policies-and-guidelines/category/91-2011p# 2. world health organization. leprosy elimination programme resources. available online at http://www.who.int/lep/en/ 3. World Health Organization. Guide to eliminate leprosy as a public health problem. First edition, published 2000. Available online at:http://www.who.int/lep/resources/Guide_Int_E.pdf?ua=1 4. The Leprosy Mission Southern Africa website: http://leprosymission.co.za/ 5. world health organization. global leprosy situation, 2012. weekly epidemiological record 2012; 34(87) 317-28.
6. white c, franco-paredes c. leprosy in the 21st century. clin microbiol rev 2015; 28 80-94. available online at http />/cmr.asm.org/content/28/1/80.full
7. Ukpe IS. A study of health workers’ knowledge and practices regarding leprosy care and control at primary care clinics in the Eerstehoek area of Gert Sibande district in Mpumalanga Province, South Africa. SA Fam Pract 2006; 48(5): 16
8. Durrheim DN, Fourie A, Balt E et al. Leprosy in Mpumalanga Province South Africa – eliminated or hidden? Lepr Rev 2002; 73: 326-333
9. Lawn SD, Wood C, Lockwood DN. Borderline tuberculoid leprosy: an immune reconstitution phenomenon in a human immune deficiency virus-infected person. Clin Infect Dis 2003; 36: 5-6.
10. Martiniuk F, Rao SD, Rea TH et al. Leprosy as Immune Reconstitution Inflammatory Syndrome in HIV-positive persons. Emerg Infect Dis 2007; 13(9): 1438-9

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