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Leprosy (Hansen’s disease)

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About

Due to obligate intracellular aerobic acid-fast bacillus Mycobacterium leprae
Transmission is from human to human

Aetiology

Lives in the phagolysosomes of macrophages and vacuoles of Endothelial and Schwann cells
Transmission possibly by the respiratory route, older age and close contact increase risk
Chronic granulomatous disease affects nerves and skin.
Bacterium can only be grown in footpad of mice and nine-banded armadillos.
It cannot be grown in vitro. Growth rate very slow time to double is 13 days

Epidemiology

Affects 4 million people worldwide
70% of whom live in India
Also Brazil, Indonesia, Mozambique, Madagascar, Tanzania and Nepal.

Clinical

Tuberculoid/Paucibacillary (High levels of CMI with elimination of leprosy bacilli)
- Incubation period is 2–5 yrs
- Five or fewer skin lesions without detectable bacilli on skin smears
- Tuberculoid patients have a few hypopigmented lesions.
- localised infection
Multibacillary lepromatous (Defective Cell Mediated response)
- Six or more lesions and may be skin smear positive
- Lepromatous leprosy, papules, nodules or diffuse infiltration of the skin
- Confluent lesions on the face can lead to a ‘leonine facies'
- Immune complex mediated - widespread
- Untreated lepromatous patients discharge bacilli from the nose.
- Then haematogenous spread to skin and nerve.
- Skin lesions with anaesthesia
- Thickened peripheral nerves : ulnar, median, radial, facial and other nerve palsies
- Acid-fast bacilli on skin smear or biopsy.
- The incubation period is 8–12 yrs for lepromatous cases.

Ridley-Jopling classification

Lepromatous leprosy (LL) - Low cell-mediated immunity and high Bacterial count
Borderline Lepromatous (BL)
Borderline Borderline (BB)
Borderline Tuberculoid (BT)
Tuberculoid (TT) - High cell-mediated immunity and low Bacterial count and do better than LL

Investigations

Investigation	Details
Skin Smear Microscopy	A smear is taken from the skin, typically from an earlobe, lesion, or other areas of suspected involvement. Staining with Ziehl-Neelsen stain is used to identify acid-fast bacilli (AFB). Positive results indicate the presence of Mycobacterium leprae, confirming the diagnosis. Commonly used in multibacillary leprosy.
Skin Biopsy	A sample of skin tissue is taken from a lesion or affected area. Histopathological examination shows granulomas, AFB, and changes in nerve fibers. Helps differentiate between the various forms of leprosy (tuberculoid, lepromatous, etc.). Useful in cases where skin smear microscopy is negative.
Lepromin Skin Test	An intradermal injection of inactivated Mycobacterium leprae antigen is administered. Used to assess the immune response and classify the type of leprosy. Positive in tuberculoid and borderline forms; typically negative in lepromatous leprosy. Not a diagnostic test but helps in understanding the immune status of the patient.
Polymerase Chain Reaction (PCR)	Used to detect the DNA of Mycobacterium leprae in tissue samples. Highly sensitive and specific, especially in paucibacillary cases where AFB may not be visible. Useful for early diagnosis and monitoring treatment response.
Nerve Biopsy	Biopsy of an affected peripheral nerve, often used in cases of neuritic leprosy. Histological examination shows granulomas and inflammatory infiltrates around nerves. Helps in diagnosing pure neural leprosy where skin lesions are absent. Can confirm the diagnosis when skin biopsies are inconclusive.
Serological Tests	Detect antibodies against phenolic glycolipid-1 (PGL-1), a component of Mycobacterium leprae. Not routinely used due to variability in sensitivity and specificity. Can be helpful in certain cases, especially in monitoring multibacillary patients.
Slit-Skin Smear	A slit is made in the skin and a small amount of tissue fluid is extracted. The sample is stained and examined under a microscope for acid-fast bacilli (AFB). Provides a bacterial index (BI) to assess the bacterial load and disease severity. Helps monitor treatment efficacy in multibacillary leprosy.

Summary

Form of Leprosy	Clinical Features	Management
Tuberculoid Leprosy	Few, well-defined hypopigmented skin lesions. Peripheral nerve involvement with loss of sensation. Strong cell-mediated immunity with low bacterial load.	6 months of multidrug therapy (MDT): Rifampicin: 600 mg once monthly Dapsone: 100 mg daily Regular follow-up to monitor nerve function and potential reactions.
Lepromatous Leprosy	Numerous, poorly-defined skin lesions. Symmetrical nerve involvement with widespread loss of sensation. High bacterial load with weak cell-mediated immunity.	12 months of multidrug therapy (MDT): Rifampicin: 600 mg once monthly Clofazimine: 300 mg once monthly and 50 mg daily Dapsone: 100 mg daily Management of leprosy reactions, often requiring corticosteroids.
Borderline Leprosy	Features between tuberculoid and lepromatous leprosy. Variable skin lesions and nerve involvement. Immune response fluctuates, leading to a variable bacterial load.	Treatment similar to lepromatous leprosy: 12 months of multidrug therapy (MDT): Rifampicin: 600 mg once monthly Clofazimine: 300 mg once monthly and 50 mg daily Dapsone: 100 mg daily Close monitoring for leprosy reactions, which may require corticosteroids or other immunosuppressants.
Indeterminate Leprosy	Early, mild form with few hypopigmented skin lesions. Uncertain prognosis; may progress to other forms of leprosy.	6 months of multidrug therapy (MDT): Rifampicin: 600 mg once monthly Dapsone: 100 mg daily Regular monitoring for progression to other forms of leprosy.

Drugs Used

Drug	Typical Dose (Adults)	Common Side Effects
Rifampicin (Rifampin)	600 mg once monthly	Hepatotoxicity (liver toxicity) Red-orange discoloration of body fluids Gastrointestinal upset (nausea, vomiting) Flu-like syndrome (fever, chills, myalgia) Thrombocytopenia (low platelet count)
Dapsone	100 mg daily	Haemolysis (especially in G6PD deficiency) Methaemoglobinemia Peripheral neuropathy Skin rashes Hepatotoxicity (rare)
Clofazimine	300 mg once monthly and 50 mg daily	Skin discoloration (darkening) Gastrointestinal upset (nausea, vomiting, diarrhoea) Dry skin and ichthyosis (scaly skin) Photosensitivity Eosinophilic enteritis
Ofloxacin	400 mg daily	Tendonitis and tendon rupture (rare) Gastrointestinal upset (nausea, diarrhoea) CNS effects (headache, dizziness, insomnia) Photosensitivity
Minocycline	100 mg daily	Photosensitivity Gastrointestinal upset Dizziness and vertigo Skin pigmentation changes Hepatotoxicity (rare)
Clarithromycin	500 mg daily	Gastrointestinal upset (nausea, diarrhoea, abdominal pain) Taste disturbances Hepatotoxicity QT prolongation (heart rhythm disorder)
Ethionamide	250-500 mg daily	Gastrointestinal upset (nausea, vomiting, abdominal pain) Hepatotoxicity Hypothyroidism Peripheral neuropathy Depression and psychiatric symptoms

PLEASE NOTE LEGAL ADVICE: The contents are under continuing development and improvements and may contain errors of omission or fact. Feedback vital and always welcome at drokane at gmail.com. This is not to be used for the assessment, diagnosis or management of patients. It should not be regarded as medical advice. It is only for educational purposes. Please adhere to your local protocols. If you are unwell please seek healthcare advice from your doctor. This does not replace senior or specialist advice. If you do not accept this then please do not use the website. If you need medical advice, please consult a doctor or other appropriate medical professional. If you are a medical professional and you need advice then speak to your senior or colleagues.

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