Leprosy

Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae and, in a proportion of cases, the more recently identified Mycobacterium lepromatosis. The organism is obligate intracellular, with a particular tropism for peripheral nerves and skin.

It is transmitted predominantly through prolonged close contact, via respiratory droplets from untreated lepromatous disease.

The clinical spectrum is determined by the host cell mediated immune response. It ranges from paucibacillary tuberculoid disease at one pole (strong cell mediated immunity, limited bacterial burden) to multibacillary lepromatous disease at the other (poor cell mediated immunity, extensive bacterial burden).

Early diagnosis and treatment are essential, because delay risks irreversible nerve damage and disability.

Pathophysiology and classification

• The organism is obligate intracellular and replicates extremely slowly (doubling time of approximately two weeks). This underlies the prolonged incubation period, typically two to ten years, and the need for prolonged multidrug treatment.
• The Ridley Jopling classification describes a spectrum from tuberculoid through borderline tuberculoid, borderline, borderline lepromatous, to lepromatous leprosy.
• The World Health Organization operational classification is more widely used to guide treatment duration. Paucibacillary disease generally has five or fewer skin lesions; multibacillary disease has six or more.
• Nerve damage results from direct bacterial invasion of Schwann cells and from immune mediated inflammatory reactions (leprosy reactions).
• The immune mediated component explains why nerve damage can develop or worsen even after antibacterial treatment has reduced the bacterial burden.

• Hypopigmented or erythematous skin patches with sensory loss (reduced or absent sensation to light touch, pain and temperature within the lesion) are the characteristic and most useful diagnostic finding. The number and distribution of lesions reflect the position along the immunological spectrum.
• Peripheral nerve involvement presents with sensory loss, motor weakness and, characteristically, palpable nerve thickening. This is most readily examined at the ulnar nerve at the elbow, the common peroneal nerve at the fibular head, and the posterior tibial nerve at the ankle.
• It reflects the neurotropism of the organism and underlies the substantial disability burden if treatment is inadequate.
• Lepromatous disease presents with widespread, often symmetrical skin infiltration and diffuse thickening of the skin, ears and face. Advanced untreated disease causes the historically described leonine facies.
• Lepromatous disease also brings more extensive nerve involvement and nasal mucosal involvement. In longstanding disease, direct organ infiltration causes testicular atrophy and gynaecomastia in men.
• Leprosy reactions are immune mediated inflammatory episodes that can occur before, during or after antibacterial treatment.
• Type one (reversal) reactions present with acute inflammation of existing skin lesions and nerves. Nerve involvement is a medical emergency because of the risk of rapid, irreversible nerve damage if not promptly treated.
• Type two reactions (erythema nodosum leprosum) occur predominantly in multibacillary disease. They present with painful subcutaneous nodules, fever and systemic upset, reflecting immune complex mediated inflammation.

• Diagnosis is predominantly clinical, based on the combination of a characteristic skin lesion with associated sensory loss, thickened peripheral nerve, or a positive skin smear, with any one of these three cardinal findings sufficient to establish the diagnosis in the appropriate clinical and epidemiological context.
• Slit skin smear examination, taking scrapings from the edge of a skin lesion and examining for acid fast bacilli, supports diagnosis and classification (bacterial index), though sensitivity is limited, particularly in paucibacillary disease where organisms may not be detectable on smear despite genuine infection.
• Skin biopsy with histological examination provides more detailed characterisation, showing the specific granulomatous pattern corresponding to the position along the immunological spectrum, and polymerase chain reaction testing offers increasingly available molecular confirmation, particularly useful in paucibacillary disease with negative smear results.
• Nerve conduction studies can characterise the extent and pattern of nerve involvement where clinically indicated, supporting both diagnosis and monitoring of treatment response, particularly relevant in the assessment and management of suspected nerve function impairment or evolving reaction.

• Multidrug therapy is standard treatment. The regimen and duration depend on paucibacillary versus multibacillary classification, and it is given as fixed dose blister pack combinations to support adherence.
• Paucibacillary disease is treated with rifampicin 600 mg once monthly (supervised) combined with dapsone 100 mg once daily (self administered), for six months total duration.
• Multibacillary disease is treated with rifampicin 600 mg once monthly combined with clofazimine 300 mg once monthly (both supervised) plus dapsone 100 mg once daily and clofazimine 50 mg once daily (self administered), for twelve months total duration.
• Type one (reversal) reactions with nerve involvement are a medical emergency requiring prompt high dose corticosteroid treatment. Prednisolone starts at 40 to 60 mg once daily and is tapered gradually over weeks to months according to clinical response.
• Urgency reflects a time critical, potentially reversible window for preventing permanent neurological deficit.
• Type two reactions (erythema nodosum leprosum) are managed with corticosteroids for mild to moderate episodes. Thalidomide is highly effective for more severe or recurrent episodes, where available and with strict pregnancy avoidance given severe teratogenicity.
• Continue antibacterial treatment throughout any reaction episode. Reactions reflect an immune response to bacterial antigens, not treatment failure, and stopping treatment does not address the reaction while potentially allowing disease progression.
• Assess nerve function (voluntary muscle testing and sensory testing) regularly throughout treatment and reaction management. This monitors for evolving nerve damage and guides prompt escalation of reaction treatment when deterioration is identified.
• Prevent disability with patient education on self care of anaesthetic areas, particularly hands and feet, where unrecognised injury and ulceration are a risk. Provide appropriate footwear and physiotherapy for established motor deficit.
• Disability prevention is an essential part of long term management, given the substantial disability burden of inadequately managed nerve involvement.
• Screen household contacts. Some national programmes give single dose rifampicin post exposure prophylaxis to eligible contacts. This is an important public health measure given the transmission risk from close, prolonged contact with untreated multibacillary disease.