10.1.2 Leprosy

Hansen's disease.

Worldwide, about 720,000 new cases of leprosy are registered each year and about 2 million people suffer from leprosy-related disabilities, predominantly in India, Brazil, Indonesia, Democratic Republic of Congo, Tanzania, Angola, Central African Republic, Myanmar, Madagascar, Nepal, Mozambique, Philippines (90% of all new cases).

Age peak between 10 and 20. After puberty, there are twice as many cases in males as in females.

Leprosy is a chronic minimally contagious, granulomatous disease caused by Mycobacterium leprae, primarily affecting the peripheral nerves and skin. Incubation period 3 to 20 years.

Mycobacterium leprae, which can survive outside human hosts for many months, is an obligate intracellular gram-positive acid-fast bacillus. M leprae from the nasal mucosa spreads via the recipient's nasal mucosa to skin and nerves. The organism can survive outside human hosts for many months. Household contact with a person with leprosy is a strong risk factor for infection. There seems to be little evidence for the impact of  an association with HIV infection, nutrition, or socioeconomic status.

The clinical picture depends on the individual's immune response to M leprae according to the  Ridley–Jopling scale:

• Tuberculoid leprosy: good cell mediated immunity and few skin lesions.

• Lepromatous leprosy: low reactivity for M leprae, causing uncontrolled bacterial spread and skin and mucosal infiltration.

Skin: poorly defined hypopigmented or erythematous macules in early lesions.

• Tuberculoid leprosy: single or very few scaly, dry, and hairless macules or plaques with central flattening and well-defined edges. In dark skin lesions are hypopigmented rather erythematous, which is found in lighter skin. Reduced sensation and loss of sweating.

• Lepromatous leprosy: widely and symmetrically distributed, poorly defined hypopigmented or erythematous macules. Papules and nodules (leproma) may be present. Peripheral edema of the legs and ankles due to increased stasis. The skin of the face and especially at the ear lobes gets thicker due to dermal infiltration, featuring a leonine face. Eyelashes and eyebrows loose their hair.

• Borderline leprosy: skin lesions intermediate between the 2 polar tuberculoid and the lepromatous forms. They may be macular, papulonodular, plaquelike, annular, or large geographic.

Nerves: sensory, motor, and autonomic function of peripheral nerves are affected.

• Nerve damage may occur before, during, or after treatment across the total spectrum of the disease. Some people have no nerve damage, while others develop anaesthesia of the hands and feet, putting them at risk of developing neuropathic injuries, with loss of the fingers and toes, due to repeated injury.
• Weakness and paralysis of the small muscles of the hands, feet, and eyes puts people at risk of developing deformity and contractures.
• Palpable thickening of nerves (e.g. ulnar), impaired sensation, motor and sensory problems (muscle atrophy), neuropathic ulcers. 
• Eye involvement: lagophthalmia, uveitis, cataract, corneal involvement, optic neuropathy, diffuse involvement (panophthalmia leprosa), which can lead to loss of vision and blindness.

Hypopigmented macules with sensitivity loss can occur anywhere on the body. Leproma nodules are frequently located on the face, ears or hands.

Most commonly involved are the posterior tibial nerve, leading to anesthesia on the soles of the feet followed by the ulnar, median, lateral popliteal, and facial nerves.

There are 2 systems used for classification of leprosy:

• The Ridley-Jopling System is based on clinical (number of skinlesions; WHO) and histopathological features. It spans from indeterminate leprosy (IL, potential initial stage), tuberculoid leprosy (TT), to lepromatous leprosy (LL) and borderline leprosy (spectrum of transient forms, BT, BL, BB).

  • Single lesion leprosy.

  • 2-5 skin lesions (Paucibacillary leprosy).

  • More than 5 skin lesions (Multibacillary leprosy).

• The bacteriologic index of lesions reflects the density of leprae bacilli in the smear. It uses a logarithmic scale and ranges from 0 (No bacilli in any of the 100x oil-immersion fields) to 6+ (more than 1000 bacilli, on an average, in each oil-immersion field).

• Determination of the bacteriologic index in smears.

• Skin biopsy.

• A polymerase chain reaction in skin can be used to identify Mycobacterium leprae but can be negative in tuberculoid forms without ruling out the diagnosis.

• Tuberculoid leprosy: granulomas surrounding neurovascular elements and extend into the papillary dermis. Acid-fast bacilli are not seen.

• Lepromatous leprosy: atrophic epidermis with loss of the rete ridges. The papillary dermis is free, whereas the deeper dermis is diffusely infiltrated with macrophages (Virchow cells), lymphocytes, and plasma cells. Abundant acid-fast bacilli singly or in clumps.

• Borderline leprosy: small granulomas becoming more diffuse from borderline tuberculoid (BT) to borderline lepromatous (BL) disease.

• Histoid leprosy: This is a variant of lepromatous leprosy occurring in patients with lepromatous leprosy and inadequate or irregular therapy.Histology shows interlacing bundles of spindle‐shaped fusiform histiocytes in the dermis arranged in storiform or crisscross pattern.

Tuberculoid infection may resolve spontaneously, whereas borderline status gradually develop lepromatous infection.  

• Complications of leprosy include nerve damage, immunological reactions, and bacillary infiltration.

• Immune-mediated reactions may induce further  nerve damage and neuritis.

  • Type 1: type IV immunologic reaction; flare-up of old skin lesions and neuritis. Occurs during therapy.

  • Type 2: type III immunologic reaction in lepromatous or borderline leprosy. Skin changes known as erythema nodosum leprosum.

• Erythema nodosum leprosum (type 2 reactions, occurring in in 20% lepromatous leprosy) is an immune complex mediated reaction with fever, malaise, and neuritis. It may be superficial or deep, causing panniculitis.

• Secondary impairments like wounds, contractures, malum perforans (osteopathia ulceromutilans), chronic ulcers, mutilations due to digit resorption and blindness occur in 30-50 % of patients with nerve involvement.

• Lucio phenomenon is a vasculitis with inflammatory microthromboembolicocclusion of the dermal vasculature. It rarely occurs in lepromatous leprosy, presenting as painful irregular patches, which become purpuric, bullous and ulcerative and may be fatal.

Skin lesions with definite sensory loss and neurological defectsThe diagnosis is confirmed by the existence of a specific leproid granuloma histologically, and/or by the identification of M. leprae (by Ziehl-Neelsen or Fite, and immunohistochemistry staining and/or PCR) especially in lepromatous form.

Hypopigmented lesions: nevus depigmentosus, eczema, psoriasis, dermatophytes infection, seborrheic dermatitis, mycosis fungoides, vitiligo, pityriasis versicolor, dermatophyte infections, pityriasis rosea, cutaneous tuberculosis, granuloma anulare, hereditary sensory motor neuropathy type III, Refsum’s disease, amyloidosis.

Nodules: sarcoidosis, cutaneous lymphoma, leishmaniasis, syphilis. 

Vaccination is the most efficient method of preventing the contraction of leprosy:

• Bacillus Calmette Guerin (BCG) vaccination.

• Bacillus Calmette Guerin (BCG) vaccination plus killed M leprae.

Multidrug therapy (MDT) can cure leprosy and prevent disability.

• Paucibacillary leprosy: Rifampicin 600 mg administered once per month and Dapsone 100 mg/daily over 6 months.

• Multibacillary leprosy: Rifampicin 600 mg + clofazimine 300 mg administered once per month and Clofazimine 50 mg + dapsone 100 mg/daily over 12 months.

Erythema nodosum leprosum: immunosuppression.

Severe psychologic and socioeconomic impact. Rehabilitation is very important.