This is described in Chapter 9.
Leprosy
Leprosy (Hansen’s disease) is a chronic granulomatous disease affecting skin and nerve and is caused by Mycobacterium leprae. The clinical form of the disease is determined by the degree of cell-mediated immunity (CMI) expressed by that individual towards M. leprae. High levels of CMI with elimination of leprosy bacilli produce tuberculoid leprosy, whereas absent CMI results in lepromatous leprosy. Complications arise as a result of nerve damage, immunological reactions and bacillary infiltration. It affects 4 mil- lion people worldwide, 70% of whom live in India; it is also endemic in Brazil, Indonesia, Mozambique, Madagascar, Tanzania and Nepal.
Untreated lepromatous patients discharge bacilli from the nose. Infection occurs through the nose, followed by haematogenous spread to skin and nerve. The incubation period is 2 to 5 years for tuberculoid cases and 8 to 12 years for lepromatous cases.
Clinical features
The cardinal features are skin lesions with anaesthesia, thickened periph- eral nerves and acid- fast bacilli on skin smear or biopsy. The features of the two principal types of leprosy are compared in Box 5.17.
Skin: The most common skin lesions are macules or plaques. Tubercu- loid patients have a few hypopigmented lesions. In lepromatous leprosy, papules, nodules or diffuse infiltration of the skin occur. Confluent lesions on the face can lead to a ‘leonine facies’ (Fig. 5.9).
Anaesthesia: In skin lesions, the small dermal sensory and autonomic nerve fibres are damaged, causing localised sensory loss and loss of sweating. Anaesthesia can occur in the distribution of a large peripheral nerve, or in a ‘glove and stocking’ distribution.
Nerve damage: Peripheral nerve trunks are affected at ‘sites of predi- lection’, including the ulnar (elbow), median (wrist), radial (humerus, caus- ing wrist drop), radial cutaneous (wrist), common peroneal (knee), posterior tibial nerves and the sural nerves at the ankle; the facial nerve as it crosses the zygomatic arch; and the great auricular nerve in the posterior triangle
5
Management
B. anthracis can be cultured from swabs of skin lesions. Skin lesions are readily curable with early antibiotic therapy. Treatment is with ciprofloxacin until penicillin susceptibility is confirmed; the regimen can then be changed to benzylpenicillin IM. The addition of an aminoglycoside may improve the outlook. Two months of ciprofloxacin or doxycycline is then given to eradi- cate spores. Prophylaxis with ciprofloxacin is recommended for anyone at high risk of exposure to biological warfare.
Bacterial infections with neurological involvement
Bacterial meningitis, botulism and tetanus are dealt with in Chapter 16.
Mycobacterial infections
TuberculosisThis is described in Chapter 9.
Leprosy
Leprosy (Hansen’s disease) is a chronic granulomatous disease affecting skin and nerve and is caused by Mycobacterium leprae. The clinical form of the disease is determined by the degree of cell-mediated immunity (CMI) expressed by that individual towards M. leprae. High levels of CMI with elimination of leprosy bacilli produce tuberculoid leprosy, whereas absent CMI results in lepromatous leprosy. Complications arise as a result of nerve damage, immunological reactions and bacillary infiltration. It affects 4 mil- lion people worldwide, 70% of whom live in India; it is also endemic in Brazil, Indonesia, Mozambique, Madagascar, Tanzania and Nepal.
Untreated lepromatous patients discharge bacilli from the nose. Infection occurs through the nose, followed by haematogenous spread to skin and nerve. The incubation period is 2 to 5 years for tuberculoid cases and 8 to 12 years for lepromatous cases.
Clinical features
The cardinal features are skin lesions with anaesthesia, thickened periph- eral nerves and acid- fast bacilli on skin smear or biopsy. The features of the two principal types of leprosy are compared in Box 5.17.
Skin: The most common skin lesions are macules or plaques. Tubercu- loid patients have a few hypopigmented lesions. In lepromatous leprosy, papules, nodules or diffuse infiltration of the skin occur. Confluent lesions on the face can lead to a ‘leonine facies’ (Fig. 5.9).
Anaesthesia: In skin lesions, the small dermal sensory and autonomic nerve fibres are damaged, causing localised sensory loss and loss of sweating. Anaesthesia can occur in the distribution of a large peripheral nerve, or in a ‘glove and stocking’ distribution.
Nerve damage: Peripheral nerve trunks are affected at ‘sites of predi- lection’, including the ulnar (elbow), median (wrist), radial (humerus, caus- ing wrist drop), radial cutaneous (wrist), common peroneal (knee), posterior tibial nerves and the sural nerves at the ankle; the facial nerve as it crosses the zygomatic arch; and the great auricular nerve in the posterior triangle
of the neck. All these nerves should be examined for enlargement and tenderness, and tested for motor and sensory function. The CNS is not affected.
Eye involvement: Blindness is a devastating complication for a patient with anaesthetic hands and feet. Eyelid closure is impaired when the facial (7th) nerve is affected. Damage to the trigeminal nerve causes anaesthesia of the cornea and conjunctiva. The cornea is then susceptible to trauma and ulceration.
Other features: These include nasal collapse caused by destruction of bone and cartilage, and hypogonadism from testicular atrophy.
Borderline cases
Borderline tuberculoid (BT): The skin lesions are more numerous than in tuberculoid leprosy, and there is more severe nerve damage. These patients are prone to type 1 reactions (see later) with consequent nerve damage.
Borderline leprosy (BB): Patients have numerous skin lesions varying in size, shape and distribution. Annular lesions are characteristic, and nerve damage is variable.
5.17 Clinical characteristics of the polar forms of leprosy Clinical and tissue-
specific features Lepromatous Tuberculoid Skin and nerves
Number and distribution Wide dissemination Few sites, asymmetrical Skin lesions
Margin–definition Poor Good
–elevation Never Common
Colour–dark skin Slight hypopigmentation Marked hypopigmentation
–light skin Slight erythema Coppery or red
Surface Smooth, shiny Dry, scaly
Central healing None Common
Sweat, hair Impaired late Impaired early
Loss of sensation Late Early, marked
Nerve enlargement/
damage Late Early, marked
Bacilli Many Absent
Natural history Progressive Self- healing
Other tissues Upper respiratory mucosa, eye, testes, bone, muscle None
Reactions Immune complexes
(type 2) Cell- mediated (type 1)
Borderline lepromatous leprosy (BL): There are widespread small macules and nerve involvement. Patients may experience both type 1 and type 2 reactions.
Pure neural leprosy: This type occurs principally in India, and accounts for 10% of cases. Asymmetrical peripheral nerve involvement occurs with- out skin lesions.
Leprosy reactions
These are events superimposed on the cardinal features described above.
Type 1 (reversal) reactions: These occur in 30% of borderline patients (BT, BB, BL), and are delayed hypersensitivity reactions. Skin lesions become erythematous; peripheral nerves become tender and painful with sudden loss of nerve function. Reversal reactions may occur spontaneously, after starting treatment or after completion of multidrug therapy.
Type 2 (erythema nodosum leprosum (ENL)) reactions: Partly caused by immune complex deposition, these occur in BL and lepromatous patients who produce antibodies and have a high antigen load. Patients develop malaise, fever and crops of small pink nodules on the face and limbs. Iritis and episcleritis are common. Other signs are acute neuritis, lymphadenitis, orchitis, bone pain, dactylitis, arthritis and proteinuria. ENL may continue intermittently for several years.
Investigations
• Slit skin smears: dermal material is scraped on to a glass slide and stained, then acid- fast bacilli are counted by microscopy. • Skin biopsy:
histological examination may aid diagnosis. • Neither serology nor PCR testing is sensitive or specific enough for diagnosis.
Fig. 5.9 Lepromatous leprosy. Widespread nodules and infiltration with loss of the eyebrows. This man also has early collapse of the nose.
5
Management
Multidrug treatment (MDT) is required for all leprosy patients (Box 5.18).
Rifampicin is a potent bactericidal for M. leprae, but should always be given with other drugs, as a single mutation can confer resistance. Dapsone is bacteriostatic. It commonly causes mild haemolysis and, rarely, anaemia.
Clofazimine is a red, fat- soluble crystalline dye that is weakly bactericidal for M. leprae. Skin discoloration (red to purple- black) and ichthyosis are troublesome side effects, particularly on pale skins. Newer drugs such as perfloxacin, ofloxacin, clarithromycin and minocycline are now established second- line options.
Treatment of reactions: Most reactions respond to high- dose oral pred- nisolone. Thalidomide may also be used, but teratogenicity limits its use in women who may become pregnant. Hydrocortisone eye drops are used for ocular symptoms.
Patient education and rehabilitation: Patients should be reassured that after 3 days of chemotherapy they are not infectious and can lead a normal social life. Additional measures include:
• Patients with anaesthetic hands or feet need to avoid and treat burns or other minor injuries. • Good footwear is important. • Ulceration: the cause of the injury should be identified, and the patient advised not to weight- bear until the ulcer has healed. • Physiotherapy: can help prevent contractures and muscle atrophy.
Prognosis
Tuberculous leprosy may self- heal, but lepromatous leprosy has high mor- bidity if untreated.
Most patients, especially those without nerve damage at the time of diag- nosis, do well on MDT, with resolution of skin lesions. Borderline patients are at risk of developing type 1 reactions, which may result in devastating nerve damage.
5.18 Modified WHO- recommended multidrug therapy regi- mens in leprosy
Type of leprosya Monthly super- vised treatment
Daily self- administered
treatment Duration of treatmentb Paucibacillary Rifampicin 600 mg Dapsone 100 mg 6 months Multibacillary Rifampicin 600 mg
Clofazimine 300 mg
Clofazimine 50 mg Dapsone 100 mg
12 months Paucibacillary
single lesion Ofloxacin 400 mg Rifampicin 600 mg Minocycline 100 mg
Single dose
a WHO classification for field use when slit-skin smears are not available:
• paucibacillary single lesion (1 lesion) • paucibacillary (2–5 skin lesions) • multibacillary (>5 skin lesions).
b Multibacillary patients with a high bacillary index need at least 24 moths treatment
Prevention and control
Programmes aimed at case detection and provision of MDT are now in place in many of the countries affected by leprosy. BCG vaccination has been shown to give good but variable protection against leprosy; adding killed M. leprae to BCG does not give enhanced protection.