Leprosy (ORPHA:548)
A chronic infectious disease affecting primarily the skin and peripheral nervous system.
Epidemiology
Worldwide annual incidence is estimated at 250,000 cases, with a large majority in India and Brazil.
Clinical description
A wide clinical spectrum has been described from a polar tuberculoid (localized) form (TT) to a polar lepromatous (disseminated) one (LL). Borderline forms exist: borderline tuberculoid, borderline borderline and borderline lepromatous (BT, BB, BL). Tuberculoid leprosy (TLep) or paucibacillary form includes TT and BT and lepromatous leprosy (LLep) or multibacillary form includes LL, BL and BB. The incubation time ranges from several months to more than 20 years and does not exceed 5 years in TLep. After contact with Mycobacterium leprae, only 5% of patients develop the disease, almost all with cutaneous lesions and variably severe peripheral neuropathy. In TLep, initially a few large lesions are found (1 to 10). They appear as well demarcated hypopigmented, macules or erythematous plaques. A characteristic loss of sensation at the skin lesion is always present. In LLep, the cutaneous lesions are numerous (10 to 100 or more), normoesthesic, poorly demarcated hypopigmented macules or erythematous papules or nodules and sometimes plaques and may induce diffuse infiltration causing a leonine facies. Mucosas are affected leading in severe cases to nasal destruction, and corneal or laryngeal impairment. Visceral involvement (adenopathies, hepato-splenomegaly or orchiepididymitis) may be present. Neural involvement affects especially the ulnar, median, radial, external popliteal and tibial posterior nerves, with a greater risk in TLep than LLep of distal (hands and feet) anesthesia, palsy (foot drop or clawed hands) and amyotrophy. About 40% of patients may develop 2 types of reactional states: 1) reversal reaction (RR; inflammation of the skin lesions and severe acute neuritis) or down-grading reaction (increased number of lesions) and 2) erythema nodosum leprosum (ENL; vasculitis with painful and eruptive erythematous nodules, fever, neuritis and joint swelling) or Lucio's phenomenon (granulomatous vasculitis with painful necrotic macules).
Etiology
The disease is caused by M. leprae, a mycobacterium for which the main reservoir is humans and some species of armadillos. Recently M. lepromatosis was identified as causing some LLep cases. Possible predisposing genetic factors have been found.
Diagnostic methods
Diagnosis is based on clinical, histopathological and bacteriological findings. Skin biopsy is used to determine the form. Examination of slit skin smears enables quantitative evaluation of the bacterial load, usually low or nil in TLep and always high in LLep. PCR assays in tissue may accurately detect M. leprae's 16s rRNA in LLep cases and gene mutations inducing antibiotic resistance. It is generally negative in TLep and only gives a qualitative score.
Differential diagnosis
Differential diagnosis includes hypochromic eczematides, annular granuloma, annular erythema, dermatophyties and annular sarcoidosis in TLep, and pityriasis versicolor, post-inflammatory hypomelanosis, hypochromic or papulo-nodular sarcoidosis, Kaposi sarcoma, syphilis, lymphoma, cutaneous leukemia in LLep.
Management and treatment
There are 2 treatment groups: paucibacillary (PB; up to 5 skin lesions) and multibacillary (MB; more than 5). The recommended therapy combines 2 antibiotics (for PB) or 3 (for MB): rifampicin, dapsone and clofazimine. In some cases, other drugs can be used (ofloxacin, minocycline, clarithromycin). Treatment duration is 6 months for PB and at least 1 year for MB. Reactional states can be treated with systemic corticosteroids and sometimes surgical neurolysis for RR, and thalidomide, corticosteroids or pentoxifylline for ENL.
Prognosis
Prognosis is favorable when antibacillary and anti-reactional treatments are rapidly instituted. If not, the disease may lead to definitive neurological disabilities.

                            Last update: 
                            September 2011


                            - Expert reviewer(s): 
                            Dr Béatrice FLAGEUL