Enfermedad de Hansen

Leprosy as immune reconstitution disease has been reported in patients receiving antiretroviral therapy for HIV infection in countries where leprosy is endemic (BMJ 2007 Feb 3)

Infliximab reported to be effective for recurrent erythema nodosum leprosum (N Engl J Med 2006 Aug 17)
Description: mycobacterial infection, leprosy is also called Hansen's disease (Hansen discovered M. leprae)

Organs Involved: skin and peripheral nerves

Causes: Mycobacterium leprae and deficient cell-mediated immunity

Pathogenesis:

• M. leprae is psychrophilic, acid-fast bacillus (AFB) with high lipid content, very slow growing
• transmission via prolonged contact with respiratory secretions + skin lesions
• incubation period 2-6 years

Likely risk factors:

• recent immigrants
• endemic focus of Hansen's disease exists in Texas along Gulf of Mexico coast (Am J Trop Med Hyg. 1999 Mar;60(3):449 PDF in JAMA 1999 Jun 23/30;281(24):2270f)

Possible risk factors:

• leprosy as immune reconstitution disease has been reported in patients receiving antiretroviral therapy for HIV infection in countries where leprosy is endemic (BMJ 2007 Feb 3;334(7587):217)

Complications:

• trauma due to sensory loss
• chronic neuropathic pain described in 16 patients with multibacillary leprosy (Lancet 2000 Sep 23;356(9235):1080  , commentary can be found in Lancet 2001 Jan 27;357(9252):313  
•  

Associated conditions: erythema nodosum leprosum (ENL, type II Lepra reaction) develops in 10-50% patients treated for lepromatous leprosy; reactive syndrome with painful skin nodules, fever, malaise, wasting, vasculitis and peripheral neuritis; use of thalidomide for severe or recurrent ENL is associated with rapid relief of symptoms and signs and a decrease in elevated TNF-alpha (The Medical Letter 1996 Feb 16;38(968 ):15)

General Physical: possibly lymphadenopathy

Skin:

multiple nodular skin lesions

• differential diagnosis of annular lesions includes
• tinea corporis
• pityriasis rosea
• granuloma annulare
• sarcoidosis
• Hansen's disease (leprosy)
• urticaria
• subacute cutaneous lupus erythematosus
• erythema annulare centrifugum (case presentation and discussion in J Fam Pract 2005 Feb;54(2):131  picture in Am Fam Physician 2005 Aug 15;72(4):671)
• erythema chronicum migrans (Lyme disease)
• erythema multiforme
• psoriasis
• nummular eczema
• Reference – Am Fam Physician 2001 Jul 15;64(2):289

Testing to consider:

skin biopsy of lesions or nasal scrapings

• acid-fast bacilli (AFB) (Z-N/Fite) smear and histology
• Mycobacterium leprae polymerase chain reaction (PCR)

Blood tests: false positive for syphilis

Pathology tests:

• many AFB, foamy histiocytes
• picture can be found in N Engl J Med 2001 Apr 26;344(17):1293

Other diagnostic testing: negative lepromin skin test

Prognosis: multibacillary leprosy and nerve-function loss predict nerve-function impairment after 6 months of chemotherapy

• prospective study of 2510 patients with new diagnosis of leprosy followed for 2 years
• 166 developed nerve-function impairment
• risk of nerve-function impairment was
• 65% (95% confidence interval 56-73%) for patients with multibacillary leprosy and nerve-function loss at baseline
• 1.3% (95% CI 0.8-1.8%) for patients with paucibacillary leprosy and no nerve-function loss at baseline
• 16% (95% CI 12-20%) for patients with 1 of these 2 risk factors
• Reference – Lancet 2000 May 6;355(9215):1603 , commentary can be found in Lancet 2000 Nov 18;356(9243):1767 

Medications:

• recommended treatment of Hansen's disease
• treatment of paucibacillary disease
• rifampin (Rifadin) 600 mg monthly and dapsone 100 mg daily for 6 months (recommended by World Health Organization [WHO])
• rifampin 600 mg and daily and dapsone 100 mg daily for 12 months (has been recommended in United States)
• treatment of multibacillary disease
• rifampin 600 mg monthly, clofazimine (Lamprene) 300 mg monthly, dapsone 100 mg daily and clofazimine 50 mg daily for 12 months (recommended by WHO)
• rifampin 600 mg, dapsone 100 mg and clofazimine 50 mg daily for 2 years (has been recommended in Unites States, or use WHO regimen)
• single doses of rimpanin, ofloxacin (Floxin) and minocycline (Minocin) may be adequate for single skin lesions in paucibacillary leprosy
• Reference – Am Fam Physician 2002 Apr 1;66(7):1280
• antibiotic selection
• drug of choice – dapsone plus rifampin with or without clofazimine
• alternatives – minocycline, ofloxacin, clarithromycin
• Reference – Treatment Guidelines from The Medical Letter 2004 Mar;2(9):13
• adverse effects of dapsone
• frequent side effects – rash, transient headache, GI irritation, anorexia, infectious mononucleosis-like syndrome
• occasional side effects – cyanosis due to methemoglobinemia and sulfhemoglobinemia, other blood dyscrasias including hemolytic anemia, nephrotic syndrome, liver damage, peripheral neuropathy, hypersensitivity reactions, increased risk of lepra reactions, insomnia, irritability, uncoordinated speech, agitation, acute psychosis
• rare side effects – renal papillary necrosis, severe hypoalbuminemia, epidermal necrolysis, optic atrophy, agranulocytosis, neonatal hyperbilirubinemia after use in pregnancy
• case report of dapsone hypersensitivity syndrome can be found in Journal of Occupational Medicine and Toxicology 2006 Jun 6;1:9
• thalidomide
• thalidomide has shown efficacy in thousands of leprosy patients with painful sores, FDA approval expected with strictest controls in history such as signed informed consent, provision of pregnancy testing + birth control information, + possibly even picture of birth-deformed child on packaging (Cortlandt Forum 1997 Nov;10(11);79)

thalidomide (Thalomid) FDA approved for erythema nodosum leprosum, immune reaction to dead bacteria after treatment of leprosy, call 732-271-1001 for details (Monthly Prescribing

• Reference 1998 Sep;A-23)
• thalidomide (Thalomid) 50 mg costs pharmacist $630 for 84 capsules, special registration of physician + pharmacists required for prescription; adverse effects include teratogenicity even with small doses, peripheral neuropathy (may be irreversible), sedation, constipation, orthostatic hypotension, dry mouth, dry skin, rash, edema, hypothyroidism, neutropenia (The Medical Letter 1998 Oct 23;40(1038):103)
• low dose prednisolone during first 4 months of multidrug treatment for leprosy reduces short-term incidence of new reactions and nerve function impairment (l)
• 636 patients aged 15-50 years with newly diagnosed multibacillary leprosy treated with multidrug treatment for 1 year and randomized at onset to prednisolone (20 mg/day for 3 months then tapered over 1 month) vs. placebo
• 90% follow-up rates and intent to treat analysis
• comparing prednisolone vs. placebo
• 4% vs. 15% had skin or nerve reaction at 4 months (NNT 9)
• effect not sustained at 1 year when 22% vs. 17% had skin or nerve reaction (not significant)
• prednisolone only effective in patients without pre-existing nerve function impairment
• Reference – BMJ 2004 Jun 19;328(7454):1459, editorial can be found in BMJ 2004 Jun 19;328(7454):1447
• non-significant increased risk at 1 year suggests that prednisolone may delay instead of prevent reactions (DynaMed commentary)
• infliximab reported to be effective for recurrent erythema nodosum leprosum in case report (N Engl J Med 2006 Aug 17;355(7):739)

Prevention: dapsone for close family contacts

References including Reviews and Guidelines

Reviews:

• discussion of leprosy can be found in Lancet 1999 Feb 20;353(9153):655
• review of leprosy can be found in CMAJ 2004 Jan 6;170(1):71  
• review of leprosy can be found in Lancet 2004 Apr 10;363(9416):1209  commentary can be found in Lancet 2004 Jun 5;363(9424):1911
• cohort of 184 leprosy patients in Canada described in CMAJ 2004 Jan 6;170(1):55  case presentation and discussion can be found in Postgrad Med 2000 May 1;107(5):87
• case presentation can be found in Lancet 2006 Apr 29;367(9520):1458  case presentation can be found in N Engl J Med. 2004 Jan 8;350(2):166
• review of antimycobacterial therapy can be found in Mayo Clin Proc 1999 Oct;74(10):1038 (summary can be found in Am Fam Physician 2000 Feb 1;61(3):861)

Authors:

Brian S. Alper MD, MSPH (Editor-in-Chief, DynaMed, Ipswich, Massachusetts, USA)