History

Fact Explanation
Painless skin patch. Histological changes in the skin including chronic inflammatory infiltrates, epithelioid granulomata with giant cells and epidermal erosions lead to the appearance of these skin patches [1].
Muscle weakness and wasting. Due to Mycobacterium leprae attacking peripheral nerves causing subsequent muscular denervation [2].
Paresthesia. Due to the neuropathy as a result of chronic granulomatous inflammation secondary to mycobacterial invasion of the schwann cells [3].
Foot drop. Due to leprous peripheral neuropathy of the peroneal nerve [4].
Corneal ulceration. Due to reduced corneal and conjunctival sensation as a result of involvement of the ophthalmic branch of the trigeminal nerve [5].
Ulceration of hands and feet. Due to involvement of the posterior tibial nerve causing anaesthesia on the soles of the feet as well as involvement of the ulnar and median nerves producing anaesthesia of the palms of the hands resulting in unrecognized trauma [5].
Sudden onset of skin redness. It's an inflammatory reaction due to delayed-type hypersensitivity and an increase in cell mediated immunity to M. leprae antigens [6]. (It's also known as Type 1 reversal reaction)
Skin nodules associated with fever and muscle and joint pain. This occurs as part of a systemic inflammatory response in patients with a high bacterial load and with little or no cellular immunity to M. leprae [7]. (It's also known as Erythema nodosum leprosum)
History of travel to an endemic area. People with lepromatous leprosy act as important reservoirs for M. leprae. Transmission occurs via the respiratory route, through nasal discharge or skin-to-skin contact [8].
References
  1. FACER P., et al. Correlation of quantitative tests of nerve and target organ dysfunction with skin immunohistology in leprosy. Brain[online] 1998, vol 121(12): 2239-2247. [viewed 18 April 2014] Available from: DOI: 10.1093/brain/121.12.2239
  2. WERNECK Lineu Cesar, Hélio AG TEIVE, and Rosana Herminia SCOLA. Muscle involvement in leprosy: study of the anterior tibial muscle in 40 patients. Arquivos de neuro-psiquiatria[online] 1999, 57, no. 3B: 723-734. [viewed 18 April 2014] Available from: DOI: 10.1590/S0004-282X1999000500001
  3. KIRAN C.M. and Roshni MENON. Fine needle aspiration cytology as an aid to diagnosis, categorization and treatment when pure neuritic leprosy presents as nerve abscess. J Cytol.[online] 2013, vol 30(4): 237–240. [viewed 18 April 2014] Available from: DOI: 10.4103/0970-9371.126648
  4. CHOE W. Leprosy presenting as unilateral foot drop in an immigrant boy. Postgrad Med J [online] 1994, 70:111-112 [viewed 18 April 2014] Available from: DOI: 10.1136/pgmj.70.820.111
  5. WALKER S. L. and D. N. J. LOCKWOOD. The clinical and immunological features of leprosy. Br Med Bull[online] 2006, 77-78 (1): 103-121. [viewed 18 April 2014] Available from: DOI: 10.1093/bmb/ldl010
  6. ANDERSSON Anna K., et al. Effects of Prednisolone Treatment on Cytokine Expression in Patients with Leprosy Type 1 Reactions. Infect. Immun.[online] June 2005, vol. 73(6): 3725-3733. [viewed 18 April 2014] Available from: DOI: 10.1128/IAI.73.6.3725-3733.2005
  7. STEFANI Mariane M., et al. Potential plasma markers of type 1 and type 2 leprosy reactions: a preliminary report. BMC Infectious Diseases[online] 2009, 9:75. [viewed 18 April 2014] Available from: DOI: 10.1186/1471-2334-9-75
  8. BRICKELL K., R. FRITH and R. ELLIS-PEGLER. Leprosy in a Backpacker. Journal of Travel Medicine[online] 2005, 12: 161–163. [viewed 18 April 2014] Available from: DOI: 10.2310/7060.2005.12307

Examination

Fact Explanation
Skin lesions range from solitary hypopigmented macules to bilaterally symmetric nodules/plaques/papules which are commonly found in the face, buttocks and extensor surfaces of the limbs. M. leprae favors the cooler areas of the body [1]. Hypopigmented macules occur in tuberculoid leprosy while the bilateral lesions occur in lepromatous leprosy.
Loss of sweating over the skin lesions. Sweat glands are a target for inflammation in the affected sites, which leads to glandular destruction and atrophy [2]. This is more commonly a feature of tuberculoid leprosy.
Thickened peripheral nerves. The chronic granulomatous immune response to infection of the nerves with Mycobacterium leprae results in nerve damage and thickening [3]. This is more commonly a feature of tuberculoid leprosy.
Muscle atrophy. Due to Mycobacterium leprae attacking peripheral nerves causing subsequent muscular denervation [4]. This is more commonly a feature of tuberculoid leprosy.
Saddle deformity of the nose. Due to septal perforation and destruction of the anteriornasal spine as a result of infiltration of these structures by M. leprae [5]. This is a feature of lepromatous leprosy.
Leonine facies. Due to skin thickening as a result of dermal infiltration [5]. This is a feature of lepromatous leprosy.
Axillary and inguinal lymphadenopathy. Due to the multisystem involvement of lepromatous leprosy and type 2 reactions giving rise to a picture of leprous lymphadenitis [6].
References
  1. ERICSSON Charles D., et al. Update on Leprosy in Immigrants in the United States: Status in the Year 2000. Clin Infect Dis.[online] 2001, 32 (6): 930-937.[viewed 18 April 2014] Available from: DOI: 10.1086/319357
  2. FACER P., et al. Correlation of quantitative tests of nerve and target organ dysfunction with skin immunohistology in leprosy. Brain[online] 1998, vol 121(12): 2239-2247. [viewed 18 April 2014] Available from: DOI: 10.1093/brain/121.12.2239
  3. JAIN Suman, et al. High-resolution sonography: a new technique to detect nerve damage in leprosy. PLoS neglected tropical diseases[online] 2009, 3(8): e498.[viewed 18 April 2014] Available from: DOI: 10.1371/journal.pntd.0000498
  4. WERNECK Lineu Cesar, Hélio AG TEIVE, and Rosana Herminia SCOLA. Muscle involvement in leprosy: study of the anterior tibial muscle in 40 patients. Arquivos de neuro-psiquiatria[online] 1999, 57, no. 3B: 723-734. [viewed 18 April 2014] Available from: DOI: 10.1590/S0004-282X1999000500001
  5. WALKER S. L. and D. N. J. LOCKWOOD. The clinical and immunological features of leprosy. Br Med Bull[online] 2006, 77-78 (1): 103-121. [viewed 18 April 2014] Available from: DOI: 10.1093/bmb/ldl010
  6. MALIK A., et al. Fine Needle Aspiration Cytology of Reactions in Leprosy. Acta Cytologica[online] 1999, 43:771-776 [viewed 19 April 2014] Available from: DOI: 10.1159/000331290

Differential Diagnoses

Fact Explanation
Vitiligo. It is characterized by autoimmune destruction of epidermal melanocytes resulting in depigmentation rather than hypopigmentation [1].
Hereditary sensory motor neuropathy type III. Nerve thickening is a feature [2].
Sarcoidosis. It causes granulomatous skin lesions [2].
References
  1. OGG Graham S., et al. High Frequency of Skin-homing Melanocyte-specific Cytotoxic T Lymphocytes in Autoimmune Vitiligo. JEM[online] 1998, vol 188(6): 1203-1208. [viewed 19 April 2014] available from: DOI: 10.1084/jem.188.6.1203
  2. WALKER S. L. and D. N. J. LOCKWOOD. The clinical and immunological features of leprosy. Br Med Bull[online] 2006, 77-78 (1): 103-121. [viewed 18 April 2014] Available from: DOI: 10.1093/bmb/ldl010

Investigations - for Diagnosis

Fact Explanation
Slit skin smear- The lesion is pinched until it blanches and an incision is made through the thickness of the dermis. The cellular exudates obtained can be assessed for acid fast bacilli using the Zeihl-Neelsen technique [1].
Skin/ peripheral nerve biopsy- Skin biopsies should be full dermal thickness obtained from the edge of the lesion. For the detection of inflammatory infiltrates and the presence of large numbers of bacilli [2].
Polymerase chain reaction (PCR) for amplification of Mycobacterium leprae DNA It is more sensitive than microscopic examination for direct detection of bacilli [3].
Serological tests to detect IgM immunoglobulin to PGL-I. PGL-I is a glycolipid specific to M. leprae. It has also proved to be useful as a predictive tool for leprosy reactions [4].
Mitsuda test. It measures the granulomatous immune response to intradermally injected heat-killed leprosy bacilli (lepromin), and is an indicator of efficient anti-leprosy immunity because it has a good prognostic value for susceptibility (when negative) or resistance (when positive) to the lepromatous form of the disease [5].
References
  1. SINGH N., A. BHATIA, K. GUPTA and M. RAMAN. Cytomorphology of Leprosy Across the Ridley-Jopling Spectrum. Acta Cytologica[online] 1996, 40:719–723 [viewed 19 April 2014] Available from: DOI: 10.1159/000333945
  2. DE FREITAS Marcos R.G., et al. Small-fiber polyneuropathy in leprosy without skin changes: study of 17 cases. Arq. Neuro-Psiquiatr[online] 2003, vol 61(3A) [viewed 19 April 2014] Available from: DOI: 10.1590/S0004-282X2003000400003
  3. SANTOS A.R. Use of PCR-mediated amplification of Mycobacterium leprae DNA in different types of clinical samples for the diagnosis of leprosy. J Med Microbiol[online] October 1993, vol 39(4): 298-304 [viewed 19 April 2014] Available from: DOI: 10.1099/00222615-39-4-298
  4. DE MOURA Rodrigo Scaliante, Karla Lucena CALADO, Maria Leide W. OLIVEIRA and Samira BUHRER-SEKULA. Leprosy serology using PGL-I: a systematic review. Revista da Sociedade Brasileira de Medicina Tropical[online] 2008, 41(2): 11-18. [viewed 19 April 2014] Available from: DOI: 10.1590/S0037-86822008000700004
  5. ALCAIS A., et al. Granulomatous Reaction to Intradermal Injection of Lepromin (Mitsuda Reaction) Is Linked to the Human NRAMP1 Gene in Vietnamese Leprosy Sibships. J Infect Dis.[online] 2000, vol 181(1): 302-308. [viewed 19 April 2014] Available from: DOI: 10.1086/315174

Investigations - Followup

Fact Explanation
Full blood count. Dapsone which is used in the treatment of leprosy is known to cause haemolytic anemia and agranulocytosis [1].
Liver function tests. Rifampicin which is used in the treatment of leprosy is known to cause liver impairment [2].
References
  1. KOBE Yoshiro, Daisuke SETOGUCHI and Nobuya KITAMURA. Dapsone-induced agranulocytosis leading to perianal abscess and death: a case report. Journal of medical case reports[online] 2011, 5(1): 1-4. [viewed 20 April 2014] available from: DOI: 10.1186/1752-1947-5-107
  2. IJAZ Kashef, et al. Severe or Fatal Liver Injury in 50 Patients in the United States Taking Rifampin and Pyrazinamide for Latent Tuberculosis Infection. Clin Infect Dis.[online] 2006, 42 (3): 346-355. [viewed 20 April 2014] available from: DOI: 10.1086/499244

Management - Specific Treatments

Fact Explanation
Dapsone: Paucibacillary- 100mg daily (6-12 months) Multibacillary- 100mg daily (24 months) It has antimicrobial activity against M. leprae, anti inflammatory activity and immunostimulatory activity [1].
Rifampicin: Paucibacillary- 600mg monthly (6-12 months) Multibacillary- 600mg monthly (24 months) It has a strong bactericidal effect against Mycobacterium leprae [2].
Clofazimine: Multibacillary- 50mg daily 300mg monthly Should be taken for 24 months. It has antimycobacterial activity and anti inflammatory activity [3].
High dose steroids (eg: Prednisolone 60mg daily) for type 1 and 2 leprosy reactions. These reactions occur as acute inflammatory episodes. Therefore treatment requires immnuosuppressive drugs [4].
Thalidomide for erythema nodosum leprosum (ENL). TNF alpha plays a role in the pathogenesis of ENL. Thalidomide inhibits its production [5].
References
  1. ANDERSON R., et al. In vitro and in vivo effects of dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy. Antimicrob. Agents Chemother.[online] 1981, 19(4):495. [viewed 20 April 2014] Available from: DOI: 10.1128/AAC.19.4.495
  2. MOET F. Johannes, David PAHAN, Linda OSKAM, and Jan H. RICHARDUS. Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial. Bmj [online] 2008, 336(7647): 761-764. [viewed 20 April 2014] Available from: DOI: 10.1136/bmj.39500.885752.BE
  3. VAN RENSBURG C.E., E.M. GATNER, F.M. IMKAMP and R. ANDERSON. Effects of clofazimine alone or combined with dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy. Antimicrob. Agents Chemother.[online] May 1982, vol 21(5): 693-697. [viewed 20 April 2014] Available from: DOI: 10.1128/AAC.21.5.693
  4. GARBINO José Antonio, et al. A randomized clinical trial of oral steroids for ulnar neuropathy in type 1 and type 2 leprosy reactions. Arq. Neuro-Psiquiatr.[online] 2008, vol 66(4): 861-867. [viewed 20 April 2014] Available from: DOI: 10.1590/S0004-282X2008000600016
  5. SAMPAIO Elizabeth P., et al. The Influence of Thalidomide on the Clinical and Immunologic Manifestation of Erythema Nodosum Leprosum. J Infect Dis. [online] 1993, 168 (2): 408-414. [viewed 20 April 2014] Available from: DOI: 10.1093/infdis/168.2.408