Leprosy

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Leprosy

  1. 1. LEPROSY
  2. 2. INTRODUCTION  Chronic granulomatous infectious disease.  Caused by Mycobacterium leprae  Mainly involves the peripheral nerves and skin  Other organs may involve: Mucosa of mouth Upper respiratory tract Eyes Bones & Muscles. Testes etc. Commonly involves every organ except : CNS, Ovary and Lungs.
  3. 3. Epidemiology WORLDWIDE AND INDIA
  4. 4. Distribution  Prevalence  Worldwide distribution but essentially a disease of developing countries.  The prevalence rate has dropped by 90 percent from 21.1cases/10000 in 1985 to <1/10000 in 2000.  To date there has been no resistance to antileprosy medicines when used as MDT.
  5. 5. WORLDWIDE PREVALENCE AT THE TURN OF CENTURY
  6. 6. Leprosy Situation in India The goal of leprosy elimination at National level (i.e. PR of <1 case/10,000 population) as set by National Health Policy 2002 had been achieved in the month of December 2005.
  7. 7.  associated with poverty and rural residence  not associated with AIDS, perhaps because of leprosy's long incubation period  time of peak onset is in the second and third decades of life  India and Africa, 90% of cases are tuberculoid  most severe lepromatous form of leprosy is twice as common among men as among women and is rarely encountered in children
  8. 8. Bacteriology
  9. 9. Lepra bacilli  Gram positive Obligate intracellular bacillus - due to its large pool of non functional genes.  Acid fast stained with modified Fite stain or ZN stain  Occurs characteristically in clumps or bundles( “globi”)  Affinity for Schwann cells & cells of R-E system .  M. leprae grows best in cooler tissues (the skin, peripheral nerves, anterior chamber of the eye, upper respiratory tract, and testes), sparing warmer areas of the skin (the axilla, groin, scalp, and midline of the back).  Optimal temp. for growth is 30-33 centigrade
  10. 10. M. leprae remains one of the few bacterial species that still has not been cultivated on artificial medium or tissue culture and produces no known toxins, but can grow in  Nude mouse  Nine banded armadillos(best)
  11. 11. The Leprosy Bacteria
  12. 12. Reservoir of infection  Main reservoir : Human being  Lepromatous case> Non lepromatous cases  Animal reservoirs  9-banded armadillos  Chimpanzees  Mangabey monkeys  Sphagnum moss
  13. 13. Portal of exit  Major portal of exit : Nasal Mucosa  LL cases harbour millions of M. leprae in their nasal mucosa discharged when they sneeze or blow nose.  Ulcerated or broken skin of bacteriologically positive cases
  14. 14. Mode of transmission  Transmission by inhalation  Droplet infection(most common)  Transmission by contact  Skin to skin contact with infectious cases  Contact with soil or fomites  Other Routes  Insect Vectors e.g.. Mosquito, Bedbugs  Tattooing needles NB : Breast feeding and Transplacental infection do not occur.
  15. 15. Incubation period  Long incubation period  Ranged: 2 to 40 years or more  Average: 3-5 years  Generation time : 12 days(1 day and 20 min for M. tuberculosis and Escherichia coli, respectively)  Infectivity : Leprosy is a highly infectious disease with low pathogenicity. Among household contacts of lepromatous cases about 5 to 12 percent is expected to show signs of leprosy within 5 yrs.
  16. 16. VIRULENCE FACTOR  The bacterium's complex cell wall contains large amounts of an M. leprae–specific phenolic glycolipid (PGL-1), which is detected in serologic tests.  The unique trisaccharide of M. leprae binds to the basal lamina of Schwann cells; this interaction is probably relevant to the fact that M. leprae is the only bacterium to invade peripheral nerves.
  17. 17. Host Factors  Leprosy affects all age groups but incidence generally rises to a peak between 10 to 20 years of age and then fall.  Higher incidence is seen in males, more marked among adults, more marked among lepromatous cases.  Cell Mediated Immunity is responsible for resistance to infection with M.leprae. In lepromatous leprosy there is complete breakdown of CMI.
  18. 18. CLASSIFICATION OF LEPROSY
  19. 19. Various Classifications  Indian Classification : clinicobacteriological  Madrid Classification : clinicobacteriological  Ridley Jopling classification : immunohistological  Classification by WHO Study Group on Chemotherapy of Leprosy : clinicobacteriological.
  20. 20. Ridley- Jopling 1966 (Research purposes)  Most widely accepted  Divides Leprosy cases into five groups according to their position on an immunohistological scale.  It can be used only when full research facilities are available :  Tuberculoid (TT)  Borderline Tuberculoid (BT)  Borderline Borderline (BB)  Borderline Lepromatous (BL)  Lepromatous (LL)
  21. 21. Indian classification  Indeterminate type  Tuberculoid type  Borderline type  Lepromatous type  Pure neuritic type
  22. 22. Immunity in leprosy (-) (+) LLHD BLHD BBHD BTHD TTHD TT -paucibacillary state, few lesions due to high immune response LL - multibacillary state with multiple lesions due to low immune response
  23. 23. Contd..  Borderline forms (BB, BT and BL) lie between these two poles and are immunologically unstable, tending to move towards one of the polar forms
  24. 24. Immunology & bacteriology in leprosy (spectrum) Bacilli Bacilli (-) (+) (++) (+++) (+++) (++) (+) (-) Immunity Immunity LLHD
  25. 25. Clinical Feature on Skin Lesion Paucibacillary Leprosy PB Multi Bacillary Leprosy MB Including macular flat lesion, papules & nodules 1 to 5 lesion Asymmetrical distribution Definite loss of sensation  BI <2 at all sites in the initial skin smear More than 5 lesion Symmetrical distribution Loss of sensation may or may not be present  BI >= 2 at any site in the initial skin smear WHO Classification(1981,87,93)
  26. 26. W H O classification (For chemotherapy – M. leprae) Paucibacillary  Indeterminate - I  Tuberculoid – TT  Borderline Tuberculoid – BT  If any of these have positive bacterial index they should be classified as multibacillary for multidrug therapy Multibacillary  Mid borderline – BB  Borderline Lepromatous – BL  Lepromatous – LL  All smear positive cases
  27. 27. Clinical Feature
  28. 28. Indeterminate Leprosy  Earliest & transitory stage  One or two vague hypopigmented macule with definite sensory impairment.
  29. 29. Indeterminate Leprosy  If untreated may progress towards tuberculoid, borderline or lepromatous leprosy  Spontaneous regression may occur  Bacteriologically Negative
  30. 30. Tuberculoid Leprosy  less severe end of the spectrum  encompasses TT and BT disease  symptoms confined to the skin and peripheral nerves  most commonly affected are the ulnar, posterior auricular, peroneal, and posterior tibial nerves  TT leprosy is the most common form of the disease encountered in India
  31. 31. TT  Single or a few lesions  Asymmetrically distributed on trunk and limbs  Sharply defined, dry, flat or raised, erythematous or hypopigmented, and are anesthetic.  One or two nerves may be enlarged near the skin lesion  SS for AFB: Negative  Lepromin test may be strongly positive
  32. 32. Tuberculoid Leprosy
  33. 33. Borderline Tuberculoid  Four or more lesions, asymmetrically distributed  Macules or plaques of variable sizes with well or ill- defined margins & satellite lesions  Peripheral nerves enlarged asymmetrically  Sensation: hypoesthesia  SS for AFB: may or may not be positive.  Lepromin test may be weakly positive
  34. 34. Borderline Tuberculoid
  35. 35. Borderline Leprosy  BB, BL  Intermediate between BT- and LL-type lesions; ill-defined plaques with an occasional sharp margin; few or many in number  Hypesthetic or anesthetic skin lesions; nerve trunk palsies, at times symmetric
  36. 36. Borderline Borderline  Multiple erythematous macules & plaques  Various sizes and shapes with punched out center and ill defined slopping outer margin  Tend to be symmetrical  Nerves may be asymmetrically enlarged  Sensation:+/-  SS for AFB: seen +/-  Lepromin test-usually negative, may be doubtful
  37. 37. Borderline Borderline
  38. 38. Borderline Lepromatous  Numerous, symmetrically distributed lesions  Hypopigmented or erythematous irregularly shaped maculopapular, infiltrative nodules, or plaques, with smooth surfaces & ill defined borders, sloping outwards  Nerves may be symmetrically or asymmetrically enlarged  Sensation:+/-  SS for AFB: numerous seen  Lepromin test -negative
  39. 39. Borderline Lepromatous
  40. 40. Lepromatous Leprosy  Numerous macules, plaques, nodules or diffusely infiltrated lesions, shiny, smooth, symmetrically distributed on face (leonine facies), trunk and extremities with ill-defined margin which may be slightly hypopigmented or erythematous  Symmetrical nerve enlargement is seen  Sensation: normal  SS for AFB: numerous seen  Lepromin test - negative
  41. 41. Lepromatous Leprosy
  42. 42. Ear lobes involvement
  43. 43.  Diffuse thickening of the skin, with loss of hair (eyebrows and eyelashes) : madarosis.  Saddle nose deformity  Leonine facies
  44. 44. Clinical, Bacteriologic, Pathologic, and Immunologic Spectrum of Leprosy Feature Tuberculoid (TT, BT) Leprosy Borderline (BB, BL) Leprosy Lepromatous (LL) Leprosy Skin lesion One or a few sharply defined annular asymmetric macules or plaques with a tendency toward central clearing, elevated borders Intermediate between BT- and LL-type lesions; ill-defined plaques with an occasional sharp margin; few or many in number Symmetric, poorly marginated, multiple infiltrated nodules and plaques or diffuse infiltration; xanthoma-like or dermatofibroma papules; leonine facies and eyebrow alopecia Nerve lesion Skin lesions anesthetic early; nerve near lesions sometimes enlarged; nerve abscesses most common in BT Hypoesthetic or anesthetic skin lesions; nerve trunk palsies, at times symmetric Hypoesthesia a late sign; nerve palsies variable; acral, distal, symmetric anesthesia common BI(Bacteriological index) 0-1+ 3-5+ 4-6+ lymphocytes 2+ 1+ 0-1+ Macrophage differentiation Epitheloid Epitheloid in BB,usually undiff but may have foamy changes in BL Foamy change is the rule,may be undifferentiated in early lesions Langhans giant cells 1-3+ - - Lepromin skin test +++ - - Lymphocyte transformation test Generally positive 1 to 10 1 to 2 CD4 : CD8 ratio 1.2 BB(NT),BL:0.48 0.50 PGL1 antibodies 60 85 95
  45. 45. General Findings  Eye : The anterior chamber can be invaded in LL with resultant glaucoma and cataract formation. Iritis/Iridocyclitis  Testes : May be involved in LL with resultant hypogonadism.  Systemic involvement – Respiratory, Bones, Kidneys, Lymph glands, etc.
  46. 46. Nerve involvement in Leprosy
  47. 47. M. Leprae : superficial nerve involvement W Britton
  48. 48. Nerve Involvement  Neural involvement leads to muscle weakness, muscle atrophy, severe neuritic pain, and contractures of the hands and feet.  Ulnar nerve at elbow is most commonly involved , least common is radial.  Most common cranial nerve involved is Trigeminal.  >30 percent neural loss required for loss of sensation.  First sensation to go is thermal (cold>fine touch). Proprioception is usually preserved.
  49. 49. Face Facial Nerve  Lagophthalmos  Facial droop Trigeminal Nerve  Corneal anesthesia
  50. 50. NERVE DAMAGE UPPER LIMB
  51. 51. Ulnar S  Anesthesia medial 1/3 palm M Claw ring and little fingers A  Dryness medial 1/3 palm
  52. 52. Median S Anesthesia lateral 2/3 palm M Claw mid + index + loss Opposition A Dryness lateral 2/3 palm
  53. 53. Radial S Anesthesia dorsum hand M Wrist drop
  54. 54. NERVE DAMAGE LOWER LIMB
  55. 55. Lateral (common) Popliteal  Foot drop
  56. 56. Posterior Tibial S Sole anesthesia M Claw Toes A Dryness in sole
  57. 57. DIAGNOSIS  HISTORY  CLINICAL EXAMINATION  BACTERIOLOGICAL EXAMINATIONS  FOOT-PAD CULTURE  HISTAMINE TEST  BIOPSY  IMMUNOLOGICAL TEST
  58. 58. DIAGNOSIS HISTORY History should include the following points :  Patients Bio data : name, age, sex, address  Presenting complaints  Family history of leprosy  Contact with leprosy cases  Previous history of treatment for leprosy, if any
  59. 59. DIAGNOSIS CLINICAL EXAMINATION Physical examination should include :  A thorough inspection of the body surface(skin).  Palpation of commonly involved superficial nerves: 1. Ulnar N. near the medial epicondyle. 2. Greater Auricular N as it turns over SCM muscle. 3. Lateral Popliteal N. 4. Dorsal branch of Radial N.  Testing for : 1. Loss of sensation : heat, cold, pain, touch . 2. Paresis or paralysis of muscles of hands and feet.
  60. 60. Nerve palpation
  61. 61. DIAGNOSIS BACTERIOLOGICAL EXAMINATION This includes :  Skin Smears :  Nasal Smears or blows :  Nasal Scrapings :
  62. 62. DIAGNOSIS BACTERIAL INDEX  Bacterial index is the only objective way of monitoring benefit of treatment.  According To Ridley’ Logarithmic Scale It Ranges From 0 To 6+ and is based on the no. of bacilli seen in an average microscopic field.  B 0 stands for no bacilli in any of 100 oil immersion field.
  63. 63. DIAGNOSIS BACTERIAL INDEX
  64. 64. DIAGNOSIS BACTERIAL INDEX
  65. 65. DIAGNOSIS BACTERIAL INDEX
  66. 66. DIAGNOSIS MORPHOLOGICAL INDEX  The MI is calculated after examining 200 pink-stained free standing bacilli.  The percentage of solid staining bacilli in a stained smear is referred to as MI.  It is a valuable indicator of the patient’s response to treatment during the first few months and helps to signal drug resistance.  SOLID FRAGMENTED GRANULAR(SFG) PERCENTAGE : similar to MI but a more sensitive indicator of the patient’s response to treatment.
  67. 67. DIAGNOSIS FOOT-PAD CULTURE  Only certain way of identifying M. Leprae.  10 times more sensitive at detecting the bacilli than slit skin smear.  Time consuming : requires 6 to 9 months.  Used for : 1. Detecting drug resistance. 2. Evaluating the potency of anti-leprosy drugs. 3. Detecting the viability of bacilli during treatment.  Newer in vitro macrophage culture which takes only 3 – 4 weeks.
  68. 68. DIAGNOSIS HISTAMINE TEST  Reliable test for detecting at an early stage peripheral nerve damage due to leprosy.  Method : carried out by injecting 0.1ml of a 1:1000 solution of histamine phosphate into hypopigmented patches or in areas of anesthesia.  Result : in normal person it gives rise to a wheal surrounded by erythematous flare(Lewis triple response). In case of leprosy where the nerve supply is destroyed, flare response is lost.  Particularly useful in cases of indeterminate leprosy.
  69. 69. DIAGNOSIS BIOPSY  Usually resorted to when there is high clinical suspicion but the other test are unyielding. It also gives information about the bacterial content of skin.
  70. 70. DIAGNOSIS IMMUNOLOGICAL TESTS  Tests for cell mediated immunity(CMI)  LEPROMIN TEST  Tests for humoral antibodies(serological tests)  FLA-ABS test : used for detecting subclinical infections. 92.3 percent sensitive and 100 percent specific in detecting specific antibodies in all types leprosy irrespective of type and duration of disease.  Monoclonal antibodies  Others : RIA, ELISA.
  71. 71. DIAGNOSIS LEPROMIN TEST Method : it is performed by injecting 0.1ml of lepromin into inner aspect of the forearm. The reaction is read at 48 hours and 21 days. Two types of reaction have been described : EARLY REACTION(FERNANDEZ REACTION) : an inflammatory reaction develops within 24 to 48 hours and this tends to disappear in 3 to 4 days. If the diameter of the red area is more than 10mm the test is considered positive. It is a delayed type hypersensitivity reaction to soluble constituents of lepra bacilli and indicates whether or not a person has been sensitized by exposure to and infection by lepra bacilli.
  72. 72. DIAGNOSIS LEPROMIN TEST LATE REACTION(MITSUDA REACTION) : It is characterized by the appearance of a nodule which becomes apparent in 7 to 10 days and reaches its maximum in 3 to 4 weeks. The test is read at 21 days. If the nodule is more than 5 mm it is considered positive. It is induced by the bacillary component and indicates cell mediated immunity.  In the first six months of life most children are lepromin negative  BCG vaccination is capable of converting lepra reaction from negative to positive.
  73. 73. DIAGNOSIS LEPROMIN TEST VALUE OF LEPROMIN TEST :  Useful tool for evaluating the immune status of leprosy patients.  Aid to classify the type of disease.  Estimating the prognosis  Strongly positive in a typical tuberculoid case and getting weaker towards the lepromatous end, the typical lepromatous case being lepromin negative indicating failure of CMI. The greatest drawback being high false positive and false negative cases hence not used as a diagnostic test. OTHER TESTS FOR CMI :  Lymphocyte transformation test(LTT)  Leucocyte migration inhibition test(LMIT)
  74. 74. TREATMENT MULTIDRUG CHEMOTHERAPY In the absence of effective primary prevention by a leprosy vaccine leprosy control is based on effective multidrug chemotherapy(secondary prevention). OBJECTIVES :  To interrupt transmission of infection  Early detection and treatment of cases to prevent deformities  To prevent drug resistance
  75. 75. TREATMENT MULTIDRUG CHEMOTHERAPY  First line drugs : rifampicin, dapsone, clofazimine, ethionamide and prothionamide.  Second line drugs : quinolones, minocycline, clarithromycin, aminoglycosides
  76. 76. TREATMENT MULTIDRUG CHEMOTHERAPY WHO RECOMMENDED REGIMENS OF CHEMOTHERAPY : MULTIBACILLARY LEPROSY  Rifampicin : 600mg once monthly under supervision  Dapsone : 100mg daily self administered  clofazimine : 300mg once monthly under supervision 50mg daily self-administered Where clofazimine is unacceptable due skin coloration it may be substituted by 250 to 375mg daily dose of ethionamide or prothionamide. The above regimen needs to taken for 12 months within 18 months
  77. 77. TREATMENT MULTIDRUG CHEMOTHERAPY WHO RECOMMENDED REGIMENS OF CHEMOTHERAPY : PAUCIBACILLARY LEPROSY : The above regimen needs to be taken for 6months within 9 months
  78. 78. TREATMENT MULTIDRUG CHEMOTHERAPY
  79. 79. TREATMENT MULTIDRUG CHEMOTHERAPY Important points :  MDT is not contraindicated in patients with HIV infection.  MDT is safe during pregnancy.  Drugs are excreted in breast milk but no reports of adverse reaction except for mild discoloration of infants skin by clofazimine  Leprosy is exacerbated during pregnancy, it is important that MDT is continued
  80. 80. TREATMENT MULTIDRUG CHEMOTHERAPY Drugs Rifampicin : highly bactericidal, a single 1500mg dose kills 99 percent of viable organisms Toxic effects includes anorexia, nausea, vomiting, abdominal discomfort and orange discoloration of body secretions. It is hepatotoxic Dapsone : weakly bactericidal. Adverse effects include hemolytic anemia, methemoglobinemia, agranulocytosis, hepatitis, neuropathy, psychosis and rarely…
  81. 81. TREATMENT MULTIDRUG CHEMOTHERAPY DDS syndrome ch. by fever, maculopapular rash, enlarged lymph nodes, hepatitis and exfoliative dermatitis. Clofazimine : was originally synthesized for TB. Less effective than dapsone but has added advantage of preventing lepra reaction. More expensive but less toxic which includes dark red discoloration of skin, mucus membranes, sweat and urine.
  82. 82. TREATMENT MULTIDRUG CHEMOTHERAPY Ethionamide and Prothionamide : highly bactericidal killing 98 percent of viable bacilli in 3 to 4 days. Relatively more expensive and more toxic.
  83. 83. LEPRA REACTIONS  During the course of leprosy, immunological mediated episodes of acute or subacute inflammation known as reaction may occur.  There are two types of reactions :  Type 1 or Reversal reaction  Type 2 or erythema nodosum leprosum Both types can occur before the start of MDT, during treatment or after completion of treatment.
  84. 84. REVERSAL/DOWNGRADING REACTION  occur in almost half of patients with borderline forms of leprosy but not in patients with pure lepromatous disease  Manifestations include classic signs of inflammation within previously involved macules, papules, and plaques and, on occasion, the appearance of new skin lesions
  85. 85.  nerve trunk most commonly involved in this process is the ulnar nerve at the elbow, which may be painful and exquisitely tender  most dramatic manifestation is footdrop, which occurs when the peroneal nerve is involved.  (less commonly) fever—generally low-grade
  86. 86.  type 1 lepra reactions precede the initiation of appropriate antimicrobial therapy, they are termed downgrading reactions, and the case becomes histologically more lepromatous  when they occur after the initiation of therapy, they are termed reversal reactions, and the case becomes more tuberculoid  often occur in the first months or years after the initiation of therapy
  87. 87. LEPRA REACTIONS ERYTHEMA NODOSUM LEPROSUM  In ENL new inflamed, red nodules appear under the skin, while the original lesions remain same. Commonly on face, arm and legs & bilaterally symmetrical. They appear in crops and subside within few days even without treatment  It is antigen antibody reaction.  Seen in MB cases only.  Nerves may be affected but is uncommon  Other organs like testis, eye, kidney may be affected  General symptoms of fever, joint pain, red eyes and watering may be associated.
  88. 88. ERYTHEMA NODOSUM LEPROSUM  occurs exclusively in patients near the lepromatous end of the leprosy spectrum (BL- LL)  90% of cases it follows the institution of chemotherapy, generally within 2 years  most common features of ENL are crops of painful erythematous papules that resolve spontaneously in a few days to a week but may recur; malaise; and fever
  89. 89.  may also experience symptoms of neuritis, lymphadenitis, uveitis, orchitis, and glomerulonephritis and may develop anemia, leukocytosis, and abnormal liver function tests  Elevated levels of circulating tumor necrosis factor (TNF) have been demonstrated in ENL; thus, TNF may play a central role in the pathobiology of this syndrome  thought to be a consequence of immune complex deposition
  90. 90. LEPRA REACTIONS TREATMENT  Because of high risk of permanent nerve damage reversal reaction needs to be promptly diagnosed and treated adequately  Standard 12 wk. regimen of prednisolone is the treatment of choice.  ENL varies in severity, duration and organ involvement, and can be treated with prednisolone as reversal reaction.  Treatment includes bed rest, splinting of affected nerves, analgesics and prednisolone.
  91. 91. LEPRA REACTIONS TREATMENT Prednisolone regimen Add clofazimine in ENL 40mg daily for first 2 weeks 30mg daily or week 3 and 4 100mg tds x 4 weeks 20mg daily for week 5 and 6 15mg daily for week 7 and 8 100mg bd x 4weeks 10mg daily for week 9 and 10 5mg daily for week 11 and 12 100mg od x 4 weeks For neuritis, treatment with prednisolone 20mg onwards Should be prolonged to four weeks from
  92. 92. LEPRA REACTIONS TREATMENT  For pregnant women prednisolone should be started at 30mg dose instead of 40mg and limit the course for 10weeks in PB cases and 20 weeks for MB cases.  For children dose should be started at 1mg/kg of body wt. per day.  Thalidomide : was reintroduced for the treatment of ENL, mainly because of its antipyretic action. WHO does not recommend the use of thalidomide in leprosy. Prednisolone is more effective in controlling ENL and associated neuritis, clofazimine is the drug of choice for the management of chronic, recurrent ENL reactions. Another drug claimed to be useful in ENL is pentoxyfylline.
  93. 93. Thank You

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