LEPROSY dermatology microbiology - hansen

Dermatology

1. Hansen’s Disease Dr. Arul Postgraduate DVL

2. CONTENTS History Transmission of leprosy Etiopathogenesis Global and national scenario of leprosy Immunity and leprosy Microbiology of M.Leprae Classification of leprosy Clinical spectrum Systemic involvement in leprosy Differential diagnosis Diagnosis Treatment Lepra reactions Deformities Physiotherapy Prevention Rehabilitation in leprosy MCQs Photoquiz

3. History Oldest infection known to mankind India considered as point of origin of leprosy First written reference appeared in Egyptian document written around 1550 BC Dr Gerhard Henrik Armauer Hansen first described M.leprae to be the causative organism in 1873. Synonyms: Hansen’s disease, ‘ Kushtha roga ’ Definition : Leprosy is a chronic systemic disease caused by Mycobacterium leprae manifesting as development of specific granulomatous or neurotrophic lesions in the skin, mucous membrane, eyes nerves, bones and viscera.

4. Transmission of Leprosy Respiratory route : inhalation of bacilli-laden droplets Cutaneous : skin to skin contact GIT : ingestion of food In utero transmission Transmission through breast milk Intradermal : inoculation by tattoos Incubation period : 5-7 years (on average) Not Yet Proven

5. Epidemiological Factors Occurs at all age groups Peak age of onset : Between 20-30 years Males > Females (M:F: 2:1) (male predominance seen in adults, in children gender distribution is nearly equal) Less common in children and women Commonest type of leprosy in children : Borderline tuberculoid Occurrence of disease depends on immune status Genetic susceptibility reported Migration from rural to urban areas: increase in cases Overcrowding, lack of personal hygiene, humidity favor disease transmission

6. Global & National Scenario of Leprosy Registered prevalence globally(2009) : 213036 Total cases detected in India (2011-12) : 1.27 lakh Annual case detection rate in India : 10.35 per one lakh population Increased no of new case detected (2011-12): Orissa, Gujarat, Maharashtra, Madhya Pradesh, Andhra Pradesh

7. Immunity and Leprosy Host resistance Excellent Good Fair Poor Very poor Clinical manifestation No infection Subclinical infection with spontaneous regression Indeterminate, pure neuritic , tuberculoid Mid-borderline, borderline- lepromatous Lepromatous

8. Immunopathogenesis of leprosy Entry of M.Leprae in the body via nose Invasion Multiplication in dermal lymphatics and vascular endothelial cells Hematogenous spread Invasion of M.Leprae into nerves Immunological response

9. Mycobacterium Leprae Obligate, non motile, nonspore forming microaerophilic intracellular, acid-fast bacillus that forms curved or straight rods Components include : Cell wall, cell membrane, cytoplasm and capsule Affinity for skin, nerves and muscle tissue Found in macrophages, histiocytes and Schwann cells Non cultivable Grown in animal models(armadillo and mice) Closely resembles M. Tuberculosis , but less acid-fast. Multiplies (generation time) in 11-13 days

10. Classification Ridley Jopling classification Indeterminate Tuberculoid Borderline borderline- tuberculoid mid-borderline borderline- lepromatous Lepromatous

11. Classification Indian Classification Lepromatous Tuberculoid Maculoanesthetic Borderline Pure neuritic Indeterminate

12. Classification NLEP Classification Nonlepromatous Tuberculoid Maculoanesthetic Polyneuritic Indeterminate Borderline Indeterminate Lepromatous Lepromatous

13. Tuberculoid (TT) Single or few ( upto 3), large,dry , asymmetrical, erythematous / hypopigmented patches with well-defined margins. Sweating – Lost Sensations – Absent Nerves - Thickened, presence of feeding nerves, abscesses Skin smears – Negative Lepromin test - Strongly positive Course-Polar TT stable and sub polar TT may downgrade.

14. Borderline Leprosy Common type of leprosy Subdivided into BT, BB & BL. Course - Unstable with variable prognosis, may progress to sub-polar LL leprosy. Most prone to reactions. Lepromin test -Negative, weakly positive in BT.

15. Borderline Tuberculoid (BT) Few( upto 10),large, asymmetric, hypopigmented or skin coloured macules , plaques with ill defined margins Surface-Dry with hair loss Presence of satellite lesion near the advancing margin of patch Sensory impairment - Marked Nerve involvement-Irregular and asymmetrical Deformities are common Lepromin test-Weakly positive Satellite lesion

16. Borderline tuberculoid leprosy

17. Midborderline leprosy (BB) Unstable form, reactions frequent Multiple and symmetric lesions Lesions range from papules, macules and plaques Plaques show well demarcated edges with characteristic punched out centre (inverted saucer shaped) Face may show infiltration with nodules on ears Sensory impairment - Moderate. Nerve involvement-Many nerves involved and asymmetrical

18. Borderline lepromatous leprosy (BL) This type classically start as macule , widespread and symmetrical, later become infiltrated centrally Papules, nodules and plaques with sloping edges Sensory impairment- Variable (more in centre) Nerve involvement - Widespread and asymmetrical Glove & stocking hypoaesthesia occurs late Lepromin reaction-Negative Prognosis-Variable

19. Lepromatous leprosy Lesions symmetrically distributed, small, multiple, shiny and waxy. Macular, infiltrated, nodular, diffuse or ulcerative Macules -Small, widespread, ill defined margins Nodules- Arise from macules or infiltrated lesions Sensory impairment-Normal or mild Leonine facies - Infiltration of skin with nodules, loss of eyebrows and eyelashes. Nerve involvement -Symmetrical, not markedly enlarged, fibrotic and shrunken in late stages. Glove and stocking anaesthesia Lepromin test - Negative

20. Ear infiltration in lepromatous leprosy

21. Indeterminate leprosy Commonest presentation in children (20-80%) Flat erythematous or hypopigmented , asymmetrical, macules varying in number, size and location with vague margins Common sites : Face, limbs, thighs Sensation - Normal or slightly impaired Peripheral nerves - Normal Skin smears - Negative Lepromin test - Unpredictable and variable Course - Usually self limiting, may progress to other forms of leprosy.

22. Pure Neuritic leprosy Commonly reported from India and Nepal Male preponderance seen Sensory loss without skin lesion Neuritic manifestations -Tingling, heaviness and numbness, paresis, hypotonia , atrophy, claw hand and toes, wrist-drop, foot-drop. Other changes- Anhidrotic , dry glossy skin, blisters, neuropathic ulcers, decalcification, bone resorption Dry skin in leprosy

23. Lepromin test -Slightly positive Course-Spontaneous regression or progression to TT leprosy Silent neuritis (silent neuropathy) Sensory or motor impairment without skin signs of reversal reaction or ENL, tenderness, paresthesia or numbness Pure Neuritic leprosy

24. Special forms of Leprosy Lucio Leprosy/ Lepra Bonita’/Beautiful leprosy Rare form of lepromatous leprosy, described in Mexico. Diffuse widespread infiltration of skin, loss of body hair, loss of eyebrows & eyelashes, and widespread sensory loss. Histoid leprosy Seen in LL, but also in borderline and indeterminate cases. Seen in patients taking irregular or inadequate treatment and in drug resistant cases. Nodules are firm, reddish or skin colored, dome shaped with shiny skin. Skin smears- Many bacilli seen. Lazarine leprosy Diffuse ulceration seen as a part of lepra reaction in undernourished patients.

25. Histoid leprosy

26. Eye Involvement in Leprosy Eyebrows/eyelashes- Madarosis , trichiasis leading to corneal vascularity and opacity Facial nerve palsy- Lagophthalmos (partial/complete, unilateral/bilateral) and ectropion Trigeminal nerve palsy-Exposure keratitis and vision loss Lacrimal gland-Dry eye and Dacryocystitis (acute, subacute or chronic) Cornea- Enlarged nerves, ulcers, lepromata, punctate keratitis and pannus Sclera-Nodules on sclera, scleritis and episcleritis Uvea- Granulomatous and chronic uveitis Iris-Iris pearls Lens-Cataract Retina-Impaired contrast sensitivity

27. Nerve Involvement in Leprosy Sensory involvement - Anaesthesia in hands & feet, glove and stocking anaesthesia , repeated trauma Motor involvement- Wasting and paralysis of muscles Autonomic involvement - Ichthyosis, loss of hair and sweating Other features Nose : Nasal stuffiness / crusting, epistaxis, nasal deformity (Saddle nose) Ear : Infiltration/nodules, ulceration Liver : Lepromatous hepatitis,amyloidosis Hoarseness of voice Gynaecomastia Bone resorption Lymphadenopathy

28. Differential Diagnosis Macular lesions ( hypopigmented ) Vitiligo Occupational leucoderma Tinea versicolor Pityriasis alba Post kala azar dermal leishmaniasis Naevus depigmentosus and nevus anemicus Postinflammatory hypomelanosis Polymorphic light eruption

29. Differential Diagnosis Macular lesions ( erythematous ) Pityriasis rosea Seborrhoeic dermatitis Tinea incognito Secondary syphilis

30. Differential diagnosis of hypopigmented conditions Post kala azar dermal leishmaniasis Vitiligo vulgaris P. Alba

31. Differential diagnosis of hypopigmented conditions Polymorphus light eruption P. Versicolor

32. Differential Diagnosis Annular lesions Anular psoriasis Erythema multiforme Granuloma annulare Sarcoidosis Infiltrated lesions Lupus vulgaris Lupus erythematosus Granuloma annulare Annular syphilides Post kala azar dermal leismaniasis (infiltrated lesions) Sarcoidosis Psoriasis

33. Differential diagnosis of annular lesions Lupus vulgaris Psoriasis vulgaris

34. Differential diagnosis of annular lesions Granuloma Annulare Annular Syphillis Tinea Corporis

35. Nodular Lesions Post kala azar dermal leismaniasis Cutaneous leishmaniasis Syphilis Sarcoidosis Leukaemia cutis Mycosis Fungoides Nodules of neurofibromatosis Kaposi’s sarcoma Tuberous sclerosis

36. Differential diagnosis of nodular lesions Neurofibromatosis Leukemia Cutis

37. Differential diagnosis of neurological conditions Sensory impairment with or without muscle wasting Peripheral neuropathy Diabetic neuropathy Primary amyloidosis of peripheral nerves Congenital sensory neuropathy Syringomyelia Tabes dorsalis Thoracic outlet syndrome Alcoholic neuropathy Hereditary motor and sensory neuropathy

38. Diagnosis Cardinal signs of leprosy Anesthetic skin lesions Nerve enlargement Demonstration of M.Leprae Only one of these three features needed to make diagnosis

39. Clinical Examination Detailed history Number of skin lesions : >10, 10-15, 15-20 or numerous Distribution Size Colour : Hypopigmented / erythematous / coppery Shape : Circular, oval, irregular, annular Morphology : Macule / patch / plaque / papule / nodule Margin : Raised / flat, well / ill defined, sloping / punched out Surface : dry, scaly, smooth, shiny, edematous, ulcerated

40. Clinical Examination Symmetrical appearance Cutaneous nerve twig over the patch Earlobe infiltration Sensory impairment Motor examination Nerve examination Trophic ulcers Gynecomastia Loss of hair / sweating

41. Clinical Examination Sensory Touch : Tested with wisp of cotton Temperature : Tested with two test tubes one containing hot water and other cold Pain : Tested by pin prick Semmes-Weinstein monofilament testing Corneal reflex : Tested with a wisp of sterile cotton wool Motor Testing of motor power- Done clinically Electro-diagnosis - Employed in very early cases. Electrical stimulator using faradic and galvanic current used to test muscle power Monofilaments

42. Nerve Examination Check for enlargement, tenderness,nodularity and abscess and scoring system Scoring system for enlarged nerves Normal 0 Enlarged + Moderately enlarged ++ Very much enlarged +++

43. Nerves Supra/ infraorbital Greater auricular Ulnar Median Radial Lateral popliteal Anterior/posterior tibial Sural Cutaneous branch of radial nerve Enlarged greater auricular nerve

44. Investigations for M. Leprae Bacteriological examination Skin smears : Made by slit and scrape method from the most active looking edge of skin lesion and stained with Ziehl-Neelsen method. Reading of smears : Bacteriological index - Indicates density of leprosy bacilli (live & dead) in the smears and ranges from 0 to 6+ Morphological index - It is the percentage of presumably living bacilli in relation to total number of bacilli in the smear

45. Other Investigations Histopathological examination Nerve biopsy Sweat function test Nasal mucosal smears Nerve biopsy Histamine tests Lepromin test FNAC Animal Models : Armadillo, Thymectomised , irradiated nude mice, Korean chipmunk etc.

46. Newer Investigations Serological assays: FLA-ABS, RIA, ELISA PGL, PCR Other techniques: Chemical, Immunological, Molecular biological, Bioluminescent techniques, Strain specific probes Indications : To confirm diagnosis in c/o inconclusive histopathological /smear reports. To distinguish between reaction and relapse To demonstrate M. leprae or its components To elicit strain differentiation for molecular epidemiology To detect drug susceptibility or resistance

47. Treatment MDT-WHO Paucibacillary leprosy (6 months) Cap. Rifampicin (600 mg) monthly, supervised Tab. Dapsone (100 mg) daily Multibacillary leprosy (1 year) Cap. Rifampicin (600mg) monthly, supervised Cap. Clofazimine (300mg) monthly, supervised Tab. Dapsone (100mg) daily Cap. Clofazimine (50mg) daily

48. Blister packets for MDT Easy to use, handy and of convenient size Provide complete treatment Improve clinical attendance Drugs are better protected against moisture, heat and accidental damage Ensures quicker dispensing of the drugs Can be dispensed by non medical person

49. Blister Packets

50. Other New Regimens ROM Rifampicin - 600 mg Ofloxacin - 400 mg, Minocycline - 100mg Single dose - Single patch (WHO accepted) ROM-6 (Monthly for 6 months)- Paucibacillary ROM-12(Monthly for 12 months)- Multibacillary Ofloxacin based regimes RO (continuous treatment for 28 days) ROM trial (intermittent therapy) Moxifloxacin based regimes

51. Immunomodulatory Drugs Drugs - Levamisole , Zinc Antigenically related mycobacteria B.C.G vaccine M.leprae +B.C.G vaccine Mycobacterium welchii vaccine ICRC vaccine Other immunomodulators -Gamma interferons , interleukins

52. Newer Drugs / Regimens Fluoroquinlones ( eg pefloxacin , ofloxacin , sparfloxacin , moxifloxacin) Minocycline Macrolides ( Clarithromycin ) Ansamycin - Rifabutin , rifapentine , isobutylpiperazinyl rifampicin, R-76-1 Cephalosporins Beta lactamase inhibitors Fusidic acid Dihydrofolate reductase inhibitors- Brodimoprim , epiroprim Hydrozone derivaties-PH-22 and PQ-22 Deoxy - Fructo -Serotonin

53. Lepra Reactions Acute episodes or bouts of exacerbations occurring in course of chronic disease It is a sudden tissue response resulting from liberation of bacilli or their products into the tissues, manifestations of which are local or systemic Sudden increase in activity of existing lesions, appearance of fresh lesions with or without constitutional symptoms Type I reaction - All borderline cases (BT, BB,BL) Type II reaction - LL and sometimes BL cases

54. Precipitating Factors Pregnancy / lactation Drugs- Antileprosy drugs, iodides Severe physical or mental stress, surgical stress Infections Alcohol

55. Type I Reaction Type IV hypersensitivity reaction Sub - types Upgrading (Reversal) Downgrading Existing lesions worsen / New lesions may appear (have typical characteristic of TT leprosy) Lesions become erythematosus and / or edematous and may ulcerate Neuritis / Nerve abscesses Systemic disturbances - Unusual

56. Type I Reaction Diagnosis : Clinical, histopathology ( epitheloid cell granuloma , dermal edema, plasma cells and foreign body giant cells) Complications : Neuritis, dactylitis , edema of hands/ feet, corneal anesthesia, conjunctivitis, sudden occurrence of claw hand, foot-drop, facial palsy

57. Type I reaction with enlarged nerve and nerve abscess

58. Type II Reaction (ENL- erythema nodosum leprosum ) Occurs in BL and LL cases Type III hypersensitivity reaction Crops of tender, warm, recurrent, evanescent, erythematous nodules distributed bilaterally symmetrically located on thighs ,legs and face Vesicular lesions can occur which break down to form ulcers ( erythema necroticans ) ENL precedes fever, malaise, headache and joint pains Other manifestations : Rhinitis, epistaxis, Iridocyclitis , episcleritis , dactylitis , epididymo-orchitis , arthritis, neuritis, bone pain and lymphadenitis Diagnosis : Clinical, slit skin smears show broken bacilli, biopsy ( vasculitis )

59. ENL and necrotic ENL

60. Type II Reaction - complications Frozen hand Laryngitis Non-paralytic deformity Polyarthritis / RA-like syndrome Multiple dactylitis Leucocytosis , anaemia , raised ESR Albuminuria / nephrotic syndrome Liver / spleen enlargement Epididimytis / orchitis , testicular atrophy / sterility Gynaecomastia Adrenal gland hypofunction Eye involvement

61. Type 3 reaction ( Lucio phenomenon) Rare form of reaction observed only in Lucio leprosy Acute ,severe, necrotizing vasculitis occurring in patients of Mexican ancestry Presents as painful erythematosus patches that become necrotic and ulcerated Treatment of Lepra reactions Principles of treatment Early initiation of treatment for reaction Continuation / initiation of MDT Removal of precipitating factor Rest, physical and mental

62. Treatment Modalities Mild reaction Analgesics (aspirin or paracetamol) Severe reaction Corticosteroids Antimalarials Clofazimine Thalidomide Methotrexate Cyclosporine Azathioprine Mycophenolate mofetil

63. Treatment Modalities Supportive management Surgical decompression of nerves, splints / padding, treatment of steroids / atropine eye drops for iridocyclitis , steroids / scrotal support for epipdidymoorchitis Newer drugs for ENL : Leukotriene inhibitors, thalidomide derivatives, infliximab

64. Deformities/Disabilities in leprosy Deformity : Visible alteration in the appearance which results in disability. Disability : Restriction or lack of ability to perform an activity considered normal for a human. Primary : Are caused by the tissue reaction to infection with M.Lepra e.g. leonine facies , flat-nose, claw hand. Secondary : Occur as a result of damage to the anesthetic parts of the body e.g. planter ulcers, corneal ulcers.

65. Grading of Deformities/Disabilities : WHO disability grading Grade 0 : No anaesthesia , no visible deformity or damage in hands and feet, or no problems in eye or no visual loss. Grade 1 : Anaesthesia present, but no visible deformity or damage, eye problems due to leprosy present but vision not severely affected (6/60 or better) and can count fingers at 6 metres . Grade 2 : Visible deformity or damage present in hands or feet , and severe visual impairment (vision worse than 6/60) i.e unable to count fingers at 6 metres or lagophthalmos or iridocyclitis or corneal opacities.

66. Deformities Primary Deformities Leonine facies Loss of eyebrows and eyelashes Depressed nose Gynaecomastia Palatal perforation Secondary deformities Corneal ulcers and opacities Plantar ulcers Palmar ulcers and ulcers on tips of fingers Resorption Charcot joints Plantar ulcer

67. Deformities : Nerve Damage Claw hand ( ulnar , median) Clawing of the toes (posterior tibial ) Wrist-drop (radial) Foot-drop (lateral popliteal ) Lagophthalmos , facial palsy (facial)

68. Trophic Ulcer : Stages Threatened ulcer : Process of tissue damage starts associated with inflammation Presents as edema and warmth in region of metatarsal head with associated deep tenderness and increase in inter digital gap Concealed ulcer : Damage to subcutaneous tissue presents as necrosis and blisters at the site of damage Open ulceration : Skin breaks down and tissue damage site is exposed to form frank ulcer Types of ulcers : Acute ulcer/ Chronic ulcer Complicated/uncomplicated ulcer

69. Prevention of Deformities Adequate treatment of leprosy patient Early detection of nerve damage Prevention of nerve damage Protection of anesthetic hands from injury Care of hands with weakness/paralysis Use of protective footwear Adequate hydration of skin Physiotherapy

70. Management of Deformities Education of patient regarding prevention of injuries Daily examination of hands and feet and prompt treatment for minor injuries Using adapted tools and appliances after training Reconstructive surgery Rehabilitation

71. Physiotherapy Oil massage/Wax Therapy-Uses To make the skin soft and supple and loosen stiff joints As a preliminary to exercises To strengthen muscles and keep joints mobile To reduce pain in acute neuritis To stimulate innervated sweat glands to increase blood flow Exercises : Active and assisted exercise : To increase the strength of muscles and retain their tone Electric stimulation – Uses To maintain the tone of denervated muscle Helpful in breaking post operative adhesions Before tendon surgery could be used as a means of documenting nerve damage and the progress of the nerve recovery with treatment.

72. Splints Indication Acute neuritis Mobile deformities(to prevent fixed deformities), Fixed deformities(to correct the deformities). Various splints For radial neuritis-Static or dynamic wrist drop splint For mobile deformity- Static or dynamic splint For fixed deformity-Gutter splints, finger loops etc. Splints for various deformities Hand deformities : Gutter splints, finger loop splints, opponens splints and adductor bands Foot deformity : “Y” strap with spring, single elastic strap

73. Prevention and Control of leprosy Prevention of leprosy Early detection through survey and initiation of treatment Families of patients to be kept under surveillance Immunoprophylaxis -Use of leprosy vaccines Improvement in socio-economic conditions Leprosy control Three activities of a leprosy control unit Case detection Case holding, including treatment Health education of public and patients

74. Prevention and Control of leprosy Leprosy Organizations UNICEF LEPRA, DANIDA, SIDA, CIDA, Leprosy mission, American leprosy mission (ALM), German leprosy relief association(GLRA), LEPRA, Netherland leprosy relief (NLR) Leprosy control Programmes National leprosy control programme (NLCP) 1954 Triad of Survey, Education and Treatment (S.E.T). National leprosy eradication programme (NLEP) 1982

75. Prevention and Control of leprosy National Leprosy Eradication Programme (NLEP), 1982 Eradicate leprosy from the country by 2000. ‘Vertical’ health programme - In areas where prevalence of leprosy is more than 5 per 1000. ‘Horizontal’ programme - In areas where the prevalence rate is less than 5 per 1000. Three main units for programme operation : Basic tier : Survey, education and treatment unit, leprosy control unit and urban leprosy control unit. Second tier : District/zonal leprosy office. Third tier : Leprosy division of the state Directorate of the health services.

76. Rehabilitation in Leprosy Rehabilitation : Physical and mental restoration of patients to normal activities, so that they are able to assume their place in the home, society and industry. Treatment of physical disability Education of patient, family and public Rehabilitation in special homes or institutional rehabilitation Community based rehabilitation

77. MCQ’S Q.1) What is the incubation period of leprosy? 1-10 yrs 11-20 yrs 21-30 yrs 31-40 yrs Q.2) When was National leprosy eradication programme (NLEP) started? 1982 1983 1984 1985

78. MCQ’S Q.3) What is the generation time of leprosy? 1-10 days 11-20 days 21-30 days 31-40 days Q.4) Satellite lesion is commonly seen in which type of leprosy? Indeterminate Lepromatous Borderline tuberculoid Tuberculoid

79. MCQ’S Q.5) Cardinal signs of leprosy include all except Anesthetic lesions Enlarged Nerves Demonstration of M. Leprae Trophic ulcer Q.6) What is the duration of multi-bacillary treatment? 6 Months One Year Two Years Three Years

80. A 14 year old boy presented with a flexion of interphalangeal joints of little and ring finger? What is the deformity and which nerve causes it? Photo Quiz

81. A 15 year old boy presented with multiple asymptomatic lesions with asymmetric enlarged ulnar nerve. What is the likely diagnosis? Photo quiz

82. A 4 year old girl presented with aysmptomatic non scaly, whitish patch with intact sensations. What is the likely differential diagnosis? Photo Quiz

83. Thank You!