Digital Lecture Series: Chapter 08
Hansens Disease Digital Lecture Series: Chapter 08 Dr. Meghana Phiske MD, DNB, DVD, DDV Assistant Professor Department of Dermatology L.T.M.M.Cand L.T.M.G. HospitalSion, Mumbai 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 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: Hansens 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. 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 Epidemiological Factors
Occurs at all age groups Peak age of onset : Between 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 Global & National Scenario of Leprosy
Registered prevalence globally(2009) : Total cases detected in India ( ) : 1.27 lakh Annual case detection rate in India : per one lakh population Increased no of new case detected ( ): Orissa, Gujarat,Maharashtra, Madhya Pradesh, Andhra Pradesh Immunity and Leprosy Host resistance Excellent Good Fair Poor
Very poor Clinical manifestation No infection Subclinical infection with spontaneousregression Indeterminate, pure neuritic, tuberculoid Mid-borderline, borderline-lepromatous Lepromatous 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 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 days Classification Ridley Jopling classification Indeterminate Tuberculoid
Borderline borderline-tuberculoid mid-borderline borderline-lepromatous Lepromatous Classification Indian Classification Lepromatous Tuberculoid
Maculoanesthetic Borderline Pure neuritic Indeterminate Classification NLEP Classification Nonlepromatous Tuberculoid
Maculoanesthetic Polyneuritic Indeterminate Borderline Lepromatous Tuberculoid (TT) Single or few (upto 3), large,dry, asymmetrical, erythematous / hypopigmented patches withwell-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. 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. 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 Borderline tuberculoid leprosy 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 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 andasymmetrical Glove & stocking hypoaesthesia occurs late Lepromin reaction-Negative Prognosis-Variable 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 Ear infiltration in lepromatous leprosy 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. 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 Pure Neuritic leprosy 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 Special forms of Leprosy
Lucio Leprosy/Lepra Bonita/Beautifulleprosy 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. Nodulesare firm, reddish or skin colored, dome shapedwith shinyskin. Skin smears- Many bacilli seen. Lazarine leprosy Diffuse ulceration seen as a part of lepra reaction in undernourished patients. Histoid leprosy 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 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 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 Differential Diagnosis
Macular lesions (erythematous) Pityriasis rosea Seborrhoeic dermatitis Tinea incognito Secondary syphilis Differential diagnosis of hypopigmented conditions
Post kala azar dermal leishmaniasis Vitiligo vulgaris P. Alba Differential diagnosis of hypopigmented conditions
Polymorphus light eruption P. Versicolor Differential Diagnosis
Annular lesions Anular psoriasis Erythema multiforme Granuloma annulare Sarcoidosis Infiltrated lesions Lupus vulgaris Lupus erythematosus Annular syphilides Post kala azar dermal leismaniasis (infiltrated lesions) Psoriasis Differential diagnosis of annular lesions
Lupus vulgaris Psoriasis vulgaris Differential diagnosis of annular lesions
Granuloma Annulare Tinea Corporis Annular Syphillis Nodular Lesions Post kala azar dermal leismaniasis
Cutaneous leishmaniasis Syphilis Sarcoidosis Leukaemia cutis Mycosis Fungoides Nodules of neurofibromatosis Kaposis sarcoma Tuberous sclerosis Differential diagnosis of nodular lesions
Neurofibromatosis Leukemia Cutis 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 Diagnosis Cardinal signs of leprosy Anesthetic skin lesions
Nerve enlargement Demonstration of M.Leprae Only one of these three features needed to make diagnosis Clinical Examination Detailed history
Number of skin lesions : >10, 10-15, 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 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 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 motorpower- Done clinically Electro-diagnosis - Employed in very early cases. Electrical stimulator using faradic and galvanic current used to test muscle power Monofilaments 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 +++ Nerves Supra/ infraorbital Greater auricular Ulnar Median Radial
Lateral popliteal Anterior/posterior tibial Sural Cutaneous branch ofradial nerve Enlarged greater auricular nerve 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 Other Investigations Histopathological examination Nerve biopsy
Sweat function test Nasal mucosal smears Histamine tests Lepromin test FNAC Animal Models : Armadillo, Thymectomised, irradiated nude mice, Korean chipmunk etc. 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 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 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 Blister Packets 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 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 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 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 Precipitating Factors
Pregnancy / lactation Drugs-Antileprosy drugs, iodides Severe physical or mental stress, surgical stress Infections Alcohol 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 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 Type I reaction with enlarged nerve and nerve abscess 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 andjoint 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) ENL and necrotic ENL 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 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 Treatment Modalities Mild reaction Analgesics (aspirin or paracetamol)
Severe reaction Corticosteroids Antimalarials Clofazimine Thalidomide Methotrexate Cyclosporine Azathioprine Mycophenolate mofetil 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 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. 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 leprosypresent 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. 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 Deformities : Nerve Damage
Claw hand (ulnar, median) Clawing of the toes (posterior tibial) Wrist-drop (radial) Foot-drop (lateral popliteal) Lagophthalmos, facial palsy (facial) Trophic Ulcer : Stages Threatened ulcer : Process of tissue damage starts associated with inflammation Presents as edemaand warmth in region of metatarsal head with associated deep tenderness and increase in inter digital gap Concealed ulcer : Damage to subcutaneous tissue presents asnecrosis 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 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 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 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 Beforetendon surgery could be used as a means ofdocumenting nerve damage and the progress of the nerverecovery with treatment. 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 Prevention and Control of leprosy
Prevention of leprosy Early detection through survey and initiation oftreatment 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 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 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 leprosyis 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. Rehabilitation in Leprosy
Physical and mental restoration of patients to normal activities, sothat 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 MCQS Q.1) What is the incubation period of leprosy? 1-10 yrs
Q.2) When was National leprosy eradication programme (NLEP) started? 1982 1983 1984 1985 Ans : Q. 1 A, Q. 2 A MCQS Q.3) What is the generation time of leprosy? 1-10 days
Q.4) Satellite lesion is commonly seen in which type of leprosy? Indeterminate Lepromatous Borderline tuberculoid Tuberculoid Ans : Q. 3 B, Q. 4 C MCQS 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 Ans : Q. 5 D, Q. 6 B Photo Quiz Ans : Claw hand caused by affection of ulnar nerve 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 Ans : Borderline tuberculoid leprosy A 15 year old boy presented with multiple asymptomaticlesions with asymmetric enlargedulnar nerve. What is the likely diagnosis? Photo Quiz Ans : Vitiligo vulgaris, P. alba A 4 year old girl presented with aysmptomatic non scaly, whitish patch with intact sensations. What is the likely differential diagnosis? Thank You!