Hansen’s Disease Chapter Notes | Dermatology and Venereology - NEET PG PDF Download

Organism

• Mycobacterium leprae grows best at 30°C, below human core temperature, leading to lesions in cooler superficial areas like ear lobes, nose, testes, liver, and superficial nerves (e.g., ulnar, facial).
• Prefers cooler areas, avoiding deeper, warmer nerves.
• Best cultivated in armadillos, but also in mouse footpads, nude mice, and thymectomized mice.
• Phenolic glycolipid-1 (PGL-1) is a unique glycolipid on the bacillus surface, contributing to pathogenesis.
• Bacilli doubling time is 11-13 days (average 12 days).

Classification

Ridley-Jopling Classification

• Based on four criteria: Clinical, Bacteriological (slit skin smear - SSS), Histological (skin biopsy), and Immunological (lepromin testing).
• Classifies leprosy into five types: Tuberculoid (TT), Borderline Tuberculoid (BT), Borderline-Borderline (BB), Borderline Lepromatous (BL), Lepromatous-Polar (LLp).
• Includes a subpolar form (LLs) between IL-polar and BL.
• Borderline leprosies include BT, BB, and BL.
• Does not include indeterminate or pure neural types of Hansen's disease.

Pathogenesis

• BB is the most unstable form of leprosy.
• Stable leprosy (TT, LLp) does not change or shift immunologically.
• Unstable leprosies (BT, BB, BL) can shift between each other.

Disease Behavior

• TT has strong T-cell immunity (Th-1 response), forming tuberculoid granulomas, killing many bacilli, making it paucibacillary (PB).
• LL has absent T-cell immunity and high B-cell immunity (Th-2 response), leading to numerous bacilli in macrophages (foam cells), making it multibacillary (MB).
• Without treatment, immunity slides toward LL (downgrading), reducing tuberculoid granulomas and increasing foam cells.
• TT is stable and does not downgrade; BT, BB, BL can downgrade to LL-subpolar (LLs), but LLs does not downgrade to LL-polar (LLp).
• Treatment improves immunity (upgrading): T-cell improvement causes Type 1 lepra reaction; B-cell improvement causes Type 2 lepra reaction.
• BT and BB show Type 1 lepra reaction post-treatment due to increased T-cell immunity.
• LLs shows Type 2 lepra reaction post-treatment due to increased B-cell immunity.
• BL may show either Type 1 or Type 2 lepra reactions post-treatment.
• TT and LLp are stable and typically do not show reactions.

Types of Leprosy

1. Indeterminate Hansen's Disease

• Early form where the immune system has not yet determined its response to the bacillus.
• Many patients self-heal; some progress to TT, BT, BL, or LL.
• Presents as a solitary, ill-defined, hypopigmented macule or patch on cheeks, arms, thighs, or buttocks.
• Normal sensations and sweating; peripheral nerves not enlarged.
• Histology shows periadnexal and perineural lymphocytic infiltrate without granulomas; few or no bacilli seen on biopsy.

2. Tuberculoid Leprosy (TT)

• Characterized by tuberculoid granulomas forming in the dermis and cutaneous nerves, driven by a Th-1 immune response.
• Exhibits a robust cell-mediated immune response.
• Nerve granulomas cause compression, leading to symptoms such as sensory loss, loss of sweating, and hypopigmentation (occasionally erythematous) in the affected skin area.
• Typically involves a single thickened nerve and a single skin lesion, though up to three lesions may occur.
• The characteristic lesion is a plaque with a well-defined, hypopigmented (sometimes erythematous) elevated border that slopes to a flattened center, resembling a "saucer right side up."
• Well-defined lesion borders reflect strong immunity, in contrast to the ill-defined borders seen in lepromatous leprosy (LL).

3. Borderline Tuberculoid (BT)

• Most common type in India.
• Similar to TT but with more lesions (3-10) and few thickened nerves.
• Features 'satellite lesions' around the main lesion.

Satellite lesion in BT

4. Mid-Borderline, Borderline-Borderline (BB)

• Many countable lesions (10-30) and many thickened nerves.
• Lesions increasingly cross the midline.
• Shares features of TT (well-defined inner border) and LL (ill-defined outer border).
• Lesions described as inverted saucer, Swiss-cheese, punched out, dimorphic, or annular, with normal skin at the center.
• Sensations and sweating improve as granuloma size reduces and foam cells increase, reducing nerve compression.
• Most unstable form of leprosy.

5. Borderline Lepromatous (BL)

• Numerous small, uncountable lesions and numerous thickened nerves.
• Lesions cross the midline, becoming almost completely symmetrical.
• Sensations and sweating return to near normal due to minimal nerve compression from fewer granulomas and more foam cells.
• Features inverted saucer, Swiss-cheese, punched out, or dimorphic lesions.

6. Lepromatous Leprosy (LL)

• Dominated by foam cells (lepra cells) on biopsy due to Th-2 response with IL-4 and IL-10 prominence.
• Diffuse skin infiltration with ill-defined borders due to lack of immune response, allowing bacilli dissemination.
• Nodules and infiltration thicken skin, causing prominent skin folds.
• Perfectly symmetrical lesions; no granulomas, so no initial nerve compression, maintaining normal sensations and sweating early on.
• Gradual bacilli invasion of nerves leads to peripheral neuropathy and glove-and-stocking anesthesia.
• Earliest signs include nasal stuffiness and epistaxis; nasal discharge is a primary infection source.
• Other features: ear lobe infiltration (buddha ears), madarosis, gynecomastia (testicular involvement), saddle nose, nasal septal perforation.
• Histopathology shows foam cells in the dermis with an uninvolved papillary dermis (grenz zone, best seen in LL).

Histoid Leprosy

• A type of LL, often with dapsone resistance, more common with past dapsone monotherapy.
• Presents with shiny papules and nodules with intervening normal skin.
• Skin biopsy shows spindle-shaped foam cells.

Lucio Leprosy

• Non-nodular LL, also called 'lepra bonita' (pretty leprosy).
• Common in Mexico and Central America.
• Features diffuse skin infiltration, no wrinkles, and a shiny, youthful face.

Nerve Involvement in Leprosy

• 100% of patients have nerve involvement.
• Toward TT: rapid nerve compression, non-symmetrical involvement, no glove-and-stocking anesthesia.
• Toward LL: slower peripheral nerve invasion, leading to symmetrical peripheral neuropathy and glove-and-stocking anesthesia.
• Trophic ulcers occur due to loss of peripheral sensations.
  Trophic ulcer
• Pure neural Hansen’s occurs when only nerves are involved without clinical skin involvement.
• Order of sensory loss: hot and cold differentiation > cold > hot > light touch > pain > deep touch.

Eye Involvement in Leprosy

• 7th nerve involvement causes corneal erosions, exposure keratitis, iridocyclitis, and lagophthalmos.
• In BL and LL, the iris may show micro-granuloma deposits ('iris pearls').

Systemic Involvement in Leprosy

• Secondary amyloidosis with renal impairment is common.
• Renal involvement: secondary amyloidosis is the most common lesion; among glomerulonephritis, mesangioproliferative glomerulonephritis > MPGN > MPN.
• CNS, female reproductive system, lungs, prostate, and breasts are not involved.
• Between ovary and uterus, the uterus is less likely to be involved.

Histopathology in Leprosy

• Uses routine H&E stains and Fite-Faraco stain for acid-fast bacilli (AFB).
• From TT to LL: tuberculoid granulomas decrease, while foam cells, grenz zone formation, and bacilli numbers increase.
• Foam cells are dermal histiocytes filled with lipids, appearing foamy on histology.

Reactions in Leprosy

Type 1 Lepra Reaction (Reversal/Upgrading)

• Occurs during or within 3 years post-treatment, primarily cell-mediated (Type 4 hypersensitivity).
• Mainly in borderline spectrum (BT, BB, BL), most severe in BL.
• Involves inflammation of existing lesions (red, painful, edematous) and/or neuritis (red, painful, inflamed nerves).
• Sudden neuritis can cause permanent nerve damage; nerve abscesses (most in BT) may form.
• Severe cases may cause ulceration (Lazarine leprosy).
• No systemic inflammation (no fever).
• Treatment for skin reaction: NSAIDs, oral steroids (DOC, 1 mg/kg prednisolone tapered over 12 weeks), azathioprine, chloroquine, methotrexate, cyclosporine.
• Treatment for neuritis: splinting of limb, oral steroids (DOC), incision and drainage for nerve abscesses (especially ulnar nerve) to restore function.

Type 2 Lepra Reaction (Erythema Nodosum Leprosum - ENL)

• Primarily humoral (Type 3 hypersensitivity) with immune complex deposits in tissues and vessels (leukocytoclastic vasculitis).
• Cytokine involved: TNF-α.
• Presents with new, tender, red papules or nodules on extremities and face; existing lesions unchanged.
• Systemic inflammation: fever, arthralgia, conjunctivitis, keratitis, iritis, synovitis, nephritis, hepatosplenomegaly, orchitis, generalized lymphadenopathy.
• Treatment for first episode: prednisolone (1 mg/kg, tapered over 12 weeks, DOC).
• Treatment for recurrent/chronic ENL: prednisolone + thalidomide or prednisolone + clofazimine.
• Thalidomide is the fastest-acting drug (suppresses ENL in 48-72 hours) but not supported by WHO due to risks of phocomelia and peripheral neuropathy.

Lucio Phenomenon

• Seen only in Lucio leprosy.
• Caused by severe ischemia from thrombosis of dermal vessels, leading to hemorrhagic infarcts with serrated margins and ulceration (ulceronecrotic lesions).
• Accompanied by systemic inflammation: fever, arthralgia, conjunctivitis, keratitis, iritis, synovitis, nephritis, hepatosplenomegaly, orchitis, generalized lymphadenopathy.
• Treatment: NSAIDs (for mild cases), oral steroids (DOC), thalidomide, clofazimine, azathioprine, chloroquine, colchicine.

Diagnosis

WHO Definition of Leprosy

• In endemic countries, leprosy is diagnosed if one or more cardinal signs are present: hypopigmented or reddish skin lesions with definite sensory loss, thickened nerves, positive skin smears.
• Mnemonic: LEProsy - L = Loss of sensation, E = Enlarged nerves, P = Positive AFB on smear.
• Skin biopsy confirms diagnosis; nerve biopsy used for pure neural Hansen’s.

Slit Skin Smear (SSS)

• Slits made on skin with a blade, stained for AFB; WHO recommends 4 sites (minimum 3: one ear lobe, two active lesions).
• AFB staining patterns: Solid bacilli (S) = viable, Fragmented (F) = dead, Granular (G) = dead.
• Bacterial Index (BI): Counts S + F + G (dead + living) on a 0-6 scale, indicating total bacillary load; remains positive post-therapy.
• Morphological Index (MI): Counts only solid (living) bacilli, reported as a percentage (e.g., 50% means 50% bacilli are alive); better for treatment efficacy and drug resistance, becomes negative post-therapy.
• BI reduces by 1+ annually on treatment; relapse diagnosed if BI increases by 2+ from baseline.
• SSS negative = paucibacillary (PB); SSS positive = multibacillary (MB).
• SSS may yield false negatives due to superficial sampling; histological biopsy is the gold standard.
• Best site for SSS: untreated cases - ear lobes; treated cases - dorsa of fingers.
• SSS detects bacilli only if >10,000/gm of tissue, so negative in TT, indeterminate, and pure neural Hansen’s.
• Lepromin Test
  • Intradermal antigen injection to assess cell-mediated immunity (CMI).
  • Prognostic test, useful for classifying leprosy (negative = lepromatous side, positive = tuberculoid side).
  • Not diagnostic, as it is positive in healthy individuals.
  • Readings: Fernandez response (within 48 hours), Mitsuda response (at 4 weeks, better CMI indicator).
• FNAC of Nerves
  • Used for pure neural leprosy; aspirate stained for cells and bacilli.

Treatment

Most patients have established nerve damage, so hypoesthesia and crib change may persist post-treatment; patients need counseling on this.

Drugs in Leprosy

• Dapsone: Weakly bactericidal, inhibits dihydrofolic acid. Side effects: anemia, dapsone hypersensitivity syndrome (erythroderma, fever, lymphadenopathy, hepatitis after 5 weeks).
• Rifampicin: Powerful bactericidal, cornerstone of leprosy management. Monthly dosing suffices due to M. leprae’s slow 12-day doubling time. Resistance is a major concern. WHO guideline for rifampicin-resistant patients: Intensive phase (6 months, daily supervised): moxifloxacin 400 mg, clofazimine 50 mg, clarithromycin 500 mg, minocycline 100 mg; Continuation phase (18 months, monthly supervised): moxifloxacin 400 mg, clarithromycin 1000 mg, minocycline 200 mg.
• Rifapentine: Long-acting rifampicin derivative, more potent than rifampicin.
• Clofazimine: Weakly bactericidal, orange-colored dye. Side effects: ichthyosis, reversible skin discoloration/darkening. Used for both anti-leprosy and anti-reactional (ENL) treatment.
• Ethionamide/Prothionamide: Bactericidal, less potent than rifampicin.
• Fluoroquinolones (Ofloxacin/Moxifloxacin): Bactericidal; moxifloxacin is as effective as rifampicin.
• Minocycline: Bactericidal.
• Clarithromycin: Bactericidal.

WHO Disability Grading of Leprosy

Hands and Feet

• Grade 0: No anesthesia, no visible deformity/damage.
• Grade 1: Anesthesia present, no visible deformity/damage.
• Grade 2: Visible deformity present (e.g., claw hand, deformed foot).

Eyes

• Grade 0: No eye problem due to leprosy.
• Grade 1: Eye problem present, but vision not severely affected (vision 6/60 or better).
• Grade 2: Severe visual impairment (vision <6/60, cannot count fingers), lagophthalmos, iridocyclitis, corneal opacities.

Immunoprophylaxis in Leprosy (Vaccines)

• Limited to high-endemicity pockets, close family contacts, and high-risk groups.
• Vaccines: BCG, BCG + Killed M. leprae (Convit vaccine), Mycobacterium indicus pranii (MIP), Indian Cancer Research Institute (ICRC) vaccine, Mycobacterium vaccae vaccine.