Leprosy (Hansen disease)

Meet the patient

A 38-year-old farmer from a leprosy-endemic district is referred for a single, well-demarcated hypopigmented patch on his forearm that he "cannot feel". The patch is anaesthetic to cotton wool, and the ulnar nerve at the elbow is thickened and tender. He has noticed his little finger catching when he grips.^[2][9]

Two exam questions are now live, and the rest of this page exists to answer them: is this paucibacillary or multibacillary disease (which fixes the MDT regimen and duration), and is the tender nerve a type 1 reversal reaction (which makes this a steroid emergency, not a wait-and-see)?^[1][8]

The spectrum decides everything — recognise it first

The single most important skill in leprosy is reading the spectrum, because it sets the treatment and predicts the reactions. A patient with one anaesthetic patch and a strong cell-mediated response is paucibacillary and stable; a patient with leonine facies and anergy is multibacillary, infectious, and headed for type 2 erythema nodosum leprosum. Get the pole wrong and you mistime the MDT.^[1][9]

^{[1] [4] [10]}

The mantra for the viva: anaesthetic patch, thickened nerve, slit-skin smear — then PB or MB, six months or twelve. Say it in one breath and you have the spine of the whole topic.^[1]

The bacterium, the nerve, and the spectrum

Mycobacterium leprae is an obligate intracellular, acid-fast bacillus that lives in Schwann cells and dermal macrophages — the cooler tissues. Its doubling time of roughly 14 days is why leprosy is chronic, indolent and famously slow to declare itself; incubation runs years, and the bacillus has discarded so much of its genome that it cannot be cultured in artificial media.^[3][6]

Mechanism of nerve tropism, one line: the bacillus binds the G-domain of laminin-α2 in the Schwann-cell basal lamina through phenolic glycolipid-1 (PGL-1), then reprogrammes and demyelinates the Schwann cell — which is why a "skin disease" is, fundamentally, a peripheral-nerve disease.^[6][7]

Transmission is by prolonged close contact and respiratory droplets from bacilliferous lepromatous disease; most exposed people never become ill, because the clinical face of leprosy is set almost entirely by the host's Th1-versus-Th2 balance.^[3][12]

• Strong Th1 (IL-2, interferon-gamma) — organised epithelioid granulomas, few bacilli, tuberculoid disease.
• Th2 dominance (IL-4, IL-10, antibody) — disorganised foamy macrophages stuffed with bacilli (globi), lepromatous disease.
• Borderline poles sit between and are immunologically unstable — the natural home of the type 1 reversal reaction.^[6][12]

Etymology for viva gold: Hansen disease honours Armauer Hansen, who in 1873 demonstrated the bacillus in skin nodules — the first bacterium ever linked to a human disease, a full decade before Koch cultured M. tuberculosis. Lepra is Greek for "scaly", borrowed by the Latin physicians who could not yet tell it from psoriasis.^[3]

Read the spectrum — Ridley-Jopling, then the WHO split

The Ridley-Jopling spectrum places the patient along a continuum of cell-mediated immunity; the WHO split then collapses it into two treatment buckets. Examiners expect both, in that order, and they expect you to keep them separate. Five poles plus an indeterminate early form:^[1][9]

• TT (tuberculoid) — one to three large, well-demarcated anaesthetic plaques with a single thickened nerve, strong Th1 epithelioid granulomas; bacterial index 0, lepromin strongly positive; paucibacillary and stable.
• BT (borderline tuberculoid) — several asymmetric plaques with satellite lesions, definite sensory loss and multiple thickened nerves; BI 0-1+; the pole most prone to type 1 reversal reactions, especially in the first year of MDT.
• BB (mid-borderline) — annular "punched-out" lesions with an erythematous rim, normal midzone and anaesthetic centre (the "Swiss cheese" look); BI 2-3+; the most unstable pole, drifting either way.
• BL (borderline lepromatous) — many symmetric, ill-defined, shiny plaques and nodules with patchy sensory loss; BI 3-4+; at risk of both type 1 (downgrading) and type 2 reactions.
• LL (lepromatous) — diffuse symmetric infiltration, leonine facies, madarosis, saddle-nose, testicular atrophy, ichthyotic shins; foamy Virchow cells packed with globi; BI 4-6+; anergic, Th2-dominated and highly infectious.
• Indeterminate (I) — a single faint hypopigmented macule with equivocal sensation; 70-80 percent resolve, 20-30 percent declare themselves along the spectrum.^[9][12]

^{[9] [2] [12]}

Pure neuritic leprosy (a WHO category, not on the Ridley-Jopling spectrum) presents with thickened tender nerves and sensorimotor loss but no skin lesions — nerve biopsy shows granulomatous neuritis with acid-fast bacilli, and the PB-or-MB call is made on the nerve biopsy bacterial index.^[8][9]

The three cardinal signs — and why anaesthesia is the gate

Leprosy has exactly three cardinal signs, and any one of them obliges you to look hard for the other two.^[2]

1. A hypopigmented or erythematous skin patch with definite loss of sensation — the single most reliable bedside sign; loss of temperature and light touch precedes motor loss.
2. A thickened or tender peripheral nerve — palpate ulnar (elbow), common peroneal (fibular head), posterior tibial (medial malleolus), median (wrist) and greater auricular (neck).
3. Acid-fast bacilli on slit-skin smear — positive only in multibacillary disease.^[2][11]

The classic trap: labelling the patch pityriasis versicolor, vitiligo or post-inflammatory change because it "looks dermatological" — and never testing sensation. A hypopigmented patch that cannot feel cotton wool is leprosy until proven otherwise, and a thickened tender nerve settles it.^[2][13]

The mimic face-off every candidate reproduces:^[2][13]

Confirm at the slit-skin smear

Diagnosis is clinical and parasitological — there is no useful serology. The tools, in the order you reach for them:^[2]

• Slit-skin smear from the earlobe and the active lesion edge, stained with Ziehl-Neelsen or Fite-Faraco — gives the bacterial index; positive in MB, often negative in PB.
• Skin biopsy with Fite-Faraco stain — granulomatous dermatitis with perineural inflammation and acid-fast bacilli; confirms and classifies the pole.
• PCR for M. leprae DNA — confirms and is especially useful in indeterminate and PB disease where smears are negative.
• Lepromin (Mitsuda) test — measures host cell-mediated immunity, not infection; strongly positive in TT, negative in LL. It classifies the pole; it never diagnoses the disease.^[2][9]

Multidrug therapy — PB six months, MB twelve

WHO multidrug therapy is the only first-line treatment, it is free to every patient through national programmes, and the regimen has not changed since 1981 — a durability most guidelines can only dream of. Three rules fix everything: the monthly rifampicin dose is supervised, the daily doses are self-administered, and the duration is fixed regardless of how the skin looks. Doses below are for adults.^[1][10]

• Paucibacillary (PB) — 6 months of supervised monthly rifampicin plus daily dapsone:^[1][16]

  • Rifampicin 600 mg once monthly, supervised.
  • Dapsone 100 mg daily, self-administered.^[16]
  • Single-lesion PB alternative (ROM): rifampicin 600 mg plus ofloxacin 400 mg plus minocycline 100 mg, all as one supervised dose — the regimen trialled for single-lesion, smear-negative PB without nerve-trunk involvement.^[14][15]

• Multibacillary (MB) — 12 months of rifampicin, dapsone and clofazimine:^[1][17]

  • Rifampicin 600 mg once monthly, supervised.
  • Clofazimine 300 mg once monthly supervised plus 50 mg daily.
  • Dapsone 100 mg daily, self-administered.^[17][18]

• Children: a 10-year-old treated on the MB regimen in a published report received the standard monthly triplet (rifampicin 600 mg, clofazimine 300 mg, dapsone 100 mg) with daily clofazimine 50 mg and dapsone 100 mg — paediatric dosing follows the same supervised-monthly-plus-daily structure.^[18]

^{[1] [14] [15] [28]}

Leprosy reactions — immunological, not treatment failure

Reactions are abrupt immune shifts against M. leprae antigens — they are not drug failure, and MDT must continue through them. They are the commonest reason a leprosy patient comes to harm, and the discriminator between the two is the one thing you must hold in your head at 3am.^[1][8]

^{[8] [12]}

The confession every consultant makes: we all under-treat the first type 1 reaction because the skin "does not look that bad" — and then the nerve is dead by morning. New nerve tenderness or new motor weakness in a borderline patient is a steroid emergency, full stop.^[8]

Type 1 reversal reaction — nerve-damage emergency

A type 1 reaction is a delayed-hypersensitivity flare in borderline disease, occurring in roughly a quarter to a third of borderline cases, most often in the first 6 to 12 months of MDT as immunity "upgrades". It is an emergency because the swollen nerve ischaemias inside its sheath and can die within hours.^[8]

The bedside signs to elicit actively: existing lesions become red, indurated and tender; new lesions appear; and — critically — nerve tenderness and new weakness appear in the ulnar (elbow), median (wrist), common peroneal (fibular head) or posterior tibial (medial malleolus) distributions, with oedema of hands, feet or face. A reaction with neuritis is a steroid emergency.^[8]

Treat with prednisolone 1 mg/kg daily, tapered over roughly 12 weeks as the reaction settles; splint the limb in a functional position, give analgesia and physiotherapy, and continue the MDT.^[8][21]

^{[8] [21]}

Type 2 erythema nodosum leprosum — systemic emergency

Erythema nodosum leprosum (ENL) is an immune-complex phenomenon of BL and LL disease, affecting 20-50 percent of lepromatous patients; it may be acute, recurrent or chronic, and it can persist for years after MDT completes. Unlike type 1, the nodules are new lesions, not inflamed old plaques.^[1][12]

Look for crops of tender erythematous subcutaneous nodules on the trunk, face and extensor limbs with fever, malaise and arthralgia, and ask specifically for the systemic targets — neuritis, iritis or uveitis (slit-lamp mandatory), orchitis, dactylitis and lymphadenitis, with proteinuria from renal immune-complex deposition.^[8][12]

Thalidomide is the classic drug for ENL: the approved options are non-steroidal anti-inflammatory drugs, systemic corticosteroids, thalidomide and clofazimine, and published regimens span 100-400 mg/day — low-dose 100 mg/day proved effective even in severe, steroid-recalcitrant disease.^[19] Thalidomide was withdrawn originally for limb-reduction defects and remains a major human teratogen, with embryopathy cases still appearing where controls slip, so regulatory conditions apply: signed informed consent and adequate contraceptive measures.^[25][26]

• Corticosteroids and clofazimine are the other first-line options: oral prednisolone 1 mg/kg/day, gradually tapered; high-dose oral clofazimine 300 mg/day, later reduced to 100 mg/day, for chronic ENL.^[19][20]
• Steroid-sparing agents for chronic, recalcitrant or steroid-dependent ENL: azathioprine, methotrexate and ciclosporin.^[20]

^{[19] [25] [26]}

Disability grading — the EHF score

The WHO disability grade is the audit instrument of every leprosy programme, and the score you must record whenever you assess a patient. A grade of 0-2 is assigned to each of six body sites — both eyes, both hands, both feet — and the highest grade of any site serves as the person's overall grade; the sum across all six sites is the EHF (Eye-Hand-Foot) score, to a maximum of 12.^[22][23]

• All six sites are graded 0 to 2, with the highest single-site grade acting as the overall grade — so one visible deformity drags the whole patient to grade 2.^[22]
• Hands and feet are screened for sensory loss with monofilament testing — the 10 g monofilament was the field standard in leprosy control, since partly replaced by the ballpoint pen.^[24]
• Grade 2 means visible deformity — the grade whose proportion at diagnosis marks delayed detection, and the target of every early-case-finding programme.^[27]

^{[22] [24] [27] [8] [11]}

The nerve map and the disabling cascade

Leprosy is the leading infectious cause of disability worldwide, with a cumulative nerve-damage rate of 30-50 percent in untreated disease. The damage falls into four layers — the primary nerve palsies, the cascade that anaesthesia then unleashes, the eye, and the systemic complications of lepromatous disease.^[2][8]

^{[8] [11]}

• Ulnar nerve at the elbow — the commonest lesion; claw hand (MCP hyperextension with IP flexion of the fourth and fifth digits), first dorsal interosseous wasting and sensory loss on the ulnar border and little finger.
• Median nerve at the wrist — thenar wasting and loss of thumb opposition; combined ulnar and median palsy gives a total claw hand.
• Common peroneal at the fibular head — the commonest lower-limb lesion; foot drop with a high-stepping gait and sensory loss on the dorsum of the foot.
• Posterior tibial behind the medial malleolus — loss of intrinsic foot muscles and sole sensation; with foot drop this produces a flail, anaesthetic, ulcer-prone foot.
• Facial nerve (zygomatic and temporal branches) — lagophthalmos, corneal anaesthesia, exposure keratitis and, untreated, blindness; greater auricular and posterior auricular nerves provide useful diagnostic thickening signs.^[8]

The disabling cascade that follows anaesthesia is what the patient actually fears — repetitive unnoticed trauma on the anaesthetic sole produces callus, sub-callus haemorrhage, plantar ulceration (mal perforans), deep infection, osteomyelitis and amputation; in the hand, burns, cuts and contractures; in the foot and occasionally the hand, a painless Charcot joint. The eye adds lagophthalmos, exposure keratitis, chronic iritis, cataract and blindness. In LL, direct testicular invasion brings atrophy, gynaecomastia and infertility, and chronic inflammation brings renal AA amyloidosis — historically a leading cause of death.^[2][8][12]

^[1]

Ward-round test

Stem 1. A 40-year-old man has three hypopigmented anaesthetic plaques and a thickened tender ulnar nerve; slit-skin smear is negative. What regimen, what duration, and why not ROM?^[1]

AnswerShowHide

This is paucibacillary leprosy (up to 5 lesions, smear negative) — 6 months of rifampicin 600 mg once monthly plus dapsone 100 mg daily, the standard PB regimen. Not ROM: ROM was adopted for single-lesion, smear-negative PB without nerve-trunk involvement, and in PB with two to five lesions it relapsed more often than PB MDT — this patient has three lesions.^{[1][16][15][28]}

Stem 2. Six weeks into PB MDT, a borderline-tuberculoid patient's existing plaques turn red and tender, and she cannot spread her fingers against resistance. Name the reaction and the first drug.^[8]

AnswerShowHide

Type 1 (reversal) reaction with neuritis — a steroid emergency. Start prednisolone 1 mg/kg daily and continue MDT; do not wait, because the swollen nerve dies within hours. Splint the limb and arrange physiotherapy.^[8][21]

Stem 3. A lepromatous patient on month 8 of MB MDT develops crops of tender nodules on his shins with fever, painful testes and a red eye. What is the reaction, the first-line drug, and the one absolute contraindication?^[1]

AnswerShowHide

Type 2 erythema nodosum leprosum (ENL) — immune-complex in BL/LL, with orchitis and iritis. First-line options are thalidomide (regimens from 100 mg/day up to 400 mg/day), systemic corticosteroids (prednisolone 1 mg/kg/day) and clofazimine; pregnancy is the absolute contraindication to thalidomide — it is a major human teratogen that causes limb-reduction defects.^[19][20][25]

Stem 4. A patient with a single hypopigmented patch is offered "the one-dose treatment". Which regimen, and what are its three components?^[1]

AnswerShowHide

Single-dose ROM for single-lesion PB: rifampicin 600 mg plus ofloxacin 400 mg plus minocycline 100 mg as one supervised dose. Confirm the indication is truly single-lesion, smear-negative PB without nerve-trunk involvement — that is the population ROM was adopted for.^[14][15]

Stem 5. A patient's EHF score rises from 2 to 4 over six months of MDT. What does the change mean, and what do you do?^[8]

AnswerShowHide

A two-point rise is a sentinel event — new disability is appearing, most likely smouldering neuritis. Repeat a full nerve-function assessment (voluntary muscle testing, monofilament), look hard for a type 1 reaction, and treat neuritis with corticosteroids immediately; grade 1 anaesthesia is reversible, grade 2 deformity usually is not.^[8][11]

Stem 6. A hypopigmented patch on a child's cheek is faintly scaly, KOH shows "spaghetti and meatballs", and sensation is intact. Is this leprosy, and what single feature rules it out at the bedside?^[2]

AnswerShowHide

No — this is pityriasis versicolor (Malassezia, fine scale, positive KOH, no anaesthesia). The bedside feature that rules leprosy in or out is sensation: a leprosy patch has definite sensory loss and often a thickened nerve; versicolor, vitiligo and pityriasis alba never do.^[2][13]

^{[1] [8]}

References28ShowHide

1. [1]Grijsen ML, Nguyen TH, Pinheiro RO, et al. Leprosy Nat Rev Dis Primers, 2024.PMID 39609422
2. [2]Maymone MBC, Laughter M, Venkatesh S, et al. Leprosy: Clinical aspects and diagnostic techniques J Am Acad Dermatol, 2020.PMID 32229279
3. [3]Britton WJ, Lockwood DN. Leprosy Lancet, 2004.PMID 15081655
4. [4]Chen KH, Lin CY, Su SB, et al. Leprosy: A Review of Epidemiology, Clinical Diagnosis, and Management J Trop Med, 2022.PMID 35832335
5. [5]Li X, Ma Y, Li G, et al. Leprosy: treatment, prevention, immune response and gene function Front Immunol, 2024.PMID 38440733
6. [6]Mungroo MR, Khan NA, Siddiqui R. Mycobacterium leprae: Pathogenesis, diagnosis, and treatment options Microb Pathog, 2020.PMID 32931893
7. [7]Sugawara-Mikami M, Tanigawa K, Kawashima A, et al. Pathogenicity and virulence of Mycobacterium leprae Virulence, 2022.PMID 36326715
8. [8]Ebenezer GJ, Scollard DM. Treatment and Evaluation Advances in Leprosy Neuropathy Neurotherapeutics, 2021.PMID 34799845
9. [9]Alrehaili J. Leprosy Classification, Clinical Features, Epidemiology, and Host Immunological Responses: Failure of Eradication in 2023 Cureus, 2023.PMID 37809252
10. [10]Gupte M. Global leprosy scenario: Eradication, elimination or control? Indian J Med Res, 2023.PMID 37040220
11. [11]Makhakhe L. Leprosy review S Afr Fam Pract (2004), 2021.PMID 34797098
12. [12]Froes LAR Junior, Sotto MN, Trindade MAB. Leprosy: clinical and immunopathological characteristics An Bras Dermatol, 2022.PMID 35379512
13. [13]Franco-Paredes C, Marcos LA, Henao-Martínez AF, et al. Cutaneous Mycobacterial Infections Clin Microbiol Rev, 2018.PMID 30429139
14. [14]Deshmukh AR, Dhurat RS, Jerajani HR A comparative clinico-pathological study of single dose ROM in paucibacillary leprosy patients with 1-3 skin lesions. Indian J Lepr, 2003.PMID 15267190
15. [15]Diniz LM, Catabriga MD, Souza Filho JB [Evaluation years in leprosy patients treated with single dose alternative scheme ROM (rifampin, ofloxacin, minocycline), after seven to nine]. Rev Soc Bras Med Trop, 2010.PMID 21181026
16. [16]Kar PK, Arora PN, Ramasastry CV, et al. A clinicopathological study of multidrug therapy in borderline tuberculoid leprosy. J Indian Med Assoc, 1994.PMID 7822849
17. [17]Damasco MH, Sarno EN, Lobão AS, et al. Effect of cutaneous cell-mediated immune response to rIFN gamma on Mycobacterium leprae viability in the lesions of lepromatous leprosy. Braz J Med Biol Res, 1992.PMID 1342221
18. [18]Di Martino Ortiz B, Masi MR, Knopfelmacher O, et al. [Childhood leprosy: Report of a case]. Dermatol Online J, 2011.PMID 21272504
19. [19]Savitha B, Sardana K, Kumari R, et al. Case Report: Rapid Response to Low-Dose Thalidomide in a Case of Severe Steroid Recalcitrant Erythema Nodosum Leprosum. Am J Trop Med Hyg, 2021.PMID 34662871
20. [20]Jitendra SSV, Bachaspatimayum R, Devi AS, et al. Azathioprine in Chronic Recalcitrant Erythema Nodosum Leprosum: A Case Report. J Clin Diagn Res, 2017.PMID 28969152
21. [21]Safa G, Darrieux L, Coic A, et al. Type 1 leprosy reversal reaction treated with topical tacrolimus along with systemic corticosteroids. Indian J Med Sci, 2009.PMID 19770527
22. [22]Nienhuis WA, van Brakel WH, Butlin CR, et al. Measuring impairment caused by leprosy: inter-tester reliability of the WHO disability grading system. Lepr Rev, 2004.PMID 15508899
23. [23]Raposo MT, Caminha AV, Heukelbach J, et al. Assessment of physical impairments in leprosy patients: a comparison between the world health organization (who) disability grade and the Eye-Hand-Foot score. Rev Inst Med Trop Sao Paulo, 2011.PMID 21537754
24. [24]Koelewijn LF, Meima A, Broekhuis SM, et al. Sensory testing in leprosy: comparison of ballpoint pen and monofilaments. Lepr Rev, 2003.PMID 12669932
25. [25]de Jong-van den Berg LT, Rutgers J, Cornel MC [Thalidomide once more in the spotlight]. Ned Tijdschr Geneeskd, 1998.PMID 10028338
26. [26]Schuler-Faccini L, Soares RC, de Sousa AC, et al. New cases of thalidomide embryopathy in Brazil. Birth Defects Res A Clin Mol Teratol, 2007.PMID 17676592
27. [27]Srinivas G, Muthuvel T, Lal V, et al. Risk of disability among adult leprosy cases and determinants of delay in diagnosis in five states of India: A case-control study. PLoS Negl Trop Dis, 2019.PMID 31247040
28. [28]Manickam P, Nagaraju B, Selvaraj V, et al. Efficacy of single-dose chemotherapy (rifampicin, ofloxacin and minocycline-ROM) in PB leprosy patients with 2 to 5 skin lesions, India: randomised double-blind trial. Indian J Lepr, 2012.PMID 23484334