Leprosy
Leprosy, also called Hansen’s disease, is a chronic, slowly transmitted granulomatous infection caused by the obligate intracellular bacillus Mycobacterium leprae (and Mycobacterium lepromatosis). It is known for targeting two tissues in particular: keratinocytes and immune cells in the skin, and the Schwann cells of the peripheral nerves. Unlike most infections, the way leprosy looks clinically is not driven simply by how aggressive the bacteria are; it is determined by the host’s cell-mediated immunity (CMI). The Ridley-Jopling spectrum runs from tuberculoid leprosy (TT), where strong CMI walls off the bacteria, to lepromatous leprosy (LL), where CMI has failed and bacilli multiply unchecked inside Virchow cells (foamy histiocytes). The classic triad of discolored skin patches, loss of superficial sensation (pain, temperature, touch) and enlarged or tender peripheral nerves is the direct result of inflammation destroying nerve fibers. At Haute-Derma, our diagnostic workup is comprehensive: sensory testing with Semmes-Weinstein monofilaments, palpation of the nerves, earlobe slit-skin smears stained with Fite-Faraco for acid-fast bacilli (AFB), and skin biopsy for histopathology. Treatment combines the standard WHO multidrug therapy (MDT) with urgent control of lepra reactions to prevent permanent disability.
How the disease develops in the skin and immune system:
- The Ridley-Jopling spectrum and the Th1/Th2 shift:
- Tuberculoid (TT, high CMI): The immune response is dominated by T-helper 1 (Th1) cells, which release large amounts of IL-2 and interferon-gamma. Fully activated macrophages become epithelioid cells and Langhans giant cells that surround the bacteria, forming non-caseating granulomas. The bacterial load is very low (paucibacillary, PB), and acid-fast bacilli are rarely seen on slides.
- Lepromatous (LL, low CMI): CMI has collapsed and the response shifts to T-helper 2 (Th2) cells producing IL-4, IL-10 and IL-13, which blunt the macrophages’ ability to kill bacteria. Macrophages engulf huge numbers of bacilli but cannot digest them, turning into Virchow cells (foamy histiocytes) packed with parallel bundles of bacilli called globi. The bacterial load is very high (multibacillary, MB).
- Schwann cell tropism and peripheral nerve damage:
- The lipid coat of M. leprae contains a unique compound, phenolic glycolipid-1 (PGL-1), which binds specifically to the alpha-dystroglycan complex on the surface of the Schwann cells that wrap nerve fibers.
- The bacteria invade and multiply inside Schwann cells, triggering demyelination and apoptosis of nerve cells. Inflammatory infiltration makes the nerve swell inside its rigid sheath, causing ischemic damage to the nerve fibers and leading to loss of temperature, pain and touch sensation, as well as muscle wasting.
- How lepra reactions arise:
- Type 1 reaction (reversal reaction, RR): a delayed-type (type IV) hypersensitivity reaction seen in the borderline forms (BT, BB, BL). A sudden surge in Th1 immunity makes existing skin lesions swollen, red and painful and causes acute neuritis, with a high risk of disability.
- Type 2 reaction (erythema nodosum leprosum, ENL): an immune-complex (type III) reaction occurring in BL and LL leprosy. Mass breakdown of bacteria releases antigen that combines with IgG/IgM to form immune complexes. These deposit in vessel walls, activate complement and unleash large amounts of TNF-alpha, producing painful red nodules scattered over the body together with high fever.
Clinical Features
| Type | Typical Clinical Features | Mechanism and Bacterial Load |
|---|---|---|
| Tuberculoid leprosy (TT) | A few (1–3) hypopigmented or red patches with sharp, raised borders; dry, hairless, with complete loss of sensation within the lesion. | Strong Th1 immunity; bacteria almost entirely cleared; paucibacillary (PB); AFB (–); enlargement of a single nerve. |
| Lepromatous leprosy (LL) | Numerous symmetrical macules, papules and nodules; leonine facies; loss of eyebrows/eyelashes (madarosis); “glove and stocking” sensory loss. | Exhausted cell-mediated immunity; M. leprae multiplies unchecked in Virchow cells; multibacillary (MB); AFB 4+ to 6+. |
| Type 1 reaction (reversal reaction, RR) | Existing skin lesions suddenly become swollen, bright red, painful and may ulcerate; nerves become enlarged and very painful, with acute loss of motor function. | Delayed-type (Th1) hypersensitivity; immune flare against residual bacterial antigen; a neurological emergency. |
| Type 2 reaction (ENL, erythema nodosum leprosum) | Sudden crops of bright red, very painful nodules on the limbs and face; high fever, iritis, orchitis. | Immune-complex (type III) vasculitis with a burst of TNF-alpha; seen in BL/LL, often after MDT is started. |
Our Approach
At Haute-Derma, our diagnostic process for leprosy is designed to pick up nerve damage early and classify the disease accurately:
- Sensory and peripheral nerve assessment (neurological and sensory panel):
- Superficial sensation: We test three modalities (hot/cold temperature, pain with a pin, and light touch with cotton wool and Semmes-Weinstein monofilaments) in the affected skin, comparing it with healthy skin on the opposite side.
- Palpation of superficial nerves: We check for thickening, firmness and sharp tenderness of the ulnar nerve (elbow), common peroneal nerve (knee), great auricular nerve (neck) and median nerve (wrist).
- Slit-skin smear of the earlobe and lesions with AFB staining:
- A shallow scalpel incision (about 5 mm long and 2–3 mm deep) is made in the earlobe or the edge of a skin lesion, which is pinched to stop bleeding while tissue fluid is scraped off.
- Fite-Faraco stain (or modified Ziehl-Neelsen): Identifies acid-fast M. leprae bacilli, which appear red inside foamy cells.
- We calculate the Bacterial Index (BI) on a scale of 0 to 6+ and the Morphological Index (MI), which estimates the proportion of live bacteria.
- Skin biopsy, histopathology and diagnostic PCR:
- A 4 mm punch biopsy is taken from the active edge of a lesion.
- The pathologist assesses the granuloma pattern (epithelioid granulomas in TT, Virchow cells in LL) and looks for inflammation surrounding the small nerves of the deep dermis (neurotropism).
- Real-time PCR targeting the RLEP or rpoB gene regions of M. leprae is used when leprosy is suspected but AFB tests are negative.
Treatment at Haute-Derma
Leprosy treatment follows the World Health Organization (WHO) standard multidrug therapy (MDT) to eradicate the bacteria, prevent drug resistance and promptly control lepra reactions:
- WHO MDT regimen:
- Paucibacillary (PB: 1–5 skin lesions, AFB negative):
- Rifampicin: 600 mg once a month (supervised).
- Dapsone: 100 mg daily (self-administered).
- Duration: 6 doses completed within 6–9 months.
- Multibacillary (MB: more than 5 skin lesions or AFB positive):
- Rifampicin: 600 mg once a month (supervised).
- Clofazimine: 300 mg once a month (supervised) plus 50 mg daily (self-administered).
- Dapsone: 100 mg daily (self-administered).
- Duration: 12 doses completed within 12–18 months.
- Paucibacillary (PB: 1–5 skin lesions, AFB negative):
- Emergency management of lepra reactions:
- Type 1 reaction (RR) and acute neuritis:
- Nerve damage must be halted immediately with oral corticosteroids (prednisolone), starting at 40–60 mg/day and tapering over 12–20 weeks.
- MDT is continued throughout treatment of the reaction.
- Type 2 reaction (ENL):
- Thalidomide: the drug of choice for moderate to severe ENL (100–300 mg/day), with a dramatic response thanks to its TNF-alpha–suppressing effect (absolutely contraindicated in pregnancy).
- Prednisolone or high-dose clofazimine (300 mg/day) is used when thalidomide is not an option.
- Type 1 reaction (RR) and acute neuritis:
- Disability prevention at Haute-Derma: We teach patients with sensory loss how to soak their feet, apply moisturizer, wear protective footwear that offloads pressure and use protective eyewear to avoid injuries they cannot feel.
