Cutaneous Tuberculosis & Nontuberculous Mycobacterial Infections
Cutaneous tuberculosis (CTB) and nontuberculous mycobacterial (NTM) infections are complex chronic infections that challenge both clinical and histopathologic diagnosis in dermatology. Classic cutaneous TB is caused by Mycobacterium tuberculosis (or, less often, M. bovis), whereas NTM infections are caused by environmental mycobacteria such as M. marinum (fish tank granuloma), M. ulcerans (Buruli ulcer), M. fortuitum, M. chelonae and M. abscessus (often linked to invasive or cosmetic procedures and thread embedding). Skin findings range widely, from papules, nodules and hardened plaques to chronic non-healing ulcers and suppurating necrotic nodules, depending on the route of entry (primary or secondary), the bacterial load and, above all, the host's cell-mediated immunity (CMI). Whether caseating or non-caseating granulomas form reflects the prolonged struggle between macrophages and acid-fast bacilli (AFB). At Haute-Derma, our diagnostic workup brings together dermoscopy, Mantoux/IGRA testing, urgent Ziehl-Neelsen staining, skin biopsy with histopathology, culture on specialized media and PCR-RFLP molecular testing, so that long-term multidrug therapy can be tailored precisely.
Pathogenesis and immune response in the skin:
- Route of entry and the CMI-dependent spectrum:
- Primary inoculation through the skin: Bacilli enter through a scratch (for example tuberculosis verrucosa cutis from direct contact, or M. marinum from a fish tank). In hosts with strong CMI, a rapid delayed-type (type IV) hypersensitivity reaction draws in T lymphocytes and macrophages to wall off the bacteria, producing warty, fibrotic lesions with few organisms (paucibacillary).
- Secondary spread from a deeper focus (endogenous or contiguous): Bacteria reach the skin from underlying TB of bone, joint or lymph node (scrofuloderma) or through the bloodstream (miliary tuberculosis of the skin). In immunocompromised people with weak CMI, the body cannot contain the bacteria, resulting in extensive necrotic ulcers with a very high bacterial load (multibacillary).
- Caseating granulomas and epithelioid macrophages:
- Mycobacteria escape destruction in the macrophage phagolysosome thanks to a cell wall rich in mycolic acid and cord factor.
- Macrophages release IL-12, recruiting T-helper 1 (Th1) cells that secrete IFN-gamma. IFN-gamma transforms macrophages into epithelioid cells and multinucleated Langhans giant cells, whose nuclei form a horseshoe pattern.
- The center of the granuloma becomes ischemic and, under the action of lytic enzymes, undergoes the caseous necrosis typical of cutaneous TB. NTM lesions, by contrast, usually form suppurative granulomas that combine neutrophilic microabscesses with epithelioid cells.
- Mycolactone toxin in M. ulcerans infection (Buruli ulcer):
- Unlike M. tuberculosis, M. ulcerans secretes a lipid exotoxin called mycolactone. It is strongly cytotoxic (triggering apoptosis of keratinocytes and fat cells) and suppresses local immunity by blocking inflammatory cytokine production.
- The result is a deep, wide ulcer in the subcutis with ragged, undermined edges that is entirely painless and shows little surrounding inflammation.
Clinical Features
| Form | Typical Clinical Findings | Pathogenesis and Bacterial Load |
|---|---|---|
| Tuberculosis verrucosa cutis | Firm, rough, warty hyperkeratotic plaque with a red-purple border; the center may be atrophic or slightly suppurative; usually on the hands and fingers. | Direct reinfection in a person with strong CMI; very few bacteria (paucibacillary); strongly positive Mantoux reaction. |
| Scrofuloderma | Firm lymph node or deep tissue that tethers to the skin, suppurates and ruptures, forming sinus tracts that drain caseous pus and heal with puckered, cord-like scars. | Direct extension from a deep TB focus (cervical nodes, bone); moderate CMI; moderate to high bacterial load. |
| Lupus vulgaris | Red-brown or pale gray macules or plaques, smooth or scaly; "apple-jelly" sign on diascopy. | Spread via blood or lymphatics in a person with stable CMI; very slowly progressive, with a risk of squamous cell carcinoma (SCC) developing in the scar. |
| M. marinum infection (fish tank granuloma) | Chronic red-purple papules or nodules on the hand that progress to a chain of draining nodules along the lymphatics (sporotrichoid spread). | Opportunistic infection through a scratch while cleaning a fish tank or handling seafood; forms suppurative granulomas; grows best at 30°C. |
| Rapidly growing NTM (M. fortuitum/abscessus) | Painful red nodules, cold abscesses and slow-healing ulcers after cosmetic procedures, injections, thread embedding, liposuction or tattooing. | Environmental bacteria introduced via contaminated instruments or water; resistant to many standard antibiotics. |
Our Approach
At Haute-Derma, suspected cutaneous TB and NTM lesions are worked up through a standardized pathway so that no diagnosis is missed:
- Digital dermoscopy and diascopy:
- Diascopy: Pressing a glass slide on a lupus vulgaris lesion blanches the vascular redness and reveals yellow-orange to red-brown "apple-jelly" nodules, which are tuberculous granulomas in the dermis.
- Dermoscopy: Shows arborizing vessels over irregular gray-orange structureless areas, along with thick, fissured keratin scale in tuberculosis verrucosa cutis.
- Immunologic and microbiologic testing:
- Mantoux tuberculin skin test (TST) and IGRA (QuantiFERON-TB Gold): Assess systemic infection with M. tuberculosis.
- Ziehl-Neelsen (AFB) stain: Performed on pus smears or biopsy tissue. Note that in paucibacillary cutaneous TB, AFB are found in only about 10–30% of cases.
- Punch biopsy and molecular PCR testing:
- The skin biopsy is split in two: one half goes to pathology (H&E and ZN stains), the other is sent fresh for culture and real-time Mycobacterium PCR.
- PCR-RFLP: Identifies M. tuberculosis DNA precisely or distinguishes NTM species (M. marinum, M. abscessus, M. chelonae) within 24–48 hours.
Treatment at Haute-Derma
Treating cutaneous TB and NTM means combining several antibiotics at the right dose for the full duration, to prevent resistance and eradicate dormant bacteria:
- Cutaneous TB regimen (2RHZE / 4RH):
- Intensive phase (2 months): Four drugs taken daily by mouth: rifampicin (10 mg/kg), isoniazid (5 mg/kg), pyrazinamide (25 mg/kg) and ethambutol (15 mg/kg).
- Continuation phase (4 months): Two drugs: rifampicin and isoniazid.
- Note: Vitamin B6 (pyridoxine 10–25 mg/day) is added to prevent isoniazid-induced peripheral neuropathy.
- Targeted treatment of nontuberculous mycobacteria (NTM):
- M. marinum: Clarithromycin (500 mg orally twice daily) plus doxycycline (100 mg orally twice daily) or rifampicin for 3–6 months, continued for at least 4–8 weeks after the skin has fully healed.
- Rapidly growing NTM (M. abscessus / M. chelonae): Because resistance is so common, treatment is guided by susceptibility testing. It usually starts with clarithromycin/azithromycin plus IV amikacin plus tigecycline or imipenem, followed by newer oral agents (bedaquiline or clofazimine) for 6–12 months.
- Surgical support and cosmetic repair at Haute-Derma:
- Large cold abscesses are drained and localized fibrotic warty plaques are removed once antibiotics have been running steadily for at least 2–4 weeks.
- Disfiguring, puckered scrofuloderma scars are revised with fractional CO2 laser combined with autologous fat grafting once the patient is confirmed to be fully cured.
