Cutaneous tuberculosis

Meet the patient

A 42-year-old woman from a high-burden region has had a slowly enlarging, soft, reddish-brown plaque on her nose for eight years. Press a glass slide against it and the nodules turn the colour of apple jelly. The plaque has eaten into her nasal cartilage, and a biopsy shows caseating granulomas.[1][2]

Two questions frame every cutaneous TB stem: what route did the organism take to reach the skin? — because the route sets the morphology and the name — and how strong is the host's cell-mediated immunity? — because immunity sets the bacillary load and, with it, whether the biopsy will teem with organisms or show none at all.[1][3]

One organism, one signature, four routes — the spine of the topic

The clinical form is the visible product of two variables: the route and the host's immunity. A strong cell-mediated response in a BCG-vaccinated adult walls off the organism into paucibacillary, granulomatous forms such as warty TB or lupus vulgaris, in which acid-fast bacilli are scarce on biopsy. A weak or anergic response — advanced HIV, malnutrition, overwhelming disseminated disease — produces multibacillary forms such as scrofuloderma, orificial TB, and miliary TB. The bacillary load is the inverse of the immunity is the single most rewarding concept in the topic.[1][3]

The unifying histological signature is the caseating (necrotising) granuloma: central caseation (cheese-like, structureless necrosis) ringed by epithelioid macrophages, Langhans giant cells (with a horseshoe rim of peripheral nuclei), and an outer cuff of lymphocytes. That pattern is the morphological signature of a vigorous Th1 response to a persistent intracellular pathogen.[1]

Exogenous inoculation — the organism enters through broken skin

In exogenous cutaneous TB, M. tuberculosis (or M. bovis) enters through an abrasion, a wound, a laboratory or autopsy accident, or contact with contaminated material. The form depends on whether the host has been previously sensitised.[3][5]

The primary tuberculous chancre arises in a tuberculin-negative host with no prior immunity — a painless ulcer with a granular base and an undermined edge at the inoculation site (commonly a hand or finger), with regional lymphadenopathy two to four weeks later. This is the primary inoculation complex, the cutaneous analogue of the Ghon focus. It is seen most often in children, heals spontaneously over months, and the tuberculin skin test converts to positive as immunity develops.[3][5]

Tuberculosis verrucosa cutis (warty TB) is what the same inoculation produces in a host with good cell-mediated immunity — previously infected or BCG-vaccinated, tuberculin-positive. A hyperkeratotic, verrucous, warty plaque with a violaceous inflammatory rim grows slowly over years on the dorsum of the hand, a finger, the knee, or the foot. It is painless, tends not to ulcerate, and is paucibacillary — strong host containment of the organism. This is the cutaneous form that best reflects a strong host response.[5]

Contiguous spread — the lesion reflects the underlying disease

When tuberculosis in a deeper structure extends directly into the overlying skin, the clinical form reflects the underlying disease.[1]

Scrofuloderma is the breakdown of a tuberculous lymph node — most often a cervical node, less often axillary or inguinal — that enlarges, softens, and finally erupts through the skin, discharging caseous material through bluish, undermined sinus tracts. Over time the tracts heal with characteristic bridged, keloidal, or papery scarring. It is the commonest form of cutaneous TB in children in endemic regions such as India, where the organism is usually M. tuberculosis — in contrast to atypical mycobacterial cervical adenitis seen in high-income countries.[3][5]

Orificial tuberculosis is TB from an active pulmonary source spreading to the oral mucosa and lips, or from an intestinal source to the anal and genital mucocutaneous junctions, producing painful, shallow, ragged ulcers with undermined bluish edges. Its presence indicates advanced systemic tuberculosis and poor host immunity, and it carries a poor prognosis.[5]

Haematogenous spread — bloodborne seeding, indolent to fulminant

Haematogenous seeding of the skin produces a spectrum from indolent to fulminant, again modulated by immunity.[1]

Lupus vulgaris is the classic, indolent, paucibacillary form — soft, reddish-brown, translucent plaques and nodules most often on the face (nose, cheeks, ear lobes), neck, and buttocks. On diascopy (pressing a glass slide against the lesion), the nodules show the pathognomonic apple-jelly (yellow-brown) colour. The plaque enlarges centrifugally over years, healing with central atrophic scarring while remaining active at the edges, and may destroy underlying nasal and auricular cartilage. It is the commonest form of cutaneous TB in many developed-country series.[2][5][7]

Acute miliary tuberculosis of skin is the rare, fulminant face of disseminated TB — tiny, widespread erythematous papules, pustules, vesicles, petechiae, and small ulcers seeding the skin with systemic toxicity. It occurs in immunosuppressed patients (advanced HIV) and in young children, is multibacillary, and is rapidly fatal if untreated. This is the dermatological face of a systemic emergency.[5]

Metastatic tuberculous abscess (tuberculous gumma) — firm, subcutaneous, cold abscesses arising from haematogenous spread in malnourished or immunosuppressed patients, which may rupture to form sinus tracts.[6]

The tuberculids — sterile skin, strong Mantoux, resolves with therapy

The tuberculids are not organisms in the skin — they are a hypersensitivity reaction to haematogenously disseminated TB antigens. Three diagnostic criteria define a tuberculid: the skin lesion is sterile (negative AFB stain and culture), the patient is strongly tuberculin-positive, and the eruption resolves with anti-TB therapy.[8]

[1] [8]

The discriminator line: the tuberculids have sterile skin, a strongly positive Mantoux or IGRA, and resolve with anti-TB therapy — the underlying focus must always be sought and treated.[8]

The face-off table — ten forms, one discriminator each

Examiners reward a precise description of each form, paired with its mimics. The discipline is to match each form to the mimics that share its morphology and distinguish them on histology, AFB or PCR, and the systemic context.[2]

[1] [3]

The can't-miss mimics. Squamous cell carcinoma (Marjolin) arising in chronic lupus vulgaris — biopsy any change within a plaque. Miliary TB in the immunosuppressed patient with atypical widespread papules is a systemic emergency. Atypical (non-tuberculous) mycobacteria — M. marinum (swimming-pool or fish-tank granuloma), M. fortuitum, chelonae, abscessus (rapid growers, post-procedure abscesses), and M. scrofulaceum or avium (paediatric cervical adenitis) — mimic any cutaneous TB form and are distinguished only by culture and PCR.[4][6]

Investigations — tissue is the answer, and a negative AFB never excludes

The diagnosis rests on tissue-based demonstration of the organism or its genome, supported by the immune response and the systemic work-up. Because the paucibacillary forms are often smear-negative, histology plus culture plus PCR together give the highest yield, and a negative AFB stain never excludes the diagnosis.[1][5]

A punch or incisional biopsy of lesional skin through the active edge is the single most important investigation, divided for three simultaneous tests. Histopathology looks for the caseating granuloma — AFB are scanty or absent in the paucibacillary forms (lupus vulgaris, warty TB) and abundant in the multibacillary forms (chancre, scrofuloderma, orificial, miliary). AFB stain (Ziehl-Neelsen) and mycobacterial culture on Lowenstein-Jensen or liquid MGIT medium is the gold standard — confirming species and allowing drug-susceptibility testing — but takes two to six weeks. PCR or NAAT (GeneXpert MTB/RIF) detects M. tuberculosis complex DNA and identifies rifampicin resistance within hours; WHO-endorsed and now first-line.[4]

For the tuberculids, the skin is sterile — AFB stain, culture, and tissue PCR are all negative — and the diagnosis rests on the clinical morphology, a strongly positive tuberculin skin test (Mantoux) or IGRA, histology consistent with a hypersensitivity vasculitis or granulomatous reaction, and resolution with anti-TB therapy. The tuberculin test is positive in most forms but negative in the primary chancre (before immunity develops) and in anergic miliary TB. An HIV test is mandatory in every case.[8]

Management — RIPE for six months, and notify

[1]

The definitive treatment is standard anti-tuberculous therapy — the same regimen used for pulmonary disease — because the organism in the skin is the same organism and the goal is its eradication. The WHO standard category I regimen for drug-susceptible tuberculosis combines four drugs daily for the 2-month intensive phase, then two for the 4-month continuation phase — 6 months in total.[1][5]

[1] [5]

Pyridoxine (vitamin B6) 10 to 25 mg daily is given alongside isoniazid to prevent the peripheral neuropathy caused by isoniazid's interference with B6 metabolism — particularly important in pregnancy, malnutrition, diabetes, alcoholism, HIV, and renal failure.[5]

Monitoring targets the predictable toxicities. Baseline and monthly liver function tests — all three of rifampicin, isoniazid, and pyrazinamide are hepatotoxic, and a rise to more than three to five times the upper limit of normal with symptoms mandates stopping the offending drug. Visual acuity and colour vision (Ishihara plates) at baseline and periodically for ethambutol's dose-dependent retrobulbar optic neuritis, which can be irreversible — stop at the first visual symptom. Serum uric acid for pyrazinamide-induced hyperuricaemia and gout.[1][5]

Drug-resistant TB — if culture or GeneXpert shows rifampicin resistance (a proxy for MDR-TB) — the standard RIPE regimen is not adequate. MDR or XDR-TB requires prolonged second-line therapy under specialist guidance: fluoroquinolones (moxifloxacin, levofloxacin), second-line injectable aminoglycosides (amikacin), ethionamide, cycloserine, para-aminosalicylic acid, and the newer agents bedaquiline and delamanid, with linezolid and clofazimine in shorter all-oral regimens.[6]

Surgical adjuncts — debridement or drainage of scrofuloderma and large gummas, or excision of chronic sinus tracts, are reserved for after medical therapy has controlled the infection; reconstructive surgery for the disfiguring scarring of lupus vulgaris and scrofuloderma is deferred until disease is quiescent. Tuberculids resolve with standard anti-TB therapy once the underlying focus is treated.[5][8]

In every case, cutaneous tuberculosis is a statutorily notifiable disease in many jurisdictions (including India under the National TB Elimination Programme). Management is never complete without notification, contact tracing, and the offer of directly observed therapy to secure adherence and protect public health.[3]

The subtypes that bite — lupus vulgaris, scrofuloderma, HIV, the tuberculids

Lupus vulgaris — the indolent facial plague. Its danger is twofold: relentless destruction of facial cartilage over years, and the long-term risk of squamous cell carcinoma (Marjolin) in chronic lesions. Management is prolonged anti-TB therapy (6 months standard, sometimes extended to 9 to 12 months), with biopsy of any nodular, ulcerative, or verrucous change within a chronic plaque to exclude malignant transformation.[2][5]

Scrofuloderma in children. In endemic regions it is the commonest form of cutaneous TB and reflects breakdown of a tuberculous cervical lymph node. In India the organism is usually M. tuberculosis; in high-income countries the same picture in a child is more often an atypical mycobacterium (M. avium, M. scrofulaceum), distinguished by culture and managed by surgical excision rather than prolonged ATT. Tuberculous scrofuloderma is treated with standard ATT, with surgical debridement of sinus tracts as an adjunct once medical control is achieved.[3]

HIV-associated cutaneous TB. HIV co-infection increases the incidence of cutaneous TB and biases it toward multibacillary and disseminated (miliary) forms, with atypical morphology that mimics common dermatoses and delays diagnosis. Management pairs anti-TB therapy with antiretroviral therapy (ART), coordinated to avoid the rifampicin-protease-inhibitor interaction (rifampicin is a potent CYP3A4 inducer; rifabutin is substituted) and to anticipate the immune reconstitution inflammatory syndrome (IRIS).[4]

The tuberculids — sterile-skin reactions. Papulonecrotic tuberculid must be distinguished from PLEVA and leukocytoclastic vasculitis; erythema induratum from erythema nodosum (which is septal, on the anterior shin, and non-ulcerative — whereas erythema induratum is lobular, on the calves, and often ulcerates). The task is always to find and treat the underlying focus.[9][10]

How patients with cutaneous TB come to harm — the preventable list

• A chronic facial plaque called eczema or sarcoid for years while lupus vulgaris destroys cartilage underneath — biopsy any non-healing plaque.[2]
• Miliary TB missed in an immunosuppressed patient with atypical widespread papules sent home as a drug rash — a fatal delay.[4]
• A negative AFB stain used to exclude the paucibacillary forms (lupus vulgaris, warty TB) — PCR and culture are needed.[5]
• Failure to test for HIV in every case of cutaneous TB.[4]
• Inadequate ATT duration inviting relapse and resistance.[5]
• Squamous cell carcinoma (Marjolin) arising unnoticed in chronic lupus vulgaris — biopsy any change.[2]
• The rifampicin-oral contraceptive interaction overlooked, with unintended pregnancy.[5]

Special populations and regional differences

Children. Paediatric cutaneous TB is dominated by scrofuloderma (cervical lymphadenitis), the primary chancre, and lichen scrofulosorum. ATT is dosed by weight, and pyridoxine is given with isoniazid. Children are at particular risk of TB meningitis and miliary disease, so any child with cutaneous TB needs careful systemic evaluation, and survivors need follow-up for post-TB sequelae — bronchiectasis, skeletal deformity, and impaired pulmonary function.[3][11]

Pregnancy. Anti-TB therapy is generally safe and indicated, because untreated TB endangers mother and fetus. Rifampicin, isoniazid, and ethambutol are considered safe; pyrazinamide has less established safety data but is widely used. Pyridoxine is supplemented. Aminoglycosides (streptomycin, amikacin) are contraindicated because of fetal ototoxicity. Breastfeeding is permitted on ATT.[5]

Immunocompromised and anti-TNF therapy. Patients on anti-TNF agents (infliximab, adalimumab, etanercept) carry a markedly elevated risk of TB reactivation, including cutaneous forms; all should be screened for latent TB (IGRA plus chest imaging) before biologic therapy and treated for latent infection when positive.[4][6]

[1]

Prevention

BCG vaccination at birth is the cornerstone of population-level prevention. It does not prevent infection but substantially reduces the risk of disseminated (miliary) TB and TB meningitis in children — the fatal forms — and biases any cutaneous TB that does occur toward the contained, paucibacillary forms such as warty TB. Individual prevention rests on prompt diagnosis and complete treatment of infectious pulmonary cases, contact tracing and screening, and treatment of latent TB infection (isoniazid or shorter rifamycin-based regimens) in high-risk contacts and before anti-TNF therapy.[3][4]

The mantra, and the memory device

[1]

The mantra: read the immunity from the morphology — strong immunity gives paucibacillary warty plaques and apple-jelly nodules, weak immunity gives multibacillary sinuses and miliary papules — and treat with six months of RIPE.[1][5]

Ward-round test — three stems, thirty seconds each

Stem 1 — the apple-jelly plaque on the nose (answer)

A 45-year-old woman has a slowly enlarging, soft, reddish-brown plaque on her nose for eight years. Diascopy shows apple-jelly nodules. What is the diagnosis, the key long-term risk, and the management? Model: The diagnosis is lupus vulgaris, a paucibacillary haematogenous cutaneous tuberculosis confirmed by the apple-jelly sign on diascopy. The key long-term risk is squamous cell carcinoma (Marjolin ulcer) arising in the chronic plaque — any nodular, ulcerative, or verrucous change demands biopsy. Management is skin biopsy for histology (caseating granulomas), AFB stain, culture, and GeneXpert MTB/RIF; HIV testing; chest X-ray; and standard RIPE anti-TB therapy (rifampicin, isoniazid, pyrazinamide, ethambutol for 2 months intensive, then rifampicin plus isoniazid for 4 months continuation, 6 months total), sometimes extended to 9 to 12 months for lupus vulgaris, with reconstructive surgery deferred until the disease is quiescent.[2][5]

Stem 2 — the child with sinus tracts on the neck (answer)

A 6-year-old boy in an endemic region has a firm, bluish swelling overlying a cervical lymph node that has broken down, discharging caseous material through bluish, undermined sinus tracts. What is the diagnosis, the organism, and what distinguishes it from the high-income-country equivalent? Model: The diagnosis is scrofuloderma — breakdown of a tuberculous cervical lymph node to the skin via sinus tracts, healing with bridged, keloidal, or papery scarring. In endemic regions such as India the organism is usually Mycobacterium tuberculosis, and the treatment is standard RIPE anti-TB therapy with surgical debridement of sinus tracts as an adjunct once medical control is achieved. In high-income countries the same clinical picture in a child is more often an atypical mycobacterium (M. avium, M. scrofulaceum), distinguished by culture and managed by surgical excision rather than prolonged ATT — a distinction examiners test deliberately.[3][5]

Stem 3 — the three criteria of a tuberculid (answer)

A 30-year-old man has symmetric necrotic papules on his extensor limbs healing with pock-like scars. The skin biopsy shows a wedge-shaped necrotising vasculitis; AFB stain, culture, and tissue PCR are all negative; the Mantoux is strongly positive. What are the three defining criteria, and why is the skin sterile? Model: The diagnosis is a papulonecrotic tuberculid, defined by three criteria: (1) a sterile skin lesion — negative AFB stain, mycobacterial culture, and tissue PCR; (2) a strongly positive tuberculin test or IGRA, confirming exposure to TB antigens; and (3) resolution of the eruption with anti-TB therapy, establishing the aetiological link. The skin is sterile because the eruption is a type III and type IV hypersensitivity reaction to haematogenously disseminated M. tuberculosis antigens (and sometimes scant bacilli) from a distant, often occult focus — the inflammation is driven by antigen, not by multiplying organisms in the skin. The underlying focus must always be sought and treated with standard RIPE therapy.[8][9][10]

References

1. [1]Kaul S, Kaur I, Mehta S, et al. Cutaneous tuberculosis. Part I: Pathogenesis, classification, and clinical features J Am Acad Dermatol, 2023.PMID 35149149
2. [2]Chen Q, Chen W, Hao F. Cutaneous tuberculosis: A great imitator Clin Dermatol, 2019.PMID 31178102
3. [3]Bravo FG, Gotuzzo E. Cutaneous tuberculosis Clin Dermatol, 2007.PMID 17350496
4. [4]Franco-Paredes C, Marcos LA, Henao-Martínez AF, et al. Cutaneous Mycobacterial Infections Clin Microbiol Rev, 2018.PMID 30429139
5. [5]Hill MK, Sanders CV. Cutaneous Tuberculosis Microbiol Spectr, 2017.PMID 28233513
6. [6]Gardini G, Gregori N, Matteelli A, et al. Mycobacterial skin infection Curr Opin Infect Dis, 2022.PMID 35067521
7. [7]Tobin EH, Warda K, Gropper C, et al. Cutaneous Tuberculosis 2026.PMID 29489274
8. [8]Dhattarwal N, Ramesh V. Tuberculids: A Narrative Review Indian Dermatol Online J, 2023.PMID 37266079
9. [9]Palaniappan V, Sadhasivamohan A, Karthikeyan K. Papulonecrotic tuberculid Clin Exp Dermatol, 2022.PMID 35724330
10. [10]Zhang LW, Wu J, Chen T. Papulonecrotic tuberculid CMAJ, 2024.PMID 38346781
11. [11]Igbokwe V, Ruby LC, Sultanli A, et al. Post-tuberculosis sequelae in children and adolescents: a systematic review Lancet Infect Dis, 2023.PMID 36963920