Cutaneous tuberculosis Epidemiology

 Cutaneous tuberculosis occurs worldwide; incidence of different forms varies globally.  India: Affected 2% of all skin outpatients (1950s and 1960s) and then 0.1% by 1980s; due to the availability of effective drugs and improvement in the living standards.  In India, scrofuloderma is common in children; lupus vulgaris commonest in adults.  Resurgence in tuberculosis, and consequently in cutaneous tuberculosis; due to the HIV pandemic, resistant strains of M. tuberculosis, use of immunosuppressive therapy, ease of global travel and migration, poverty, malnutrition. Aetiology

 Caused by M. tuberculosis, M. bovis and under certain conditions, the bacillus Calmette-Guérin (BCG), an attenuated strain of M. bovis.

 M. tuberculosis and M. bovis cause identical skin manifestations in humans.

 In HIV-infected individuals, even atypical saprophytic strains of Mycobacterium may cause infection and bizarre forms of disease. Cutaneous tuberculosis

 Spectrum of cutaneous changes induced by M. tuberculosis depend upon: ◦ Route of infection ◦ Immunological state of the host

 Mere presence of mycobacteria in the skin does not lead to the clinical disease. Routes of infection

 Exogenous ◦ From an external source, through breach in the skin at the site of trauma.  Endogenous ◦ Through contiguous involvement of skin ◦ Through lymphatic spread ◦ Through haematogenous dissemination

 Autoinoculation Classification (Modified from Beyt et al.)

 Inoculation tuberculosis (exogenous source)  Secondary tuberculosis (endogenous source)  Haematogenous tuberculosis  Eruptive tuberculosis (tuberculides) Classification (Modified from Beyt et al.)

 Inoculation tuberculosis (exogenous source) ◦ Tuberculosis chancre ◦ Warty tuberculosis (verrucosa cutis) ◦ Lupus vulgaris (some) Classification (Modified from Beyt et al.)

 Secondary tuberculosis (endogenous source) ◦ Contiguous spread: Scrofuloderma ◦ Auto-inoculation: Orificial tuberculosis Classification (Modified from Beyt et al.)

 Haematogenous tuberculosis ◦ Acute miliary tuberculosis ◦ Lupus vulgaris (some) ◦ Tuberculous gumma Classification (Modified from Beyt et al.)

 Eruptive tuberculosis (tuberculides) ◦ Micropapular  Lichen scrofulosorum ◦ Papular  Papular or papulonecrotic tuberculide ◦ Nodular  Erythema induratum (Bazin)  Nodular tuberculide  Erythema nodosum Tuberculous chancre

 Occurs following M. tuberculosis inoculation through breach in the skin of an individual, not previously infected with tuberculosis.  Initially, a small papule, scab, nodule or a poorly healing wound; gradually forms a painless ulcer with a shallow, granular or haemorrhagic base and undermined edges.  Spontaneous healing within 3 to 12 months, with atrophic scar and often, calcified nodes. Warty tuberculosis (Syn: Tuberculosis verrucosa cutis Pathogenesis  Previously infected individual with moderate or high immunity  Accidental superinfection from exogenous sources: physician, pathologists  Autoinoculation with sputum  Common sites ◦ Adults - fingers and hands ◦ Children - ankles and buttocks Warty tuberculosis Clinical features Small, solitary, indurated, red or brown, papule or nodule

Verrucous plaque (finger-like projections; fissured surface)

Spontaneous involution with atrophic scarring

Regional lymph nodes may enlarge due to secondary bacterial infection.

Warty tuberculosis Course  Verrucous lesions persist; but seldom ulcerate.  Lesions run a chronic course, and if untreated, remain inactive for months or years.  Lesions may involute spontaneously, resulting in sunken, atrophic scars. Warty tuberculosis Differential diagnosis  Common warts  Hypertrophic lichen planus  Verrucous epidermal nevus  Blastomycosis  Chromomycosis  Actinomycosis Lupus vulgaris Pathogenesis  Most common form of cutaneous tuberculosis  Occurs in sensitized individuals with moderate to high immunity  Affects all age groups Lupus vulgaris Pathogenesis  Lesions arise by: ◦ Haematogenous dissemination ◦ Lymphatic spread ◦ Contiguous spread from tuberculous tissue ◦ Exogenous inoculation Lupus vulgaris Clinical features Small, solitary reddish-brown nodule

Plaque

Elevated, infiltrated, deep brown in colour

Slowly expands at one end; heals with scarring at the other end

Asymptomatic lesions, commonly affects the buttocks and trunk Lupus vulgaris Clinical forms  Plaque forms  Ulcerative and mutilating forms  Vegetating forms  Tumor-like forms  Papular and nodular forms

Lupus vulgaris Course  Chronic, indolent course over years, if left untreated.  Lesions undergo ulceration, and superficial scarring.  Characteristically thin, white, smooth scars; may break down or become keloidal.  Complications comprise scarring, contractures, tissue destruction, development of squamous cell carcinoma in the scars (8%). Lupus vulgaris Differential Diagnosis  Borderline tuberculoid leprosy  Psoriasis  Sarcoidosis  Discoid lupus erythematosus  Syphilitic gumma  Deep fungal infections Scrofuloderma Pathogenesis  Contiguous involvement of the skin overlying a tuberculous focus, usually a lymph node, an infected bone or joint or epididymis.  Common in children, adolescents and aged; may affect all age groups.  Usually affects the face and neck, often bilaterally.  Commonly involves the cervical, parotid, submandibular and supraclavicular lymph nodes; less commonly, axillary and inguinal. Scrofuloderma Clinical features Initially, a firm, subcutaneous nodule, fixed to the overlying skin

Cold abscess formation

Secondary ulceration, sinus tract formation

Ulcer has undermined edges and granulating floors

Scrofuloderma Course  Numerous sinus tracts and fistulae develop over a period of several months.  Spontaneous healing may occur, with puckered and cord-like scars.  Scar tracts characteristically bridge the areas of ulceration or even normal skin. Scrofuloderma Differential Diagnosis  Atypical mycobacterial infection  Lymphogranuloma venereum  Actinomycosis  Sporotrichosis  Syphilitic gummas  Acne conglobata  Hidradenitis suppurativa  A rare form of tuberculosis of the mucous membranes and skin adjoining the orifices.  Presents as a nodule which ulcerates with undermined edges Orificial tuberculosis

 A rare form of tuberculosis of the mucous membrane and skin adjoining the orifices

 Presents as a nodule which ulcerates with undermined edges Orificial tuberculosis

 Site affected depends on the site of internal tuberculosis: ◦ Pulmonary tuberculosis: mouth ◦ Tuberculosis of pharynx, larynx: lips ◦ Intestinal tuberculosis: external genitalia; anus; perianal ◦ Genitourinary tuberculosis in women: vulva  Prognosis: poor due to advanced internal disease and compromised immunity. Acute miliary tuberculosis of the skin

 Rare manifestation of fulminating tuberculosis due to haematogenous dissemination of mycobacteria into the skin, from a meningeal or pulmonary focus.  Crops of numerous, minute, erythematous to bluish, macules, papules, vesicles, pustules or purpuric lesions occur on all parts of the body, especially the trunk.  Usually occurs in infants, young children or immunosuppressed patients, co-existing HIV infection, measles. Tuberculous gumma

 Haematogenous dissemination of mycobacteria from a primary tuberculous focus, during periods of lowered resistance.  Commonly involves the trunk, extremities or head.  Lesions arise as a single or multiple, firm subcutaneous nodule or fluctuant abscesses.  Ulcers with undermined edges, sinuses and fistulae may occur  Healing occurs with cord-like and puckered scarring. Tuberculides

 Occur as a hypersensitivity reaction to  M. tuberculosis or its products in a patient with moderate to high immunity, following haematogenous spread of the mycobacteria.  Salient features: ◦ A positive tuberculin test ◦ Evidence of obvious or past tuberculosis ◦ A positive response to anti- tuberculous therapy Tuberculides Types  Micropapular: lichen scrofulosorum  Papular: papulonecrotic tuberculide  Nodular: Erythema induratum of Bazin Erythema nodosum Erythema induratum of Bazin (Nodular tuberculide)

 A chronic, recurrent, nodular and ulcerative disorder  Commonly affects young, or middle-aged, obese women; men affected occasionally  Predominantly affects calves; may also occur on upper limbs, thighs, buttocks and trunk  The nodules run an indolent course and form ulcers  Ulcers are ragged, irregular and shallow, with bluish edge Diagnosis Absolute diagnosis established by:  A positive culture of M. tuberculosis from the lesion  Identification of mycobacterial DNA by Polymerase Chain Reaction (PCR) technique Other diagnostic criteria The diagnosis is suggested by:  Clinical history and physical signs  A positive reaction to tuberculin  Demonstration of tuberculoid granuloma on histolopathology  Demonstration of acid-fast bacilli in the lesion  Presence of culture-proven active tuberculous focus elsewhere in the body  Effect of specific therapy

Cutaneous tuberculosis treatment General principles

 Notification

 Identification and treatment of the underlying tuberculous focus

 Identification and treatment of co-existent infections such as HIV

 Specific chemotherapy

 Ancillary measures Cutaneous tuberculosis Drug regimen The standard regimens comprise:  Initial intensive phase (Phase I) Rapidly destroys large populations of multiplying mycobacteria.

 Continuation phase (Phase II) Eliminates persistent dormant organisms. Drug therapy: 6 months regimen (for adults)

1. Rifampicin 450mg/600mg (wt 50kgs) - 6 months 2. Isoniazid (300mg daily) - 6months (add pyridoxine 10mg/day) 3. Pyrazinamide - for 1st 2months 1.5gm daily for patient <50 kg 2gm daily for patient >50 kg 4. Ethambutol for the 1st 2 months Dose: 15mg/kg body weight daily All drugs taken on empty stomach once daily Re-introduction of AKT following drug reactions (WHO)

Drugs D1 D2 D3 INH 50mg 300mg 300mg (Least) Rcin 75mg 300mg Full

PZA 250mg 1mg Full

ETB 100mg 500mg Full SM 125mg 500mg Full (Highest)

If severe reactions, start with smaller dosage (1/10th) Revised National Tuberculosis Control Programme (RNTCP) Extra-pulmonary tuberculosis: Diagnosis

One culture-positive specimen from extrapulmonary site, or

Histological evidence, or

Strong clinical evidence consistent with active extrapulmonary TB Revised National Tuberculosis Control Programme (RNTCP) Cutaneous TB:

Category III (sputum smear negative)

Regimen: 2(HRZ)3 + 4(HR)3

Category II (sputum smear positive)

2(HRZES)3 + 1(HRZE)3 + 5(HRE)3 Cutaneous tuberculosis treatment Special considerations  Surgical intervention coupled with AKT in scrofuloderma; small lesions of lupus vulgaris; tuberculosis verrucosa cutis.

 Plastic Surgery in cases of disfigurement due to lupus vulgaris

 Standard regimens: effective in HIV-positive.

 HIV-infected individuals: higher drug reaction and infection rates. Thank you