Cutaneous Tuberculosis

Dr. (Prof.) Archana SingalUniversity College of Medical Sciences

& GTB Hospital, New Delhi

Digital Lecture Series : Chapter 09

CONTENTS

Introduction Epidemiology Etiopathogenesis-

• Etiological agent• Host-Pathogen interaction• Presdisposing factors

Clinical classification• Exogenous/inoculation• Endogenous• Tuberculide

Differential diagnosis

Management• General Principles• Investigations• Treatment• Resistance

MCQs Photoquiz

Introduction

Tuberculosis (TB), one of the oldest infectious disorders Organism identified 130 yrs back by Robert Koch(1882) Intradermal Skin test developed 100 yrs back by Charles Mantoux TB vaccine in use for 80 yrs (1928) Chemotherapy in use for 50 yrs (1963)

STILL

2nd most common infectious cause of death after HIV/AIDS worldwide Pulmonary TB remains to be the most common form of TB TB of extra-pulmonary sites such as lymph nodes, bone, skin, abdomen

and pelvis is on a steady rise.

Globally - Cutaneous TB (CTB) is less common clinical forms of TB About 1% to 2% of total extrapulmonary cases Incidence of 0.07% has been reported in a 10-year survey from

Hong Kong.

India - CTB constitutes 10% cases of all extrapulmonary TB And 0.1% - 2% of total skin OPD patients Lupus vulgaris is considered the commonest form of CTB in adults

and Scrofuloderma in children Tuberculides especially lichen scrofulosorum (LS) has emerged as

the commonest variant in many regions including India

Epidemiology

Life time risk with HIV – 50%

In developing world 50% are co-infected

World over 4 million people are co-infected

5% develop disseminated infection which is the cause of death

HIV Infection & TB

M. Tuberculosis major etiological agent M. bovis 1 – 1.5%

WITH HIV

M. avium complex 2 / 3 cases M. tuberculosis 10% cases M. kansasii M. scrofulaceum

Etiology

No known endotoxin Tissue destruction mediated by host immune response

Skin manifestation depends on• Sensitization status of the patient• Cellular immunity• Route of infection

Pathogenesis

contd.

EXPOSURE (BCG/Pri. Pulm. Infection/Skin Inoculation)

Mycobacteria engulfed by macrophages

Antigen presented to CD4+ TH1 cell

(In 2-3 weeks)

Hypersensitivity / Granuloma Formn / Caseous Necrosis

Disease Arrested Latent Infection Progressive Disease (5-10%)

Pathogenesis

HIV pandemic leading to resurgence in TB & drug resistant strains of M. tuberculosis,

Use of immunosuppressive therapy, Ease of global travel and migration, Poverty and malnutrition

Factors affecting host-pathogen interaction Virulence of the infecting mycobacteria Route of infection Prior contact with the bacilli Host’s immune response Environmental factors

Predisposing factors

Exogenous Direct inoculation of TB bacilli from an infected person to susceptible one,

through breach in the skin at the site of trauma

Endogenous Through contiguous involvement of skin Through lymphatic spread Through haematogenous dissemination

Autoinoculation

Routes of infection

Exogenous cutaneous tuberculosisTuberculous chancreTuberculosis verrucosa cutis (TBVC)

Endogenous cutaneous tuberculosisBy contiguity or autoinoculation Scrofuloderma (SFD) Orificial tuberculosis Lupus vulgaris (some cases) LV

Classification of Cut TB (Beyt et al)

contd.

By hematogenic dissemination Lupus vulgaris (LV) Tuberculous gumma Acute miliary tuberculosis

Tuberculids Papulonecrotic tuberculid (PNT) Erythema induratum of Bazin (EIB) Lichen scrofulosorum (LS) Phlebitic tuberculid*

Classification of Cut TB (Beyt et al)

*Phlebitic’ or ‘nodular granulomatous phlebitis’ has been recently proposed as a new tuberculid

Rare form of CTB, develop in adults without previous sensitization to Mycobacterium Tuberculosis; natural or artificial

Usually follows• Abrasion, cuts and ulcers• Circumcision• Tattooing and Ear piercing with unsterilized needles• Contact with infected sputum

Localized form Site - Face and extremities

Tuberculous chancre (Primary Inoculation TB)

Firm, painless and brownish papule

2-3 weeks 3-8 weeks Firm, non-tender ulcer Regional LAPwith undermined bluish margins (Primary Complex)

- Slow healing in up to Subsides with calcification - 12 months with scars Rarely cold abscess

- Rarely progression to & sinuses develop - LV or SFD in untreated

After 2-4 weeks of inoculation

Post Tattoo inoculation TB in two brothers that progressed to LV.

Exogenous inoculation at trauma prone sites in pre-sensitized hosts with moderate to high degree of immunity• Accidental – physicians, pathologists, post mortem attendants• Autoinoculation by sputum in active pulmonary TB patients• Accidental inoculation from infected sputum

Clinically - Wart like papule & verrucous plaque Regresses or heals with a thin scar Lymphadenitis is rare

Sites- Finger, hands & feet, ankle

Tuberculosis verrucosa cutis (TBVC)Syn: warty tuberculosis

Warty lesions of TBVC in adults with good immunity on extremities

(trauma prone sites) Left foot, left palm and sole of the left foot.

Hypertrophic lichen planus

Verruca vulgaris

Chromoblastomycosis

Leishmaniasis

Differential Diagnosis of TBVC

SFD occurs as a result of contiguous spread from an underlying primary tubercular focus like• Lymph nodes or• Bone• Joints or• Testicles

Age - More common in children but affects all age groups Lymph nodes - Cervical lymph nodes most common followed by

axillary, pre and post auricular, submandibular, Inguinal

Scrofuloderma (SFD)

Firm, subcutaneous nodule, fixed to theoverlying skin

Cold abscess formation overlying LN/ Bone/ Joint

Secondary ulceration, sinus tract formation

Ulcer has undermined edges and bluish boggy margin

Clinical features of Scrofuloderma

Clockwise:1. Tubercular abscess overlying rib cage with impending rupture. Pus smear from aspirate on ZN staining showed numerous AFB i.e M. tb2. Scrofuloderma overlying cervical and supraclavicular TB lymphnodes3. Scrofuloderma overlying TB focus in the bone i.e 2nd metacarpal bone which shows a lytic lesion on x-ray

Young girl with SFD with underlying TB focus in cervical Lymph nodes

Scrofuloderma runs a very protracted course.

It tends to heal spontaneously over months and years.

Leave behind cerebriform or bridging scars and pockets of

retraction.

Underlying focus of TB in bone/ joint, may reveal osteolytic

lesions in bone

Course

Bacterial abscesses / Bacterial osteomyelitis

Hidradenitis suppurativa

Atypical mycobacterial infection (M.avium and M. scrofulaceum)

Sporotrichosis

Actinomycosis

Tumor metastasis

Differential Diagnosis

Rare form that affects middle-aged / elderly man with impaired CMI .

Follow autoinoculation of Mycobacterium Tuberculosis into skin/ mucosa of the adjoining orifices in patients with advanced

• intestinal or • Genitourinary• pulmonary TB

Site -• Around mouth• Perianal region• Ext genitalia

Orificial TB (Syn Tuberculosis cutis orificialis)

Small, edematous reddish nodule Breaks down Painful, non-healing, shallow ulcers with undermined bluish edges

Course – Prognosis : is poor due to• Advanced internal disease and• Compromised immunity

Orificial Tuberculosis

Most common type of Cut TB Paucibacillary disease in pts. with moderate to high immunity Affects all age group Sites - Head & neck, Gluteal region

The infection is acquired by Lymphatic spread or Hematogenous spread or Direct extension from a tuberculous focus At site of inoculation

Lupus vulgaris (LV)

Reddish brown, flat plaque Extends slowly, peripherally with central atrophy and scarring. May

result in contractures Apple jelly nodules at the advancing edges May lead to destruction of underlying cartilage Regional lymphadenopathy present SCC may develop in scar or chronic ulcer

Clinical Features

Plaque

Ulcerative & mutilating

Hypertrophic

Vegetating & tumor like

Atrophic and plantar

Clinical Variants

Clockwise: Lupus vulgaris ( LV)1. LV of nose in a young girl child leading to destruction and mutilation of nose (cartilage and bone both)2. Multi focal LV with characteristic central clearing and advancing margins in a young boy3. Lesion of LV on buttock in an adult male

Classic lesions of LV with central clearing and advancing margin on the elbow and face of young boys

LUPUS VULGARIS

Sarcoidosis

Hansen’s disease

Lupus erythematosus

Granuloma faciale

Leishmaniasis

Squamous cell carcinoma

Differential Diagnosis of Lupus Vulgaris

Hematogenous dissemination of Mycobacterium Tuberculosis from a primary TB focus during lowered resistance/decreased immunity

Undernourished children, immunocompromised patient Single/multiple firm, nontender,erythematous nodule

Breakdown to form undermined ulcers & sinuses Subsequent course similar to scrofuloderma Pus may be positive for AFB

Tuberculous gumma (Syn. Metastatic Tuberculous Abscess)

Tuberculosis Gumma

Rare and severe form of TB seen in very ill patients Massive hematogenous dissemination of Mycobacterium Tuberculosis into skin Affects young children, immunosuppressed, HIV co-infected and following

measles or other exanthems

Clinically Profuse crops of minute bluish papules, vesicles, pustules May become necrotic to form ulcers Poor prognosis but occasionally may respond to Rx.

Differential Diagnosis Varicella, enteroviral exanthem, Pityriasis lichenoides et varioliformis acuta

(PLEVA)

Acute miliary tuberculosis

Tuberculides represent cutaneous immunologic reaction to the presence of Mycobacterium Tuberculosis or their products in a patient with significant immunity.

Diagnostic Criteria Tuberculoid histology on skin biopsy Absence of organism in smears Negative mycobacterial culture Evidence of tubercular focus elsewhere; Active or healed Strongly positive tuberculin test and Swift resolution of the lesions with ATT

Tuberculides: Definition and diagnostic criteria

Micropapular- Lichen scrofulosorum (LS) Papular- Papulonecrotic tuberculid (PNT) Nodular- Erythema induratum of Bazin (EIB)

The recently described ‘phlebitic tuberculid’, ‘nodular granulomatous phlebitis’ or ‘superficial thrombophlebitic tuberculid’ may necessitate its inclusion as the fourth member of the tuberculide spectrum

Classic Tuberculide

LS is one of the most common presentations in children. Asymptomatic, 0.5-3mm, closely grouped, skin coloured to

erythematous, follicular or perifollicular, flat-topped to spinous papules on truck, back and proximal limbs

LS confined to the vulva; genital tuberculid Underlying focus of TB include

• TB LAP• Pulmonary TB• Skin TB• Rarely Abdominal, intracranial and endometrial foci

A systemic focus of TB is detected in a majority of LS cases

Lichen Scrofulosorum (LS)

Grouped, skin colored, mildly scaly follicular papular lesions of LS in a patient with strongly positive Mantoux and Pulm focus of TB

Positive Mantoux test with blistering after 48 hrs

Pulmonary Kochs

Recurrent crops of Symmetrically distributed Firm, dusky red necrotizing papules and pustules Predominantly over the extremities Isolated lesions involving male genitalia (genital tuberculid) in

children as well as adults Lymphadenopathy may be present Associated pulmonary TB Constitutional symptoms such as fever and asthenia may precede

cutaneous manifestationsDifferential diagnosis: Varicella and PLEVA

Papulonecrotic Tuberculide

Multiple extensive PNT lesions in a severely malnourished and febrile young girl with Pulmonary Koch’s

Erythema Induratum of Bazins

Indolent and recurrent nodular lesions Site: calves; may occur on upper

limbs, thighs, buttocks and trunk Affects young or middle-aged obese

women Tend to ulcerate during winters

forming ragged, irregular & shallow ulcers with a bluish edge

Resolution is slow even with adequate ATT

Notification

Identification and treatment of the underlying tuberculous focus

which is identifiable in ½ to 1/3rd of cases

Identification and treatment of co-existent infections such as HIV

Specific chemotherapy

Family screening

Ancillary measures

Management of Cutaneous TuberculosisGeneral Principles

Hematological CBC with ESR LFT RFT

Mantoux testSputum for AFBRadiological

X-ray chest Radiograph of the affected region- bone USG Abdomen CECT – chest And MRI – selected cases

Investigations

FNAC Skin Biopsy Mycobacterial culture-

• LJ medium (Lowenstein Jensen)• BACTEC 460 liquid medium

PCR Antigen detection Biochemical characteristics

Investigations

Hall mark is presence of characteristic granuloma composed of epitheloid cells, lymphocytes and Langhan’s giant cells.

Based on host immune response, histology of CTB may be grouped into three groups_ • Well-formed granulomas with absence of caseous necrosis:

Lupus Vulgaris and Lichen Scrofulosorum.• Granulomas with caseous necrosis: TBVC, tubercular chancre,

acute military tuberculosis, tuberculosis orificialis and Papulonecrotic tuberculide.

• Presence of poorly formed granulomas with intense caseous necrosis: Scrofuloderma and TB gumma

Histology of Cutaneous TB

Compact epithelioid cell granuloma in mid and upper dermis in LV

Absolute criteria Positive culture from lesion

• LJ (Lowenstein Jensen) medium• BACTEC Culture

Successful guinea-pig inoculation Identification of mycobacterial DNA by PCR

Other indicators Characteristic histopathology Positive tuberculin test Presence of active proven TB elsewhere Presence of AFB in the lesion Response to ATT

Diagnosis

The standard regimens comprise of:

Initial intensive phase (Phase I) Rapidly destroys large populations of multiplying mycobacteria.

Continuation phase (Phase II) Eliminates persistent dormant organisms.

Drug Regimen

Duration6 months Category I Regimen2 (HRZE) + 4 (HR) Daily or DOTS Thrice weekly

Treatment

Drug Daily Txmg/kg/d (Total)

DOTSmg/kg/d (Total)

Isoniazid 5 (300) 10 (600)

Rifampicin 10 (450) 10 (450)

Pyrazinamide 25 (1500) 25 (1500)

Ethambutol 15 (800) 20 (1200)

Surgical intervention may be required along with ATT Plastic Surgery in cases of disfigurement due to Lupus Vulgaris, to

release contractures HIV-positive- Standard regimen is effective HIV-infected individuals: higher drug reaction and infection rates

Special Considerations

Multidrug-resistant tubercle bacilli (MDR-TB) are isolates showing resistance to Rifampicin & INH , with or without resistance to other drugs

Extensively drug-resistant TB (XDR-TB) as tubercular infections caused by Mycobacterium Tuberculosis resistant to both INH and Rifampicin as well as a fluoroquinolone, and at least one second-line injectable agent (capreomycin, amikacin,or kanamycin)

Recently few cases of MDR Cut TB have been reported from India. MDR TB should be thought of when reasons such as poor Rx

compliance, inadequate doses and wrong diagnosis have been carefully excluded

Drug Resistance in Cut TB

Q.1) What is the classification system used for Cutaneous Mycobacterial infection?

A. Schobinger's classificationB. Freidrikson's classificationC. Beyt's classification D. Luxar and Zulian classification

Q.2) Which of these precludes a diagnosis of Tuberculid?E. Positive tuberculin testF. Partial response to Antituberculous therapyG. Negative Mycobacterial CultureH. Past history of Pulmonary Tuberculosis

MCQ’s

Q.3) Which of the following malignancies are known to occur in long standing case of lupus vulgaris?

A. Squamous cell carcinomaB. Basal cell carcinomaC. SarcomaD. Malignant melanoma

Q.4) Which of the lymph nodes are commonly involved in cutaneous tuberculosis ?

E. AxillaryF. CervicalG. InguinalH. Epitrochlear

MCQ’s

Q.5) A 25 year old male presented with an asymptomatic plaque on the right side buttock with active spreading edge at one end and scarring at the other end since 1 year. What is the likely diagnosis?

A. Scar sarcoidB. Lupus vulgarisC. Hypertrophic lichen planusD. Tuberculosis verrucosa cutis

MCQ’s

Q. Identify the type of tuberculosis and describe evolution of lesion ?

Photo Quiz

Q. Identify the type of Cut TB?

Photo Quiz

Q. Identify the type of Cut TB ?

Photo Quiz

Thank You!