TUBERCULOSIS OF SKIN

Caused by Mycobacterium tuberculosis, an acid fast bacteria

📌Classification of mycobacteria

A) SLOW GROWERS

1) PHOTOCHROMOGENS - M. marinum, M. kansasii

2)SCOTOCHROMOGENS-M. scrofulaceum, M. szulgai, M. gordonae

3)NON- CHROMOGENS-  M. tuberculosis, M. avium- intracellurae, M. ulcerans

B) RAPID GROWERS-M. smegmatis,M. fortuitum,M.chelonae/abscessus

📌IMMUNOLOGY OF TB

Following infection, only 5-10% develop progressive disease, but some bacilli remain viable in tissues of sub clinically infected individuals

Both innate and adaptive T cell response takes part in the disease process

Recogniton and phagocytosis by innate immune cells by  TLR 2 & TLR 9

IL-12 from macrophages– CD4+ Tcell activation

Antigen presentation by MHC class II

Th cells release IL-2, IFN-gamma

TNF –alpha from activated macrophages will contribute to the granuloma formation

🔍CUTANEOUS  TB

The wide clinical spectrum of cutaneous tuberculosis is dependent on:-

*Route of infection (endogenous or exogenous)

*Immune status of the patient

*Previous sensitization with tuberculosis.

📌Primary Inoculation Tuberculosis 

(Tuberculous Chancre ; Tuberculous Primary Complex)

📍Due to direct inoculation to skin of a naïve host

📍It is a multibacillary type

📍Most affected individuals are children, also occur in adolescents and young adults.

📍Bacillus enters through a injury in skin- abrasion or minor injuries,ritual circumcision, infections with inadequately sterilized syringes, wounds, operations, ear- piercing

📍Clinical features:-

*The earliest lesion 2 to 4 weeks after inoculation.

*Brownish papule /nodule / painless ulcer with an undermined edge and a granular haemorrhagic base.

*Most commonly on face, hands and lower extremities

*Regional LN often develops after 4 to 8weeks.

📍Clinical variants:- –

*Mucosal infections result in painless ulcers or fungating granulomas.

*Inoculation tuberculosis of the finger may present as a painless paronychia

📍HISTOPATHOLOGY

*The early changes are those of acute neutrophilic inflammation with necrosis.

*Numerous bacilli are present.

*After 3-6 weeks, the infiltrate becomes more granulomatous and caseation appears, coinciding with the disappearance of the bacilli.

*Central caseation necrosis with dense macrophage and lymphocyte surround

📍Tuberculin skin test : early stages-negative, late stages- positive

📍Differential diagnosis : syphilis, tularemia, bartonellosis, sporotrichosis, actinomycosis and ulcerative lesions of other mycobacterioses (especially M. marinum infections)

📍COURSE

*Without treatment, last up to 12 months.

*Lesions heal by scarring,

*Lupus vulgaris develops at healed lesion(rarely)

*Calcification of regional nodes.

*Hematogenous spread may give rise to tuberculosis of other organs,

particularly of the bones and joints.

*Can progress to acute miliary disease with fatal outcome.

*Erythema nodosum is a feature in approximately 10 % .

📌Tuberculosis Verrucosa Cutis (Warty tuberculosis, Prosector’s wart)

📍An indolent, warty, plaque-like form of tuberculosis

📍Direct inoculation to skin of a previously sensitized individual

📍Paucibacillary

📍Exogenous inoculation arise due to:

*Accidental superinfection from extraneous sources:- physicians, pathologists etc.

*Autoinoculation with sputum in a patient with active tuberculosis

📍CLINICAL MANIFESTATIONS

*Small, symptomless, indurated, warty papule with inflammatory areola.

*Extension to verrucose plaque - serpiginous outline with finger-like projections.

*Firm consistency with areas of relative softening.

*The centre may involute - white atrophic scar

*Whole lesion may form a massive, infiltrated papillomatous excrescence with purplish, red or brown colour

*Pus may be expressed from these soft areas 

*The appearance may be psoriasiform or keloidal.

*Occasionally, exudative and crusted features are predominant.

*Very rarely, sporotrichoid spread

📍Sites:

Asia- knees,ankles,buttocks are mainly involved.

Europe- hands

📍CLINICAL VARIANTS

*Deeply destructive papillomatous & sclerotic forms-cause deformity of limbs.

*Generalised form associated with papulonecrotic & lupoid lesion occur in patients with active disease

*Tumour like forms can occur

📍HISTOPATHOLOGY

*The most prominent histopathologic features are pseudoepitheliomatous hyperplasia with marked hyperkeratosis, acanthosis

*Abscesses in the superficial dermis or within the pseudoepitheliomatous rete pegs.

*Epithelioid cells and giant cells are found in the upper and middle dermis

*Mid dermis –tuberculoid granuloma with moderate necrosis are usually present.

*Mycobacteria can occasionally be seen.

*Epidermis acanthosis, superficial dermis neutrophils and lymphocytes,Deep to which there are granulomas

📍DIFFERENTIAL DIAGNOSIS

*Subungual and digital lesions must be distinguished from warts, and those on the hands from keratoses.

*Blastomycosis, chromoblastomycosis and actinomycosis may simulate exuberant forms .

*Crusted lesions may resemble leishmaniasis.

*Tertiary syphilis may be confused when the central scarring is surrounded by a serpiginous edge.

📍Course :

*Responds to ATT

*Without treatment they extend very slowly& remain inactive for months

*Spontaneous remission may occur & usually result in atrophic scars.

*Active disease of other organs-bone,glandular or pulmonary tuberculosis may coexist

📌Scrofuloderma (Tuberculosis Colliquativa Cutis)

📍Involvement and breakdown of the skin overlying a contiguous tuberculosis focus, usually a lymph gland but sometimes an infected bone, joint or even a lacrimal gland or duct.

📍Most commonly after cervical gland infection; less often with axillary, inguinal, epitrochloear & retroauricular gland infection.

📍More common in children and first three decades of life.

📍Clinical features :

*Asymptomatic bluish red noduleoverlying the infected gland/joint

*Ulceration with undermined edges and granulating tissue at the base.

*Numerous fistulae may intercommunicate beneath ridges of a bluish skin.

*Produce irregular adherent masses –fibrosis and discharging.

*Excessive granulation tissue 

*Sporotrichoid spread reported.

*heals with scarring.

*Clinical variant- extensive ulceration of scalp

📍Histopathology:

*In the center of the lesion ulcerated dermal abscess with an ill defined histiocytic component.

*In the deeper portions & periphery of the lesion contain tuberculoid granulomas with numerous bacteria.

📍Tuberculin skin test -+

📍COURSE

*Spontaneous healing can occur.

*Course is very protracted and leaves typical cord like scars

📍DIFFERENTIAL DIAGNOSIS

*Sporotrichosis

*Actinomycose

*Syhilitic gummata

*Hidradenitis suppurativa

📌Orificial Tuberculosis (Tuberculosis Ulcerosa Cutis et Mucosae/Tuberculosis cutis orificialis)

📍Acute tuberculous ulcer

📍Rare form of tuberculosis of the mucous membranes and the skin of the orifices

📍Due to autoinoculation of mycobacteria from progressive tuberculosis of internal organs.-(pulmonary,intestinal or rarely genitourinary)

📍Multibacillary type

📍CLINICAL MANIFESTATIONS

*Majority are males

*The affected patient – severely ill middle aged or elderly adult with impaired CMI, who has long-standing tuberculosis of one or more internal organs.

*Pulmonary TB-Ulcerated lesions occur most commonly in the mouth, especially on the tongue (tip and the lateral margins),

* In advanced cases the lips how granulomatous swelling.

*Intestinal tuberculosis--lesions develop around the anus

*In females with active genitourinary TB- vulva is involved.

*A large, very painful ulcer on the lips of this patient with advanced cavitary pulmonary tuberculosis

*Variants- lupus vulgaris like/ TBVC like

📍Histopathology:- 

Nonspecific inflammatory infiltrate; tuberculoid granuloma; numerous AFB

📍Tuberculin test- variable, positive in early stage and negative in late stages

📍D/D: oral lesions differentiated from Crohn disease, mucocutaneous leishmanisis, oral paracoccidiomycosis.

📍Slow response to ATT

📌Acute cutaneous miliary Tuberculosis
(Tuberculosis cutis disseminata)

📍Hematogenous dissemination of mycobacteria into the skin of individual with low immunity

📍Multibacillary

📍The initial focus of infection is either meningeal or advanced pulmonary.

📍Seen in infants /young children/HIV patients/measles

📍Rare

📍Profuse crops of bluish papules, vesicles, pustules, or haemorrhagic lesions in a patient who is obviously ill.

📍Common site- trunk,thighs,and buttocks

📍The vesicles may become necrotic to form small ulcers.

📍HPE-Necrotising tuberculous granulomas with multiple AFB

📍Tuberculin test –negative

📍Poor prognosis

📌Lupus Vulgaris (Tuberculosis luposa )

📍A chronic progressive post-primary,paucibacillary form of cutaneous TB in a person with a moderate or high degree of immunity.

📍The most common  type of cutaneous TB in india

📍More common in women than men.

📍It originates by hematogenous, lymphatic, or contiguous spread from tuberculosis elsewhere in the body,

📍Rarely, it follows primary inoculation tuberculosis or BCG vaccination.

📍CLINICAL MANIFESTATIONS

*Lupus vulgaris commonly appears in normal skin as a solitary lesion.

*The earliest lesion is a tiny, reddish-brown, flat plaque of soft consistency.

*Slowly extends peripherally to form a gyrate or discoid plaque with areas of atrophy

📍Diascopy- apple jelly nodules

📍Sites –

*India:buttocks and trunk;in children, lower limb and buttocks

*Europe- face(perinasal)

📍Clinical forms – 5 types

1)PLAQUE FORM :

*flat plaques with irregular or serpiginous edge.

*Surface – smooth,or covered with psoriasiform scales.

*Large plaque : irregular areas of scarring with islands of active lupus tissue.

2) ULCERATIVE AND MUTILATING FORMS :

*Necrosis and ulceration of plaques

*Scarring deformities and mutilations

3) VEGETATING FORMS:

*Necrosis and ulceration with minimal scarring.

*Mucous membranes are invaded and cartilage is slowly destroyed . This may lead to disfigurements.

*Response to chemotherapy is excellent

4)TUMOUR LIKE FORMS :

*Hypertrophic form presents either as soft tumour like nodules or epithelial hyperplasia

with production of hyperkeratotic masses.

*‘Myxomatous’ form-huge soft tumours occur on ear lobes ,grossly enlarged

5. PAPULAR AND NODULAR TYPE:

*Multiple papules and nodules occur simultaneously in disseminated lupus—true ‘miliary lupus’.

*This usually occurs after temporary immunosuppression as described in post-exanthematous forms, such as after measles

📍Lupus vulgaris of mucous mebranes:

*Primarily involved or secondary to extension of skin lesions.

*Nasal, conjuctival, buccal mucosa are involved

*Small, soft, gray or pink papules, nodule, ulcers,(nose) or vegetating or granulating masses that bleed easily. (buccal)

*Scarring deformities and disfigurement can occur.

*Scarring of the soft palate and stenosis of the larynx may also result.

📍Histopathology:

*Tubercles with scanty or absent central caseation surrounded by epitheloid histiocytes & MNG cells in superficial dermis

.*Peripheral lymphocytes are prominent

*Acid-fast bacilli are present in small numbers, hard to demonstrate

*Secondary changes may be superimposed: epidermal thinning and atrophy or acanthosis with excessive hyperkeratosis or pseudoepitheliomatous hyperplasia.

📍Lupus postexanthematicus

*After a transient impairment of immunity, particularly after measles, multiple disseminated lesions may arise simultaneously in different regions of the body -hematogenous spread from alatent tuberculous focus.

*Clinically and histopathologically, the lesions of are typical for lupus vulgaris, and their appearance distinguishes the condition from acute miliary tuberculosis of the skin.

📍Apple jelly nodules

*These nodules are seen on diascopic examination at the edge of the plaque as yellow brown macules and their color is similar to apple jelly.

*They do not exhibit this color in indian skin.

📍Match stick test – These nodules are soft and can be easily pierced by probe or match stick .

A nodule represents a collection of tubercles in dermis with degenerative changes.

Their presence is not pathognomic of lupus vulgaris.

📍D/D:

Sarcoidosis – nodules resemble grains of sand rather than ‘apple jelly’, on probing.

DLE

Leprosy-firmer nodules

Lupoid leishmaniasis

Tertiary syphilis

Blastomycosis

📍COURSE & PROGNOSIS

*If untreated has a progressive course.

*Scarring and Contractures are common.

*Contractures lead to ectropion ,microstomia

*Squamous cell carcinomas ,less commonly BCC can occur .

*Active lupus vulgaris can reappear in scar tissue.

📌Metastatic Tuberculous Abscess(Tuberculous Gumma)

The metastatic tuberculous abscess is caused by hematogenous spread of mycobacteria from a primary focus during a period of lowered resistance, resulting in single or multiple cutaneous and subcutaneous lesions.

It usually occurs in undernourished children or in immunodeficient or severely immunosuppressed patients.

📍CLINICAL MANIFESTATIONS

*Subcutaneous nodule or fluctuant abscesses -Singly or as multiple lesions.

*Extremities are more often affected than trunk.

*Overlying skin may break down to form undermined ulcer, often with sinuses.

*Metastatic tuberculous abscesses may occur with progressive organ TB or in miliary TB but also without an underlying focus.

*Tuberculin sensitivity is usually negative

*Occasionally, it may cause a carpal tunnel syndrome

📌THE TUBERCULIDS

📍First described by Darier in 1896

📍Tuberculids are considered as cutaneous hypersensitivity reaction to hematogenous dissemination of M. tuberculosis or its products from a primary source in a patient with significant immunity.

📍The main features of tuberculids are

1)A positive tuberculin test.

2)Tuberculoid histology on skin biopsy

3)A positive response to ATT.

4)Absence of bacilli in skin biopsy specimens and culture.

📍True tuberculids can be grouped as follows

a)Micropapular : Lichen Scrofulosorum

b)Papular : Papulonecrotic Tuberculid

c)Nodular : Erythema Induratum of Bazin or nodular tuberculid

📍Lichen Scrofulosorum/ tuberculosis cutis lichenoides

*It is a lichenoid eruption of minute papules

*Common in children and adolescents

*Has an underlying focus of tuberculosis-cervical/hilar or mediastinal(65%),lung,bone or intracranial sites.

*Tuberculin reaction is usually strongly positive.

*Associated with lupus vulgaris, TBVC, or tuberculous gumma.

*Clinical features:

-Asymptomatic closely grouped lichenoid papules,

-Slightly scaly and occasionally surmounted by a minute pustule.

-Perifollicular & appear in groups / in an annular arrangement of plaques

 

*Site- trunk and proximal limbs. Also on face.

*Spontaneous involution occur slowly, over a period of months, without scarring.

*HPE-Superficial dermal granulomas usually surround follicles and sweat ducts,usually no caseation.Mycobacteria are not seen in the sections.

*DIFFERENTIAL DIAGNOSIS-Lichen nitidus, Keratosis pilaris ,Keratosis spinulosa, Secondary syphilis,Micropapular forms of sarcoidosis,Drug eruptions.

📍Papulonecrotic Tuberculid

*An eruption of necrotizing papules, mainly affecting the  extensor aspects of extremities and occurring in symmetrical crops.

*Children and adolescents

*the tuberculin test is positive

*Associated pulmonary or extrapulmonary tuberculosis is frequently found.

*CLINICAL MANIFESTATIONS:-

-Recurrent crops of asymptomatic n symmetrical, hard, dusky-red papules. These crust or ulcerate. Heals with atrophic, varioliform scars, and hyperpigmentation over the course of a few weeks .New crops may continue over months or years.

-Sites- legs,knees, elbow,hands and feet

-Phlyctenular conjunctivitis may be present.-in children

-Lesions may progress or coexist with lupus vulgaris

*HPE:-

-Subacute lymphohistiocytic vasculitis that causes thrombosis and destruction of small dermal vessels In fully developed lesions a large central zone of coagulation necrosis is surrounded by inflammation extending from the superficial to the deep dermis, and sometimes into the subcutaneous tissues.

*D/D- pityriasis lichenoides,lekocytoclastic vasculitis.

📍Erythema Induratum of Bazin

*Most common form of tuberculid

*Young to middle aged females

*Tuberculosis associated lobular panniculitis

*Recurrent crops of small tender and painful erythematous or dusky nodules or deep seated plaques.

*Posterior aspect of legs

*Plaques are indurated with scaly surface

*Ulcerate following cold weather or venous stasis

*Heals with atrophic,hyperpigmented scarring

*HistoPathology:-

subcutaneous fat- lobular or septolubular granulomatous panniculitis with neutrophilic vasculitis of large or small blood vessels

*Clinical variants:

1)Nodular tuberculid- pathology in junction of dermis and subcutaneous fat.

2)Nodular granulomatous phlebitis- non ulcerating subcutaneous nodules along the course of great saphenous vein

*D/D:

erythema nodosum ,lupus profundus, polyarteritis nodosa

📌Prognosis of cutaneous TB

Tuberculosis confined to the skin, however, usually responds well to treatment & clinical response will occur within 4- 6 weeks, with lupus vulgaris showing faster response time than scrofuloderma