1. Cutaneous Tuberculosis Dr. (Prof.) Archana Singal University College of Medical Sciences & GTB Hospital, New Delhi Digital Lecture Series : Chapter 09

2. 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

3. 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  2 nd 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.

4. 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

5.  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

6.  M. Tuberculosis major etiological agent  M. bovis1 – 1.5% WITH HIV  M. avium complex2 / 3 cases  M. tuberculosis10% cases  M. kansasii  M. scrofulaceum Etiology

7.  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.

8. EXPOSURE (BCG/Pri. Pulm. Infection/Skin Inoculation) Mycobacteria engulfed by macrophages Antigen presented to CD4+ T H 1 cell (In 2-3 weeks) Hypersensitivity / Granuloma Form n / Caseous Necrosis Disease Arrested Latent Infection Progressive Disease (5-10%) Pathogenesis

9.  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

10. 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

11. Exogenous cutaneous tuberculosis Tuberculous chancre Tuberculosis verrucosa cutis (TBVC) Endogenous cutaneous tuberculosis By contiguity or autoinoculation  Scrofuloderma (SFD)  Orificial tuberculosis  Lupus vulgaris (some cases) LV Classification of Cut TB (Beyt et al) contd.

12. 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

13.  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)

14. Firm, painless and brownish papule 2-3 weeks 3-8 weeks Firm, non-tender ulcer Regional LAP with 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

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

16.  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

17. Warty lesions of TBVC in adults with good immunity on extremities (trauma prone sites) Left foot, left palm and sole of the left foot.

18.  Hypertrophic lichen planus  Verruca vulgaris  Chromoblastomycosis  Leishmaniasis Differential Diagnosis of TBVC

19.  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)

20. Firm, subcutaneous nodule, fixed to the overlying 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

21. Clockwise: 1. Tubercular abscess overlying rib cage with impending rupture. Pus smear from aspirate on ZN staining showed numerous AFB i.e M. tb 2. Scrofuloderma overlying cervical and supraclavicular TB lymphnodes 3. Scrofuloderma overlying TB focus in the bone i.e 2 nd metacarpal bone which shows a lytic lesion on x-ray

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

23.  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

24.  Bacterial abscesses / Bacterial osteomyelitis  Hidradenitis suppurativa  Atypical mycobacterial infection (M.avium and M. scrofulaceum)  Sporotrichosis  Actinomycosis  Tumor metastasis Differential Diagnosis

25.  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)

26.  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

27.  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)

28.  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

29.  Plaque  Ulcerative & mutilating  Hypertrophic  Vegetating & tumor like  Atrophic and plantar Clinical Variants

30. 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 boy 3. Lesion of LV on buttock in an adult male

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

32.  Sarcoidosis  Hansen’s disease  Lupus erythematosus  Granuloma faciale  Leishmaniasis  Squamous cell carcinoma Differential Diagnosis of Lupus Vulgaris

33.  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)

34. Tuberculosis Gumma

35.  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

36.  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

37.  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

38.  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)

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

40. Positive Mantoux test with blistering after 48 hrs Pulmonary Kochs

41.  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 manifestations Differential diagnosis: Varicella and PLEVA Papulonecrotic Tuberculide

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

43. 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

44.  Notification  Identification and treatment of the underlying tuberculous focus which is identifiable in ½ to 1/3 rd of cases  Identification and treatment of co-existent infections such as HIV  Specific chemotherapy  Family screening  Ancillary measures Management of Cutaneous Tuberculosis General Principles

45. Hematological  CBC with ESR  LFT  RFT Mantoux test Sputum for AFB Radiological  X-ray chest  Radiograph of the affected region- bone  USG Abdomen  CECT – chest And MRI – selected cases Investigations

46.  FNAC  Skin Biopsy  Mycobacterial culture- LJ medium (Lowenstein Jensen) BACTEC 460 liquid medium  PCR  Antigen detection  Biochemical characteristics Investigations

47.  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

48. Compact epithelioid cell granuloma in mid and upper dermis in LV

49. 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

50. 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

51.  Duration6 months  CategoryI  Regimen2 (HRZE) + 4 (HR) Daily or  DOTS Thrice weekly Treatment DrugDaily Tx mg/kg/d (Total) DOTS mg/kg/d (Total) Isoniazid5 (300)10 (600) Rifampicin10 (450) Pyrazinamide25 (1500) Ethambutol15 (800)20 (1200)

52.  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

53.  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

54. Q.1) What is the classification system used for Cutaneous Mycobacterial infection? A.Schobinger's classification B.Freidrikson's classification C.Beyt's classification D.Luxar and Zulian classification Q.2) Which of these precludes a diagnosis of Tuberculid? A.Positive tuberculin test B.Partial response to Antituberculous therapy C.Negative Mycobacterial Culture D.Past history of Pulmonary Tuberculosis MCQ’s

55. Q.3) Which of the following malignancies are known to occur in long standing case of lupus vulgaris? A.Squamous cell carcinoma B.Basal cell carcinoma C.Sarcoma D.Malignant melanoma Q.4) Which of the lymph nodes are commonly involved in cutaneous tuberculosis ? A.Axillary B.Cervical C.Inguinal D.Epitrochlear MCQ’s

56. 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 sarcoid B.Lupus vulgaris C.Hypertrophic lichen planus D.Tuberculosis verrucosa cutis MCQ’s

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

58. Q. Identify the type of Cut TB? Photo Quiz

59. Q. Identify the type of Cut TB ? Photo Quiz

60. Thank You!