Cutaneous tuberculosis Dermatology

Cutaneous tuberculosis

1. CUTANEOUS TUBERCULOSIS Dr.Shanmathi Sethumadhavan ,Postgraduate ,TVMCH Moderator : Dr.M.Kalaiarasi

2. Epidemiology TB of the skin is uncommon, accounting for around 1.5 %of EPTB cases. Cutaneous TB often coexists with other forms of TB, especiallypulmonary TB and lymph node TB. Tuberculosis is the second leading cause of death from an infectious disease(after HIV infection ) Approximately one‐third of the world’s population is infected with M. tuberculosis bacteria HIV -positive people are approximately 20 times more likely than HIV-negative people to develop TB in countries with a generalized HIV epidemic, and between 26 and 37 times more likely to develop TB in countries where HIV prevalence is lower.

3. INTRODUCTION ‘mycobacterium’ – a large group of bacteria producing mould ‐like pellicles when grown on liquid media . All are slender, non‐motile, aerobic, non‐ sporing rods with a waxy coating that makes them resistant to most stains. Once stained , however, they are not easily decoloured (acid‐fast).

4. INTRODUCTION Tuberculosis of the skin is caused by Mycobacterium tuberculosis Mycobacterium bovis 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.

5. MC form in India – Overall- Lupus vulgaris Adults - Lupus vulgaris Children- scrofuloderma > lichen scrofulosorum MC form in world - Scrofuloderma

6. 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

7. Host immunity Method of inoculation Disease Multibacillary forms AFB can be demonstrated Low immunity host – Mantoux negative Naive host Low Low Low Low Direct inoculation Contiguous spread Autoinoculation Haematogenous spread Haematogenous spread TB chancre Scrofuloderma Orificial TB Tuberculous gumma (abscess) Acute miliary cutaneous TB Paucibacillary forms Difficult to demonstrate AFB High immunity host – Mantoux positive High High High High Direct inoculation Direct inoculation < Haematogenous spread Haematogenous spread TBVC (warty TB) Lupus vulgaris Lupus vulgaris Tuberculids

8. CLASSIFICATION (Modified from Beyt et al. ) Inoculation tuberculosis (exogenous source ): a.Tuberculous chancre b.Tuberculosis verrucosa cutis c.Lupus vulgaris(some ) 2. Secondary tuberculosis (endogenous source) a.Contiguous spread  S crofuloderma b.Autoinoculation  O rificial tuberculosis

9. 3 . Haematogenous tuberculosis Lupus vulgaris(some ) Tuberculous gumma Miliary tuberculosis of skin 4 . Eruptive tuberculosis ( Tuberculids ) Micropapular Lichen scrofulosorum Papular Papular or Papulonecrotic tuberculid Nodular Erythema induratum ( B azin’s disease ) Nodular tuberculide Erythema nodosum

10. Predi s po s ing factor : Underlying tuberculou s focus Close contact w ith kno w n TB Immunocompromised Overcro w ding Lo w SES Poor living condition

11. TUBERCULOUS CHANCRE Naive host: not previously infected with tuberculosis and have no immunity. MOT :direct inoculation Preceded by s ome type of injury/ breach in skin Common age - children Common sites: limbs and face Predi s po s ing factor : children (especially not BCG vaccinated and exposed to pulmonary tuberculo s i s) Health care w orker( esp in endemic areas)

12. Organisms: M.Tb M.Bovis BCG After t wo to 4 wks of inoculation Bro w ni sh papule or n odule  painless nonhealing ulcer w ith firm undermined edges and granulomatous hemorrhagic base ,adherent crust regional lymphadenopathy (after 4-8 wks ) TB chancre + regional LNE = cutaneous equivalent of Ghon’s focus in lung COURSE : Spontanoeus healing with scar or develop into lupus vulgaris or warty tuberculosis Miliary TB,EN Calcified nodes, Cold abscess , scrofuloderma ,

13. SCROFULODERMA/ TB COLLIQUATIVA CUTIS/ King’s evil Direct invasion of TB Bacillus into skin from underlying contiguous tuberculosis focus present either in a lymph node,bone , joint, lacrimal gland /duct ,breast ,epididymis or testes . Sites of predilection: Cervical(most common) ,axillary and inguinal lymph nodes. a/w Osteomyelitis of scalp, ribs,limbs a/w Systemic TB, Sweet’s syndrome Site : MC- face and neck (often B/L) Age : Children, 1 st 3 decades of life .any age M:F : 1.5:1 Org : M.Tb

14. Bluish red painless s ubcutaneous swelling/nodule  cold abscess  suppurates  ulcer with undermined edge and granulating tissue at the base . Numerous fistulae and nonhealing sinus tracts may intercommunicate beneath ridges of a bluish skin . Progression and scarring produce irregular adherent masses. Cour se : spontaneous healing may occur with puckered cord like scars

15. Differential Diagnosis   Atypical mycobacterial infection   Lymphogranuloma venereum   Actinomycosis   Sporotrichosis   Syphilitic gummas   Acne conglobata   Hidradenitis suppurativa

16. Scrofuloderma

17. Scrofuloderma - Ulcerated dermal abscess superficially - deep dermis tuberculoid granulomas with casseation and plenty AFB

18. ORIFICIAL TUBERCULOSIS TB cutis orificialis Orificial tuberculosis is characterized by painful ulcerated lesions due to tuberculous infection of the mucosa or the skin adjoining orifices . Patient Is severely ill with advanced internal TB or impaired CMI MOA: autoinoculation Age : middle age and elderly male Organism : M.tb

19. Site affected depends on the site of internal tuberculosis : Pulmonary TB ,TB of pharynx, larynx : oral , nasal Intestinal tuberculosis : perianal, external genitalia Genitourinary tuberculosis : perineum (vulva, urinary meatus )

20. C onstitutional symptoms-fever, w eight loss,night s w eats Site : around orifices (oral ,anus, vulva , penis ) Mc : oral mucosa (tongue –tip and lateral margin), gingivitis, granulomatous swelling of lips Small red edematous nodule  break to form painful s h allo w ulcers < 2 cm with undermined blue edge No tendency to heal spontaneously , very s low response to ATT Prognosis: poor due to advanced internal disease and compromised immunity.

21. Orificial tuberculosis

22. Acute miliary tuberculosis of skin / TB cutis miliaris disseminata Acute miliary tuberculosis is due to the haematogenous spread of tubercle bacilli into the skin . Commonly seen in advanced pulmonary or meningeal and disseminated tuberculosis . It affects infants and young children Predisposing facotrs : Immunosuppressed HIV infection following viral infections such as measles malnutrition

23. Site : can occur all over the body. most frequently found on the trunk, thighs, buttocks and genitalia . The cutaneous lesions consist of crops of minute bluish papules vesicles , pustules or hemorrhagic lesions in a patient who is obviously ill . vesicles may become necrotic to form small ulcers. Poor Px

24. Miliary tuberculosis of skin

25. TUBERCULOUS GUMMA / METATATIC TUBERCULOUS ABSCESS It occurs due to disseminated hematogenous spread of mycobacteria from primary focus during periods of lowered resistance Predisposing factors : malnourished children immunosuppressed adults . Venepucture Lymphoma

26. Site : extremities > trunk . Single /multiple , firm dermal subcutaneous nodules  nontender fluctuant mass(abscess)  break down to form undermined ulcers with sinus , fistula . Healing with cordlike , puckered scars No underlying tissue involvement May cause carpal tunnel syndrome Tubreculin test usually positive ; negative if poor condition of the patient Slow improvement w ith treatment

27. Tuberculous gummata

28. Tuberculous gummata Marked casseation with well-defined granulomatous infltrate Few bacilli

29. TUBERCULOSIS VERRUCOSA CUTIS

30. also known as anatomist’s warts, prosector’s warts and verruca necrogenica Common in laborers and manual workers ( walking barefoot ) Common site : lower limbs ( area exposed to trauma or s putum) hand, feet, buttocks, knees , ankle Small, solitary, indurated, red or brown, papule (with inflammatory areola) or nodule  Verrucous plaque ( serpiginous outline , finger -like projections; fissured surface )  centre involute l/t w hite thin atrophic scar s

31. Warty tuberculosis

32. Pseudoepitheliomatous hyperplasia Hyperkeratosis and acanthosis with abscess formation in upper dermis.illdefined caseating granuloma in the mid dermis. Deep dermis showing granulomatous inflammatory cell infiltrate.

33. Differential diagnosis Warts Keratoses Hypertrophic lichen planus Verrucous epidermal nevus Blastomycosis Chromoblastomycosis Actinomycosis Leishmaniais Tertiary syphilis Other mycobacterial infections

34. Lupus vulgaris 1808, Robert willan Founder of british derma. Gave term LUPUS To nodular eruption on face 1887 , William Tilburg Fox used term LUPUS VLGARIS for skin TB LUPUS word Origin ? Latin word of wolf ? Greek word lepros

35. LUPUS VULGARIS Most common form of cutaneous tuberculosis in adults in India Chronic progressive paucibacilary form Occurs in sensitized individuals with moderate to high immunity- tuberculin sensitive Affects all age groups . F> M

36. MOT   Haematogenous dissemination-face   Lymphatic spread   Contiguous spread from tuberculous tissue   Exogenous inoculation – extremities Site head and neck—nose, eyelid,pinna Europe Lower limb (Buttocks) and trunk > face --- children in India Site of tattoo in the scar of scrofuloderma at the site of a BCG vaccination

37. Soliatay ,small , reddish brown , flat plaque with soft , gelatinous , consistency. On diascopy ,- the diagnostic ‘apple jelly’ nodules-yellow brown The lesion gradually becomes elevated, infiltrated, discoid with areas of atrophy peripheral extension and central scarring D isseminated forms-multiple lesions Sporotrichoid ‐like spread can occur

38. Clinical types of lupus vulgaris Plaque type Psoriasiform scale Ulcerative or mutilating type Scarring , contracture, deformity Vegetating type minimal scarring Tumor-like Myxomatous form - earlobe Papulonodular

39. PLAQUE TYPE ULCERATIVE/MUTILATING TYPE

40. TUMOR-LIKE VEGETATING TYPE

41. Lupus vulgaris

42. Diascopy apple jelly nodules

43. Lupus vulgaris epitheloid cell granuloma in the deep dermis Epitheloid cell granuloma and L anghans giant cell

44. TUBERCULIDS Immune reactions in the skin due to hematogenous dissemination of M.tuberculosis (or its antigens) from a primary source, in an individual with strong cell-mediated immunity .

45. LICHEN SCROFULOSORUM Firm, typically perifollicular pink or yellow-brown tiny 0.5 to 3mm papules topped by scale. Asymptomatic lichenoid papules in clusters predominantly over trunk . Lesions persist for months and disappear without scarring. Cutaneous marker of underlying TB Age : children adolecent

46. LICHEN SCROFULOSORUM

47. Lichen scrofulosorum Superficial dermal granulomas around the hair follicles or sweat ducts. The granulomas are composed of epithelioid cells with some Langhans giant cells and a narrow margin of lymphoid cells at the periphery. C aseation necrosis is absent.

48. PAPULONECROTIC TUBERCULID M. tuberculosis, M. kansassi , M. avium complex and M. bovis infections Asymptomatic recurrent crops of hard erythematous small , symmetrical papules  pustules  with central necrosis(ulcer)  crust spontaneously heals with varioliform scarring & hyperpigmenation Common in children and young adults extensor of extremities ( legs , knees ,elbows , hands and feet) . [

49. PAPULONECROTIC TUBERCULID

50. Papulonecrotic tuberculid Wedge shaped infarctio n of the epidermis and dermis due to vasculitis . Necrotizing lymphohistiocytic vasculitis of the dermal artery with surrounding granuloma.

51. ERTHEMA INDURATUM(BAZIN’S DISEASE) MC Tuberculid young/middle aged women . Recurrent Painful erythematous or dusky red nodules over calves central necrosis  ulcers with ragged, irregular blue edge  heal with atrophic, hyperpigmented scarring. focal./diffu s e Lobular/ septolobular granulomatous panniculitis with neutrophilic va s culitis

52. ERYTHEMA INDURATUM Lobular granulomatous panniculitis with vasculitis

53. Patients who should be investigated for cutaneous TB Presumptive cutaneous TB Patients with the following clinical presentations: Ulcers or discharging sinuses over the sites of lymph nodes , bones and joints Persistent , asymptomatic raised reddish/reddish brown skin lesion of more than 6 months’ duration, which may show scarring at one end Persistent warty skin lesion of more than 6 months’ duration

54. Mantoux tes ( tuberculin skin testing) The Mantoux test is not usually part of the diagnosis of active TB infection. in selected cases where diagnosis was equivocal However, only a strongly positive result (with a diameter of 22 mm or more at reading) supports a diagnosis of cutaneous TB ( Ramam , 2011). A negative or weakly positive result does not rule out TB. Sensitivity and specificity estimates for this test vary widely across case series, and the result must be interpreted in the context of the other clinical findings.

55. All patients with the following results should be treated for cutaneous TB: Patients with histology diagnostic of cutaneous TB Patients with positive culture of Mtb or microscopy for AFBs from skin biopsy Patients with equivocal histology findings and negative microscopy and culture , but strongly positive Mantoux test

56. Treatment Drugs 2RHZE/4RHE Duration 6 months

57. PICTURE QUIZ

58. WORKOUT

59. Case A ten year-old boy presented with a generalized papular rash on the trunk and proximal parts of the upper and lower extremities with mild itching since the last two months. There was no history of fever, cough, anorexia, weight loss or any other systemic symptoms. General physical examination revealed a thin built boy with moderate pallor and matted, nontender , firm, 2 to 1.5 cm-sized lymph nodes in the right axilla. The overlying skin was not involved . No other significant lymphadenopathy or organomegaly was present . .

60. Cutaneous examination showed multiple, grouped, skin-colored to reddish-brown, follicular and extrafollicular lichenoid papules with mild scaling located on the front and back of the trunk, upper arms, thighs and sides of the face . The lesions were asymptomatic and densely distributed over the upper back . Examination of hair, nails and mucosal surfaces did not reveal any abnormalities

61. Laboratory examination: hemoglobin level of 8 g % anemia ESR  50mm/hour Mantoux test with an induration of 18 x 14 mm . Fine needle aspiration cytology from the right axillary lymph node showed a few epitheloid cell clusters . Skin biopsy from a papule on the trunk showed noncaseating , epitheloid cell granulomas in the superficial dermis surrounding a hair follicle . Tubercular bacilli could not be detected on acid-fast staining . Culture for  Mycobacterium tuberculosis  was sterile. Chest radiography and all the other routine investigations were normal.

62. Lichen scrofulosorum

63. Case 40-year-old male presented with an ulcerated plaque over the plantar aspect of left foot for one year that was associated with swelling, pain and occasional watery discharge  . He also gave history of low grade fever and cough over two months . No other significant co-morbidities or contact with tuberculosis was present . No h/o any previous anti-tubercular therapy.

64. CBC,RFT,LFT  NORMAL Cultures from the wound discharge (bacterial, fungal and tubercular) were negative . Chest X-ray revealed bilateral miliary mottling   . Computed tomography of the chest showed characteristic miliary nodules bilaterally. Mantoux test was negative . Sputum smear and cultures (on Lowenstein-Jensen medium) were also negative. AFB were not seen or grown from bronchial washings and mycobacteria were not detected by PCR.

65. A skin biopsy from the plantar lesion revealed granulomas in the dermis composed of epithelioid cells, Langhans giant cells and lymphocytes in the dermis with marked hyperkeratosis and parakeratosis of the overlying epidermis

66. MILIARY TUBERCULOSIS WITH TUBERCULOSIS VERUCOSA CUTIS

67. CASE A 7-year-old Kashmiri girl presented with multiple painful swellings over both hands, left forearm and right foot, which was associated with fever for six months . The lesion initially appeared over the lateral aspect of the left thumb, increased in size over a period of 15 days, followed by rupture and oozing of thick straw colored fluid. Similar lesions appeared over the right hand, left forearm and right heel . She had evening rise of temperature, night sweats and weight loss. There was no history of prior injury.

68. She was treated with oral antibiotics and analgesics but reported no relief. Her general physical and systemic examination was normal except for discrete left axillary lymphadenopathy . Cutaneous examination showed multiple, ill defined, tender, indurated crusted plaques and depressed ulcers with violaceous margins and nodules varying in size from 1 cm to 4 cm over the left thumb, right thumb and index finger, left forearm, left elbow and right foot posterior to the ankle.

69. NCNC anemia. Raised ESR and lymphocytosis . serum calcium, phosphate and alkaline phosphatase was normal . Mantoux test was strongly positive (20 × 20 mm ). Smears for acid fast bacilli, bacteria and fungi were negative . Histopathological examination of the skin biopsy showed epithelioid cell granulomas with Langhans giant cells and foci of caseation necrosis . PCR and culture for  Mycobacterium tuberculosis  on Bactec medium was positive . The chest radiograph was normal.  

70. Radiographs of the hands revealed a cystic expansile lesion of the diaphysis in the first left and second right metacarpals with sclerosis of the shaft. There were cortical erosions on the lateral aspect of the respective metacarpals with no periosteal reaction. Similar findings were seen in the right calcaneum and metaphysis of the left distal radius

71. Scrofuloderma overlying tuberculous dactylitis

72. Case A 36-year-old female presented with multiple asymptomatic raised red lesions on both the forearms, dorsum of hands, and back for a period of 4 months. She was not suffering from cough, fever, or weight loss . She had no past history of tuberculosis (TB) or contact with case of TB . She had undergone tuberculin testing 2 days back. .

73. On examination, She had multiple, erythematous to violaceous papules over both the forearms , dorsum of hands, and a few over the back. Examination of tuberculin test site revealed indurated plaque (20 × 18 mm) and multiple erythematous papules at the periphery of the positive tuberculin reaction. There was no evidence of lymphadenopathy and hepatosplenomegaly , and rest of her systemic examination was unremarkable

74. Her routine blood investigations ( Hb , complete blood count, liver, and renal function tests) were normal . ESR 110mm/hour. Chest X-ray and abdominal ultrasonography examination were normal . Her enzyme-linked immunosorbent assay (ELISA) test for HIV was negative

75. Biopsy of the papule on forearm and the papule around the site of tuberculin test showed wedge-shaped area of necrosis involving the dermis, overlying epidermis along, and vasculitis at the base of necrotic dermis . Moderately dense lymphohistiocytic infiltrate was noted in the surrounding dermis.

76. Papulonecrotic tuberculid

77. Diagnostic criteria ABSOLUTE: Positive culture of M.tuberculosis from the lesion Polymerase chain reaction on tissue specimen. RELATIVE: Clinical history and signs. Presence of active proven tuberculosis elsewhere in the body. Presence of acid-fast bacilli in the lesion. Histopathology . Positive reaction to tuberculin or quantiferon TB Gold test. Effect of specific therapy.

78. Thank you.