Granulomatous - Resident PPT for 1st year.pptx

Granulomatous - Resident PPT

1. Definition Granuloma is a focus of chronic inflammation consisting of a microscopic aggregation of macrophages that are transformed into epithelium-like cells, surrounded by the collar of mononuclear leukocytes, principally lymphocyte & occasionally plasma cells.

2. Classification BACTERIAL RHINOSCLEROMA SYPHILIS TUBERCULOSIS LUPUS LEPROSY FUNGAL RHINOSPORIDIOSIS ASPERGILLOSIS MUCORMYCOSIS CANDIDIASIS HISTOPLASMOSIS BLASTOMYCOSIS UNSPECIFIED CAUSE WEGENER’S GRANULOMATOSIS PERIPHERAL T-CELL NEOPLASM (NON-HEALING MIDLINE GRANULOMA) SARCOIDOSIS CHURG-STRAUSS SYNDROME

3. Rhinoscleroma Causative organism- Klebsiella rhinoscleromatis or Frisch bacillus. Endemic in india (northern)

4. Rhinoscleroma Pathology Progressive granulomatous lesion begins at the nose and extends up to nasopharynx , Larynx( subglotic ), trachea and lower airway can also be involved.

5. Rhinoscleroma Clinical Features Atrophic stage – The features resemble that of atrophic rhinitis, including crust formation and a foul smelling discharge. (Carpenter’s Glue) Granulation / nodular stage – (Sub dermal infiltration) Nodules are non ulcerative in nature. These nodes are initially bluish red and rubbery and upper lip giving a “woody” feel Hebra nose- expansion of the anterior nares and deformity of the upper lip

6. Rhinoscleroma Cicatrizising stage – Adhesions and scarring is a feature of this stage. Stenosis distort normal nasal anatomy. Shape of the nose changes and is classically name the Tapir’s nose . There may be glottic stenosis with respiratory distress.

7. Rhinoscleroma Accumulated inflammatory cells include: Plasma cells, lymphocytes, eosinophils and scattered large foam cells (Mikulicz cells) & Russell bodies. Mikulicz cells- identified morphologically as a macrophage, not a plasma cell. These foam cells have a central nucleus and a vacuolated cytoplasm containing bacillli . Russell bodies-Homogenous eosinophillic inclusion bodies found in plasma cells.

8. Rhinoscleroma Accumulated inflammatory cells include: Plasma cells, lymphocytes, eosinophils and scattered large foam cells (Mikulicz cells) & Russell bodies. Mikulicz cells- identified morphologically as a macrophage, not a plasma cell. These foam cells have a central nucleus and a vacuolated cytoplasm containing bacillli . Russell bodies-Homogenous eosinophillic inclusion bodies found in plasma cells.

9. Rhinoscleroma Levin test – complement fixation test based on reaction of patient’s serum with suspensions of K. Rhinoscleromatis High titres of antibodies to K. rhinoscleromatis has been demonstrated in these individuals Tissue biopsy is diagnostic Investigations

10. Rhinoscleroma Treatment Usually self limiting course of its own accord ending in the cicatrizing stage Traditionally Used : streptomycin (1gm i.m ) and tetracycline (2 g/day) for 4-6wks, Recently used : Oral rifampicin (450mg for a period of 6 weeks), sulphamethoxazole -trimethoprim combination, and ciprofloxacin. Local application of 2 % acriflavin for a period of 8 weeks has been noted to be both efficacious and nontoxic. Intralesional steroids have been tried.

11. Rhinoscleroma Kailasa Regime : Carbolic acid (0.2ml) + Glacial acetic acid (0.2ml) + Glycerine (0.4ml) + 10ml distilled water is injected locally as 1 to 2 ml twice weekly at multiple sites of the lesion. Usually 8-10 injections lead to complete regression of granuloma and restoration of normal nasal patency. S/E-chemical necrosis of granuloma. Irradiation Total dose of 3000-3500 Gy over three weeks

12. Syphillis Can affect any age neonate to elderly. Causetive organism- Treponema pallidum Two types- I.Congenital II.Acquired 1. Primary syphilis 2. Secondary syphilis 3. Tertiary syphilis

13. Hereditary/congenital syphilis Any of lesions of secondary and tertiary forms of syphilis of nose may occur In infants- snuffles most common First appears as simple catarrhal rhinitis, then becomes purulent with secondary fissuring and excoriation of nasal vestibule and upper lip. Obstruction may interfere with suckling and nutrition. Gummatous and destructive lesions occur at puberty.

14. Bulging of the frontal bones and depression of the nasal bridge ("saddle nose"), both due to periostitis Rhinitis from weeping nasal mucosal lesions ("snuffles") Circumoral rash.

15. Hutchinson's triad Interstitial keratitis, sensory-neural deafness and hutchinson's teeth. Upper central incisors peg-shaped and widely spaced.

16. Primary Syphillis Also known as Sore/chancre develops at site of inoculation with regional lymphadenitis. occur on external nose or inside vestibule Hard, non painful, ulcerated papule, associated with rubbery non tender nodes Self limiting lesion Diagnosis- Smears from ulcer or node examined by dark ground illumination shows the spirochaete, Treponema pallidum . Serological tests- VDRL TPHA FTA-ABS Biopsy

17. Secondary Syphillis Most infectious Manifests 6-10weeks after inoculation Clinical symptoms- Simple catarrhal rhinitis Crusting and fissuring of nasal vestibule Secondary syphilis rarely recognized in the nose, as mucous patches hardly ever occur on such a thin, attenuated mucous membrane. Diagnosis suggested by appearance of other secondary lesions- mucous patches in pharynx, roseolar or papular rash, pyrexia, enlargement of lymph nodes.

18. Tertiary Syphillis Only 1/3 rd of cases of secondary syphilis progress to tertiary stage. Pathological lesion- gumma - begins as subcutaneous nodule, progresses to involve overlying skin, and then breaks down to form a punched out destructive ulcer. Bony portion of septum most commonly involved Lateral nasal wall, frontal sinus, nasal bones, floor of nose may be involved late.

19. Ulcerated Gumma Cicatrization of bony nasal dorsum

20. Symptoms- pain, swelling, obstruction, offensive discharge, crusting, bleeding, anosmia. Tenderness over bridge nose is characteristic sign Sequelae- collapse of bony support of nose, atrophic rhinitis. Diagnosis- characteristic organ involvement, histopathology, serological tests, response to antibiotics

21. Treatment Penicillin is the drug of choice: benzathine penicillin 2.4 million units i.m. every week for 3 weeks with a total dose of 7.2 million units. Nasal crusts are removed by irrigation with alkaline solution. Bony and cartilaginous sequestra should also be removed. Cosmetic deformity is corrected after disease becomes inactive.

22. Complications Vestibular stenosis Perforations of nasal septum and hard palate Secondary atrophic rhinitis Saddle nose deformity.

23. NASAL TUBERCULOSIS Cause-Mycobacterium tuberculosis. Always associated with primary pulmonary tuberculosis Modes of infection-Inhalation(Most common),ingestion and inoculation. Most common affecting form is-Lupus vulgaris/cutaneous tuberculosis.

24. Lupus Vulgaris Associated with painfull skin lesion most often on face around nose,eyelids,lips,cheek,ear,neck . Macroscopic apperance - 1.Nodular foam (MC) 2.Ulcerative foam 3.Sinus granuloma

25. Lupus Vulgaris Clinical features- Nasal discharge / obstruction Presence of non foul smelling crusts Epistaxis Ulceration of nasal mucosa is followed by fibrosis, and contraction of nares

26. Apple jelly nodules – Early lesion. Reddish brown nodule at the mucocutaneous junction of nasal septum. Cartilagenous portion of nasal septum undergoes destruction

27. Diagnosis lupus nodules Blanching on pressure- When pressure is applied to adjoining nasal mucosa using glass slide, pinkish nodules will stand out because the adjacent areas undergo blanching Tissue biopsy- epitheloid cell granulomas, features of caseation, AFB. Direct demonstration or culture of organism DNA amplification by PCR Monteaux test Associated pulmonary tuberculosis- chest x-ray Treatment Anti tubercular Therapy

28. Leprosy cause Mycobacterium leprae Mode of transmission- via nasal secretions or skin. The nose is involved as a part of systemic disease, more often in the lepromatous than tuberculoid or dimorphous forms of disease.

29. Tuberculoid Type Skin lesion extend upto vestibule Cranial nerve palsy (Vth and VIIth )

30. Lepromatous Type These nodules are commonly seen in the anterior end of inferior turbinate Nasal obstruction. Collapse of the anterior bridge of the nose with destruction of anterior nasal spine is a feature. Both bony and cartilagenous portions of nasal septum are destroyed,Saddle nose deformity. Nasal crust formation, serosanguinous nasal discharge. Presence of nodular thickening of nasal mucosa is the earliest feature.

31. Diagnosis Skin lesions, thickened nerves Demonstration of M. leprae on microscopy of the nasal discharge or scrapings of nasal mucosa Histopathology of nasal mucosa. Skin biopsy may be required to demonstrate the bacillus.

32. Treatment Triple therapy- rifampicin 600 mg on the first two days of each month clofazimine 100 mg on alternate days three times a week, and dapsone 100 mg daily. Direct intranasal administration of rifampicin Cosmetic surgery.

33. Rhinosporodiasis It is a chronic granulomatous disease caused by Rhinosporidium seeberi which predominantly affects the mucous membrane of the nose and nasopharynx. characterized by formation of papillomatous and polypoid lesions. It has also been described as a strawberry like mulberry mass.

34. Incidence / geographical description More than 90% of cases have been reported from India / Sri Lanka and Pakistan. In India disease is more common in southern states. It is prevalent in the states of Tamilnadu , Kerala, Madhya Pradesh, Chhattisgarh, and Andhra Pradesh (Madurai, Ramnad , Rajapalayam , and Sivaganga are endemic zones in Tamilnadu .) Age: B/W 20 -40yrs M:F 4:1

35. The mode of Infection Stagnant pools of fresh water Dust from the dung of the infected horses and cattle. Contact transmission by contaminated finger nails.

36. Etiologic agents Stagnant pools of fresh water Dust from the dung of the infected horses and cattle. Contact transmission by contaminated finger nails.

37. Life Cycle Spore is the basic infecting unit . Life cycle Of Rhinosporidium seeberi is completed in 3 stages. These are as follows: MATURATION OF TROPHOCYTE DEVELOPMENT OF SPORANGIA AND ENDOSPORES RELEASE OF ENDOSPORES

38. Clinical Fetures Mass in the nose 72 % Nasal obstruction 66% Bleeding from the nose 28% Nasal discharge 24% Change in voice 2-4% Headache 3-6% It present as a leafy, friable , bright pink to purple in colour, highly vascular , polypoid mass in the nose attached to nasal septum or lateral wall.

39. Site Distribution Lateral wall 44% Nasal septum 36% Nasal floor 6% Nasopharynx 2% Multiple sites 12% Growth may extend posterior up to nasopharynx, oropharynx, and anteriorly may hang up to lips .

40. Diagnosis Microscopically examination of nasal discharge will show spores . Biopsy and histological examination shows several sporangia, oval or round in shape and filled with spores which may be seen bursting through it chitinous wall.

41. 1 Mature sporangium 2 Spores 3 ImmatureSporangium

42. Treatment Surgical : Complete excision of the mass with diathermy knife and cauterization of it base. Recurrence is not uncommon. Medical : Recently Dapsone ( diaminodophenylsulphone ) has been shown to be effective in controlling Rhinosporidiosis . 100 mg/day – 6 months

43. Aspergillosis CAUSATIVE ORGANISMS Aspergillus niger Aspergillus fumigatus or Aspergillus flavus Aspergillosis invades the nasal tissues in those who handles doves and other captive birds when host’s defence mechanism are compromised

44. Clinical Features SYMPTOMS Nasal obstruction Sneezing and watery Mouldy – smelling discharge On examination The nasal mucous membrane is covered with greyish (fumigatus) or black ( niger ) false membrane. The infection usually invades the antrum. Exploration of maxillary sinus reveals a fungus ball containing semisolid cheesy-white or blackish material.

45. DIAGNOSIS The organism can be seen on culture examination of Membrane and special staining for fungus. TREATMENT The specific treatment consists of repeated cleaning and local application of 1% aqueous solution of gentian violet and nystatin. Antifungal AMPHOTERICIN B may be given systemically. When the sinuses are involved, operative clearance should be performed.

46. Sarcoidosis Chronic systemic disease of unknown etiology which may involve any organ with non- caseating (hard) granulomatous inflammation Female preponderance 2:1 Etiology- Unknown immunological response to antigen (include mycobacteria, fungi, chemicals{Exposure to Beryllium, zirconium, pine pollen and peanut dust})

47. Clinical Features

48. Nasal mucosa gives a characteristic appearance- strawberry skin because of the tiny pale granulomas against hypertrophic erythematous mucosa. Anterior nasal septum(MC) may perforate, collapse of nasal bridge may occur. Lupus pernio thickening and purplish discoloration of the overlying skin. Salivary gland enlargement is seen in 5–10% of cases

49. Pulmonary involement Staging Stage I is bilateral hilar lymphadenopathy, Stage II is hilar lymphadenopathy and pulmonary infiltrates, Stage III is pulmonary infiltrates alone Stage IV is pulmonary fibrosis

50. Diagnosis Kveim test- withdrawn due to fears of virus and prion transfer ACE, ESR, serum globulin and serum and urinary calcium levels CXR, CT Biopsy Coronal CT scan showing sclerosis and osteolysis of the nasal bones associated with a soft tissue mass in nasal sarcoid .

51. Treatment Limited disease- spontaneous resolution without specific treatment Oral steroids, methotrexate, hydroxychloroquine Topical intranasal steroids, nasal douching. Recent interest in TNF-alpha inhibitors such as infliximab and etanercept. Symptomatic laryngeal disease may be treated with transoral laser and intra-lesional steroid injections.

52. WEGENER’S GRANULOMATOSIS Granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small- to medium-sized vessels (e.g. capillaries, venules, arterioles and arteries) with necrotizing glomerulonephritis. Triad of airways, lung and renal disease.

53. Age of presentation: 15-75yrs Aetilogy unknown Hypersensitivity reaction with immune response to unknown stimuli (inhaled bacteria such as S.aureus ).

54. The European Vasculitis Study Group classification Localized Respiratory tract involvement only with no features of systemic vasculitis Early systemic generalized disease

55. Clinical Features The head and neck is the most common site of involvement at presentation, in 73–93% of cases. Nose and sinuses are involved in more than 80% Nasal obstruction, crusting, discharge and bleeding Destruction of the intra-nasal structures may follow, including the septum, turbinates and sinuses with formation of a single large cavity.

56. Otitis media with effusion with associated CHL Sensorineural hearing loss also occurs in 35%. Facial nerve paralysis has been recorded in 8–10% Subglottic or upper tracheal stenosis occurs in 16% of cases Oral symptoms are rare but ulceration may be seen and ‘strawberry’ gingival hyperplasia is said to be pathognomonic

57. Diagnosis cANCA (positive in 95% cases) CBC, ESR, CRP, ACE, serum urea and creatinine CXR Tissue biopsy- A micrograph of biopsy depicts collections of epithelioid histiocytes ( granulomas ) surrounding small vessels

58. Coronal CT showing typical appearances of Wegener’s in the nose with septal destruction hyperostosis and opacification of the sinuses together with orbital infiltration.

59. Treatment Steroids and cytotoxic drugs Prednisolone (60-80mg/day)and cyclophosphamide (2mg/kg)/azathioprine (200mg/day) Plasma exchange immunoglobulin infusion, methotrexate, cyclosporin, mycophenolate mofetil. Nasal symptoms- intranasal steroids, glucose and glycerine drops and nasal douching and irrigation.

60. Deoxyspergualin an immunomodulatory agent inhibits lymphocyte differentiation, appears to be effective in maintaining remission and reducing steroid requirements Surgery is generally reserved for cases that are refractory to medical treatment,or for complications.

61. Eosinophillic Granuloma/ Langerhans cell histiocytosis/ Langerhans granulomatosis A clonal proliferation of Langerhans cells associated with a heterogeneous inflammatory infiltrate of eosinophils, histiocytes, lymphocytes, plasma cells and neutrophils. now regarded as a neoplastic condition.

62. Pathology Macroscopically, the lesions are soft and yellow or red-brown in colour Microscopically, the Langerhans cells are mixed with other inflammatory cells. The cytoplasm of the Langerhans cells may be eosinophilic and Charcot–Leyden crystals

63. Clinical Features Predominantly occurs in bones. Skull is a common site of involvement, in particular the temporal, frontal and parietal bones. Involvement of the temporal bone may simulate acute mastoiditis. Mandibular lesions produce toothache, gum ulceration and loose teeth.

64. Diagnosis Radiological punched out bony lesion. Lesion in the skull show bevelled margin due to angulated destruction of cortical bone.

65. In the jaws radiolucent areas around the teeth.

66. Treatment Solitary, or ‘type II disease’ combination of curettage/excision and radiotherapy is usually curative Generalized or ‘type Idisease ’ additional chemotherapy At present, the most effective chemotherapy regime appears to be etoposide and steroids given for periods of 12 months Recently, alpha interferon and bone marrow transplantation have also been used successfully.

67. COCAINE-INDUCED MIDLINE DESTRUCTIVE LESION Intra-nasal inhalation is known to cause mucosal inflammation Patients predisposed to produce ANCA Pathology- Nearly 90% have a positive p- anca against human neutrophil elastase (HNE), which may increase apoptosis and the local inflammatory response to injury

68. Clinical Features Rarely systemic symptoms chronic nasal obstruction and bleeding, change in shape of the nose and nasal regurgitation variable degree of destruction of the septum, turbinates , lateral nasal wall and floor

69. Treatment No role for immunosuppression Must stop using cocaine to prevent further progression. Conservative treatment includes nasal douching, debridement of necrotic areas and topical or systemic antibiotic therapy. Surgical correction of septal perforation or nasal deformity should not be attempted until the patient has been clear of cocaine for at least 6–12 months.

70. NON-HEALING MIDLINE GRANULOMA Synonyms Stewart's granuloma Midline lethal granuloma Polymorphic reticulosis Sinonasal lymphoma T / NK cell lymphoma Aetiology - caused by the Epstein-Barr virus.

71. Clinical Features Usually present with aggressive destruction of the middle of the face. Usually arises in the nasal cavity and spreads to involve adjacent structures including the orbits, oral cavity, skin and paranasal sinuses. intra-nasal granulomatous mass initially causes symptoms of obstruction,discharge and bleeding.

72. early ulceration and significant central destruction

73. Diagnosis Histology- infiltrates are polymorphic and atypical cells may to be arranged in a necrotizing angiocentric growth pattern. Immunohistochemistry is usually positive for CD56, CD2 and cytoplasmic CD3

74. Treatment Initially low dose radiotherapy was preferred Now a days full course of radiotherapy is administered covering the entire area Chemotherapy is indicated only for high grade lesions

75. CHURG-STRAUSS SYNDROME Eosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels associated with asthma and eosinophilia. Bronchial asthma, nasal polyps, eosinophilia, systemic vasculitis. Treatment- oral steroids, treatment of nasal polyps.

76. Conclusion Any patient with blood-stained discharge and crusting in the nose has a granulomatous condition until proven otherwise. No one test is completely reliable and a combination of clinical findings combined with diagnostic investigations is required. Patients on long-term systemic steroids should be monitored for complications. Surgery is generally reserved for refractory cases or complications of disease.