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Nasal Granulomas. Dr. Vishal Sharma. Definition of granuloma. Granulomas result from chronic inflammation & consist of: a. macrophages b. epithelioid cells (active macrophages resembling epithelial cells)

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Nasal Granulomas

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Nasal granulomas l.jpg
Nasal Granulomas

Dr. Vishal Sharma


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Definition of granuloma

Granulomas result from chronic inflammation &

consist of:a. macrophages

b. epithelioid cells (active macrophages

resembling epithelial cells)

c. multi-nucleated giant cells

+ d. vasculitis

+e. necrosis



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A. BacterialC. Fungal

1. Rhinoscleroma1. Mucormycosis

2. Tuberculosis2. Aspergillosis

3. Syphilis D. Non-specific:

4. Leprosy1.Sarcoidosis

B. Aquatic parasite2.Wegener’s granuloma

1.Rhinosporidiosis3.Allergic granuloma

4. Sinonasal lymphoma ?



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Definition

Rhinoscleroma or scleroma is progressive granulomatous disease caused by gram negative Klebsiella rhinoscleromatis [von Frisch bacillus]

Commences in nose  nasopharynx, para nasal sinus, oropharynx, larynx, trachea & bronchi


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Nasal involvement staging

1. Catarrhal Stage: foul smelling purulent nasal discharge (carpenter’s glue), not responding to conventional antibiotics2. Atrophic stage:foul smelling, honey-comb coloured crusting in stenosed nasal cavity (in contrast to roomy nasal cavity of atrophic rhinitis)


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Nasal involvement staging

3. Nodular/ granulation stage: Non-ulcerative,

painless nodules (soft & bluish–red  pale & hard)which widen lower nose (Hebra nose)

4. Cicatrizing stage:Adhesions & stenosis  coarse & distorted external nose (Tapir nose). Lower external nose & upper lip have woody feel.






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Involvement of other sites

Nasopharynx:Ear block & ed hearing (fibrosis of eustachian tube orifice). Nasal intonation & nasal regurgitation (fibrosis of soft palate).Oropharynx: Sore throatLarynx & tracheo-bronchial tree:Dry cough, hoarseness, respiratory distress


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Investigations

  • X-ray PNS: sinusitis + bone destruction

  • Nasopharyngoscopy:obliteration of nasopharynx due to adhesions b/w deformed V-shaped soft palate & posterior pharyngeal wall (Gothic sign)

  • Flexible laryngoscopy: subglottic stenosis

  • Biopsy & H.P.E.:Mikulicz cell & Russel body

  • Complement fixation test: b/w pt’s serum & Frisch bacillus suspension. Done if biopsy is inadequate.


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Histopathology

Granulomatous tissue characterized by:1. Mikulicz (foam) cells:histiocytes with foamy vacuolated cytoplasm + central nucleus & containing Frisch bacilli

2. Russel (Hyaline) body: degenerated plasma cells with large round eosinophilic material





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Medical treatment

  • Total duration= 6 wk to 6 months (or negative cultures from 2 consecutive biopsy materials)

  • Streptomycin: 1g OD intramuscularly + Tetracycline: 500 mg QID orally

  • Rifampicin: 450 mg OD orally

  • 2% Acriflavine solution: applied locally OD


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Radiotherapy & Surgery

  • R.T.: 3500 cGy over 3 wk along with antibiotics halts progress of resistant cases

  • Removal of granulations & nodular lesions with cautery or laser

  • Dilatation of airway combined with insertion of Polythene tubes for 6 – 8 wk

  • Plastic reconstructive surgery: after 3 negative cultures from biopsies



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Sino-nasal Tuberculosis

  • Rare. Usually due to spread from pulmonary TB

  • Ulcers, nodules, polypoid masses in cartilaginous part of septum, lateral wall & inferior turbinate

  • H.P.E.: epithelioid granulomas with Langhan’s multi-nucleate giant cells, caseating necrosis

  • AFB may be found on nasal smears

  • Treatment: INH + Rmp + Etb + Pzn X 6 – 9 mth





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Lupus Vulgaris

  • Tuberculosis of skin (of nose & face)

  • Can mimic a squamous cell carcinoma

  • Rapid course / indolent chronic form

  • Nodules have apple jelly appearanceon diascopy

  • Nodules ulcerate & crust  scarring + distortion of nasal alae, nasal tip & vestibule

  • Tx: A.T.T.  surgical reconstruction if required





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Primary syphilis

  • Lesions develop 3-4 wks after contact

  • Chancre on external nose / vestibule

  • Hard, painful, ulcerated papule

  • Enlarged, rubbery, non-tender node

  • Spontaneous regression in 6-10 wks



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Secondary syphilis

  • Most infectious stage

  • Symptoms appear 6-10 wks after inoculation

  • Persistent, catarrhal rhinitis

  • Crusting / fissuring of nasal vestibules

  • Mucous patches in nose/pharynx

  • Roseolar, papular rashes on skin

  • Pyrexia, shotty enlargement of lymph nodes




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Congenital syphilis

  • Infants: snuffles, 3 wks to 3 mth after birth

  • Fissuring / excoriation of upper lip / vestibule

  • Mucosal rashes, atrophic rhinitis, saddle nose deformity, palatal perforation

  • Prenatal h/o syphilis, stillbirths, miscarriages

  • Hutchinson’s incisors, Moon’s mulberry molars, interstitial keratitis,corneal opacities, SNHL



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Tertiary syphilis

  • Commonest manifestation of nasal syphilis

  • Gumma: red, nodular, submucous swelling with infiltration. Ulcerates with putrid discharge / crusting. Ulcer margins irregular, overhanging, indurated, bare bone underneath.

  • Sites: mucosa, periosteum, bony septum, lateral wall, floor of nose, nasal dorsum, nasal bones



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Investigations

  • Dark-ground illumination examn of nasal smear

  • Venereal Disease Research Laboratory test

  • Rapid Plasma Reagin

  • Fluorescent Treponemal Antibody Absorption

  • Treponema Pallidum Haem-agglutination Assay

  • H.P.E.: peri-vascular cuffing by lymphocytes &

    plasma cells. Endarteritis: narrowing of

    vascular lumen, necrosis, ulceration.



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Treatment

1. Benzathine penicillin G, IM, 2.4 MU single dose

2. If penicillin allergic: Doxycycline or Tetracycline

 Doxycycline: 100 mg orally BD for 2 weeks

 Tetracycline: 500 mg orally QID for 2 weeks

3. Sequestrectomy

4.Augmentation Rhinoplastyfor nasal deformity


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Complications of untreated syphilis

  • Secondary infection with pyogenic organisms

  • Sequestration of bone

  • Perforation & collapse of bony nasal septum

  • Perforation of hard palate

  • Scarring / stenosis of choanae

  • Atrophic rhinitis

  • Meningitis



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Leprosy

  • Etiology: Mycobacterium leprae

  • Types:a. tuberculous

    b. lepromatous

    c. borderline

  • C/F: nodules, inflammation of nasal mucosa, nasal obstruction, septal cartilage perforation

  • X-ray:erosion of anterior nasal spine

  • Sequelae: saddle nose, atrophic rhinitis, stenosis





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W.H.O. treatment regimen

A. Tuberculoid (pauci-bacillary) leprosy: for 6 mth

Dapsone: 100 mg daily, unsupervised

+ Rifampicin: 600 mg monthly, supervised

B. Lepromatous (multi-bacillary) leprosy: for 1–2 yr

Dapsone: 100 mg daily unsupervised

+ Clofazimine: 50 mg daily unsupervised

+ Rifampicin: 600 mg monthly supervised

+ Clofazimine: 300 mg monthly supervised



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Definition

Chronic granulomatous infection by Rhinosporidium seeberi, mainly affecting mucous membranes of nose & nasopharynx; characterized by formation of friable, bleeding or polypoidal lesions

  • Other sites: lips, palate, antrum, conjunctiva, lacrimal sac, larynx, trachea, bronchus, ear, scalp, skin, penis, vulva, vagina, hand & feet.


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What is Rhinosporidium seeberi?

  • Bizarre fungus: obsolete theory

  • Microcystis aeruginosa:a unicellular prokaryotic cyanobacterium (Karwitha Aluwalia)

  • Aquatic parasite (Protoctistan Mesomycetozoa) according to recent 18S ribosomal ribonucleic acid (rRNA) gene analysis


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Epidemiology

  • 88 – 95% cases are found in India & Sri Lanka

  • Common in Kerala, Karnataka & Tamil Nadu

  • Age : 20 – 40 yrs.

  • Male: Female ratio = 4 : 1

  • People with blood group “O” more susceptible


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Classification

Benign

a. Nasal---------------------------------------------------- 78%

b. Nasopharyngeal-------------------------------------- 16%

c. Mixed (naso-nasopharyngeal, nasolacrimal) -- 05%

d. Bizarre (Conjunctival / Tarsal / Cutaneous) --- rare

Malignant------------------------------------------------- rare

Generalized, deep seated & difficult to eradicate


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Clinical Presentation

Epistaxis + viscid nasal discharge + nose block

Nasal mass:papillomatous or polypoid, granular, friable, bleeds on touch, pedunculated or sessile, pink surface studded with white dots [Strawberry apperance], involves septum & turbinates

Nasal mucosa:edematous, hyperemic, covered with copious viscid secretions containing spores

Lymph nodes:not affected









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Mode of transmission

1. Bathing (head dipping) in infected water: infective

spores enter via breached nasal mucosa

2. Droplet infection by cattle dung dust

3. Contact transmission:contaminated fingernails

are responsible for cutaneous lesions

4. Haematogenous: to other sites in infected pt



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Life cycle begins as oval / spherical Trophocyte

[8 μm] with single nucleus. Nuclear + cytoplasmic

division of Trophocyte results in intermediate

Sporangium. This enlarges into a mature

Sporangium [120 – 300 μm] with chitinous wall &

contains 16,000 Endospores. Mature sporangium

ruptures during sporulation & releases infective

endospores via its Germinal pore. Endospores

enter another host & grow into trophocyte.


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Differential diagnosis

  • Infected antrochoanal polyp

  • Inverted papilloma

  • Other granulomas:

     Rhinoscleroma

     Tuberculosis

     Leprosy

     Fungal (aspergillosis, mucormycosis)

  • Malignancy of nose / paranasal sinus


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Investigations

  • Biopsy & Histo-pathological examination

  • Microscopic examination of nasal discharge for spores





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Medical Treatment

  • Dapsone: arrests maturation of spores (inhibits folic acid synthesis) & increases granulomatous response with fibrosis

  • Dose: 100 mg OD orally (with meals) for one year

  • Give Iron & Vitamin supplements

  • Side effects:Methemoglobinemia & anemia


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Surgical management

  • At least 2 pints blood to be kept ready

  • General anesthesia with Oro-tracheal intubation

  • 2% Xylocaine (with 1:2 lakh adrenaline) infiltrated till surrounding mucosa appears blanched

  • Mass avulsed using Luc’s forceps & suction

  • After removal of mass, its base cauterized

  • Avoid traumatic implantation during surgery

  • Laser excision: minimal bleeding, no implantation



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Fungal Sinusitis

A. Invasive (hyphae present in submucosa)

1. Acute invasive or fulminant (< 4 weeks)

2. Chronic invasive or indolent (> 4 weeks)

 Granulomatous  Non - granulomatous

B. Non-invasive

1. Allergic 2. Fungal ball 3. Saprophytic

Aspergillosis & Mucormycosis are common


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Predisposing factors for invasive fungal infection

  • Uncontrolled diabetes mellitus

  • Profound dehydration

  • Severe malnutrition

  • Severe burns

  • Leukemia, lymphoma

  • Chronic renal disease, septicemia

  • Long term tx with (steroids, anti-metabolites, broad spectrum antibiotics)


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Clinical Features

  • Acute invasive fungal sinusitis by Mucormycosis

  • Unilateral nasal discharge + black crusts due to ischaemic necrosis, proptosis, ophthalmoplegia

  • Cerebral & vascular invasion may be present

  • Significant inflammation with fibrosis & granuloma formation seen in chronic invasive fungal sinusitis

  • Locally destructive with minimal bone erosion



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Treatment

  • Remove precipitating factors

  • Surgical debridement of necrotic debris

  • Amphotericin B infusion:1 mg / kg / day IV daily / on alternate days (total dose of 3 g). Liposomal Amphotericin B less toxic & more effective

  • Itraconazole:100 mg BD for 6-12 months

  • Hyperbaric oxygen:fungistatic +  tissue survival



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Allergic fungal sinusitis

  • Associated with ethmoid polyps & asthma

  • Unilateral thick yellow nasal discharge with mucin, eosinophils & Charcot Leyden crystals

  • C.T. scan: radio-opaque mass with central area of hyper density (due to hyphae)

  • Tx:Surgical debridement + anti-histamines + steroids (oral & topical)






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Fungal ball (Mycetoma)

Refractory sinusitis with foul smelling cheesy material in maxillary sinus

Tx:Surgical removal. No anti-fungal drugs.

Saprophytic fungal sinusitis

Seen after sino-nasal surgery due to proliferation of fungal spores on mucous crusts

Tx:Surgical removal. No anti-fungal drugs.


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Investigations

  • Biopsy & HPE: Tissue invasion by broad, non-septate, 900 branching hyphae. Fungal penetration of arterial walls with thrombosis & infarction. Staining by Periodic Acid Schiff or Grocott – Gomori Methenamine Silver nitrate stain.

  • X-ray PNS:Sinusitis + focal bone destruction

  • CT scan: rule out orbital & intracranial extension

  • MRI:for vascular invasion & intracranial extension





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Definition & etiology

  • Synonym:Boeck’s sarcoid or Besnier – Boeck –

    Schaumann syndrome

  • Definition:chronic systemic disease of unknown

    etiology which may involve any organ with non-

    caseating (hard) granulomatous inflammation

  • Etiology: 1. Special form of Tuberculosis (?) 2. Unidentified organism


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Clinical features

  • Nasal discharge, nasal obstruction, epistaxis

  • Mucosal: reveals yellow nodules surrounded by hyperaemic mucosa on anterior septum & turbinates

  • Skin (Lupus Pernio or Mortimer’s malady):nasal tip shows symmetrical, bulbous, glistening violaceous lesion (resembling perniosis or cold induced injury) Similar lesions on cheeks, lips & ears [Turkey ears]. Diascopy reveals yellowish – brown appearance.



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Heerfordt’s syndrome

Synonym:Waldenström’s uveo-parotid fever

Special form of sarcoidosis with:

1. Transient B/L Facial palsy

2. Parotid enlargement

3. Uveitis

4. Fever


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Probe test

  • Probing of nodular lesion to look for penetration

  • Negative in sarcoidosis: probe does not penetrate nodular swelling because of hard granulomas

  • Positive in Lupus vulgaris:probe penetrates up to soft granulation tissue in centre of nodule


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Investigations

  • Biopsy of nodule & HPE:Non-caseating hard granuloma with ill-defined rim of surrounding lymphoid cells (naked tubercle). Giant cells contain asteroid inclusion or Schaumann bodies

  • Kveim Siltzbach Test:Intradermal injection of spleen extract from case of sarcoidosis followed 6 wks later by skin biopsy shows development of non-caseating nodules





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Chest X-ray findings

  • Stage I= B/L Hilar lymph node enlargement

  • Stage II=B/L Hilar lymph node enlargement +

    diffuse parenchymal infiltrates

  • Stage III= Diffuse parenchymal infiltrates without

    Hilar lymph node enlargement

  • Stage IV =Diffuse parenchymal infiltrates +

    fibrosis with cor pulmonale



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Treatment

1. Prednisolone: 1 mg/kg/d x 6 wk, taper over 3 mth.

Good response in mucosal disease only.

2. Chloroquine / Methotrexate + Prednisolone:

in pt not responding to steroids

Chloroquine =250 mg PO on alternate days x 9 mth

Methotrexate =5mg PO weekly x 3mth

3. Cutaneous lesions: excised & skin grafted



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Definition

Autoimmune (?) condition characterized by necrotizing granulomas within nasal cavity & lower respiratory tract,

generalised vasculitis &

focal glomerulonephritis


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Clinical Features

Nose & paranasal sinus:epistaxis, nasal block, extensive crusts, septal destruction & nasal collapse. Rule out nasal substance abuse.

Pulmonary:Cough, haemoptysis

Renal: Hematuria & oliguria

Otological:Otalgia, deafness, facial nerve palsy

Oral & pharyngeal: Hyperplastic, granular lesions


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Clinical Features

Laryngo-tracheal: laryngitis, subglottic stenosis

Ophthalmological:scleritis, conjunctivitis, corneal ulceration, dacryocystitis, proptosis, optic neuritis, blindness

Others: Skin ulceration, polymyalgia, polyarthritis

If untreated:death within 6 mth due to renal failure





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Differential diagnosis

VASCULITISGRANULOMAS + VASCULITIS Polyarteritis nodosa Allergic granulomatosis S.L.E. Loeffler’s syndrome Rheumatoid arthritisPULMONARY + RENAL Sjogren’s syndrome Goodpasture’s syndromeOTHER GRANULOMASNEOPLASMSpecific Sinonasal lymphoma T.B. Metastatic bronchial cancer SyphilisOTHERSNon-specific Nasal substance abuse Sarcoidosis Systemic myiasis


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Investigations

E.S.R.: raised

Urine microscopic examn:RBC casts & RBCs

CT PNS: bone destruction in nasal cavity

Chest X-ray & CT scan:pulmonary nodules

Serum urea & creatine: ed renal function

Biopsy of lesion & HPE:Granulomas + Vasculitis+ Fibrinoid vascular necrosis




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C.T. scan lungs

nodular lung infiltrate with cavitation


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HPE: Granulomatous vasculitis

L = small pulmonary artery lumen surrounded by inflammatory infiltrate including a giant cell (black arrow)


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Segmental glomerular necrosis

early crescent formation (black arrows)


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c-A.N.C.A.

  • Anti-Neutrophil Cytoplasmic Antibody (ANCA) titre by immuno-fluorescence.

  • c-ANCA = cytoplasmic fluorescence

  • Raised c-ANCA titres = 65-96% sensitive in WG

  • Becomes -ve when disease is controlled

  • p-ANCA = peri-nuclear fluorescence

  • p-ANCA titres raised in Polyangitis


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C – ANCA by indirect immuno-fluorescence


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Medical Treatment immuno-fluorescence

1. Triple therapy:

Prednisolone: 1 mg/kg/d x 1 mth  Taper over 3 mth

+ Cyclophosphamide: 2mg/kg / day x 6-12 mth

+ Cotrimoxazole: 960 mg OD X indefinitely

2. Plasma exchange & intravenous immunoglobulin

3. Alkaline nasal douche for crusts



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Synonyms immuno-fluorescence

  • Stewart’s granuloma

  • Lethal midline granuloma

  • Non-healing midline granuloma

  • Idiopathic midline destructive disease (IMDD)

  • Sinonasal T-cell lymphoma

  • Necrosis with atypical cellular exudate (NACE)

  • Midline malignant reticulosis


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Clinical Features immuno-fluorescence

  • Prodromal stage: Blood-stained nasal discharge

  • Active stage:Nasal crusting, ulceration, septal perforation

  • Terminal stage: Tumour sloughing, mid-face mutilation

  • D/D:Wegener’s granuloma, Basal cell carcinoma

  • Rx: Radiotherapy (5000 cGy) + chemotherapy


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Mid-face mutilation immuno-fluorescence


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Churg & Strauss Syndrome immuno-fluorescence

  • Synonym:allergic granulomatosis

  • C/F:nasal polyps + bronchial asthma

  • Chest X-ray: pulmonary lesions

  • HPE of nasal polyp:necrotizing granulomas with abundant eosinophils without vasculitis

  • Tx: 1. Corticosteroids (topical & systemic)

    2. Nasal polypectomy


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Thank You immuno-fluorescence


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