Granulomatous Diseases of nose and

PNSPresenter – Dr Pulkit AgarwalModerator – Dr K.P.Basavaraju

What is Granuloma ?

Immune system tries to wall off foreign substances but fails

Bacteria, Fungi, keratin, suture material. Histopathologically – Chronic inflammation• Epitheloid cells• Multinucleate giant cells• Lymphocytes & fibroblasts Necrosis and Vasculitis.

Granuloma as misnomer “Granuloma" loosely to mean "a small

nodule". Vocal cord granuloma Pyogenic granuloma Intubation granuloma Pulmonary hyalinizing granuloma i.e. keloid-

like fibrosis in the lung Radiologists - calcified nodule on X-ray or CT

scan of the chest. Most accurate use – Pathologists who observe

stained tissue under microscope.

Granulation tissue

Tuberculosis : Nasal Mucosa involvement rare. Portal – Inhalation (commonest), ingestion,

inoculation. Asso with Primary pulm. Tuberculosis M. tuberculosis and M. bovis - main

pathogens. Most common affection of nose – Lupus

Vulgaris Macroscopic appearance:• Nodular form (Lupus)• Ulcerative form• Sinus granuloma

Indolent and chronic from of tb infection affecting the skin and mucous membrane of nose.

F:M = 2:1 (young adults) Temperate Climate disease Starts at Vestibule, extends to adjoining

skin and mucosa with mucocutaneous junction as MC location.

Pathogenesis – Direct dermal inoculation (patient having immunity to infection due to previous exposure)

Scarring of Vestibule common in later stages

HPE – Shows tuberculous granulomas, RE cells at centre which soon necrose & coalesce, surrounded by ring of living RE cells.

Around it is ring of Lymphocytes, plasma cells & fibroblasts.

Multinucleate giant cells scattered throughout

Symptoms : Nasal discharge Nasal obstruction Presence of non foul smelling crusts Epistaxis Evening rise of temperature Mild fetor if ulcerated Pain is unusual Apple jelly nodules (Early lesions) - reddish firm

nodules at mucocutaneous junction of nasal septum.

May later coaslesce & break down to form characteristic ulcers with a pale granular base and undermined edges

Diagnostic Features :

Blanching (glass slide) Bacterial examination Biopsy (diagnostic)

Culture - Lowenstein-Jensen slope Recent - BACTEC

Complications: Pulmonary tuberculosis Corneal ulceration Dacryocystitis Nasopharyngeal lupus Lupus of face Atrophic rhinitis Development of epithelioma (rare sequlae) Sudden increase in size, hardness of the

node in an elderly with increasing tendency to bleed should arouse the suspicion of epithelioma formation.

Ulcerative Form Ulcers are commonly found on the anterior part

of the cartilagenous nasal septum, inferior turbinate and anterior choanae.

Ulceration Fibrosis Distortion of Nasal Alae If turbinates are involved extensively, the lining

ciliated columnar epithelium is not renewed leading to secondary atrophic rhinitis.

Spread usually occurring in a backward direction from the primary site

Only cartilagenous septum involvement so no sinking of nasal bridge.

Sinus Granuloma Isolated sinus involvement may occur without

any signs or symptoms in the nose. Usually presented with a diffuse soft tissue

swelling and multiple discharging sinuses in the supraorbital region secondary to osteomyelitic involvement of the frontal bone.

The computed tomography (CT) and magnetic resonance imaging (MRI) characteristics are nonspecific and demonstrate a soft tissue mass with or without bone destruction.

Inv. of the orbit & its nerves may occur. Diagnosis by an external or endoscopic biopsy.

Specific Investigations

Montaux test AMTD (Amplified Mycobacterium

Tuberculosis Detection) PCR Fluorescence microscopy

Treatment Antituberculous drugs Short Course Chemotherapy : Extends over 6-9 months and consists of

Rifampicin, INH, Ethambutol and Pyrizinamide

DOTS : Initial Phase - 2 mnths - HRZE Rifampicin (R) - 450mg INH (H) - 600mg Ethambutol (E) - 1200mg Pyrizinamide (Z) - 1500mg

Treatment Maintainence treatment (4 months) - (HR)3

(thrice weekly under observation) Vit D supplementation - hastens sputum

culture conversion (only in vit D deficient cases)

Surgical correction

Leprosy

Caused by M. Leprae which is morphologically similar to M. Tuberculi

Non culturable, inoculated into experimental animals

Based on the host's immunological status and clinical, histological and microbiological features leprosy divided into types.

Types of leprosy : Tuberculoid leprosy: Immunocompetent patients Solitary lesions (anesthetic patches) Involvement of one / more related

sensory or motor nerves. Nasal Vestibule involved without mucosa

involvement Isolated cranial nerve palsies (V and

VIIth) have also been documented

Lepromatous Leprosy :

Least immunological resistance to the organism.

Diffuse infiltration of skin, nerves and mucosal surfaces.

Cutaneous infiltration is more common over the edges of pinna, chin, nose and eyebrows.

Highly infectious nasal discharge.

Signs and Symptoms

Earliest sign - nodular thickening of nasal mucosa

Crust formation Nasal obstruction (out of proportion) Sero sanguineous dischargeNodules are paler than the surrounding

mucosa with a yellowish tinge. Commonly begin at the anterior end of

inferior turbinate, progresses to gross inflammation of nasal mucosa.

Both the bony and cartilaginous portions of nasal septum are destroyed due to perichondritis and periosteitis (nasal bridge collapse)

Anterior nasal spine destruction seen Radiographs showing the absence /

erosion of anterior nasal spine are virtually diagnostic of Lepromatous leprosy

Hyposmia is seen in 40% Nasal mucosa scraping microscopy

shows typical cigar pattern Lepra bacilli

Borderline leprosy

Poor immunological resistance May progress to lepromatous leprosy Skin lesions are more numerous and are

seen around eyes, nose and mouth In pure borderline lesions - nasal mucosa

involvement is not seen Nasal mucosal inv suggests progression

to LL.

Diagnosis

Early diagnosis is essential since nasal discharge is principle route of transmission of the disease

Clinical findings of anaes. on the skin, thickened peripheral nerves and skin lesions, & supplemented by bacteriological examination.

Confirmed by dem. of M. leprae on microscopy of the nasal discharge or scrapings of nasal mucosa, or histopathology of nasal mucosa.

Skin biopsy in tuberculoid leprosy

Treatment

Dapsone reduces the bacilli count of nasal discharge to zero or near zero within a couple of months BUT increased resistance

Modern drugs like Rifampicin and Clofazimine can reduce the bacilli count to zero within 10 days

Triple therapy: Rifampicin – 600 mg on first two days of a

month taken before breakfast Clofazimine – 100 mg on alternate days for

three times a week Dapsone – 100 mg a day

Rifampicin stopped after 3 mnths Rest 2 continued till 9 mnths Intranasal Rifampicin much faster than

oral route Nasal douching for removal of crusts Betnovate (1 part) in Unguentum (2

parts) has been used with good results

syphilis Nasal syphilis an occur at any age Uncommon as signs symptoms difficult to elicit

in early stages especially if antibiotics given Causative org. – Treponema

Pallidum(Spirochete) Pathogenesis - The organisms usually reside

and multiply in the perivascular lymphatics of the blood vessel wall.

Local host reaction results in an infiltration by polymorphs, activated lymphocytes (CD4+ and CD8+), plasma cells and histiocytes which are typical of syphilis.

The resultant endarteritis of small blood vessels with secondary hypertrophic changes in the endothelium, may lead to endarteritis obliterans and luminal obliteration.

HPE - Diagnosis is purely histopathological Characterized by oedema, stromal

infiltration with lymphocytes, plasma cells and endothelial cells

Perivascular cuffing by these cells and endarteritis will cause a reduction in the lumen of blood vessels causing necrosis and ulceration

Nasal syphilis can be classified into: Primary syphilis Secondary syphilis Tertiary syphilis Primary syphilis : Also known as Chancre, seen at external

nose or inside the vestibule. Appears as a hard, non painful ulcerated

papule always associated with enlarged, rubbery, and non tender lymphadenopathy

A sore or chancre develops at the site of inoculation 10-90 days (average 21 days) following infection

These lesions undergo spontaneous resolution within 6-10 weeks

Should be differentiated from malignant neoplasms and furunculosis

Malignant neoplasms – affect older ages, relentless progression

Furunculosis – Painful condition, progresses to suppuration.

Treatment

Anti syphilitic Rx - i.m. penicillin. The chancre may be cleansed with 1:2000

solution of per chloride of mercury and the surface smeared with 2% yellow mercuric oxide ointment.

The following points should be borne in mind :

Cultures from the surface of the lesion will always be negative

Smears when examined under dark ground illumination will show the spirochete Treponema palladium

Serological tests for syphilis may be positive – VDRL, TPHA, FTA-ABS. (The VDRL is a nontreponemal test and is relatively nonspecific but becomes positive early (four to five weeks) and correlates well with disease activity.)

A biopsy from suspicious lesion may confirm the diagnosis

Secondary Syphilis

Most infectious of all the three stages Symptoms 6-10 weeks after

inoculation Secondary syphilis is rarely

recognized in the nose, as mucous patches hardly ever occur on such a thin, attenuated mucous membrane.

The symptoms include:

Simple catarrhal rhinitis (persistent) Crusting & fissuring of nasal vestibule Other secondary lesions like mucous

patches in the pharynx are also seen Roseolar / papular skin rashes Shotty enlarged non tender lymph

nodes. The scar of the primary lesion in the

genitals or elsewhere may be visible.

Serological tests for syphilis are positive.

Dark-field examination of moist or intentionally abraided dry lesions may demonstrate the organism.

Lymph node aspirates or tissue specimens (lymph nodes, liver, skin or mucous membrane) may also be examined by silver stains or immunofluorescence for detection of spirochaetes

These patients respond to antisyphilitic drugs.

Tertiary Syphilis :

Only 1/3rd of secondary syphilis cases progress to show clinical manifestations of tertiary syphilis.

This stage is commonly encountered in the nose.

Lesion is also known as gumma. This lesion invades the mucous membrane,

periosteum and bone. The bony portion of the nasal septum is

frequently affected causing septal perforation.

Rarely the following portions of the nose can also be involved :

Lateral nasal wall Frontal sinus Nasal bones Floor of the nose

Symptoms include:

1. Pain / headache (worse during night)2. Swelling / obstruction of nose - swelling may

be diffuse / localized associated with offensive discharge, bleeding and crusting of the nose

3. Olfactory acuity diminishes4. Perforation of bony portion of nasal septum

associated with collapse of the bridge of the nose can cause structural damage to the nasal architecture

5. There may also be associated secondary atrophic rhinitis

Nasal complications of gumma:

1. Secondary infections with pyogenic organisms

2. Sequestration3. Perforation of bony portion of nasal septum,

palate or nasal walls4. Collapse of bridge of nose with deformity of

nose5. Scarring / stenosis of nasal passages6. Atrophic rhinitis7.Intracranial complications due to

involvement of meninges

Treatment :

1.DOC for all stages – parentral Penicillin2.Alkaline nasal douches one to three times a

day.3.Local yellow mercury oxide ointment.

Dilute mercuric nitrate ointment should be applied freely to the nasal vestibules.

4.Atrophic rhinitis and deformity may persist after the disease is cured and this may need further surgery.

Congenital syphilis “Snuffles”: :

Any of the lesions of secondary and tertiary forms of syphilis of nose can occur.

Classically begin during the 3rd week of life. May appear around 3rd month also At First – simple catarrhal rhinitis. Later becomes purulent with sec.

fissuring and excoriation of the nasal vestibule and upper lip.

Gummatous and destructive lesions occur most commonly at puberty.

Mucous membrane, periosteum and bone may all be affected.

Other stigmata of syphilis, particularly Hutchinson's incisors and Moon's molars, interstitial keratitis, corneal opacities and sensorineural deafness may be present, and there may be a family history of syphilis, miscarriages and still births.

Serologic tests for syphilis will invariably be negative

Treatment :

In snuffles, the airway must be restored for suckling

The nasal discharge is removed by gentle suction and irrigation and the use of local drops of 0.5 percent ephedrine solution or simple normal saline, and by hyper extending the head before feeding

In the tertiary forms, simple nasal toilet by syringing with isotonic alkaline douche solution will remove the crusts and discharge, and yellow mercuric oxide ointment may be applied frequently to the nasal vestibules

Yaws (framboesia) Closely resembles syphilis in its pathology.

Causative organism : Treponema Pertenue Morphologically this organism is indistinguishable

from Treponema pallidum.

Transmission : Is by direct extra genital contact. It has a high incidence in infancy and childhood.

Clinical features : Primary, secondary and tertiary stages occur as in

syphilis Yaws principally affects the skin.

Mucous membrane are usually spared but for the mucocutaneous junctions.

Nasal lesions are very rare and do not differ in appearance from that of syphilis.

Advance nasal lesions are associated with extensive destruction of the nose, palate.

Destruction also may involve the whole of the maxilla, face and pharynx.

Serologic tests for syphilis is positive. These lesions characteristically respond to

conventional antisyphilitic treatment.

Rhinoscleroma (scleroma) Progressive granulomatous disease

commencing in the nose and later extending into the nasopharynx and oropharynx, the larynx and sometimes the trachea and bronchi.

Laryngeal involvement may occur in almost half the cases and the disease is perhaps better designated as respiratory scleroma, rather than rhinoscleroma.

Aetiology is multifactorial and usually seen in low socio economic status and poor domestic hygiene

Pathology :

Caused by gram negative bacilli Klebsiella rhinoscleromatis / Frisch bacilli / diplo bacillus.

F>M, any age This organism could be a secondary invader

following a viral infection. Resides intracellularly and can be difficult to

isolate in the laboratory. The characteristic histological features include

granulomatous tissue infiltrates in the submucosa, characterized by the presence of plasma cells, lymphocytes and eosinophils.

Besides, there are scattered large foam cells (Mikulicz cells) which have a central nucleus and a vacuolated cytoplasm containing frisch bacilli and Russel bodies.

The Mikulicz cells are transformed macro phages which have ingested the bacillus, but the bacillus being resistant to digestion by the macrophage persists intracellularly.

The Russel bodies resemble plasma cells with an eccentric nucleus and deep eosin staining cytoplasm.

Histochemical studies have indicated a high content of mucopolysaccharides around the walls of the bacillus

it is hypothesized that this may be responsible for the protection afforded to the organism from antibiotics and the hosts antibodies

Clinical features :Three stages –

1.The atrophic stage The features resemble that of atrophic rhinitis,

including crust formation and a foul smelling discharge (carpenter's glue)

2. Granulomatous or proliferative (or nodular) stage.

Nonulcerative nodules develop which are at first bluish red and rubbery and later become paler and indurated.

These nodules never break down but fibrose and progressively decrease in size. Regional lymph node involvement is extremely infrequent.

3. Cicatrizing stage Adhesions and stenosis distort the normal

anatomy The disease may extend to involve the lacrimal

sac, maxillary sinus, nasopharynx, hard palate, trachea and main bronchi

Bone involvement has also been reported The shape and contour of the nose changes

causing a condition known as “Tapir’s nose”(woody feeling on palpation of nose)

Lymphatic spread is uncommon because of extensive fibrous tissue deposition

This deposition blocks the lymphatics. Occasionally, malignant change has been reported

Gothic Sign - because of fibrosis the pharyngeal wall is pulled up and resembles the top of a church.

Complications : 1. External nose deformity2. Vestibular stenosis3. Cicatrization of soft palate4. Nasal regurgitation5. Tracheal stenosis

Diagnosis :Levin test (complement fixation test) :High titres of antibodies against K.

Rhinoscleromatis has been demonstrated. This indicates humoral immunity to be intact in

these patientsDiagnosis in the atrophic stage is extremely

difficult and the disease is usually recognized only in the granulomatous or cicatrizing stage

MRI in the hypertrophic stage shows a soft tissue mass with mild to marked high signal intensity in both Tl- and T2-weighted images.

Microbiological examination and a confirmatory Biopsy

Treatment :

Usually self limiting course of its own accord ending in the cicatrizing stage, the organism can nevertheless be extremely difficult to eradicate by antimicrobials.

Bactericidal antibiotics in large doses are given for a minimum of four to six weeks and are continued until two consecutive cultures from biopsy material are proven negative.

Traditionally Used : streptomycin (im 1gm for 4-6wks) and tetracycline

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

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. This mixture causes chemical necrosis of granuloma

Rifampicin :

Nasal Instillation - 1 Amp of rifampicin 125mg diluted in 20mL saline solution and 2mL of the solution is applied twice daily locally for a period of 8 weeks.

Nasal Infiltration - 1 Amp of rifampicin 125mg infiltrated into granulomas every other day

Irradiation to a total dose of 3000-3500 Gy over three weeks destroys scleroma but, with the currently available antimicrobials, is unlikely to be required

Actinomycosis

Caused by Actinomyces species such as Actinomyces israelii or A. gerencseriae. The condition is likely to be polymicrobial

aerobic anaerobic infection. Actinomycosis occurs rarely in humans but

rather frequently in cattle as a disease called lumpy jaw

Cervicofacial disease is caused most commonly secondarily to dental infection, intraoral trauma or manipulation

Signs and symptoms :

Characterised by the formation of painful abscesses in the mouth.

In severe cases, they may penetrate the surrounding bone and muscle to the skin, where they break open and leak large amounts of pus, which often contains characteristic granules (sulphur granules).

The purulent leakage via the sinus cavities contains "sulphur granules," not actually sulphur-containing but resembling such particles. These granules contain progeny bacteria

Diagnosis : In addition to microbiological examinations

(requires anaerobic processing of culture specimens) magnetic resonance imaging and immunological blood analyses may also be helpful

Treatment :Generally sensitive to penicillinIn cases of penicillin allergy, doxycyclin is usedSulfonamides such as sulfamethoxazole may be

used as an alternative regimen at a total daily dosage of 2-4 grams. Response to therapy is slow and may take months.

Fungal conditions :Rhinosporidiosis

Chronic granulomatous infection that affects the nasal mucosa, ocular conjunctiva and other mucosa.

Aetiological Agent : Rhinosporidium seeberi 15-40 yrs age group, M>F It has long been unclear whether this organism

is a fungus Natural habitat - stagnant pools of fresh water The disease is most prevalent in rural

districts, among persons bathing in public ponds or working in stagnant water, such as rice fields

Classification :

Benign :Nasal - Septal Mucous Membrane

Floor of Nose / Spur

Nasopharyngeal - Nasopharyngeal surface of soft palate.

Mixed - Nasolacrimal

Bizzare - Conjuctival / Cutaneous

Malignant :Generalised

Clinical Manifestations :

Nose commonest site (70% cases)The fungus causes the production of large

sessile or pedunculated lesions that affect one or both nostrils

Goes unnoticed till nasal obstruction developsNasal discharge & epistaxisARE - reveals leafy, papular or nodular, smooth-

surfaced lesions that become pedunculated and acquire a papillomatous or proliferative appearance

The lesions are pink, red or purple in colour, vascular (bleeds on touch) studded with white dots

Spontaneous remission is unusual and, left untreated, the polyps will continue to enlarge

Diagnosis :HPE of tissue sections. These contain large, round

or oval sporangia up to 350 µm in diameter, with a thick wall and an operculum

Management Options :The treatment of choice is surgical excision of

lesions, with or without cauterization of baseNo drug treatment has proved effectiveDapsone said to prevent maturation of sporangia

& promotes fibrosis, 50mg BD, 3 months preop and 6 months postop

Aspergillosis

Causative Organisms include : Aspergillus fumigatus (90%)

Aspergillus niger, Asp. flavus

Granulomatous invasive fungal rhinosinusitis :

An asymptomatic period frequently occurs, symptoms appearing only when the orbit or skull base are involved

Pain is the main symptom Chronic headache, proptosis and cranial nerve

deficits Maxillary sinus - major site

Nasal endoscopy reveals nasal congestion or polypoid mucosa and sometimes a soft tissue mass covered by a normal or ulcerated mucosa

Radiological appearances usually show opacification with bone erosion extending to the orbit and/or skull base

Histopathology reveals fungal invasion of the tissue: bone, mucous membrane, vessels.

Mycologic cultures lead to identification of the species.

TreatmentMost patients have been treated with a

combination of surgery and antifungal chemotherapy (Itraconazole and amphoterecin B)

Mucormycosis

Caused by fungi in the order Mucorales Generally, species in the Mucor, Rhizopus,

Absidia, and Cunninghamella genera are most often implicated

This disease is often characterized by hyphae growing in and around vessels

Rowe Jones Classification : Non invasive Semi invasive Invasive

Types :

1. Cerebral2. Ocular3. Pulmonary4. Superficial5. Disseminated

Signs & Symptoms :MC Oral or cerebral mucormycosisInvolves sinuses, brain, or lungs as the areas of

infectionCan also manifest in the GIT, skin &other organ

systems.

Rarely maxilla may be affected The rich vascularity of maxillofacial areas

usually prevents fungal infectionsl Athough more virulent fungi, such as those

responsible for mucormycosis, can often overcome this difficulty

Key signs which point towards mucormycosis Fungal vascular invasion resulting in

thrombosis and death of surrounding tissue If the disease involves the brain then

symptoms may include a one-sided headache behind the eyes, facial pain, fevers, nasal stuffiness that progresses to black discharge, and acute sinusitis along with swelling of the eye

Affected skin may appear relatively normal during the earliest stages of infection

This skin quickly progresses to an erythemic (reddening, occasionally with edema) stage, before eventually turning black due to necrosis

Diagnosis As swabs of tissue or discharge are generally

unreliable, the diagnosis of Mucormycosis tends to be established by a biopsy specimen of the involved tissue

Treatment Amphotericin B - 4–6 weeks Posaconazole shown effective against

mucormycosis Liposomal drug available but expensive

Non Specific Inflammatory Granulomatous Conditions Sarcoidosis May affect any part of the body, but most

frequently involves lymph nodes, skin, lungs, eyes, liver, spleen and the small bones of the hands and feet

F:M = 2:1, 3rd to 5th decade

Aetilogy : Chemicals (including beryllium and

zirconium) Pine pollen Peanut dust

Immunology in patients with Sarcoidosis:

Type IV delayed hypersensitivity is depressed Cell mediated immunity is normal Type I humeral immunity is normal Total plasma protein levels are raised There is an increase in the amount of

circulating immune complexes Process initiated by APC (probably alveolar

macrphage) IL1 IL2 mediated T lymphocyte proliferation IL8 attracts monocytes and held at the site of reaction by macrophage migration inhibition factor Monocyte activation by IFN γ

Monocyte activation leads to Calcitriol production causes macrophage fusion to epithelioid cells and granuloma formation

The persistence of the granuloma may be ascribed to

1. Continued antigenic stimulation, 2. Failure of suppressor-regulating mechanisms 3. Abnormalities in the regulation of the cytokine

network

Histology Scadding and Mitchell defined Sarcoidosis as a

disease characterized by formation in all of the several affected organs / tissues of epitheloid tubercles, without caseation.

These granules either resolve on their own or get converted into hyaline fibrous tissue

So Epithelioid cells surrounded by lymphocytes and fibroblasts but devoid of caseation

Crystalline or calcified inclusion bodies are sometimes seen, e.g. Schaumann bodies.

Histological picture is not diagnostic and similar granulomas can occur in a number of other conditions including berylliosis and fungal disease

Clinical features:

1. Nasal stuffiness / obstruction2. Crusting3. Blood stained discharge4. Purulent discharge5. Facial pain6. Mucoid discharge7. Anosmia Nasal cavity mucosa has a characteristic

granular appearance (i.e. also called as strawberry skin).

Nasal mucosa hyperemic and friable leading on to blood stained discharge

There may also be crusting of the nasal mucosa associated with mucopurulent discharge.

The anterior portion of the nasal septum may perforate, especially if traumatized for example during surgery.

The paranasal sinuses may also be affected by the process and/or become secondarily infected

As a consequence, facial pain is experienced by one in five patients with nasal sarcoid.

Sense of smell may be affected due to mechanical obstruction of the olfactory cleft by crusting and fibrosis, or due to direct neuropathy

Adenoid enlargement or lymphoid hyperplasia may lead to middle ear effusion

The soft tissue of the supraglottic larynx may become thickened and increasingly swollen producing dyspnoea and change in voice quality

Diagnosis : Diagnosis usually relies on a combination of

histology, imaging, haematology and clinical acumen.

Kveim test : intradermal injection of a filtered extract of spleen from a patient with sarcoid. Six weeks later a skin biopsy is taken. The test is positive when the histology shows features of Sarcoidosis

Withdrawn in the UK over fears of virus and prion transfer though without any substantive evidence for this

Elevated Angiotensin converting enzyme (83% of cases)

But it is also elevated in a number of other conditions such as tuberculosis, leprosy and primary biliary cirrhosis

ESR levels, serum globulin and serum and urinary calcium levels are sometimes raised

Full blood count may show mild anaemia, leucopenia, thrombocytopenia and eosinophilia, but clearly none of these tests are specific

Other investigations include (chest x-ray, computerized tomography (CT), perfusion studies, bronchoalveolar lavage and gallium-67 scanning)

Biopsy of nasal mucosa is only of use if it appears abnormal as random biopsy of macroscopically normal mucosa is usually negative (in 92 percent of cases).

Plain x-rays of the nasal bones may show rarefraction or punctate osteolysis in up to a quarter of cases and this, together with soft tissue changes, may be shown by CT scanning

Treatment : Some patients with limited disease

undergo spontaneous remission without specific treatment

Rx consists of Combination of oral steroids, methtotrexate and hydroxychloroquine, depending on the severity of the disease.

Topical treatment may be offered for nasal symptoms including intranasal steroids, either sprays or drops, glucose and glycerine drops and various forms of nasal douching and irrigation

Wegner's Granulomatosis

Classically pulmonary, renal, and head and neck manifestations and skin involvement

Nose and PNS MC affected site in the head and neck.

Affects age gp of 15 – 70 yrs M:F = 1:1 Aetiology : Unknown It could represent some

form of hypersensitivity reaction to an unknown stimulus

The stimulus could be a form of inhaled bacteria. This could explain the frequency with which the

respiratory tract is involved

Pathology : Necrotizing vasculitis affecting small- to medium-

sized vessels (e.g. capillaries, venules, arterioles and arteries) with necrotizing glomerulonephritis, is common

The pathological hallmark is the coexistence of vasculitis and granulomas and classically involves a triad of airway, lung and renal disease

Immunology: Antibodies reacting with the cytoplasm of granulocytes

and Monocytes have been demonstrated by van der Woude.

Two main forms of anti nuclear cytoplasmic antibodies have been demonstrated. Perinuclear (pANCA) and cytoplasmic (cANCA).

Clinical features : Necrotizing granulomas with vasculitis of the

upper and lower respiratory tracts. Focal necrotizing glomerulonephritis. Nose and sinuses involved in 80% cases There may be intra nasal destruction of bone and

cartilage leading to collapse of nasal bridge Rapid diagnosis remains of great importance

since a fulminating course with a fatal outcome can occur in as little as 48 hours

Nasal symptoms : blood stained nasal discharge, crusting, granulation

and can even lead to septal perforations

Minor nasal surgery and/or repeated biopsies during this period may add to the problem

many patients may complain of significant facial pain

There can be destruction of the eye, orbit, palate, oral cavity,oropharynx and sometimes middle ear

Oral Symptoms MC - hyperplastic granular lesion of the gingiva If a tooth is lost, the socket may fail to heal Extensive ulcerative stomatitis has also been

reported Otological Symptoms AOM, SOM There may be deafness, pain and suppuration. Facial nerve paralysis has also been recorded

Wegener's granulomatosis of the temporal bone with necrotizing granulation tissue filling the tympanic cavity has been documented

Laryngeal and Tracheal symptoms Laryngeal involvement is unusual, but when

present the subglottis and upper trachea are most commonly affected

May lead to laryngotracheal obstruction Biopsies nonspecific and are contraindicated

leading to further inflammation and scarring. positive c-ANCA test seen in idiopathic

subglottic stenosis

Extensive laser resection of subglottic stenosis caused by Wegener's is frequently not only unsuccessful, but also causes further stenosis.

Diagnosis : The cANCA test is positive in 95 percent of

patients with generalized active disease. ESR is found to be elevated Serum angiotensin enzyme levels are increased Presence of vasculitis Granulomas are of epitheloid cell type Multinucleated giant cells have also been

demonstrated

ACR criteria for diagnosis of wegner’s granulomatosis:

Nasal oral inflammation : Development of painful /

painless oral ulcers / purulent or bloody

nasal discharge. Abnormal x-ray chest : Shows presence of

nodules, infiltrates and cavities. Urinary sediment : Micro hematuria Biopsy : Granulomatous

inflammation within the wall of an artery / arteriole

Treatment :

The following drugs can be used in combination.

1. Steroids – Prednisolone 60 – 80mg/day

2. Cyclophosphamide – 2mg/kg/day3. Azathioprine – can be used instead of

Cyclo phosphamide in doses of 200mg /day.

Neoplastic Conditions :Non Healing Midline Granuloma Also known as Stewart's granuloma, Midline lethal

granuloma, Polymorphic reticulosis and Sinonasal lymphoma, T / NK cell lymphoma

Classical destruction of the midface. In the past, death resulted from intercurrent

infection of disseminated lymphoma due to a failure of diagnosis or insufficiently aggressive oncologic treatment.

Recently, similar appearances of aggressive mid facial destruction caused by cocaine abuse have been reported in which tests for granulomatous diseases and lymphoma have been negative

Classification:

• Generalized lymphoma involving the Sinonasal tract

• Lymphomas of waldayer’s ring extending to the nasopharynx

• Peripheral – Sinonasal lymphoma the classic T cell lymphoma

T/NK cell lymphoma may occur at any age from the 1st – 9th decade though the median is 5th – 6th decade, M>F

Clinical Features :Three Stages

Prodromal stage: Only Nasal obs & Rhinorrhoea, may last many years.

Period of activity: Areas of necrosis develop on and around the nasal

cavity with purulent nasal discharge, crusting and tissue loss. There is also progressive destruction of the nasal framework, palate, upper lip extending in to the pharynx. Orbit and skull base also could be involved.

Terminal stage: Gross mutilation of the face, exhaustion and

eventual death. Systemic metastasis is also seen in this stage

HPE : Biopsy material from tissue beneath the

slough and crust is essential for diagnosis. Atypical cell (Atypical T lymphocytes) infiltrates

are found dispersed in necrotic areas. Immuno histochemistry using a panel of

monoclonal antibodies against T cell differentiation antigen should be applied as 80% of peripheral T cell lymphomas show aberrant phenotypes.

Thrombosis and necrosis are common findings Granulomas and giant cells are not present in

this condition.

Treatment : Initially treated with low-dose radiotherapy

but no long term cures were found. Now, radical full course radiotherapy of 55

Gy or more with wide field coverage including the nose, sinuses and palate.

Recurrence or development of disseminated lymphoma worsens the prognosis and chemotherapy may be advocated in those lesions classified as high grade