OTOLOGIC MANIFESTATIONS OF SYSTEMIC DISEASES

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Isfahan university of medical sciencesM.Rogha M.D.

1- GRANULOMATOUS & INFECTIOUS DIS.2- NEOPLASTIC DIS.3- DISEASE OF BONE4- STORAGE DIS.5- COLLAGEN VASCULAR DIS.6- IMMUNODEFICIENCY DISORDER (PRIMARY, ACQUIRED )

classification

Systemic disease that can affect the ear• 1- Granulomatous and

infectious disease• a. Langerhans cell

histiocytosis (LCH)• b. Tuberculosis• c. Wegners

granulomatosis• d. Sarcoidosis• e. Syphilis• f. Lyme disease• g. Mycotic disease• 2- Neoplastic disease• a. Multiple myeloma• b. Leukemia• c. Metastatic neoplasm• d. Paraganglioma• 3- Disease of bone• a. Pagets disease• b. Osteogenesis

imperfecta• c. Fibrous dysplesia• d. Osteopetroses• e. Osteitis fibrosa cystica

• 4- Storage and metabolic disease

• a. Mucopolysaccharidoses• b. Gout• c. Ochronosis• 5- Collagen vascular and

autoimmune disease• 6- Immunodeficiency

disorders• a. Primary or congenital• i. Humoral

immunodeficiency disorders• ii. Cellular

immunodeficiency disorders• iii. Disorders of phagocyte

function• iv. Complement system

defects• b. Acquired• i. Acquired

immunodeficiency syndrome

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- Proliferation of cytologically benign histiocytes - Etiology and pathogenesis remain unknown a- unifocal eosinophilic granuloma - M>F, No systemic manifestation, prognosis is excellent - Dx: Local curettage + low dose irradiation, Follow-up with radiographic

skeletal survey b- Hand-Schuller-Christian disease - <5 y, Multifocal osteolytic lesions, With limited

Involvement of skin, lymph nodes & viscera - Systemic manifestations include fever, anorexia, recurrent URTI, anterior

cervical lymphadenopathy, otitis media, and hepatosplenomegaly - Dx: Low dose chemotherapy C- Letterer-Siwe disease - <3y, diffuse involvement of multiple organs, manifestations include

fever, Seborrheic or eczema-like rash. Oral lesions, lymphadenopathy,

hepatosplenomegaly,Multiple bony lesions, diffuse replacement of marrow, and pulmonary

infiltration - Virulent, poor prognosis and high mortality ate - Dx: Corticosteroids and cytotoxic drugs

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Langerhans cell histiocytosis (LCH)Histiositosis X

OTOLOGIC MANIFESTATION- Mastoid is a common site of involvement- Otic capsule & facial nerve are relatively resistant- Otorrhea is the most common symotom followed by postauricular swelling, HL, & vertigo- The most common sign is granulation tissue or aural polypsPerforation of the TM, otitis media, otitis external, a fistula between the mastoid and the external canal- Diagnosis of LCH is suggested by an inflammatory disorder of middle ear and mastoid that does not respond to routine antibiotic therapy, bilateral destructive ear disease, an elevated ESR in the absence of acute infection, exuberant granulation tissue after mastoid surgery, and associated skin and systemic lesions - Radiographs show destructive lesions in the mastoid - The diagnosis is established by biopsy - A definitive diagnosis of LCH is made by immunostaining and

electron microscopic studies

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two lytic lesions of the skull showing beveled edges (arrows) and nonsclerotic margins, which are typical of histiocytosis X.

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TUBERCULOSIS Tuberculosis otitis media 0.05% to 0.9% of all cases of COM Hematogenous or lymphatic or by extension through

eustachian tube TM becomes thickened, CHL due SOME No pain or tenderness, lymphanopathy in high jugular chain Multiple small perforation of the TM The middle ear mucosa appears to be hyperemic with

polypoid granulation Destruction of mastoid tip may result in Bezolds abscess Definitive diagnosis is made by histopathologic examination Of tissue from the ME or mastoid showing a granulomatousProcess with multinucleated giant cells (langerhans cells) and

histologic demonstration of acid-fast organismsD.D with wegener granulomatosis and distinguished on the

basis of skin test, cultures of the ME, ANCADx: Systemic use of standard anti-TB chemotherapy however

mastoid surgery may be required to remove sequestrated bone

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The TM is intact, but greatly thickened by tuberculous granulation tissue containing the typical epithelioid cells, round cells, and multinucleated giant cells

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WEGENER’S GRANULOMATOSIS A granulomatouse inflammatory process with necrotizing

vasculitis Primarily affects the upper and lower respiratory tract and

kidneys but can involve any organ M=F, mean age 40 y Common presenting symptom: headache, sinusitis, rhinorrhea,

otitis media, fever, arthralgia Upper airway and sinus involvement in 75% to 90%, pulmonary

manifestations(couph, pleuritic chest pain, hemoptysis and nodular or cavitary infiltrates) in 65% to 85%

Glomerulonephritis in 60%-75%, eye involvement (conjunctivitis, iritis, scleritis, proptosis) in 15%-50%, dermatologic findings (necrotic ulceration, vesicles or petechiae)

Laboratory findings: normochromic, normocytic anemia, thrombosytosis, positive RF, hyperglobulinemia particularly IgA, elevated ESR

Positive ANCA test, especially proteinase 3, specificity>95%, sensitivity>90% in active and systemic, in limited or inactive 65% to70%

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CONTINUE The diagnose of WG is made histologically by the presence

of necrosis granulomatous inflammation with multinucleated giant cells, vasculitis and microabscess formation

Etiology and pathogenesis unknown, but currently considered to be an autoimmune disease that is perhaps the result of stimulation by an infectious agent (or agents)

Prognosis of WG has dramatically improved from mortality rate of 80% to the current remission rate of >75%

Dx. High doses of corticosteroids, cyclophosphamide or methotrexate for 3 to 6 m followed by maintenance of remission using lower doses of corticosteroids and less toxic immunosuppresants such as azathioprime, methotrexate, trimethoprime-sulfamethoxazole

Otologic manifestation: Middle ear and mastoid are the most common sites within the temporal bone, SOM due to obstruction of the eustachian tube, purulant OM, granulomatous involvement of the ME & mastoid, facial nerve involvement and inner ear can be involved

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13Segmental vasculitis in Wegener granulomatosis with inflammation involving a portion of the arterial wall

SARCOIDOSIS Chronic multisystem disease of unknown etiology that’s

characterized by noncaseating granulomas It most frequently affects lungs, F>M, and is 10 times more

common in blacks, third to fourth decade Common presenting symptoms: Bilateral hilar adenopathy,

cough, granulomatous skin rash Others: iridocyclitis, keratocojectivitis, peripheral

lymphadenopathy, hepatosplenomegaly, cardiac failure, myalgia, and arthralgia

The facial & optic nerves are the most commonly affected cranial nerves

Laboratory findings: Hilar adenopathy in CXR, hypercalcemia, and elevated serum ACE

It has been suggested that the etiology is linked to genetically determined enhancement of the T-helper immune response to a limited number of microbial pathogens

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CONTINUE

Spontaneous resolution occurs in many patients Corticosteroids are beneficial for those with progressive

symptoms or with ocular, cardiac or CNS involvement Infliximab (inhibits release of TNF) has been reported as

being effective for some cases that are refractory to other treatments

Otologic manifestation: SNHL, vestibular dysfunction and facial nerve paralysis, or occasionally granulomatous disease of the external or middle ear and mastoid

The facial nerve is the most commonly affected cranial nerve, it is often bilateral, it may resolve spontaneously and is usually involved as part of the triad of uveoparotid fever (Heerfordts syndrome) parotitis, uveitis, facial nerve paralysis, and mild pyrexia 15

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Bilateral hilar adenopathy and linear parenchymal densities in pulmonary sarcoidosis.

sarcoidosis

SYPHILIS• Both congenital and acquired syphilis may affect the middle ear in the late

latent and tertiary forms • In late latent form the ME & mastoid affected by rarefying osteitis with

leukocytic infiltration• In tertiary the gumma demonstrates obliterative arteritis and central

necrosis, A gumma of the ear canal or ME may result in perforation of TM and a granulomatous appearance of mucosa

• Definitive diagnosis of syphilis requires a positive serologic test and a histologic demonstration of Treponema pallidum

• Syphilis may mimic TB• Heneberts sign (induction of ocular deviation with positive or negative

pressure in the external canal) probably due to fibrous adhesion between the stapes footplate and the membranous labyrinth

• Dx: Combined antibiotic and corticosteroid17

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active round cell osteitis (O)

19Syphilitic gumma

LYME DISEASE

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Multisystem inflammatory disorder that affects skin, nervous system, heart, joints

Spirochete Borrelia burgdorferiTransmitted by Ixodes TicksPrimary reservoirs are white-footed mice and white-tailed

deerThree clinical stages are recognized : a- The first stage (early, localized infection) begins 3 to 33

days after a tick bite (erythema migrans), this lesion occursin 60%-80% of patients and may accompanied by minor

constitutional symptoms b- The second stage (early, disseminated infection) occurs

within days or weeks after inoculation, symptoms include fever, migratory arthralgia, myalgia, headache, meningismus, generalized lymphadenopathy, malaise, fatigue, and secondary annular skin lesion

c-The third stage occurs more than a year after onset and can result in chronic, prolonged arthritis, chronic encephalomyelitis, chronic axonal peripheral polyradiculopathy, keratitis, acrodermatitis chronic`atrophicans, localized scleroderma-like lesions

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Erythema migrans

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acrodermatitis chronica atrophicans

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Inflammatory innate immune responses are critical in the pathogenesis

Diagnosis is based on the recognition of the characteristic clinical features, a history of exposure and detection of a specific antibody to B. burgdorferi

Dx: The spirochete is highly sensitive to doxycycline, other effective antibiotics include amoxicillin, erythromycin, cefuroxime, ceftriaxone, imipenem. Steroids for carditis and arthritis.

Vaccine is now availableOtologic manifestation: Facial nerve paralysis is the most

common Otologic manifestation (3% to 11%), bilateral in (25%), in second stage, in all ages and both sexes, acute in onset, return is spontaneous and complete, antibiotics or steroids do not appear to influence the duration or outcome

Lymphocytoma a red and violet nodules occur on the earlobe during the second stage

SNHL, sudden hearing loss, vertigo, meniere-like symptom have been described

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Skin lesion of lyme disease, ” lymphocytoma”

MYCOTIC DISEASE Systemic invasive clinical disease reflects some

defect in host defense, such as DKA, chemotherapy, AIDS

Diagnose is made by biopsy and culture Treatment consists of control of the underlying

predisposing condition, surgical debridement of necrotic tissue and Amphotercin- B

Otologic manifestation: destruction of the middle ear cleft ensues, often with extention to the surrounding structures , including thrombosis or rupture of the internal carotid artery

Other routes: hematogenous embolic dissemination 25

NEOPLASTIC DISEASE Multiple myeloma: malignancy of plasmacells derived from B

lymphocytes, M>F, 60 y Severe bone pain, pathologic fractures, renal failure, failure of the

bone marrow, hypercalcemia and recurrent infections. Laboratory findings: M component on serum or urine electrophoresis

normochromic, normocytic anemia, hypercalcemia and elevated BUN. Otologic manifestation: Lytic lesions of the temporal bone and otic

capsule, Symptoms are usually overshadowed by manifestation of diffuse

disease Tx: Autologous stemcell transplantation, thalidomide, bisphosphonate

and erythropoietin Extramedullary plasmacytoma (soft tissue) and solitary bone

plasmacytoma (bone): in younger individual, M component in 30%, indolent course, survival rates of 10y or more

Dx: local radiotherapy (4000 cGY), Periodic evaluation should be performed to detect conversion to

multiple myeloma 26

27large lytic destructive lesion (arrows) of the clivus (CL), petrous temporal bone,middle ear, and jugular foramen area caused by multiple myeloma

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Coronal CT scan with contrast enhancement and a soft tissue technique shows a slightly enhancing mass that has destroyed the mastoid bone and extends to the posterior fossa (PF) and upper neck (UN).

LEUKEMIA

• Common in the submucosa of the pneumatized areas of middle ear and mastoid and bone marrow of the petrous apex

• Secondary bacterial infection due to immunocompromised state or chemotherapy, hemorrage in ME, mastoid or inner ear

• Clinical manifestation: ME effusion, acute and chronic suppuration in the ME and mastoid, thickening of the TM, CHL, SNHL, vertigo, facial paralysis, skin lesions in the external auditory canal

• Granolocytic sarcoma or chloroma: exteramedullary tumore in AML or CML

• Management is by local irradiation and chemotherapy 29

PARAGANGLIOMA

• Is the most common neoplasm after the acoustic neuroma• Divided into two groups: the glomus tympanicum and glomus

jugulare• Symptom: • The glomus tympanicum appears with pulsatile tinnitus and a

CHL• The glomus jugulare appears late, after considerable growth and

bony destruction, may cause a neurologic defect in CNs IX to XII, facial nerve paresis caused by tumor extension into the mastoid, or SNHL caused by bony erosion of the labyrrinth

• Both may erode the TM and presenting by bleeding mass• 10% of nonfamilial and 50% of familial have at least one

additional Lesion

• A few PG, both benign and malignant may secrete catecholamines• A history of headache, hypertension and flushing • Dx: surgery, radiotherapy is useful for management of

recurrences and unresectable lesions

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Hematogenous disseminationThe most common sites: Breast, lung, prostate, skinPetrous apex and internal auditory canalThe otic capsule relatively resistantCHL, pain, SNHL, vertigo, facial paralysisIn meningial carcinomatosis unilateral or bilateral

SNHL is a common presenting symptom, diagnosis is made by cytology of the CSF

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METASTATIC NEOPLASM

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metastatic breast adenocarcinoma showing a large lytic lesion(arrows) destroying the mastoid.

Diseases of the bone

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PAGETS DISEASE (osteitis deformans)

Osteolytic and osteoblastic changes affect the axial skeletonAD, 3% of the population, 40y old and older, M>FEnlarging skull, progressive kyphosis, deformities of the pelvis,

femur, tibiaEtiology is uncertain, slow virus infection have suggestedTx: bisphosphonate, calcitonin, mithramycin, ipriflavone, gallium

nitrateOtologic manifestation: HL, tinnitus, mild vestibular dysfunction,

facial nerve is sparedHL 5% to 44%, SN, mixed or rarely conductiveD.D: otosclerosis, paget is late in onset, old age, greater SNHL,

enlarged calvaria, enlargement of the superficial temporal artery, elevated serum ALP

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Paget's disease. There is diffuse expansion of the skull table andinvolvement of both temporal bones, with patchy demineralization.

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Lateral skull radiograph in a patient with Paget's disease. Findings include thickening of the skull table, multiple patchy densities, and platybasia.

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The pagetic bone encroaches on the posterior margin (arrow) of the internal auditory canal (IAC). The mastoid is largely replaced by pagetic bone

OSTEOGENESIS IMPERFECTA Type I through IV Type I: AD, mildest form, blue sclera, nondeforming fructures, normal

stature, HL in 30%-50% Type II: most severe, multiple fracture in uterus, stillbirth, AR or sporadic Type III: multiple fracture, bone deformity, HL in 50% Type IV: AD, similar to type I except that the sclera are white, HL in 10%-

30% Tx: management of fractures, orthopedic surgery, bisphosphonate Otologic manifestation: SNHL in 40%, high correlation with gray or white

sclera, CHL accompanies blue sclera, CHL reflects structural change in the ossicles, microfractures of the manuberium, fragility of the long process of the incus, fracture or resorption of the crura of the stapes

Rehabilitation by amplification or surgery Stapedectomy can give similar results to otosclerosis

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Osteogenesis imperfecta

FIBROUS DYSPLASIA• Benign, chronic, slowly progressive, unknown etiology• Replacement of normal bone with fibrous tissue and woven

bone• 7% as part of Albrights syndrome (bony lesions, abnormal

pigmentation, endocrine dysfunction, precocious puberty in women)

• 70% monostotic form: most common, skull, ribs, femur, tibia, may become quiescent at puberty

• 23% polystotic form: skull lesions in more than 50%, can continue to progress

• Clinical manifestation: bony deformity, pathologic fracture, cranial nerve palsy

• Normal serum calcitonin and phosphorus levels, elevated serum ALP in polystotic form

• Radiographic finding: radiolucent area, ground-glass appearance

• Otologic manifestation: progressive narrowing of the external auditory canal with CHL is the most common (80%), facial nerve paralysis, SNHL, vertigo

• Management is symptomatic, radiotherapy is contraindicated

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Lateral radiograph of the skull of a patient with fibrous dysplasia showing lytic (L) and fibrous (F) phases of disease. Spicules of new bone are responsible for the ground-glass appearance of the fibrous phase.

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Coronal tomographic radiograph of a patient with fibrous dysplasia. New bone formation causes a dense appearance of the involved left temporal bone.

OSTEOPETROSES

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Rare genetic disorder, greatly increased bone density,

Defective function of osteoclasts, Malignant osteopetrosis ; AR, high mortality

rate, anemia, thrombocytopenia, hepatosplenomegaly, susceptibility to infection, encroachment of the neural foramina, optic atrophy, facial paralysis, SNHL, hydrocephalus, MR, and death

Otologic manifestation: mastoid is non pneumatized, inner ear normal, herniation of facial nerve a consistent finding, recurrent episodes of AOM, SOM, CHL, SNHL, unilateral or bilateral facial nerve paralysis

Tx: symptomatic, decompression of the facial nerve

OSTEITIS FIBROSA CYSTICA

Von Recklinghausens disease Excess parathormone Osteoclastic bone resorption, marrow fibrosis,

bone cysts, bone pain, and fractures In most cases is caused by hyperparathyroidism

due to an adenoma Involvement of temporal bone is very rare, the

otic capsule is replaced by abnormal bone, SNHL has been attributed to osteitis fibrosa

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Metabolic & storage disease

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MUCOPOLYSACCHARIDOSES

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MPS an inherited deficiency of one of several lysosomal enzymes that degrade MPS

Classified into seven types, all are AR except for Hunters syn (MPS II) which is X-linked recessive

Management is supportive and symptomaticMPS III: Hurlers syn, accumulation of heparan sulfate,

corneal clouding, abnormal facies, hepatosplenomegaly, MR, joint stiffness, and hernias

MPS II: Hunters syn, accumulation of heparan sulfate and dermatan sulfate, similar to hurler, but corneal clouding is not seen

MPS IV: Moquios syn, spondyloepiphyseal dysplasiaOtologic manifestations: CHL( Eustachian tube

dysfunction & thickening of the mucosa ), SNHL ( may be a result of abnormal metabolism of the inner ear).

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MUCOPOLYSACCHARIDOSIS

GOUT

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Deposition of crystals of monosodium urate within joint space & cutaneous structures

Serum urate level>7mg/dl, risk factors include: alcohol use, exposure to loop diuretics, hypertension & renal insufficiency

Clinical manifestation: acute gouty arthritis, tophi, urate urolithiasis, and gouty nephropathy

Otologic manifestation: Tophaceous deposits in the helical rim of the pinna, asymptomatic

Treatment: bed rest, analgesics, colchicine, probencid, allopurinol

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Tophus

Ochronosis

Ochronosis is a rare disease that is caused by an inherited lack of the enzyme homogentisic acid oxidase.

The presence of homogentisic acid in urine is called alkaptonuria. The result of this inborn error of metabolism is the deposition of a dark pigment in tissues that are rich in collagen.

Patients often present with symptoms and signs during the third decade of life.

Manifestations include ochronotic arthropathy, ocular andcutaneous pigmentation, obstruction of the genitourinary tract by ochronotic calculi, and cardiovascular manifestations as a result of ochronosis affecting the aortic valve.

Ochronosis has manifestations in the external ear; cartilage is a site of predilection for the deposition of the pigment of ochronosis. Blue or mottled-brown macules can appear on the pinna and in other areas of the head and neck, including the nose, buccal mucosa, tonsils, pharynx, larynx, and esophagus. 50

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Ochronosis

Collagenvascular &

Auto immune diseases

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Relapsing polychondritis

Episodic & progressive autoimmune inflammatory dis, F>M, auricles & nasal septom are most common & first sites. nonerosive & nondeforming arthritis of hands & knees. Other cartilaginous sites…, eyes, aorta, heart & skin.

Sudden, painful, tender uniform reddish swallowing of auricle, lobule remains NL in color. CHL( as a result of Eustachian tube involvement ), SNHL & vestibular symptom( because of endorgan vascular etiology ).

DDx: erysipelas( irregular margin of erithema extend to priauricular

skin ), chondritis & prichondritis( don’t uniformly involve the entire auricle, often fluctuance, not spare the lobule ).

Dx is clinical, non specific lab findings ( ↑ ESR, no ↑ WBC), Bx is

unnecessary.

Corton & immunosupresive for sever ,progresive & lethal cases. In less sever cases Dapsone , NSAID, Colchicine, Salisylates.

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Relapsing poly chondritis

Immunodeficiency disorders

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Immunodeficiency disorders

Primary:- Humoral: recurrent & chronic RTI with extracellular bacteria.

- Cellular: dysfunction of T lymp, recurrent infection with intracellular opportunistic ( viruses, fungi, protozoa & some bacteria ).

- Dis of phagocyte: pyogenic bacteria & fungi.

- Complement sys:C5, C6, C7, C9( Neisseria ), C3b inactivator ↓ ( staphylococcus) , C1, C2, C4( lupus like syn ), C1 esterase inhibitor ↓( angioedema ).

- Otologic manifestations: recurrent AOM, SOM, refractory COM. anomalies of external, middle & inner ear with CHL, SNHL or mixed HL and high incidence of Mondini’s dysplasia, in DiGeorge’s syn.

Cont.

Acquired

- Otologic manifestations are rare, except in children( SOM ), microbiology is similar to non AIDS population with addition of unusual opportunistic organism. Severity depends on immune status, Bx or tympanocentesis is indicated before Tx.

- Pneumocystis carinii is common cause of middle & external

ear, may be the initial presenting sym of AIDS, Tx is cotri.

- SNHL( otosyphilis, cryptococcal, tuberculous, toxoplasmosis meningitis ), vertigo, tinnitus, facial paralysis by Herpes zoster.

AIDS

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• The virus is lymphotropic & attacks T helper lymphocytes

• Otologic manifestation: infrequent except in children, SOM is common, microbiology is similar to non AIDS

• AOM, acute mastoiditis, SOM, and bullous myringitis

• Otitis externa, Kaposi sarcoma

• Pneumocystis carinii is common cause of middle ear & external ear disease, subcutaneous masses, aural polyps, CHL, otorrhea, otalgia,

• Dx: co-trimoxazol

• SNHL, vertigo, tinnitus, facial nerve palsy

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