In the name of god

Otologic manifestations of systemic disease Department Oto-rhino-Laryngology Of

Isfahan Medical Science Chapter 127

1- Granulomatous & infectious dis2- Neoplastic dis3- Disease of bone4- Storage dis5- Collagen vascular dis6- Immunodeficiency disorder (primary, acquired )

Granulomatous & infectious dis

√ Langerhans cell histiocytosis

– Proliferation of cytologically benign histiocytes (monoclonal).

– Sub type: * unifocal; solitary osteolytic lesion in children & young

adults, M>F, asymptomatic or presents with pain, swelling, pathologic Fx. prognosis is excellent. Tx is local curettage ± irradiation(600cGy).

* multifocal; <5 Y, multifocal osteolytic lesion + systemic manifestations, skin, LN, visera. in 25% classic triad (skull lesion, exophthalmos, diabetes insipidus). low dose chemotherapy may be required.

* disseminated; <3Y, multiple organ, systemic manifestations, BM & pulmonary involvement. poor

prognosis, high mortality rate. corton + cytotoxic or chemo & radio + BM transplantation.

Granulomatous & infectious dis

√ Langerhans cell histiocytosis - Otologic manifestations; 15-61%. any portion of temporal bone ( otic capsule & facial

canal are relatively resistant ).

Most common symptoms: otorrhea, postauricular swelling, HL,vertigo.

Most common signs: granulation tissue or polips.

COM with early ear destruction, ↑ ESR, granulation tissue after mastoidectomy, skin & systemic lesions & lytic lesion with nonsclerotic margin in radiographs are diagnostic clues.

definitive Dx is by immunostaining & electron microscopic study of the tissue sample.

Granulomatous & infectious dis

√ tuberculosis

- Mycobacterium tuberculosis is the most. Hematogenous or lymphatic or through Eustachian tube or direct inoculation through a perforation.

- Characteristic signs & symptoms ; multiple perforation of TM, non tender LAP in high jugular, intractable OM with polypoid granulation. Early loss of inner ear function , facial nerve involvement & Bezold’s abscess in mastoid tip may occur.

- Important DDx is WG. PPD test, acid fast organism in granulation tissue,+ cANCA test in WG & systemic manifestations help for Dx.

- Tx is classic chemotherapy .

Granulomatous & infectious dis

√ Wegener’s granulomatosis

- Inflammatory dis with necrotizing vasculitis that primarily affects URT & LRT & kidneys, M=F, 40 Y. etiology & pathogenesis are unknown ( autoimmune dis result of stimulation by infectious agent ).

- Signs & symptoms; headache, fever & arthralgia, Upper airway & sinus in 75-90%, pulmonary involvement( cough, pleuritic chest pain, hemoptysis, nodule or cavity on CXR ) in 65-85%, glomerulonephritis( 60-75% ), eye involvement( 15-50% ), necrotic ulcerations, vesicles, petechiae.

- Lab findings; anemia, ↑PLT, RF+, hyperglobulinemia(Ig A), ↑ESR, c ANCA + ( specificity; >95%sensitivity; variable & parallels the activity of dis ).

- Tx; corton, cyclophosphamide, MTx, for 3-6 mon, followed by lower doses of corton & less toxic drug. Prognosis; 82% mortality rate → 75% remission rate.

- Otologic manifestations; middle ear and mastoid are the most common site, SOM & conductive HL, COM with granulation tissue, early involvement of inner ear & facial nerve.

Granulomatous & infectious dis

√sarcoidosis

- Noncaseating granuloma. lung is the most common site, but all body can be affected. F>M. black/white=10/1. 30-40Y.

- Presenting manifestations; cough, skin rash, eye involvement, LAP, hepatosplenomegaly, cardiac failure, myalgia, arthralgia, CNS & PNS involvement( facial & optic nerve ).

- Hypercalcemia &↑ serum ACE in lab data & bilateral hilar adenopathy in CXR.

- Spontaneous resolution in many Pts. corton in progressive Dis or ocular , cardiac or CNS involvement. cytotoxic is 2nd line

Tx. INFLIXIMAB is a TNF inhibitor that is effective in chronic Dis.

- Otologic manifestations; SNHL, vestibular dysfunction, granolation in Ext & middle ear, Heerfordt’s syndrome or uveoparotid fever( facial paralysis is sudden & often bilateral & resolves spontaneously).

Granulomatous & infectious dis

√ syphilis

- Congenital & acquired Dis may affect middle ear in the late latent( rarefying osteitis ) and tertiary( gumma ) forms. gumma → TM perforation + granulation tissue that mimic TB. Inner ear involvement even in the absence of TM or middle ear changes( SNHL ).

- Hennebert’s sign; ocular deviation with positive or negative presure in external auditory canal, indicates true fistula because of rarefying osteitis of otic capsule or most commonly, fibrous adhesions between the stapes footplate & membranous labyrinth as a result of endolymphatic hydrops.

- Dx; +serologic test & +histology for Treponema pallidum

- Ab + corton for management of SNHL.

Granulomatous & infectious dis

√ Lyme disease- Multisystem inflammatory disease affects skin, nervous system

heart & joints. It’s cause is Borrelia burgdoferi transmitted by Ixodes ticks. Reservoirs are white-footed mice & white-tailed deer.

- 3 stages; 1st; early localized infection, 3-33d after bite, minor

constitutional symptoms + erythema migrans in 60-80%. 2nd ; early disseminated infection, days or weeks after

inoculation, mimic a systemic viral infection, secondary annular skin lesions, nervous Sys, heart, joints( knee ).

3th; late or persistent infection, >1Y after onset, arthritis, encephalomyelitis, polyradiculopathy, kerititis, acrodermatitis chronic atrophycans, localized scleroderma-like lesions.

- Dx; clinical features, Hx of exposure, Ab ( ELISA or Western

blotting ).

- highly sensitive to doxy, moderate to penicillin. amoxi, erythro, cefuroxime, cefria, imipenem. Corton for sever carditis & arthritis. Vaccine is available.

Granulomatous & infectious dis

√ Lyme disease

- Otologic manifestations; facial paralysis is the most( 3-11% ), bilateral in up to

25%, in 2nd stage. Acute onset, duration of weeks to months, almost always spontaneous complete remission occurs, no Ab no corton no surgury.

lymphocytoma, intensely red & violet nodules on the ear

lobe in 2nd stage consists of benign, hyperplasic lymphocytic follicles in dermis.

SNHL, positional vertigo, menier’s like symptoms have

been described.

Granulomatous & infectious dis

√ Mycotic diseases

- In diabetic ketoacidosis, chemotherapy, corton therapy, AIDS.

- Dx; biopsy & culture.

- Tx; surgical debridement, control of underlying dis, amphotericin B.

- Mastoid and middle ear involvement through eustachian tube & tensor tympani( mucor ) or superinfection of COM or hematogenous. Cryptococcal infection of CNS can cause degeneration of the nerve trunks in the IAC.

Neoplastic diseases

√ Multiple myeloma; temporal bone involvement is common, rounded lytic lesions of calvaria & temporal bone. Plasmacytoma of the temporal bone….

√ leukemia; middle ear effusion, AOM & COM, thickening of TM, CHL & SNHL( may be sudden ), vertigo, facial paralysis, skin lesions in

auricle & auditory canal, chloroma of temporal bone.

√ metastatic neoplasms;

Hematogenous from breast, lung, prostate, skin. Usually destructive & ostelytic but breast & prostate may be osteoblastic. petrous apex & IAC are the most, otic capsule is relatively resistance.

CHL, SNHL( in meningeal carcinomatosis rapidly progresive unilateral that mimic CPA tumors or bilateral that mimic AIED ) , vertigo, facial paralysis.

√ Paraganglioma; in nonfamilial, 10% & in heredofamilial up to 50% is multiple. AD with genomic imprinting of the paternal allele. 11q13 & 11q23 deffect. Catecholamin secretion story !….

Diseases of the bone

√ Paget’s disease( osteitis deformans )- Chronic & progressive dis with osteolytic & osteoblastic changes

mainly affect axial skeleton with unknown etiology ( slow virus infection ). AD with ↑ penetrance. 3% of ≥ 40Y, 11% of ≥ 80y. M>F.

- Manifestations; enlarging skull, progressive kyphosis, deformity of pelvis, femur& tibia in 6th decade. Facial nerve is spared.

- Radiographic findings; thickened skull table, patchy ill defined densities & patchy demineralization of skull, poor definition of cortical margin of inner ear & IAC particularly in lytic phase.

- Progressive HL in 5-44%( often mixed with descending pattern of BC and relatively flat AC, rarely only CHL ). DDx is otosclerosis & distinguished by later age of onset, greater SNHL with a descending pattern, enlargement & tortuosity of super temporal art, ↑ ALP, radiographic evidence. No ossicular fixation & no compression of cochlear nerve → No surgery. Significant correlation between mineral density of cochlear capsule in CT scan & hearing threshold.

Diseases of the bone

√ Osteogenesis imperfecta- Connective tissue dis characterized by fragile bones break

with minor trauma. 80-90% have mutation of COL1A1 or COL1A2 or both.

- 4 types;

type I: AD, mildest form, blue sclerae, nondeforming Fx, NL stature. HL is common ( 30-50% ).

type II: AR or sporadic new mutation, most severe form, multiple Fx in utero & stillbirth.

type III: AD or AR or mutation, multiple Fx & progressive bones deformity during childhood, blue sclerae at birth & white later !, HL in 50%, dental abnormalities & wormian bone in the skull table.

type IV: AD, similar to type I except that sclerae is NL & HL is less common( 10-30% ).

Diseases of the bone

√ Osteogenesis imperfecta

- Otologic manifestations:

CHL( in blue sclerae ), SNHL( sever in 40%, in gray or white sclerae ). no relationship between HL & severity & frequency of Fx.

CHL due to structural changes, Fx of manoberium, fragility of long process, fixation of footplate.

DDx is otosclerosis & distinguished by early onset, high compliance in IA, Hx of Fx after minor trauma, FH +, blue sclerae. stapedectomy may cause pathologic Fx and platinum ribbon is preferred to stainless steel wire.

histopathology of temporal bone in type I is very similar to otosclerosis.

Diseases of the bone

√ fibrous dysplasia

- Replacement of NL bone with fibrous tissue & woven bone. Monostotic or polyostotic or Albright’s Syn( bone lesions, precocious puberty in women ). Monostotic is most common. Skull is the most …, etiology is unknown (ɑ subunit of G prot)

- Clinical manifestations: bony deformity, pathologic Fx, cranial nerve palsy. starts in childhood, monostotic quiescent in puberty but polyostotic continue to progress. Sarcomatous transformation in 0.4% .↑ALP in 30% of polyostotic, NL Ca, NL P. in XR presents as well defined radiolucent area & ground glass appearance.

- Otologic manifestation: temporal bone in 100 case(70% mono, 23% poly, 7% Albright), progresive narrowing of EAC with CHL is the most & mistaken for exostoses, facial paralysis, SNHL, vertigo, glomus tympanicum like lesion.

- Tx is symptomatic ( canal wall down mastoidectomy ). Radiotherapy is contraindcated.

Diseases of the bone

√ osteopetroses- Characterized with ↑ bone density because of ↓ osteoclasts

function. - Four types:

2 AR types; Malignant that presents in infancy, progressive, high mortality rate, encroachment of BM leads to anemia, ↓ PLT, hepatosplenomegaly, infection, encroachment of neural foramen → optic atrophy, facial paralysis, SNHL, hydrocephalus, mental retardation. death in 1st or 2nd decade of life. Another type is very rare with distal renal tubular acidosis.

2 AD types; type I, extremely rare, asymptomatic( some suffer from pain & HL ), no ↑ Fx rate. Type II , the most frequent, ↑ rate of Fx, mandible osteomyelitis from dental infection, progressive enlargement of head & mandible, cranial neuropathy… , synductyly & Ab NL fingernails.

Diseases of the bone

√ osteopetroses

- Otologic manifestations:

in malignant form: no pneumatized mastoid. stapes is in fetal form, inner ear is NL, dehiscence of tympanic segment of facial often with herniation in to the oval window niche. Recurrent episode of AOM, SOM, CHL, SNHL, uni or bilateral facial paralysis .

in AD form: sclerosis of temporal bone, CHL( narrowing of eustachian tube, overgrowth of bone of tympanic cavity, ossicular ankylosis, obliteration of oval & round window niche), SNHL, inner ear is NL, recurrent uni or bilateral facial paralysis with progressive residual weakness( radiologic study ), total decompression….

Diseases of the bone

√ Oseitis fibrosa cystica

- ↑ PTH → bone resorption, marrow fibrosis, bone cysts, pain, Fx. The most common cause is primarily ↑PTH due to adenoma.

- Otic capsule replaced by abNL bone and fibrous tissue → SNHL.

Storage & metabolic dis

√ Mucopolysaccharidoses: - deficiency of one of lysosomal enzymes that degrade

mucopolysaccharides. 7 type, all are AR exept for Hunter’s syn( MPS II ) that is X-linked.

- CHL( Eustachian tube dysfunction & thichening of the mucosa ), SNHL( may be a result of abNL metabolism within neural elements ).

√ Gout: - deposition of crystals of monosodium urate within joint

spaces & cutaneous structures → INL1 & other interleukin → inflammation & tissue damage.

- clinical manifestations: arthritis, tophi, urate urolithiasis, nephropathy. Hyperuricemia, leukosytosis, ↑ESR. Helical rim

of pinna is the classic site of involvement, no Tx if asymptomatic.

Collagenvascular & autoimmune dis

√ 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.

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 ↓( staphylococ ), 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.

Immunodeficiency disorders

√ 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 meningiti ), vertigo, tinnitus, facial paralysis by Herpes zoster.

Thanks for your attention