Otitis Externa

Introduction

Background

ΦλεγμΟνη στον εξω ακουστικο πορο – ΤΑΧΕΙΑ ΔΙΑΓΝΩΣΗ κ ΔΙΑΧΕΙΡΗΣΗ ΕΠΙΤΥΓΧΑΝΕΙ ΙΑΣΗ ΣΤΗΝ ΠΛΕΙΟΨΗΦΙΑ ΤΩΝ ΠΕΡΙΠΤΩΣΕΩΝ

ΕΝΔΕΧΟΜΕΝΩΣ ΑΠΕΙΛΗΤΙΚΗ ΓΙΑ ΤΗ ΖΩΗ : [ Σ ΔΙΑΒΗΤΗΣ – ΑΝΟΣΟΚΑΤΑΣΤΟΛΗ – ΧΩΡΙΣ ΘΕΡΑΠΕΙΑ ] = ΚΑΚΟΗΘΗΣ ΕΞΩΤΕΡΙΚΗ ΩΤΙΤΙΔΑ

ΧΡΟΝΙΟΤΗΤΑ = > 4 ΕΒΔΟΜΑΔΕΣ ‘Η >4 ΕΠΙΣΟΔΙΑ ΤΟ ΤΕΛΕΥΤΑΙΟ ΕΤΟΣ

Pathophysiology

ΕΔΩ ΠΑΡΑΓΕΤΑΙ ΕΝΑ ΠΡΟΣΤΑΤΕΥΤΙΚΟ ΣΤΩΜΑ ΚΕΡΙΟΥ / ΚΥΨΕΛΙΔΑ = ΟΞΙΝΟ ΠΕΡΙΒΑΛΛΟΝ ΠΛΟΥΣΙΟ ΣΕ ΛΥΣΟΖΥΜΗ. ΕΛΑΤΤΩΣΗ ΕΚΚΡΙΣΗΣ ΚΥΨΕΛΙΔΑΣ ΠΡΟΔΙΑΘΕΤΕΙ ΣΕ ΒΑΚΤΗΡΙΑΚΗ ΑΝΑΠΤΥΞΗ – ΑΥΞΗΜΕΝΗ ΕΚΚΡΙΣΗ ΚΥΨΕΛΙΔΑΣ ΣΥΝΥΣΦΕΡΕΙ ΣΕ ΚΑΤΑΚΡΑΤΗΣΗ ΥΓΡΑΣΙΑΣ κ ΞΕΝΩΝ ΣΩΜΑΤΩΝ ΟΠΟΤΕ κ ΠΑΛΙ ΥΦΙΣΤΑΤΑΙ ΕΝΑ ΠΕΡΙΒΑΛΛΟΝ ΙΔΑΝΙΚΟ ΓΙΑ ΒΑΚΤΗΡΙΑΚΗ ΑΝΑΠΤΥΞΗ – ΔΥΤΕΣ – ΚΟΛΥΜΒΗΤΕΣ – ΑΜΕΣΗ ΒΑΚΤΗΡΙΑΚΗ ΛΟΙΜΩΞΗ ΕΠΕΤΑΙ ΤΡΑΥΜΑΤΙΣΜΟΥ ΑΠΟ ΞΕΝΟ ΣΩΜΑ

Η ΕΓΚΑΤΑΣΤΑΣΗ ΤΗΣ ΛΟΙΜΩΞΗΣ ΕΠΙΦΕΡΕΙ ΕΜΒΡΟΧΗ κ ΦΛΕΓΜΟΝΗ ΟΠΟΤΕ ΕΜΦΑΝΙΖΟΝΤΑΙ ΤΑ ΦΥΣΙΚΑ ΕΥΡΗΜΑΤΑ

ΣΠΑΝΙΩΣ Η ΛΟΙΜΩΞΗ ΕΞΑΠΛΩΝΕΤΑΙ ΣΤΑ ΒΑΘΥΤΕΡΑ ΟΡΓΑΝΑ / ΜΑΛΑΚΑ ΜΟΡΙΑ ΔΥΝΑΤΟ ΜΕΧΡΙ ΚΑΤΑΣΤΡΟΦΗΣ ΤΟΥ ΜΑΣΤΟΕΙΔΟΥΣ ΟΣΤΟΥ = ΚΑΚΟΗΘΗΣ ΕΞΩΤΕΡΙΚΗ ΩΤΙΤΙΔΑ ΚΑΤΑ ΚΑΝΟΝΑ ΣΕ ΑΣΘΕΝΕΙΣ ΥΠΟ ΑΝΟΣΟΚΑΤΑΣΤΟΛΗ Pseudomonas species > Staphylococcus > Streptococcus species > Fungi

Frequency

United States

4 : 1000 people annually,

the chronic form affects 3-5% of the population.

swimmers, divers, and those whose ears are regularly exposed to or submerged in water.

Mortality/Morbidity

ΑΝΕΥ ΑΓΩΓΗΣ , ΘΝΗΤΟΤΗΤΑ = 50%. – ΚΛΙΝΙΚΗ ΥΠΟΨΙΑ : [ ΕΥΑΙΣΘΗΣΙΑ – ΕΡΥΘΗΜΑ – ΟΙΔΗΜΑ ΣΤΟΝ ΕΞΩ ΑΚΟΥΣΤΙΚΟ ΠΟΡΟ ‘Η ΠΕΡΙΞ ΙΣΤΟΥΣ ]

Σ ΔΙΑΒΗΤΗΣ – AIDS – ΧΗΜΕΙΟΘΕΡΑΠΕΙΑ – ΥΠΟ ΓΛΥΚΟΚΟΡΤΙΚΟΕΙΔΗ

Race

People in some racial groups have small ear canals, which may predispose them to obstruction and infection.

Sex

Rates of occurrence of otitis externa are equal in males and females.

Age

Although otitis externa is seen in all age groups, the peak incidence is in children aged 7-12 years.1

Clinical

History ΠΡΟΟΔΕΥΤΙΚΟ ΑΛΓΟΣ ΑΠΟ 48ΩΡΟΥ – ΙΣΤΟΡΙΚΟ ΕΚΘΕΣΗΣ ΣΕ ΥΔΑΤΑ – ΚΝΗΣΜΟΣ ΕΝΤΟΣ ΤΟΥ ΕΞΩ ΑΚΟΥΣΤΙΚΟΥ ΠΟΡΟΥ – ΠΥΩΔΕΣ ΕΚΚΡΙΜΑ – ΒΑΡΗΚΟΙΑ ΑΓΩΓΙΜΟΤΗΤΑΣ – ΑΙΣΘΗΜΑ ΠΛΗΡΟΤΗΤΑΣ / ΠΙΕΣΗΣ

Physical Η sine qua non [= ΑΠΑΡΑΙΤΗΤΗ ΠΡΟΥΠΟΘΕΣΗ] = ΑΛΓΟΣ ‘Η ΑΙΣΘΗΜΑ ΕΛΞΗΣ ΤΩΝ ΔΟΜΩΝ ΣΤΟΝ ΕΞΩ ΑΚΟΥΣΤΙΚΟ ΠΟΡΟ – ΔΥΝΑΤΟ ΠΕΡΙΩΤΙΚ ΑΔΕΝΙΤΙΔΑ ΑΛΛΑ ΔΕΝ ΕΙΝΑΙ ΑΠΑΡΑΙΤΗΤΗ ΠΡΟΥΠΟΘΕΣΗ ΓΙΑ ΤΗ ΔΙΑΓΝΩΣΗ – ΕΡΥΘΗΜΑ – ΟΙΔΗΜΑ – ΣΤΕΝΩΣΗ – ΣΥΓΚΕΝΤΡΩΣΗ ΥΓΡΑΣΙΑΣ κ ΞΕΝΩΝ ΣΩΜΑΤΩΝ – Η ΟΠΤΙΚΗ ΕΠΑΦΗ ΜΕ ΤΗΝ ΤΥΜΠΑΝΙΚΗ ΜΕΜΒΡΑΝΗ ΔΕΝ ΕΙΝΑΙ ΠΑΝΤΑ ΕΥΙΚΤΗ ΑΛΛΑ ΚΑΤΑ ΚΑΝΟΝΑ ΑΚΟΜΗ κ ΑΝ ΕΙΝΑΙ ΕΛΑΦΡΑ ΦΛΕΓΜΟΝΩΔΗΣ ΘΑ ΠΡΕΠΕΙ ΝΑ ΕΧΕΙ ΚΙΝΗΤΙΚΟΤΗΤΑ ΜΕ ΕΜΦΥΣΗΣΗ – ΣΠΟΡΙΑ / ΥΦΑΙΜΑΤΑ ΔΥΝΑΤΟ ΝΑ ΑΝΕΥΡΕΘΟΥΝ – ΔΥΝΑΤΟ ΝΑ ΑΝΕΥΡΕΘΕΙ ΕΚΖΕΜΑ ΤΟΥ ΛΟΒΟΥ ΤΟΥ ΩΤΟΣ – ΚΑΤΑ ΚΑΝΟΝΑ ΔΕΝ ΥΠΑΡΧΕΙ ΣΗΜΕΙΟΛΟΓΙΑ ΣΥΖΥΓΙΩΝ ΣΕ ΑΠΛΗ ΕΞΩΤΕΡΙΚΗ ΩΤΙΤΙΔΑ : [VII and IX-XII ]

Causes ΤΡΑΥΜΑΤΙΣΜΟΣ – ΒΑΚΤΗΡΙΑ – 10% ΜΥΚΗΤΕΣ Aspergillus species – ΖΥΜΕΣ Candida species – ΕΚΖΕΜΑΤΩΔΕΙΣ ΝΟΣΟΙ : [ ΕΚΖΕΜΑ – ΣΜΗΓΜΑΤΟΡΟΙΑ – ΝΕΥΡΟΔΕΡΜΤΙΤΙΔΑ – ΔΕΡΜΑΤΙΤΙΔΑ ΕΠΑΦΗΣ ΑΚΟΥΣΤΙΚΑ / ΕΝΩΤΙΑ ] – ΕΥΑΙΣΘΗΣΙΑ ΣΕ ΤΟΠΙΚΑ ΣΚΕΥΑΣΜΑΤΑ

ΠΥΩΔΗΣ ΜΕΣΗ ΩΤΙΤΙΔΑ : ΔΙΑΤΡΗΣΗ ΤΥΜΠΑΝΙΚΟΥ ΥΜΕΝΑ – ΑΠΟΧΕΤΕΥΣΗ [= drainage ] ΥΓΡΟΥ – ΑΝΕΥ ΑΛΓΟΥΣ – ΑΝΕΥ ΟΙΔΗΜΑΤΟΣ

Differential Diagnoses

Foreign Bodies, Ear Herpes Zoster Herpes Zoster Oticus Otitis Media Pediatrics, Otitis Media

Other Problems to Be Considered

Chondritis Cranial nerve palsy Hearing loss Wisdom tooth eruption Intracranial abscess Cavernous sinus thrombosis

Workup

Laboratory Studies ΧΡΩΣΗ ΚΑΤΑ ΓΚΡΑΜ κ ΚΑΛΛΙΕΡΓΕΙΕΣ ΕΙΔΙΚΑ ΕΠΙ ΥΠΟΨΙΑΣ ΜΥΚΗΤΩΝ – Γ ΔΙΑΓΝΩΣΗ ΕΙΝΑΙ ΚΛΙΝΙΚΗ

Imaging Studies ΑΠΟΛΥΤΗ ΕΝΔΕΙΞΗ = ΣΗΜΕΙΑ ΣΥΣΤΗΜΑΤΙΚΗΣ ΤΟΞΙΚΟΤΗΤΑΣ – ΟΣΤΙΚΗΣ ΣΥΜΜΕΤΟΧΗΣ

• , CT scanning of the temporal and mastoid bones is appropriate.

Other Tests ΓΛΥΚΟΖΗ ΑΙΜΑΤΟΣ – urine dipstick test ΓΙΑ ΤΕΚΜΗΡΙΩΣΗ ΛΑΝΘΑΝΟΝΤΟΣ Σ ΔΙΑΒΗΤΗ

Procedures ΚΑΘΑΡΙΣΜΟΣ : ΘΕΡΜΟ ΥΔΩΡ + ΥΠΕΡΟΞΕΙΔΙΟ ΑΛΛΑ ΘΑ ΠΡΕΠΕΙ ΝΑ ΔΙΑΣΦΑΛΙΣΘΕΙ ΟΤΙ ΔΕΝ ΥΦΙΣΤΑΤΑΙ ΤΥΜΠΑΝΙΚΗ ΔΙΑΤΡΗΣΗ – ΩΤΟΣΚΟΠΗΣΗ ΑΞΙΟΛΟΓΗΣΗ ΕΑΝ ΠΡΟΚΕΙΤΑΙ ΓΙΑ ΜΕΣΗ ΩΤΙΤΙΔΑ

Treatment

Emergency Department Care

ΚΛΙΝΙΚΗ ΤΕΚΜΗΡΙΩΣΗ – ΚΑΘΑΡΙΣΜΟΣ ΕΑΝ ΕΙΝΑΙ ΕΥΙΚΤΟΣ – ΤΟΠΟΘΕΤΗΣΗ ΤΟΛΥΠΙΟΥ ΓΙΑ ΠΡΟΣΤΑΣΙΑ κ ΔΙΑΣΦΑΛΙΣΗ ΕΜΠΟΤΙΣΜΟΥ ΤΟΥ ΤΟΠΙΚΟΥ ΦΑΡΜΑΚΟΥ

Otitis externa with ear wick in place. Note discharge from canal and swelling of canal. {{mediacaption:763995_1}}

ΠΑΛΑΙΑ : [ ΣΤΥΠΤΙΚΑ ΜΕΣΑ – ΟΞΕΙΚΟ ΟΞΥ ] = ΕΠΩΔΥΝΑ

ΕΥΡΑΙΑ ΧΡΗΣΗ : ΑΜΥΝΟΓΛΥΚΟΣΙΔΗ + 2Ο ΑΝΤΙΜΙΚΡΟΒΙΑΚΟ + ΣΤΕΡΟΕΙΔΕΣ [neomycin-polymyxin B-hydrocortisone ] – ΑΠΙΤΕΙΤΑΙ ΠΡΟΣΟΧΗ ΓΙΑ ΥΠΕΡΕΥΑΙΣΘΗΣΙΑ / ΩΤΟΤΟΞΙΚΟΤΗΤΑ ΣΤΗ ΝΕΟΜΥΚΙΝΗ

ΣΕ ΠΕΡΙΠΤΩΣΗ ΜΕΣΗΣ ΩΤΙΤΙΔΑΣ Η ΧΡΗΣΗ ΩΤΙΚΟΥ ΔΙΑΛΥΜΑΤΟΣ ΑΥΞΑΝΕΙ ΤΟΝ ΚΙΝΔΥΝΟ ΩΤΟΤΟΞΙΚΟΤΗΤΑΣ ΑΠΟ ΤΗΝ ΑΜΙΝΟΓΛΥΚΟΣΙΔΗ ΟΠΟΤΕ ΕΙΝΑΙ ΠΡΟΤΙΜΗΤΕΑ Η ΧΡΗΣΗ ΕΝΑΙΩΡΗΜΑΤΟΣ ΣΕ ΣΤΑΓΟΝΕΣ

ΣΥΜΦΩΝΑ ΜΕ ΤΗ ΒΙΒΛΙΟΓΡΑΦΙΑ ΘΕΩΡΕΙΤΑΙ ΑΣΦΑΛΕΣ : [ciprofloxacin 0.3%/dexamethasone 0.1% otic suspension ]

ΟΙ ΦΘΟΡΙΟΚΙΝΟΛΟΝΕΣ ΔΕΝ ΣΥΣΧΕΤΙΖΟΝΤΑΙ ΜΕ ΩΤΟΤΟΞΙΚΟΤΗΤΑ κ ΘΕΩΡΟΥΝΤΑΙ ΑΣΦΑΛΗ ΣΕ ΤΥΧΟΝ ΔΙΑΤΡΗΣΗ ΤΥΜΠΑΝΙΚΟΥ ΥΜΕΝΑ

ΜΥΚΗΤΙΑΣΗ : [acetic acid solution - antifungal such as 1% clotrimazole ]

ΣΕ ΕΛΑΦΡΑ ΝΟΣΟ ΧΩΡΙΣ ΠΥΡΕΤΟ ΣΥΝΙΣΤΑΤΑΙ ΑΓΩΓΗ ΜΕ ΑΝΤΙΜΙΚΡΟΒΙΑΚΟ ΩΣ ΕΞΩΤΕΡΙΚΟΣ ΑΣΘΕΝΗΣ κ ΠΑΡΑΚΟΛΟΥΘΗΣΗ

ΕΝΙΟΤΕ ΥΠΑΡΧΕΙ ΕΝΔΕΙΞΗ ΓΙΑ : [ ΑΝΑΛΓΗΤΙΚΟ – ΑΝΤΙΠΥΡΕΤΙΚΟ – ΑΝΤΙΙΣΤΑΜΙΝΙΚΟ ]

Clinical guidelines are available from the American Academy of Otolaryngology - Head and Neck Surgery Foundation.4

Consultations

ΠΑΡΑΠΟΜΠΗ ΣΕ ΩΡΛ (ENT) : [ ΠΥΩΔΕΣ ΕΚΚΡΙΜΑ – ΔΙΑΤΡΗΣΗ ΤΥΜΠΑΝΙΚΟΥ ΥΜΕΝΑ – ΥΠΟΨΙΑΣ ΚΑΚΟΗΘΟΥΣ ΕΨΩΤΕΡΙΚΗΣ ΩΤΙΤΙΔΑΣ

Medication

ΑΝΑΛΓΗΤΙΚΑ – ΠΑΡΑΓΟΝΤΕΣ ΟΞΙΝΟΠΟΙΗΣΗΣ + ΤΟΠΙΚΑ ΑΝΤΙΜΙΚΡΟΒΙΑΚΑ + ΣΤΕΡΟΕΙΔΗ – ΔΕΝ ΕΧΕΙ ΑΠΟΔΕΙΧΘΕΙ ΟΦΕΛΟΣ ΑΠΟ ΣΥΝΔΥΑΣΜΟ ΤΟΠΙΚΟΥ κ PER OS ΑΝΤΙΜΙΚΡΟΒΙΑΚΟΥ

Analgesics

ΔΥΝΑΤΟ ΝΑ ΑΠΙΤΗΘΕΙ ΑΝΑΛΓΗΣΙΑ ΠΡΟΣ ΕΞΕΤΑΣΗ / ΚΑΘΑΡΙΣΜΟ ΤΟΥ ΕΞΩ ΑΚΟΥΣΤΙΚΟΥ ΠΟΡΟΥ

Acetaminophen and codeine

Indicated for treatment of mild to moderate pain.

Adult

1-2 tab PO q4-6h; not to exceed 4 g/d acetaminophen

Precautions

ΝΑ – ΗΑ – ΠΡΟΣΟΧΗ ΣΕ ΑΣΘΕΝΗ ΜΕ Σ/ΜΟ ΣΤΕΡΗΣΗΣ

Acidifying agents

ΟΞΙΝΟΠΟΙΗΣΗ ΕΝΑΝΤΙ ΨΕΥΔΟΜΟΝΑΔΑΣ : [acetic acid solutions (eg, VoSol) ]

Acetic acid solution (VoSol)

Inexpensive agent; works well in treating superficial bacterial infections of otitis externa.

Adult

1-2 gtt q4-6h in canal or on ear wick

Precautions

For external use only; systemic acidosis may result from absorption

Otic antibiotics

These agents are commonly prescribed for treating otitis externa and are associated with cure rates between 87% and 97%.3

Ciprofloxacin-dexamethasone otic (Ciprodex otic suspension)

ΦΑΣΜΑ : [ ΨΕΥΔΟΜΟΝΑΔΑ – ΣΤΡΕΠΤΟΚΟΚΚΟΙ – MRSA – ΣΤΑΦΥΛΟΚΟΚΚΟΣ ΕΠΙΔΕΡΜΙΚΟΣ – ΤΑ ΠΕΡΙΣΟΤΤΕΡΑ ΓΚΡΑΜ (-) ] - ΔΕΝ ΚΑΛΥΠΤΕΙ ΤΑ ΑΝΑΕΡΟΒΙΑ

Ο ΡΟΛΟΣ ΤΗΣ ΔΕΞΑΜΕΘΑΖΟΝΗΣ ΕΙΝΑΙ Η ΕΛΑΤΤΩΣΗ ΤΟΥ ΟΙΔΗΜΑΤΟΣ κ Η ΑΝΑΚΟΥΦΗΣΗ ΑΠΟ ΤΟ ΑΛΓΟΣ

Adult

4 gtt q12h into affected ear

Precautions

ΠΑΡΑΤΕΤΑΜΕΝΗ ΧΡΗΣ : [ ΠΡΟΔΙΑΘΕΣΗ ΓΙΑ ΜΥΚΗΤΙΑΣΗ ]

Superinfections (usually fungal) may occur with prolonged or repeated antibiotic use

Neomycin, polymyxin B, and hydrocortisone (Cortisporin Otic)

Adult

4-5 gtt q6h into affected ear

Precautions

ΑΝΤΕΝΔΕΙΞΗ :ΜΕΣΗ ΩΤΙΤΙΔΑ

ΠΑΡΑΤΕΤΑΜΕΝΗ ΧΡΗΣΗ : [ ΑΝΘΕΚΤΙΚΟΤΗΤΑ ΜΙΚΡΟΒΙΑΚΗ – ΔΕΡΜΑΤΙΚΗ ΑΤΡΟΦΙΑ ]

1/3 : ΑΝΑΠΤΥΞΗ ΥΠΕΡΕΥΑΙΣΘΗΣΙΑΣ ΣΤΗ ΝΕΟΜΥΚΙΝΗ : [ ΕΡΥΘΡΟΤΗΤΑ κ ΦΛΕΓΜΟΝΗ ΜΙΜΟΥΜΕΝΗ ΕΠΙΜΟΝΗ ΛΟΙΜΩΞΗ ] – ΣΕ ΜΙΚΡΟΤΕΡΟ ΠΟΣΟΣΤΟ ΑΝΑΠΤΥΞΗ ΕΚΤΕΝΟΥΣ ΤΟΠΙΚΗΣ ΑΝΤΙΔΡΑΣΗΣ

Ofloxacin (Floxin Otic)

Pyridine carboxylic acid derivative with broad-spectrum bactericidal effect.

Adult

5-10 gtt q12h into affected ear

Precautions

Superinfections (usually fungal) may occur with prolonged or repeated antibiotic use

Ciprofloxacin (Ciloxan, Cipro HC Otic)

Adult

3-5 gtt q12h into affected ear

Follow-up

Further Outpatient Care

Patients may follow up with an otorhinolaryngologist (ENT) physician.

Deterrence/Prevention

• Patients who have recurrent episodes of otitis externa should be taught to use acidifying drops in their ears after every exposure to water to prevent recurrences.

• Attention to elimination of water after swimming or bathing may help prevent recurrence. The use of a blow dryer on a low setting after swimming to dry the ear canal has been suggested as a preventive measure. No studies have demonstrated the effectiveness of this suggestion.

Complications

• Malignant otitis externa is the only significant complication.

• Most frequently, the disease occurs in diabetic and immunocompromised patients and involves bacterial spread to the cartilage of the external ear with resulting pain and edema.

• It may be accompanied by a fever and systemic manifestations of infection.

• Treatment requires parenteral antibiotics with coverage for Pseudomonas species, in addition to local care.

• These patients require specialty consultation and hospitalization.

• Acute otitis externa may spread to the pinna, resulting in a chondritis, particularly in patients with newly pierced ears.

• Diabetic ketoacidosis is often present in diabetics with this condition.

Prognosis

• Most patients with otitis externa improve within 48-72 hours of antibiotic administration.

• Failure to improve within 2-3 days should call the diagnosis into question and prompt the physician to reevaluate the patient.

• Surgical intervention is sometimes necessary for chronic otitis externa.

• Resolution of eczematous otitis externa occurs with control of the primary skin condition.

Patient Education

• Prevention by using acidifying drops is encouraged in patients with recurrent episodes of otitis externa.

• Avoidance of cotton-tipped swabs to avoid ear canal trauma should be discussed with patients. Improper use of cotton-tipped applicator sticks simply packs cerumen into the canal and can cause trauma to the tympanic membrane.

Miscellaneous

Medicolegal Pitfalls

• Failure to recognize the occasional patient with malignant otitis externa and provide systemic antibiotic therapy may have significant complications.

• Adult patients diagnosed with malignant otitis externa should be screened for diabetes.

Special Concerns

• Children may insert a foreign body (FB) in their ear canal and not mention it to parents.

• If any pain accompanies purulent drainage, consider the presence of a FB.

• The patient with a FB will not improve until it is removed. Also, see Foreign Body Removal, Ear.

External Ear, Malignant External Otitis

Background

Toulmouche1838

1959, Meltzer : ΑΝΑΦΟΡΑ ΟΣΤΕΟΜΥΕΛΙΤΙΔΑΣ ΑΠΟ ΨΕΥΔΟΜΟΝΑΔΑ ΣΤΟ ΜΑΣΤΟΕΙΔΕΣ ΟΣΤΟ

1968, Chandler : ΤΕΚΜΗΡΙΩΣΗ ΤΗΣ ΚΑΚΟΗΘΟΥΣ ΕΞΩΤΕΡΙΚΗΣ ΩΤΙΤΙΔΑΣ ΩΣ ΞΕΧΩΡΙΣΤΗΣ ΝΟΣΟΛΟΓΙΚΗΣ ΟΝΤΟΤΗΤΑΣ : [ ΕΠΙΘΕΤΙΚΗ ΣΥΜΠΕΡΙΦΟΡΑ – ΦΤΩΧΗ ΕΚΒΑΣΗ ΤΗΣ ΘΕΡΑΠΕΙΑΣ – ΥΨΗΛΗ ΘΝΗΤΟΤΗΤΑ ]

Η ΠΡΟΟΔΟΣ ΗΤΑΝ ΣΗΜΑΝΤΙΚΗ ΜΕ ΤΗ ΧΡΗΣΗ ΑΝΤΙΜΙΚΡΟΒΙΑΚΩΝ ΕΝΑΝΤΙ ΤΗΣ ΨΡΥΔΟΜΟΝΑΔΑΣ

Anatomy of the ear.

Pathophysiology

ΨΕΥΔΟΜΟΝΑΔΑ – ΗΛΙΚΙΩΜΕΝΟΙ ΜΕ ΣΔ – ΕΞΩΤΕΡΙΚΗ ΩΤΙΤΙΔΑ ΕΞΕΛΙΣΣΟΜΕΝΗ ΣΕ ΟΣΤΕΟΜΥΕΛΙΤΙΔΑ ΤΟΥ ΜΑΣΤΟΕΙΔΟΥΣ ΟΣΤΟΥ – ΔΙΑΣΠΟΡΑ ΠΕΡΙΞ ΔΙΑ ΤΩΝ ΑΥΛΑΚΩΝ ΤΟΥ Santorini and the osseocartilaginous junction

Frequency

United States

Malignant external otitis (MEO) is more common in humid and warm climates than in other climates.

Mortality/Morbidity ΣΥΜΕΤΟΧΗ ΣΥΖΥΓΙΩΝ : ΚΑΤΑ ΕΠΕΚΤΑΣΗ ΙΣΤΩΝ ΣΤΗ ΒΑΣΗ ΚΡΑΝΙΟΥ ‘Η ΜΕ ΨΕΥΔΟΜΟΝΑΔΙΚΗ ΝΕΥΡΟΤΟΞΙΝΗ – VII ΣΤΟ ΣΤΥΛΟΜΑΣΤΟΕΙΔΙΚΟ ΠΟΡΟ – ΚΑΤΟΠΙΝ + IX – X – XI STO SFAGITIDIKO PORO – XII STON ΥΠΟΓΛΩΣΣΙΟ ΠΟΡΟ – V + VI : ΣΕ ΕΠΕΚΤΑΣΗ ΣΤΟ ΛΙΘΟΕΙΔΕΣ – 1977, Chandler reported a 32% incidence of facial nerve paralysis – The incidence of facial nerve paralysis appears to have decreased with the development of more effective medical therapy as shown by Franco-Vidal et al who reported a 20% incidence of facial nerve paralysis in 46 treated patients – ΕΚΤΟΣ ΑΠΟ ΤΗΝ 7Η ΣΥΖΥΓΙΑ ΟΙ ΛΟΙΠΕΣ ΣΠΑΝΙΩΣ ΣΥΜΜΕΤΕΧΟΥΝ – Η ΑΝΑΡΡΩΣΗ ΤΗΣ VII ΕΙΝΑΙ ΠΤΩΧΗ κ ΑΠΡΟΒΛΕΠΤΗ ΕΝΩ ΟΙ ΛΟΠΙΕΣ ΣΥΖΥΓΙΕΣ ΑΝΑΡΩΝΟΥ ΤΑΧΥΤΕΡΑ

ΕΝΔΟΚΡΑΝΙΑΚΕ Σ ΕΠΙΠΛΟΚΕΣ : [ ΜΗΝΙΓΓΙΤΙΔΑ – ΑΠΟΣΤΗΜΑ – dural sinus thrombosis ] – ΝΕΥΡΟΠΑΘΕΙΕΣ ΜΕ ΤΕΚΜΗΡΙΩΜΕΝΗ ΣΥΜΜΕΤΧΟ ΤΟΥ ΣΦΑΓΙΤΙΔΙΚΟΥ ΠΟΡΟΥ ΘΕΤΟΥΝ ΠΡΟΣΟΧΗ ΓΙΑ ΕΝΔΕΧΟΜΕΝΟ : sigmoid sinus thrombosis – ΣΥΜΜΕΤΟΧΗ ΤΩΝ V , VI ΘΕΤΕΙ ΠΡΟΣΟΧΗ ΓΙΑ ΘΡΟΜΒΩΣΗ ΣΤΟΝ Cavernous sinus

ΕΧΟΝΤΑΣ ΥΠΟ ΟΨΙΝ ΟΤΙ Ο ΑΣΘΕΝΗΣ ΠΑΣΧΕΙ ΑΠΟ ΣΔ κ ΛΟΙΠΑ ΣΥΝΔΡΟΜΑ : Chandler found some deaths related to pneumonia, uremia, myocardial infarction, strokes, and liver failure. Franco-Vidal showed that patients with systemic immunodeficiencies had a worse prognosis.3

Sex

Malignant external otitis (MEO) is more common in males than in females.

Age

Malignant external otitis (MEO) has been reported in all age groups but is most common in patients who are elderly (age, >60 y).

Clinical

History

• Diabetes (90%) or immunosuppression (illness or treatment related)

• Severe, unrelenting, deep-seated otalgia

• Temporal headaches

• Purulent otorrhea

• Possibly dysphagia, hoarseness, and/or facial nerve dysfunction

Physical

• Inflammatory changes are observed in the external auditory canal and the periauricular soft tissue.

• The pain is out of proportion to the physical examination findings.

o Marked tenderness is present in the soft tissue between the mandible ramus and mastoid tip.

o Granulation tissue is present at the floor of the osseocartilaginous junction. This finding is virtually pathognomonic of malignant external otitis (MEO). Otoscopic examination may also reveal exposed bone.

• The cranial nerves (V-XII) should be examined.

• Mental status examination should be performed. Deterioration of the mental status may indicate intracranial complication.

• The tympanic membrane is usually intact.

• Fever is uncommon.

Causes

• Diabetes (90% of patients) o Diabetes is the most significant risk factor

for developing malignant external otitis (MEO).

o Small-vessel vasculopathy and immune dysfunction associated with diabetes are primarily responsible for this predisposition.

o The cerumen of patients with diabetes has a higher pH and reduced concentration of lysozyme, which may impair local antibacterial activity.

o No difference in predisposition is found between diabetes types I and II.

o The predisposition is not necessarily related to the severity of glucose intolerance or periods of hyperglycemia.

• Immunodeficiencies, such as lymphoproliferative disorders or medication-related immunosuppression

• AIDS o Malignant external otitis (MEO) associated

with AIDS may have a different pathophysiology than classic malignant external otitis (MEO).

o Patients present with similar symptoms but are generally younger and do not have diabetes.

o Granulation tissue may be absent in the external auditory canal.

o Pseudomonas is not necessarily the dominant causative organism.

o Patients with AIDS generally have a poorer outcome than patients with diabetes.

• Aural irrigation: As many as 50% of cases of malignant external otitis (MEO) have been reported to be preceded by traumatic aural irrigation in patients with diabetes.

Differential Diagnoses

Malignant Tumors of the Temporal Bone

Workup

Laboratory Studies ΛΕΥΚΑ κ.φ – ΧΩΡΙΣ ΑΡΙΣΤΕΡΑ ΣΤΡΟΦΗ – ESR 87 mm/h : ΥΠΟΣΤΡΕΦΕΤΑΙ ΣΤΗ 2Η ΕΒΔΟΜΑΔΑ ΕΠΙ ΑΓΩΓΗΣ ΑΛΛΑ ΣΕ ΜΗΝΕΣ ΕΠΑΝΕΡΧΕΤΑΙ ΣΤΟ ΦΥΣΙΟΛΟΓΙΚΟ – ΤΕΚΜΗΡΙΩΣΗ Σ ΔΙΑΒΗΤΗ ΟΡΟΛΟΓΙΚΗ κ ΕΛΕΓΧΟΣ ΤΥΧΟΝ ΑΠΟΡΥΘΜΙΣΗΣ – ΕΛΕΓΧΟΣ ΓΙΑ ΔΥΣΑΝΕΞΙΑ ΓΛΥΚΟΖΗΣ ΣΕ ΙΣΤΟΡΙΚΟ ΕΛΕΥΘΕΡΟ Σ ΔΙΑΒΗΤΗ – ΚΑΛΛΙΕΡΓΕΙΑ κ ΕΥΑΙΣΘΗΣΙΕΣ ΑΠΟ ΤΝ ΕΞΩ ΑΚΟΥΣΤΙΚΟ ΠΟΡΟ – ΑΝ ΕΙΝΑΙ ΔΥΝΑΤΟ ΠΡΙΝ ΤΗΝ ΕΝΑΡΞΗ ΑΝΤΙΜΙΚΡΟΒΙΑΚΗΣ ΑΓΩΓΗΣ – Paeruginosa (95%) : ΔΙΑΚΡΙΝΕΤΑΙ ΓΙΑ ΒΛΕΝΝΩΔΕΣ ΠΕΡΙΒΛΗΜΑ ΠΟΥ ΤΗΝ ΠΡΟΣΤΑΤΕΥΕΙ ΑΠΟ ΤΑ ΦΑΓΟΚΥΤΤΑΡΑ – Exotoxins (ie, exotoxin A, collagenase, elastase)ΠΟΥ ΠΡΟΚΑΛΟΥΝ ΙΣΤΙΚΗ ΝΕΚΡΩΣΗ κ ΜΕΡΙΚΑ ΕΙΔΗ ΠΑΡΑΓΟΥΝ ΝΕΥΡΟΤΟΞΙΝΗ ΥΠΕΥΘΥΝΗ ΓΙΑ ΤΗΝ ΠΡΟΣΒΟΛΗ ΤΩΝ ΣΥΖΥΓΙΩΝ – ΛΙΓΟΤΕΡΑ ΣΥΧΝΑ ΑΙΤΙΑ : [Aspergillus and Proteus species, Candida species, Staphylococcus aureus, and Staphylococcus epidermidis ]

Imaging Studies

• These are important adjuncts for determining the presence of osteomyelitis, the extent of disease, and response to therapy.

• Technetium Tc 99 methylene diphosphonate bone scanning is based on binding to osteoblasts.

o This scan depicts as little as a 10% increase in osteoblastic activity. However, this test is not specific since tumors or bony dysplasias, in addition to osteomyelitis, can cause osteoblastosis.

o It is useful in the initial evaluation because a positive finding in the correct clinical context can lead to confirmation of the diagnosis.

o The test is not useful for assessing the response to therapy since results remain persistently positive long after clinical improvement because of continuous bone remodeling and reformation.

o This test may also have limited usefulness for patients with a prior history of mastoiditis or otologic surgery.

o The application of single-photon emission computed tomography (SPECT) technology has improved the poor spatial resolution traditionally associated with this test.

• Gallium citrate Ga 67 scan is very sensitive but is not specific because gallium binds to actively dividing cells, including inflammatory cells, tumor cells, and osteoblasts.

o Uncertainty is possible regarding whether a positive test result represents an inflammatory condition, soft tissue, or bone disease.

o This test is most helpful when used as a monitor of successful treatment. Improvement of a positive test result correlates with therapeutic response.

o A baseline test is usually obtained at the initial diagnosis for comparison with follow-up studies during treatment.

o A quantitative comparison of the lesion to the nonlesion side may improve the interpretation of these studies for distinguishing acute external otitis from malignant external otitis (MEO) and for determining the efficacy of therapy.

o The application of SPECT technology has improved the poor spatial resolution traditionally associated with this test.

• Indium In 111–labeled leukocyte scan attempts to provide the same sensitivity as a gallium citrate Ga 67 scan but is more specific to an inflammatory process.

o It does not appear to provide an improvement in scintigraphic technique for helping to establish the diagnosis.

o It may be better than gallium citrate Ga 67 scans for assisting in establishing the correct timing of disease resolution.

o This test can be unreliable for imaging chronic osteomyelitis in other areas of the body. Thus, the accuracy of this application needs further study.

• CT scanning and MRI are both useful for evaluating the anatomic extent of soft tissue inflammation, abscess formation, and intracranial complications.

o CT scanning fails to diagnose early osteomyelitis because 30-50% of bone destruction is required to detect osteomyelitis by CT scanning.

o MRI provides poor bone resolution. o The soft tissue manifestations regress on

CT scanning and MRI with response to therapy.

o Bone changes remain persistently abnormal on CT scans for at least one year and are not well demonstrated by MRI studies. Thus, neither of the tests can be used to determine osteomyelitis resolution.

o Most authors advocate obtaining a CT scan with the initial evaluation for all patients, whereas Benecke advocates obtaining this test selectively for patients with cranial neuropathy, extensive bone changes on technetium scan, or poor clinical response to treatment. Grandis et al and Okpala et al support obtaining a CT scan early in the diagnostic/treatment algorithm. Peleg et al showed that there is a correlation between clinical course and the extent of anatomical areas involved as measured on initial CT scan findings.6

o MRI and CT scanning are equally sensitive in detecting the soft tissue extent of the disease, but MRI is more sensitive for detecting intracranial complications.

Procedures

• Obtain a biopsy of the external auditory canal to exclude carcinoma or other etiologies.

Histologic Findings

Nadol described the histopathology of 2 temporal bones affected by malignant external otitis (MEO). The infection did not spread through the pneumatized air tracts of the temporal bone. Rather, it spread along the vascular and fascial planes on exiting the temporal bone through the external auditory canal osseocartilaginous junction or fissures of Santorini. The otic capsule appeared to be resistant to the disease process. Linthicum described histopathologic findings in 5 temporal bones. Extensive destruction in the wall of the bony external auditory canal and osteomyelitic destruction of the wall of the fallopian canal in the descending portion of the facial nerve was seen. The infection spread beneath the otic capsule to erode the wall of the carotid canal and then extended into the central skull base.

Staging

• Levenson et al, Corey et al, Benecke, and Davis et al have proposed staging systems for malignant external otitis (MEO).7,8,9

o These staging systems are generally based on extent of soft tissue/bony involvement or development of neurologic complications.

o None of these staging systems has been widely adopted.

Treatment

Medical Care Treatment includes meticulous glucose control, aural toilet, systemic and ototopic antimicrobial therapy, and hyperbaric oxygen therapy.10

• Systemic antibiotic choice: Until the development of third-generation antipseudomonal cephalosporins, long-term intravenous antibiotics using an antipseudomonal penicillin and aminoglycoside were the mainstay of medical treatment.

o Several authors have demonstrated the effectiveness of intravenous ceftazidime monotherapy in the treatment of malignant external otitis (MEO).

o Fluoroquinolones that attain high soft tissue and bone levels with oral doses were then developed. Subsequently, several authors have demonstrated the efficacy of oral ciprofloxacin monotherapy.

o Although no established treatment guidelines are available, case series and anecdotal experience suggest that initial outpatient therapy with oral ciprofloxacin is efficacious for patients without a fluoroquinolone allergy, cranial neuropathy, or intracranial complication and who do not require hospital admission for diabetes or pain management.

o The widespread use of fluoroquinolones for upper respiratory infections and simpler ear infections is beginning to confound the typical clinical spectrum of malignant external otitis (MEO). Ciprofloxacin-resistant P aeruginosa has been increasingly isolated in patients with malignant external otitis (MEO), accounting for as many as 33% of isolates in patients who failed outpatient management in a study by Berenholz et al.11 Most notably in this patient population, 63% of isolates from 1998-2001 were resistant to ciprofloxacin, whereas only 15% of isolates were found to be resistant in the 10 years before this 3-year period. No increased morbidity or mortality was found in patients with ciprofloxacin-resistant Pseudomonas. Patients with resistant P aeruginosa require parenteral antibiotics with antipseudomonal beta-lactam antibiotics with or without an aminoglycoside.

• Duration of therapy

o Symptoms and examination findings improve with appropriate therapy, but these changes do not correlate with the length of needed therapy. Despite symptom relief, prolonged antimicrobial treatment as indicated for osteomyelitis is still indicated.

o Imaging studies are helpful in determining the adequate length of treatment for each patient.

o Treatment response should be evaluated with a gallium citrate Ga 67 scan every 4-6 weeks during treatment. Benecke recommended ending treatment 1 week after the gallium citrate Ga 67 scan findings return to normal and confirming this with a repeat scan 1 month after the treatment is stopped. Using this protocol for 13 patients, the average duration of treatment was 8.8 weeks with a range of 4-17 weeks.

• Hyperbaric oxygen therapy o This should be used only as an adjunct to

antimicrobial therapy; it should not be used alone.

o Hyperbaric oxygen therapy may be helpful for patients with complications, experiencing a poor response to therapy, or with recurrent cases.

Surgical Care

• Chandler advocated surgery in his original report when appropriate antimicrobials were not available; he had very poor results, with a 50% mortality rate.

• Surgical removal of the lesion requires resection of large portions of the temporal bone.

• Because of the histopathology of malignant external otitis (MEO), removal of contiguous areas of bone may not be sufficient because of the spread of infection through vascular and fascial planes.

• Surgery is now reserved for local debridement, removal of bony sequestrum, or abscess drainage.

• Facial nerve decompression is not indicated for patients with facial paralysis.

Consultations ΔΙΑΒΗΤΟΛΟΓΟΣ – ΛΟΙΜΩΞΙΟΛΟΓΟΣ ΓΙΑ ΤΗΝ ΕΠΙΛΟΓΗ ΑΝΤΙΜΙΚΡΟΒΙΑΚΟΥ ΣΕ ΕΠΙΠΛΕΓΜΕΝΑ ΠΕΡΙΣΤΑΤΙΚΑ

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Antibiotics

ΕΞΑΤΟΜΙΚΕΥΕΤΑΙ ΕΑΝ ΘΑ ΧΟΡΗΓΗΘΕΙ ΑΠΟ ΤΟ ΣΤΟΜΑ ‘Η ΕΝΔΟΦΛΕΒΙΩΣ ΤΟ ΑΝΤΙΜΙΚΡΟΒΙΑΚΟ

Ciprofloxacin (Cipro)

A DNA gyrase inhibitor that prevents DNA replication.

Adult

1500-2250 mg/d PO/IV divided bid/tid

Precautions

ΑΝΤΕΝΔΕΙΞΗ ΣΕ ΙΣΤΟΡΙΚΟ ΕΠΙΛΗΨΙΩΝ – ΣΕ ΠΑΡΑΤΕΤΑΜΕΝΗ ΑΓΩΓΗ : [ ΕΛΕΓΧΟΣ ΤΑΚΤΙΚΟΣ ΝΕΦΡΙΚΟΣ – ΗΠΑΤΙΚΟΣ – ΑΙΜΑΤΟΛΟΓΙΚΟΣ ] – ΤΡΟΠΟΠΟΙΗΣΗ ΔΟΣΗΣ ΣΕ ΝΑ – ΚΙΝΔΥΝΟΣ ΥΠΕΡΛΟΙΜΩΞΕΩΝ – ΝΑ ΑΠΟΦΕΥΓΟΝΤΑΙ ΑΦΥΔΑΤΩΣΗ κ’ ΑΛΚΑΛΟΠΟΙΗΣΗ ΟΥΡΩΝ

Ceftazidime (Fortaz, Tazicef, Tazidime)

Third-generation cephalosporin that inhibits bacterial cell wall synthesis by adhering to penicillin-binding proteins. Can be either bactericidal or bacteriostatic depending on the organism, tissue penetration, and drug dosage.

Adult

1-2 g IV q8h

Precautions

ΠΡΟΣΟΧΗ ΣΕ ΝΑ

Ticarcillin/clavulanate (Timentin)

Extended-spectrum penicillin/beta-lactamase inhibitor. Ticarcillin binds to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. Clavulanate binds irreversibly to beta-lactamases, thus preventing inactivation of ticarcillin.

Adult

3.1 g IV q6h

Precautions

ΠΡΟΣΟΧΗ ΣΕΝΑ – ΑΣΘΕΝΕΙΣ ΥΠΟ ΔΙΑΙΤΑ ΧΑΜΗΛΗ ΣΕ ΝΑΤΡΙΟ

Gentamicin (Garamycin, Jenamicin)

Binds to 30S ribosomal subunit, thus inhibiting bacterial protein synthesis. Aminoglycosides have bactericidal activity against P aeruginosa. Bacterial strains resistant to one aminoglycoside still may be sensitive to other antibiotics within this category.

Adult

3-5 mg/kg/d IV in equally divided doses q8h or 5-7 mg/kg/d IV administered qd; dose is adjusted based on serum drug levels

Follow-up

Prognosis ΕΠΑΝΕΜΦΑΝΙΣΗ : 9-27%- ΣΥΝΗΘΩΣ ΣΕ ΒΡΑΧΥΧΡΟΝΗ ΘΕΡΑΠΕΙΑ – Η ΕΠΑΝΕΦΦΑΝΙΣΗ ΔΕΝ ΣΥΝΙΣΤΑΤΑΙ ΣΕ ΩΤΟΡΟΙΑ ΑΛΛΑ ΣΕ : [ ΔΙΑΛΕΙΠΟΥΣΑ ΚΕΦΑΛΑΓΙΑ – ΩΤΑΛΓΙΑ ] – ΑΥΞΑΝΕΤΑΙ ΠΑΛΙ Ο ESR – ΔΕΝ ΠΡΕΠΕΙ ΝΑ ΘΕΩΡΗΘΕΙ ΜΕΧΡΙ ΤΟ ΠΕΡΑΣ ΕΝΟΣ ΕΤΟΥΣ ΤΟΥΛΑΧΙΣΤΟ, ΕΧΕΙ ΑΝΑΦΕΡΘΕΙ ΕΠΑΝΑΛΟΙΜΩΞΗ ΜΕΧΡΙ κ 1 ΕΤΟΣ ΜΕΤΑ – Chandler reported a mortality rate of 50% in the original series

o The mortality rate has decreased to 20% with the introduction of appropriate antibiotics, improved imaging modalities, and increased awareness of the disease.

o Most current studies report a mortality rate of less than 10%, but mortality remains high for patients with cranial neuropathies (other than VII), intracranial complications, or with irreversible systemic immunosuppression.

Miscellaneous

Medicolegal Pitfalls

• Failure to exclude a malignant neoplastic process

• Delays in diagnosis

Special Concerns

ΒΡΕΦΗ κ ΠΑΙΔΕΣ ΕΩΣ 15 ΕΤΩΝ

In 1988, Rubin et al reported : [ ΚΕΩ ΣΕ ΠΑΙΔΕΣ 15 ΕΤΩΝ – ΧΩΡΙΣ ΣΔ – ΣΥΜΜΕΤΟΧΗ VII – ΤΟ ΜΑΣΤΟΕΙΔΕΣ ΑΚΟΜΗ ΝΑΠΤΥΣΣΕΤΑΙ – ΤΑ ΤΡΗΜΑΤΑ ΤΟΥ Santorini ΕΧΟΥΝ ΠΛΕΟΝ ΚΕΝΤΡΙΚΗ ΕΝΤΟΠΙΣΗ – ΣΥΜΜΕΤΟΧΗ ΤΟΥ ΤΥΜΠΑΝΙΚΟΥ ΥΜΕΝΑ ΗΤΑΝ ΣΥΧΝΟΤΕΡΗ ΑΠ ΟΤΙ ΣΕ ΕΝΗΛΙΚΟΥΣ – ΒΑΚΤΗΡΙΑΙΜΙΑ ΣΥΧΝΟΤΕΡΗ ΑΠ ΟΤΙ ΣΕ ΕΝΗΛΙΚΟΥΣ – ΣΥΝΗΘΩΣ ΧΩΡΙΣ ΕΠΙ ΜΑΚΡΟΝ ΝΟΣΗΡΟΤΗΤΑ

ΟΙ ΚΙΝΟΛΟΝΕΣ ΔΕΝ ΕΧΟΥΝ ΕΝΔΕΙΞΗ ΑΠΟ ΤΟΝ FDA ΣΤΟΝ ΠΑΙΔΙΑΤΡΙΚΟ ΠΛΗΘΥΣΜΟ ΜΕ ΕΞΑΙΡΕΣΗ ΤΗΝ ΚΥΣΤΙΚΗ ΙΝΩΣΗ – ΩΣΤΟΣΟ ΧΡΗΣΙΜΟΠΟΙΗΘΗΚΑΝ ΣΤΗΝ ΚΕΩ ΜΕ ΑΣΦΑΛΕΙΑ κ ΕΠΙΤΥΧΙΑ

ΕΝΟΧΟΠΟΙΕΙΤΑΙ Η ΛΑΘΟΣ ΔΙΑΧΕΙΡΗΣΗ ΩΣ ΑΠΛΗΣ ΕΞΩΤΕΡΙΚΗΣ ΩΤΙΤΙΔΑΣ ΑΠΟ ΟΙΚΟΓΕΝΕΙΑΚΟΥΣ ΙΑΤΡΟΥΣ – Η ΒΡΑΧΕΙΧΡΟΝΙΑ ΘΕΡΑΠΕΙΑ -