Asocierea dintre otita externă malignă și diabetul zaharat

Introduction

Malignant or necrotizing external otitis (MEO) is an aggressive type of infection originating in the external acoustic canal, most frequently seen in diabetic patients, characterized by extensive skin inflammation, with a tendency to develop osteomyelitis. The term malignant does not refer to the development of cancer, but to the rapid spread of the inflammation to healthy tissues^(1-3).

MEO progresses from the external auditory meatus, and it may affect the mastoid bone, the skull base, the cranial nerves, and spread intracranially^(2,4). The progression of MEO has been divided into three clinical stages. Stage I is characterized by the presence of the infection at the level of the external auditory meatus and adjacent soft tissues, with intense pain, with or without facial nerve damage. Stage II is characterized by the extension of infection with osteitis of the skull base and temporal bone or multiple cranial nerve damages, and stage III implies intracranial extension with meningitis, epidural and subdural empyema, or brain abscess⁽⁵⁾.

The association between malignant external otitis and diabetes mellitus was well established by numerous studies. Franco-Vidal et al. published in 2007 a retrospective study reviewing a series of 46 patients with necrotizing external otitis: 30 patients (65.2%) had diabetes⁽⁶⁾. A retrospective study reviewing a series of 19 patients with MEO highlighted the fact that 14 patients (respectively, 82.3%) had diabetes⁽⁷⁾. Arsovic et al. evaluated a total of 30 patients diagnosed with MEO, and found diabetes mellitus in 76% of the subjects, which was their most common comorbidity⁽¹⁾.

This review summarizes information on the association between malignant external otitis and diabetes.

MEO and diabetes

The affliction occurs in most situations in elderly patients with diabetes mellitus or other diseases resulting in immunodeficiency. The most common causative pathogen is Pseudomonas aeruginosa. Proteus species, Staphylococcus epidermis and Klebsiella have also been isolated in cultures. Aspergillus fumigates and Candida are commonly associated fungi^(1,3). Diabetes mellitus increases the susceptibility to develop infections. The pathogenic mechanism involved can be represented by: hyperglycemia, low production of anti-inflammatory interleukins in response to infection, impaired chemotaxis and phagocytic activity, immobilization of polymorphonuclear leukocytes, increased virulence of pathogens⁽⁸⁾. In addition, infectious diseases may result in metabolic complications such as microangiopathy and neuropathy. The mechanism of tissue damage involves coagulation tissue necrosis generated by the microangiopathy of the small vessels⁽¹⁾.

Diagnosis and management of MEO

The diagnosis of malignant external otitis is based on the clinical evaluation and confirmed by laboratory tests and imaging techniques.

Clinical evaluation

The most common clinical manifestations include severe otalgia persisting for more than one month, chronic otorrhea, hearing impairment and possible cranial nerve involvement (VII most commonly affected, IX, X, XI, XII). The infection originates at the osseous-cartilaginous junction of the external acoustic canal, usually sparing the eardrum. Otoscopic changes include edema of the external ear canal with granulation tissue at the osseous-cartilaginous junction, and rarely only edema and aural polyps^(1-3,5,9).

There is still a heterogeneity in diagnostic criteria of malignant external otitis. In1987, Cohen and Friedman described a set of diagnostic criteria that were divided into two categories: obligatory (pain, edema, granulation, microabscess, possibly Pseudomonas in culture, positive bone scan or failure of local therapy after more than a week) and occasional (cranial nerve involved, pathological radiography, debilitating condition and old age)⁽¹⁰⁾. Lee et al. included Pseudomonas infection and diabetes mellitus as occasional signs, and considered that the presence of occasional criteria alone did not establish the diagnosis of MEO⁽⁴⁾.

The infection extends through the vertical fissures of Santorini to the infratemporal fossa, and may involve the stylomastoid foramen or the mastoid process, which generates facial nerve palsy. The infection may spread to the jugular foramen, generating jugular vein thrombosis, and it also may involve cranial nerves IX, X and XI. Cranial nerves V and VI may be affected if the inflammatory process includes the petrous apex. The extension through the petro-occipital fissure generates intracranial complications as subperiosteal abscess or epidural or subdural empyema⁽²⁾.

Laboratory tests

Mandatory laboratory test are blood inflammatory markers such as white blood cell count, erythrocyte sedimentation rate and C-reactive protein⁽⁴⁾. Diabetes tests include blood glucose levels and glycated hemoglobin (HbA1c). Fasting plasma glucose and glucose tolerance tests are to be done after the reduction of the inflammation. Monitoring of the renal and hepatic function is also mandatory. Before the initiation of antibiotic therapy, cultures of ear secretions should be obtained to assess the pathogen and its resistance to treatment. A biopsy of the granulation tissue should be performed for differential diagnosis from malignant external otitis and tumor which may present as nonresponding inflammatory disease⁽³⁾.

Imaging techniques

Imaging used in the diagnosis and management of MEO include: computed tomography (CT), contrast-enhanced magnetic resonance imaging (MRI), technetium Tc-99m medronate methylene diphosphonate bone scanning and gallium citrate Ga-67 scintigraphy⁽¹¹⁾. CT and MRI evaluate the extent of the disease to bone and soft tissue – respectively, identifying cortical bone erosions, osteomyelitis, and also evaluating the intracranial spread of the infection. Tc-99m bone scanning is a radio-labeled scan based on the capability of the isotope to bind to osteoblasts, highlighting elevated osteoblastic activity, characteristic to osteomyelitis. It is highly sensitive for the diagnostic, but it is unsuitable for follow-up, because it remains positive after clinical resolution. Ga-67 binds to reticular endothelial cells and macrophages, and locates the inflammatory focus sites. Single-proton emission computed tomography bone scan with Ga-67 evaluates the response to treatment and possible recurrence⁽³⁾.

In 2023, Kim et al. published a systematic review and meta-analysis about the predictive value of radiologic studies about MEO. The authors analyzed 37 studies, confirming the high sensitivity of Tc-99m and Ga-67 for diagnosing malignant external otitis. The CT interpretation should be done with caution, because this finding alone does not confirm MEO, even though the exact location of the disease can be accurately evaluated on the CT scan. The MRI, which has a higher sensitivity for soft tissue involvement, reveals early medullary bone and dural spread of the disease⁽¹²⁾.

It is very important to diagnose the disease in the early stages. The factors related to the prognosis of MEO in diabetic patients are the duration of diabetes, the degree of glycemic control and hypoglycemic therapy. Lee et al. performed a retrospective study to identify the prognostic factors of malignant external otitis. The duration of diabetes, the presence of inflammatory markers and the responsiveness to antidiabetic therapy influenced the prognosis of disease. The data do not show significant differences in prognosis between patients treated with oral glucose-lowering therapy and those treated with insulin⁽⁴⁾. Kaya et al. published in 2018 a study that included 25 patients diagnosed with MEO. The duration of hospitalization and the HbA1c levels were retrospectively assessed. The results revealed that the mean hospitalization time was significantly longer in patient with HbA1c levels >6%⁽¹³⁾.

Treatment

The treatment of malignant external otitis includes topical and systemic antibiotics and antifungals, glycemic control and, in selected cases, surgical treatment. The selected patients may benefit from hyperbaric oxygen therapy. Despite an aggressive management, MEO remains a severe infection with significant morbidity and mortality⁽¹⁴⁾.

Antidiabetic medication

In hospitalized diabetic patients with malignant external otitis, insulin therapy is recommended. Basal, prandial and insulin correction regimen is recommended for hospitalized patients with sufficient nutritional intake, and basal insulin or basal plus bolus insulin correction for patients with inadequate oral intake. For critically hospitalized patients, continuous intravenous insulin infusion is the best option⁽¹⁵⁾. Continuation of oral antidiabetic medication is applied in some hospitalized patients alone or in combination with basal insulin and in stable patients who are adequately controlled and are able to eat^(3,16).

Drug therapy

Antibiotics have proven to be the gold standard in the treatment of malignant external otitis. Antibiotics effective against Pseudomonas aeruginosa include aminoglycosides, penicillins, piperacillin-tazobactum, ceftazidime, cefepime and imipenem^(5,7). Depending on bacterial sensitivity, a combination of antibiotics may be needed. The average duration of antibiotic administration is 15 weeks, and it can vary from 4 to 59 weeks⁽³⁾. The treatment duration must be individualized, and timing for cessation needs to take into account the clinical presentation (normalization of nocturnal ear pain, physical findings), the normalization of blood tests and imaging studies. Antifungal therapy is used in fungal and mixed infections. Variconazole, amphotericin B and itraconazol are treatment options for fungal malignant external otitis⁽¹³⁾. Analgesics are important in the treatment of malignant external otitis, but they should be administered only for a few days, since regression of the pain is an indicator of infection resolution⁽³⁾.

Surgical treatment

The main indications for surgery are the nonresponsiveness to conservative treatment, the long-term antibiotic use, and advanced disease. Resistant or undiagnosed bacteria in cultures are a relative indication for surgical intervention to obtain deep tissue samples for cultures. Facial palsy is a relative surgical indication, as it may indicate an extensive MEO. As diabetic microangiopathy secondary to prolonged diabetes may prevent sufficient antibiotic concentration to the infected tissue, the local debridement of the necrotic tissue reduces topical infective load, facilitates tissue formation with better vascularization, but can generate disease progression through fascial and vascular structures^(3,17). Surgical operations are represented by local debridement of the external ear canal under general anesthesia and tympanomastoid surgery (canal wall down mastoidectomy, canal wall up mastoidectomy and mastoidectomy with facial nerve decompression) and petrosectomy⁽¹⁷⁾.

Hyperbaric oxygen therapy

Hyperbaric oxygen therapy (HBOT) may be a treatment option for refractory or advanced malignant external otitis, where antibiotic or surgical treatment fail to cure MEO. Patients with diabetes present factors which lead to tissue hypoperfusion, hypoxia and, also, poor white blood cell chemotaxis and microangiopathy. HBOT is considered to ameliorate partial oxygen pressure on the site of infection and improve oxygen-mediated leucocyte function. Byun et al. proceeded a systematic review of the HBOT in malignant otitis externa⁽¹⁷⁾. Although heterogenous, a high cure rate was observed, even though the patients were at an advanced disease stage. However, the efficacy of HBOT remains unproven due to lack of studies with high levels of evidence⁽¹⁴⁾.

Conclusions

Malignant external otitis is an aggressive type of external otitis characterized by extensive inflammation and osteomyelitis. The affliction occurs in most situations in elderly patients with diabetes mellitus. MEO requires urgent diagnosis and treatment. The diagnosis of malignant external otitis is based on the clinical evaluation and confirmed by laboratory tests and imaging techniques. The management of the condition uses drug therapy (topical and systemic antibiotics and antifungal medication) and, in selected cases, surgical treatment. Despite an aggressive management, malignant external otitis remains a severe infection with significant morbidity and mortality.  

CONFLICT DE INTERESE: niciunul declarat.

SUPORT FINANCIAR: niciunul declarat.

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