Granulomatous Diseases of the Middle Ear

Granulomatous diseases comprise a small but important subset of diverse ear problems. By definition, a granuloma is a nodular inflammatory lesion. They are usually small and consist primarily of compact mononuclear phagocytes. Granulomas are different from other inflammatory reactions; they represent an ultimately unsuccessful localized attempt to rid the host of an offending organism or process. Granulomatous diseases in the middle ear may be localized primarily to the ear and surrounding tissues, or they may be a manifestation of a body-wide disseminated problem.

Granulomatous reactions may mimic other, far more common middle ear diseases. The common presentation of a draining ear is nearly indistinguishable from that of common otitis media. A high index of suspicion and knowledge about possible causes are required for accurate diagnosis and effective treatment.

Histology of eosinophilic granuloma.

Description

Rates of infection with Mycobacterium tuberculosis have dramatically decreased over the last century, although pockets of resurgence exist. Tuberculosis of the middle ear is a rare disease and accounts for between 0.04-0.9% of all cases of chronic suppurative otitis media. It is difficult to diagnose because the disease presents like other chronic suppurative otitis media. The significant features of aural tuberculosis are abundant granulation tissue in mastoids with good pneumatization, cervical lymphadenopathy, profound hearing loss, facial palsy, and foci of tuberculosis elsewhere.[1, 2]

Tuberculosis is usually due to M tuberculosis, but atypical mycobacteria can cause a wide variety of infections. Atypical mycobacteria belong to the same family of mycobacterial organisms as M tuberculosis but include other species such as M kansaii,M Chelonea, M fortuitum, M avium, and M intracellularea.

Concomitant pulmonary involvement is nearly always present, but isolated middle ear involvement has been reported. Inoculation is thought to occur by means of direct transmission through the eustachian tube, but aerosol contact with the tympanic membrane may be the mode of spread in rare cases. It can be transported through the blood stream from distant infected site in the form of disseminated tuberculous infection. The presence of a perforation or myringotomy increases the risk of inoculation. Very rarely infection may be acquired in early life from maternal systemic tuberculosis or as an infant passes through the birth canal of a mother with genitourinary tuberculosis.

Diagnosis

The classic triad of symptoms in tuberculous otitis media is known as a painless otorrhea, multiple small perforations of the tympanic membrane, and peripheral facial nerve palsy.

The diagnosis of middle ear tuberculosis may be delayed because of its similarity to other forms of otitis media in the early stages. A thickened tympanic membrane and exudate are the first manifestations. Later, the typical multiple perforations, along with an exuberant polypoid reaction and bony sequestration, may occur. Otitis media with early involvement of vestibular, auditory, or facial nerve function is highly suggestive of middle ear tuberculosis.

A search for pulmonary involvement always should be undertaken if tuberculosis is suspected. Chest radiographs are normal in 42-58% of these patients. High resolution CT scans of the temporal bone may demonstrate destruction of the ossicular chain, sclerosis of the mastoid cortex, and opacification of the middle ear and mastoid air cells. Presence of nontender cervical adenopathy should raise the index of suspicion. Accurate diagnosis depends on the results of skin testing, demonstration of acid-fast bacilli in histologic preparations, and culture results.

Bony sequestrum has been reported in about 10% of cases. Complications include facial palsy (20%), subperiosteal abscess, fistula formation, and labyrinthitis.[1]

Treatment

Treatment consists of standard systemic antituberculosis chemotherapy. Duration of antituberculosis medication is recommended at least 6 months by most authors. Antituberculosis drugs have provided good results in most patients and surgery is performed to remove bony sequestra, to treat complications, or to begin middle ear exploration. In the United States, reporting these cases to the Centers for Disease Control and Prevention (CDC) is mandatory.

Description

The first clinical and histopathologic description of this disease was given by Friedrich Wegener in 1936 and 1939. Wegener granulomatosis is an autoimmune, granulomatous, necrotizing vasculitis. Like tuberculosis, it rarely is isolated to the middle ear; it usually has systemic manifestations, especially pulmonary and renal manifestations.

Diagnosis

The exact etiology of Wegener granulomatosis is unknown and many authors believe that the disease is immunologically mediated. Middle ear involvement is seen in approximately 40-70% of cases. Presentation in the ear is nonspecific. Serous exudates and otalgia are common. The presence of accompanying sinonasal disease is nearly universal. Middle ear effusion probably occurs as a result of eustachian tube obstruction form luminal granulomata or from nasopharyngeal inflammation and ulceration.

Multiple tympanic membrane perforations may be present, and these may coalesce into a large single perforation. Patients with chronic suppurative otitis media secondary to Wegener granulomatosis present with severe post aural pain, deafness and otorrhea.[3] Hearing loss is the conductive type and is due to thickened, scarred, and an often perforated ear drum.

The middle ear and mastoid may also be primarily affected by granulomatous inflammation and destruction, manifesting as chronic suppurative otitis media in 24% of patients with Wegener granulomatosis. Wegener granulomatosis is differentiated from tuberculosis by both the presence of necrotizing vasculitis in histologic preparations and characteristic systemic manifestations. Other histologic features include micro abscesses and scattered multinucleated giant cells in a highly inflammatory background. Serum antibodies to neutrophil cytoplasmic antigens (ANCAs) may be present, and the erythrocyte sedimentation rate is nearly always elevated.

Wegener granulomatosis has a destructive effect on the temporal bone, and patients with Wegener granulomatosis of the temporal bone with necrotizing granulation tissue filling the tympanic cavity have been documented. Cranial nerve palsies and meningitis has been reported as complications.

Treatment

Approximately 30% of patients with Wegener granulomatosis requires tympanostomy tube placement at some point. Treatment consists of the administration of systemic corticosteroids and chemotherapeutic agents such as cyclophosphamide.[4] Remission rates are as high as 75%, but relapses are common.[5] Mastoidectomy for chronic suppurative otitis media is reserved for the minority of patients who are refractory to medical therapy. Most authors do not recommend mastoidectomy as the primary treatment in these patients.

Langerhans cell histiocytosis was previously known as histiocytosis X. It is characterized by the proliferation of histiocytes that share the characteristics of Langerhans cells. These cells have inclusion bodies (Birbeck granules) in the cytoplasm.

Three related diseases make up histiocytosis X: eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease. Although the diseases share the common finding of histiocytic granulomas, they have markedly different clinical courses. Findings of histologic structure studies show that the Langerhans cell line proliferates and predominates.

A literature review by Chen et al found that out of 631 patients with Langerhans cell histiocytosis, 246 (39%) presented with otologic symptoms. Among the otologic cases, 52% had the multisystem form of Langerhans cell histiocytosis, and otorrhea was the most common otologic presenting symptom (46%).[6]

Eosinophilic Granuloma

Description

The term eosinophilic granuloma refers to osseous disease alone and may be unifocal or multifocal. Manifesting as solitary osteolytic granulomas, these lesions may occur in almost any bone in the body, including the temporal bone. Temporal bone lesions may present as a draining, perforated eardrum that fails to respond to normal treatment. As such, it is often misdiagnosed as an infectious process, potentially leading to treatment delays. A slight male preponderance exists, and the disease occurs primarily in children and young adults.

Diagnosis

Radiologic studies, CT scan, or plain films depict the typical punched-out lytic bone lesion and should be considered when recalcitrant, nonresponding otorrhea exists. Biopsy offers a definitive diagnosis.

A retrospective study by Abdel-Azziz et al indicated that eosinophilic granuloma of the temporal bone can mimic chronic suppurative otitis media but can be diagnosed with histopathologic examination and CT scanning. The study involved 12 children with eosinophilic granuloma of the temporal bone, with presenting symptoms that included external ear canal mass (83.3% of patients), postauricular swelling (66.7% of patients), and persistent otorrhea (33.3% of patients). Histopathologic examination revealed eosinophils and Langerhans cells, with CD1-antigen and S-100-protein immunoreactivity present, while CT scanning revealed osteolytic lesions with nonsclerotic margins, that were filled with mastoid bone-associated soft tissue masses.[7]

Treatment

Direct surgical extirpation or curettage is the preferred method of treatment. Low-dose irradiation may also be used as an adjuvant in selected cases. A radiologic search should be made for other skeletal lesions

Hand-Schüller-Christian Disease

Description

This more aggressive subset involves multifocal eosinophilic granulomas that may spread beyond the skeleton to involve the skin and lymphatics. Occurring primarily in pre–school-aged children, it may present as a solitary lesion (see above) but manifests multiple lesions in a few months.

Diagnosis

Initial presenting symptoms are nonspecific and similar to those of viral upper respiratory tract infection (URI). They may include fever, lassitude, adenopathy, otitis media, and splenomegaly. Twenty-five percent of patients exhibit the triad of multiple lytic skull lesions, exophthalmos, and diabetes insipidus due to pituitary involvement. The chest radiograph may show hilar adenopathy.

Treatment

Low-dose chemotherapy is used to control symptoms. A cure is unlikely, but spontaneous regression may occur.

Letterer-Siwe disease

This disease is a disseminated form of Langerhans cell histiocytosis that occurs in very young children. It is fulminating and often fatal. If the lesion is in the temporal bone, draining otitis media is the most common presentation. The actual nature of the disease is indicated by lytic lesions, as seen on radiographs. Treatment is chemotherapy and curettage. Low-dose irradiation is reserved for difficult-to-reach areas.

In patients with Langerhans cell histiocytosis, unifocal disease has good prognosis and responds well to local treatment. Multifocal disease also responds well to the treatment. Disseminated disease has a bad prognosis. Temporal bone involvement is multifocal form of disease, and it should be treated with multidisciplinary approach (radiotherapy, chemotherapy, and steroid therapy).[8] Because of high risk of complications, only conservative surgery is recommended for temporal bone lesions.

Description

Sarcoidosis is a systemic and chronic disease with a characteristic histologic finding of noncaseating granuloma. Although it usually affects the lungs, the middle ear may be involved. Sarcoidosis is 10 times more prevalent in blacks than in persons of other races, and it affects females more often than males. Two types of presentations occur: acute and chronic. Acute sarcoidosis develops rapidly and may spontaneously resolve, while the chronic form is the more damaging type, leading to irreparable fibrosis of the pulmonary system.

Diagnosis

Otolaryngologic manifestations of sarcoidosis occur in 10-15% patients and, rarely, may be the presenting disorder. Sarcoidosis may affect the pinna and external auditory canal, as well as the middle ear. Middle ear involvement is typically secondary to eustachian tube obstruction from nasopharyngeal involvement. Granulomas of the middle ear may cause conductive hearing loss due to ossicular erosion and mass effect, but these findings alone are nonspecific. The definitive diagnosis is usually made with chest radiographs; hilar adenopathy is the dominant finding. A chronic cough often leads to chest radiographs being ordered. Other findings include iridocyclitis, keratoconjuctivitis, hepatosplenomegaly myalgias, arthralgias, and lymphadenopathy.

Heerfordt syndrome (uveoparotid fever, parotitis, and cranial nerve palsies, especially facial) is seen in patients with sarcoidosis.

Treatment

Corticosteroids are useful in controlling the systemic manifestations.

Description

Syphilis is a sexually transmitted disease caused by the bacteria, Treponema pallidum. The initial lesions are located on or around the genitalia, but if untreated (latent), dissemination may occur (tertiary syphilis). An infected mother may transmit the disease to her child (congenital).

Diagnosis

Infection with T pallidum, congenital or acquired, may manifest as middle ear disease. Early findings include a reddened mucosa and periosteum of the ossicles due to leukocytic infiltration. As larger lesions (gummas) form, infection may present as a perforated tympanic membrane, with drainage and granulomatous changes in the middle ear mucosa.

If gummas invade the inner ear, sensorineural hearing loss and dizziness may occur. Middle ear involvement with fibrosis between the incus and malleus has been reported; thus a conductive component to hearing loss does not exclude a treponemal cause. Insufflating the ear may cause nystagmus, which mimics a fistula (Hennebert sign). This is due to fibrosis between the stapes foot plate and membranous labyrinth.

Syphilitic infection is differentiated from tuberculous infection by means of serologic testing for T pallidum and histologic evaluation for acid-fast bacilli.

Treatment

Intensive antibiotic therapy, coupled with corticosteroids, is effective at eradicating the infection. However, gummatous lesions and their sequelae may persist.

Description

Lyme disease is caused by a tick-borne spirochete, Borrelia burgdorferi. It is transmitted to humans by the bite of Ixodes ricinus ticks. After the initial tick bite, a characteristic skin lesion, erythema migrans, occurs in most cases. A viruslike illness occurs as the bacteria spread throughout the body hematogenously. This spread may occur over a few days or a few weeks and may cause headache, fever, migratory arthralgia, adenopathy, and circular red skin lesions, which sometimes are present on the pinna. The last phase involves focal lesions in the joints, heart, or nervous system. The primary otologic manifestation is temporary facial nerve paralysis that is not responsive to steroids. Paralysis is bilateral in as many as 25% of all cases.

Diagnosis

The diagnosis is usually based on a history of a tick bite and the characteristic skin lesion, especially in people from endemic areas. Later diagnosis is based on the recognizable symptom complex and the annular rash. Serologic testing can confirm the diagnosis, although seroconversion can take up to 6-8 weeks.

Treatment

Treatment is the administration of tetracycline. If tetracycline is contraindicated (eg, pregnant patients, patients < 12 y), erythromycin, amoxicillin, imipenem, or ceftriaxone may be used.

Description

Fungal growths may often be found in otherwise healthy ears as opportunistic colonies growing on accumulated cerumen or keratinous debris. These are harmless and require only local cleaning. However, immunocompromised individuals may have aggressive invasive fungal infections in various regions of the body, including the temporal bone.

Among the fungi, the species of Aspergillus are considered the predominant organisms implicated in the etiology of otomycosis in tropical countries. Many studies have shown that Aspergillus species was the commonly isolated fungus and Candida was next commonly isolated fungi, in immunocompetent hosts. Studies by Kishore et al[9] and Viswanatha[10] have shown that Candida species was mainly responsible for otomycosis in immunocompromised hosts.

Infection with Candida can be more difficult to detect clinically because of its lack of characteristic appearance like Aspergillus and can present as otorrhea not responding to aural antimicrobials. Otomycosis attributed to Candida is often identified by cultural data.[11]

General cellular immunity is reduced in situations such as diabetes, steroid administration, HIV infection, chemotherapy and malignancy (especially those involving cells of immune system).This makes an immunocompromised host susceptible to fungal infections. Normal bacterial flora is one of the host defense mechanism against fungal infections. This mechanism is altered in patient patients using antibiotics ear drops and cause otomycosis.

Clinical studies have shown that otological procedures, particularly those that result in mastoid cavity, as a potential risk factor for otomycosis. The factors that predisposes to otomycosis in the previously operated ears are as follows:

• Recurrent drainage, antibiotic/antifungal applications: This may alter the local environment of the external ear canal and allow super infection by nosocomial fungi.

• Alteration in the anatomy by canal wall down procedures may also produce changes in the cerumen production or relative humidity that favor fungal growth.[11]

This occurs frequently in immunocompromised patients, and treatment should be vigorous to prevent complications like hearing loss and invasive temporal bone infection.

Tympanic membrane perforation also may occur as a complication of otomycosis that starts in an ear with an intact ear drum. The mechanism of perforation has been attributed to mycotic thrombosis of the tympanic membrane blood vessels resulting in avascular necrosis of tympanic membrane.

Tympanic membrane perforation is seen more commonly in immunocompromised patients than in immunocompetent patients.[10]

Diagnosis

The presence of hyphae in an immunocompromised individual should alert the examiner to the possibility of a systemic problem. Potassium hydroxide (KOH) preparations may be helpful in identifying the offending organism.

Treatment

Treatment consists of management of the underlying problem and aggressive local debridement. Topical and systemic antifungals are used as needed.

Bassouni et al studied the effects of antifungal agents and found that clotrimazole was the most effective antifungal agent in the treatment of otomycosis. According to Stern et al and Jackman et al, clotrimazole is the most effective antifungal agent.[12, 13]

Rarely, fungi can cause invasive otitis externa, especially in immunocompromised patients. Aggressive systemic antifungal therapy is required in these patients and often high mortality in these conditions.

Oral and intravenous preparations of antifungal agents are available for severe infections in immunocompromised patients.[14] Oral antifungal are unlikely to succeed in the absence of adequate local care.[11] These antifungal agents should be given for 3-4 weeks depending on the patient’s condition.

Fungal infections of the mastoid cavity of the immunocompromised patients who have undergone canal wall down mastoidectomy are seen quite frequently and they require prolonged treatment with antifungal ear drops and oral antifungal drugs. The recommended treatment for patients suffering from fungal otomastoiditis includes surgical debridement and systemic antifungal therapy with amphotericin B being the gold standard.[15]