Lyme Disease: A Review for the Otolaryngologist

David Goldfarb, DO• Princeton, New Jersey Robert T. Sataloff, MDh Philadelphia, Pennsylvania

Abstract

Lyme disease is an important consideration in the differ­ential diagnosis of patients seen by the otolaryngologist. Facial paralysis is the most common sign. The otolaryngologist may also see patients with temporal mandibular joint pain, cervical lymphadenopathy, facial pain, headache, tinnitus, vertigo, decreased hearing, otalgia and sore throat. The incidence is increasing and known to be endemic to certain areas of the United States and abroad. This paper reviews the various ways Lyme disease appears to the otolaryngologist. Three cases along with a discussion including epidemiology, vector, animal host relationship, clinical manifestations and pathophysiology are included. The literature is reviewed and the treatment discussed.

Introduction

Lyme disease is not a new clinical entity but rather was recently recognized as one in the mid-1970s. 1 For many decades other names were given describing the condition of lyme disease, such as: Bannwarth syndrome, Garlin-Bujadoux syndrome, chronic lymphocytic meningoradiculoneuritis, tick borne meningoradiculoneuritis and erythema chronica migrans.2

In 1977, Steer recognized Lyme disease as a systemic disease and later described three stages.3 5 It wasn't until 1982 that Burgdmfer isolated spirochetes from the tick, Ixodes dammin i. 6 Johnson, in 1984, cultured Borrelia burgdotferi, a spirochete and identified antibodies to this organism.7·8 This led to the ability to serologically test patients in order to diagnose Lyme disease.9 Lyme disease is an important factor in the differential diagnosis of many patients seen by the otolaryngologist.

"Department of Otolaryngology- Head and Neck Surgery, Medical Center at Princeton, Princeton, New Jersey 08540.

Department of Otolaryngology- Head and Neck Surgery, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107.

The purpose of this paper is to review and summarize the otolaryngologic manifestations of Lyme disease and to dis cuss its management. Review of 3 cases helps illustrate the clinical problems encountered commonly.

Case 1

The patient is a 45-year-old white man, who was camping in the woods of Maine, and noted a firm swelling in his right parotid gland, during which he also noted onset of fever, chills, malaise and myalgia.

One week after these symptoms started, he noted diffuse erythema on the right side of his face and neck from the level of the right zygoma superiorly to the level of the clavicle inferiorly and to the postauricular region posteriorly. He denied any tenderness. Initially he was started on cefadroxil for ten days. His symptoms and signs resolved until two days after completion of the cefadroxil. After a second course of cefadroxil the erythema and tenderness recurred again.

The patient was then evaluated by an otolaryngologist. A computerized tomography (CT) revealed a 2 x 2.5 x I cm. lesion in the right parotid consistent with inflammatory reaction. A few intraglandular and submandibular nodes were also noted. Several days later the patient noted some difficulty with mastication and closing his mouth. Within two to three days his problem with mastication had resolved, but he had trouble keeping his lips together. The next day the patient awakened with a right facial paralysis.

On reevaluation, the patient's facial paralysis was found to be incomplete. The marginal mandibular and buccal branches were more involved than the upper branches. Other cranial nerves were intact. No other neurologic findings were appreciated. The patient had a firm, tender, nodule two centimeters in diam ter and freely mobile, in the tail of the right parotid gland. There was no other cervical adenopathy. The patient was admitted to the hospital, lyme titers were drawn and he was started on ceftriaxone 2 grams IV ql2

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References:

May RJ. Pharmacotherapy: A pathophysiologic approach. J Allergic Rhinitis

1989;945-947.

White WB. Drugs for cough and cold symptoms in hypertensive patients.

Case 2

The second patient is a nine year old boy with a history of having two ticks removed from his right temporal region one month earlier.

Three weeks after having these ticks removed, he devel­oped fever, nausea and headaches which lasted one and a half weeks. No rash had been noted, possibly because the hair on his scalp camouflaged it.

The patient was initially treated by his pediatrician for otitis extema with drops and penicillin. He subsequently developed a complete right facial palsy. There was no history of drainage from either ear, vertigo, tinnitus, hearing loss or ear pain. Arthralgias in his knees, elbows and neck were noted. The patient had no known drug allergies. Past medical history and surgical history were negative.

His otitis extema had resolved, and his head and neck exam was normal except for posterior triangle lymphadenopathy and complete right facial palsy. No other cranial nerve abnormalities were noted.

The patient was started on amoxicillin 500mg PO four times a day and prednisone. Lyme titers and an MRI were ordered. Titers were positive for lyme disease. The lgM level was 87.0(normal <1), the lgG level was31.5 (normal <l)and the lgA level was 7.4. The elevated IgA level is associated with CNS involvement.

Magnetic resonance imaging (MRI) of the brain and internal auditory canals was carried out with gadolinium enhancement. Bilateral prominent posterior triangle lymph nodes were noted, but the study was otherwise normal.

Two days after starting the amoxicillin and prednisone the patient's facial function improved. The facial paralysis had completely resolved within one week of treatment. The steroids were weaned over a 7 day period. The antibiotic was continued for four weeks.

Case 3

A 52-year-old white woman, with a history of lyme disease 9 months earlier complained of bilateral hearing loss and ear pain, greater on the left. The left ear pain began first and the right side started two weeks prior to her initial visit. The patient was initially placed on amoxicillin 250mg twice a day by a primary physician. The antibiotic helped with the ear pain, and her hearing improved slightly. Some tinnitus was reported on the right, She had no vertigo and no otoffhea.

Examination revealed that the left tympanic membrane was normal, and the right was intact but dull. The Weber test was midline and the Rinne was positive on the left and negative on the right. Her nasal mucosa was congested and swollen. Her larynx, hypopharynx and nasopharynx were normal. There were no masses, bruits or tenderness in the neck. Hearing (using ANSI, 1969 ), was normal on the left. The right side showed a moderate sensorineural hearing loss. Stapeduis reflexes were absent on the left and present on the right at 70db (500hz), 85db(lK Hz) and 100 db(2K Hz).

The patient was treated with ceclor 250 mg three times a day for a total of ten days and blood was drawn for repeat lyme titers. On day 12, the patient stated that her hearing had improved. She was now complaining of pain in her knees, headaches and ameno IThea. She was started on doxycycline 100mg PO twice a day. Repeat audiogram was normal bilaterally. The lyme titers were positive. The IgM was 3.03 (positive>1), the lgG was 0.25 (Positive>1).

Epidemiology

Between 1984 and 1986 an annual incidence of fifteen hundred cases of Lyme disease was reported. This disease is known to be endemic in many countries including the United States, Europe, Australia, Switzerland and in Russia.11 The northeastern parts of the U.S where Iyme disease is particularIy common include: Connecticut, Delaware, Maine, Maryland, New Jersey, New York and Rhode Island.10

In the Midwest it is endemic in Michigan and Wisconsin; and in the west, in California, Nevada, Oregon and Utah.10 This disease is most common in the summer with 60% of cases occurring June through August. 2 12

Although only 2% of patients bitten by ticks carrying the disease develop a classic "bulls eye" shaped rash (erythema chronica rnigrans), almost 50% show significantly raised antibody titers. Lyme disease affects men, women and children equally.

Etiology

A spirochete, Borrelia burgdotferi, is the causative organ ism. The tick, genus Ixodes, is the primary vector. Ixodes dammini is more common in the Northeast, while Ixodes pacificus is more common in the West.10 13

The three main hosts are the white-tailed deer, white footed mouse and birds.14 Other investigators have noted certain insects and lizards to be hosts as well.9

The life cycle of the Ixodes tick is broken down into three stages: Larva, nymph and mature adult stage.14 Less than 5% of ticks are actually born infected. The majority get the infection during the larval or nymphal stage, when a blood meal is acquired from an infected host. The white footed mouse is the preferred host for the nymph in the summer. The white-tail deer is the preferred host for the adult.15 The larva sometimes acquire the spirochete during a blood meal from an infected host as well. If this occurs, the larva may become a host with the capability of spreading the disease to humans. If the larva does not acquire the spirochete during that blood meal, it may acquire the spirochete during one of its blood meals in either its nymph or adult stage. The nymph seeks its second blood meal the following spring, when humans are often bitten. The adults ai·e more active in the fall.

The nymph tick is very tiny, approximately 1 to 2 mm in size and its bite may go unnoticed. The adult is larger and more noticeable, approximately 4 to 5 mm in size.

Pathophysiology

The spirochete is transmitted through the tick saliva or fecal debris.13 After the patient is inoculated with the spirochete, universal dispersion occurs.

Evidence exists for three mechanisms of injury to the human body: 1) direct invasion, 2) direct immunological attack and 3) vasculitis. 16

Evidence for direct invasion has been demonstrated by the presence of the spirochete in skin, cerebrospinal fluid, blood, myocardium and joints.17 This may explain why certain patients develop meningitis, cranial nerve palsy, radiculopathies joint and cardiac effects. Evidence for direct immunological attack is suggested by the development of variable parenchymal abnormalities, immune complexes and immunoglobulins with complement that · have been found in biopsy specimens. Certain B cell alloantigens from the histo compatibility complex, HLA-DR4, HLA-DR2 have been noted to have an increased incidence in patients with Lyme disease.18

Vasculitis has been demonstrated on angiographic studies and may lead to injury to the vasanervosum with resulting axonal neuropathy.

As with Bell's palsy the location of the lesion can be quite variable with all segments noted topographically.

Considerations for the Otolaryngologist

The clinical course of Lyme disease is broken down into three stages.4 During stage one disease, erythema chronica rnigrans is reported in 60-80 percent of patients.12 18 This sign has been labeled the hallmark of stage one Lyme disease. The rash is characterized by a small expanding papule which forms an annular lesion with a central clear zone and an erythematous outer border.4 This erythematous outer border is produced as the spirochete migrates outward in the skin. These rashes can be found anywhere in the body. They occur initially at the site of inoculation of the spirochete.4

The lesions are usually warm to the touch and may be painful or have a burning sensation. The rash usually occurs within the first week with a range of three to thirty-two days.4 5 They may also develop multiple annular lesions secondary to erythema chronica rnigrans, and this is due to spread of the spirochete. The rash may occur simultaneously, with, before or after other signs and symptoms. 19

Other signs and symptoms are usually non-specific flu­ like symptoms such as malaise, fatigue, lethargy, headache, fever, chills, arthralgia, myalgia, anorexia, sore throat, cough, chest pain, abdominal pain, dizziness, photophobia, either generalized or regional lymphadenopathy, low grade fever, malar rash, backache, periorbital edema, conjunctivitis, splenomegaly, hepatomegaly, right upper quadrant tender­ ness and arthritis. 14

It is during stage 2 of the disease that patients see an otolaryngologist. In stage 2 of Lyme disease 15-20% of patients have been reported to develop neurologic complica­tions.18 Stage 2 is broken down into neurologic, cardiovas­cular and cutaneous manifestations.

Facial paralysis is one of the most common otolaryngologic signs.2 2° Clark et al, in 1985 noted that 10.6% of95 l patients with Lyme disease had a facial paralysis. Of these, 22.8% were bilateral.2 Seventy-four percent of patients with bilat­eral facial paralysis were male. Overall frequency of facial paralysis was equal between males and females. Complete paralysis was noted in 60.2% of those with VII nerve involvement, and there was no correlation between the laboratory results and the severity of the palsy.

Clark et. al. found that 32 patients treated with antibiotics alone had a median time to recovery of 24 days. Likewise the patient group treated with both steroids and antibiotics had a median time to recovery of 24 days. They noted that while recovery time was slightly longer for patients with bilateral facial paralysis, the rate of recovery was the same regardless of the treatment. The group of 24 patients which received no treatment had a median time to recovery of 30 days. Other authors have suggested that antibiotic treatment does have a beneficial effect on recovery time.

It is important to note that any cranial nerve may be involved, and the cranial nerve involved has nothing to do with the site of inoculation. 17 Schroeter, 1988 reported a case of recurrent laryngeal nerve paralysis secondary to Lyme disease.21 A forty-five year old healthy singer developed a sore throat and malaise followed 24 hours later by left vocal fold paralysis. The patient had positive antibodies to Borrelia burgdorferi. After six weeks of treatment for Lyme disease her titers were markedly reduced, and subsequent laryngoscopy was normal.

Krejcova, 1988 described neurotologic symptoms associ­ated with Lyme disease.22 Forty-four percent of his patients had hearing abnormalities and 81% had vestibular abnor­malities. Of his patients, 38% had either hearing or vestibular migrans is still present, or weeks later; and, if untreated, they can last months.

Lymphadenosis benigna cutis, also known as Borrelia lymphocytoma, is a cutaneous lesion usually seen during stage 2 disease. This skin lesion is characterized as a dense lymphocytic infiltrate in the dermis and/or subcutaneous tissues.19 This lesion may appear anywhere on the body, and may not develop for six to ten months after the tick bite. This lesion is said to have a tumor -like bluish red swelling or nodular appearance which is usually accompanied by a regional lymphadenopathy.19 These patients generally have increased levels of IgG against Borrelia. If untreated, these lesions may last for many months. 19 Awareness of this lesion is important to the otolaryngologist, especially when a pa­tient has a nodular neck mass. Failure to recognize this lesion may result in increased morbidity to the patient and subse­quent progression of the disease.

Stage 3 usually occurs weeks to years after tick exposure.

Approximately 60% of untreated patients have been reported to go on to Stage 3 disease.2 The patient may see the otolaryngologist complaining of temporo-mandibular joint pain.2 This is often the first joint affected and the patient may give a history of intermittent attacks lasting weeks to months.2 Arthritis has been reported in 67% of untreated patients. Usually the large joints are involved primarily. The knee, hip, shoulder, ankle and elbow are most commonly involved.10

Acrodermatitis chronica atrophicans is a cutaneous mani­festation found generally in stage 3 of Lyme disease.19 It is most commonly seen in elderly patients and consists of inflammatory and atrophic phases.

The inflammatory lesion is characterized by a bluish-red discoloration which usually starts on an extremity. It can last for years. This inflammatory phase gradually becomes replaced by atrophy of the skin and underlying bone and joints. It is important to recognize these lesions as these patients are often misdiagnosed as having venous or arterial insufficiency or scleroderma.

Diagnosis

Patients with Lyme disease have non-specific laboratory findings such as elevated sedimentation rates(ESR) and white blood cell(wbc) elevation. More diagnostic findings include positive biopsy, cultures or positive serologic testing. While the spirochete has been isolated from several areas of the body, (blood, cerebrospinal fluid, skin, joint fluid, myocardium and epineurium), serologic testing remains the mainstay of laboratory diagnosis.9 16 17 abnormalities as their first neurologic symptom. Fifty per­ cent of these patients also had facial paralysis. Other associ­ated neurologic findings included diminished concentration ability, ataxia, poor motor coordination, irritability, head­ aches, chorea, encephaliti s, cerebellar ataxia, motor and sensory radiculopathies and mononeuritis multiplex. All of these findings may arise while the erythema chronica

Cultures for growing Borrelia are very expensive and have a short half-life. The most common assays are immunofluo­rescence antibody (IFA) and Elisa tests. The Elisa test is more sensitive and specific.16 IgG takes six weeks to become elevated and therefore is useful primarily in assessing stage 2 and 3 disease. IgM, while less specific, is more useful in the early stages of Lyme disease when infection, reinfection and reactivation are suspected. Case 3 demonstrates the potential for reactivation or reinfection.

False positives have been seen in mononucleosis and rheumatic disease.10•16 False negatives may be seen in patient s who have received antibiotics during the early course of the disease, blunting the antibody response.

Unlike acquired syphilis, VDRL is negative; and rheumatoid factors are negative. Another way to distinguish rheu­matoid arthritis from Lyme disease is the lack of morning stiffness and lack of subcutaneous nodules.13

While serologic testing remains the best method of estab­lishing a diagnosis, only 50% of patients with stage 1 disease are positive. Direct detection of the spirochete is very diffi­cult, requiring a thousand spirochetes per milliliter of blood and special facilities.11 If biopsies are to be taken, it is best to take the biopsy from the leading edge of the skin lesion, the region where spirochetes are most likely to be found. 1

Treatment

In stage 1 disease for adults, oral tetracycline or doxycy­cline is usually effective in clearing the disease and prevent­ing progression to later stages. 18 2324 Tetracycline 250 mg orally four times a day for 10-30 days or doxycycline 100 mg orally twice a day for 10-30 days is recommended.1 8 Doxycycline may be preferred over tetracycline because it is only given twice a day and has better soft tissue penetration. In adults with intolerance or allergy to tetracycline, amoxicillin 500 mg four times per day over 10-30 days is recommended.18 For children less than eight years old penicillin or amoxicillin is preferred. Amoxicillin 250 mg three times a day, or 20 mg per kilogram of body weight per day in divided doses, should be used for 10-30 days.18 For children less than 8 years of age with penicillin allergy, erythromycin 250 mg three times a day, or 30 mg per kilogram per day in divided doses, for I 0- 30 days is recommended.18 For cranial nerve involvement such as facial paralysis, oral tetracycline or doxycycline as outlined above is recommended for 15-30 days. If no response is seen then IV medications should be tried. Ceftriaxone 2 grams IV per day for 14days is useful for other neurological abnormalities as well since it penetrates the blood brain barrier better than penicillin.18 In cases of allergy to cephalosporin or penicillin, doxycycline or chloramphenicol may be use d. For cardiac abnormalities of low degree, oral regimens may suffice. For high degree heart block, ceftriaxone or penicillin IV is recommended.

Progression to stage 3 disease is more common in patients who have had a severe stage 1, but may follow mild stage 1 disease which was left untreated. In such cases oral medication is tried for 30 days; and, if it fails, IV penicillin or ceftriaxone should be used. 18

Conclusion

Although facial paralysis is the most common sign of Lyme disease seen by the otolaryngologist, numerous other otolaryngologic symptoms and signs may be caused by this entity. Facial paralysis, if treated early, and other cranial nerve palsies due to Lyme disease have a good prognosis. Early antibiotic treatment is recommended to prevent late complications, and prolonged follow-up is advisable.

Because of its varied appearance and increasing incidence in the United States, the otolaryngologist must be aware of Lyme disease and be prepared to recognize and treat this multifaceted and highly responsive malady.

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Glasscock ME, Pensak ML, Gulia AJ, et al. Lyme Disease: A cause of Bilateral Facial Paralysis. Archives of Otolaryngology I 985; 111:47-49.

Schroeter V. Paralysis of Recurrent Laryngeal Nerve in Lyme Disease. Lancet I 988; 1 245.

Krejcova MB, Bojar M, Jerahek J, et al. Otoneurological Symptoma­

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Neu HC. A Perspective on Therapy of Lyme Infection. Annals New York Academy of Sciences 1 988; 539 :3 1 4-3 1 6.

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