Clinical Practice Guideline

for

LYME DISEASE

Developed for the

Aerospace Medical Association

by their constituent organization

American Society of Aerospace Medicine Specialists

 

Overview: Lyme disease is the most common tick-borne disease in the United States (US) and Europe.  It is also prevalent in Asia.  In the United States, there are 15,000 cases reported every year.  Lyme disease has been tracked by the Centers for Disease Control (CDC) since 1982.  In the United States, the spirochete Borrelia burgdorferi is transmitted through the bite of the Ixodes scapularis tick.  In Europe, the spirochete B. afzelii and B. garinii are more common than B. burgdorferi, and are the only two species found in Asia.  A cluster of cases identified in 1975 had their epidemiological epicenter in Lyme, Connecticut, for which it was named.  Documentation of this disease dates back to 1883 in Breslau, Germany by a physician named Alfred Buchwald.  He described an expanding, ring like lesion he had observed.  He further speculated that the rash came from the bite of an Ixodes tick.  This is the first known description of erythema migrans (EM), the most common symptom associated with the early stage of Lyme disease.

 

Three distinct foci occur in the United States: the Northeast (Maine to Maryland), the North Central (Wisconsin and Minnesota) and the West (northern California and Oregon).  The disease is prevalent in forested areas of Europe, particularly Germany, Australia, Slovenia and Sweden.  Other prevalent locations include Russia, China and Japan.

 

The ticks have larval, nymphal and adult stages, each stage requiring a blood meal.  In the Northeast and North Central US, an efficient cycle of infection of B. burgdorferi between nymphal ticks and white footed mice yields a high frequency of infection during the spring and summer months in humans.  An abundance of deer, the adult ticks preferred host, fulfill a similar role in the Northeast.  I. scapularis, also know as I. dammini, serves as the tick vector.  The principle vector in the Northwestern US is I. pacifica.  The frequency of human infection is relatively low in the Northwest, as I. pacifica tends to feed on lizards, who are not susceptible to the infection, and only occasionally feed on the dusky-footed woodrat while in the larval stage.  In Europe and Asia the principal vectors include I. ricinus and I. persulcatus, respectively, which also serve as vectors of tick-borne encephalitis virus.

 

Even though the likelihood of infection is twice as high in adult ticks as in the nymphal stage, most cases of transmission of early Lyme disease occur in the spring and summer months when the nymph is seeking a blood meal.  Adult ticks are much larger and easier to identify and remove, prior to transmission of infection.  Animal studies confirm that approximately 36 - 72 hours are required for transmission of the infection to the animal host once the tick has attached to itself to the host.  During this time spirochetes in the midgut of the tick multiply and migrate to the tick’s salivary glands, in preparation for transmission to the animal host.   Only ticks that are partially engorged with blood are associated with the development of erythema migrans at the site of the bite.

 

Lyme disease occurs in three broad stages.  The clinical symptoms of each stage may overlap.  Individuals may also present in a later stage without presenting with symptoms of an earlier stage.  The most common clinical manifestation of the first phase is EM. EM occurs between 3 and 30 days, although it most commonly develops between 7 and 14 days.  Seventy five to 80 percent of patients with erythema migrans present with a single primary lesion.  This lesion is usually greater than or equal to 5 cm in diameter, often with a central clearing, bull’s-eye or target like appearance.  Approximately 45 percent of patients with erythema migrans have spirochetemia.  Spirochetemia is not related to the size or duration of the presenting skin lesion.  Hematogenous dissemination from the primary infection site may yield secondary lesions.  Symptoms during the primary stage often resemble those of a viral infection, including arthralgias, fatigue, headache and neck pain.  Fever may or may not be present.  Respiratory and gastrointestinal symptoms are atypical.  Erythema migrans spontaneously resolves in approximately four weeks without treatment.

 

The second stage is manifested by dissemination of the disease within days up to 10 months following the initial tick bite.  It is associated with hematogenous spread of the spirochete to extracutaneous sites.  Sixty percent of untreated patients with erythema migrans will progress to mono or oligoarticular arthritis, usually involving the knee.  Ten percent will manifest with neurologic complications, the most common of which is facial-nerve palsy.  Five percent will manifest with cardiac complications, usually varying degrees of atrioventricular block.

 

The third stage includes late disease which may occur months to years following the initial tick bite.  Individual’s experiencing joint involvement may sustain several brief attacks of arthritis with the potential for persistent joint inflammation.  In up to 10 percent of cases, the arthritis may persist for months or years despite 30 days of intravenous (IV) or 60 days of treatment with oral antibiotics.  Large joints, especially the knee are susceptible, presenting with joint swelling and pain.

 

Neurologic involvement may occur within weeks.  Acute neuroborreliosis may develop in up to 15 percent of untreated patients in the US.  Potential manifestations include lymphocytic meningitis with episodic headache and mild neck stiffness, subtle encephalitis with difficulty with mentation, cranial neuropathy (particularly unilateral or bilateral facial palsy), motor or sensory radiculoneuritis, mononeuritis multiplex, cerebellar ataxia or myelitis.  In children blindness may result secondary to increased intracranial pressure on the optic nerve.  Acute neurologic abnormalities spontaneously improve or resolve over a period of weeks or months, even in untreated patients.  Up to five percent of untreated patients may experience chronic neuroborreliosis.  This may occur after long periods of latent infection.  In the US and Europe, a chronic axonal polyneuropathy may develop manifesting as spinal radicular pain or distal paresthesia.  In Europe, chronic encephalomyelitis may occur.  It is most often characterized by spastic paraparesis, cranial neuropathy or cognitive impairment with marked intrathecal production of antibodies against the spirochete.  In the US, Lyme encephalopathy, a mild, late neurologic syndrome with subtle cognitive disturbances, has been reported.

 

Cardiac involvement may occur several weeks after the initial onset.  Approximately five percent of untreated patients experience cardiac involvement, to include atrioventricular block, acute myopericarditis, mild left ventricular dysfunction and rarely cardiomegaly or fatal pancarditis.

 

Diagnosis in the US is usually based on the recognition of the characteristic clinical findings, a history of exposure in an area where the disease is endemic and except in patients with erythema migrans, an antibody response to B. burgdorferi by enzyme-linked immunosorbent assay (ELISA) and Western blotting.  IgM antibody titers during the first month of infection are unreliable.  IgG antibody responses are prevalent in most patients infected for one month.  Even with antibiotic treatment, IgM and IgG titers may persist for many years.6

 

Treatment recommendations during the first stage of Lyme disease include:  doxycycline 100 mg twice daily for adults; amoxicillin 500 mg three timed daily for adults; and cefuroxime axetil 5000 mg twice daily for adults.  The duration of therapy has traditionally been three weeks, although some studies suggest that a 10 to 14 day duration of therapy may be as effective.  Doxycycline is not recommended for children under 8 years of age or for pregnant or lactating women.  Of these three antimicrobials, only doxycycline is also effective against A. phagocytophilum infection (human granulocytic ehrlichiosis), also a tick born illness.   Individuals with chronic musculoskeletal pain, neurocognitive symptoms or both that persist after antibiotic treatment for well-documented Lyme disease may have considerable impairment in their health-related quality of life.  However further treatment with an extended (90 day) course of antibiotics in a controlled clinical trial in individuals without evidence of persistent infection by B. burgdorferi received no added benefit over those who received placebo. A substantial increase in the risk of morbidity and even death in patients secondary to extended antimicrobial therapy was noted in this study.

 

Second (early disseminated) and third (late) stages of Lyme disease may be treated with intravenous (IV) ceftriaxone, a third generation cephalosporin.  Recommended dosages include 2 g once daily in adults.  Similarly, cefotaxime 2 g every eight hours is also recommended in adults.  Additionally penicillin G divided into doses given every four hours in patients with normal renal function may be effectively used.  Eighteen to 24 million units per day in adults is the recommended dosage.  Recommended duration of IV therapy is two to four weeks.  Four weeks is the current standard in many communities, although there is no evidence to support greater efficacy of four versus two weeks.  There is also no evidence that treating for more than four weeks is beneficial.

 

Prevention may be accomplished through avoidance of tick-infested areas, wear of protective clothing, the use of repellents and acaricides, tick checks and modifications of landscapes in or near residential areas.  Additionally a vaccination for Lyme disease has been developed.  It utilizes a recombinant OspA in adjuvant and is commercially available in the US.  The efficacy was 49 percent after two injections and 76 percent after three injections.  The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends that vaccination be considered for persons 15 to 70 years old living in high risk areas who have frequent or prolonged exposure to I. scapularis ticks.   Vaccination is not recommended for persons with minimal or no exposure to these ticks.  Individuals who are treated for erythema migrans may become re-infected and are candidates for vaccination.  Persons with Lyme arthritis usually have high antibody titers to many spirochetal proteins and tend not to be re-infected.  Vaccination in these individuals is probably not necessary.  Three vaccinations are recommended.  The second vaccination should be given one month after the first one.  The third vaccination may be given between two and twelve months after the second.  The third vaccination should be administered in April (northern hemisphere) to ensure sufficient antibody titers against OspA during the summer months.  Booster injections may be needed annually to every three years, although official guidance has not yet been released.   Antimicrobial treatment within 72 hours of a tick bite with a single 200 mg dose of doxycycline has been suggested as effective prophylaxis against the development of Lyme disease.  Although the study reported an efficacy of 87 percent, it was limited by the number of participants in whom Lyme disease developed, resulting in a wide 95 percent confidence interval.  This study is in direct contrast to other studies demonstrating no clear protection attributable to antimicrobial prophylaxis administered after a tick bite.

 

Aeromedical Concerns The primary aeromedical concerns of this disease are its debilitating side-effects in regards to the neurologic, cardiovascular, and arthritides that may result.  If an aircrew member had one or more of these manifestations that did not resolve with treatment, he may possibly be removed from flight status, unless functional enough to be cleared by after expert evaluation.  Neuropsych testing should be accomplished for individuals in the US who develop Lyme encephalopathy.  Neuropsych testing should also be accomplished for individuals who develop acute or chronic neuroborreliosis, to include meningitis and encephalitis.  However, as with all infectious diseases, if treated early with full resolution of symptoms, the patient will mostly likely be returned to flight status.

 

Medical Work-up: Clinical and serologic confirmation of the disease is required.  For any cardiac involvement, the following studies are recommended: ECG, Holter, Echo and Treadmill.  Also, follow-up ECG, Holter and echo after resolution of clinical symptoms showing resolution of the underlying cardiac involvement (AV block, cardiac function).  In addition, at the end of the treatment period the studies performed by the local treating cardiologist to confirm resolution of the cardiac involvement must also be submitted (i.e., serial ECG’s for uncomplicated 2nd degree AV blocks; serial Holter’s/echo’s depending on the level of cardiac involvement to begin with; etc.).  In cases with neurologic involvement, the following are recommended: Neurology consult and report, Neuropsych testing results, and all available imaging studies and labs.  If there is arthritic involvement, include a rheumatology consultation report, orthopedic report (if performed) and all available imaging studies and labs.

 

Aeromedical Disposition:

Air Force: In the Air Force, any cardiac manifestations are disqualifying for all classes of aviation.  In addition, all aviators are grounded while under treatment.  Only in the case of full resolution of acute (stage I) Lyme disease may the flier be returned to flight status without an aeromedical waiver.  Waiver may be considered for stage II and III Lyme disease, depending on the success of the therapy.  In fliers with residual symptoms, a full evaluation is required as is any case of disseminated disease.  The experience of the entire DOD is scant, numbering less than 10 aircrew member cases.

 

Army: Waiver is not required for acute Lyme disease, although patients should be DNIF during antibiotic therapy.  Any case of disseminated Lyme disease, substantiated by serology requires waiver.  CNS findings will require complete resolution and a 3-month period of observation prior to consideration of waiver recommendation.

 

Navy: NOMI evaluation is recommended for all cases of suspected complicated disseminated Lyme disease.  Uncomplicated erythema migrans in the appropriate clinical setting can be diagnosed and treated at the local level.  It is not considered disqualifying if adequately treated.

 

Civilian: The civilian disposition of this condition will entirely depend on the manifestations of the involved organ system.  If Lyme disease is diagnosed it will need to be completely treated prior to any determination for medical certification.

 

Waiver Experience:

Air Force: Review of AIMWTS data base through May 07 revealed two waivers granted for fliers with a diagnosis of Lyme disease.  The first case was a 40 year old pilot who presented with a 22 month history of fatigue, fevers and myalgias of unknown etiology.  He was eventually treated with antibiotics for a history of a rash similar to EM, noted while on a family camping trip. His symptoms completely resolved within 3 weeks of the initiation of antibiotic treatment and he remained symptom free.  Despite a negative Lyme titer, a presumptive diagnosis of Lyme disease was made.  The second case was a 41 year old command pilot who presented with a progressively worsening audiogram and an abnormal Exercise Treadmill Test (ETT).  A presumptive history of neuroborreliosis was made, based on serology testing.  He was treated with 21 days of intravenous (IV) ceftriaxone.  Following this treatment, his midrange frequency hearing loss was noted to stabilize.  Repeat ETT was noted to be normal.  He also underwent a left sided L4-5 discectomy for an L4-5 herniated nucleus pulposus (HNP), manifested by a mild left foot drop.  He experienced an excellent recovery with the exception of minimal weakness of his left extensor hallucis longus, thought to have no significant occupational impact.

 

Army: The Army’s Aeromedical Epidemiological Data Registry was queried for the period of 1960 to 2009.  This case series contains 160,000 individuals.  This is a long span of time during which aeromedical policy has evolved.  There were 33 cases of Lyme disease.  Of those, 28 were retained.  Of these 20 were rated aviators.  Note that flight applicants were included in the data set, but not considered as rated aviators.

 

Navy: No numbers to report at this time.

 

Civilian: The current Path Code system has the same code for Lyme Disease and for Osteoporosis.  Those numbers as of August 2009 are: 205 for first class, 172 for second class and 666 for third class

 

ICD 9 Codes for Lyme Disease

088.81

Lyme Disease

 

References:

 

Klempner MS.  Two Controlled Trials of Antibiotic Treatment in Patients with Persistent Symptoms and a History of Lyme Disease.  N Engl J Med.  2001; 345:  84-92

 

Lipschütz B.  Zur Kenntnis der "Erythema chronicum migrans".  Acta dermato-venereologica, Stockholm.  1931; 12:  100–102. 

 

Nadelman RB.  Prophylaxis with Single-Dose Doxycycline for the Prevention of Lyme Disease after an IXODES SCAPULARIS Tick Bite.  N Engl J Med.  2001; 345:  79-84

 

Sigal LH.  Diagnosis of Lyme Disease.  UpToDate.  Online 15.1, March 12, 2007. 

 

Sigal LH.  Treatment of Lyme Disease.  UpToDate.  Online 15.1, March 10, 2007.

 

Steere AC.  Lyme Disease.  N Engl J Med.  2001; 345:  115-125. 

 

Sternbach G, Dibble C.  "Willy Burgdorfer: Lyme disease."  J Emerg Med.  1996; 14 (5):  631-34.

 

Wormser GP.  Early Lyme Disease.  N Engl J Med.  2006; 354:  2794-2800. 

 

 

 

 

Prepared by Drs. Stephen Hingson and Karen Fox

12 Sep 09