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 (U.S.) caused by the spirochete, Borrelia burgdorferi.  It occurs worldwide and has been reported on every continent except Antarctica.  Lyme disease surveillance in the U.S. began in 1982 at the Centers for Disease Control (CDC) and became a nationally reportable disease in 1991.  In the U.S., the number of reported cases has been steadily increasing from over 11,000 cases/ year in 1995 to over 28,000 cases/ year in 2009.  In 2009, the highest numbers of confirmed Lyme disease cases were in Pennsylvania (4,950), New Jersey (4,598), New York (4,134), Massachusetts (4,019), and Connecticut (2,751).   In the Northeastern and North-central U.S., the black-legged tick (or deer tick, Ixodes scapularis) transmits Lyme disease and in the Pacific coastal U.S., the disease is spread by the western black-legged tick (Ixodes pacificus).  A cluster of cases identified in 1975 had their epidemiological epicenter in Lyme, Connecticut, for which the disease 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 now known as erythema migrans (EM); the most common symptom associated with early Lyme disease, and speculated that the rash came from the bite of an Ixodes tick.

 

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).  In Europe, most cases occur in the Scandinavian countries and in central Europe (Germany, Austria, and Switzerland), although cases have been reported in the United Kingdom (South Downs and New Forest areas).  Other prevalent worldwide 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 known as I. dammini, serves as the tick vector.  The principle vector in the Northwestern US is I. pacificus.  The frequency of human infection is relatively low in the Northwest, as I. pacificus tends to feed on lizards, which are not susceptible to the infection, and only occasionally feed on the dusky-footed wood rat 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 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 EM 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.  In the U.S., EM (single or multiple) is found in about 90% of patients with objective evidence of infection with B. burgdorferi.  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 EM have spirochetemia which is not related to the size or duration of the presenting skin lesion.  Hematogenous dissemination from the primary infection site may yield secondary lesions.

 

Lyme disease has a myriad of dermatologic, neurologic, cardiac, and musculoskeletal manifestations.  The most common symptoms during the primary stage often resemble those of a viral infection, including myalgias, arthralgias, fatigue, headache, neck pain and possible fever.  Rarely, respiratory, gastrointestinal or ocular complaints such as conjunctivitis, iritis, and keratitis may be reported.  EM spontaneously resolves in approximately four weeks without treatment.  Given these vague initial symptoms, this represents a challenge in early detection and initial 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 EM 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.  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.  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.

 

The third stage includes late disease which may occur months to years following the initial tick bite.  Individuals 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 which is thought to be mediated by the immune response by the spirochete in the joint.12 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.

 

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.7

 

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 500 mg twice daily for adults.  The duration of therapy has traditionally been three weeks, although some studies suggest that 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.  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.14

 

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.  In December 1998, GlaxoSmith- Kline gained US Food and Drug Administration approval for a B burgdorferi outer surface protein A (OspA)-based Lyme disease vaccine, LYMErix.  The efficacy was 49 percent after two injections and 76 percent after three injections.7  The vaccine, however, was voluntarily withdrawn from the market because of poor sales.  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 a 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.  Regardless, it may be prudent in aircrew to consider doxycycline prophylaxis within 72 hours of a tick bite from an endemic area to preclude progression of possible Lyme disease, since doxycycline is an approved aircrew medication after ground testing.

 

Aeromedical Concerns The symptoms during primary Lyme disease, included arthralgias, fatigue, headache, neck pain and possible fever are obviously not optimal in the flying environment.  As with all infectious diseases, if recognized and treated early with full resolution of symptoms, return to flight status is appropriate.  However, if untreated, then aeromedical concerns of this disease are its debilitating effects in regards to the neurologic, cardiovascular, and arthritides that may result.  Neurocognitive impairment, cardiac arrhythmias and arthritic pain are all manifestations that could impact the safety of the individual and mission.

 

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 monitor studies and echocardiograms 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: Patients should be DNIF while symptomatic and under treatment.  Once all symptoms of the disease have resolved, the aviator can be returned to status without a waiver (true for all aviation classes).  Lyme disease is not mentioned by name as disqualifying for any aviation class, but the residual symptoms mentioned above may require a waiver.  In these cases, waiver for flying class I/IA, II, IIU, and III, as well as for ATC/GBC and SMOD personnel may be considered, depending on the success of the therapy.  An ACS review of cardiologic or neurologic complications is recommended.

 

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: The protean manifestations of the condition and the variability of the presentations dictate an individualized approach to waiver recommendation.  In general, adequately treated erythema migrans without signs of dissemination will Not be Considered Disqualifying (NCD).  Any case clinically suspicious for disseminated Lyme disease that is substantiated by appropriate serology (acute IgM titer, rising IgG titers) is Considered Disqualifying (CD).  Central nervous system findings will require complete resolution, and a period of observation before waiver recommendation will be considered.  Persistent abnormalities will be permanently disqualifying, with no waiver recommended.

 

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 the AIMWTS data base through Nov 10 revealed a total of five cases submitted for waiver consideration with the diagnosis of Lyme disease.  There was 1 FC I case, 3 FC II cases and 1 SMOD cases.  All were granted waivers except for the SMOD case which resulted in a disqualification for persistent neurological symptoms.

 

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: Review of Navy data from approximately 1986-2011 revealed 21 individuals evaluated for waiver with a diagnosis of Lyme Disease.  For 14 of these the most recent waiver recommendation was favorable.  2 were Naval Aircrew, 5 were Naval Aviators, SG1, 1 was a Naval Flight Officer, and 5 were Student Naval Aviators.

 

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:

 

Wormser GP, Dattwyler RK. Shapiro ED, et al: The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America.  Clin Infect Dis, 2006; 43:1089-1134.

 

http://www.cdc.gov/ncidod/dvbid/lyme/ld_statistics.htm (2010)

 

http://www.cdc.gov/ncidod/dvbid/lyme/ld_UpClimbLymeDis.htm (2010)

 

Wormser GP.  Early Lyme Disease.  N Engl J Med, 2006; 354: 2794-2801.

 

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

 

Murray TS and Shapiro ED.  Lyme Disease. Clin Lab Med, 2010; 30: 311-328.

 

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

 

Sexton DJ.  Diagnosis of Lyme disease.  UpToDate.  Online version 18.2.  May 2010.

 

Nadelman RB, Nowakowski J, Fish D, et al.  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.

 

Hu L.  Treatment of Lyme disease.  UpToDate.  Online version 18.2.  May 2010.

 

Nadelman, RB and Wormser GP.  Lyme borreliosis.  Lancet, 1998; 352:557-65.

 

Klig, JE.  Ophthalmologic Complications of Systemic Disease: Emerg Med Clin N Am, 2008; 26:217-31.

 

Puius YA, Kalish and RA.  Lyme Arthritis: Pathogenesis, Clinical Presentation, and Management.  Infectious Dis Clin N Am, 2008; 22: 289-300.

 

Klempner MS, Hu LT, Evans J, et al.  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.

 

Clark, RP and Hu LT.  Prevention of Lyme Disease and Other Tick-Borne Infections Infect Dis Clin N Am, 2008; 22: 381–396.

 

Gasser R, Lercher P, and Klein W.  Lyme carditis and Borrelia-associated dilated cardiomyopathy.  Heart Failure Reviews, 1999; 3: 241-248.

 

Raveche ES, Schutzer SE, Fernandes H, et al.  Evidence of Borrelia Autoimmunity-Induced Component of Lyme Carditis and Arthritis.  J Clin Microbiology, 2005; 43: 850-6.

 

Sternbach G and Dibble C.  Willy Burgdorfer: Lyme disease.  J Emerg Med, 1996; 14: 631-4.

 

 

 

 

2/19/11

Prepared by Drs. Renee Boyd and Dan Van Syoc