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:
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;
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2/19/11
Prepared
by Drs. Renee Boyd and Dan Van Syoc