Pre-trial Discovery Findings
In the course of pre-trial discovery, a Notice for discovery and Inspection of xxxxxxxx Lyme Disease Medical Policy
was served upon xxxxxxxxx attorney. The document to follow was produced in response to that pre-trial discovery
demand and sets forth the criteria that has been used by xxxxxxxx when deciding whether it will pay for prescribed
treatment of Lyme Disease:
MEDICAL POLICY
SUBJECT
Lyme Disease Treatment
DATE
December 8, 1995
Effective Date: Immediately and retroactive to claims under review
COVERED CPT PROCEDURE
CODES
86617 - Borrelia burgdorferi (Lyme disease) confirmatory test (e.g., Western blot or immunoblot)
86618 - Borrelia burgdorferi (Lyme disease) - listed with codes described by CPT as qualitative or semiquantitative immunoassays performed by multistep methods.
RELATED CPT PROCEDURE CODES
83898 - Nucleic acid probe with amplification, e.g., polymerase chain reaction (PCR)
83912 - interpretation and report
84181 - Western Blot, with interpretation and report, blood or other body fluid
84182 - Western Blot, with interpretation and report, blood or other body fluid, immunologic probe for band identification, each.
90780 - I.V. Infusion for therapy/diagnosis, administered by physician or under direct supervision of physician; up to one hour
90781 - each additional hour, up to 8 hours
LOCAL CODES FOR HOME
ANTIBIOTIC THERAPY
X6060 - Home antibiotic therapy
X6062 - Antibiotic therapy, daily (per diem) rate
- See "General Guidelines for Coding TPN and other Supplies" in the Precomputer Manual for coding instructions.
COVERED ICD-9 DIAGNOSIS
CODE
088.81- Lyme Disease
DESCRIPTION
Lyme disease is an infectious disease caused by a bacterium that is spread by an insect, the deer tick. It can cause a large number of symptoms including rashes, arthritis, and neurological symptoms. The coverage issue concerns the long term use of intravenous antibiotic therapy in the treatment of Lyme disease.
POLICY
Medical Necessity/Appropriateness
Intravenous antibiotic therapy for Lyme disease is regarded as medically necessary only in certain subgroups of Lyme disease patients. These are:
Disseminated early infection:
Meningitis
Late infection:
Objective evidence of these Lyme disease manifestations must be documented. See "Medical Policy Background" and "Documentation Requirements" that follow.
Also see the "Utilization Parameters" section for specific guidelines on the maximum number of services allowed.
All proposals for treatment of Lyme disease with intravenous antibiotics require medical necessity preauthorization. The information listed in the section "Documentation Requirements", or a completed "Statement of Medical Necessity" (see attachment), must be sent to the nurse case management unit prior to Initiating treatment for every Lyme patient who is requesting benefits coverage for such treatment.
Claims which have not been preauthorized should be denied.
Coding GuidelinesDiagnostic Testing
The following diagnostic tests are generally accepted tests to assist in the clinical diagnosis of Lyme disease:
Current recommendations are to perform two stage testing (ELISA/EIA or IFA -86618) followed by Western immunoblotting (86617), if the ELISA/EIA or IFA are positive or equivocal. Therefore, claims for both tests on one service date are payable.
UTILIZATION REVIEW PARAMETERS
Repeated Lyme Disease Testing
Intravenous Antiobiotic Therapy
DOCUMENTATION REQUIREMENTS
1. For preauthorization review, the attached information request, "Statement of Medical Necessity", should be completed with copies of supportive documentation attached (lab reports, etc.), as required. The key elements of the information required for review are also listed here for retrospective review.
2. For individual case review, medical records or a detailed summary of medical course must be supplied and include the following, including specific dates of key events (diagnosis, treatment, etc.):
Medical Policy Background Disease Characteristics:
Disease Characteristics:
Lyme disease is an infection that results from the spirochete bacterium Borrellia burgdorferi that is transmitted to humans by the bite of a deer tick. Lyme disease was first described as a distinct entity in the US in 1977 because of a clustering of cases resembling juvenile rheumatoid arthritis around Lyme, Connecticut. Lyme disease is now the most common insect borne infection in the United States. The infection usually begins with flu-like or meningitis like symptoms accompanied by a characteristic rash, termed erythema migrans, at the site of the tick bite. After days to weeks, the spirochete often disseminates from the skin and can effect multiple organ systems, most commonly the joints, nervous system and heart. Months to years later, intermittent attacks of arthritis commonly develop, and in some patients, chronic joint, neurologic, or skin involvement may occur years after disease onset. In rare instances, infection may affect other organ systems and has been associated with a wide range of clinical manifestations.
Most cases have been reported in the coastal northeast between Maryland and Massachusetts, in the upper Midwest Wisconsin and Minnesota) and in the west (California and Oregon). There is no gender or age predilection for the illness. People whose occupations or recreational activities involve exposure in grassy or wooded tick-infested areas are at increased risk of acquiring Lyme disease.
Diagnosis:
The diagnosis of Lyme disease is based primarily on the presence of a characteristic clinical picture, exposure in an endemic area, and an elevated antibody response -to B. Burgdorferi. In the absence of typical clinical manifestations or exposure in an endemic area, one should consider alternative diagnoses regardless of the results of diagnostic tests. The Centers for Disease Control (CDC) criteria for Lyme disease case reporting include:
Presence of erythema chronicum migrans (the typical expanding bull's eye rash at the site of the tick bite)
OR
Musculoskeletal system: recurrent brief attacks of objective joint swelling in one or a few joints, sometimes followed by chronic arthritis in one or a few joints. Not considered as criteria for diagnosis are: chronic progressive arthritis not preceded by brief attacks; chronic symmetrical polyarthritis; arthralgias, myalgias, or fibromyalgia syndromes alone.
Nervous system: Lymphocytic meningitis, cranial neuritis (particularly facial palsy), radiculoneuropathy, or encephalomyelitis. Encephalomyelitis must be confirmed by showing antibody production in the cerebrospinal fluid (CSF) by demonstrating a higher titer of antibody in the CSF than in serum. Not considered as criteria for diagnosis are:
headache, fatigue, paresthesias, or mild stiff neck alone.
Cardiovascular: Acute onset, high grade (2nd or 3rd degree) atrioventricular conduction defects that resolve in days to weeks, sometimes associated with myocarditis. Not considered as criteria for diagnosis are: palpitations, bradycardia, bundle branch block, or myocarditis alone.
Serologic Testing:
In October, 1994, the Second National Conference on Serologic Diagnosis of Lyme Disease issued recommendations for Lyme disease test performance and interpretation. This conference included a number of professional, research, and regulatory groups including the NIH, FDA, and the CDC. Their recommendation was that a two test approach for active disease and previous infection detection be adopted. This should involve initial testing using a sensitive enzyme immunoassay (EIA) or immunofluorescent assay (IFA) followed by a Western immunoblot. All specimens that are positive or equivocal by a sensitive EIA or IFA should be tested by a standardized Western immunoblot. Specimens negative by a sensitive EIA or IFA need not be tested further.
When Western immunoblot is used during the first 4 weeks of disease (early Lyme disease) both IgM and IgG procedures should be done. A positive IgM test result alone is not recommended for use in determining active infection in persons with illness > 1 month's duration because the likelihood of a false positive result is high. If a patient with suspected early Lyme disease has a negative serology, serologic evidence is best obtained by testing of paired acute and convalescent phase serum samples. Serum samples from persons with disseminated or late-stage Lyme disease almost always have a strong IgG response to Borrelia burgdorferi antigens.
It was recommended that an IgM Western immunoblot be considered positive if two or more of the following three bands are present (designated by the unit of measure, kiloDaltons, kDa, the molecular weight of the protein band). Each band represents a specific protein component of the Borrellia burgdorferi organism:
24 (or 21 dependent on the strain being tested)
39
41
It was also recommended that IgG Western immunoblot be considered positive if five of the following 10 bands are present (also in kDa):
18
21 (or 24, dependent on the strain being tested)
28
30
39
41
45
58
66
93
These tests may also be used to detect leptomeningeal production of antibodies in the CSF in patients with suspected neurologic involvement. However the finding of IgG antibody in the spinal fluid may be the result of passive diffusion from the serum. The amount of specific antibody in the serum and CSF must be compared (CSF antibody concentration must exceed the serum concentration to be suggestive). Patients with Lyme meningitis usually have intrathecal (CSF) antibody production, but as with serum antibodies, IgG and IgM may persist for years in some, even after antibiotic treatment.
Efforts to standardize testing methods continue, however there remains considerable potential for false positive/false negative and interlaboratory variability in EIA/ELISA results. The criteria for Western immunoblotting are described in the conference document as "interim,, subject to further refinement of protein identification and techniques that will allow consistency. Though this testing protocol represents a forward step towards consistent testing and reporting methodology, it does not imply that use of these tests can be taken as sole evidence for the presence of clinical Lyme disease.
Polymerase chain reaction PCR) is a technique that can detect the presence of small amounts of DNA in various body fluids or tissue specimens. PCR has been used to detect B. burgdorferi DNA from various sources, however the sensitivity of PCR in published reports appears to vary dependent on the DNA segment chosen for PCR targeting and on the body fluid testing. There is also risk of contamination leading to false positive tests such that positive PCR tests must be interpreted with caution. PCR has not advanced to general clinical use.
The T-cell lymphoproliferative assay detects the cellular immune response to B. Burgdorferi. Its potential use may be in a small percentage of patients in whom late manifestations of the disorder still develop despite antibiotic therapy during the first several weeks of infection. Results have been inconsistent and many healthy controls have had positive results in published reports. T-cell lymphoproliferative assay has limited potential utility, and has not advance to general clinical use.
Clinical Stages of Lyme Disease:
The clinical manifestations of Lyme disease can be divided into those that occur early, within days to a few months following the bite of an infected tick, and those that occur late, generally months to years after the bite. Early stage disease is further divided into localized and disseminated "sub-stages". It is clear that the majority of symptoms and signs associated with both early and late Lyme disease are the result of direct invasion of various organs and tissues by B. burgdorferi. It is not clear, however, whether all of the symptoms and signs of this illness, particularly the chronic neurologic and musculoskeletal manifestations, are the result of the persistence of microorganisms in the tissues. This latter concept is extremely important in the evaluation of prolonged duration or repeated courses of therapy.
The conceptual division of Lyme disease into early and late infection also assists the evaluation and recommendations for therapy. The following table summaries the clinical manifestations that have been noted with each stage of infection.
Table 1. Manifestations of Lyme Disease by Stage. Systems are listed from the most to the least commonly affected System
* Indicates manifestations that have been reported, but are rare and limited to one or a few case reports.
Treatment:
All stages of Lyme disease can usually be treated effectively with antibiotic therapy, although most untreated patients eventually recover antibiotics hasten the resolution of symptoms, and appropriate treatment of early Lyme disease prevents the development of the illness. Again, it is important to emphasize that some patients may not recover completely. The recommended treatment of Lyme disease depends on the clinical manifestations and the stage of illness.
Early stage :
Early, localized infection is treated with oral antibiotics. In the absence of meningitis, radiculoneuritis, or high-degree atrioventricular block, early disseminated infection can usually be treated successfully with oral antibiotics. With the exception of residual fatigue, symptoms usually disappear within the 14 to 30 day period of treatment. Patients with meningitis, radiculoneuritis, and high-degree (2nd or 3rd) AV block seem to require intravenous therapy. First degree AV block and isolated Bells (facial, or seventh cranial nerve) palsy can be managed with oral antibiotics as both manifestation resolve even without treatment.
Late stage:
Although the late manifestations of Lyme disease can also be treated successfully with antibiotic therapy, the duration of treatment may need to be longer, the response is often slower, and the likelihood of treatment failure is greater. For patients with late (persistent) arthritis, oral antibiotics are successful in a majority of cases, however recurrence or appearance of other late manifestations may still occur. Intravenous antibiotic treatment of persistent Lyme arthritis lessens the chance of recurrence or progression, but does not eliminate this risk entirely. Persistence despite complete and appropriate therapy has been associated with the presence of histocompatibility antigen HLA-DR4. This raises suspicion that certain patients may be predisposed to a reactive, persistent arthritis on a genetic basis. In summary, Lyme arthritis can usually be treated successfully with oral antibiotics for 30 days. In patients who do not respond, it is reasonable to retreat with oral antibiotics or a 2 to 4 week course of intravenous ceftriaxone.
The late neurologic manifestations of Lyme disease can also be successfully treated with intravenous antibiotic therapy, but the response is slow. It is important to note that improvement in late neurologic Lyme manifestations occurs over a period of months following a course of therapy. Improvement is noted over a 2 to 6 month (or longer) period following treatment. Current recommendations are for a 1 month course of intravenous ceftriaxone for patients with chronic neurologic manifestations of Lyme disease. Improvement of symptoms while on antibiotic therapy, with rapid recurrence as soon as antibiotic therapy is stopped is not typical of the course taken by
true neurologic Lyme disease. Occasionally, true relapse of late objective neurologic Lyme manifestations occur. In such cases, retreatment with a second 1 month course of intravenous ceftriaxone is warranted. However, true recurrence of active neurologic infection with B. burgdorferi is rare, and should be accessible by objective evidence of active infection or neurologic dysfunction
There is nothing in the Lyme disease scientific literature that supports the practice of treating until symptoms disappear. There is also nothing in the literature that supports following prolonged intravenous treatment (many months) with a longer period of continued oral antibiotic therapy, or the use of alternate (other than penicillin or ceftriaxone) or combination intravenous antibiotic regimens. Long term antibiotic therapy can also be associated with serious toxicities such as pseudomembranous colitis, biliary sludging (leading to cholescytectomy), cytopenias/coagulation disorders, and intravascular line-related sepsis.
Though several early case report suggested the possible transmission of B. burgdorferi transplacentally from mother to fetus, epidemiologic and laboratory study have not shown that this occurs. Currently, recommendations are that pregnant women need not be treated differently form other patients except that they should not receive tetracycline. Healthy newborns, born to women who were treated for Lyme disease during pregnancy do not need additional antibiotic therapy. Newborns of women not treated during pregnancy should be observed with a high index of suspicion, but if ill, are much more likely to have a diagnosis other than Lyme disease.
There are a number of possible explanations for the persistence of symptoms after treatment:
Intravenous antibiotic regimens currently recommended in published recommendations for Lyme disease treatment include:
Adults:Ceftriaxone 2 gm/day IV
Penicillin G 20 million units/ day, 6 divided doses daily
Children:Ceftriaxone 75 - 100 mg/kg/day
Penicillin G 300,000 units/kg/day IV, 6 divided doses daily
(These doses are provided for reference purposes only, and are not intended to be limits of coverage policy.)
The following table summarizes the Lyme stage/manifestation and the required confirmatory findings that would substantiate the medical necessity of treating Lyme disease manifestations with intravenous antibiotics.
Table 2. Summary of Indications for IV Antibiotics. For all the following, three conditions must be satisfied:
1. Characteristic exposure/epidemiologic, and early localized disease history,
2. Positive Lyme serology confirmed with Western immunoblot,
3. Exclusion of other common medical illness that can explain clinical findings.
Early Disseminated Stage
Manifestations:
1. Confirmatory findings required:Duration of therapy (per published recommendations)Meningitis1. Clinical signs and symptoms similar to those of aseptic (viral)
meningitis.
2. CSF analysis showing lymphocytic pleocytosis (usually = 100 cells/cc), mild protein elevation, normal glucose. 3. CSF serology demonstrative of meningeal antibody production (optional if #2 met)14 to 30 daysRadiculoneuritis1. Asymmetric radiculoneuropathy, motor, sensory, or mixed, affecting limbs, trunk, or both.
And/or
Cranial neuropathy OTHER THAN isolated peripheral 7th nerve (facial, Bell's) palsy
Confirmed by:
a. Detailed neurologic physical exam, preferably by a neurologist, or
b. EMG/NCV studies.14 - 30 days2 or 3 AV block (cardiac)1. Characteristic electrocardiographic findings, often fluctuating in degree
And/or
Carditis (rare)1O-30 days Late Stage
Manifestations: 1. Confirmatory findings required:Duration of therapy (per published recommendations)Persistent arthritis1. Recurrent attacks of asymmetrical oligoarticular arthritis joint effusion and pain, not arthralgia, alone), most commonly the knee
2. Prior treatment of Lyme arthritis with 30 day course of appropriate oral antibiotic therapy.14-30 days Neurologic/encephalomyelitis1. Objective evidence of neurological dysfunction as documented by either:
· Neurologic physical exam
· Organic deficit demonstrable by neuropsychological testing
· MRI showing small round areas of increased ~ signal intensity in peripheral white matter.
OR
2. Continued evidence of intrathecal antibody production to B. burgdorferi.
OR
3. CSF analysis showing lymphocytic pleocytosis30 daysNeurologic/radiculoneuritis1 Objective evidence by neurologic physical exam or EMG/NCV studies of polyneuropathy.
Suggestive/not required:
2. Continued evidence of intrathecal antibody production to B. burgdorferi or other CSF abnormalities.
3. Sural nerve biopsy showing axonal injury with perivascular lymphoplasmacytic infiltrates.30 days
Lyme Disease - Statement of Medical Necessity for IV Antibiotic Therapy Outline for new information request form:
Patient name/ID
Prescribing MD/Address/Phone#
Other MD's following patient for Lyme disease /PCP if different from prescribing MD
Other ID information as needed
LYME DISEASE STAGE/MANIFESTATION FOR WHICH IV THERAPY IS PRESCRIBED (CURRENT CLAIM OR PREAUTHORIZATION)
HISTORY (include dates)
initial exposure/manifestations
prior treatment: list in chronologic order from first treatment to most recent. Include specific drug(s) used, duration, route of administration, treatment result and side effects
CURRENT PHYSICAL FINDINGS: focus on objective findings that are manifestations of Lyme infection
LABORATORY AND OTHER TEST FINDINGS: Including confirmatory Lyme serology, CSF analysis, EMG/NCV studies, electrocardiogram, neuropsychologic testing, imaging studies, as needed to establish that objective findings are the result of Lyme disease.
CONSULTATION REPORTS, from any other physician(s) attending the case.
TREATMENT PLAN: Drug, dose, frequency, route, duration, infusion provider, projected cost per service item (drug, ancillary supplies, professional services, etc)
