Traditionally, the public has been advised to suspect Lyme
(LD) if a round or oval, expanding, red rash develops 3-32 days after a deer tick bite
associated with or followed by a flu-like illness. This limited description will apply to
only some cases. About 50% of patients do not recall one or more of tick bite, rash or
flu-like illness. The rashes associated with LD can assume a variety of morphologies
including vesicular, urticarial, eczematoid or atrophic (Acrodermatitis Chronicum
Atrophicans). For many patients, neurologic, cardiac, arthritic, cognitive and/or
psychological complications predominate. While deer ticks and LD have a well known
affiliation, other potential vectors can carry the spirochete that causes LD (Borrelia
burgdorferi; Bb). These include, the lone star tick, fleas, the biting flies (e.g.
green-headed fly) (and mosquitoes?). A case of suspected transmission via blood
transfusion has been reported by Dr. Burrascano.
The demonstration of Bb by PCR in two museum mouse
specimens dating from 1894 (Massachusetts) and in ticks collected during WW II, provides a
mechanism for potential life long exposure and disease which predates the formal 1975
discovery of LD. An occasional patient will date their symptoms which resolved on
antibiotic therapy for LD to early childhood. Before the diagnosis was made, patients
would dismiss those symptoms with the statement: "I've always had those
problems". That resigned characterization implies that the longevity of the symptoms
rules out a reversible cause. Subsequent resolution of the long standing symptoms on
antibiotic therapy for LD belies that notion. Symptoms of LD can begin within days of
inoculation with Bb or appear belatedly, but usually in the first to fourth month. Mice
inoculated intraperitoneally had Bb demonstrated in the brain on biopsy 12 hours later
with a peak at 48 hours (Stockholm Conference, 1990). Dr. Luft has published the detection
of Bb by PCR (Polymerase Chain Reaction) in the CSF (Cerebrospinal fluid) of humans 2
weeks after the appearance of non-CNS related symptoms!
If dissemination can occur early, then staging the disease
according to the temporal appearance of symptoms may be irrelevant. The absence of
symptoms related to a particular organ system doesn't necessarily exclude the presence of
Bb from that organ. Conversely, due to the possibility of symptoms being engendered by
chemical mediators and autoimmune reactions by the host (against non-viable but
immunoreactive DNA blebs), organ dysfunction and attendant symptoms can appear at sites
removed from the actual spirochetes. The diagnostic and therapeutic problems that these
phenomenon entail should be obvious.
Rapid dispersion of Bb could lead to the prompt appearance
of complications; e.g., meningitis. There is no absolutely predictable clinical sequence
for LD. The flu-like syndrome may be absent from the initial presentation and may endure
once established without treatment. Cardiac and neurologic complications can be observed
sometime within the first 3 months after microbiologically contracting the disease.
Arthritis (i.e., joint inflammation; distinct from arthralgias; i.e., joint pain) can also
accompany the initial clinical course, but more often develops later on between the second
and sixth month from inoculation. The onset of complaints can not only be subtle and
desultory, but delayed for a year or more. One of my patients denied all LD related
symptoms until her husband died, whereupon, a plethora of complaints cascaded into her
life beginning that very day. Another had an annual flare of LD as part of an anniversary
reaction centered on the date of his mother's death.
Moreover, the early constellation of symptoms can have a
paucity of findings with unidimensional presentations: the onset of solitary problems such
as vertigo, or recurrent upper respiratory tract infections. Over time, as the untreated
LD percolates, symptoms accrue to the burgeoning clinical picture until a multisystem
presentation is created. Other patients can have their manifold symptoms complex develop
in the manner of an avalanche. These patterns represent the extremes of a clinical
continuum between which there are many variations on the theme ranging from mild to severe
disease. Thus, The failure of a pathognomonic (unique and specific) presentation to
consistently unfold causes sufficient clinical confusion, that a punctual diagnosis is
problematic. Therefore, a high index of suspicion is placed at a premium. If a clinician
can't reconcile preconceived notions about how LD should announce itself with a patient's
history and physical findings, it is a disservice to the patient and an abdication of
professional imperatives to presumptuously conclude that the symptoms are psychosomatic or
that the patient is faking!
Antecedent or concomitant factors which can cause symptoms
and physical changes de novo or aggravate contemporary problems are reliably solicited on
close questioning of LD patients. Females experience an exacerbation of their LD symptoms
before or during their menses, while pregnant and with oral contraceptive hormones. Many
patients have symptoms intensify or reappear with physical and emotional stress, if sleep
deprived, after exercise, in a hot bath, after alcohol consumption, with fasting
(hypoglycemia) or dehydration. Humidity, low barometric pressure, cold or rainy weather
can elicit arthralgias, fatigue, encephalopathy or headache. A cold draft of air can
precipitate the appearance of pain in exposed skin and the underlying bone, or even VII
cranial nerve (Bell's) palsy. Patients with poor control of symptoms abhor the extremes of
ambient temperature. Typically, heat intolerance is revealed as irritability, headache,
excessive perspiration or sleepiness. Photophobia can enhance the somnolent propensity
that can occur while driving a car. Significant head trauma has incited severe symptoms
that later resolved with antibiotic therapy for LD. A sudden acceleration of
encephalopathy (see below), headache and dizziness, thought of as putative post-concussion
syndrome, can be evoked by head trauma. Diagnostic inaccuracy will be minimized by not
indolently attributing all problems following head trauma to the most obvious cause. I
routinely advise my patients with LD to abstain from cigarettes, alcohol and steroids
because therapeutic inadequacy or an avoidably prolonged convalescence is frequent
(Dattwyler, RJ, Lancet 1:687, 1987 - on steroid use). Patients have described clinical
deterioration when steroids were used fortuitously or intentionally when hypoadrenalism
was absent. Another hazard attending palliative steroid use is that some symptoms will be
concealed, rendering the clinical picture less interpretable. In a private communication,
a physician related that one of his LD patients succumbed to fatal cardiomyopathy after
receiving steroids. One helpful caveat is to avoid the use of electric blankets or
sleeping in water beds with the electric current activated, otherwise you might wake up
with one or more LD symptoms. Allergic and chemical hypersensitivities can enhance or
cause symptoms to emerge temporarily.
Symptoms vary stereotypically during the day. Joint
stiffness and "brain fog" are often reported on rising in the AM (but not solely
in the AM). Fatigue can be unrelieved by sleep, or develop between noon and 4 PM,
whereupon a short nap provides refreshment. "Madman Syndrome" (explosive
irritability) may appear toward the end of stressful work period or late in the evening. A
"mad face" can herald imminent detonation.
Prior to proper diagnosis, patients habitually report that
they were assigned the following diagnoses most often: Chronic Fatigue Syndrome, Multiple
Sclerosis, Fibromyalgia, Lupus, Candidiasis, Chronic mononucleosis, Hypoglycemia, and
Stress-related illness. If these appear in a differential diagnosis, then LD should be
considered.
On cursory inspection, many patients with LD appear
deceptively well but in fact feel awful Don't be fooled! The mien of a Lyme patient ranges
from phlegmatic, sullen, staring off into space, to one of agitated anxiety and
hyperkineticism. Their oral and written recitations similarly vary from cryptic to being
overinclusive and circumstantial. Geschwind's Syndrome embraces some varieties of LD
encephalopathy precisely (Textbook of Internal Medicine, Ed: Kelly, 1989, p. 2509).
Stuttering was reported by several patients to coincide with the onset of their LD and
often proved reversible.
Patients most frequently report fatigue that varies from
mild to debilitating. Usually there is a loss of interest and initiative so that lounging
around becomes habitual. This derives not from laziness, but results from lassitude.
Attempts to indulge avocational or vocational pursuits is frequently interdicted by either
the languor of Lyme or by encephalopathy. There is a tendency to nap, sleep that is not
rejuvenating, and hypersomnolence at inopportune moments; e.g., in the classroom or during
a favorite pastime. Sleeping away entire days is not unknown. Paradoxically, at usual
bedtimes, patients often experience insomnia or frequent awakenings. Sleep does not always
provide respite as ferocious or vivid nightmares can occur. Childhood night terrors can be
due to LD or more mundane causes.
Intermittent fevers range from low grade to 104.5 degrees
F. The typical context for high fevers is in the first week of antibiotic therapy
especially if multiple agents and/or IV drugs are used. While fever is the hallmark of the
classic Jarisch-Herxheimer (J-H) reaction, its appearance is inconstant. Compared with
most causes of high fever, the patient can look and feel their best during or shortly
after the fever with a relatively non-toxic demeanor. This can sometimes be diagnostically
helpful. The differential diagnosis of febrile seizures in infants should include LD. Many
LD patients have routinely subnormal body temperatures so that the appearance of a
temperature of 98.6 degrees F may be compatible with a low grade fever analogous to
diabetics.
Very often, the pinna and ear lobes are varying shades of
red. Less commonly, a similar erythema can be observed on the hands or malar (upper
cheeks) areas. A malar rash is not pathognomonic of Lupus, if in fact SLE is distinct from
LD (Abstract 55A, V LD Symposium). Fifth Disease (slapped face) is suspected of being due
to LD. Lymphocytoma of the ear lobes has been encountered more often in Europe. Cold hands
and feet even in warm environments occurs and some patients have Raynaud's phenomenon.
Potentially contributing to this vasoconstriction are excessive levels of vasoconstricting
hormones, magnesium and potassium deficiency, limbic or hypothalamic dysfunction due to
CNS infection, local inflammation of capillary sphincter or hypothyroidism. Eczema and
psoriasis can appear in conjunction with LD. A female LD patient had generalized psoriasis
covering 40% of her body. Antibiotics for LD gave total relief.
Alterations of cutaneous sensation are very common. Most
often there is numbness and tingling (paraesthesias)of the central face, fingertips, scalp
and in the extremities. Muscle twitching usually occurs in the eyelids and extremities.
Tremors, myoclonic jerking of entire extremities or truncal shudders can suggest
pseudoseizures but is attributed to neuritis. Patients also report electric shocks,
dysesthesias (abnormal sensory responses to stimuli), painful or itchy skin and flushing.
An inordinate amount of exertional or non-exertional sweating may be described in the
absence of hyperthyroidism. One of my patients experience anhydrosis (inability to sweat)
for 27 years until antibiotics were given for LD.
Dizziness, imbalance and clumsiness can become very
frustrating as patients drop objects or knock them over, trip a lot, turn into the wall
when rounding corners, and develop sloppy and slower handwriting.
Many use the phrase "a vibration in my head".
Others remark that they feel "toxic". Along with the "brain fog",
these colloquialisms connote LD until proven otherwise.
Eventually the majority, but not all, complain of one or
more of "foggy brain", forgetfulness, anxiety, mood swings, loss of initiative,
depression, impairment of concentration, inattention, easy confusion or disorientation
when attempting intellectual tasks. Paper shuffling can be the end result when patients
attempt to organize or assimilate even limited amounts of information. These problems, and
the others described below, constitute the salient features of Lyme encephalopathy.
Short term memory impairment causes patients to forget
what they were going to say, why they entered a room, where objects were placed, the
previous sentence or plot content, calendar dates, their schedules, names and faces of
familiar people, even family members. Cognitive neglect caused one patient to wander
around the room looking for the room looking for the pencil clenched between his teeth. A
mother left her infant and baby carriage in my office parking lot and went home. Others
forgot how to spell even simple words, how to read or must re-read with varying degrees of
comprehension. One patient drove to Philadelphia instead of the desired Princeton
destination because the initial letters were identical and confused him. After shopping
for groceries, another patient placed her shoes in the refrigerator and stored the food in
the clothes closet. Lyme patients can lose their way home or on the way to work, bypassing
otherwise familiar exits or plain forgetting where they are in time and space or how they
got there. This is known as topographical disorientation or environmental agnosia.
Elementary math problems may prove insurmountable. numerical errors are common. Sequential
task performance is compromised in Lyme. Lyme patients have a penchant for saying,
"Wait a minute", 2-3 times rapidly when the only demand on them is to record a
phone number, which also speaks of perseveration.
Inattention frequently characterizes the way patients
relate to the world. Some patients participate passively, unable to initiate or engage in
the usual forms of social and intellectual exchange. Verbal and written forms of
expression have a typical Lyme flavor. The content demonstrates disorganization, an
inability to follow a train of thought and there is a proclivity to ramble on and on in
great detail which propels further confusion amongst the forest of details. Ubiquitous
among the myriad cognitive flaws are the frequent errors of word selection or
pronunciation and the consistent word and number reversals.
Concentration on a task can be problematic because
attention span is abbreviated. As increasing amounts of information have to be processed,
the Lyme patient becomes proportionally lost, disoriented, frustrated, fatigued and
finally must desist from further intellectual activity. The desire to initiate projects
and social interaction is often blunted if not absent altogether. Thus a deterioration in
academic and vocational performance is a frequent manifestation of LD in children and
adults..
Miklossy (NeuroReport 4:841-848, 1993) reported the
detection of Bb spirochetes on dark-field microscopic examination of post-mortem brain
biopsy specimens FROM PATIENTS WITH ALZHEIMER'S DISEASE! CSF and blood cultures grew out
Bb from those cases. In my view, a child assigned a diagnosis of Attention Deficit
Hyperactivity Syndrome (ADH) or PNI (Perceptual Neurologic Impairment) should be evaluated
for LD. A 16 year old boy whose Tourette's Syndrome began at age 5, had Osp A antigen
detected in his CSF. LD treatment resolved the Tourette manifestations. Another patient of
mine with ADH had a positive IgM Lyme antibody in the serum. The manifestations of ADH
were eradicated while on antibiotics. Distinguishing causality from mere exacerbation of
ADH or Tourette by Lyme is moot, and therefore, I suggest an evaluation LD for these
patients. Parenthetically, the boy with Tourette also had cognitive impairment, familial
nephritis with early renal insufficiency and OCD (Obsessive Compulsive Disorder). These
clinical features all remitted with antibiotics! A real estate agent's prominent
encephalopathy resolved with LD treatment whereupon his commercial output jumped to a
record zenith and became the recipient of numerous corporate awards. The benefits of
arresting LD are self evident to him.
Personality changes are nearly universal in Lyme
encephalopathy with emotional and expressive incontinence being typical. Usually there is
a baseline irritability which fluctuates. Patients with LD encephalopathy react to even
mild degrees of stress with frustration, anger or crying spells out of proportion to the
situation. Emotions can reach escape velocity and rages can become volcanic with a
momentum beyond volitional control. Unpleasantness is inevitable due to volatile tempers,
super critical dispositions, and impatience with themselves or others. Lyme patients can
be easily irritated by anyone just walking into the same room even though eye contact is
never made or words exchanged. Low threshold exasperation in unexpected circumstances is
not uncommon. Thus a parent responds to an infant's needs with anger and frustration.
Perpetrators of "shaken baby syndrome" recapitulate an emotional response
indistinguishable from that of a Lyme patient whose encephalopathy is out of control.
Many express morbid fears of occult illness, impending
death and can be generally pessimistic or maudlin. Some develop intricate paranoid
theories regarding imagined conspiracies against them. Lyme patients often evince a
tendency for being overly sentimental. Hyperbolic thought finds expression in obstinacy,
self-righteousness, being contentious, speaking in categoricals, and inappropriate and
atypical vulgarity. Internalized anxiety results in the perception of being hurried even
without a deadline or the inability to remain calm when there is no reason for not feeling
calm. Panic attacks are the extreme of this anxious state and should arouse a suspicion of
LD. I suspect that in addition to CNS infection of the limbic system, these phenomenon
could also be the result of elevated adrenaline levels, Mg++ deficiency or
hypoglycemia. A rare LD patient will admit to agoraphobia or claustrophobia.
Depression alternating with anxiety is very common in LD.
Psychiatrists should routinely evaluate a depressed patient for LD before/when initiating
psychotropic medication. A patient with LD may have a plausible reason to be depressed,
but their emotional response can not only be incongruous with their usual coping style but
also the depression can be ablated or ameliorated with control of the LD infection. Lyme
encephalopathy typically vitiates an otherwise mature and functional emotional repertoire.
With a loss of voluntary and subconscious editorial
control of emotions and expression in word or behavior, a patient with encephalopathy
gives the general impression of being erratic, inappropriate, if not dysfunctional. Less
frequently, mania, obsessive-compulsiveness, schizoaffective disorders and
homicidal/suicidal ideation is encountered and has been reported. Fatal attractions are
consistent with the LD style.
Adolescent hormonal surges and the emotional turmoil
wrought by LD at once camouflage and exacerbate each other mutually. Thus, children tend
to be unruly, hard to please and prone to atypical emotional reactions. A child who is
misbehaving in class should not be dismissed as a "bad kid". Lyme can catalyze
inappropriate behavior and commentary. Many patients retrospectively realize that they
were out of control but in the event were unable to intercept their behavior.
Misattribution as to the origin of behavioral perturbations is the rule. The development
of aberrant personality traits can be gradual or even situational, further obscuring the
medical etiology. An acute break from normal behavior can serve to highlight the
abnormalities and suggest the need for evaluation. thus, dysfunctional behavior and
intellectual incapacitation are bitterly recalled by LD patients when they finally realize
how their interpersonal relationships, school and vocational conduct were negatively
impacted.
Clinically, there is considerable overlap between LD and
Chronic Fatigue Syndrome (CFS). In their masterful review of the pathophysiology of CFS,
Drs. Rosenbaum and Susser (Solving the Puzzle of CFS, 1992) describe SPECT scan findings
of brain perfusion (blood) in CFS patients. Hypoperfusion of the left temporal, right
parietal and left frontal lobes were consistently seen. These regions control the very
areas of functioning which are abnormal in both LD and CFS, namely verbal capacity,
memory, emotions and higher order information processing. Dr. Jay Goldstein has proposed
the term "limbic encephalopathy" to describe the disorders of memory, appetite,
temperature and appetite regulation, libido and hormonal homeostasis seen in CFS. He
advances the concept of an "agent X" which incites CFS and causes dysregulation
of the immune system and the limbic components of the CNS. I feel "agent X" is
Bb. I am encouraged in this view by anecdotal experience whereby CFS responded to
antibiotics given either fortuitously or by way of Lyme treatment, due to positive
serologies (antibody tests) for LD in some CFS patients and the development of a J-H
reaction in CFS patients who take antibiotics. Crimson crescents, portrayed as diagnostic
for CFS, I have detected in LD where the diagnosis was secure.
Limbic encephalopathy elegantly embraces the preceding
observations in Lyme encephalopathy. It is a potential mechanism to explain my suggestion
that LD can be responsible for anorexia nervosa/bulimia. Anorexia was documented in
earlier studies on LD. Uncinate fits and are characterized by hypersexuality, rage states
and vulgarity, are compatible with LD. Indeed, disinhibition, the release of the usual
brakes on behavior, would be part of limbic dysfunction.
LD could cause reversible disturbances in brain physiology
through cytokine mediators, direct infection; e.g., encephalitis and perivasculitis,
demyelination, metabolic aberrations within the CNS such as regional hypoperfusion,
altered rheologic (flow) characteristics of blood, intracellular acidosis and the
depletion of ATP. Permanent changes may include demyelination or loss of neurons leading
to atrophy.
Neurologic complications in earlier reports were said to
occur in 20% of LD cases. In my experience, and as published by Dr. Logigian, 90% of
patients have one or more of encephalopathy, cranial neuritis or psychiatric changes.
Early in the course of LD, these problems may be absent or muted, but eventually intrude
and can become dominant aspects of LD.
Many patients are told that they have Multiple Sclerosis
(MS) because of brain MRI findings or a spinal tap was positive for oligoclonal bands
(OCB) or myelin basic protein (MBP). The medical literature is quite emphatic that MRI
does not reliably distinguish between MS an LD because there is too much overlap in their
supposedly distinct appearance and location of plaques. Plaques have been detected with
both disorders in the brain and spinal cord. OCB's and MBP are non-specific markers for
demyelination (loss of sheath around nerves) and do not signify a cause of the
demyelination. In Miklossy's study above, senile plaques stained avidly for Bb
spirochetes. Vincent Marshall reviewed the MD literature in Medical Hypothesis (Vol 25:
89-92, 1988) and advances the notion that LD is causing MS! His survey revealed that
multiple studies prior to 1951 were able to demonstrate spirochetes in the spinal fluid of
MS patients (by inoculation into animals and on silver stain of CNS tissues). Dr. Coyle
has documented the presence of antibodies to Bb in MS patients (Neurology Vol. 39:760-763,
1989). The encephalopathy attributed to MS is very reminiscent of LD. Both MS and LD are
associated with sinusitis (Lancet, 1986). Dr. Leigner has reported a case of LD which
fulfilled all criteria for MS. The epidemiology of MS and the geographic distribution
parallels that of LD. The symptoms of both LD and MS can be aggravated if the patient
takes a hot bath. Anecdotally, patients with LD, who previously had been identified as MS,
responded to antibiotic therapy.
LD has been documented to cause strokes, paralysis, a
variety of seizures, transient or permanent blindness, Parkinsonian-like movement
disorders, motor and/or sensory neuropathies, mononeuritis multiplex, radiculoneuritic
pains, meningitis and encephalitis. It has been affiliated with Lou Gehrig's disease and
the Guillain-Barre Syndrome.
Recent reports suggest that the spectrum of neurologic LD
is actually similar in both Europe and the USA (Jacqueline, MS; Surv Opthalmol 35:191-204,
1990) and belies the assertion that European LD research holds no relevance for LD in the
USA.
The more commonly noticed neurologic deficits involve one
or more cranial nerves (I thru XII), most often the sensory divisions of the trigeminal
(V) and the motor components of the facial (VII) nerves in my patients. In declining
order, deficits to pain sense are detected in V2, V3, and V1.
V2 neuritis appears as paraesthesias or dullness in the central face and
cheeks. Gum and tooth pain can be another manifestation of trigeminal neuritis. Rule out
dental abscess or sinusitis which can present with similar tooth pain.
The most common cranial neuritis I see is that of the VII
nerve. Abnormalities of the VII nerve can be varied. Usually there is symmetry of the
central facial creases, the lips at rest or in motion, or overt deviation of the mouth or
smile to one side. Colleagues have dismissed these asymmetries as normal findings, saying
"well, everyone has those". I feel there is significance when antibiotics cause
these so-called innate or normal findings to resolve.
When Bell's palsy is present, there are the facial defects
described above for VII neuritis plus a wider eye on the same side as an elevated eyebrow,
often attended by complaints of tearing and drooling (usually at night) on the affected
side. 10.6% of 951 LD cases were found with Bell's palsy and 25% of those have had
bilateral Bell's palsy (Clark, JR et al. Laryngoscope 1985: 95: 1341-45). Bilateral Bell's
promulgated as pathognomonic for LD, actually can be associated with intrapontine lesions,
diabetes mellitus, syphilis, sarcoid, leukemia, Guillain-Barre, viruses or diphtheria.
Considering the incidence of Bell's palsy in LD, it is improper to treat it as viral in
origin without a work-up for LD.
Incidentally, hyperaccusis (sound sensitivity) can be a
feature of VII neuritis. Olfactory neuritis (I) is attended by dysosmia (unusual smells).
Neuritis of the III, IV and VI cranial nerves will show up as double vision. When the VIII
nerve is involved, vertigo and impaired hearing can result. I have had at least two cases
of Meniere's Disease respond to treatment for LD. Dysphagia (difficulty swallowing) can be
associated with X neuritis but not invariably. More often in my experience, a deviated
uvula or soft palate is perceived. Dysphonia (altered voice) can occur with X neuritis
when the branches that serve the larynx are affected. Recurrent laryngeal nerve paralysis
has been seen with LD (Schroeter, V. et al. Lancet 2:1245, 1988). IX neuritis
(glossopharyngeal) can cause a unilateral sore throat which was reported by 3 of my
patients. XI neuritis (spinal accessory) presents as trapezial or sternocleidomastoid
muscle weakness resulting in a drooped shoulder or weakness on resisted head rotation
respectively. Do not confuse this with a unilateral dystonia where the affected shoulder
girdle will be elevated with preserved motor strength on both sides. Hypoglossal (XII)
neuritis can be associated with a heaped up tongue on the unaffected side or deviation of
the tongue on protrusion toward the abnormal side.
LD related headaches can have a wide variety of patterns
and can broadcast the early onset of LD or a flare of LD. The headaches incorporate the
characteristics of migraines, muscle tension or cervical/radicular headaches. Pseudotumor
cerebri (elevated CSF pressure with normal CSF analysis in the absence of intracranial
masses) can complicate the course of LD and cause headaches. Papilledema (swelling) of the
optic disc is usually present when CSF pressures are elevated, but not invariable. A
spinal tap will have high opening pressures and be therapeutic as well. Depending on the
characteristics of the headaches, sinusitis and brain tumors may have to be ruled out.
Cluster headaches have characteristics compatible with some LD headaches including
responsiveness to 100% oxygen.
Immunosuppression due to LD has been reported. Therefore,
it is not surprising that recurrent or intractable upper respiratory tract infections
(URI's) have been noted. LD can cause or worsen pre-existing sinusitis, asthma,
bronchitis, otitis, mastoiditis. Frequently, the pediatric history of LD contains a
pattern of repetitive URI's. Mastoiditis can also be associated with a Bell's Palsy. LD
can be affiliated with the appearance of new onset allergies for the first time in a
patient's life or magnify an atopic predisposition. The usual medications for sinusitis
and allergies will have a predictably diminished effect, when LD is operant.
Another concomitant reported by an incidental patient is
the occurrence of motion sickness which can be reversed with LD treatment.
Eye related problems in LD are commonplace and can include
conjunctivitis, ocular myalgias, keratitis, episcleritis, optic neuritis, pars planitis,
uveitis, iritis, transient or permanent blindness, temporal arteritis, vitritis and
periorbital edema (Jacqueline MS; Ibid). Horner's syndrome, ocular myasthenia gravis, and
an Argyll-Robertson pupil are also reported. Optic neuritis has been observed to become
recurrent or intractable after treatment with steroids. Given the earlier remarks about
the detrimental effects of steroids on LD, recidivous optic neuritis may be due to occult
LD.
Lyme hepatitis occurs in approximately 15-20% of patients.
Liver tenderness is inconstant and the elevated liver enzymes respond to antibiotics.
Sometimes, the hepatitis appears temporarily in the early phases of treatment with
subsequent resolution.
In many of my patients, cysts are found not uncommonly in
various locations: thyroid, breast, liver, bone, ovary, skin, pineal gland, and kidney.
Some forms of Polycystic Kidney and Fibrocystic Breast Disease may be LD manifestations.
LD can cause an interstitial cystis leading to bladder
pain relieved by urination. A neurogenic bladder can develop with either hesitancy,
frequency, loss of bladder awareness, urinary retention, incontinence or the symptoms of
UTI (urinary tract infection). I suspect that some cases of chronic pyelonephritis are
actually LD. Pediatricians may want to consider that nocturnal enuresis (bedwetting) is
secondary to LD.
Constipation severe enough to cause fecal impaction can
occur. Many LD patients will experience a spastic (irritable) colon and that diagnosis
should spark a search for LD. I have treated LD attended by ulcerative colitis with
substantial remission of the colitis when antibiotics were inaugurated. Fecal incontinence
due to impaired rectal sphincter tone can occur. Dr. Martin Fried has demonstrated Bb
spirochete in the gastric and duodenal mucosa of children with LD who complained of
abdominal pain and who were documented to have gastritis and/or duodenitis. It is
appropriate to work up LD when confronted by these clinical entities.
Among untreated patients with LD, arthritis can ultimately
develop in up to 60%. The joint swelling, which may or may not be painful, frequently is
episodic, recurrent and migratory if multiple joints are involved. Any joint can be
affected including the TMJ (temporomandibular) and small joints of the fingers (contrary
to earlier reports). Up to 10% of untreated LD arthritis can develop into
destructive/deforming synovitis almost identical to Rheumatoid Arthritis (RA). Dr. Lavoie
has published the coincident findings of LD with RA, and SLE (lupus) with LD. The SLE was
associated with positive DS-DNA (double stranded DNA) which is considered diagnostic for
lupus. This marker improved with antibiotic treatment for the LD. The author felt that the
LD might be causing/aggravating the SLE.
I would like to present a case of a 38 y.o. white female
who, 24 days postpartum, presented with Seropositive LD. She had a prior history of a
round rash 6" diameter in 6/90, DS-DNA =320 in 12/90 and previously treated Lyme
(seronegative) by various physicians (including myself) from 12/90 to 12/92 with
eradication of all symptoms. The patient became pregnant 7/93 and her former Lyme symptoms
were revived. She declined to take amoxil prescribed by her OB-GYN until 11/93. this was
followed by 10 days of Zithromax with minimal results. The exacerbation accelerated about
2 weeks prior to her 3/28/94 visit to me. In addition to Lyme, her contemporary problems
included SLE, episodic Sjogren's Syndrome (dry mouth/eyes, parotiditis), anticardiolipin
antibodies without thrombotic events, polyarthritis (in ankles, knees, hips, shoulders and
PIP's of the fingers), a left IX neuritis, a right Bell's Palsy, ptosis of the left upper
eyelid, myositis of the rectus abdominus muscle, generalized fibrositis and periostitis,
degenerative changes in several finger joints and a few costochondral joints, and
fibrocystic breast disease. Encephalopathy was absent! The lab findings included: Lyme
Elisa IgG = 1.4 (+), Lyme IgM = 320 (++), Lyme LgM by IFA = 640 (+++), a NEGATIVE Western
Blot (only 41 KDA) and IgG by IFA for LD, positive Lyme IgG Antibody in synovial fluid
(Class II exudate) obtained from the right knee = 1.94, DS-DNA = 5, 120 (less than 10 is
normal), ANA = 2,560 (+++), positive Sjogren antibody (SSB = 33), positive anticardiolipin
antibodies (IgG = 66, IgM = 44.9), leukopenia (wbc = 2,800), and anemia (Hgb = 11.4), 10
bands and 1736 PMN's on CBC differential, ESR = 32, slightly depressed complement levels:
C3 = 55, C4 = 14. Lyme PCR (a test for the DNA of Bb) in synovial fluid was negative.
Concurrent vaginal bleeding prevented us from obtaining an immediate U/A.
Other lab tests : Fe = 34, Ferritin = 64, transferrin
saturation = 9.36%, Bun = 18, Creatine - 0.9, Rheumatoid Factor and SSA negative; thyroid
and coagulation profiles, TSH and PTH normal; CH50 = 222, CXR and EKG noncontributory.
The patient acutely developed (after using Motrin on her
own, instead of the prescribed Percocet for relief of arthralgias while the work up was in
progress) leukopenia (wbc = 1,700),neutropenia (PMN's = 1,074), and an acute hepatitis
with abnormal liver enzymes (LFT's) : Total Bilirubin = 1.58, alkaline phosphatase = 328,
LDH = 344, GGTP = 113, SGOT = 246, SGPT = 285.
Within 72 hours of stopping Motrin use, the wbc rebounded
to 4,700 but by then the patient had developed an acute partial paralysis of her legs
(3/5), with deltoid, biceps and vastus lateralis myositis, a new left VII neuritis, and
the polyarthritis was more ebullient and painful. A fever of 101 degrees F had appeared.
Subsequently, hypertension (BP = 154/94), a small posterior pericardial effusion and
hypokalemia (K+ = 3.3 mmol/L) were appreciated. Urine and Blood Cultures were negative.
Urine analysis (U/A) contained 30-35 wbc, but proteinuria and cylindruria were absent.
Elevated LFT's were again encountered. The patient declined, at various times: an MRI of
brain, a bone marrow aspiration, spinal tap, EEG, and EMG.
On admission to the hospital, IV Claforan was initiated.
At 41 hours, a crescendo J-H reaction attained a fever apex of 103 degrees F, but the wbc
count again fell to a nadir of 1,800 with neutropenia (67.2% = 1200 PMN's). As the patient
gradually defervesced (temp = 100 degrees F at 75 hours), the wbc count slowly ascended to
2,700 (PMN's = 2100) in spite of continued Claforan, The paralysis remitted over the
initial 48 hours. concomitantly, the LFT's normalized rapidly, the Sjogren manifestations
and cranial neuropathies disappeared, the BP became 120/70, muscle tenderness was reduced
and the U/A was devoid of abnormalities.
By discharge to home on the 6th hospital day, the
polyarthritis (as judged by joint swelling) had resolved in 75% of the involved joints and
was ameliorated in the rest, and the fever = 99.6 degrees F. However, the knees were still
painful and hobbled the patient, and range of motion was impaired in the knees, shoulders
and hips. Biaxin, begun day 6, caused a transient acute memory loss from day 8-9 without
fever.
Features supportive of the SLE diagnosis include:
leukopenia, positive ANA, a high DS-DNA titer, arthritis (R/O erosions).
During the hospital stay, a more thoughtful insurance
medical director rescinded an earlier prohibition for intravenous antibiotics. Had the
first "reviewer" acceded to my initial plan of care, the paralysis and the
hospitalization it prompted could have been avoided. Treatment is advancing. Repeat
DS-DNA, ESR, ANA, CPK, C3, CH50, and X-Ray and MRI evaluation of joints is anticipated.
The anemia is being investigated.
The tabulation of rheumatologic syndromes, either caused
by LD or affiliated with it, is growing. Drs. Weber and Schwartzberg have reported
Polymyalgia Rheumatica apparently caused by LD. As in the case above, Sjogren's Syndrome
with LD has been published. Antibodies to Bb in the context of Psoriatic arthritis,
systemic sclerosis and Reiter's Syndrome have been documented.
An expanding cohort of patients in my practice appear to
have long-standing LD that dates to their "growth spurt" years and their past
medical history contains the previous development of Osgood-Schlatter's Syndrome (water on
the knee) in their teens. A relationship to LD can't be excluded.
Arthralgias and bone pain in LD can be excruciating. It is
the imprudent clinician or parent who lackadaisically attributes these symptoms to
"growing pains" or aging.
Another patient of mine recalled recurrent and migratory
polyarthritis since he was 18 (1966). Monthly Medrol Dose Packs (steroids) failed to alter
the clinical picture. In 1987, he was hospitalized with an acute exudative synovitis of
the knee, whereupon ear lobe biopsy demonstrated the classic histologic feature of
Relapsing Polychondritis, a very rare disorder with a peak onset in the 5th decade of
life. In spite of continual high dose steroid treatment, (and later methotrexate with
non-steroidal anti-inflammatory agents), he eventually developed a deforming arthropathy
in his hands which progressed slowly between 6/90 to 12/92. Earlier physicians had
discounted the significance of a positive Lyme Elisa = 1.09 in 4/91 as "low
titer". An unsuspected encephalopathy betrayed its existence as memory and
concentration impairment beginning 1/91. The patient presented for LD evaluation 1/93.
Laboratory values include: an IgG by Elisa = 14.7, IgM by IFA = 80 and the Western Blot
had bands at 31 and 41 KDA. the polysynovitis and encephalopathy proved rapidly responsive
to antibiotics for LD. The patient was quickly emancipated from the other medications
although steroids had to be slowly tapered and are now down to an inconsequential dose
without recurrence of rheumatologic complications. The patient, although symptom free
while on antibiotics, has permanent crippling deformities of the hands.
Cardiac complications arise in 8-12% of LD cases.
Conduction defects and heart block, of which first-degree is the most common, can be
discovered on EKG. A long rhythm strip should be employed to detect intermittent blocks.
Higher degrees of heart block can result in fainting or death and may require cardiac
pacemaker.
Sudden death can also result from arrythmias. Fast and
slow heart rates occur, usually at the time of symptom flares, and sometimes in the manner
of Sick Sinus Syndrome (tachy/brady). Ventricular tachycardia has been documented to
attend LD infection in the heart, confirmed on cardiac biopsy. The cardiomyopathy may be
complicated by congestive heart failure (CHF) as the following case might illustrate.
I had been treating a white male in his 60's for several
years for LD with (initially IV antibiotics) oral antibiotics and in the main, his
symptoms were controlled. However, he would occasionally complain of "traveling
pains" (arthralgias). I was impressed with mild encepahalopathy (confusion) and he
had a brief monoarticular arthritis of the right knee.
In concert with numerous consultants, our work up over a
few years also uncovered: Diabetes mellitus (non-insulin dependent), COPD; hypertensive,
ischemic and dilated cardiomyopathy (enlarged heart); both diabetic and hepatitis C
related liver involvement confirmed on liver biopsy (not helped by a prior preference for
alcohol); colon cancer for which he underwent a transverse colectomy (partial removal of
the colon),colonic polyps; and Barrett's esophagus. A fall at work caused a LEFT sided
appendix to rupture (talk about being thrown a curve?!).
Most significantly, he had been troubled with recurrent
non-sustained ventricular tachycardia, atrial fibrillation and episodic CHF all of which
increasingly escaped therapeutic control with the usual measures. This resulted in
frequent hospitalizations, He had a small myocardial infarction of the diagonal branch in
the past. A MUGA scan revealed an ejection fraction (a measure of cardiac output and pump
function) of only 21% which is quite low. His exercise intolerance due to shortness of
breath fluctuated but interfered substantially with his quality of life.
During a 1993 hospitalization for acute CHF compounded by
ventricular arrythmias, we found that these problems were resisting attempts to completely
regulate pharmacologically. In the past, I had noted that when his LD was flaring up, his
cardiac status would deteriorate. As the patient had incurred Pulmonary Fibrosis
(ultimately reversible) as a side effect of an antiarrythmic drug, he was not deemed a
suitable candidate for cardiac biopsy.
Intravenous Claforan was begun empirically and to our
astonishment, he recuperated from his CHF in short order. A repeat MUGA scan on day 5 of
IV Claforan showed a NORMAL ejection fraction of 51%! This welcome and salutary change in
status was maintained by prolonged IV therapy. On a program of continued oral antibiotics,
CHF was controlled to such good effect that he was able to walk 5 miles in the dead of
winter to my office without any shortness of breath or chest pain.
To my mind, one of the more remarkable aspects of this
case was the disproportionate way in which cardiac complications dominated the clinical
course relative to the other LD symptoms and yet all responded fortuitously to IV
antibiotics. Thus treatment may not eradicate symptoms synchronously. The other salient
lesson here is that he probably has CHRONIC LD, a diagnosis made purely on clinical
grounds as serologies were always negative.
Again, differentiating Lyme cardiomyopathy from a mere
exacerbation of cardiomyopathy (due to other causes) by LD remains an unresolved issue.
Intuitively, we might suppose that the other component etiologies which contributed to his
cardiomyopathy would not respond so briskly to antibiotics, unless there was an as yet
undefined relationship with the LD. His cardiac and BP medications are now providing the
customary benefits in a predictable fashion. On oral therapy alone, mild shortness of
breath to stairs is once again emerging over time. Further evaluation is forthcoming.
Mitral valve prolapse is not uncommonly found in LD. MVP
can be associated with confounding chest pain and ventricular arrythmias. It is often
accompanied by Mg++ deficiency and LD can cause Mg++ levels to be
low. In a few of my patients, MVP developed only after the onset of LD and resolved with
LD treatment. Chest pain due to LD may arise from numerous causes: myocarditis,
pericarditis, angina, asthma, bronchitis, periostitis of the ribs, pectoral myositis and
tendinitis, sternoclavicular and costochondral arthritis, esophagitis and esophageal
spasm, stomach acid reflux, and gastritis.
Elevated ACE (angiotensin converting enzyme) levels have
been detected in LD (Leigner, 1990). The relationship between high ACE levels and heart
disease may provide a mechanism to explain LD's anecdotally suspected tendency to
accelerate Coronary Heart Disease and incite hypertension. Possibly, Syndrome X (angina
with normal coronary arteries at catheterization) is due to LD induced arterial spasm, an
event that might be enhanced by direct perivasculitis and/or Mg++ deficiency
(see Grisold, M abstract No. 55F, V Int'l Lyme Symposium).
Potassium deficiency without an obvious origin irregularly
evolves in LD. Rarely, the K+ losses are profound. This could be due to Mg++
deficiency. New onset or difficult to control hypertension is more likely to be seen. LD
should be part of the evaluation of hypertension. LD treatment has permitted easy BP
control in several patients, some of whom were able to forego using their traditional
hypertension medications. Increasingly, I am encountering thyroid disease in LD. A local
endocrinologist has remarked to me privately that the incidence of thyroid involvement in
LD may be greater than expected from the normal population. A final judgement awaits
formal statistical analysis. In many of these patients, the thyroid dysfunction was seen
to originate in the pituitary or hypothalmus. Remaining alert to the possibility of
thyroid disease is essential because there can be considerable clinical overlap with LD.
Subacute thyroiditis is the most prevalent thyroid phenomenon I see in LD. Hypoadrenalism
can uncommonly develop. Uncorrected hormonal aberrations can vitiate otherwise effective
LD therapy. Like any infection, LD can provoke the onset of hyperglycemia and alter the
facility with which diabetes is managed.
Impaired fertility and a loss of libido is not infrequent
in LD. A reversible cause of infertility should be sought and ought to include LD. Reduced
sexual interest without an ostensible justification is usually misinterpreted by the
partner with predictable social and psychological turmoil. LD infection in the CNS or in
the sex glands may be causal. In a few female LD patients, disturbed estrogen and
progesterone levels were found. Early "menopause", skipped menses, and heavy
menstrual flow represent a few of the perturbations in LD.
Women with symptomatic LD can experience new onset or
heightened PMS (ballistic mood swings and irritability), or perimenstrual headache or
cramps. The last of these theoretically could also be due to Pelvic LD infection
(ooperitis or salpingitis) and/or elevated PGE-2 (prostaglandin E-2) levels, the latter
having been reported in LD. A surfeit of PGE-2, free radicals, altered fat metabolism and
general immunosuppression by LD may contribute to a predilection (stimulate or predispose)
for oncogenesis (forming cancer). Carcinomas are not unknown in LD: melanoma, thyroid
cancer, and lymphoma have been published. Free radicals, by engendering connective tissue
cross-linking, could be responsible for intra-abdominal adhesions to form, and for some LD
patients to appear older than their stated age, or have a haggard facial appearance.
Breast pain due to mastitis and testicular pain from
orchitis have been described by some of my patients. So far, there are 3 men in our files
whose chief complaint with LD was pelvic pain due to chronic prostatitis. The therapeutic
strategems for LD provided superior relief whereas using Cipro or Doxycycline alone gave
partial or temporary improvement
Flawed studies have created the impression that pregnancy
outcomes are not influenced by LD. There is substantial documentation to suggest a causal
relationship between LD and stillbirths, congenital abnormalities, spontaneous abortion,
low birth weight babies, prematurity and intrauterine fetal infection acquired from the
mother. An outcome of untreated LD arising from Mg++ deficiency could be
pre-eclampsia (hypertension) or eclampsia (hypertension with seizures). Magnesium is often
relied on to treat these problems. Women with LD in pregnancy can experience severe
morning sickness, gestational diabetes mellitus and prominent flares of Lyme related
symptoms. As both LD and Sudden Infant Death Syndrome are attended by sleep apnea, this
should impel further research to determine if some babies with SIDS are actually suffering
from LD. Bb can appear in the breast milk.
Lyme patients very often complain of heel pain. This may
be due to an underlying plantar fasciitis, with or without a heel spur, or periostitis of
the heel. Epicondylitis (tennis elbow) is another complication. Carpal Tunnel Syndrome can
also develop in untreated LD.
Lyme patients tend to heal slowly and are prone to
musculoskeletal injuries, sometimes without the usual antecedents. One patient sustained a
vertebral facet dislocation while shaving ( the usual context is athletic). Even in the
well conditioned athlete, there can be an unexpected spate of muscle cramps, sprains,
tendinitis and bone or joint pains at the sites of load bearing.
Muscle weakness occurs in some LD patients, More commonly,
exertional performance is limited by shortness of breath, poor coordination,
musculoskeletal discomfort, or fatigue. Exercise without or early in treatment can
precipitate a flare of fatigue, especially the following day.
Low back ache can arise from sacroilitis, paravertebral
lumbosacral muscle strain/spasm, and herniated vertebral discs. In a few patients, spinal
stenosis is encountered.
Inflammation of the abdominal wall muscles, in particular
the rectus abdominus is not an infrequent problem. Usually the tender sites are focal,
involving more often than not, the lateral borders of the rectus abdominus muscle. Nausea
is often present as well. The sites are best located when the patient is performing a
Valsalva maneuver or doing a partial sit up. Failure to appreciate the abdominal myositis
may lead to avoidable extensive GI workup.
A very helpful diagnostic maneuver is palpatory tenderness
of the medial tibia shaft due to periostitis (inflammation of the tissue around the bone
if not the bone itself). Periostitis is also common in another spirochetal disease,
syphilis (Textbook of Medicine, Ed: Kelley, 1989, p. 1587) and is responsible for the bone
pain that both syphlitic and Lyme patients experience. Tenderness is easily elicited in
95% or more of LD patients simply by pressing the bony aspect of the thumb joint against
the medial aspect of the tibia about 3-6 inches above the ankle. The intensity of the pain
experienced by the patient can vary, but is often exquisite and will cause the leg to
recoil abruptly. The pain often lingers after this procedure. In a minority of LD cases,
periostitis is generalized and I have appreciated skull involvement in a few instances. A
small proportion of LD patients have periostitis.
As a result of fibrositis, myositis, periostitis, is it
any wonder that the ill LD patient view hugs as potential torment? The chagrin of
mystified family members is understandable. Self-examination for periostitis can be
unreliable. Periostitis pubis (of the pubic bone) can mimic bladder pain or be the origin
of lower midline abdominal pain, especially in children.
Lyme (and Brucella) should be included in the differential
diagnosis of Desert Storm Syndrome, with which LD shares many features.
The abundant research opportunities should be clear to
all. It is unnecessary to give Lyme Disease the "Galileo" treatment. Thank you
for your interest. Comments and criticisms are welcome.
Visitors here: 
ALL content at this site is copyright © 1996-2010, the author.
Site most recently modified:
June 16, 2008.
