Interstitial cystitis as a manifestation of Lyme Disease
Deborah A. Metzger, PhD, MD
For those who have ever had a bladder infection, you have an inkling of what it is like to
have interstitial cystitis (IC) or painful bladder syndrome (PBS). IC is an inflammatory
condition of the bladder producing symptoms of urgency, frequency, and nocturia
(waking up at night to urinate). At its worst, patients may urinate every 10 minutes during
the day and get up at night 3-8 times to urinate.
The urological symptoms often found in association with Lyme disease resemble those of
interstitial cystitis (IC): frequency, urgency and nocturia. Borrelia burgdorferi spirochete
has been found both in bladder biopsies and the urine of patients with Lyme disease.
This article is intended to examine this syndrome in the context of Lyme disease and to
offer suggestions as to symptomatic treatment and resolution of IC.
What is Interstitial Cystitis?
IC is considered a urinary bladder disease of unknown cause characterised by urinary
frequency, urgency, pressure and/or pain in the bladder and/or pelvis. Pain typically
increases as the bladder fills and reduces after voiding. Patients may also experience
nocturia, pelvic floor dysfunction (thus making it difficult to start their urine stream),
pain with sexual intercourse, and difficulty driving, travelling or working.
The signs and symptoms of interstitial cystitis vary from person to person. The severity
of symptoms caused by interstitial cystitis often fluctuates, and some people may
experience periods of remission. In addition, the symptoms of each affected person may
vary over time, periodically flaring in response to common triggers such as menstruation,
seasonal allergies, stress, Herxheimer reactions, and sexual activity.
IC appears to have an as yet unexplained association with certain other chronic diseases
and pain syndromes such as vulvodynia, vulvar vestibulitis, chronic fatigue, migraine
headaches, irritable bowel, chronic pelvic pain, endometriosis, fibromyalgia, and
autoimmune diseases. All of these conditions are related to inflammatory processes and
have a predominance of female sufferers. The question with IC in general and in Lyme
disease in particular, is whether the bladder symptoms are a separate disease process or
whether a general inflammatory condition in the body is expressed by a variety of
vulnerable tissues and organs.
IC affects men and women of all cultures, socioeconomic status, and ages. IC is more
common in females than in men by a ratio of 10:1. Epidemiological data suggest that up
to 12% of women may have symptoms of IC. In men, IC may be diagnosed as prostatitis,
pelvic myoneuropathy or chronic pelvic pain syndrome. There have been no studies to
determine the prevalence among those with Lyme disease, however, I find Lyme disease
frequently among those with IC. Research has determined that the quality of life of IC
patients is equivalent to those with end stage renal disease.
Cause of IC
Regardless of the proposed causes of IC: autoimmune, hereditary, infectious, hormonal,
neurologic or allergic, the common thread that ties them all together is inflammation.
Mast cells play a central role in all of these inflammatory processes to initiate and
coordinate a person’s immune responses to invasion by viruses, bacteria, and parasites.
Mast cells are found in the bladder muscle and the bladder mucosa of patients with IC,
but not in controls. Once stimulated, these cells produce a wide range of chemicals
(histamine, TNF-alpha, inflammatory prostaglandins, leukotrienes) that cause pain,
inflammation and the symptoms of sterile prostatitis, urethritis, orchalgia (testicular
pain), epididymitis, and/or IC.
Mast cells are known to be involved in immediate or IgE-mediated allergies. Mast cells
are localized in tissues in which contact with pathogens is likely to occur: mucosal
surfaces of the airways, gastrointestinal, and urogenital tracts as well as the connective
tissue of the skin. These are also the tissues that are prone to be affected by allergies. IgE
is bound to mast cell receptors and when antigen binds to IgE, degranulation (release of
inflammatory chemicals) of the mast cell occurs. Allergies were found in 40% of IC
patients (I have found in my patients that it is more like 100%).
In their role as a first line of defense against pathogens, receptors on the surface of the
mast cell bind to proteins on the cell wall of bacteria which results in mast cell
degranulation (release of inflammatory chemicals). There are many studies that have
examined the relationship between IC and infection. Compared to controls, women with
IC have a higher prevalence of anaerobic bacteria in midstream urine samples. Others
have found DNA evidence of chronic infection with cell wall deficient bacteria (i.e.,
Mycoplasma, Ureaplasma, Chlamydia pneumoniae and gram negative bacteria). Borrelia
burgdorferi has been found in bladder biopsies and urine of patients with Lyme disease.
Persisting bacteria in the urinary could be the initiating factor in a complex cascade of
mast cell/bacterial interactions resulting in inflammation.
Mast cells may actually be the mediator through which female hormones play a role,
accounting for the 10:1 female to male preponderance of the disease. Estradiol augments
the secretion of mast cell histamine in response to substance P (one of the inflammatory
chemicals). Bladder mast cells express high-affinity estrogen receptors, and there is a
higher number of such cells present in patients with IC compared with controls. Although
this may help explain why IC is so common in women, the hormonal role can only
account for the propensity of IC to occur in females, not the ultimate etiology.
Chronic inflammatory stimuli can also activate sensory nerves, specifically pain fibers, to
trigger neurogenic inflammation through release of neuropeptides such as substance P,
neurokinin A, and calcitonin gene–related protein which have been shown to cause
degranulation of mast cells. A correlation was found in patients with IC between the
number of nerve fibers and numbers of mast cells as well as between the number of nerve
fibers and the amount of histamine.
Regardless of the origin, it is clear that the majority of IC patients struggle with a
damaged bladder lining. When the surface glycosaminoglycan (GAG) protective layer is
damaged by inflammation, urinary chemicals can “leak” into surrounding tissues, causing
pain, inflammation, and urinary symptoms. This produces a profound sensitivity to acidic
foods and certain chemicals found in foods and medications.
Often, a diagnosis IC is made only after a patient has been seen by a number of
physicians and treated with antibiotics for presumed urinary tract infection without
resolution of symptoms.
One method of screening for IC is to use a questionnaire. There are three published IC
symptom questionnaires. The University of Wisconsin IC Scale is of interest to those
with Lyme disease because of the surprising similarity to Lyme symptoms:
Bladder discomfort Swollen ankles Heart pounding
Bladder pain Difficulty sleeping because
Nasal congestion Other pelvic discomfort
Headache Flu of bladder symptoms
Backache Abdominal cramps Sore throat
Dizziness Numbness or tingling in Urgency to urinate
Feelings of suffocation fingers or toes Coughing
Chest pain Nausea Burning sensation in
Ringing in ears Going to the bathroom bladder
Getting up at night to go frequently during the day
to the bathroom Blind spots or blurred
Aches in joints vision
IC is a diagnosis of exclusion primarily based on symptoms of urgency/frequency and
pain in the bladder and/or pelvis and the failure to find any other causes such as vulvar
vestibulitis, vulvodynia, pudendal neuralgia, urethritis, endometriosis, bladder cancer,
urethral diverticulum, urinary tract infection, prostatic hypertrophy/cancer, irritation from
medications, cystocele, vaginal infections, neurological disorders, sexually transmitted
infections, pelvic floor myalgia or occult inguinal hernias.
The minimum workup of suspected IC should include a history, physical exam, urine
culture and sensitivity (a dipstick or urinalysis is insufficient), urine cytology, vaginal
culture, PSA, and STD testing. Some urologists also recommend urodynamic studies,
office cystoscopy, and cystoscopy and hydrodistension with biopsy under anesthesia. A
potassium chloride challenge has also been promoted as a test for IC, but it has been
found to be invalid.
At this time there is no cure for IC, nor is there an effective treatment which works for
everyone. However, the vast majority of IC patients are helped by one or more of the
Diet*. The proper diet can decrease symptoms and decrease inflammation.
Bladder irritants include alcohol, smoking, coffee, tea, sugar substitutes, fruit
juices, tomatos, citrus, cranberries, B vitamins, Vitamin C, and chocolate. To
decrease inflammation, I have found great success in my patients with a
combination of a low glycemic diet, avoidance of allergenic foods
(determined by skin testing) and a gluten free diet if gluten sensitive
Self-help*. Self-help techniques can improve the quality of life and reduce the
incidence and severity of flare-ups. These include acupuncture, stress
reduction, visualization, biofeedback, bladder retraining and exercise, among
Over-the-counter aids*. Medications such as Cysta-Q®, Prelief®, Algonot-
Plus®, Desert Harvest’s Aloe Vera® and Quercitin have few side effects and
surprising efficacy at reducing symptoms of IC.
Prescription medications for bladder irritability. Bladder analgesics (such
as Urimax® or Pyridium®), anticholinergic muscle relaxants (such as
Ditropan® and Detrol®) and antispasmodics (Urispas®) almost universally
have no benefit for those with IC. Failure to respond to these medications can
be used as a screening tool for those with urgency and frequency.
Decrease inflammation*. Since inflammation is one of the central issues of
IC, it seems logical to decrease inflammation by treating systemic infections,
prescribing a low glycemic diet, avoiding food allergens, identifying and
desensitizing environmental allergies, detoxification, treating dysbiosis,
treating Lyme and eliminating parasites.
Antihistamines and leuketriene inhibitors*. Atarax® has been traditionally
used for symptomatic relief of IC, but it is very sedating. I have found that a
combination of a non-sedating antihistamine with a leukotriene inhibitor can
significantly reduce symptoms with fewer side effects.
FDA approved medications. Elmiron® (pentosan polysulfate sodium)
received FDA approval in 1996. It is the only oral medication approved
specifically for use in IC and it is believed to work by repairing a thin or
damaged bladder lining. Unfortunately, it only works in 30-40% of patients
and it may take as long as 6 months to see improvement.
Tri-cyclic antidepressants. Amitriptyline has become a staple treatment for
IC because of its anticholinergics effects (bladder relaxation), antihistamine
effects, and sedation. The side effects of even small doses (10mg) can limit
the usefulness of TCA’s.
Antibiotics*. It is of interest to the Lyme community that doxycycline can
benefit about 70% of those with IC which implies that Lyme, Mycoplasma,
Ureaplasma, C. pneumonia, or other organisms are involved in some aspect of
Pelvic floor treatments*. Pain in the bladder and/or pelvis can trigger long
term, chronic pelvic floor tension which is often described by men and women
as a burning sensation, particularly in the vagina, tip of the penis, or prostate.
In 9 out 10 IC patients struggling with painful sexual relations, muscle tension
is the primary cause of that pain and discomfort. Physical therapists specially
trained in pelvic floor rehabilitation can treat this condition.
Bladder instillations. Bladder distension under general anesthesia and office
bladder instillations with DMSO, BCG (currently undergoing trials),
hyaluronic acid, chlorpactin or silver nitrate have been used to control
Pain control* The pain of IC has been rated equivalent to cancer pain and
should not be ignored. The use of a variety of prescription pain medications,
acupuncture, massage, and biofeedback are beneficial and improve the IC
patients’ quality of life.
Sacral nerve stimulator. Electronic pain-killing options include
transcutaneous electrical nerve stimulation (TENS), percutaneous tibial nerve
stimulation (PTNS), and sacral nerve stimulation implants may help some
Surgery. For a small minority of patients whose symptoms are severe and
who do not respond to other IC treatments, bladder surgery may be
considered. However in some cases, IC symptoms may not improve. Several
types of surgery have been used to treat IC, including cystectomy (removing
the bladder) and urinary diversion.
*Particularly helpful in those with Lyme disease and IC
Whether IC is found in Lyme patients or Lyme is found in IC patients is the proverbial
chicken and egg problem. More awareness of the relationship between the two diseases
will lead to earlier, better treatment approaches. The good news for those with Lyme and
IC symptoms, is that there are effective treatments.
Dr. Metzger has been treating chronic pelvic pain for 20 years and was one of the editors of
the first book on the subject (Chronic Pelvic Pain: An Integrated Approach, Saunders, 1998).
Most of her chronic pain patients have Lyme disease. Email: firstname.lastname@example.org. References
for this article are available on request.
View of the lining of the bladder with a cystoscopy. The picture on the right is of a normal
bladder while the picture on the left shows a bladder with glomerulations (small hemorrhages
from the superficial blood vessels).