Interstitial cystitis: another IgG4–related inflammatory disease? (2022)

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Annals of Diagnostic Pathology

Volume 17, Issue 5,

October 2013

, Pages 403-407

Abstract

Interstitial cystitis (IC) is a disease of undetermined etiology and pathogenesis. Inflammation is thought to play a key role in many patients, characteristically with an increase in mast cells within the detrusor muscle of the bladder. We observed that some patients with IC had prominent plasma cells in bladder tissue, which elicited our interest in their possible pathogenic role in patients with IC. A total of 44 cases of IC were collected, including 42 bladder biopsies and 2 cystectomies. Patient age ranged from 18 to 92 years (average age of 49.5 years) and included 7 male and 37 female patients. The histology and immunostains for IgG, IgG4 and tryptase were examined, and the results were correlated with clinical and cystoscopic findings. Four cases showed a significant increase in IgG4-positive plasma cells, with greater than 30 IgG4 plasma cells per high-power field and an IgG4/IgG ratio greater than 0.5. In addition, statistically significant differences were found between IC with IgG4-positive plasma cells vs IgG4-negative cases. The IgG4-positive patients were of older age and had increased severe inflammation and decreased bladder capacity as compared with the IgG4-negative patients. We propose that a subset of patients with IC may have an IgG4-related disease, and further study including serum IgG4 measurement is required to better define this relationship.

(Video) IGG4 Related Diseases

Introduction

Interstitial cystitis (IC) is characterized by bladder pain that is associated with chronic inflammation and/or injury to the bladder wall. The disease is found more commonly in women, and a recent epidemiologic study in the United States estimated that 3.3 to 7.9 million women are affected [1].

The etiology and pathogenesis of IC are unknown. Differing theories have been proposed, and potential causes have been attributed to autoimmune disorders, infection, neuropathies, toxicities, and genetic susceptibilities [2]. Many suspect that the disease may have multiple routes of pathogenesis owing to the wide spectrum of symptoms, severity, and clinicopathologic findings [3].

A lack of understanding of IC makes it difficult to prescribe effective treatment regimens. Often, multiple treatments are used empirically or in combination to provide relief of symptoms. Furthermore, a poor understanding of the pathogenesis makes IC a difficult diagnosis for clinicians and pathologists. The current definition of IC endorsed by the American Urology Association (AUA) is “an unpleasant sensation (pain, pressure, and discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of six weeks duration, in the absence of infection or other identifiable causes” [4]. The associated urinary symptoms include increased frequency, nocturia, and urgency. The supportive histologic criteria defined by the European Society for the Study of Interstitial Cystitis include inflammatory infiltrate, granulation tissue, detrusor mastocytosis (>28 mast cells/mm2), and intrafascicular fibrosis [5]. As noted in the AUA definition, IC is often a diagnosis of exclusion. A better understanding of the pathogenesis may aid in more effectively diagnosing and treating patients.

It was observed that some of the patients with IC in our institution had prominent plasma cell infiltration and fibrosis in affected bladder tissue, raising a suspicion that IC could be an IgG4–related disease. This study was designed to determine if a subset of patients with IC also had increased IgG4-positive plasma cells. This knowledge may offer new understanding of the pathogenesis and treatment options for patients with IC.

Section snippets

Specimens

Slides and paraffin-embedded tissue blocks from a total of 44 cases seen in our institution from 2006 to 2011 were evaluated from patients with clinical symptoms compatible with a diagnosis of IC and biopsy or cystectomy supporting the diagnosis.

All cases were evaluated under a protocol approved by the institutional review board of The Methodist Hospital Research Institute (Institutional Review Board (2)1111-0227). The cases included 42 biopsies and 2 cystectomy specimens. No urothelial

Results

The 44 cases shared many similar histologic features including the presence of scattered chronic inflammation, mast cells, vascular congestion, and surface erosion. Many of the mast cells were found in a perivascular or perineural location.

The 44 cases were stratified into 4 groups based on the number of IgG4-positive plasma cells per HPF. Group 1 included 25 cases with no IgG4-positive plasma cells/HPF; group 2 had 11 cases with 1 to 4 IgG4-positive plasma cells/HPF; group 3 included 4 cases

Discussion

Our study identified a subgroup of IC cases with increased IgG4-positive plasma cells in affected bladder tissue. In our study of 44 IC cases, we found statistically significant differences between IC cases with any number of IgG4-positive plasma cells and those without (Table). Although only a small subset (4 cases) met the established definitions for IgG4-related disease in other body sites, clinicopathologic trends were identified and associated with increasing numbers of IgG4-positive

Acknowledgments

The authors would like to thank Jiaqiong (Susan) Xu, PhD, at Center for Biostatistics at The Methodist Hospital Research Institute for assistance with the statistical analysis.

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    Hum Pathol

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  • B.E. Leiby et al.Discovery of morphological subgroups that correlate with severity of symptoms in interstitial cystitis: a proposed biopsy classification system

    J Urol

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  • T.C. Theoharides et al.Mast cell involvement in interstitial cystitis: a review of human and experimental evidence

    Urology

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  • J.P. van de Merwe et al.Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal

    Eur Urol

    (2008)

  • P.M. Hanno et al.AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome

    J Urol

    (2011)

    (Video) What's the difference between Interstitial Cystitis and Bladder Pain Syndrome?

  • G.R. Sant et al.Interstitial cystitis: current issues and controversies in diagnosis

    Urology

    (2001)

  • S.H. Berry et al.Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States

    J Urol

    (2011)

  • S. Grover et al.

    Role of inflammation in bladder function and interstitial cystitis

    Ther Adv Urol

    (2011)

  • G.R. Sant et al.

    The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis

    Urology

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There are more references available in the full text version of this article.

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FAQs

What autoimmune diseases are associated with interstitial cystitis? ›

Clinical associations have been found between IC and allergy, irritable bowel syndrome, fibromyalgia, inflammatory bowel disease (Crohn's disease and ulcerative colitis), and generalized autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS) (Table 1).

Is Interstitial Cystitis an inflammatory disease? ›

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory disease characterized by recurrent pain, discomfort, or tenderness in the urinary bladder and pelvic region and can be accompanied by various urinary symptoms, such as urinary frequency, persistent urge to void, and nocturia.

What is the root cause of interstitial cystitis? ›

Cationic metabolites in the urine of patients with interstitial cystitis (IC) might be responsible for initiating the process that ultimately leads to bladder pain symptoms, according to C.

Is interstitial cystitis related to rheumatoid arthritis? ›

IC tends to develop in people with a number of other conditions including endometriosis, hay fever and asthma, inflammatory bowel disease, lupus, migraine headaches, rheumatoid arthritis, and fibromyalgia.

What mimics interstitial cystitis? ›

Similar to IC, overactive bladder is a condition that results in the sudden need to urinate (urgency). OAB is caused by a sudden involuntary contraction of the detrusor, a muscle in your bladder wall which is controlled by the nervous system.

Does interstitial cystitis make me immunocompromised? ›

There are no data to suggest that IC/BPS patients are immunosuppressed. Thus, having IC/BPS alone does not make you more susceptible to the virus.

Is interstitial cystitis a mast cell disorder? ›

The mast cell appears to be involved in the pathogenesis of interstitial cystitis. Although it is not pathognomonic of the disease, mastocytosis does occur in a significant subset of interstitial cystitis patients.

Are there stages of interstitial cystitis? ›

Excessive frequency of urination, urinary urgency, and urethra, bladder or pelvic pain are common symptoms. Treatment is divided into five phases, ranging from lifestyle changes to injections to surgery.

What foods trigger interstitial cystitis? ›

Coffee, soda, alcohol, tomatoes, hot and spicy foods, chocolate, caffeinated beverages, citrus juices and drinks, MSG, and high-acid foods can trigger IC symptoms or make them worse.

What is end stage interstitial cystitis? ›

End-stage interstitial cystitis is defined as a hard bladder that triggers intense pain and possesses very low bladder capacity. Many cases of end-stage interstitial cystitis involve Hunner's ulcers. Also known as “end-stage IC”, only about 5% of IC patients develop this severe condition.

What is the latest treatment for interstitial cystitis? ›

Dimethylsulfoxide — Dimethylsulfoxide (DMSO) is a liquid medication that has been approved by the US Food and Drug Administration (FDA) to treat interstitial cystitis/bladder pain syndrome (IC/BPS).

How serious is interstitial cystitis? ›

IC is a chronic disease. Patients may find some comfort in the fact that it is not life-threatening and it does not lead to cancer. However, because the symptoms are always present, patients need to develop coping skills to deal with them.

Does interstitial cystitis cause extreme fatigue? ›

A small subset of interstitial cystitis (IC) patients also have chronic fatigue syndrome (CFS). Though most at-risk group for CFS appears to be women, CFS strikes people in every age, racial, ethnic, and socioeconomic group. As the name “chronic fatigue syndrome” suggests, this illness is accompanied by fatigue.

What autoimmune disease causes bladder pain? ›

If you have Sjogren's syndrome, you are also more likely to have a condition called painful bladder syndrome, or interstitial cystitis. This condition causes signs and symptoms similar to those of a urinary tract infection — urinary frequency, urgency and pain — without evidence of infection.

Is interstitial cystitis related to lupus? ›

In lupus development, interstitial cystitis may also occur [1–4]. Lupus cystitis is a rare complication of SLE but may lead to permanent bladder dysfunction, and its complications may include irreversible impairment of renal function [7].

Why do antihistamines help interstitial cystitis? ›

Antihistamines such as hydroxyzine (Atarax, Vistaril) interfere with the mast cells' release of histamine, helping to relieve bladder inflammation and pain, urinary frequency, and nighttime voiding.

Does magnesium help interstitial cystitis? ›

o The B-Complex vitamins can also cause problems with IC. o The fat soluble vitamins (A, D E, and K) and minerals, such as calcium and magnesium, are usually well-tolerated by most IC patients. C. Physical Therapy: helpful if you have trigger points or muscle spasms on pelvic exam.

What is the best medication for interstitial cystitis? ›

Antihistamines, such as loratadine (Claritin, others), which may reduce urinary urgency and frequency and relieve other symptoms. Pentosan polysulfate sodium (Elmiron), which is approved by the Food and Drug Administration specifically for treating interstitial cystitis.

Can interstitial cystitis cause fibromyalgia? ›

A subset of interstitial cystitis (IC) patients also have fibromyalgia (FM), a chronic pain disorder with a multitude of symptoms. Although 80 to 90 percent of those affected are women, men and children can have fibromylagia, too.

Which antihistamine is best for interstitial cystitis? ›

Though the most widely used antihistamine to treat IC is hydroxyzine, some people with IC find relieve from Claritin, Benadryl, and Singulair.

What are the symptoms of mast cell activation syndrome? ›

People who have mast cell activation syndrome might have a lot of allergy symptoms and lots of episodes of anaphylaxis without a clear cause.
...
These include:
  • Expanding blood vessels.
  • Itchy skin.
  • Swollen skin.
  • Mucus buildup.
  • Tightened airways.
  • Wheezing.
  • Headaches.
  • Anaphylaxis.
Apr 12, 2021

Can histamine cause bladder problems? ›

Mast cell degranulation and histamine release contribute to painful bladder syndrome, urinary tract infections, interstitial cystitis and other bladder disorders. The effects of histamine are well-studied in other tissues, but little is known about the role of histamine and histamine receptors within the bladder.

What medications are mast cell stabilizers? ›

List of Mast cell stabilizers:
Drug NameAvg. RatingReviews
Intal Inhaler Generic name: cromolyn106 reviews
Intal (Pro) Generic name: cromolyn7.03 reviews
Gastrocrom (Pro) Generic name: cromolyn8.33 reviews
Tilade Generic name: nedocromil8.0No reviews
1 more row

Is interstitial cystitis an autoimmune disease? ›

Interstitial cystitis (IC) is an autoimmune related condition that causes discomfort or pain in the bladder and a need to urinate frequently and urgently. It is far more common in women than in men. The symptoms vary from person to person. Some people may have pain without urgency or frequency.

Does IC progressively get worse? ›

It does not spread in the body and does not seem to worsen with time. It is not a cause of bladder cancer. Though more research is needed, IC does not seem to affect fertility or the health of a fetus. For some women, the symptoms of IC improve or disappear during pregnancy; for other women, they get worse.

How do you calm an interstitial cystitis flare up? ›

Here are some general self-help techniques to keep your bladder calm and help you reduce the possibility of a flare:
  1. Try relaxation techniques.
  2. Use meditation tapes and/or visualization.
  3. Learn self-hypnosis.
  4. Receive massages or learn self-massage.
  5. Go to psychotherapy to learn coping skills and stress reduction techniques.
Mar 25, 2015

What vitamins help interstitial cystitis? ›

Supplements For An Interstitial Cystitis Diet

2 supplements have shown consistent success in treating IC: calcium glycerophosphate (Prelief) and sodium bicarbonate (baking soda). Multiple studies have shown these supplements help improve IC symptoms, particularly when taken with flare-inducing foods.

Are bananas good for interstitial cystitis? ›

Allowed: Bananas, coconuts, dates, blueberries, melons and pears Avoid: All other fruits and juices (especially acidic and citrus fruits) Special note: Avoid cranberry juice. The acid is a strong bladder irritant. Avoid: Benzyl alcohol, citric acid, MSG, NutraSweet, saccharin.

Does exercise help interstitial cystitis? ›

Being active and getting yourself up and moving is important when you have interstitial cystitis (IC). Regular exercise helps maintain your heart, lungs, muscles, bones, joints, bowel, and brain function.

Can interstitial cystitis affect the kidneys? ›

Some possible complications of interstitial cystitis include: decreased bladder capacity. kidney damage due to long-term high bladder pressure. permanent or chronic pain.

Can you live a normal life with interstitial cystitis? ›

Living with IC can be difficult. Because there is no cure for IC, eating well and managing health is an important way to fend off flare-ups. Planning ahead for travel and other activities can make daily life easier as well. The Interstitial Cystitis Foundation has some tips for eating, exercise and travel.

Can cystitis damage your kidneys? ›

It can also cause a urinary tract infection (UTI). Cystitis occurs in 1-3% of adult women per year. If the infection continues up to the kidneys, it can cause kidney infection. This problem is rare but it can be severe.

Has anyone cured interstitial cystitis? ›

Interstitial cystitis most often affects women and can have a long-lasting impact on quality of life. Although there's no cure, medications and other therapies may offer relief.

How can I rebuild my bladder lining? ›

Pentosan polysulfate sodium is the only FDA-approved oral medication for interstitial cystitis. The drug binds to the walls of the bladder, helping replace and repair the lining. Symptom improvement can take up to six months, but several studies have shown moderately positive results.

Can a urologist help with IC? ›

Managing a chronic illness like interstitial cystitis (IC) depends, in part, on your choice of doctor. Your primary care physician (PCP) may refer you to a specialist. A urologist is a doctor specializing in bladder diseases. Some gynecologists and urogynecologists (women's health doctors) also treat people with IC.

How long does a flare up of interstitial cystitis last? ›

In the early phase of IC the symptom flares are intermittent in most patients. Over time symptoms increase and pain cycles may appear and last for 3-14 days. When these cycles become more frequent and last longer they are likely to be referred to a specialist.

What does an IC flare feel like? ›

Pain: Flares can provoke mild to severe pain. During most IC flares, the pain worsens as the bladder fills with urine and may be relieved after urination. Bladder pain is most commonly felt in the subrapubic region, directly above the pubic bone.

Does interstitial cystitis cause back pain? ›

Symptoms of interstitial cystitis may vary, although they typically include the following: chronic pelvic pain. pain in the perineum, urethra, lower abdomen, and lower back.

Can interstitial cystitis cause neuropathy? ›

Small Fiber Polyneuropathy Is Associated With Non-Bladder-Centric Interstitial Cystitis/Bladder Pain Syndrome Patients.

Is interstitial cystitis linked to IBS? ›

About one-third of interstitial cystitis (IC) patients have irritable bowel syndrome (IBS). IBS is a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habits. The cause of IBS is not completely understood.

What is the IC diet? ›

A balanced diet with a wide variety of items from all food groups is the best diet for interstitial cystitis (IC). It is also the best diet for everyone. The only the difference is that those with IC should limit some foods and beverages. Restricting too many foods and beverages can affect your well-being in a bad way.

Is interstitial cystitis an inflammatory disease? ›

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory disease characterized by recurrent pain, discomfort, or tenderness in the urinary bladder and pelvic region and can be accompanied by various urinary symptoms, such as urinary frequency, persistent urge to void, and nocturia.

How do they test for interstitial cystitis? ›

Doctors may use cystoscopy to look inside the urethra and bladder. Doctors use a cystoscope, a tubelike instrument, to look for bladder ulcers, cancer, swelling, redness, and signs of infection. A doctor may perform a cystoscopy to diagnose interstitial cystitis (IC).

Can interstitial cystitis cause positive ANA? ›

Of 96 interstitial cystitis patients 35 (36%) were positive for antinuclear antibodies at titers of 1/40 or greater.

Is interstitial cystitis related to rheumatoid arthritis? ›

IC tends to develop in people with a number of other conditions including endometriosis, hay fever and asthma, inflammatory bowel disease, lupus, migraine headaches, rheumatoid arthritis, and fibromyalgia.

Does interstitial cystitis cause joint pain? ›

Symptoms associated with this condition include pain, painful urination, urinary frequency, urinary urgency, and painful intercourse. Other symptoms might include muscle and joint pain, migraines, allergies and gastrointestinal problems.

Can autoimmune disease cause bladder problems? ›

Autoimmune diseases and LUTS

Autoimmune disease can directly affect the lower urinary tract function by attacking the central nervous system, upregulating the peripheral neurotransmission receptors, or depositing immune complexes in the bladder.

What autoimmune diseases affect the bladder? ›

An autoimmune response to a bladder infection destroys the lining of the bladder wall. An unexplained association of IC has been found to exist with other autoimmune diseases such as inflammatory bowel disease, systemic lupus erythematosus, scleroderma, Sjogren syndrome, fibromyalgia, and atopic allergy.

Can lupus cause interstitial cystitis? ›

In lupus development, interstitial cystitis may also occur [1–4]. Lupus cystitis is a rare complication of SLE but may lead to permanent bladder dysfunction, and its complications may include irreversible impairment of renal function [7].

Does interstitial cystitis cause a positive ANA test? ›

Of 96 interstitial cystitis patients 35 (36%) were positive for antinuclear antibodies at titers of 1/40 or greater.

Can interstitial cystitis cause fibromyalgia? ›

A subset of interstitial cystitis (IC) patients also have fibromyalgia (FM), a chronic pain disorder with a multitude of symptoms. Although 80 to 90 percent of those affected are women, men and children can have fibromylagia, too.

Is interstitial cystitis a mast cell disorder? ›

The mast cell appears to be involved in the pathogenesis of interstitial cystitis. Although it is not pathognomonic of the disease, mastocytosis does occur in a significant subset of interstitial cystitis patients.

Are there stages of interstitial cystitis? ›

Excessive frequency of urination, urinary urgency, and urethra, bladder or pelvic pain are common symptoms. Treatment is divided into five phases, ranging from lifestyle changes to injections to surgery.

What foods trigger interstitial cystitis? ›

Coffee, soda, alcohol, tomatoes, hot and spicy foods, chocolate, caffeinated beverages, citrus juices and drinks, MSG, and high-acid foods can trigger IC symptoms or make them worse.

What autoimmune disease causes bladder pain? ›

If you have Sjogren's syndrome, you are also more likely to have a condition called painful bladder syndrome, or interstitial cystitis. This condition causes signs and symptoms similar to those of a urinary tract infection — urinary frequency, urgency and pain — without evidence of infection.

Does interstitial cystitis cause joint pain? ›

Symptoms associated with this condition include pain, painful urination, urinary frequency, urinary urgency, and painful intercourse. Other symptoms might include muscle and joint pain, migraines, allergies and gastrointestinal problems.

How is lupus cystitis diagnosed? ›

It is most often diagnosed by cystoscopy (bladder examination under anesthesia) in which typical findings are low bladder capacity, Hunner's ulcer and petechial hemorrhages. We report an unusual presentation of SLE as lupus cystitis with paralytic ileus, who later developed lupus nephritis.

How do doctors test for interstitial cystitis? ›

Doctors may use cystoscopy to look inside the urethra and bladder. Doctors use a cystoscope, a tubelike instrument, to look for bladder ulcers, cancer, swelling, redness, and signs of infection. A doctor may perform a cystoscopy to diagnose interstitial cystitis (IC).

How long do interstitial cystitis flare ups last? ›

In the early phase of IC the symptom flares are intermittent in most patients. Over time symptoms increase and pain cycles may appear and last for 3-14 days. When these cycles become more frequent and last longer they are likely to be referred to a specialist.

Is interstitial cystitis inherited? ›

Interstitial cystitis (IC), also called Bladder Pain syndrome (BPS), or chronic pelvic pain syndrome(CPPS) is a common condition with no known cause or cure. Twin studies and family accounts have suggested that the condition may be genetic or passed down (inherited) from one generation to another.

Is interstitial cystitis an autoimmune disease? ›

Interstitial cystitis (IC) is an autoimmune related condition that causes discomfort or pain in the bladder and a need to urinate frequently and urgently. It is far more common in women than in men. The symptoms vary from person to person. Some people may have pain without urgency or frequency.

Has anyone cured interstitial cystitis? ›

There's no cure for interstitial cystitis, but many treatments offer some relief, either on their own or in combination. Treatment (see chart) is aimed at relieving pain and reducing inflammation.

How do you calm an interstitial cystitis flare up? ›

Here are some general self-help techniques to keep your bladder calm and help you reduce the possibility of a flare:
  1. Try relaxation techniques.
  2. Use meditation tapes and/or visualization.
  3. Learn self-hypnosis.
  4. Receive massages or learn self-massage.
  5. Go to psychotherapy to learn coping skills and stress reduction techniques.
Mar 25, 2015

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