What is interstitial cystitis. How does it relate to autoimmune disorders. What are the symptoms and prevalence of IC. How is IC diagnosed and treated. What is the role of mast cells in IC. How does stress affect IC symptoms. What genetic factors are associated with IC. How does IC impact quality of life.

Understanding Interstitial Cystitis: An Overview

Interstitial cystitis (IC), also known as painful bladder syndrome, is a chronic and debilitating condition that primarily affects women. This complex disorder is characterized by a range of urinary symptoms and pelvic pain, often leading to significant distress and reduced quality of life for those affected.

Key features of interstitial cystitis include:

• Excessive urgency and frequency of urination
• Suprapubic pain
• Dyspareunia (painful sexual intercourse)
• Pelvic pain
• Negative urine cultures

What sets IC apart from other bladder conditions? Unlike urinary tract infections or bladder cancer, IC presents with these symptoms in the absence of other definable pathologies. The condition typically follows a course of flare-ups and remissions, persisting throughout a patient’s life.

The Prevalence and Demographics of Interstitial Cystitis

How common is interstitial cystitis? According to the 2001 Nurses’ Health Study, IC may affect as many as 700,000 women in the United States alone. This translates to a prevalence of up to 67 per 100,000 women, making it a significant health concern.

Who is most likely to develop IC? The condition demonstrates a clear gender disparity:

• Women comprise up to 90% of IC patients
• Onset typically occurs between ages 30 and 70
• The median age of onset is 43 years

Why does IC often go undiagnosed for extended periods? The complex nature of the condition and its overlapping symptoms with other disorders often lead to a prolonged diagnostic journey. Most patients consult at least five physicians, including psychiatrists, over a period of more than four years before receiving an IC diagnosis.

The Autoimmune Connection: Unraveling the Etiology of IC

What causes interstitial cystitis? While the exact etiology remains elusive, mounting evidence points to autoimmune and allergic factors playing a crucial role. How do these factors contribute to IC development?

Several studies have identified a defect in the glycosaminoglycan (GAG) component of the mucin layer that protects the bladder urothelium. This breakdown leads to:

1. A hyperpermeable bladder wall
2. Stimulation of pain receptors
3. Inflammatory symptoms

What evidence supports the autoimmune nature of IC? The condition exhibits several hallmarks of autoimmune diseases:

• Chronic symptoms with exacerbations and remissions
• Organ-specific and non-organ-specific mononuclear cell infiltrates
• Absence of a clearly defined pathogen
• Response to steroids or other immunosuppressants

The Historical Perspective: Tracing IC’s Autoimmune Roots

When was the link between IC and autoimmune disorders first established? The connection dates back to 1915 when GL Hunner described two patients with “a rare type of bladder ulcer in women.” However, it was researcher G.M. Fister who first demonstrated a clear link between autoimmune disease and IC in a patient with systemic lupus erythematosus (SLE) in 1938.

How did subsequent research build on this foundation? Several key studies advanced our understanding of IC’s autoimmune nature:

• 1983: Orth et al. confirmed Fister’s findings, introducing the term “lupus cystitis”
• 1970: Silk reported bladder-specific antibodies in IC patients, suggesting it belonged to the group of organ-specific autoimmune diseases
• 1972: Jokinen et al. found tissue autoantibodies against both non-organ-specific and organ-specific antigens in 94% of IC patients

What conclusion did researchers draw from these findings? Based on their observations, Jokinen et al. proposed that IC “belongs to the group of autoimmune diseases that lies between organ-specific and non-organ-specific systemic diseases. The disease is confined to one organ, but the tissue antibodies are non-organ-specific.”

The Role of Mast Cells in Interstitial Cystitis

How do mast cells contribute to IC pathogenesis? Mast cells play a crucial role in the inflammatory and autoimmune aspects of interstitial cystitis. What evidence supports their involvement?

• Mastocytosis has been reported in the bladders of 30%-65% of IC patients
• Increased levels of histamine have been found in the bladder wall epithelium of IC patients
• Mast cells are known to be involved in autoimmunity

What triggers mast cell activation in IC? Corticotrophin-releasing hormone (CRH) secreted from non-CNS sites has proinflammatory actions that may be mediated via mast cell activation. This connection helps explain the impact of stress on IC symptoms.

Stress and IC: A Complex Interplay

How does stress affect IC symptoms? Stress is known to exacerbate IC symptoms through various mechanisms:

• Vasodilation
• Flushing
• Itching
• General skin hypersensitivity in the genital area, upper thighs, and abdomen

Why is understanding this stress-symptom relationship important? Recognizing the impact of stress on IC can help patients and healthcare providers develop more comprehensive management strategies that address both physical and psychological aspects of the condition.

Genetic Factors and Familial Predisposition in IC

Is there a genetic component to interstitial cystitis? Several lines of evidence suggest a genetic predisposition to IC:

• Reports of IC in monozygotic female twins
• Cases of IC in mother-daughter pairs
• Association with specific HLA types

What specific genetic factors have been identified? A study by Christmas and Bottazzo demonstrated that IC is associated with HLA-DR6, which appears to convey a relative risk factor of 4.91. Additionally, researchers found evidence of HLA class I inappropriate hyperexpression in the urothelial cells of IC patients.

How do these genetic factors contribute to IC pathogenesis? The expression of HLA-DR molecules in the urothelium cells, along with class I hyperexpression, allows them to activate CD4+ and CD8+ lymphocytes. These lymphocytes appear to be the main effectors in the autoimmune response observed in IC.

Diagnostic Challenges and Treatment Approaches for IC

Why is diagnosing IC often challenging? The complex nature of IC, with its overlapping symptoms with other conditions, can make diagnosis difficult. What steps are typically involved in the diagnostic process?

1. Detailed medical history
2. Physical examination
3. Urinalysis and urine culture to rule out infection
4. Cystoscopy with hydrodistention
5. Potassium sensitivity test
6. Biopsy (in some cases)

What treatment options are available for IC patients? Treatment typically involves a multifaceted approach, which may include:

• Oral medications (e.g., pentosan polysulfate sodium, antihistamines, antidepressants)
• Intravesical treatments (e.g., DMSO, heparin, lidocaine)
• Dietary modifications
• Stress management techniques
• Physical therapy
• Neuromodulation

How effective are current treatments? While there is no cure for IC, many patients experience significant symptom relief with appropriate management. However, treatment response can vary widely among individuals, emphasizing the need for personalized approaches.

Living with IC: Impact on Quality of Life and Coping Strategies

How does interstitial cystitis affect patients’ daily lives? IC can have a profound impact on various aspects of life, including:

• Physical well-being
• Emotional health
• Sexual relationships
• Work productivity
• Social interactions

What strategies can help patients cope with IC? Effective management of IC often involves a combination of medical treatment and lifestyle adjustments:

1. Adhering to an IC-friendly diet
2. Practicing stress reduction techniques (e.g., meditation, yoga)
3. Engaging in gentle exercise
4. Joining support groups
5. Working closely with healthcare providers to optimize treatment

How can healthcare providers better support IC patients? Recognizing the chronic nature of IC and its impact on quality of life is crucial. Providers should adopt a patient-centered approach, addressing both physical symptoms and psychological well-being.

Future Directions in IC Research and Treatment

What areas of IC research show promise for the future? Ongoing and future research efforts are focusing on several key areas:

• Identifying more specific biomarkers for IC diagnosis
• Developing targeted therapies based on individual patient profiles
• Investigating the role of the microbiome in IC pathogenesis
• Exploring novel drug delivery methods for intravesical treatments
• Studying the long-term outcomes of various treatment approaches

How might advances in autoimmune research benefit IC patients? As our understanding of autoimmune mechanisms grows, new treatment modalities may emerge that could offer more effective and targeted approaches to managing IC.

The Role of Interdisciplinary Care in IC Management

Why is an interdisciplinary approach important in IC care? The complex nature of IC often requires input from various specialists, including:

• Urologists
• Gynecologists
• Pain management specialists
• Psychologists or psychiatrists
• Physical therapists
• Nutritionists

How can coordinated care improve outcomes for IC patients? By addressing all aspects of the condition – physical, emotional, and social – an interdisciplinary approach can lead to more comprehensive and effective management strategies.

Raising Awareness: The Importance of IC Education and Advocacy

Why is raising awareness about IC crucial? Increased awareness can lead to:

• Earlier diagnosis and treatment
• Improved public understanding and support
• Increased funding for research
• Better workplace accommodations for IC patients

What role can patients play in advocacy efforts? IC patients can contribute to awareness and advocacy by:

1. Sharing their experiences
2. Participating in support groups and online communities
3. Engaging with local and national IC organizations
4. Participating in research studies when possible

How can healthcare providers contribute to IC awareness? Providers can play a crucial role by:

• Staying informed about the latest IC research and treatment options
• Educating colleagues about IC, especially in primary care settings
• Advocating for better recognition of IC in medical curricula and continuing education programs

Conclusion: The Road Ahead for Interstitial Cystitis Research and Care

As our understanding of interstitial cystitis continues to evolve, what key challenges remain? Despite significant progress in IC research, several important questions persist:

• Can we develop more sensitive and specific diagnostic tools for IC?
• How can we better predict individual treatment responses?
• What role do environmental factors play in IC development and progression?
• How can we improve long-term outcomes for IC patients?

What gives hope to IC patients and researchers? The growing recognition of IC as a significant health issue, combined with advances in autoimmune research and personalized medicine, offers promise for improved diagnosis, treatment, and quality of life for those affected by this challenging condition.

As we move forward, a multidisciplinary approach that combines cutting-edge research, patient-centered care, and increased public awareness will be crucial in addressing the complex needs of individuals living with interstitial cystitis. By continuing to unravel the autoimmune connections and underlying mechanisms of IC, we can work towards more effective management strategies and, ultimately, better outcomes for patients.

Interstitial Cystitis and the Autoimmune Connection – Naturopathic Doctor News and Review

Arlene B. Donar, ND

Interstitial cystitis (IC) is a chronic, debilitating, multifactorial syndrome characterized by excessive urgency and frequency of urination, suprapubic pain, dyspareunia and pelvic pain along with negative urine cultures. The course of the disease is usually marked by flare-ups and remissions. IC generally persists throughout the patient’s life. On clinical evaluation, patients presenting with IC should have no other definable pathology such as urinary infections, carcinoma or radiation-induced cystitis (Metts, 2001). This symptom complex has also been referred to as painful bladder syndrome, leaky bladder syndrome and irritative bladder syndrome (Marshall, 2003).

According to a 2001 Nurses’ Health Study, IC may affect as many as 700,000 women in the U.S., suggesting that the prevalence among women may be as high as 67 per 100,000. Women comprise up to 90% of patients with IC. Onset usually occurs between the ages of 30 and 70 years of age with a median age of 43 (Metts, 2001).

Most patients will consult at least five physicians, including psychiatrists, over a period of more than four years before IC is diagnosed (Metts, 2001).

Etiology

While the exact cause of IC is not known, it is most likely related to autoimmune and allergic etiologies. Numerous studies have demonstrated that symptoms originate from a defect in the glycosaminoglycan (GAG) component of the layer of mucin that covers and protects the bladder urothelium. This breakdown of the bladder protective layer leads to a hyperpermeable bladder wall, stimulation of pain receptors and inflammatory symptoms (Marshall, 2003).

Stress is also known to contribute to symptoms. Patients may report vasodilation, flushing and itching and general skin hypersensitivity in the genital area, upper thighs and abdomen. Corticotrophin-releasing hormone (CRH) secreted from non-CNS sites has proinflammatory actions that may be mediated via mast cell activation. Mast cells are also involved in autoimmunity (Sant et al., 2007). Mastocytosis has been reported in the bladders of 30%-65% of patients with IC. Further evidence of mast cell involvement comes from increased levels of histamine in bladder wall epithelium in IC patients (Marshall, 2003).

IC has the classic picture of autoimmune disease: symptom chronicity with exacerbations and remissions, organ-specific and non-organ-specific mononuclear cell infiltrates, the lack of a clearly defined pathogen and response to steroids or other immunosuppressants (Metts, 2001).

Autoimmune Connection

IC was first reported in 1915 when GL Hunner described two patients with “a rare type of bladder ulcer in women.” Researcher G.M. Fister, MD was among the first to demonstrate a link between autoimmune disease and IC in a patient with systemic lupus erythematosus (SLE). He suggested that patients with IC shared a clinical picture with autoimmune connective tissue disease (Fister, 1938). A 1983 study by Orth et al. confirmed Fister’s findings, and the term “lupus cystitis” was introduced (Orth et al., 1983). Histologically, no immune deposits of IgG, IgA, IgM or complement C1q were found in the mucosa and perivascular regions of urinary bladder specimens (Shibata et al., 2004).

Silk (1970) reported that he had found bladder-specific antibodies in IC patients. His findings indicated that IC belonged to the group of organ-specific autoimmune diseases (Silk, 1970). In a separate 1972 study by Jokinen et al., 31 of 33 (94%) patients with IC were found to have tissue autoantibodies against both non-organ-specific and organ-specific antigens.

On the basis of their findings, they stated that it seems probable that IC “belongs to the group of autoimmune diseases that lies between organ-specific and non-organ-specific systemic diseases. The disease is confined to one organ, but the tissue antibodies are non-organ-specific” (Jokinen et al., 1972).

A familial predisposition to IC was proposed after a report of IC in monozygotic female twins and a mother and daughter (Oravisto, 1980). A study by Christmas and Bottazzo demonstrated that IC is associated with HLA-DR6, and the allele seems to convey a relative risk factor of 4.91. There was evidence of HLA class I inappropriate hyperexpression in the urothelial cells; however, the most striking difference between the bladder tissue of IC patients and the normal control group was that the expression of HLA-DR molecules in the urothelium cells was positive for all three antibodies used in the study. In addition, large numbers of infiltrating cells expressing HLA class II CD3+T cells were evident within the submucosa. This class II expression along with class I hyperexpression in the urothelial cells allows them to activate CD4+ and CD8+ lymphocytes, which appear to be the main effector in the mechanism in destruction of the urothelial cells in IC (Christmas and Bottazzo, 1992).

Naturopathic Treatment

When considering an autoimmune etiology, an effective approach to treatment must address symptom relief, tissue repair and immune function.

• Nutrition       Dietary modification is the cornerstone of IC therapy. Between 53%-63% of IC patients can identify foods that exacerbate symptoms or cause a flare-up. High acidic foods such as alcoholic beverages, carbonated drinks, caffeine, spicy foods, tomatoes, vinegar, chocolate and citrus fruits are among the worst offenders. Arylalkylamines (tryptophan, tyrosine, phenylalanine and tyramine) have also been implicated as triggers, particularly those found in bananas, beer, mayonnaise, nuts, onions, raisins and yogurt (Marshall, 2003). Acid or potassium is often the suspected mechanism (Hudson, 2001). Since the response to these foods is highly variable, an elimination/challenge is quite useful to identify individual triggers. Essential fatty acids in the form of fish oil or flaxseed oil should be included, along with buffered vitamin C (non-citrus source) as both antioxidants and mast cell stabilizers. Pro-inflammatory saturated fats should be greatly reduced or eliminated from the diet, with a focus on anti-inflammatory fruits and vegetables tolerable by the patient.
• Herbal Supplementation Anti-inflammatory and anti-oxidative supplementation is essential in an autoimmune protocol. Botanicals to consider either in capsule or tincture form include, but are not limited to: Boswellia, Curcuma longa, Glycyrrhiza glabra, Camellia sinensis, pycnogenol, Vitis vinifera L. Quercetin should also be included as a mast cell stabilizer.

Botanical methyl donors such as onion and garlic have an anti-inflammatory and analgesic effect on damaged mucosal lining (Hudson, 2001) – again, only if tolerable by the patient.

Other herbs to consider are: 1) Those in the demulcent family for their ability to protect and soothe the damaged mucosal lining, such as Ulmus rubra, Althaea officinalis, Avena sativa, Symphytum officinale or Zea mays; and 2) anti-spasmodics for pain relief, including Viburnum opulus, Dioscorea villosa and Piscidia piscipula.

• Immune System Modulation of the immune system must be addressed when considering an autoimmune etiology. Plant sterols and sterolins in a ratio of 200:1 (beta-sitosterol:beta-sitosterolin) can selectively enhance the activity of T-helper 1 cells (Th-1) while leaving unchanged or inhibiting the T-helper 2 cells (Th-2). The stimulation of the Th-1 pathway leads to the destruction of inflammatory cells and a reduction in the resulting Th-2 mediated cytokines. Plant sterols can also maintain cortisol levels while elevating DHEA, thereby decreasing the cortisol:DHEA ratio and buffering a negative stress response (Bouic et al., 1996).

Proteolytic enzymes taken on an empty stomach provide a dual function in their ability to balance the immune system and act as a potent anti-inflammatory.

Patients should be willing to commit to a treatment program of a minimum of 3-6 months, with some level of symptom relief within the early stages of their protocol. An autoimmune approach to treatment must address inflammation, oxidative damage as well as modulation of the immune system. Therapy specific to IC includes healing of the bladder wall, histamine inhibition and anti-spasmodics for pain relief.

Arlene B. Donar, ND earned her naturopathic degree from the University of Bridgeport College of Naturopathic Medicine. She is board certified and licensed as an ND in Connecticut. Dr. Donar also holds a Master of Arts degree in speech and language pathology, and has worked as both a private consultant and adjunct professor in speech communications. Dr. Donar is the former medical director of the supplement manufacturer Heartguardian. She maintains a private practice in Manhattan, working primarily with clients with chronic health conditions, and lectures locally on prevention and treatment of disease using botanical medicine and clinical nutrition.

References

Metts JF: Interstitial cystitis: urgency and frequency syndrome, Am Fam Physician 64:1199-206, 2001.

Marshall K: Interstitial cystitis: understanding the syndrome, Altern Med Rev 8(4):426-437, 2003.

Sant GR et al: The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis, Urology 69(4 Suppl):S34-S40, 2007.

Fister GM: Similarity of interstitial cystitis (Hunner’s Ulcer) to lupus erythematosus, J Urol (40):37-41, 1938.

Orth RW et al: Lupus cystitis: primary bladder manifestations of systemic lupus erythematosus, Ann Intern Med 98(3):323-6, 1983.

Shibata S et al: Severe interstitial cystitis associated with Sjogren’s syndrome, Intern Med 43:248-252, 2004.

Silk MR: Bladder antibodies in interstitial cystitis, J Urol 103(3):307-309, 1970.

Jokinen EJ et al: Antitissue antibodies in interstitial cystitis, Clin Exp Immunol 11:333-339, 1972.

Oravisto KJ: Interstitial cystitis as an autoimmune disease, a review, Eur Urol 6:10-13, 1980.

Christmas TJ, Bottazzo GF: Abnormal urothelial HLA-DR expression in interstitial cystitis, Clin Exp Immunol 87:450-454, 1992.

Hudson T: Interstitial cystitis: a new approach, Townsend Letter 211:172-173, 2001.

Bouic PJ et al: Beta-sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: implications for their use as an immunomodulary vitamin combination, Int J Immunopharmacol 18:693-700, 1996.

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Interstitial cystitis and systemic autoimmune diseases

Is IC an Autoimmune Condition?

Behind the redness, swelling, heat and pain of any infection or injury, a biological war is occurring. Injured cells release chemicals that alert our immune system that something is wrong. One of these chemicals, chemokines, attract and direct white blood cells (i.e. macrophages, lymphocytes) to the injured area where they swarm and kill invading bacteria or microbes, ingest debris, eliminate foreign matter and trigger the repair of tissue. This acute inflammation response also causes an increase in blood flow (vasodilation), swelling, pain and heat that usually lasts only a few hours or days.

Inflammation is essential to healing. Without it, even the smallest of infections could become life threat- ening but when uncontrolled, inflammation plays a role in almost every major disease, including cancer, heart disease, diabetes, Alzheimers and depression. A poor diet, smoking, alcoholism and obesity are well known to promote chronic inflammation.

In 2016, several studies sought to determine what role, if any, inflammation plays in IC, especially Hunner’s lesions. They produced yet more compelling evidence that Hunner’s lesions are a separate, distinct disorder of the bladder.

Urine levels of Macrophage Migration Inhabitory Factor Are Increase In Patients With Inflammation

In an interesting international study, researchers sought to determine if macrophage inhibitory factor, a pro-inflammatory cytokine, increased in patients with inflammatory diseases of the bladder. They studied IC patients with and without Hunner’s lesions, as well as patients with UTI and radiation cystitis.Their results found that patients with

Hunner’s lesions had higher levels of MIF when compared to IC patients without, suggesting that MIF could serve as a marker to distinguish between the two conditions. It’s worth noting that a study in 2014 (Polyomavirus BK–a potential new therapeutic target for painful bladder syndrome/interstitial cystitis?) found that patients with Hunner’s lesions had a virus in their urine which could explain the increased inflam- matory response. Not surprisingly, patients with UTI and radiation cystitis also had higher levels which makes sense given the fact that the body is defending itself against infection and radiation damage.

Source: Ma, F, et al. Urine levels of macrophage migration inhibitory factorare increased in patients with bladder inflammation. AUA 2016 Abstract MP72-01

B-Cell Lymphocytes Found In Higher Quantities in Hunner’s Lesions Patients

A second study also sought to determine the type of immune response that occurs in Hunner’s lesions. Researchers in Japan took biopsies from 27 lesion patients, 39 non lesion IC patients and 15 non- IC patients and studied the infiltration, if any, of T-lymphocytes, B-lymphocytes, (lymphocytes created by bone marrow), plasma cells and the depth of the bladder epithelium. Their study demonstrated that B-cell lymphocytes were found in significantly higher levels in patients with lesions. They also found that the epithelium was significantly smaller when compared to other patients. They conclude that Hunner’s lesions are, indeed, a distinct inflammatory disorder.

Source: Akiyama Y, et al. Frequent expansion of clonal B-cells suggestive of specific immune responses in Hunner type IC. AUA 2016 Abstr act MP72-02

Urinary Chemokines May Predict IC/BPS in Patients With Urinary Symptoms

Researchers in Japan compared both immune and inflammatory urine markers in IC patients with Hunner’s lesions, IC patients without lesions, overactive bladder patients and controls. They found that IC/BPS patients had increased levels of vascular endothelial growth factor, fibroblast growth factor and several T-helper related chemokines. They did not find, however, a distinct difference between the two groups of IC patients. However, they did find that urinary symptoms did correlate with specific markers, particularly CSCL10.

Source: Furata A, et al. Urinary chemokines as predictors of IC/BPS in patients with lower urinary tract symptoms. AUA 2016 Abstract MP72- 03

Urinary Chemokines Predict Functional Bladder Capacity

Researchers in Michigan and Taiwan collaborated to determine if inflammatory chemokine/cytokine levels correlated with functional bladder capacity. They took urinary specimens from non ulcerative IC patients who had decreased bladder capacity vs. normal bladder capacity. Thirteen specific cytokines were measured demonstrating that there was a strong and significant correlation between inflammation and functional bladder capacity. They suggest that these measurements could be used in the phenotyping of IC patients as well.

Source: Lamb L, et al. Dexpression of multiplex urine cytokines discriminate functional bladder capacity in IC patients. AUA 2016 Abstract MP72-07

(PDF) Interstitial cystitis and systemic autoimmune diseases

r e v i e w

490 nAtUre clinicAl prActice UROLOGY vAn De meRWe septembeR 2007 vOL 4 nO 9

www.nature.com/clinic alpractice/uro

KEY POINTS

■ The association within patients and families

between interstitial cystitis (IC) and known

autoimmune diseases and a female

preponderance suggest an autoimmune nature

of IC, although direct evidence clearly showing

autoimmune mechanisms is lacking

■ The strongest association is between IC

and Sjögren’s syndrome, a disease in

which autoantibodies to the muscarinic M3

receptor on exocrine cells are important in the

pathogenesis

■ Muscarinic M3 receptors are also expressed

on detrusor smooth muscle cells, where they

mediate cholinergic contraction of the urinary

bladder

■ Autoantibodies that target muscarinic M3

receptors might therefore have a role in the

pathogenesis of IC

References

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suspected of having interstitial cystitis (IC). Eur Urol 45:

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interstitial cystitis symptoms in women participating in

a health screening project. Eur Urol 51: 803–808

8 Propert KJ et al. (2000) A prospective study of interstitial

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in the United States. J Urol 151: 423A

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update. Curr Opin Urol 12: 321–332

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in patients with interstitial cystitis. J Rheumatol 20:

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© 2007 Nature Publishing Group

Establishment of a Novel Autoimmune Experimental Model of Bladder Pain Syndrome/Interstitial Cystitis in C57BL/6 Mice

Interstitial Cystitis (Painful Bladder Syndrome): Causes & Treatment

Overview

What is interstitial cystitis (IC)?

Interstitial cystitis (IC) or painful bladder (PBS) is defined as a pain, pressure, or discomfort in the suprapubic or bladder area which can cause urinary frequency or the urge to urinate that has been present for at least six weeks.

Who gets interstitial cystitis (IC)?

Men, women and children can all be diagnosed with IC. It is estimated that approximately 83,000 men and 1.2 million women in the US suffer from IC.

Symptoms and Causes

What causes interstitial cystitis (IC)?

The causes for IC are not completely understood. IC may be related to such medical conditions as:

• Autoimmune disease.
• Allergies.
• Defects in the lining of the bladder.
• Vascular (blood vessel) disease.
• Mast cell (cells that cause allergic symptoms) abnormalities.
• Presence of abnormal substances in the urine.
• Unidentified infections.

What are the symptoms of interstitial cystitis (IC)?

Symptoms of IC/PBS vary from case to case, and can be mild, severe, occasional or constant. The symptoms may be similar to those of a bladder infection. Women’s symptoms often get worse during menstrual periods.

Symptoms of interstitial cystitis (IC) include the following:

• Suprapubic or pelvic pain.
• Pressure or discomfort when the bladder is filling.
• Having to urinate frequently.
• Urinating small amounts.

Diagnosis and Tests

How is interstitial cystitis (IC) diagnosed?

There are no definitive tests to diagnose IC/PBS. It is important to rule out other infections and conditions so your doctor may run different tests, including:

• Urine sample and urinalysis: The patient provides a urine sample, and the doctor examines it with a microscope to learn if there are any organisms, germs, pus, or white blood cells, which could mean that there is an infection. The doctor can treat the infection with antibiotics. If the urine is sterile for weeks or months and the symptoms continue, doctors may make a diagnosis of IC.
• Biopsy of the bladder wall and urethra: A biopsy is a sample of tissue taken from the body in order to examine it more closely. This procedure will be done under anesthesia. Tissue may be taken from the bladder wall and urethra (the tube through which urine passes out of the body) to rule out other conditions. A biopsy can help rule out bladder cancer.
• Cystoscopy: The doctor may examine the inside of the bladder with an instrument called a cystoscope. This is a long, thin scope with an eyepiece on one end. The cystoscope is gently placed up the urethra and into the bladder. The doctor can see into the bladder by looking through the eyepiece. The patient is not under anesthesia during this procedure. A cystoscopy can rule out bladder cancer. If a bladder biopsy is also planned, the cystoscopy may be performed at the same time, but this may require anesthesia.
• Cystoscopy under anesthesia with bladder distension: A cystoscopy may also be done with bladder distention (stretching). The doctor will perform a cystoscopy as described above and will distend (stretch) the bladder to its maximum capacity by filling it with water. This procedure can reveal cracks in the bladder. This procedure requires anesthesia because the stretching is painful for people with IC. After this procedure, many IC/PBS patients experience temporary relief of their symptoms.

Management and Treatment

How is interstitial cystitis (IC) treated?

Although IC/PBS cannot be cured, there are many ways to treat it. There is no way to predict who will respond best to certain treatments. Symptoms of IC/PBS may become more severe, or may disappear. Even if symptoms disappear, they may return after days, weeks, months or years.

Treatments for IC/PBS are aimed at relieving symptoms. Doctors will help decide the appropriate treatment for the patient. For some patients, treatments are combined.

Interstitial cystitis/painful bladder treatments can include:

• Diet: Some people with IC/PBS find that certain foods or drinks make their symptoms worse. You may find it helpful to keep a diary of what you eat and drink to see if any foods or drinks cause symptoms and/or flare-ups. For patients who have IC/PBS, acidic foods may irritate the bladder. If this is the case, your doctor may recommend taking an antacid with meals to reduce the amount of acid that gets into the urine. You may also want to remove certain foods from your diet, such as:
  • Alcohol
  • Caffeine
  • Carbonated beverages
  • Chocolate
  • Tomatoes
  • Artificial sweeteners
• Physical activity: Exercise and physical activity may help relieve the symptoms of IC/PBS. Exercises can include:
  • Walking
  • Biking
  • Gentle stretching
• Reducing stress: Stress can trigger flare-ups and symptoms in someone who has IC/PBS. Learning stress reduction methods and setting aside time for relaxation may make living with IC/PBS easier.
• Physical therapy: The pelvic muscles hold the bladder in place and help control urination. Exercising these muscles may help reduce the symptoms of IC/PBS. Your doctor or physical therapist can help you perform this exercises correctly.
• Bladder retraining: A person who has bladder pain can get in the habit of using the bathroom as soon as he or she feels pain or urgency, even if the bladder is not full. As a result, his or her body may get used to going to the bathroom often. Bladder retraining is a treatment to try to overcome this habit by helping you hold urine for a longer period of time. To use bladder retraining, keep a diary of how often you urinate, and how often you have the urge to urinate. Use the diary to gradually increase the length of time between bathroom breaks.
• Oral medications: Pentosan polysulfate sodium (Elmiron®) is a medication approved for treating the pain of IC. This medication may have to be taken for up to six months before any improvement is noticed. Medicines that treat heartburn may help the symptoms of IC by reducing the amount of acid made by the body. Muscle relaxants can help relieve the symptoms by keeping the bladder from squeezing at the wrong time. Antidepressants can be used to relieve pain in patients with IC. Tricyclic antidepressants such as amitriptyline (Elavil) have been shown to improve pain and reduce frequent urination in patients with IC. Narcotic pain medications are not routinely used to treat pain in IC patients.
• Bladder instillations: Another treatment is to fill the bladder with a liquid medicine. You place a small catheter or tube in the urethra and fill the bladder with medicine.
• Bladder stretching/hydrodistension: Bladder stretching or hydrodistension is a procedure that is performed in the operating room under anesthesia. The bladder is filled with sterile water in order to distend the bladder and increase the amount of urine you can hold.
• Nerve stimulation: Nerve stimulation is a treatment that helps regulate the bladder. These treatments are more helpful in reducing urgency and urinary frequency but sometimes can help with the bladder/suprapubic pain.
• Surgery: Surgery to treat IC/PBS is used as a last resort. The surgery may remove parts of the bladder or even the entire bladder. If the patient has tried every other treatment option and pain is unbearable, surgery may be considered.

Interstitial Cystitis | Johns Hopkins Medicine

What is interstitial cystitis?

Interstitial cystitis (IC) is an inflamed or irritated bladder wall. It can lead to scarring and stiffening of the bladder. The bladder can’t hold as much urine as it did in the past. It is a chronic disorder. IC may also be known as:

What causes interstitial cystitis?

The cause of interstitial cystitis (IC) is unknown. Researchers are looking at many theories to understand the causes of IC and find the best treatments.

Most people with IC find that certain foods make their symptoms worse. These include:

What are the symptoms of interstitial cystitis?

These are the most common symptoms of interstitial cystitis (IC):

• Frequent urination

• Urgency with urination

• Feelings of pressure, pain, and tenderness around the bladder, pelvis, and the area between the anus and vagina or anus and scrotum (perineum)

• Pain during sex

• In men, discomfort or pain in the penis and scrotum

• In women, symptoms may worsen around their period

Stress may also make symptoms worse, but stress does not cause symptoms.

The symptoms of IC may look like other conditions or medical problems. Always talk with a healthcare provider for a diagnosis.

How is interstitial cystitis diagnosed?

No single test can diagnose IC. And symptoms of IC are a lot like those of other urinary disorders. For these reasons, a variety of tests may be needed to rule out other problems. Your healthcare provider will start by reviewing your medical history and doing a physical exam. Other tests may include:

• Urinalysis. Lab testing of urine to look for certain cells and chemicals. This includes red and white blood cells, germs, or too much protein.

• Urine culture and cytology. Collecting and checking urine for white blood cells and bacteria. Also, if present, what kind of bacteria there are in the urine.

• Cystoscopy. A thin, flexible tube and viewing device, is put in through the urethra to examine the bladder and other parts of the urinary tract. This checks for structural changes or blockages.

• Bladder wall biopsy. A test in which tissue samples are removed from the bladder (with a needle or during surgery) and checked under a microscope to see if cancer or other abnormal cells are present.

• Lab exam of prostate secretions (in men). This is done to look for inflammation and/or infection of the prostate.

How is interstitial cystitis treated?

There is no cure for IC and it can be hard to treat. Treatments are aimed at easing symptoms, and may include:

• Bladder enlargement. This method increasing bladder capacity. It also interferes with pain signals being sent by the nerve cells in the bladder.

• Bladder wash. The bladder is filled with a solution that is held for varying times, from a few seconds to 15 minutes. Then it is drained out through a catheter.

• Medicine. Medicine may be taken by mouth or put right into the bladder. There are many different drugs that may be used.

• Transcutaneous electrical nerve stimulation (TENS). Mild, electric pulses enter the body for minutes to hours, 2 or more times a day. The pulses are sent through wires placed on the lower back, or through special devices put into the vagina in women or into the rectum in men. For some people, TENS eases bladder pain and urinary frequency and urgency.

• Bladder training. You urinate at specific times and use relaxation techniques and distractions to help keep to the schedule. Over time, you try to lengthen the time between the scheduled voids.

• Surgery. Surgery to remove all or part of the bladder may be done in severe cases, if other treatments do not work.

Management of IC may also include:

• Diet changes. No proof links diet to IC, but some believe that alcohol, tomatoes, spices, chocolate, caffeinated and citrus beverages, and high-acid foods may contribute to bladder inflammation. Removing these from the diet may help to decrease some symptoms.

• Not smoking. Many people with IC find that smoking makes their symptoms worse.

• Exercise. Exercise may help ease symptoms or make them stop for a while.

• Reducing stress. There is no proof that stress causes IC. But, if a person has IC, stress can make the symptoms worse.

Talk with a healthcare provider with any questions of concerns you may have about this health problem.

Key points about interstitial cystitis

• Interstitial cystitis (IC) is an inflamed or irritated bladder wall.

• The cause of IC is unknown and it does not get better with antibiotics.

• Symptoms of IC include changes in urination such as frequency and urgency; pressure, pain, and tenderness around the bladder, pelvis, and the area between the anus and vagina or anus and scrotum; and pain during sex.

• There is no best way to diagnose IC. A variety of tests may be needed. Urine tests will be done and imaging tests may be used to look at the different parts of the urinary tract and make sure everything is normal. Tissue samples may be removed from the bladder (with a needle or during surgery) and examined under a microscope to see if cancer or other abnormal cells are present.

• Treatments are aimed at easing symptoms. A variety of procedures, medicines, and lifestyle changes may be advised.

90,000 Markers of autoimmune diseases – Paracelsus Medical Center

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Hematological manifestations of autoimmune gastritis | Moosie

1. Chanarin I. A history of pernicious anemia.Br J Haemat 2000; 111: 407-41.

2. Faber K., Bloch C.E. Ueber die pathologischen Veranderungen am Digestionstractus bei der perniciosier Anamie und uber die sogenannte Darmatrophie. Ztschr f klin Med 1900; 40:98.

3. Taylor K.B., Morton J.A. An antibody to Castle’s intrinsic factor. J Path Bact 1959; 77: 117.

4.Irvine W.J., Davies S.H., Teitelbaum S., Delamore I.W., Williams A.W. The clinical and pathological significance of gastric parietal cell antibody. Ann N Y Acad Sci 1965; 124: 657-91.

5. Lahner E., Annibale B. Pernicious anemia: New insights from a gastroenterological point of view. World J Gastroenterol 2009; 15: 5121-8.

6. Irvine W.J. Clinical and pathological significance of parietal cell antibodies. Proc R Soc Med 1966; 59: 695-8.

7. Andres E., Serraj K. Optimal management of pernicious anemia. J Blood Med 2012; 3: 97-103.

8. Ye W., Nyrén O. Risk of cancers of the oesophagus and stomach by histology or subsite in patients hospitalized for pernicious anemia.Gut 2003; 52: 938-41.

9. Lechner K., Födinger M., Grisold W., Püspök A., Sillaber C. Vitamin B12 deficiency. New data on an old theme. Wien Klin Wochenschr 2005; 117: 579-91.

10. Oh R.C., Brown D.L. Vitamin B12 deficiency. Am Fam Physician 2003; 67: 993-4.

11.Gisbert J.P., Gomollón F. A short review of malabsorption and anemia. World J Gastroenterol 2009; 15: 464452.

12. Okorokov A. N. Diagnostics of diseases of internal organs. Diagnosis of diseases of the blood system. M .: Med. Litter; 2001.

13. Froese D.S., Gravel R.A. Genetic disorders of vitamin B12 metabolism: eight complementation groups – eight genes.Expert Rev Mol Med 2010; 12:37.

14. Beghé C., Wilson A., Ershler W.B. Prevalence and outcomes of anemia in geriatrics: a systematic review of the literature. Am J Med 2004; 116: 3-10.

15. Chulilla J.A.M., Colás M.S.R., Martín M.G. Classification of anemia for gastroenterologists. World J Gastroenterol 2009; 15: 4627-37.

16.Cabot R.C. Pernicious anemia (cryptogenic). A System of Medicine. London, 1908.

17. Andrès E., Vogel T., Federici L., Zimmer J., Ciobanu E., Kaltenbach G. Cobalamin deficiency in elderly patients: a personal view. Curr Gerontol Geriatr Res 2008: 848267.

18. Nafil H., Tazi I., Sifessalam M., Bouchtia M., Mahmal L. Clinical, biological and therapeutic profile of anemia by vitamin B12 deficiency in the department of hematology of Marrakech (Morocco).Bull Soc Pathol Exot 2013; 106: 83-8.

19. Song I. C., Lee H. J., Kim H. J., Bae S.B., Lee K. T., Yang Y. J., et. al. A multicenter retrospective analysis of the clinical features of pernicious anemia in a Korean population. J Korean Med Sci 2013; 28: 200-4.

20. Carmel R. Pernicious anemia. The expected findings of very low serum cobalamin levels, anemia, and macrocytosis are often lacking.Arch Intern Med 1988; 148: 1712-4.

21. Xiao S.D., Jiang S.J., Shi Y., Zhang D.Z., Hu Y.B., Liu W.Z., Yuan J.M. Pernicious anemia and type A atrophic gastritis in the Chinese. Chin Med J (Engl) 1990; 103: 192-6.

22. Alonso N., Granada M.L., Salinas I., Lucas A.M., Reverter J.L., Juncà J., Oriol A., Sanmartí A. Serum pepsinogen I: an early marker of pernicious anemia in patients with type 1 diabetes.J Clin Endocrinol Metab 2005; 90: 5254-8.

23. Muñoz M., Villar I., García-Erce J.A. An update on iron physiology. World J Gastroenterol 2009; 15: 4617-26.

24. Wang J., Pantopoulos K. Regulation of cellular iron metabolism. Biochem J 2011; 434: 365-81.

25.Bermejo F., García-López S. A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. World J Gastroenterol 2009; 15: 4638-43.

26. Colacci E., Pasquali A., Severi C. Exocrine gastric secretion and gastritis: pathophysiological and clinical relationships. Clin Ter 2011; 162: 19-25.

27. Johnson-Wimbley T.D., Graham D.Y. Diagnosis and management of iron deficiency anemia in the 21st century. Ther Adv Gastroenterol 2011; 4: 177-84

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Cofactor of anti-lipid antibodies in syphilis, Lyme borreliosis and autoimmune diseases | Voicechovskaya

1.

Flow Cytometric Analysis of Lymphocyte Infiltration in Central Nervous System during Experimental Autoimmune Encephalomyelitis

This study is a protocol for inducing and monitoring EAE using MOG35-55 in C57BL / 6 mice, considered a typical neuroimmune experimental animal model of MS. EAE can be induced by changing the strains of mice or the type of protein used for induction in accordance with the purpose of the study.For example, the use of the PLP139-151 peptide in SJL mice can induce a relapsing-remitting course of EAEU disease, which is particularly well suited for evaluating the therapeutic effect on 90,085 relapses 15 . The experimental procedure outlined here can be applied to other protocols ^{EAE 7.} In this model, C57BL / 6 mice are inoculated with the MOG35-55 peptide and develop monophasic disease. A 5-point scoring system is used to assess the severity of the EAE. Although several scoring systems ranging from 0-3 points or 0-10 points are used to assess ^{disease severity 7 , 16 , 17} , these results indicate that a 5-point scoring system can statistically determine significant differences in disease scores between groups and other EAE scoring systems do not lead to obvious improvement.

The severity of EAE is generally assessed by the clinical EAE score taking into account the severity of neurological dysfunction 11 ^{, 13} . To ensure comparability of the experiment for all mice, it is important to keep them under the same conditions, including cell changes, administration of food and water, and especially mouse housing conditions. In addition, cross-immunization should also be carried out in order to avoid cell-specific events caused by the investigator.

This study provides a method for separating mononuclear cells from the central nervous system, which is suitable for FACS analysis or functional research. To ensure that blood is removed from CNS tissue, mice must be infiltrated prior to tissue dissociation. Purification of mononuclear cells in a density gradient centrifuge is a key step in isolation. To provide a separation effect, the acceleration and deceleration of the centrifuge must be set to 1 and 0, respectively. Using this method, the yield of unicellular cells is generally low from a normal brain, but higher from a diseased brain with EAE.Representative results show that there is an apparent increase in CD3 ^and CD4 ^and T lymphocytes, especially IFN-γ producing cells and IL-17 producing cells believed to contribute to the worsening of the disease.

There are some limitations to this protocol. The EAE model induced with MOG35-55 shows a basically ^{immunological} cd4 and T cell response. If ^{role of} CELL8 and group B T cells is to be analyzed, alternative protocols should be considered.As an inflammatory disease of the CNS, a severe pathological phenotype is also found in the spinal cord in the EAE model. However, due to the large amount of myelin present, it is difficult to obtain a sufficient number of single cells from the spinal cord for FACS analysis. In this case, it is necessary to use immunohistochemistry or immunofluorescence to analyze the tissues of the spinal cord. There are also researchers who put the brain and spinal cord together to separate mononuclear cells for FACS analysis ¹² .This protocol separates single cells from the brain for FACS analysis and spinal cord tissue for immunohistochemistry and immunofluorescence analysis.

The importance of T-lymphocytes in the immune regulation of MS and EAO has recently received more and more attention. Most of the published literature is devoted to the spleen and lymph nodes 90,085 11; however, lymphocytes are found throughout the CNS of EAE mice and thus a characteristic analysis of T lymphocytes in the CNS is required. Immunohistological staining of sections can identify invading cells in the CNS.However, phenotypic and functional analyzes are limited. After the isolation of immune cells from the central nervous system of normal or diseased mice, more detailed phenotypes can be analyzed. With this method, T lymphocytes in the brain can be studied on a cellular basis, and the expression of various surface markers, cytokines, chemokine and transcription factors (eg, intracellular proteins) can be analyzed better. The protocol will be useful for future research to assess the phenotype and function of T lymphocytes in the brain during MS and EAE.

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News of world thyroidology | Sviridonova

1. Yoshihara A., Noh J.Y., Ohye H. et al. Reference limits for serum thyrotropin in a Japanese population // Endocr. J. 2011. May 7

2. Døssing H., Bennedbäk F.N., Hegedus L. Long term outcome following interstitial laser photocoagulation of benign cold thyroid nodules // Eur.J. Endocrinol. 2011. May 6

3. Welch K.C., McHenry C.R. Total thyroidectomy: is morbidity higher for graves’ disease than nontoxic goiter? // J. Surg. Res. 2011. Apr 19

4. Balta A.Z., Filiz A.I., Kurt Y. et al. Prognostic value of oncoprotein expressions in thyroid papillary carcinoma // Med. Oncol. 2011 May 6

5.Ahmed S., Van Gelder I.C., Wiesfeld A.C. et al. Determinants and outcome of amiodarone-associated thyroid dysfunction // Clin. Endocrinol. 2011. Apr 30

6. Oppo A., Franceschi E., Atzeni F. et al. Effects of hyperthyroidism, hypothyroidism and thyroid autoimmunity on female sexual function // J. Endocrinol. Invest. 2011. Apr

7.Gumez Q C.H., Vesga G J.F., Lowenstein De. et al. Mass screening for hypothyroidism in a cohort of HIV infect- ed patients in a Bogotb hospital, Colombia // Rev. Chilena. Infectol. 2011. V. 28 (1). P. 59–63.

8. Kuppens S.M., Kooistra L., Wijnen H.A. et al. Neonatal thyroid screening results are related to gestational maternal thyroid function // Clin. Endocrinol. 2011. Apr

9.Rotondi M., Cappelli C., Magri F. et al. Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome // Clin. Endocrinol. 2011. Mar

10. Tagami T., Kimura H., Ohtani S. et al. Multi-center study on the prevalence of hypothyroidism in patients with hypercholesterolemia // Endocr. J. 2011

11. Erbil Y., Ozbey N.C., Sari S. et al. Determinants of postoperative hypocalcemia in vitamin D-deficient Graves’ patients after total thyroidectomy // Am. J. Surg. 2011. V. 201 (5). P. 678-684.

12.