What is the relationship between interstitial cystitis and autoimmune diseases. How does interstitial cystitis affect the bladder. What are the potential autoimmune mechanisms involved in interstitial cystitis. Why is there a strong association between interstitial cystitis and Sjögren’s syndrome.

Understanding Interstitial Cystitis: A Chronic Bladder Condition

Interstitial cystitis (IC) is a chronic condition that affects the bladder, causing pain and discomfort. Despite extensive research, the exact cause of IC remains unknown. However, there is growing evidence suggesting a potential link between IC and autoimmune diseases.

Key points about interstitial cystitis:

• It is a chronic bladder condition
• The exact cause is unknown
• It predominantly affects women
• Symptoms include bladder pain and frequent urination

Is interstitial cystitis an autoimmune disease?

While IC is not definitively classified as an autoimmune disease, several factors suggest a potential autoimmune component:

1. Presence of autoantibodies in some patients
2. Strong association with other autoimmune diseases
3. Female predominance, which is common in autoimmune conditions
4. Familial clustering of IC and autoimmune diseases

Autoantibodies in Interstitial Cystitis: Cause or Consequence?

Researchers have identified various autoantibodies in patients with interstitial cystitis, including those targeting nuclear and bladder epithelium antigens. However, it’s crucial to understand that the presence of these autoantibodies does not necessarily indicate a causal relationship.

Are autoantibodies the primary cause of interstitial cystitis?

Current evidence suggests that autoantibodies found in IC patients are likely secondary to the disease process rather than the primary cause. This means that while autoantibodies are present, they may be a result of tissue damage and inflammation rather than the initiating factor in IC development.

The Intriguing Link Between Interstitial Cystitis and Sjögren’s Syndrome

Among the various autoimmune diseases associated with interstitial cystitis, Sjögren’s syndrome stands out as having the strongest connection. This association provides valuable insights into potential shared mechanisms between the two conditions.

Why is there a strong association between IC and Sjögren’s syndrome?

Several factors contribute to the strong link between IC and Sjögren’s syndrome:

• Both conditions affect exocrine glands and mucous membranes
• Shared genetic susceptibility factors
• Similar inflammatory processes
• Potential involvement of autoantibodies targeting muscarinic receptors

The Role of Muscarinic M3 Receptor Autoantibodies

Recent research has shed light on the potential role of autoantibodies targeting the muscarinic M3 receptor in both Sjögren’s syndrome and interstitial cystitis. This discovery offers a promising avenue for understanding the pathogenesis of both conditions.

How do muscarinic M3 receptor autoantibodies relate to IC and Sjögren’s syndrome?

The muscarinic M3 receptor is present in various tissues, including:

• Salivary and lacrimal glands (affected in Sjögren’s syndrome)
• Detrusor muscle cells of the bladder (relevant to IC)
• Other smooth muscle tissues throughout the body

Autoantibodies targeting this receptor may interfere with normal cholinergic signaling, leading to dysfunction in multiple organ systems. This shared mechanism could explain the frequent co-occurrence of IC and Sjögren’s syndrome.

Exploring the Autoimmune Hypothesis in Interstitial Cystitis

While direct evidence for an autoimmune cause of interstitial cystitis is lacking, several indirect factors support this hypothesis:

What evidence supports an autoimmune component in IC?

1. Strong female preponderance (similar to many autoimmune diseases)
2. Clinical association with other autoimmune conditions
3. Familial clustering of IC and autoimmune diseases
4. Response to immunomodulatory therapies in some patients
5. Presence of inflammatory markers and immune cell infiltration in bladder tissue

The Two-Phase Model of Interstitial Cystitis Pathogenesis

Emerging evidence suggests that the development of interstitial cystitis may involve two distinct phases, each potentially influenced by autoimmune mechanisms.

What are the proposed phases of IC development?

The two-phase model of IC pathogenesis includes:

1. Early non-inflammatory phase: Characterized by subtle changes in bladder function and sensitivity
2. Late inflammatory phase: Marked by more pronounced inflammation and tissue damage

Autoantibodies, particularly those targeting the muscarinic M3 receptor, may play a role in both phases of the disease process. In the early phase, they could contribute to altered bladder function, while in the later phase, they may exacerbate inflammation and tissue damage.

Implications for Diagnosis and Treatment of Interstitial Cystitis

Understanding the potential autoimmune aspects of interstitial cystitis has important implications for both diagnosis and treatment strategies.

How does the autoimmune hypothesis impact IC management?

Considering the autoimmune component in IC can influence management in several ways:

• Screening for associated autoimmune conditions in IC patients
• Exploring immunomodulatory therapies as potential treatment options
• Investigating biomarkers related to autoimmune processes for diagnosis and monitoring
• Developing targeted therapies aimed at specific autoantibodies or immune pathways

Future Directions in Interstitial Cystitis Research

The complex relationship between interstitial cystitis and autoimmune diseases opens up numerous avenues for future research and therapeutic development.

What are the key areas for future IC research?

Important areas for further investigation include:

1. Elucidating the precise role of autoantibodies in IC pathogenesis
2. Identifying genetic factors that predispose individuals to both IC and autoimmune diseases
3. Developing more specific and sensitive diagnostic tools based on autoimmune markers
4. Exploring novel immunomodulatory therapies tailored to IC pathophysiology
5. Investigating the potential for preventive strategies in high-risk individuals

As research in this field progresses, our understanding of the intricate relationship between interstitial cystitis and autoimmune diseases continues to evolve. This growing knowledge base holds promise for improved diagnosis, treatment, and ultimately, better quality of life for individuals affected by these challenging conditions.

The Impact of Interstitial Cystitis on Quality of Life

Interstitial cystitis can have a significant impact on the quality of life of those affected. The chronic nature of the condition, combined with its often unpredictable symptoms, can lead to various challenges in daily life.

How does IC affect patients’ daily lives?

The impact of IC on quality of life can be far-reaching:

• Chronic pain and discomfort
• Frequent urination, including during the night
• Disrupted sleep patterns
• Limitations in physical activities
• Emotional distress and anxiety
• Challenges in maintaining social relationships
• Potential impact on work productivity

Understanding these impacts is crucial for healthcare providers to offer comprehensive care that addresses both the physical and psychosocial aspects of living with interstitial cystitis.

Multidisciplinary Approach to Interstitial Cystitis Management

Given the complex nature of interstitial cystitis and its potential links to autoimmune processes, a multidisciplinary approach to management is often beneficial.

Which specialists may be involved in IC care?

A comprehensive care team for IC patients may include:

1. Urologists
2. Rheumatologists
3. Immunologists
4. Pain management specialists
5. Physical therapists
6. Psychologists or psychiatrists
7. Nutritionists

This multidisciplinary approach allows for a holistic treatment strategy that addresses the various aspects of IC, including potential autoimmune components and associated conditions.

Emerging Therapies for Interstitial Cystitis

As our understanding of the potential autoimmune aspects of interstitial cystitis grows, new therapeutic approaches are being explored.

What are some promising new treatments for IC?

Emerging therapies for IC include:

• Targeted immunomodulatory drugs
• Stem cell therapies
• Novel intravesical treatments
• Neuromodulation techniques
• Personalized medicine approaches based on genetic and immunological profiles

These innovative treatments offer hope for improved management of IC symptoms and potentially addressing the underlying autoimmune mechanisms that may contribute to the condition.

The Role of Diet and Lifestyle in Managing Interstitial Cystitis

While the potential autoimmune aspects of interstitial cystitis are important to consider, lifestyle factors also play a crucial role in managing the condition.

How can diet and lifestyle changes help manage IC symptoms?

Several lifestyle modifications may help alleviate IC symptoms:

1. Identifying and avoiding dietary triggers
2. Stress management techniques
3. Pelvic floor exercises
4. Bladder training
5. Adequate hydration
6. Regular, gentle exercise
7. Smoking cessation

These lifestyle interventions, when combined with medical treatments, can significantly improve quality of life for many IC patients.

Genetic Factors in Interstitial Cystitis and Autoimmune Diseases

The association between interstitial cystitis and autoimmune diseases suggests that shared genetic factors may play a role in their development.

Are there genetic links between IC and autoimmune diseases?

Research into the genetic basis of IC and associated autoimmune conditions has revealed:

• Certain HLA (Human Leukocyte Antigen) types may increase susceptibility to both IC and autoimmune diseases
• Polymorphisms in genes involved in immune regulation have been identified in IC patients
• Familial clustering of IC and autoimmune diseases suggests a genetic component
• Epigenetic factors may contribute to the development of IC and related conditions

Understanding these genetic links could lead to improved risk assessment and potentially new therapeutic targets for both IC and associated autoimmune diseases.

The Importance of Early Diagnosis in Interstitial Cystitis

Early diagnosis of interstitial cystitis is crucial for optimal management and prevention of complications. However, the lack of specific diagnostic markers can make early detection challenging.

Why is early diagnosis of IC important?

The benefits of early IC diagnosis include:

1. Prompt initiation of appropriate treatment
2. Prevention of bladder damage and fibrosis
3. Improved quality of life
4. Opportunity to screen for associated autoimmune conditions
5. Better long-term outcomes

Efforts to improve early diagnosis of IC, potentially through the identification of autoimmune markers or genetic risk factors, remain an important area of research.

The Global Impact of Interstitial Cystitis

Interstitial cystitis affects individuals worldwide, with variations in prevalence and presentation across different populations.

How does IC impact different populations globally?

Global perspectives on IC reveal:

• Variations in prevalence rates across countries and ethnic groups
• Differences in clinical presentation and associated conditions
• Variability in diagnostic criteria and treatment approaches
• Challenges in access to specialized care in some regions
• Cultural factors influencing symptom reporting and help-seeking behaviors

Understanding these global variations is crucial for developing culturally sensitive and globally applicable strategies for IC management.

Patient Advocacy and Support in Interstitial Cystitis

Patient advocacy plays a vital role in raising awareness about interstitial cystitis, supporting affected individuals, and driving research efforts.

How do patient advocacy groups contribute to IC care and research?

Patient advocacy organizations contribute in several ways:

1. Providing education and support to patients and families
2. Raising public awareness about IC
3. Advocating for increased research funding
4. Facilitating patient participation in clinical trials
5. Collaborating with healthcare providers to improve care standards
6. Supporting the development of patient-centered outcome measures

These efforts are crucial in advancing our understanding of IC, improving patient care, and ultimately working towards better treatments and potential cures for this challenging condition.

As research into the relationship between interstitial cystitis and autoimmune diseases continues, it holds promise for improved understanding, diagnosis, and treatment of this complex condition. The multifaceted nature of IC necessitates a comprehensive approach that considers both its potential autoimmune aspects and the broader impact on patients’ lives. By advancing our knowledge in these areas, we can hope to provide better care and support for individuals affected by interstitial cystitis and associated autoimmune conditions.

Interstitial cystitis and systemic autoimmune diseases

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Review

. 2007 Sep;4(9):484-91.

doi: 10.1038/ncpuro0874.

Joop P van de Merwe 
¹

Affiliations

Affiliation

• ¹ Erasmus MC, University Medical Center Rotterdam, Departments of Immunology and Internal Medicine, Dr Molewaterplein 50, Rotterdam, The Netherlands. [email protected]

• PMID:

  17823601

• DOI:

  10.1038/ncpuro0874

Review

Joop P van de Merwe.

Nat Clin Pract Urol.

2007 Sep.

. 2007 Sep;4(9):484-91.

doi: 10. 1038/ncpuro0874.

Author

Joop P van de Merwe 
¹

Affiliation

• ¹ Erasmus MC, University Medical Center Rotterdam, Departments of Immunology and Internal Medicine, Dr Molewaterplein 50, Rotterdam, The Netherlands. [email protected]

• PMID:

  17823601

• DOI:

  10.1038/ncpuro0874

Abstract

The cause of interstitial cystitis, a chronic disease that affects the bladder, is unknown. Autoantibodies, such as those against nuclear and bladder epithelium antigens, have been found in patients with interstitial cystitis, but these are likely to be secondary to the disease. No data support a direct causal role of autoimmune reactivity in the pathogenesis of interstitial cystitis. Indirect evidence, however, does support a possible autoimmune nature of interstitial cystitis, such as the strong female preponderance and the clinical association between interstitial cystitis and other known autoimmune diseases within patients and families. The strongest association occurs between interstitial cystitis and Sjögren’s syndrome. Increasing evidence suggests a possible role of autoantibodies to the muscarinic M3 receptor in Sjögren’s syndrome. The M3 receptor is also located on the detrusor muscle cells of the bladder and mediates cholinergic contraction of the urinary bladder and other smooth muscle tissues. Autoantibodies to the M3 receptor might be important in both the early noninflammatory and the late inflammatory features of interstitial cystitis.

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ICS 2021 Abstract #455 The severity of bladder pain syndrome in patients with autoimmune disease

The severity of bladder pain syndrome in patients with autoimmune disease

Vogiatzi G

¹, Akrivou D², Skriapas K², Samarinas M²

	Abstract 455
	On Demand Pelvic Pain Syndromes / Sexual Dysfunction Scientific Open Discussion Session 29
	On-Demand
	Pain, Pelvic/Perineal Painful Bladder Syndrome/Interstitial Cystitis (IC) Questionnaire
	1. General Hospital of Larissa, Department of Internal Medicine, 2. General Hospital of Larissa, Urology Department
G Georgia Vogiatzi
Edit Abstract Abstract Centre

Abstract

Hypothesis / aims of study

Bladder Pain Syndrome (BPS) is a clinical diagnosis that relies on symptoms of pain in the bladder and pelvis, including also urgency and frequency [1].  BPS has been defined as chronic (>6 months) pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom such as persistent urge to void or frequency [2]. The International Continence Society (ICS) has defined BPS as the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms such as increased daytime and night-time frequency, in the absence of proven urinary infection or other obvious pathology [9]. ICS, also, reserved the diagnosis Interstitial Cystitis (IC) to patients with typical cystoscopic and histological features. However, it has been shown that only a fraction of patients with BPS fulfils this definition. Apart from the relationship of BPS with overactive bladder (OAB) symptoms, there is some literature supporting a correlation of BPS with systemic diseases. In our study we investigated the possible association of BPS with autoimmune syndromes.

Study design, materials and methods

This is an observational comparative study including patients from the Pelvic Pain Syndrome specific outpatients’ office of the Urology Department and the Internal Medicine outpatients’ office of our hospital.  Patients have been allocated into two groups. Group A included patients with BPS and an autoimmune disease in their medical history, while Group B included those with BPS but without autoimmune disease. All patients have been evaluated with visual analogue scale (VAS), Interstitial cystitis symptom index (ICSI) and Interstitial cystitis problem index (ICPI) as separate parts of O’Leary- Saint score (OSS). Additionally, all patients underwent a cystoscopy under general anesthesia in order maximum bladder capacity (MBC) to be evaluated. Patients with neurological medical history and diabetes mellitus have been excluded from the study. The collected data have been statistically analyzed with the use of SPSS v.24 and the appropriate methods for non-parametric samples.

Results

The study enrolled 26 patients, 16 women and 10 men with a mean age of 45.5 years old. Group A included 14 patients (8 women and 6 men) and Group B 12 (8 women and 4 men).  Regarding autoimmune diseases, 6 patients had rheumatoid arthritis, 4 had Sjogren Syndrome, 2 had Wilson Disease, 1 had rheumatic polymyalgia and 1 was with Lupus. In Group A the mean VAS was 8.5 for the whole patients with a prevalence for women comparing to men, documented with a statistical difference (p= 0.02). In Group B the mean VAS was 7.25 without specific differences between genders. VAS has been found statistically different between two groups (p= 0.01). Considering ICSI, patients of Group A have documented a mean score of 16.5, but there was a significant difference between genders with women to be evaluated with higher scores when compared to men (p= 0.03). In Group B, the mean ICSI was 13.25 without any difference inside genders subgroup. In parallel, the evaluation of ICPI resulted to a mean score of 12.5 for Group A with a statistical prevalence for women (p= 0.03), while the mean score for ICPI in Group B has been measured at 10.25 without difference between genders. Both indexes have been found to be statistically different comparing the two groups (p= 0. 03 and p= 0.02 respectively). Inside Group A, it seemed that patients with Sjogren Syndrome documented the highest scores among all other with autoimmune diseases in the evaluation questionnaires (mean VAS= 9, mean ICSI= 17.5, mean ICPI= 13.5). Cystoscopy revealed only one case with Hunner’s lesion, in a patient with Sjogren Syndrome. Also, the mean MBC under anesthesia was 550ml for patients of Group A and 575ml for those of Group B without any statistical difference between them.

Interpretation of results

Bladder pain syndrome may have a basic research association with autoimmune diseases, but their clinical correlation has to be confirmed. In our study, patients with both BPS and autoimmune disease have been found to have more severe lower urinary tract symptoms and pain than those with BPS alone. Moreover, women seem to suffer more than men. The limitation of our study is that the difference among autoimmune diseases, regarding lower urinary tract dysfunction and pain, cannot be evaluated due to the small recruitment. 

Concluding message

Patients with bladder pain syndrome seem to have a more severe lower urinary symptoms and discomfort when there is a medical history of a concomitant autoimmune disease.

References

Van De Merwe, J., Nordling, J., Bouchelouche, K. et.al: Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an essic proposal. Eur Urol, 53: 60, 2008.
Hanno, P., Nordling, J., van Ophoven, A.: What is new in bladder pain syndrome/interstitial cystitis? Curr Opin Urol, 18: 353, 2008
Abrams, P. H., Cardozo, L., Fall, M., et al.: The standardisation of terminology of lower urinary tract function: report from the standardisation sub-committee of the international continence society. Neurourology and Urodynamics, 21: 167, 2002.

Disclosures

Funding none Clinical Trial No Subjects Human Ethics Committee Scientific Council of General Hospital of Larissa Helsinki Yes Informed Consent Yes

20/06/2023 21:25:45

Ecoantibiotics – Interstitial cystitis: autoimmune or infectious?

According to the classification, cystitis can be of infectious and non-infectious nature (chemical, autoimmune, radiation, after radiation therapy), it can be acute and chronic.

According to the type of inflammatory process, the following types of cystitis are distinguished:

• catarrhal
• hemorrhagic
• ulcerative
• phlegmonous
• necrotic
• interstitial
• polyposis.

Interstitial cystitis is of particular interest. This is a clinical syndrome, the causes of which are still being discussed. The medical community considers the most likely cause of interstitial cystitis to be autoimmune damage to urothelial cells and a violation of the innervation of the bladder wall.

There are two forms of the disease: ulcerative (with the formation of an ulcer in the bladder) and non-ulcerative.

Symptoms that characterize interstitial cystitis include chronic pelvic pain, painful frequent urination, including at night. All this leads to sexual dysfunction, psychological problems, neuroses and, ultimately, social maladaptation.

Predisposing factors for the development of interstitial cystitis include:

• history of autoimmune diseases
• bronchial asthma
• irritable bowel syndrome
• drug allergy
• surgical interventions in the pelvic area, etc.

The treatment of interstitial cystitis is based on the following principles:

• maintaining the integrity of the bladder epithelium
• decreased neurogenic activation
• prevention of the allergic cascade.

Groups of drugs used to treat this pathology include NSAIDs, antihistamines, anticholinergics and antispasmodics. is a process that requires high adherence to treatment from patients. In case of secondary infection, antibiotics are prescribed.

Secondary infection in interstitial cystitis

The most common causative agent of acute infectious inflammation of the bladder, including secondary – against the background of existing interstitial cystitis, is the gram-negative flora of the intestinal group, in particular E. coli.

Factors predisposing to the development of this disease are:

• anatomical features of the structure (wide and short urethra in women)
• proximity to natural reservoirs of infection
• frequency and nature of sexual intercourse
• violations of urodynamics due to the presence of concomitant diseases (prostate adenoma in men).

Among the most common symptoms of acute infectious cystitis are pain above the pubis, painful frequent urination. In uncomplicated acute cystitis, there is no fever, chills, weakness, loss of appetite, and other general symptoms. Their appearance will indicate the addition of complications and requires an immediate response from the medical worker.

In case of untimely and inadequate treatment, acute cystitis may become chronic.

Chronicity of the process is facilitated by:

• the presence of resistant forms of uropathogenic microorganisms
• violation of urine outflow
• the presence of foreign bodies in the bladder (stones).

The diagnosis of cystitis is made on the basis of the patient’s complaints of frequent and painful urination, history, and laboratory results.

In the general analysis of urine, the presence of leukocytes and bacteria can be noted. A clinical blood test is characterized by classic signs of inflammation: an increase in the number of leukocytes, a shift of the leukoformula to the left, and an increase in ESR.

Urine culture and antibiotic susceptibility testing recommended to identify the causative agent. Among the instrumental methods, ultrasound of the bladder is of the greatest importance. In the acute period of infection, cystoscopy is not recommended.

In the case of a chronic course of the process, urine culture for Mycobacterium tuberculosis and cystoscopy are additionally prescribed.

Treatment of bacterial complications of interstitial cystitis

Etiopathogenetic treatment of cystitis is based on the elimination of provoking factors and the appointment of etiotropic antibiotic therapy. The drugs of choice are antibiotics from the group of fluoroquinolones.

Given the negative impact of antibacterial drugs on the natural intestinal microflora, it is advisable to use the most gentle drugs in patients with interstitial cystitis. So, ecoantibiotics Ecolevid (levofloxacin) and Ecocifol (ciprofloxacin) contain a prebiotic component – anhydro lactulose, which contributes to the preservation of normal intestinal microflora. The presence of an additional component helps the patient to better tolerate antibiotic treatment and reduces the likelihood of developing negative effects from the gastrointestinal tract.

In case of chronic cystitis, antispasmodics, local therapy (instillations of medicinal solutions into the bladder) are also prescribed, if indicated, immunotherapy is performed.

Painful bladder syndrome in women ᐉ more details on the website

Painful Bladder Syndrome (BPS) is common among women of all ages. You can also find the name interstitial cystitis. This is an inflammation of the bladder, but unlike ordinary cystitis, it is usually not associated with infections. Such a disease is extremely unpleasant and definitely needs treatment, otherwise the price of a neglected syndrome will be too high.

Summary of

Patients who have suffered from interstitial cystitis most often describe the disease as “toilet addiction”. Indeed, the most frequent and accurate symptom is a sudden and sharp urge to urinate. This symptom is especially pronounced at night. The following symptoms of the manifestation of the disease are also distinguished:

• pain in the lower abdomen, especially when filling the bladder;
• painful urination;
• feeling of incomplete emptying of the bladder;
• discomfort in the womb;
• possible pain during sex and blood when urinating.

The causes of the syndrome are varied. It can be hypothermia, decreased immunity, circulatory disorders of the bladder, inflammation of the genital organs, hormonal changes, autoimmune diseases, stress. Also, the consumption of salty, spicy and fatty foods, alcohol, and certain foods can become a provoking factor.

Sometimes the symptoms of the disease go away on their own, but in most cases the acute phase recurs. Therefore, when the first signs appear, be sure to consult a doctor for help. Prolonged course of the disease can lead to serious health problems.

Methods for diagnosing SBPS

To diagnose painful bladder syndrome, a comprehensive examination is necessary. It includes:

1. Clinical analysis and urine culture
2. Ultrasound of the genitourinary system
3. Cystometry
4. Endoscopy of the bladder
5. Taking swabs from the urethra, vagina
6. Gynecological consultation.

According to the results of the examination and tests, appropriate treatment is prescribed.

What does self-treatment lead to?

Doctors urge not to start self-treatment in any case. Often, patients confuse BPS with cystitis and take antibiotics. This treatment may be ineffective and provoke intestinal or vaginal dysbiosis and lead to other bad consequences. Also, taking the wrong drugs can lead to the appearance of forms of bacteria that are resistant to therapy and complicate treatment.

Treatments for painful bladder syndrome

Methods of treatment are individual and selected by a doctor. Most often, patients are prescribed complex therapy, which includes:

1. Diet. At the time of treatment, it is worth giving up fried, salty and spicy foods, sweets. You need to drink more water, fruit drinks, and also eat fresh vegetables, berries and fruits, especially those that have a diuretic effect. You can eat dairy products.
2. Medical therapy. Usually prescribe drugs that relieve excessive excitability of the bladder, painkillers, anti-inflammatory drugs, antidepressants and antihistamines.
3. Topical therapy. This is the introduction into the bladder of drugs, hyaluronic acid and other drugs to alleviate the condition and stabilize the bladder.
4. Magnetic laser therapy – external or internal.

Doctors also often have to deal with complications that arise during the long course of the disease. This is the destruction of the protective membrane of the bladder, spasm of the pelvic floor muscles, fibrosis, irritable bowel syndrome, sexual disorders and other consequences.

Treatment of interstitial cystitis is usually long and requires patience.