Interstitial Cystitis: Symptoms, Types, Causes and Treatment

Interstitial cystitis (IC), also known as bladder pain syndrome (BPS), is a chronic and often misunderstood condition that can severely impact quality of life. Characterized by pelvic pain and urinary symptoms, IC/BPS remains a diagnostic and therapeutic challenge for both patients and clinicians. This article offers a detailed, evidence-based overview of the symptoms, types, causes, and treatment options for interstitial cystitis, with the aim of empowering patients and healthcare providers with up-to-date information.

Symptoms of Interstitial Cystitis

Interstitial cystitis is notorious for its wide range of symptoms, which often overlap with other urological and gynecological conditions. Recognizing these symptoms early is crucial for timely diagnosis and management. The most common complaints involve pain, urinary urgency, and frequent urination, but every patient’s experience can be unique.

Symptom	Description	Distinguishing Features	Sources
Pain	Bladder/pelvic pain or discomfort	Often worsens with bladder filling, relieved after voiding	2 4 5 7
Frequency	Frequent urination, day and night	Absence of infection, persists at night (nocturia)	2 4 5 7
Urgency	Sudden, strong urge to urinate	Not always related to incontinence	2 4 5 7
No Infection	Negative urine cultures	Symptoms persist despite antibiotics	2 4 7

Table 1: Key Symptoms

The Core Symptom Cluster

The hallmark symptoms of IC/BPS include:

• Bladder or pelvic pain: Patients often describe a deep, aching discomfort, burning, or pressure in the bladder area, which may radiate to the lower abdomen, pelvic floor, or perineum. Pain typically worsens with bladder filling and may improve after urination 2 4 5 7.

• Increased urinary frequency: Many individuals feel the need to urinate far more often than normal, both during the day and night (nocturia). It's not uncommon for patients to void every hour, or even more frequently in severe cases 2 4 5.

• Urgency: There is a pronounced and sometimes sudden need to urinate—a sensation of pressure that can be very distressing. Unlike overactive bladder, this urgency is less often associated with urge incontinence 2 5.

Overlapping and Distinguishing Symptoms

Because IC/BPS symptoms overlap with urinary tract infections (UTIs), overactive bladder, endometriosis, vulvodynia, and other pelvic pain disorders, diagnosis can be delayed or missed 2 5. However, some features help distinguish IC/BPS:

• Persistently negative urine cultures, even during symptomatic episodes, help rule out infection 2 4 5.
• Chronicity and lack of response to antibiotics are red flags that suggest IC/BPS over recurrent UTIs 2 4.
• Pain as a core symptom: Pain with bladder filling or urgency is more characteristic of IC/BPS than overactive bladder, which is primarily associated with urgency and frequency without significant pain 2.

Impact on Quality of Life

IC/BPS can be severely disabling, affecting daily activities, work, relationships, and mental health. Many patients report significant distress, feelings of isolation, and reduced quality of life 1 5. Symptom severity can fluctuate, with periods of exacerbation and remission.

Types of Interstitial Cystitis

IC/BPS is not a single disease but a spectrum, with distinct clinical and biological subtypes. Understanding these types is essential for accurate diagnosis and targeted treatment.

Type	Key Feature(s)	Bladder Findings / Pathology	Sources
Hunner-type IC	Presence of Hunner lesions	Severe inflammation, epithelial denudation, lymphoplasmacytic infiltration	6 7 8 9 10
Non-Hunner IC/BPS	No Hunner lesions	Little or no inflammation, glomerulations or normal bladder mucosa	6 7 8 9 10
Bladder Pain Syndrome	Symptoms without clear bladder pathology	May have glomerulations post-distension, no Hunner lesions	7 8 9

Table 2: Classification of IC/BPS Types

Hunner-type Interstitial Cystitis

• Defining Feature: Presence of Hunner lesions (ulcer-like inflammatory patches) visible on cystoscopy.
• Pathology: Marked by severe bladder wall inflammation, urothelial denudation, and infiltration by immune cells (mainly lymphocytes and plasma cells). Increased microvessel density is also observed 6 7 8 9 10.
• Distinct Entity: Genomic and histological studies confirm that Hunner-type IC is a distinct inflammatory bladder disease and should be considered separately from other IC/BPS forms 6 7 8 10.

Non-Hunner-type IC/BPS (Bladder Pain Syndrome)

• Defining Feature: Absence of Hunner lesions on cystoscopy.
• Pathology: Bladder mucosa may appear normal or show mild changes (such as glomerulations—small, red petechial hemorrhages after bladder distension), but significant inflammation is lacking 6 7 8 9.
• Mechanisms: This type is less likely to involve overt bladder inflammation, and is thought to be related to urothelial dysfunction, altered nerve signaling, or even central nervous system sensitization 8.

Why Classification Matters

• Diagnosis and Treatment: Accurate subtype classification (especially identification of Hunner lesions via cystoscopy) is crucial, as treatment approaches differ significantly 7 8.
• Research and Outcomes: Studies emphasize the need to analyze outcomes separately for Hunner-type and non-Hunner-type IC/BPS to improve understanding and therapy 6 7 8.

Causes of Interstitial Cystitis

The exact cause(s) of IC/BPS remain elusive, but research points to a complex interplay of factors involving inflammation, immune system dysregulation, epithelial barrier defects, and possibly infections. Let’s delve into the current understanding.

Factor	Role in IC/BPS	Supporting Evidence	Sources
Inflammation	Central in Hunner-type IC	Cytokine elevation, immune cell infiltration	3 6 7 8 10
Urothelial Defect	Increased bladder permeability	Glycosaminoglycan layer disruption, increased solute penetration	12 13
Immune Dysregulation	Autoimmunity, abnormal responses	Lymphoplasmacytic infiltration, cytokines	3 6 7 8
Infection (Viruses)	Possible trigger/maintainer	Epstein-Barr virus, others in lesions	11
Neural Factors	Sensitization, altered pain processing	Central and peripheral nervous system changes	3 8 13 14
Psychosocial Stress	Exacerbates symptoms	HPA axis dysregulation, stress/anxiety links	3 13 14

Table 3: Proposed Causes and Contributing Factors

Inflammation and Immune Dysfunction

• Hunner-type IC is defined by robust, chronic inflammation involving immune cell infiltration and upregulation of inflammatory mediators such as interleukin-6 and interleukin-1β 3 6 7 8.
• Toll-like receptor (TLR) activation has been linked to pain severity and may drive ongoing inflammation in IC/BPS 3.
• Candidate genes such as VEGF and BAFF, involved in immune response and neovascularization, are overexpressed in Hunner-type IC and correlate with symptom severity 6.

Urothelial Barrier Defect

• The bladder’s protective surface (glycosaminoglycan layer) is often compromised in IC/BPS, especially in non-Hunner types. This defect allows urinary solutes to penetrate and irritate underlying tissue, triggering inflammation and pain 12 13.
• The cause of this barrier dysfunction may involve changes in growth factors, proteins, or an unidentified toxic urinary factor 12.

Infectious Triggers

• Chronic bacterial infection is not a cause (cultures are negative), but viral infections, particularly Epstein-Barr virus (EBV), have been detected more frequently in the bladders of Hunner-type IC patients than controls, suggesting a potential role in persistent inflammation 11.
• Other viruses and latent infections remain subjects of ongoing research 11.

Neural and Psychological Factors

• Altered nerve signaling (neurogenic upregulation) in the bladder and central nervous system may underlie symptoms, particularly in non-Hunner IC/BPS 3 8 13.
• Chronic pain conditions like IC/BPS often co-occur with other syndromes (e.g., irritable bowel, fibromyalgia, anxiety), pointing to broader nervous system sensitization 14.
• Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and stress responses can exacerbate symptoms and may even contribute to disease onset 3 13 14.

A Multifactorial Syndrome

• No single cause explains all IC/BPS cases; it is likely a multifactorial syndrome, with the interplay of inflammation, barrier defects, immune responses, and neural mechanisms varying between individuals and subtypes 6 8 12 13 14.

Treatment of Interstitial Cystitis

Managing IC/BPS is challenging due to its heterogeneity and the incomplete understanding of its mechanisms. Treatment must be individualized, often involving a combination of strategies. The goal is to maximize symptom control and quality of life while minimizing adverse effects.

Treatment	Approach/Example	Best For	Sources
Behavioral	Diet modification, stress management, bladder training	All patients, first-line	15 16 18
Oral Medications	Pentosan polysulfate, amitriptyline, antihistamines, cyclosporine	Moderate/severe symptoms, stepwise	15 16 17 18
Bladder Instillations	DMSO, heparin, lidocaine	Patients with persistent symptoms	15 17 18
Procedures	Cystoscopic lesion resection, hydrodistension	Hunner-type IC, refractory cases	15 16 17 18
Surgery	Cystectomy, urinary diversion	Severe, intractable cases	17 18 19

Table 4: Overview of Treatment Options

Behavioral and Non-Pharmacologic Therapies

• First-line management: For all patients, education, dietary modifications (avoiding potential bladder irritants), stress reduction, physical therapy, and bladder retraining are recommended 15 16 18.
• These approaches carry minimal risk and can provide substantial symptom relief, especially when initiated early 16 18.

Oral Medications

• Pentosan polysulfate sodium (PPS): Believed to restore the bladder’s protective glycosaminoglycan layer; some evidence supports its use, but concerns about potential side effects (e.g., maculopathy) exist 15 16 17 18.
• Amitriptyline: A tricyclic antidepressant with pain-modulating properties; effective for some patients 15 17.
• Antihistamines (e.g., hydroxyzine): Target potential mast cell involvement in bladder wall inflammation 15 17.
• Cyclosporine A: An immunosuppressant reserved for severe cases, especially with Hunner lesions 17.

Bladder Instillations

• Dimethyl sulfoxide (DMSO), heparin, or lidocaine can be instilled directly into the bladder to reduce inflammation and pain 15 17 18.
• These are typically used when oral medications and behavioral therapy are insufficient.

Procedures and Surgery

• Cystoscopic treatment of Hunner lesions: Lesion resection, fulguration, or steroid injection can provide significant relief for Hunner-type IC 17 18.
• Hydrodistension: Controlled bladder stretching under anesthesia; may offer temporary improvement 15 18.
• Major surgery: Reserved for the most severe, treatment-refractory cases. Options include partial or total cystectomy with urinary diversion. Surgery improves symptoms in most but carries significant risks and is a last resort 17 18 19.

Individualized, Multi-Modal Care

• Guidelines emphasize individualizing therapy based on symptoms, subtype (Hunner vs. non-Hunner), patient preferences, and response to previous treatments 16 18.
• For most, multi-modal therapy—combining behavioral, oral, and intravesical approaches—yields the best outcomes 18.
• Ongoing research into biomarkers and subtyping will likely further refine treatment strategies in the future 6 14 18.

Conclusion

Interstitial cystitis/bladder pain syndrome is a complex, often underdiagnosed condition that profoundly affects those who live with it. While the path to diagnosis and effective treatment can be challenging, advances in research are paving the way for more precise subtyping and individualized therapies.

Key Points:

• IC/BPS presents with a distinctive cluster of bladder/pelvic pain, frequency, and urgency, often without infection 2 4 5 7.
• Two main types exist: Hunner-type (with inflammatory lesions) and non-Hunner-type/bladder pain syndrome (without lesions) 6 7 8 9 10.
• The causes are multifactorial, involving inflammation, immune dysfunction, epithelial barrier defects, possible viral triggers, and nervous system sensitization 3 6 7 8 11 12 13 14.
• Treatment is stepwise and individualized, ranging from behavioral adjustments and oral medications to bladder instillations, procedures for Hunner lesions, and, in rare cases, surgery 15 16 17 18 19.
• Accurate classification and a multidisciplinary approach are essential for optimal management and improved patient outcomes.

Living with IC/BPS is challenging, but with greater awareness, early recognition, and tailored treatment, patients can experience meaningful improvements in their symptoms and quality of life.