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Interstitial Cystitis-Evaluation and Treatment February 27, 2006. Seine Chiang, MD 41 yo married nonsmoker WF presents with 5 year history of chronic pelvic pain, urinary urgency/frequency, and dyspareunia. Pain is worse with menses and after sex. She has been treated for UTIs (not culture-proven) and anticholinergic therapy without relief of pain. She had a negative laparoscopy three years ago and has been managed with pain medications without significant improvement. Exam is normal. Cervical/urine cultures and urinalysis are negative. How would you proceed in this patient’s evaluation? Have a high degree of suspicion for interstitial cystitis (IC) in any patient with a pelvic pain syndrome that has failed to respond to traditional therapy. Evaluation should include: • Pelvic pain and urgency/frequency symptom scale (PUF questionnaire) which correlates with potassium sensitivity test (PST) results. PUF score of 10-15 (+PST in 75%), PUF 1519 (+PST in 79%), PUF >20 (+PST in 94%). • Potassium sensitivity test (PST) uses a Likert scale (1 to 5) to rate pain and urgency during the instillation of 40 ml sterile water vs 40 ml KCl solution (40 mEq in 100 mL sterile water). Considered positive if there is at least 2 point higher score with instillation of KCl than with water. What condition is IC frequently misdiagnosed as? Gyn: endometriosis, CPP, recurrent UTIs, vulvodynia Other: irritable bowel, spastic colon, nonbacterial prostatitis/prostadynia in men What other conditions frequently co-exist with IC? Allergies (drugs, environmental, food), irritable Bowel Syndrome (IBS), migraines, chronic fatigue syndrome, fibromyalgia, and endometriosis. Symptoms in each of these conditions are exacerbated by stress and suggest a generalized (central) lowering of pain threshold. Describe the postulated pathogenesis of interstitial cystitis? IC is a multifactorial disease with GAG dysfunction, leading to sensory hyperstimulation • Glycosaminoglycans (GAG): mucoprotein in the urothelium results in pathologic permeability to noxious solutes and inflammatory/allergic response. • Activation of C-fibers and release of Substance P causes Pain & Urgency • Bladder mastocytosis (mast cells): Mast cell activation and histamine release results in more injury to the urothelium • CNS and spinal cord “wind up”: sensitized to pain signals. • Visceral hyperalgesia and allodynia What are the basic principles for treating IC? • Correct Epithelial Dysfunction o Destructive/Regenerative: hydrodistension, DMSO, sodium oxychlorosene (Chlorpactin®), silver nitrate. o Protective: Pentosan polysulfate sodium (Elmiron®), Heparin, Hyaluronic acid (Cystistat™) • Inhibit Neural Hyperactivity • Control Allergies How should this patient with IC be managed? • Self-Help: Dietary modification (avoid acidic foods, caffeine, alcohol, carbonated drinks), Bladder retraining or “holding” • Intravesical therapy: o DMSO (hold in bladder 15-20mins) every 1-2 wks x 4-8 treatments has a 50-70% efficacy but 35-40% relapse rate (lower relapse with addition of heparin). o Pentosan polysulfate sodium (ELMIRON®) 100 mg+10 to 20 K units of heparin in 20 cc 1% lidocaine + 3 cc 8.4% NaHCO3 • Oral therapy: o Elmiron® 100 mg tid or 200 mg BID had a 42% response rate (vs 18% with placebo) and up to 80% response rate in those with +PST when combined with TCAs o Nocioceptive Blockers such as TCAs or Gabapentin: effective in 50-64% of patients o Hydroxyzine hydrochloride (Atarax®) resulted in a 40-50% reduction in symptoms. o oxybutynin for overactive bladder symptoms. • Surgical: Hydrodistention, Neuromodulation, Augmentation, Urinary diversion How does Elmiron® work? How long does it take before symptom relief is seen? Replaces the GAG layer, inhibits mast cell, and may also play a role in C-fiber sensory nerve modulation. It takes 3-6 months of therapy or longer. Long-term improvement with continued therapy. References: 1. Dell JR Multimodal therapy for interstitial cystitis.J Reprod Med - 01-MAR-2004; 49(3 Suppl): 243-52 2. Parsons CL The prevalence of interstitial cystitis in gynecologic patients with pelvic pain, as detected by intravesical potassium sensitivity.Am J Obstet Gynecol - 01-NOV-2002; 187(5): 1395-400 3. Parsons CL Increased prevalence of interstitial cystitis: previously unrecognized urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity.Urology - 01-OCT-2002; 60(4): 573-8 4. Parsons CL Gynecologic presentation of interstitial cystitis as detected by intravesical potassium sensitivity.Obstet Gynecol - 01-JUL-2001; 98(1): 127-32 5. Parsons CL - Intravesical potassium sensitivity in patients with interstitial cystitis and urethral syndrome.Urology - 01-MAR-2001; 57(3): 428-32; discussion 432-3