1 Katie Shaff, ND AANP July 2016Pelvic Headaches Diagnostic Evaluation and Clinical Management Urological Causes of Pelvic Pain Katie Shaff, ND AANP July 2016

2 This lecture will aim to…Review common urological contributors to pelvic pain Discuss the diagnosis and treatment of these conditions including: interstitial cystitis (IC)/painful bladder syndrome (PBS), chronic prostatitis, urinary tract infections (acute and chronic), and nephrolithiasis Review the concept of neuropathic pain and options for effective treatment Discuss treatment options and review appropriate workup and referral

3 The cause of pelvic pain, you ask?As nebulous as the safe dose of happiness.

4 Visceral Sources of Pelvic Pain12% 20% 31% 37% Gastrointestinal Urinary Reproductive Musculoskeletal/Other

5 Urinary causes of Pelvic PainInterstitial Cystitis/Painful Bladder Syndrome (PBS) Chronic prostatitis, prostadynia Epididymitis Orchalgia Scrotalgia Recurrent urinary tract infections Urolithiasis Anatomical prolapse Chronic vaginitis/vaginosis

6 Gastrointestinal Causes of Pelvic PainConstipation Irritable Bowel Syndrome/Disease Chronic Bowel Obstruction Diverticulitis Ulcerative Colitis Other Colitis Proctalgia Fissures Persistent maldigestion Hernia

7 Reproductive Cause of Pelvic PainProstatitis Testicular masses; hernia; Pelvic inflammatory disease Vaginal infections, vaginitis, vaginosis Vulvar pain syndromes Ovarian cyst Ectopic pregnancy Endometriosis Adenomyosis Adhesions Uterine fibroids Pelvic congestion syndrome

8 Musculoskeletal Dysfunction and CPP: cause or contributor?Levator ani syndrome Interstitial cystitis Piriformis syndrome Iliopsoas spasm Pelvic floor myalgia Vulvodynia Coccygodynia Pudendal neuralgia

9 Muscles of the pelvic floor -a wonderful woven web

10 Definition of Chronic Pelvic PainDuration: 3 months or more Location: Anatomic Pelvis; Abdominal wall below the umbilicus; Low back Functional impairment Gastrointestinal, Urinary, Reproductive, Etc. Non-cyclic ± dysmennorhea ± dyspareunia (men and women) Medical and/or surgical intervention is often indicated

11 How about those men? Chronic Pelvic Pain Syndrome:Affects >15% of men Health impact equal to acute M.I., acute ulcerative colitis, and unstable angina 95% of men diagnosed as prostatitis have NO EVIDENCE of infection or prostatic inflammation

13 Definition of Painful Bladder SyndromeThe complaint of suprapubic pain related to bladder filling May be accompanied by other symptoms such as increased urinary frequency and urinary urgency, in the absence of proven urinary tract infection or other obvious pathology Also referred to as Interstitial Cystitis Hunner vs non-Hunner type Crossover with Chronic Prostatitis Crossover with Endometriosis and Vulvodynia 10-20% overlap with vulvodynia Up to a 60-70% overlap with endometriosis Hunner vs non-hunner lymphoplasmacytic inflammation and epithelial denudation were observed in a diffuse manner First described in 1907 as cystitis parenchymatosa

14 Prostatitis…hand in hand with pelvic painPitfalls in Diagnosis of Prostatitis Physician does not evaluate for WBC Pudendal neuralgia has same symptoms detrusor-sphincter dyssynergia trigone infiltration by (prostate) carcinoma interstitial cystitis neurogenic inflammation of bladder

15 Urothelial dysfunction Visceral organ hyperalgesia/allodyniaInterstitial cystits/Painful bladder syndrome: pathogenesis and Integrated pathophysiology Urothelial dysfunction activation upregulation nervous system Visceral organ hyperalgesia/allodynia Gynecological Urinary Pelvic floor gastrointestinal

17 Pathogenesis of PBS/IC: Defective Urothelial BarrierIrritating Solutes GAG layer Urothelium Irritated Nerve Inflammation Parsons CL. Urol Clin North Am . 1994;21:93 100.

18 Transition from nociceptive to neuropathic pain is key…Lack of a clear, identifiable etiology of Chronic Pelvic Pain supports a heterogeneous, multi-systemic and multi-factorial disease Transition from nociceptive to neuropathic pain is key…

19 enter the concept of neurological windupIn patient’s with chronic pain normal sensations are perceived as pain… enter the concept of neurological windup

20 Pelvic Myoneuropathy A process seen in people of a particular genetic type and often with tense, anxious, and frequently atopic (allergy-prone) dispositions develop a chronic process in the pelvis that involves muscles, nerves and mast cells. Individuals tend to tense the muscles of their pelvic floors subconsciously and continuously clenching of deep muscles can be provoked either by the individual's tense disposition, or it can be the result of a "guarding" response to a preceding trauma to the pelvic or spinal area pelvic surgery, bicycling, childbirth, long periods of sitting and stress at work, and in some cases, urinary tract infections (prostatitis and cystitis) Other common events that lead to injury are: chronic tense holding patterns that develop in childhood as a result of sexual abuse, traumatic toilet training, abnormal bowel patterns, guilt surrounding sexual feelings, dance training or stress repetitive minor trauma or straining with constipation or urinary obstruction other inflammations of pelvic organs or referred pain from other attaching muscle groups or viscera or nerves

21 Add in the somatic vicious circle as well

22 Chronic Pelvic Pain – an overlapping of diseases and conditionsEndometriosis Adenomyosis Vulvar Pain Syndromes Prostatitis CHRONIC PELVIC PAIN Overlapping Conditions IBS Colitis Other GI Disorders Pelvic Infections Adhesions Musculoskeletal Disorders Interstitial Cystitis PBS Recurrent UTI

23 Treating your patient with Pelvic PainThere is no sure-fire treatment approach that will work consistently with patients who live with CPP or PBS Identify the contributors Work to optimize the function of the surrounding “asymptomatic” organs Determine how many “players” are needed in the initial as well as the ongoing treatment of the patient If possible, develop a timeline that identifies where dysfunction began. What are the legs of the stool, so to speak. Educate the patient as to patho-physiology Develop a comprehensive treatment strategy Do not continue to utilize resources on ineffective therapies

24 Painful Bladder Syndrome TreatmentPain Management Antidepressants: Tricyclic (amytryptiline, nortriptyline), venlafaxine (Effexor) SNRI, duloxetine (Cymbalta) SNRI Anticonvulsants: Gabapentin, Pregabalin Botox, Neurontin, Elavil Not Helpful: Narcotics, NSAIDS, antibiotics Anti-inflammatory therapies Quercetin Aloe Vera (whole leaf) Anti Histamine therapy Hydroxazine, Allegra, Claritin Urinary medications Urinary analgesics: pyridium, urelle, etc. Urinary alkalinizers: coffee tamer, prelief, pH control, etc. Elmiron (pentosan polysulfate sodium) heparin like compound with structural similarity to a glycosaminoglycan Anti cholinergics/Muscarinic Receptor Antagonists: Detrol (tolterodine), Sanctura (trospium chloride)

25 Bladder installations Physical therapy Psychotherapy Neuromodulation Sacral Peripheral PTNS – posterior tibial nerve stimulation Especially helpful with urinary symptoms (urgency and frequency Bladder installations Heparin, alkalinized lidocaine, Elmiron, DMSO Physical therapy Psychotherapy Acupuncture – additional to the purpose of neuromodulation Indicated for: Severe and refractory Urge Incontinence Generator implanted in buttocks or low back Lead placed in sacral foramen into S3 Nerve Inhibits detrusor muscle contractions Can test drive before you buy Highly effective

26 Naturopathic Approach to Pelvic PainIf possible, identify the origin of the pelvic pain Work diligently to get the pain symptoms under control so that other therapies can work more effectively Understand the interplay of concomitant dysfunctions Begin the process of unwinding; stop and reassess as often as necessary Keep anxiety and pain as managed as possible

27 Anti-inflammatory diet; consider testing for food sensitivitiesQuercetin or other anti-histamine therapies if appropriate GABA Support patient’s genetic predispositions Consider neurotransmitter testing Alkalinized or distilled water Cannabis (edible or vaporized) Use caution with supplements

28 Chronic Prostatitis Slow, indolent infection persisting more than 3 months Associated factors Recurrent Urinary Tract Infection Asymptomatic bacteruria despite antibiotics Causative organisms the same as in Acute Prostatitis Enterobacteriaceae (80%), Enterococcus (15%), Pseudomonas aeruginosa

29 Symptoms (sudden onset)Irritative urinary symptoms (Mild to Moderate) Dysuria, Urinary frequency, Urinary urgency, Ejaculatory pain, hematospermia Referred pain Low pack, perineum, lower abdomen, scrotum, penis, inner thighs Absent Symptoms (in contrast to Acute Prostatitis) Systemic symptoms rare Obstructive urinary symptoms uncommon Signs: on DRE the prostate is often Normal on exam, tender (TTP), boggy or indurated Prostatic calculi may be present

30 Labs: Segmented Urine Culture Differential DiagnosisChronic non-infectious prostatitis, BPH, UT Stone (prostate calculus, nephrolithiasis), bladder cancer, prostate abscess, enterovesical fistula Management General Antibiotics penetrate Chronic Prostatitis poorly Prolonged antibiotic regimens are required Treatment with antibiotics until urinalysis returns with no organisms

31 Prostatitis TreatmentTreat the symptoms that predominate and create the biggest barrier in optimizing ADL Urinary frequency, urgency Anti-cholinergics Obstructive Voiding Alpha-blockers - Especially helpful to prevent urinary retention Doxazosin (Cardura), tamsulosin (Flomax), terazosin (Hytrin), alfuzosin (Uroxatral) Prostatic Tenderness/Pain/Enlargement Quercetin, Bee Pollen, Probiotics Inhibit DHT (Finasteride/clutasteride) Infection Antibiotic treatment (see following slide) Psychosocial (depression, anxiety, catastrophic thinking) Counseling, EMDR, EFT, CBT Antidepressant therapy Exercise, stress management

32 Optimize bowel function Pelvic Neuropathic Pain Bowel Health Allergy Elimination Optimize bowel function Pelvic Neuropathic Pain Tricyclic antidepressants Gabapentinoids Muscle Spasm, tenderness, pelvic muscle tightness Physical therapy Muscle relaxants Cyclobenzaprine Botanical Formula (see above; might adjust antispasmodic herbs) Magnesium citrate (for effects on bowel as well as on other muscle) Local heat therapy, hyperthermia (TUMP, etc.) High frequency electostimulation Prostate massage Donut cushion, seating disc Hydrotherapy Sitz bath; modified sitz

33 Prostatitis Treatment: Antimicrobial TherapyAntimicrobials: 4-6 weeks of treatment (up to 12 weeks) First Line: fluoroquinolones or sulfa Ciprofloxacin 500 PO BID Levofloxacin 500 mg PO QD Norfloxacin 400 mg PO BID TMP-SMX DS (160/800) PO BID Second Line: Doxycycline 100 mg PO BID Azithromycin 500 mg PO QD Clarithromycin 500 mg PO BID DO NOT USE nitrofurantoin (Macrobid)  I don't buy the whole antibiotics forever/infection theory of chronic prostatitis, because it doesn't work. I'll have my new urology book out this summer (I hope, I'm getting really close to being done with it), but most often the problem is leaky gut --> leaky urothelium --> chronic inflammation and the bacteria are just taking advantage of a messed up system. Anyhow, I usually start with an elimination/challenge diet (my approach is atdryarnell.com in patient handouts) and leaky gut treatments (glutamine 3-5 g cc and Aloe gel 2 oz bid usually), and then once the triggers are removed, see total resolution or significant improvement in the situation. That's about 50% of patients (I've seen 141 men with chronic prostatitis since 2004; yes I keep a log of every patient and their diagnoses so I can say things like that). I almost always also start N-acetylglucosamine 750 mg bid (only Jarrow has this at this dose in one pill that I've ever found; I have no connection with them I just know this is hard to find) as a leaky urothelial repairer because it takes 6 months to work minimum. Anyhow if that doesn't work, or if on digital rectal exam I can trigger their symptoms by palpating the pelvic floor (basically by palpating the lateral walls of the anus when your finger is only about one digit in), then they likely have pelvic floor hypertonicity (only about 10% of the patients I've seen) and I'll do hot sitz baths, magnesium 200 mg bid, and Pedicularis 2-3 ml tid or Piper methysticum same dose or caps mg bid. Sometimes they also need pelvic physical therapy. If they have a bunch of gut issues like it sounds like your gent does then I would definitely look to the gut as the source of the problem. Finally, quercetin and bromelain or other inflammation modulators also sometimes do really help. Had a patient last week where those things alone at sufficient doses (quercetin 1 g tid and bromelain 3200 mcu strength 1-2 g tid away from food) completely cured him after years of pain! You might need antibiotics periodically for severe flares but otherwise they just cause dysbiosis and worsen the disease (PMID: reviews the literature supporting this idea). Sorry that's long-winded but I have strong opinions based on a lot of experience and seeing a lot of guys harmed by useless antibiotics given over and over. Finally, there is no evidence of anal sex or other sexual practices being a risk for chronic prostatitis and the incidence of chronic prostatitis is higher in heterosexual than homosexual men. Acute prostatitis is a whole other story, but the two have nothing in common and acute almost never turns into chronic prostatitis.

34 Cystitis Acute and Recurrent Cystitis (UTI)Complicated vs. uncomplicated Recurrent Urinary Tract Infection: Incidence greater than 2-3 times per year Interstitial Cystitis (IC)/Painful Bladder Syndrome (PBS) Other Cystitis Eosinophilic Cystitis

35 Recurrent Cystitis (UTI)Vast majority of recurrent UTI in women in from reinfection (99%) Vaginal colonization is the most common cause Unresolved Bacteriuria (Refractory Infection) Bacterial resistance to drug selected for treatment Resistance developed by sensitive bacteria Bacteriuria with 2 different species Rapid reinfection with a second resistant organism Analgesic abuse causing papillary necrosis Azotemia Giant staghorn calculi Noncompliance

36 Bacterial persistence (Same organism recurs)Infected Renal Calculi, Chronic Bacterial Prostatitis, Unilateral infected atrophic Pyelonephritis, Infected Diverticulae, Polycystic Kidney Disease, Ureteral reflux, Medullary sponge Kidneys, Analgesic abuse causing infected papillary necrosis Reinfection (Urine cleared, but new infection occurs) Colonization of vaginal introitus, Vesicoenteric fistulae, Vesicovaginal fistulae, Vesicoureteral Reflux, Voiding dysfunction (seen with MS, neurogenic bladder, cystocele, rectocele), Immunosuppression, Chronic Renal Insufficiency, DM, Instrumentation (stent, nephrostomy tube, catheterization)

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38 Risk Factors for recurrent UTI in women:Intercourse in the past month >9 times: Odds Ratio 10.3 Intercourse in the past month 4-8 times: Odds Ratio 5.8 Age at first UTI >15 years: Odds Ratio 3.9 Mother with Recurrent UTI: Odds Ratio 2.3 New sex partner in the last year: Odds Ratio 1.9 Spermicide use in the last year: Odds Ratio 1.8

39 Diagnostic Workup Culture Culture Culture!Antibiotic resistance is common and variable, especially in patients with recurrent cystitis Consider a standing order for patients with recurrence Consider more complete urological workup in patients with significant recurrence Evaluation for urethral diverticulm, stones, issues from past surgical interventions (esp. related to mesh) Other diagnostics to consider referring for PVR (post-void residual), urodynamics, and other imaging may be indicated

40 Treatment UTI Prophylaxis in womenIndications: Recurrent Urinary Tract Infections occurring 3 or more times annually Continuous UTI Prophylaxis (Average Course: Taken daily for 6 months) Nitrofurantoin mg PO QD TMP-SMX 40/200 PO QD or 3x per week Trimethoprim 100 mg daily Cephalexin mg PO QD Ciprofloxacin 125 mg PO QD

41 Postcoital Prophylaxis (one dose taken within 2 hours of intercourse)Nitrofurantoin mg once TMP-SMX 40/200 to 80/400 once Ciprofloxacin125 mg once Self-starting regimen Standing order for culture; patient education regarding importance and procedure Emergency prescription available to start after onset of classic UTI symptoms Choose a 3 day antibiotic course Contact provider if symptoms last more than 48 hours despite antibiotics

42 Mannose d-mannose has been shown to BOTH block bacterial adhesion on uroepithelial cells and antagonize invasion and biofilm formation Dose: 1gram TID-QID for acute management; 1 gram post coital for prophylaxis Probiotics PV and PO probiotics have been shown to decrease UTI recurrence Dose daily as well as post coital in patients with significant recurrence rates

43 Cranberry Vitamin C Daily cranberry prevents Recurrent UTIContains proanthocyanidin compounds Inhibits E. coli from adhering to urinary tract Recommended daily dosing of cranberry juice Cranberry extract mg tablet bid or Pure cranberry unsweetened juice 8 ounces tid Vitamin C 500 mg TID-QID

44 Behavior Modification and Urinary HygieneEducate patients about normal bladder function, fill volume, and general urinary hygiene Instruct women to void before and after intercourse. Patients MUST need to void in order for good bacterial clearance Consider contraceptive devices and spermicides to be potential risk factors Consider OCP to be contributory Address any atrophy Evaluate for use of sex toys/devices as well as use of hygiene products

45 A few notes about referrals…Referrals can be made for a consult (evaluation and treatment often with ongoing treatment and management being handed back to the referring physician OR for complete care (evaluation, treatment, and management) Difference is primarily a coding/billing issue, though for many specialists consults are handed back to the referring physician for management when appropriate You cannot refer for urological testing as you might for a radiological study

46 Nephrolithiasis Prevalence: 0.2% in U.S. Life-time riskMales: 10-12% vs. Females: 3-5% Recurrence of Nephrolithiasis One recurrence in 50% of patients More than 3 recurrences in 10% of patients Peak age years Overall Male: Female ratio 4:1 Males: Calcium oxalate Females: Struvite Both: Urate and Cystine Stones

47 Pathophysiology Stone formation is inhibited by CitrateWomen have much higher levels of citrate than men Low citrate levels are related to most stone forms

48 Risk Factors General Inherited ConditionsIncreases with advancing age up to 65 years Male gender (men account for 66% of cases) Geographic location (hot, arid climates) Southeastern United States ("stone belt"), Mediterranean countries, Middle Eastern countries Inherited Conditions Polycstic Kidney Disease, Renal Tubular Acidosis Type I, Hyperparathyroidism, Cystinuria, Hypocitrauria, Hypercalciuria, Primary Hyperoxaluria,

49 Medications Allopurinol Laxatives Ephedra alkaloidsCarbonic anhydrase inhibitors (Diamox, Topamax), Potassium channel blockers (Amiodarone, Sotalol, Dalfampridine) Potassium sparing diuretics (Triamterene) Protease Inhibitors (Indinavir) Sulfonylureas (Glipizide, Glyburide) Antibiotics (sulfonamides, flurolquinolones, Ceftriaxone, Ampicillin, Amoxicillin) Allopurinol (Uric Acid stones) Laxatives (Ammonium Urate Stones) Ephedra alkaloids Carbonic anhydrase inhibitors Acetazolamide (Diamox) Topiramate (Topamax) Potassium channel blockers Amiodarone Sotalol (Betapace) Dalfampridine (Ampyra) Potassium sparing Diuretics Triamterene Protease Inhibitors Indinavir (Crixivan) Sulfonylureas Glipizide Glyburide Antibiotics Sulfonamides Ampicillin or Amoxicillin Ceftriaxone Fluouroquinolones Risk Factors: Dietary and Hydration Factors Low urine volume Inadequate access to hydration or restrooms Athlete Heat exposure Bowel Disease Bowel Surgery (e.g. Ileostomy) Infammatory bowel disease (e.g. Crohn's Disease) Chronic Diarrhea Peptic Ulcer Disease Other dietary factors Animal protein intake (see aciduria below) Purine Containing Foods and other protein intake High Oxalate Containing Foods (hyperoxaluria) Excessive sodium intake (Hypercalciuria risk) Hypercalciuria (70% of stone formers) Type 1: Increased PTH (resorptive Hypercalciuria) Hyperparathyroidism Sarcoidosis Type 2: Increased Calcium absorption from gut Type 3: Increased Urinary Phosphorus loss Type 4: Increased Urinary Calcium loss Hyperoxaluria Citrate deficiency (not oxalate metabolism problem) Hypocitraturia (Distal Renal Tubular Acidosis) Hyperuricosuria Acidosis and aciduria (results in loss of citrate) Renal Tubular Acidosis Protein loading (especially with animal protein) Bowel disease

50 Dietary and Hydration FactorsLow urine volume Inadequate access to hydration or restrooms Athlete Heat exposure Bowel Disease IBD, Bowel Surgery (e.g. Ileostomy), Chronic Diarrhea, PUD Other dietary factors Animal protein intake High oxalate containing foods Excessive sodium intake Sugar intake/blood sugar levels Type 2 Diabetics at increased risk

51 Hypercalciuria (70% of stone formers)Type 1: Increased PTH (resorptive hypercalciuria) Evaluate Vitamin D; if low, normalize and retest for adequate evaluation of PTH Type 2: Increased Calcium absorption from gut Type 3: Increased Urinary Phosphorus loss Type 4: Increased Urinary Calcium loss Hyperoxaluria Citrate deficiency vs. oxalate metabolism problem Hypocitraturia (as seen in Distal Renal Tubular Acidosis) Hyperuricosuria (can be seen in gout) Acidosis and aciduria (results in loss of citrate) Bowel disease, protein loading (especially with animal protein), Renal Tubular Acidosis, Acetazolamide (Diamox)

52 Prevention of Stones Hydration: more than just waterOptimize calcium intake and utilization Weight bearing exercise, dietary evaluation of calcium sources and bioavailability Maintain adequate vitamin D levels Maintain fluid intake >2.5 Liters per day Most important single measure Ingest 8 to 12 ounces fluid on awakening and at bedtime Water and Citrus juice Maintain Urine volume > 2 Liters per day Periodically measure urine output in a 2 liter bottle Urine should be clear in appearance with minimal color

53 Dietary restrictions LifestyleLimit animal protein to 8 ounces per day (or <1 gram/kg/day) Animal protein increases urinary calcium and uric acid excretion Animal protein decreases urinary pH and urinary citrate excretion Limit sodium intake to less than 2-3 grams per day (less than 1.5 grams for some patients) Limit high oxalate foods Limit high sugar or fat content Avoid excessive vitamin C Lifestyle Move toward ideal weight for the patient Encourage daily physical exercise

54 Dietary increases or no restriction Increase fiber from vegetable sources (being mindful of oxalates) Maintain calcium intake at at least 1000 mg/day No dietary calcium restriction for most stone formers (unless absorptive hypercalciuria) Calcium binds oxalate in the intestine and decreases oxalate absorption Take supplemental calcium citrate with meals Aim for 50% daily calcium from diet and the rest from supplemental calcium citrate Encourage calcium utilization through weight bearing exercise Maintain adequate vitamin D levels

56 Imaging for Kidney StonesHelical CT Urogram Sensitivity: 95 to 100%, Specificity: 94 to 96% Preferred over IVP (intravenous pyelogram) Will evaluate: renal morphology and ureteral stone localization Abdominal US Sensitivity: 64-93%, Specificity: % Will evaluate: renal stone and hydronephrosis Indications: pregnant patients and children, suspected cholecystits or gynecological condition Abdominal XRay Sensitivity: 45-59%, Specificity: 71-77% Will evaluate: radiopaque stones (calcium oxalate and struvite; some cystine stones) Intravenous Pyelogram (IVP) Sensitivity: 64-87%, Specificity: 92-94% Will evaluate: function or kidney and ureter

57 Lab evaluation for Kidney StonesUrinalysis Acute 24-Hour Urine Metabolites Litholink Blood Work Vitamin D Really only helpful to evaluate contributing health conditions Uric acid Blood Sugar/HBA1C WBC

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