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Interstitial Cystitis and Sexually Transmitted Diseases Daniel Shoskes MD, MSc, FRCSC Professor of Urology Cleveland Clinic Department of Urology Glickman.

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Presentation on theme: "Interstitial Cystitis and Sexually Transmitted Diseases Daniel Shoskes MD, MSc, FRCSC Professor of Urology Cleveland Clinic Department of Urology Glickman."— Presentation transcript:

1 Interstitial Cystitis and Sexually Transmitted Diseases Daniel Shoskes MD, MSc, FRCSC Professor of Urology Cleveland Clinic Department of Urology Glickman Urological and Kidney Institute

2 Information for Home Study Slide show text is reproduced in handout Chapters in Textbook of Board Review Outline on AIDS (a few notes on other STDs) Relevant pages from 2010 MMWR on STDs AUA Guidelines for IC/BPS are on the web site and on your USB drive

3 CDC Guidelines “one stop” internet site –http://www.cdc.gov/STD/ latest update December 2010 –urethritis and mycoplasma –NAAT diagnosis in urine –Hep C transmission through intercourse wall charts, pocket guides, iPhone and eBook versions

4 INTERSTITIAL CYSTITIS PAINFUL BLADDER SYNDROME BLADDER PAIN SYNDROME

5 Why so many names? Disadvantages of IC name No agreement on a clinical IC definition (NIDDK criteria from 1980s were for research) “Interstitial cystitis” not scientifically correct, especially for patients without Hunner lesions May lack bladder inflammation May not involve bladder interstitium Different subspecialty groups had their own ideas

6 Painful Bladder Syndrome ICS Definition* 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 *Abrams P, Neurourol Urodynamics 2002 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 *Abrams P, Neurourol Urodynamics 2002

7 Bladder Pain Syndrome ESSIC Definition* > 6 months pelvic pain, pressure, or discomfort perceived to be related to urinary bladder At least one other urinary symptom such as persistent urge to void or frequency Must exclude confusable diseases *van de Merwe JP, Nordling J, Eur Urol 2008 > 6 months pelvic pain, pressure, or discomfort perceived to be related to urinary bladder At least one other urinary symptom such as persistent urge to void or frequency Must exclude confusable diseases *van de Merwe JP, Nordling J, Eur Urol 2008

8 IC/BPS SUFU Definition* Used in AUA Guidelines An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or other identifiable causes *Hanno P, Neurourol Urodynamics 2009 An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or other identifiable causes *Hanno P, Neurourol Urodynamics 2009

9 Does the Name Matter? Research: nuances in enrollment criteria Clinical: pros of IC name Do PBS and BPS sound like real diseases? 2 treatments FDA-approved for IC, 0 for PBS IC recognized for Social Security disability Clinical: cons of IC name Stigma? Consider put Sx (e.g. urgency) on bill Focus on bladder may forget other causes

10 AUA Guidelines All expert opinion or clinical principles All expert opinion or clinical principles Diagnostic principles Diagnostic principles Baseline assessment: history, physical exam, laboratory to exclude other disorders Obtain baseline symptom and pain levels, including frequency-volume chart > 1 day Cystoscopy and urodynamics unnecessary for diagnosis in uncomplicated presentations when diagnosis is clear (I disagree: if you don’t look for ulcers you won’t find them)

11 Main Goal of H and P is to look for other causes of symptoms and systemic features Bladder tumor Bladder or distal ureteral stone Urethral diverticulum External cause for dysuria (eg herpes) Pelvic floor muscle spasms Irritable bowel syndrome Vulvodynia

12 Lab Studies Everyone Everyone urinalysis, urine cultureurinalysis, urine culture Urine Cytology if Urine Cytology if smokersmoker unevaluated hematuriaunevaluated hematuria

13 AUA Diagnosis Guidelines Cystoscopy, urodynamics appropriate when diagnosis remains in doubt after basic assessment Potassium sensitivity test should not be used as a diagnostic tool in clinical practice because results do not change management or treatment approach Cystoscopy, urodynamics appropriate when diagnosis remains in doubt after basic assessment Potassium sensitivity test should not be used as a diagnostic tool in clinical practice because results do not change management or treatment approach

14 AUA Guidelines on Cystoscopy and Hydrodistension Cystoscopy is useful if you are looking for: Other causes for symptoms (stone, tumor, etc.) Hunner lesions Hydrodistention Not useful for making diagnosis No value in seeing glomerulations or not May create more injury and subsequent scarring May identify end-stage, low capacity bladder

15 Hunner Lesion A positive finding that can confirm the diagnosis in patients who meet the definition criteria Phases Acute: inflamed, friable, denuded area Chronic: blanched, non-bleeding area Direct treatment of Hunner lesion is recommended (fulguration, steroid injection)

16 Hunner Lesion From AUA Guidelines Slide Set

17 Glomerulations Finding of glomerulations on hydrodistention is variable and not related to clinical presentation Absence of glomerulations can lead to false negative assessment of patients who present with clinical IC/BPS Seen in many clinical situations including radiation therapy, defunctionalized bladders, bladder cancer, chemotherapeutic or toxic drug exposure, normal bladders

18 Glomerulations *Photo from AUA Guidelines Slide Set Photo shown for academic interest only; recommended for Not recommended for ruling in or ruling out diagnosis of IC/BPS!

19 A. Past history of genital herpes, rare outbreaks B. Levator muscles tender to palpation C. Inability to void on urodynamics D. Positive potassium sensitivity test E. Glomerulations after bladder distention A. Past history of genital herpes, rare outbreaks B. Levator muscles tender to palpation C. Inability to void on urodynamics D. Positive potassium sensitivity test E. Glomerulations after bladder distention A 41y/o ♀ has frequent urination and pain with bladder filling. Which of these findings will affect your treatment plan?

20 A. Past history of genital herpes, rare outbreaks B. **Levator muscles tender to palpation** C. Inability to void on urodynamics D. Positive potassium sensitivity test E. Glomerulations after bladder distention A. Past history of genital herpes, rare outbreaks B. **Levator muscles tender to palpation** C. Inability to void on urodynamics D. Positive potassium sensitivity test E. Glomerulations after bladder distention A 41y/o ♀ has frequent urination and pain with bladder filling. Which of these findings will affect your treatment plan?

21 FDA Approved Treatments Almost all treatments are off-label uses FDA approved for IC Oral pentosanpolysulfate Intravesical DMSO No treatments FDA-approved for PBS or BPS

22 Treatment Guideline Tiers 1. Education, self-care 2. Oral and intravesical medicines, physical therapy, pain management 3. Bladder distention or Hunner lesion treatment 4. Sacral/pudendal nerve stimulation* 5. Cyclosporine orally, botulinum toxin injection* 6. Substitution cystoplasty or urinary diversion* *Only for experienced, committed IC/BPS providers

23 Clinical Treatment Principles Begin with more conservative therapies Major surgery only for: End-stage, small fibrotic bladders Conservative measures have been exhausted and quality of life is poor Initial treatment type and level depend on symptom severity, clinician judgment, and patient preference Stop ineffective therapies after clinically meaningful period

24 Clinical Treatment Principles Multiple, simultaneous treatments may be considered if in the best interests of the patient. Reassess to document efficacy Continuously assess pain management. If inadequate, consider multidisciplinary approach Reconsider diagnosis if no improvement after multiple treatment approaches

25 AUA Tier 1 Therapies Education: normal bladder function, IC/BPS knowledge base, risk/burdens of available therapies, may need to try multiple treatments Self-care practices Behavioral modifications that can improve symptoms Stress management to improve coping and manage stress-induced symptom exacerbations

26 AUA Tier 2 Therapies Clinical principle: physical therapy if available Target trigger points and tissue restrictions Avoid pelvic floor strengthening exercises! Expert opinion: multimodal pain management Options (alphabetical order; no preference implied) Intravesical DMSO, heparin, lidocaine Oral amitriptyline, cimetidine, hydroxyzine, pentosanpolysulfate

27 Intravesical Therapies Numerous combinations, ingredients may include: DMSO Local anesthetic Na bicarbonate Heparin or other GAGs Cortisol or triamcinolone Antibiotic AUA Guidelines mention them Minimal research comparing one vs. another

28 AUA Tier 3 Therapies Option: cystoscopy and bladder distention Under full general or regional anesthesia Less than 10 minutes duration cm water pressure Hunner lesion Recommendation for direct treatment (should be offered, level C evidence) Fulguration (laser or electrocautery) or triamcinolone injection

29 Tier 4: Sacral or Pudendal Nerve Stimulation Not FDA-approved for IC/BPS Sacral stimulation approved for urgency-frequency An option, with caveats: Only if more conservative options have failed A treatment for frequency, not for pain! Not for general use, but limited to providers experienced with IC/BPS and willing to provide long term care of the patient after intervention

30 Tier 5 Therapies Options Oral cyclosporine (“low dose”) Intradetrusor botulinum toxin injection (patient must be willing and able to do CIC)

31 Tier 6: Major Surgery Two options Substitution cystoplasty Urine diversion +/- cystectomy For “carefully selected patients for whom all other therapies have failed to provide adequate symptom control and quality of life” Better outcome after diversion associated with: Small bladder capacity under anesthesia Absence of neuropathic pain

32 Augmentation Cystoplasty Not listed as an option in the AUA Guidelines Why it is a bad idea Pain likely to persist (urine remains in contact with bladder) Likely to have urinary retention CIC is painful for many IC/BPS patients

33 Treatments to Avoid per Guidelines Standards (A or B evidence) Long-term antibiotics Intravesical BCG Intravesical resiniferatoxin Recommendations (C evidence) High pressure, long duration bladder distention Long-term systemic corticosteroids

34 A. Pelvic floor strengthening exercises B. Pain management C. Oral pentosanpolysulfate D. Oral amitriptyline E. Intravesical DMSO A. Pelvic floor strengthening exercises B. Pain management C. Oral pentosanpolysulfate D. Oral amitriptyline E. Intravesical DMSO In AUA IC/BPS Guidelines, 2 nd tier treatments include all of these except:

35 A. **Pelvic floor strengthening exercises** B. Pain management C. Oral pentosanpolysulfate D. Oral amitriptyline E. Intravesical DMSO A. **Pelvic floor strengthening exercises** B. Pain management C. Oral pentosanpolysulfate D. Oral amitriptyline E. Intravesical DMSO In AUA IC/BPS Guidelines, 2 nd tier treatments include all of these except:

36 A. Oral pentosanpolysulfate B. Intravesical DMSO C. Trial of sacral nerve stimulation D. Fulgurate the patch of erythema E. Cystectomy and urinary diversion A. Oral pentosanpolysulfate B. Intravesical DMSO C. Trial of sacral nerve stimulation D. Fulgurate the patch of erythema E. Cystectomy and urinary diversion A 62 y/o ♀ has severe pain, frequency, 8x nocturia. Cystoscopy shows a patch of erythema; biopsy & cytology negative for cancer. AUA Guidelines recommend:

37 A. Oral pentosanpolysulfate B. Intravesical DMSO C. Trial of sacral nerve stimulation D. **Fulgurate the patch of erythema** E. Cystectomy and urinary diversion A. Oral pentosanpolysulfate B. Intravesical DMSO C. Trial of sacral nerve stimulation D. **Fulgurate the patch of erythema** E. Cystectomy and urinary diversion A 62 y/o ♀ has severe pain, frequency, 8x nocturia. Cystoscopy shows a patch of erythema; biopsy & cytology negative for cancer. AUA Guidelines recommend:

38 A. Long-term antibiotics B. Oral corticosteroids C. Oral cyclosporine D. Intravesical BCG E. 30-minute bladder distention A. Long-term antibiotics B. Oral corticosteroids C. Oral cyclosporine D. Intravesical BCG E. 30-minute bladder distention In the AUA IC/BPS Guidelines, all of these should be avoided except:

39 A. Long-term antibiotics B. Oral corticosteroids C. **Oral cyclosporine** D. Intravesical BCG E. 30-minute bladder distention A. Long-term antibiotics B. Oral corticosteroids C. **Oral cyclosporine** D. Intravesical BCG E. 30-minute bladder distention In the AUA IC/BPS Guidelines, all of these should be avoided except:

40 Personal Observations Male IC vs Prostatitis/CPPS Male IC vs Prostatitis/CPPS Pain linked to the voiding cyclePain linked to the voiding cycle Suprapubic Pain/TendernessSuprapubic Pain/Tenderness Intravesical instillations less likely to be effectiveIntravesical instillations less likely to be effective Sequential vs Staged Therapy Sequential vs Staged Therapy When treating a syndrome, best to identify clinical phenotype and individualize therapyWhen treating a syndrome, best to identify clinical phenotype and individualize therapy UPOINT (upointmd.com)UPOINT (upointmd.com)

41 SEXUALLY TRANSMITTED DISEASES HIV/AIDS AND OTHERS

42 Prevention Especially newly sexually active and the elderly

43 HIV/AIDS

44 AIDS: Basic Pathophysiology HIV virus invades cell through the CD4 receptor Macrophages and some T cells have CD4 CD4 is needed to process most types of antigen Binding also requires chemokine receptor CCR5 on macrophage; mutation is protective Loss of CD4 cells = immune deficiency Indices of disease severity Decreased CD4 cell count Increased amount of HIV RNA in bloodstream

45 AIDS: Typical Clinical Course Initial infection May have acute illness similar to mono Unlikely to present to a urologist Asymptomatic carriage of virus: average 10 years Immune deficiency leads to opportunistic infections Use of highly active antiretroviral therapy (HAART) makes HIV a chronic illness not a terminal disease

46 HIV Diagnosis Acute infection: Not enough time for antibodies to develop Order viral load assay (HIV RNA in blood) If more than 3-6 weeks after exposure: ELISA can be done with blood, urine or saliva 6 FDA-approved point-of-service tests Confirm positive ELISA with Western blot Acute infection: Not enough time for antibodies to develop Order viral load assay (HIV RNA in blood) If more than 3-6 weeks after exposure: ELISA can be done with blood, urine or saliva 6 FDA-approved point-of-service tests Confirm positive ELISA with Western blot

47 HIV Virus Replication RNA is viral genetic material Reverse transcriptase makes DNA from viral RNA DNA integrates into host genome Host DNA replicates, making new viral RNA RNA is translated to protein precursors Protease cleaves precursors, leaving viral proteins New virus is assembled & released from host cell

48 AIDS Treatments Drugs that prevent HIV virus fusing to CD4 cell Enfuvirtide binds to virus, prevents fusion Maraviroc blocks CCR5 receptor Reverse transcriptase inhibitors Nucleoside or nucleotide analogs Non-nucleoside drug Integrase inhibitor prevents integration of viral DNA into host genome (raltegravir) Protease inhibitors

49 Initial HIV Treatment 2010 CDC guidelines* recommend Emtricitabine + tenofovir (NRTIs) PLUS either: Enfiravenz (a non-nucleoside RT inhibitor) Raltegravir (integrase inhibitor) Ritonavir-boosted protease inhibitor Atripla® = emtricitabine+ tenofovir +enfiravenz, one pill a day *http://www.cdc.gov/std/treatment/2010/STD- Treatment-2010-RR5912.pdf

50 Protease Inhibitors: Relevance to Urology Booster action: inhibit Cyt P450 Some can form stones (especially indinavir) Indinavir is nephrotoxic Booster action: inhibit Cyt P450 Some can form stones (especially indinavir) Indinavir is nephrotoxic

51 Protease Inhibitor Stones Indinavir Classic test question Uncommon in real world; other PIs safer May form crystals, leading to acute renal failure Might not be seen on CT scan Usually resolve with stopping the drug, hydration, +/- urine acidification Indications for stent: persistent fever, intractable pain, solitary kidney Indinavir Classic test question Uncommon in real world; other PIs safer May form crystals, leading to acute renal failure Might not be seen on CT scan Usually resolve with stopping the drug, hydration, +/- urine acidification Indications for stent: persistent fever, intractable pain, solitary kidney

52 Caveat: AIDS Patients also Form the Usual Types of Stones Of 14 patients taking indinavir who had stones, only 4 patients' stones contained indinavir Reasons for stone formation include: Malnutrition, diarrhea, dehydration Acid urine, hypocitraturia Complete metabolic evaluation is indicated Of 14 patients taking indinavir who had stones, only 4 patients' stones contained indinavir Reasons for stone formation include: Malnutrition, diarrhea, dehydration Acid urine, hypocitraturia Complete metabolic evaluation is indicated

53 Urologic Manifestations of AIDS Opportunistic infections of GU tract Examples: TB, fungi, herpes, viral cystitis Severe infections (e.g. abscess, Fournier’s) Increased incidence of malignancies Kaposi’s sarcoma may involve genitalia Squamous genital cancers Testis cancer (germ cell tumors & lymphomas) Renal cancer Opportunistic infections of GU tract Examples: TB, fungi, herpes, viral cystitis Severe infections (e.g. abscess, Fournier’s) Increased incidence of malignancies Kaposi’s sarcoma may involve genitalia Squamous genital cancers Testis cancer (germ cell tumors & lymphomas) Renal cancer

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55 Urologic Manifestations of AIDS (2) Hypogonadism: testosterone replacement is recommended for patients with weight loss Adrenal insufficiency; may need stress steroids Neurogenic bladder (any type) *Combined bladder + bowel dysfunction with back pain/sciatica: consider CMV polyradiculopathy, may be reversible if treated early Hypogonadism: testosterone replacement is recommended for patients with weight loss Adrenal insufficiency; may need stress steroids Neurogenic bladder (any type) *Combined bladder + bowel dysfunction with back pain/sciatica: consider CMV polyradiculopathy, may be reversible if treated early

56 HIV and Prostate Cancer Screen and treat same as men without HIV Life expectancy on HAART usually > 20 years For localized cancer, outcomes similar for men with vs. without HIV Laparoscopic surgery involves less exposure to the operating team than open surgery Screen and treat same as men without HIV Life expectancy on HAART usually > 20 years For localized cancer, outcomes similar for men with vs. without HIV Laparoscopic surgery involves less exposure to the operating team than open surgery

57 Circumcision and HIV 3 randomized trials in Africa Men having vaginal sex with women Infection rates 60% lower if circumcised Possible reasons: Inner foreskin rich in Langerhans cells and other HIV target cells Inner foreskin gets tears/abrasions Thicker keratin barrier if circumcised 3 randomized trials in Africa Men having vaginal sex with women Infection rates 60% lower if circumcised Possible reasons: Inner foreskin rich in Langerhans cells and other HIV target cells Inner foreskin gets tears/abrasions Thicker keratin barrier if circumcised

58 AIDS: Other Key Points for Urologists Use universal precautions and double glove!!! Workers with exudative skin lesions (even acne) should not participate in invasive procedures Being HIV-positive does not require that a surgeon stop operating Urine not considered infectious unless bloody Use universal precautions and double glove!!! Workers with exudative skin lesions (even acne) should not participate in invasive procedures Being HIV-positive does not require that a surgeon stop operating Urine not considered infectious unless bloody

59 HIV: Postexposure Prophylaxis Most important thing: avoid exposure!!! Double glove Eye shields Impervious gowns, boots Care with sharps Why? Also avoid hepatitis Hepatitis virus more easily transmitted than HIV Hepatitis C 3-4x more common than HIV in US Most important thing: avoid exposure!!! Double glove Eye shields Impervious gowns, boots Care with sharps Why? Also avoid hepatitis Hepatitis virus more easily transmitted than HIV Hepatitis C 3-4x more common than HIV in US

60 HIV: Postexposure Prophylaxis Good news: Risk of AIDS from a single sharps injury is low, even from a known HIV+ source Usual regimen: 2 or 3 drugs combined, for 4 weeks, must start < 4hrs after exposure USA National Post-Exposure Prophylaxis Hotline PEPline Good news: Risk of AIDS from a single sharps injury is low, even from a known HIV+ source Usual regimen: 2 or 3 drugs combined, for 4 weeks, must start < 4hrs after exposure USA National Post-Exposure Prophylaxis Hotline PEPline

61 A. Are the backbone of modern HAART regimens B. Prolong the duration of action of vardenafil C. Form stones that are easily seen on CT scan D. Form stones that dissolve if urine is alkalinized E. Should be kept in operating rooms for immediate post-exposure prophylaxis in case of sharps injury A. Are the backbone of modern HAART regimens B. Prolong the duration of action of vardenafil C. Form stones that are easily seen on CT scan D. Form stones that dissolve if urine is alkalinized E. Should be kept in operating rooms for immediate post-exposure prophylaxis in case of sharps injury Protease inhibitors:

62 A. Are the backbone of modern HAART regimens B. **Prolong the duration of action of vardenafil** C. Form stones that are easily seen on CT scan D. Form stones that dissolve if urine is alkalinized E. Should be kept in operating rooms for immediate post-exposure prophylaxis in case of sharps injury A. Are the backbone of modern HAART regimens B. **Prolong the duration of action of vardenafil** C. Form stones that are easily seen on CT scan D. Form stones that dissolve if urine is alkalinized E. Should be kept in operating rooms for immediate post-exposure prophylaxis in case of sharps injury Protease inhibitors:

63 A. Avoid contact with urine of HIV-positive patients B. HAART started the day after a sharps injury C. Circumcision (for men having vaginal coitus) D. Forbid HIV-positive surgeons to operate E. Encourage screening the general population at community health fairs A. Avoid contact with urine of HIV-positive patients B. HAART started the day after a sharps injury C. Circumcision (for men having vaginal coitus) D. Forbid HIV-positive surgeons to operate E. Encourage screening the general population at community health fairs Which of the following has proven efficacy in decreasing HIV transmission?

64 A. Avoid contact with urine of HIV-positive patients B. HAART started the day after a sharps injury C. **Circumcision (men having vaginal coitus)** D. Forbid HIV-positive surgeons to operate E. Encourage screening the general population at community health fairs A. Avoid contact with urine of HIV-positive patients B. HAART started the day after a sharps injury C. **Circumcision (men having vaginal coitus)** D. Forbid HIV-positive surgeons to operate E. Encourage screening the general population at community health fairs Which of the following has proven efficacy in decreasing HIV transmission?

65 SEXUALLY TRANSMITTED DISEASES OTHER THAN HIV/AIDS

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67 STD’s by Presentation Male urethritis Male genital ulcers Women with STDs usually present to primary care providers or gynecologists, so are not included in this overview. Male urethritis Male genital ulcers Women with STDs usually present to primary care providers or gynecologists, so are not included in this overview.

68 Which STDs are Reportable? Reportable in every state: Syphilis Gonorrhea Chlamydia Chancroid HIV infection and AIDS Other STDs: reporting requirements vary by state Reportable in every state: Syphilis Gonorrhea Chlamydia Chancroid HIV infection and AIDS Other STDs: reporting requirements vary by state

69 Male Urethritis Symptoms: dysuria, itch, discharge Most common organisms: NG Chlamydia Others (Mycoplasma, Ureaplasma, Gardnerella, etc.) Symptoms: dysuria, itch, discharge Most common organisms: NG Chlamydia Others (Mycoplasma, Ureaplasma, Gardnerella, etc.)

70 Male Urethritis Diagnosis Urine nucleic acid test for NG and Chlamydia Urethral swab Seldom used but source of exam questions Gram stain Intracellular G-neg diplococci = gonorrhea WBC no bacteria: non-gonococcal urethritis Culture in Thayer-Martin medium Inhibits growth of other microbes Allows growth of Neisseria Urine nucleic acid test for NG and Chlamydia Urethral swab Seldom used but source of exam questions Gram stain Intracellular G-neg diplococci = gonorrhea WBC no bacteria: non-gonococcal urethritis Culture in Thayer-Martin medium Inhibits growth of other microbes Allows growth of Neisseria

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72 Male Urethritis: Simplest Treatments Uncomplicated gonorrhea Ceftriaxone 125 mg IM or cefixime mg 400 po, also azithromycin 1g (30% have Chlamydia) No quinolones! Too much resistance Nongonococcal urethritis Goal: cover Chlamydia and Ureaplasma Azithromycin lg single dose Uncomplicated gonorrhea Ceftriaxone 125 mg IM or cefixime mg 400 po, also azithromycin 1g (30% have Chlamydia) No quinolones! Too much resistance Nongonococcal urethritis Goal: cover Chlamydia and Ureaplasma Azithromycin lg single dose

73 Male Urethritis: Partner Treatments Longstanding recommendation: evaluate and treat all partners exposed within 60 days; if none, evaluate and treat the most recent partner New idea: expedited partner therapy Give patient Rx or meds, to take to partner Advantage: partner more likely to be treated Some states don’t allow this CDC web site Longstanding recommendation: evaluate and treat all partners exposed within 60 days; if none, evaluate and treat the most recent partner New idea: expedited partner therapy Give patient Rx or meds, to take to partner Advantage: partner more likely to be treated Some states don’t allow this CDC web site

74 Genital Ulcers STDs Remember: not all ulcers are STDs! Can also be: Carcinoma Erythema multiforme Fixed drug eruption Bechet’s disease Lichen planus STDs Remember: not all ulcers are STDs! Can also be: Carcinoma Erythema multiforme Fixed drug eruption Bechet’s disease Lichen planus

75 STDs With Genital Ulcers Uncommon in USA Granuloma inguinale Lymphogranuloma venereum Common in USA Painless: 1 o syphilis (unless superinfected) Painful Chancroid Herpes Uncommon in USA Granuloma inguinale Lymphogranuloma venereum Common in USA Painless: 1 o syphilis (unless superinfected) Painful Chancroid Herpes

76 Ulcer STDs Uncommon in USA To remember for test, both have: Granuloma in their names 1 st line treatment doxycycline > 3 weeks Different ulcer appearances Granuloma inguinale (painless ulcer) Lymphogranuloma venereum Ulcer may resolve before patient presents Often presents as inguinal adenopathy To remember for test, both have: Granuloma in their names 1 st line treatment doxycycline > 3 weeks Different ulcer appearances Granuloma inguinale (painless ulcer) Lymphogranuloma venereum Ulcer may resolve before patient presents Often presents as inguinal adenopathy

77 Granuloma Inguinale Rare in USA, common in tropics Cause: Klebsiella granulomatis (formerly called Calymmatobacterium granulomatis) an intracellular gram-negative bacterium Main symptom is ulcer Usually painless Beefy red, bleeds easily (very vascular) Rare in USA, common in tropics Cause: Klebsiella granulomatis (formerly called Calymmatobacterium granulomatis) an intracellular gram-negative bacterium Main symptom is ulcer Usually painless Beefy red, bleeds easily (very vascular)

78 Granuloma Inguinale Diagnosis Cannot be cultured Biopsy or “crush prep” ulcer Donovan bodies in monocytes Treatment Doxycycline > 3 weeks until all lesions healed Examine partners Diagnosis Cannot be cultured Biopsy or “crush prep” ulcer Donovan bodies in monocytes Treatment Doxycycline > 3 weeks until all lesions healed Examine partners

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80 Lymphogranuloma Venereum Rare in USA Caused by Chlamydia trachomatis (L1-3 strains) Symptoms at presentation Small ulcer may have resolved Large, suppurative lymph nodes If acquired rectally may get proctocolitis and colorectal fistulas and strictures (this is an invasive infection) Rare in USA Caused by Chlamydia trachomatis (L1-3 strains) Symptoms at presentation Small ulcer may have resolved Large, suppurative lymph nodes If acquired rectally may get proctocolitis and colorectal fistulas and strictures (this is an invasive infection)

81 Lymphogranuloma Venereum Diagnosis: Swab genital lesion or aspirate lymph node; test this for C. trachomatis by culture, direct immunofluorescence, or nucleic acid detection If these are not available, OK to treat empirically based on symptoms/signs Treatment Doxycycline 100 bid 3 weeks May need incision & drainage of lymph nodes Treat partners (1 g azithroymcin x 1 is OK) Diagnosis: Swab genital lesion or aspirate lymph node; test this for C. trachomatis by culture, direct immunofluorescence, or nucleic acid detection If these are not available, OK to treat empirically based on symptoms/signs Treatment Doxycycline 100 bid 3 weeks May need incision & drainage of lymph nodes Treat partners (1 g azithroymcin x 1 is OK)

82 Lymphogranuloma venereum Bilateral bubos

83 Ulcer STDs Common in USA Painful Herpes simplex Chancroid Syphilis is usually painless unless superinfected Painful Herpes simplex Chancroid Syphilis is usually painless unless superinfected

84 Genital Herpes: Diagnosis A group of vesicles on erythematous base that does not follow a neural distribution: pathognomonic* Other tests: Virus culture of lesions PCR more sensitive but not FDA-approved Point of care blood tests are good but 2 caveats Negative early (before antibodies form) Positive for life (current vs past infection?) A group of vesicles on erythematous base that does not follow a neural distribution: pathognomonic* Other tests: Virus culture of lesions PCR more sensitive but not FDA-approved Point of care blood tests are good but 2 caveats Negative early (before antibodies form) Positive for life (current vs past infection?)

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86 Genital Herpes: Treatment Acyclovir po (topical not effective) Newer drugs with better oral bioavailability Valacyclovier (valine ester of acyclovir) Famciclovir The same drugs can also be used for recurrences PRN dosing Chronic suppression Counsel patient (see next slide) Acyclovir po (topical not effective) Newer drugs with better oral bioavailability Valacyclovier (valine ester of acyclovir) Famciclovir The same drugs can also be used for recurrences PRN dosing Chronic suppression Counsel patient (see next slide)

87 Genital Herpes: Patient Counseling Expect recurrences Possible transmission to baby during delivery Ways to decrease risk of transmission to partners Abstain during symptoms (problem: may shed virus even if not having symptoms) Condoms Valacyclovir 500 mg daily taken by patient Expect recurrences Possible transmission to baby during delivery Ways to decrease risk of transmission to partners Abstain during symptoms (problem: may shed virus even if not having symptoms) Condoms Valacyclovir 500 mg daily taken by patient

88 Chancroid (Haemophilus ducreyi) Symptoms One or more painful ulcers 1/3 have tender or suppurative nodes Diagnosis Specialized culture is not widely available PCR test available but not FDA-approved OK to treat painful ulcer if not herpes or syphilis Simplest treatment Azithromycin lg po single dose Treat partners Symptoms One or more painful ulcers 1/3 have tender or suppurative nodes Diagnosis Specialized culture is not widely available PCR test available but not FDA-approved OK to treat painful ulcer if not herpes or syphilis Simplest treatment Azithromycin lg po single dose Treat partners

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90 Syphilis (Treponema pallidum) 1 o stage is painless ulcer

91 STDs with Ulcers: Sorted by Appearance Painful vesicles: herpes Bubos, ulcer small or absent: lymphogranuloma venereum: Typical raw ulcer 1 o syphilis Chancroid Granuloma inguinale Painful vesicles: herpes Bubos, ulcer small or absent: lymphogranuloma venereum: Typical raw ulcer 1 o syphilis Chancroid Granuloma inguinale

92 STDs with Typical Ulcers: Diagnosis Painful: chancroid No diagnostic test r/o syphilis and treat empirically Painless 1 o syphilis Blood tests detect antibodies If early, ulcer scrape or biopsy is only test Granuloma inguinale Biopsy is the only diagnostic test Donovan bodies Painful: chancroid No diagnostic test r/o syphilis and treat empirically Painless 1 o syphilis Blood tests detect antibodies If early, ulcer scrape or biopsy is only test Granuloma inguinale Biopsy is the only diagnostic test Donovan bodies

93 Syphilis (Treponema pallidum) Stages and Symptoms 1 o : painless ulcer (chancre) 2 o : nongenital skin lesions, adenopathy 3 o : cardiac, neuro, eye, ear, etc. Latent: no symptoms 1 o : painless ulcer (chancre) 2 o : nongenital skin lesions, adenopathy 3 o : cardiac, neuro, eye, ear, etc. Latent: no symptoms

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95 Syphilis Diagnosis Scrape base of ulcer, look for spirochetes by dark-field microscope or fluorescent antibody Best test for primary syphilis Many docs lack equipment* Serum antibody tests Nontreponemal (anti-cardiolipin antibodies) Treponemal (antibodies against Treponema) * Dowell D, Clinical Infectious Diseases 2009 Scrape base of ulcer, look for spirochetes by dark-field microscope or fluorescent antibody Best test for primary syphilis Many docs lack equipment* Serum antibody tests Nontreponemal (anti-cardiolipin antibodies) Treponemal (antibodies against Treponema) * Dowell D, Clinical Infectious Diseases 2009

96 Diagnosis of Syphilis Recent change in recommendations due to high false positive with non-treponemal test Recent change in recommendations due to high false positive with non-treponemal test now recommend starting with treponemal assay (syphilis IgG) and if reactive confirm with RPR now recommend starting with treponemal assay (syphilis IgG) and if reactive confirm with RPR If IgG positive and RPR negative use second treponemal assay (TPPA or FTA antibody) to confirm and differentiate latent vs historical If IgG positive and RPR negative use second treponemal assay (TPPA or FTA antibody) to confirm and differentiate latent vs historical

97 Treatment of 1  and 2° Syphilis Benzathine penicillin G 2.4 million units IM Bicillin L-A (benzathine PCN) Not Bicillin C-R (benzathine- procaine PCN) If allergic to penicillin, can use tetracycline or doxycycline 2 weeks, but only if: Not pregnant Reliable for follow-up Benzathine penicillin G 2.4 million units IM Bicillin L-A (benzathine PCN) Not Bicillin C-R (benzathine- procaine PCN) If allergic to penicillin, can use tetracycline or doxycycline 2 weeks, but only if: Not pregnant Reliable for follow-up

98 Situations in Which Penicillin is the Only Treatment Option for Syphilis (If Allergic, Desensitize) Pregnancy Syphilitic eye disease Neurosyphilis (MMWR says ceftriaxone OK) Patients not compliant and reliable for follow-up with a 2-4 week oral tetracycline regimen Pregnancy Syphilitic eye disease Neurosyphilis (MMWR says ceftriaxone OK) Patients not compliant and reliable for follow-up with a 2-4 week oral tetracycline regimen

99 Treatment of 1  and 2° Syphilis Recheck VDRL or RPR using same test and same lab at 6 and 12 months; if not decreased, suspect: Treatment failure Re-infection Tertiary syphilis HIV All patients with syphilis should be tested for HIV Recheck VDRL or RPR using same test and same lab at 6 and 12 months; if not decreased, suspect: Treatment failure Re-infection Tertiary syphilis HIV All patients with syphilis should be tested for HIV

100 A. Primary syphilis B. Chlamydial urethritis C. Gonococcal urethritis D. Chancroid E. Granuloma inguinale A. Primary syphilis B. Chlamydial urethritis C. Gonococcal urethritis D. Chancroid E. Granuloma inguinale All of the following STDs in men can be treated by single-dose antibiotics except:

101 A. Primary syphilis B. Chlamydial urethritis C. Gonococcal urethritis D. Chancroid E. **Granuloma inguinale** A. Primary syphilis B. Chlamydial urethritis C. Gonococcal urethritis D. Chancroid E. **Granuloma inguinale** All of the following STDs in men can be treated by single-dose antibiotics except:

102 A. Primary syphilis B. Lymphogranuloma venereum C. Human papilloma virus D. Chancroid E. Granuloma inguinale A. Primary syphilis B. Lymphogranuloma venereum C. Human papilloma virus D. Chancroid E. Granuloma inguinale Which of the following STDs involves a painful ulcer?

103 A. Primary syphilis B. Lymphogranuloma venereum C. Human papilloma virus D. **Chancroid** E. Granuloma inguinale A. Primary syphilis B. Lymphogranuloma venereum C. Human papilloma virus D. **Chancroid** E. Granuloma inguinale Which of the following STDs involves a painful ulcer?

104 A. Ulcer scraping in primary syphilis B. Lymph node aspiration in lymphogranuloma venereum C. Thayer-Martin medium in gonorrhea D. Ulcer biopsy in granuloma inguinale E. Urethral swab in Chlamydia urethritis A. Ulcer scraping in primary syphilis B. Lymph node aspiration in lymphogranuloma venereum C. Thayer-Martin medium in gonorrhea D. Ulcer biopsy in granuloma inguinale E. Urethral swab in Chlamydia urethritis Donovan bodies are seen on:

105 A. Ulcer scraping in primary syphilis B. Lymph node aspiration in lymphogranuloma venereum C. Thayer-Martin medium in gonorrhea D. **Ulcer biopsy in granuloma inguinale** E. Urethral swab in Chlamydia urethritis A. Ulcer scraping in primary syphilis B. Lymph node aspiration in lymphogranuloma venereum C. Thayer-Martin medium in gonorrhea D. **Ulcer biopsy in granuloma inguinale** E. Urethral swab in Chlamydia urethritis Donovan bodies are seen on:

106 A. Gonorrhea B. Primary syphilis C. Genital warts D. Chancroid E. Genital herpes A. Gonorrhea B. Primary syphilis C. Genital warts D. Chancroid E. Genital herpes If state laws allow it, expedited partner therapy is recommended for:

107 A. **Gonorrhea** B. Primary syphilis C. Genital warts D. Chancroid E. Genital herpes A. **Gonorrhea** B. Primary syphilis C. Genital warts D. Chancroid E. Genital herpes If state laws allow it, expedited partner therapy is recommended for:

108 HPV Over 40 serotypes that can infect Over 40 serotypes that can infect Common, most asymptomatic, self limited Common, most asymptomatic, self limited HPV 16 and 18 oncogenic HPV 16 and 18 oncogenic cervical, penile, vaginal, oropharyngeal, analcervical, penile, vaginal, oropharyngeal, anal possible link to low grade TCCpossible link to low grade TCC Pathology. 41:245, 2009 Pathology. 41:245, 2009 HPV 6 and 11 cause 90% of warts, low cancer risk HPV 6 and 11 cause 90% of warts, low cancer risk

109 HPV Lesions

110 Summary of Genital Wart Therapy Patient-Applied Patient-Applied Podofilox 0.5% solution or gelPodofilox 0.5% solution or gel Imiquimod 5% creamImiquimod 5% cream Sinecatechins 15% ointmentSinecatechins 15% ointment Provider–Administered Provider–Administered Cryotherapy with liquid nitrogen or cryoprobe. Repeat applications every 1–2 weeks.Cryotherapy with liquid nitrogen or cryoprobe. Repeat applications every 1–2 weeks. Podophyllin resin 10%–25% Podophyllin resin 10%–25% Surgical removal either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery.Surgical removal either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery.

111 HPV Prevention Quadrivalent vaccine (Gardasil) against 6, 11, 16, 18 (70% cancers, 90% warts) Quadrivalent vaccine (Gardasil) against 6, 11, 16, 18 (70% cancers, 90% warts) Must be started before sexually active Must be started before sexually active Approved for females aged 9-26 (series of 3 injections) Approved for females aged 9-26 (series of 3 injections) Safe/effective in males Safe/effective in males NEJM 364(5):401-11, Feb 2011NEJM 364(5):401-11, Feb 2011 Current debate cost benefit Current debate cost benefit improve disease reduction in femalesimprove disease reduction in females anogenital cancer reduction mostly in MSM but must be given at young ageanogenital cancer reduction mostly in MSM but must be given at young age

112


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