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External inspection (skin tags, thrombosed external hemorrhoid, erythema/induration)? Lateral traction to the
buttocks
visible ulcerations.
If significant pain reported, digital exam or instrumentation at the first presentation not indicated!
External palpation: normal/reduced sphincter tone?
Rigid/flexible sigmoidoscopy: proctitis, mass, etc.
Further colonic evaluation as per general screening guidelines (if history and findings consistent
may be deferred for 3–4
weeks until acute symptoms improved).
ADDITIONAL TESTS (OPTIONAL)
Cultures (viral, bacterial including for gonococcus, fungal, acid-fast bacilli).
Biopsy of anything unusual.
PPD test.
Possible chest x-ray.
Classification
HIV-/immunosuppression-driven diseases (causal).
HIV-associated diseases (linked without direct cause–effect).
HIV-independent diseases (coincidental).
Nonoperative Treatment
General: assessment of immune status (eg, CD4 < 50) initiation/adjustment of HAART.
HIV-associated ulcer: empirical medication with metronidazole 3
x 500 mg PO and acyclovir 3 x 800 mg PO for 14 days
results in 85% resolution; repeat if improved but not resolved.
STDs: antibiotic/antiviral treatment, supportive measures.
Pre-neoplasia: anal canal surveillance.
Hemorrhoids: banding, but contraindicated if evidence for immunosuppression.
Operative Treatment
INDICATION
HIV-associated ulcer: failure of empirical treatment.
Condylomata.
Lump/mass.
Persistent cancer after chemoradiation.
Abscess/fistula.
Treatment-refractory hemorrhoids.
OPERATIVE APPROACH
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Excision of ulcers, potentially with advancement flap open wound care.
Hemorrhoids: excisional hemorrhoidectomy. Caveat: stapled hemorrhoidectomy contraindicated in MSM (risk of injury
from residual staples).
Other pathologies: removal of warts, biopsy or excision of lumps, drainage of abscess, etc; persistent cancer after
chemoradiation
oncologic resection (see Anal Cancer later in the chapter).
Outcome
HIV-associated ulcer: 85% improvement with conservative treatment; after surgical excision improvement of pain and
discomfort in 90% of patients despite creation of even larger wounds and varying times of wound healing.
CD4 < 50
poor wound healing.
Follow–Up
Monitoring of HAART.
Immediate follow-up every 2 weeks
control and verification of local treatment success.
Long-term follow-up
health management, HAART, at least annual Pap smear, etc.
Cross-Reference
Ulceration (Ch. 1)
Anal fissure (565.0) (Ch. 4)
Perianal/-rectal abscess (566) (Ch. 4)
Sexually Transmitted Diseases (STDs, 091, 098, 099) (Ch. 4)
Anal condylomata (078.10) (Ch. 4)
Anal intraepithelial neoplasia (AIN, 235.5) (Ch. 4)
Anal cancer (154.2, 154.3) (Ch. 4)
Abdominoperineal resection (APR) (Ch. 5)
Medications against viral pathogens (App. 1)
SEXUALLY TRANSMITTED DISEASES (STDS, 091, 098, 099)
Overview
STDs are caused by transmission of pathogens during sexual activity. Affected locations: genital, anorectal, oral. Anorectal
STDs are an important health issue in patients engaging in anoreceptive intercourse. Risk behavior of either index patient or
partner(s) result in frequently repeated acquisitions of STDs. Multiple simultaneous STDs are common and facilitate
acquisition of others (eg, HIV).
Discharge syndromes: gonorrhea, chlamydia (LGV), HSV.
Anogenital ulcerations: herpes simplex, HIV-associated ulcers, primary syphilis, chancroid (Haemophilus ducreyi),
LGV, granuloma inguinale (donovanosis: Klebsiella/Calymmatobacterium granulomatis).
Pain:
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– Yes: HSV, LGV, chancroid.
– No: syphilis (chancre), granuloma inguinale.
Proctitis/proctocolitis: gonorrhea, chlamydia (LGV), syphilis, HSV.
Proliferative syndromes: HPV, HHV-8 (Kaposi sarcoma), lymphoma, syphilis (condylomata lata, gumma).
Skin rashes: secondary syphilis, disseminated gonorrhea, pediculosis pubis, scabies.
Direct anogenital pathogen infestation: HPV, Neisseria gonorrhoeae, Chlamydia trachomatis (including LGV), Treponema
pallidum (syphilis), HSV.
Indirect pathogen infestation (eg, oral or oral-anal route): Giardia lamblia, Campylobacter species, Shigella species,
Entamoeba histolytica, C trachomatis, pediculosis pubis, scabies.
HIV-positive patients: CMV, Mycobacterium avium intracellulare complex (MAI/MAC), Microsporidium, Isospora, etc.
Epidemiology
US incidence of STDs overall: up to 20 million new infections per year. Active STDs (eg, gonorrhea, syphilis, etc) increase the
risk of HIV infection if exposed.
Symptoms
General Symptoms
Proctitis: pruritus, anorectal pain, tenesmus, rectal bleeding, mucus discharge.
Proctocolitis: same as above; in addition: change in bowel habits (diarrhea), abdominal cramps.
Enteritis: diarrhea, abdominal cramping without signs of proctocolitis.
Proliferation: lump, mass, condylomata.
Specific Disease Features
Gonorrhea: asymptomatic carrier (reservoir); PID; monoarthritis; skin rash; urethritis; proctitis with thick, cloudy, or
bloody discharge; pain.
Syphilis (Lues):
– Primary: primary complex (chancre)—small, indurated, clean-based, and painless ulcer; proctitis.
– Secondary: diffuse, nonitching maculopapular skin rash, possible general symptoms (lymphadenopathy, fever,
headache), condylomata lata.
– Latent: status post infection, but no clinical evidence of disease.
– Tertiary: no primary manifestation, neurologic symptoms, aortitis, gumma.
Chancroid: deep, purulent, and painful genital ulcer with tender suppurative inguinal lymphadenopathy.
Herpes genitalis: multiple and grouped painful vesicular or shallow ulcerative lesions.
Chlamydia serovars D–K: proctitis, urethritis.
Chlamydia serovars L1–L3 (LGV): tender lymphadenopathy, proctocolitis with bloody/mucous discharge,
pain/tenesmus, constipation, fever. Long-term sequelae: lymphedema, fistulae, and strictures.
Granuloma inguinale (donovanosis): progressive, very vascular and friable, painless ulceration without regional
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lymphadenopathy.
Differential Diagnosis
Other causes of ulceration, bleeding, pain.
Primary neoplasms: anal cancer, Paget disease, Bowen disease, AIN, rectal cancer, melanoma, Kaposi sarcoma, lymphoma.
Other forms of colitis: ulcerative colitis, Crohn disease, C difficile colitis, etc.
Pathogens
Gonorrhea: N gonorrhoeae, intracellular gram-negative diplococci selective cultures (Thayer-Martin medium), PCR.
Syphilis: T pallidum (spirochetes) darkfield/immunofluorescence microscopy, serology.
Chancroid: H ducreyi, gram-negative rod special culture medium (difficult), PCR-diagnosis.
Herpes genitalis: HSV-1 and HSV-2 (herpes genitalis) isolation in cell cultures, PCR-based diagnosis.
C trachomatis serovars D–K and L1, L2, L3 (LGV), intracellular pathogen serology, culture, immunofluorescence
test.
Granuloma inguinale (donovanosis): gram-negative K granulomatis (formerly C granulomatis) culture difficult,
diagnosis on biopsy: dark-staining Donovan bodies.
Evaluation
REQUIRED MINIMAL STANDARD
History: risk behavior, HIV status, specific symptoms.
Clinical examination: inspection
mass/lump, ulcers/blisters, fistulae? Digital exam/palpation of inguinal lymph nodes;
anoscopy/sigmoidoscopy HSV, gonorrhea, LGV, syphilis? Examination of oral cavity.
All patients with STDs
HIV testing (unless known positive).
Cultures:
Direct cultures: HSV, gonorrhea, chlamydia, H ducreyi, tuberculosis.
Stool cultures, including Giardia, cryptosporidiosis, microsporidiosis.
Other examinations:
Stool WBCs?
Gram-stained smear of anorectal secretions: gram-negative intracellular diplococci?
Darkfield light microscopy: T pallidum?
Serologic testing: HSV-2, syphilis, LGV, gonorrhea.
Anogenital ulcers:
syphilis serology + darkfield examination or direct immunofluorescence, HSV culture or antigen test, H
ducreyi culture.
Reportable diseases: syphilis, gonorrhea, chlamydia, HIV, tuberculosis.
ADDITIONAL TESTS (OPTIONAL)
Chest x-ray or PPD: tuberculosis.
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Colonoscopy.
Classification
Based on specific infectious pathogen.
Nonoperative Treatment
Proctitis: ceftriaxone + doxycycline.
HSV: one of the following: acyclovir, famciclovir, valacyclovir.
Syphilis: penicillin G
caveat: Jarisch-Herxheimer in first 24 hours: acute febrile reaction, headache, myalgia; alternatives:
doxycycline, tetracycline.
Chlamydia/LGV: doxycycline; alternative: erythromycin.
Gonorrhea: ceftriaxone (plus treatment for chlamydia); alternative: spectinomycin
caveat: drug-resistant gonorrhea.
CMV: ganciclovir.
Chancroid: one of the following: azithromycin, ceftriaxone, ciprofloxacin, erythromycin.
Granuloma inguinale: doxycycline; alternatives: azithromycin, ciprofloxacin, erythromycin, or trimethoprim-
sulfamethoxazole.
Idiopathic HIV-associated ulcers: empirical treatment with acyclovir + metronidazole.
HPV: see respective chapters.
Operative Treatment
INDICATIONS
Uncertain diagnosis biopsy and culture of tissue specimen (bacterial, viral, acid-fast bacilli).
Anogenital condylomata.
Treatment-refractory HIV-associated ulcer.
OPERATIVE APPROACH
See Chapter 5.
Outcome
Higher risk of treatment failure in HIV-positive patients, particularly with low CD4 counts.
Risk factors for recurrent infections: continued risk behavior (promiscuity, unprotected intercourse), untreated partner,
uncircumcised individuals.
Follow-Up
Assessment of infection clearance follow-up should be based on specific etiology and severity of clinical symptoms.
Difficulty in distinguishing reinfection from treatment failure.
Management of sex partners: evaluation and treatment.
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Cross-Reference
Discharge (Ch. 1)
Ulceration (Ch. 1)
Perianal/-rectal fistula (565.1) (Ch. 4)
HIV-associated anorectal diseases (042) (Ch. 4)
Anal condylomata (078.10) (Ch. 4)
Anal intraepithelial neoplasia (AIN, 235.5) (Ch. 4)
Anal cancer (154.2, 154.3) (Ch. 4)
Medications against viral pathogens (App. 1)
Medications against bacterial and fungal pathogens (App. 1)
ANAL CONDYLOMATA (078.10)
Overview
Condylomata ("anogenital warts") are hyperkeratotic and often cauliflower-like, solitary or multiple skin lesions that are
caused by sexually transmitted infection of squamous epithelia with highly contagious HPV. Before activating proliferative
growth mode, HPV may be dormant within the cells for weeks, months, even years: the exact time and "donor" of the
infection can therefore not be determined with certainty.
More than 100 HPV serotypes have been identified: ~30 serotypes are sexually transmitted, serotypes 6/11 in > 90% of
cases, but coexistence of different serotypes is possible. Currently, routine serotyping is clinically not relevant:
HPV serotypes with malignant potential: 16, 18, 33, 31, 35, 39, 45, 51, 52 low- and high-grade squamous
intraepithelial lesions (LSIL, HSIL)
invasive cancer.
HPV serotypes without malignant potential: 6, 11, 42, 43, 44 genital warts, LSIL
Growth pattern ranging from (1) focal scattered diminutive warts, to (2) large and exophytic warts, (3) carpet-like, often
confluent lesions, or (4) inversely growing Buschke-Lowenstein giant condylomata.
Epidemiology
In the US: prevalence of 20 million people with genital HPV infections, annual incidence of 5.5 million people infected every
year; 50–75% of sexually active general population have genital HPV infection at some time in their life, 15% with evidence
of current infection. Majority of infections are subclinical, ie, not detectable by physical exam or cytology. Anogenital warts: in
1–2% of general population, in 3–25% of HIV-positive population; 13–30% of males with anal warts have penile warts; 70–
85% of patients with external warts have also internal warts.
Symptoms
Often asymptomatic.
Presence of indolent palpable/visible grayish or flesh-colored skin lesions (papules, nodules, lumps, masses).
Itching: difficulty with hygiene. With increasing size bleeding when traumatized.
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Caveat: pain is not a symptom of anal warts differential diagnoses: ulcer, fissure, tumor, abscess.
Differential Diagnosis
Molluscum contagiosum.
Fibroepitheliomata.
Hypertrophic anal papillae.
Seborrheic keratoses.
Sebaceous glands.
Condylomata lata (secondary syphilis).
Bowen disease.
Anal cancer or other tumors.
Paget disease.
Pathology
Papillomatous hyperkeratotic acanthotic lesions. Maintained epithelial maturation toward the surface. Characteristic
koilocytosis = perinuclear cytoplasmic vacuolization in conjunction with nuclear irregularity.
Low-grade dysplasia (AIN I)
high-grade dysplasia (AIN III): increasing epithelial disorganization, loss of maturation,
increased cellularity to the surface. Podophyllin effect: changes similar to high-grade dysplasia.
Evaluation
REQUIRED MINIMAL STANDARD
History: onset, pattern, and sites of occurrence; associated symptoms? HIV status?
Clinical examination: localization and extent of lesions? Confluence of lesions (Figure 4–7)? Estimate of internal and external
anoderm involvement. Examination of perineum, penis. GYN exam.
Figure 4–7.
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Anal condylomata.
Anoscopy/proctoscopy/sigmoidoscopy: internal involvement, associated STD proctitis, etc.
Full colonic evaluation only necessary if indicated as per general screening guidelines.
ADDITIONAL TESTS (OPTIONAL)
Cultures: if suspicion of other STDs.
Biopsy: if diagnosis in doubt, all excised lesions.
HIV test (recommended).
GYN exam.
Partner examination/treatment.
Classification
Condylomata acuminata.
Condylomata plana.
Condylomata gigantea (Buschke-Loewenstein).
Nonoperative Treatment
In HIV-infected patients: optimization of immune status (HAART).
Topical treatments for relatively limited and accessible disease, commonly multiple sessions (daily/weekly) needed,
recurrence rates > 25%:
1. Patient applied:
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a. Imiquimod 5%: topical ointment, unclear mode of action but multilevel enhancement of local immune
response which promotes host suppression of HPV proliferation. Red butt: side effect, often associated with later
treatment success. Success rate of 60–70% in HIV-negative, 10–20% in HIV-positive patients.
b. Podophyllin: 0.5 solution topically twice daily for 8 hours (3–4 days/week), protection of healthy skin
recommended; antiproliferative cytotoxic properties (cell cycle arrest in metaphase)
potential risk of
carcinogenesis, unsuited for anal canal condylomata. Local side effects: irritation, blistering, ulceration; rare
systemic toxicity reported: hepatotoxicity, oncogenicity. Caveat: podophyllin effect on pathology specimen.
c. 5-FU: 60% eradication after 3–7 days but often associated with intolerable discomfort.
2. Physician applied:
a. Podophyllin: 25% solution topically once per week (side effects: see above).
b. Liquid nitrogen: freezing of warts every 1–2 weeks, cheap, discomfort.
c. Trichloric acid (TCA): chemical burning of warts, once per week.
d. Intralesional injection of interferon: multiple sessions needed.
3. Unproven treatments: multiple other regimens.
Operative Treatment
INDICATION
Larger extent and/or number of external condylomata.
Internal condylomata.
Treatment refractoriness.
OPERATIVE APPROACH
Excision of larger lesions at their base, possible combination with injection of interferon alpha.
Fulguration of smaller/flat lesions, possible combination with injection of interferon alpha.
Wide excision with flap reconstruction (not commonly indicated).
Outcome
Risk of recurrence dependent on extent of disease, completeness of removal, HIV/immune status. HPV also present in
adjacent noncondylomatous epithelium 30–50% recurrence.
Patient education about safer sex practices (avoidance of reinfection, avoidance of associated STDs), management of sex
partner recommended.
Role, indication, timing of HPV vaccination (Gardasil) unclear at this point.
Follow-Up
Frequent follow-up in clinic removal of small recurrences using local anesthesia.
Cross-Reference
Lump or mass (Ch. 1)
Sexually Transmitted Diseases (STDs, 091, 098, 099) (Ch. 4)
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Anal intraepithelial neoplasia (AIN, 235.5) (Ch. 4)
Bowen disease (235.5) (Ch. 4)
Anal cancer (154.2, 154.3) (Ch. 4)
Excision/fulguration of anal warts (Ch. 5)
Medications against viral pathogens (App. 1)
ANAL INTRAEPITHELIAL NEOPLASIA (AIN, 235.5)
Overview
Anal dysplasia (like anal cancer) is linked to HPV infection with subtypes HPV16 or HPV18. The concept of AIN in high-risk
populations (HIV-positive MSM) is relatively young and still evolving: there is a confusing and nonstandardized overlap
between different pathologies and newer vs established terminology:
AIN (anal intraepithelial neoplasia): neither visible nor palpable, located in anal canal.
LSIL vs HSIL (low-grade vs high-grade squamous intraepithelial lesion).
ASCUS (atypical squamous cells of uncertain significance).
Carcinoma in situ, intraepithelial carcinoma.
Bowen disease: visible erythematous plaque with an irregular but usually sharp demarcation, located in anal margin
area.
AIN terminology and management "borrowed" from cervical cancer prevention/management (ie, CIN), but not entirely
applicable:
Analogies between the two entities:
– Both are considered STDs: associated with HPV, other HPV manifestations common (condylomata), eradication
of HPV difficult (dormant viral genome), identification of precancerous lesions relatively easy.
Differences:
– Cervix: common cancer with decreasing incidence (cervical cancer screening programs), precursor lesion
treatable without mutilation, early cancers hidden (not in reach of finger), cancer-specific mortality relatively
high (except for earliest stages).
– Anus: rare cancer with increasing incidence (HIV, HAART), precursor lesion difficult to treat (morbidity, risk of
mutilation and functional impairment), early cancer readily visible/palpable (in reach of finger), effective
treatment available for established cancer, cancer-specific mortality relatively low.
Problems: the concept of AIN monitoring relies on stepwise progression through different stages. Unfortunately, this
concept is not (yet) corroborated by actual data: uncertain whether/when/how AIN can regress or progresses towards
cancer or whether therapeutic intervention allows natural course to be changed. Cost-effectiveness of anal screening
has not been analyzed.
Epidemiology
HIV-positive MSM found to have AIN of any grade in 81%, AIN II or III in 52%.
Symptoms