Sexually Transmissible Infections in Clinical Practice

34. An HIV-Infected Man with Anal Pain, Anal Discharge, and Bleeding

Alexander McMillan1, 2  

(1)

Department of Genitourinary Medicine, NHS Lothian, Edinburgh Royal Infirmary, Edinburgh, Uk

(2)

University of Edinburgh, Edinburgh, Uk

Alexander McMillanFormerly, Consultant Physician, part-time Senior Lecturer

Email: a.amcmm@btinternet.com

Abstract

A 32-year-old man, Frank, presents to a Sexual Health clinic with a 1-week history of pain in the perianal region, a discharge of thick yellow material from the anal canal, a feeling of incomplete bowel emptying, and bleeding after defecation. There are no other symptoms, in particular he has not noticed fever and there has been no abdominal pain. He is HIV infected, the diagnosis having been made 5 years previously. He has never been treated with antiretroviral drugs, and he gives no history of illicit use of such agents.

A 32-year-old man, Frank, presents to a Sexual Health clinic with a 1-week history of pain in the perianal region, a discharge of thick yellow material from the anal canal, a feeling of incomplete bowel emptying, and bleeding after defecation. There are no other symptoms, in particular he has not noticed fever and there has been no abdominal pain. He is HIV infected, the diagnosis having been made 5 years previously. He has never been treated with antiretroviral drugs, and he gives no history of illicit use of such agents. A baseline genotypic assay did not identify mutations in the HIV genome likely to confer resistance to antiviral drugs. His CD4 + T-cell count was 467 per mm3(normal range 500–1500 per mm 3 ) and a plasma viral HIV concentration of 7,853 copies per mL when he was tested about 12 weeks previously. Over the past 7 years he has had six episodes of rectal and urethral gonorrhoea, three episodes of rectal chlamydial infection (the infecting genotype was unknown), and numerous infections with pubic lice. Two years previously he was treated for primary syphilis of the anal canal with two injections of benzathine penicillin, given at a week’s interval. One year after treatment, the Venereal Diseases Research Laboratory (VDRL) test was negative, an anti-treponemal IgM enzyme immunoassay was negative, and the Treponema pallidum particle agglutination (TPPA) test was weakly positive, with a titer of 40, this pattern of results being consistent with adequately treated early syphilis.

When he attended for a sexual health screen about 5 years previously, it was noted that he had had prior infection with hepatitis B virus: hepatitis B surface antigen was negative, but anti-core antibody was detected. As there was no serological evidence of prior exposure to hepatitis A, he completed a course of hepatitis A vaccine at that time. He has no past history of gastrointestinal disease.

He has a regular partner with whom he has had an open relationship for more than 3 years. His partner is also HIV-infected and is not receiving antiviral therapy. They have unprotected receptive and insertive anal intercourse with each other and with most of their numerous casual sexual contacts. The most recent occasion on which they had sex was at a party in Berlin, Germany, about 6 weeks previously. Both had unprotected receptive anal sex with five different men, and Frank also participated in insertive and receptive “fisting”1 with one man. He regularly uses oral amphetamines and inhales nitrites during anal sex, but he has never injected drugs.

34.1 What Diagnoses Do You Consider?

The symptoms are consistent with those of a distal proctitis. Table 20.1 (Case 20) indicates the causes of a distal proctitis. In the case presented here, infection with Chlamydia trachomatis genotypes D–K is an unlikely cause of such severe symptoms: most infected individuals, if symptomatic, have mild features of distal proctitis. Lymphogranuloma venereum (LGV) genotypes, however, can cause severe proctitis, and, as there have been recent outbreaks of such infection in Western Europe, this is the most likely diagnosis. Gonococcal proctitis can be severe as can primary herpetic infection, particularly in the immunocompromised. Syphilis, of course, needs to be considered. Peri-rectal cellulitis can result from receptive “fisting,” extra-peritoneal rupture of the rectum allowing passage of bacteria into the tissues surrounding the rectum. However, most cases present within a few days of the risk, and abdominal pain and fever are usual.

He looks well but is in considerable discomfort. His temperature is 37.2°C, and his pulse is 75 per minute. Other than mild seborrhoeic dermatitis of the chest wall, there are no abnormal dermatological findings. His abdomen moves well with respiration, and there is no tenderness or guarding; neither the liver nor the spleen is palpable. There is significant enlargement (>1 cm in diameter) of the posterior cervical, axillary, and inguinal lymph nodes that are not tender. The external genitalia and the perianal region appear normal. During anoscopy, a copious mucopurulent discharge is found within the distal rectum. The rectal mucosa is edematous with loss of the normal vascular pattern. The mucosa bleeds easily, and several small ulcers, about 5 mm in diameter are noted. These inflammatory changes, however, do not extend beyond the rectosigmoid junction.

34.2 How Do the Clinical Findings Aid the Differential Diagnosis?

Generalized lymph node enlargement is a feature of HIV infection, and its finding here may reflect this and not superadded infection such as syphilis. Seborrhoeic dermatitis is common among HIV-infected individuals. The absence of perianal ulceration argues against, but does not exclude, a diagnosis of primary anorectal herpes. The anoscopy findings confirm proctitis. The sexually transmitted organisms shown in Table 20.1 (Case 20) cause proctitis that is generally confined to the distal 12–15 cm of the rectum. Inflammatory changes extending more proximally would alert the physician to a diagnosis of proctocolitis, as may occur in infection with Shigella spp., Campylobacter spp, and Entamoeba histolytica, the causative organism of amoebic dysentery.2

Specimens are taken for the diagnosis or exclusion of gonococcal and chlamydial infections as described in Case 4A Gram-stained smear of rectal material shows many polymorphonuclear leucocytes, but Gram-negative diplococci are not identified. As LGV proctitis is a possible diagnosis, the microbiology laboratory is alerted to this possibility and if chlamydiae are identified by a nucleic acid amplification assay, genotyping is requested. Material from the rectal ulcers is obtained using a cotton wool-tipped applicator stick and sent in viral transport medium for the detection of herpes simplex virus DNA (seeCase 16). A further sample from the ulcers is sent for testing for T. pallidum DNA by a polymerase chain reaction. In addition, serological tests for syphilis are undertaken, and as 3 months had elapsed since his most recent HIV evaluation, blood is obtained for routine hematological and biochemical tests, the CD4+ T-cell count, HIV plasma viral load, and screening for hepatitis C virus infection.

34.3 What Is Your Immediate Management of This Case?

In this case, the symptoms are of a severity that empirical treatment is indicated (Table 34.1).

Table 34.1.

Antimicrobial drug regimens for the empirical treatment of moderate-to-severe distal proctitis caused by sexually transmitted infections (The 2007 European Guideline [International Union Against Sexually Transmitted Infections/World Health Organization] on the management of proctitis, proctocolitis, and enteritis caused by sexually transmitted pathogens).

Ceftriaxone 250 mg as a single intramuscular injection

OR

Cefotaxime 100 mg as a single intramuscular injection

OR

Cefixime 400 mg as a single oral dose

OR

Cefuroxime axetil 1000 mg as a single oral dosea

PLUS

Doxycycline 100 mg twice daily by mouth for 21 days

OR

Tetracycline 500 mg four times per day by mouth for 21 days

OR

Erythromycin base 500 mg four times per day by mouth for 21 days

PLUS

Valaciclovir 500 mg twice daily by mouth for 5–10 days

aSecond-line oral therapy.

Although Gram-negative diplococci are not seen in the smear, this test has a sensitivity of only between 70 and 80%, and the regimen used should therefore include an agent to treat gonococcal infection.

As herpetic proctitis cannot be excluded on clinical grounds, it is justified to include valaciclovir in the drug regimen.

Frank is treated with ceftriaxone, doxycycline, and valaciclovir, and he re-attends the clinic 1 week later. His symptoms have improved considerably. The results of the laboratory tests are now available (Table34.2).

Table 34.2.

Results of laboratory tests.

Investigations

Result

Microbiology

 

NAATa for Chlamydia trachomatis

POSITIVE: genotype L2a

NAATa for Neisseria gonorrhoeae

NEGATIVE

PCRb for herpes simplex virus

NEGATIVE

PCRb for Treponema pallidum

NEGATIVE

Serological tests for syphilis

VDRLc: POSITIVE, titer 512

TPPAd: POSITIVE, titer >5120

Anti-treponemal IgM:

POSITIVE

Anti-HCVe

NEGATIVE

Biochemical tests on serum

 

Bilirubin

9 μmol/L (normal <17 μmol/L)

Alanine aminotransferase (ALT)

708 Units/L (normal range 5–30 Units/L)

Alkaline phosphatase

161 Units/L (normal range 25–110 Units/L)

CD4 + T-cell count

243 per mm3

Plasma HIV viral load

86,000 per mL

aNucleic acid amplification test.

bPolymerase chain reaction.

cVenereal Diseases Research Laboratory test.

d Treponema pallidum particle agglutination assay.

eHepatitis C virus.

34.4 How Do You Interpret These Results?

The detection of a C. trachomatis LGV genotype strongly supports the diagnosis of LGV proctitis. Although most infected individuals have symptoms and signs of a severe proctitis, some patients, probably a minority, with LGV rectal infection are symptomless and finding in this case may be co-incidental.

The genotypes of LGV attack lymphatic and sub-epithelial tissues rather that the epithelial cells as occurs with infection with the oculogenital genotypes of C. trachomatis. The former invade the epithelial cells within which multiplication occurs with the release of elementary bodies from the basal cell surface to invade the underlying tissues. As a result, there is destruction of the mucosa and transmural inflammation of the rectal wall. There is also involvement of the regional lymph nodes. The histology as noted in rectal biopsies (Fig. 34.1) is similar to that found in Crohn’s disease: infiltration of the lamina propria with lymphocytes, plasma cells, and histiocytes with crypt abscess and granuloma formation. Indeed many cases in the recent western European outbreak of LGV proctitis were initially treated for inflammatory bowel disease for several months before the true diagnosis was made.

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Figure 34.1.

Granulomatous proctitis caused by lymphogranuloma venereum, genotype L-2.

The serological findings indicate that Frank has become re-infected with syphilis: (a) there is seroconversion from a negative VDRL test to one with a high titer, (b) the TPPA shows a significant increase in titer (more than eight-fold), and (c) the anti-treponemal IgM test is positive. (The non-treponemal tests for syphilis VDRL or the rapid plasma regain [RPR] are the most sensitive for detecting re-infection with T. pallidum). In some HIV-infected individuals high VDRL or RPR titers are found. Although the anti-treponemal IgM EIA was positive in this man, in at least one-third of re-infections this test is negative.

Syphilis can cause a distal proctitis, and, despite a negative PCR for T. pallidum, it cannot be entirely excluded as contributing to the disease process in this case.

The plasma enzyme tests of liver function are abnormal with a hepatitic pattern – the ALT is raised disproportionately compared with the alkaline phosphatase. Among HIV-infected individuals, abnormal liver function tests may be caused by a variety of opportunistic infections, including cytomegalovirus and Cryptosporidium spp. In this case, however, the patient is only mildly immunocompromised, and such opportunistic infections would be unusual. As he had been vaccinated previously against hepatitis A, this is an unlikely cause of hepatitis in this case. However, an anti-hepatitis A IgM test should be requested. Re-activation of hepatitis B infection has been documented in HIV-infected individuals, and repeat serological testing and a specific HBV DNA NAAT should be requested. Although the antibody test for hepatitis C virus is negative, early infection with that virus cannot be excluded as a cause of his abnormal liver function tests. A polymerase chain reaction assay should be requested to detect HCV RNA as it is detectable in the plasma several weeks before an antibody response is observed. Early syphilis, particularly secondary disease, can be associated with hepatitis. In most case reports, however, the alkaline phosphatase is disproportionately elevated compared with the transaminases. Non-Hodgkin’s lymphoma and Kaposi’s sarcoma can also affect the liver, and such conditions need to be considered in the differential diagnosis.

There are several explanations for the decline in the CD4+ T-cell count in the peripheral blood, and the increased viral load compared 3 months previously. A change in the assay systems used may account for these changes. Alternatively, intercurrent infection, for example, with syphilis, can result in these changes. A particular concern is that he has become infected with another strain of HIV. As he has had unprotected receptive and insertive anal intercourse with multiple partners, this is a plausible explanation. It is known that individuals who become super-infected with HIV progress more rapidly to a severely immunocompromised state. There is also the possibility of infection with drug-resistant virus, making the choice of future antiretroviral therapy more difficult.

Hepatitis C virus RNA is detected in a plasma sample. A genotypic resistance assay performed on his plasma HIV shows mutations likely to confer resistance to the non-nucleoside reverse transcriptase inhibitors nevirapine and efavirenz.

Hepatitis C virus is usually acquired by the parenteral route, particularly among infecting drug users. The risk of sexual transmission has generally been considered to be low, with the possible exception of HIV-infected individuals in whom the concentration of HCV in plasma and genital secretions may be high. However, outbreaks of acute hepatitis C have been described among men who have sex with men in whom other risk factors, such as injecting drug use, have not been identified. Many of these men have had multiple sexual partners, have had unprotected receptive and insertive anal intercourse, have participated in “fisting,” have been treated previously for STIs, and have participated in group sex. This patient matches such a profile. Mucosal damage from “fisting” and LGV has been shown to facilitate transmission of this virus.

The absence of resistance mutations in the baseline sample and lack of a history of taking antiretroviral medication, either prescribed or illicitly, suggests that he has subsequently acquired resistant virus. In some circles, antiretroviral drugs are shared in the mistaken notion that they will prevent acquisition of HIV during unprotected sexual contact. This does not appear to be the case here.

Frank continues on treatment with doxycycline for 21 days. Although doxycycline is a treatment for syphilis, cure is less certain than with penicillin, and he is therefore treated with benzathine penicillin (see Case 11).3 He is referred to a hepatologist for management of his acute hepatitis C. Follow-up to ensure cure of the LGV and syphilis is arranged. In addition, further one-to-one counseling about his high-risk behavior is undertaken.

Footnotes

1

“Fisting” (synonyms: fist fornication, brachioproctic eroticism) is the insertion of a closed hand through the anal canal into the distal rectum.

2

Infection with the non-pathogenic protozoan Entamoeba dispar that resembles Entamoeba histolytica microscopically is common among men who have sex with men. It is therefore important to differentiate the species before making an erroneous diagnosis of amoebiasis in a man with intestinal symptoms.

3

Some physicians treat early syphilis in an HIV-infected patient as if he/she had neuosyphilis: procaine penicillin G 2 g by intramuscular injection daily for 17 days PLUS probenecid 500 mg four times per day by mouth for 17 days.