Tuesday, 24 January 2012

Quiz











This man who has sex with men had no history of similar attacks of this painful condition in the anal area before. What is the most likely diagnosis? How to confirm it? Does a concomitant HIV infection affect your management? If it does, explain how? Standard STI screening has ensued.


Short and long answers are provided below as comments.






   This page was last updated in February 2012.

5 comments:

  1. Short answer:

    *First anal/perianal herpes simplex episode

    *Real-time polymerase chain reaction (PCR) is the preferred laboratory test to confirm the diagnosis (swabs from lesions including vesicle fluid) with virus typing to differentiate between HSV-1 and HSV-2.

    *Yes it does. In the absence of combination antiretroviral therapy (ART), first episode anogenital herpes may be severe and prolonged with risk of progressive, multifocal and coalescing mucocutaneous anogenital lesions. Moreover, serious and potentially life-threatening systemic complications, such as fulminant hepatitis, pneumonia, neurological disease and disseminated infection have been reported. Prompt initiation of HSV therapy is recommended if herpes is suspected clinically. If new lesions are still forming after 3-5 days, a repeat viral culture with susceptibility testing should be performed and the dose of HSV therapy increased (enhanced treatment) e.g. aciclovir 400 mg five times daily for 10 days. Some including the BNF recommend the enhanced treatment from the start in any HIV infected patient. In severe cases, initiation of therapy with aciclovir 5-10 mg/kg body weight IV every 8 hours may be necessary. Induction therapy should be continued intravenously for 2-7 days, or until clinical improvement, and followed by oral antiviral therapy to complete a minimum of 10 days total treatment.

    Aciclovir-resistant strains [usually Thymidine Kinase (TK)-deficient strains] have been found in around 5-7% isolates from genital herpes lesions in HIV-infected persons. Aciclovir resistance is confirmed if isolates require aciclovir concentrations >1-3 mg/L for inhibition. Thymidine Kinase (TK)-deficient strains (HSV TK, is responsible for initial phosphorylation of acyclovir to its active form) are less likely to be associated with the development of latency; hence, subsequent clinical reactivations of genital herpes are often caused by aciclovir-sensitive isolates. They may cause serious local and systemic disease in severely immunocompromised individuals. TK-deficient strains are susceptible to foscarnet and cidofovir which do not depend upon TK.

    Both topical 1% foscarnet cream and 1% cidofovir gel have been shown to produce significant benefits in lesion healing, pain reduction and virological effect in aciclovir resistant herpes but systemic therapy with either foscarnet or cidofovir is generally preferred to treat aciclovir resistant herpes in those with HIV infection. Cidofovir is administered with oral probenecid and adequate pre-hydration to reduce the risk of nephrotoxicity. It may be effective in aciclovir-resistant infections that are also resistant to foscarnet. Note that probenecid inhibits the renal tubular secretion of cidofovir, and this reduction in the renal elimination of cidofovir reduces the incidence of its nephrotoxicity and it is actually recommended that probenecid should always be used concurrently with cidofovir.

    The relevant drug interactions should be considered.

    It should be noted that anogenital herpes, including chronic erosive lesions, may occur as a manifestation of the immune reconstitution inflammatory syndrome (IRIS) following ART. HSV associated IRIS may be unresponsive to previously effective anti-herpes viral therapy in the absence of increased antiviral resistance. Management is difficult in such circumstances but topical cidofovir may be effective.

    ReplyDelete
  2. Long answer:

    *First anal/perianal herpes simplex episode. First episode might be primary (no pre-existing antibodies to HSV-1 or HSV-2), or non-primary. Recurrent episode is the recurrence of clinical symptoms due to reactivation of pre-existent HSV-1 or HSV-2 infection after a period of latency.

    *Real-time polymerase chain reaction (PCR) is the preferred laboratory test to confirm the diagnosis (swabs from lesions including vesicle fluid) with virus typing to differentiate between HSV-1 and HSV-2.

    PCR-based methods allow less stringent conditions for sample storage and transport than virus culture and new real-time PCR assays (the amplified DNA is detected as the reaction progresses in real time and thus enabling quantification of the target DNA molecules) are rapid, most sensitive and highly specific.

    HSV isolation in cell culture is the routine diagnostic method in some places (swabs from vesicle fluid, best source, with sensitivity up to 90%, ulcers with sensitivity up to 70% and crusted lesions with sensitivity up to 25%). However, it must be noted that failure to detect HSV by PCR (and by culture) does not necessarily indicate an absence of HSV infection, because viral shedding is intermittent.

    Accurate type-specific HSV IgG serologic assays (Western blot) are based on the HSV-specific glycoprotein G2 (HSV-2) and glycoprotein G1 (HSV-1). Older assays that do not accurately distinguish HSV-1 from HSV-2 antibody (despite claims to the contrary) remain on the market; providers should specifically request serologic type-specific glycoprotein G (gG)-based assays when serology is performed for their patients. IgM tests are NOT type-specific and in type specific serology the response may take up to 12 weeks to develop. Because nearly all HSV-2 infections are sexually acquired, the presence of type-specific HSV-2 antibody implies anogenital infection.

    ReplyDelete
  3. Long answer (cont.):

    *Yes it does. In the absence of combination antiretroviral therapy (ART), first episode anogenital herpes may be severe and prolonged with risk of progressive, multifocal and coalescing mucocutaneous anogenital lesions. Moreover, serious and potentially life-threatening systemic complications, such as fulminant hepatitis, pneumonia, neurological disease and disseminated infection have been reported. Prompt initiation of HSV therapy is recommended if herpes is suspected clinically. If new lesions are still forming after 3-5 days, a repeat viral culture with susceptibility testing should be performed and the dose of HSV therapy increased (enhanced treatment) e.g. aciclovir 400 mg five times daily for 10 days. Some including the BNF recommend the enhanced treatment from the start in any HIV infected patient. In severe cases, initiation of therapy with aciclovir 5-10 mg/kg body weight IV every 8 hours may be necessary. Induction therapy should be continued intravenously for 2-7 days, or until clinical improvement, and followed by oral antiviral therapy to complete a minimum of 10 days total treatment.

    There is epidemiological synergy between HSV and HIV infections, increasing transmission of both. Clinical and subclinical reactivations of genital herpes are more frequent in patients with HIV infection and may lead to persistent and progressive anogenital mucocutaneous lesions, especially with CD4 cell counts < 50 cells/uL and optimising the control of HIV replication with ART is of fundamental importance for the management of the recurrent episodes.

    Aciclovir-resistant strains [usually Thymidine Kinase (TK)-deficient strains] have been found in around 5-7% isolates from genital herpes lesions in HIV-infected persons. Aciclovir resistance is confirmed if isolates require aciclovir concentrations >1-3 mg/L for inhibition. Thymidine Kinase (TK)-deficient strains (HSV TK, is responsible for initial phosphorylation of acyclovir to its active form) are less likely to be associated with the development of latency; hence, subsequent clinical reactivations of genital herpes are often caused by aciclovir-sensitive isolates. They may cause serious local and systemic disease in severely immunocompromised individuals. TK-deficient strains are susceptible to foscarnet and cidofovir which do not depend upon TK.

    Both topical 1% foscarnet cream and 1% cidofovir gel have been shown to produce significant benefits in lesion healing, pain reduction and virological effect in fully aciclovir resistant herpes but systemic therapy with either foscarnet or cidofovir is generally preferred to treat fully aciclovir resistant herpes in those with HIV infection (partially resistant strains may sometimes be successfully treated with high dose intravenous aciclovir). Cidofovir is administered with oral probenecid and adequate pre-hydration to reduce the risk of nephrotoxicity. It may be effective in aciclovir-resistant infections that are also resistant to foscarnet. Note that probenecid inhibits the renal tubular secretion of cidofovir, and this reduction in the renal elimination of cidofovir reduces the incidence of its nephrotoxicity and it is actually recommended that probenecid should always be used concurrently with cidofovir.

    The relevant drug interactions should be considered.

    It should be noted that anogenital herpes, including chronic erosive lesions, may occur as a manifestation of the immune reconstitution inflammatory syndrome (IRIS) following ART. HSV associated IRIS may be unresponsive to previously effective anti-herpes viral therapy in the absence of increased antiviral resistance. Management is difficult in such circumstances but topical cidofovir may be effective.

    ReplyDelete
  4. NB The word "they" in the sentence "they may cause serious local and systemic disease in severely immunocompromised individuals", refers to TK-deficient strains.

    ReplyDelete
  5. Note that:

    Primary HSV type 1 infections (i.e. in a previously seronegative individual) occur mainly in infants and young children, when they are usually minimal and often subclinical but if symptomatic the severity is generally greater than in recurrences. Anogenital primary disease is more commonly symptomatic than oral. Primary anogenital herpes in some countries is equally likely to be caused by HSV-1 as by HSV-2. HSV type 2 infections occur mainly after puberty, and are often transmitted sexually. Because nearly all HSV-2 infections are sexually acquired, the presence of type-specific HSV-2 antibody implies anogenital infection.

    ReplyDelete

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Main Works of Reference List (The first eight are my top favourites)

  • British National Formulary
  • British National Formulary for Children
  • Guidelines (BAD - BASHH - BHIVA - Uroweb)
  • Oxford Handbook of Genitourinary Medicine, HIV, and Sexual Health
  • Oxford Handbook of Medical Dermatology
  • Rook's Textbook of Dermatology
  • Simple Skin Surgery
  • Weedon's Skin Pathology
  • A Concise Atlas of Dermatopathology (P Mckee)
  • Ackerman's Resolving Quandaries in Dermatology, Pathology and Dermatopathology
  • Andrews' Diseases of the Skin
  • Andrology (Nieschlag E FRCP, Behre M and Nieschlag S)
  • Bailey and Love's Short Practice of Surgery
  • Davidson's Essentials of Medicine
  • Davidson's Principles and Practice of Medicine
  • Fitzpatrick's Colour Atlas and Synopsis of Clinical Dermatology (Klaus Wolff FRCP and Richard Allen Johnson)
  • Fitzpatrick’s Dermatology in General Medicine
  • Ganong's Review of Medical Physiology
  • Gray's Anatomy
  • Hamilton Bailey's Demonstrations of Physical Signs in Clinical Surgery
  • Hutchison's Clinical Methods
  • Lever's Histopathology of the Skin
  • Lever's Histopathology of the Skin (Atlas and Synopsis)
  • Macleod's Clinical Examination
  • Martindale: The Complete Drug Reference
  • Oxford Handbook of Clinical Examination and Practical Skills
  • Oxford Textbook of Medicine
  • Practical Dermatopathology (R Rapini)
  • Sexually Transmitted Diseases (Holmes K et al)
  • Statistics in Clinical Practice (D Coggon FRCP)
  • Stockley's Drug Interactions
  • Treatment of Skin Disease: Comprehensive Therapeutic Strategies
  • Yen & Jaffe's Reproductive Endocrinology