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HIV-Associated Diarrhea and Pulmonary Kaposi's - 9/5/2012

posted Sep 5, 2012, 12:10 PM by Rohit Das   [ updated Dec 27, 2012, 6:57 AM by Purnema Madahar ]

The topic of the day revolved around HIV-AIDS, specifically around an important GI manifestation – diarrhea. HIV-associated diarrhea is a very important topic, for several reasons.

  • Firstly, it’s common – Prior to the advent of HAART, chronic diarrhea was the presenting symptom in up to 20% of newly diagnosed AIDS patients. Even after the advent of HAART, though the spectrum of etiology has changed (we’ll get to that later), the incidence of diarrhea has not, with studies reporting numbers of around 10-20%
  • More importantly, chronic diarrhea leads to significant morbidity – decreased quality of life scores in HIV patients, increased health service utilization, and depending on the organism/region of the GI tract involved – malabsorption, malnutrition, and increased mortality. 

So, let’s address some important clinical pearls about diarrhea that help to identify the responsible organism and region of GI tract involvement.        

  • Small bowel disease is characterized by large volume, watery diarrhea with associated malabsorption and weight loss. Large bowel disease, on the other hand, is more characterized by small volume, frequent, often painful bowel movements, and generally does not cause malabsorption and weight loss. Anorectal disease is characterized by tenesmus and difficulty defecating.
  • History oriented around those symptoms, along with a good knowledge of the patient’s HIV history, travel history, sexual history and other exposures can very much narrow a VERY LONG list of potential causes of diarrhea in HIV patients. For example, a small bowel history should point you more towards Crypto, Microsporidia, Giardia, etc., where as a large bowel history is more typical of CMV, HSV, and bacterial causes.
  • The spectrum of what causes of diarrhea in HIV patients is very dependent on their immune status. In patients with AIDS, Cryptosporidia (19%), Microsporidia (19%) and CMV enteritis (20%) are the most common causes.
  • As mentioned in the attached retrospective study, with the advent of HAART, the incidence of opportunistic related causes have markedly decreased, but the incidence of diarrhea has not. This is probably due to the adverse effects of ARVs (particularly protease inhibitors) and the emergence of the evil C. Difficile. Also, HIV itself has been implicated as causing diarrhea due to its effect on small bowel mucosa. 

Diagnosis of diarrhea in HIV patients is actually relatively straightforward. As cited in the Lancet review article, in patients with good CD4 counts, appropriate stool analyses will diagnose up to 80% of cases. In immunocompromised patients, stool analysis and endoscopic examination of the small and large bowel will diagnose up to 90% of cases. Management is supportive (fluids, electrolyte replacement) and directed against the responsible pathogen. As a general rule, ARV therapy is the most effective way to treat opportunistic diseases and prevent relapse. 

The patient presented today also had chest imaging revealing of bilateral infiltrates, in the absence of any respiratory symptoms or rash. Further evaluation via bronchoscopy showed pulmonary Kaposi’s. A brief review:

  • Pathologically, Kaposi’s is due to HHV-8, which is thought to be sexually transmitted. HHV-8 infects vascular endothelial cells, ultimately leading to angioproliferative tumors. However, HHV-8 infection alone is not a potent risk factor for development of KS; HIV co-infection markedly increases risk à in a natural history study of about 800 men with HHV-8 seropositivity, the 10 year probability of developing was KS with HIV/HHV-8 coinfection was 50%, where as no cases occurred in the HIV-negative cohort. The risk of getting KS also correlates with decreasing CD4 count.
  • Epidemiologically, though KS was a known entity since the mid-1800s, the incidence of this disease skyrocketed in the early 1980s. It became a disease of HIV positive men (15-fold greater in men than women), most commonly in the MSM population. During the AIDS epidemic, 40% of homosexual HIV-infected men who received a new diagnosis of AIDS had KS at the time of their presentation (I find this quite alarming…). The advent of HAART has made this a MUCH less common disease, with incidence decreasing from nearly 35 cases per 100,000 people/year in 1980 to only 3 per 100,000 persons/year in the late 90’s.
  • Pulmonary Kaposis’s occurs in about one-third of patients with mucocutaneous involvement, and at autopsy, will be present in about 50% of those patients. Clinically, the presentation is similar to other respiratory problems – dyspnea and cough being the most common presenting symptoms. Very importantly, many patients will present with asymptomatic KS (sorry, couldn’t find good numbers on this), and just an abnormal radiograph, as what occurred with today’s case. Also, pulmonary KS can present without cutaneous involvement, but this is relatively uncommon.
  • Prognosis and natural history of KS is based on a few things, including the extent of tumor involvement, CD4 status, and the presence of other HIV-associated opportunistic illnesses. A summary of this staging classification is provided on Table 2 of the attached review article. Data is a bit conflicting, but patients with extensive Pulmonary KS have a median survival of about 6-10 months.
  • Treatment, via various forms of chemotherapy and ARVs, is palliative and not curative. Though some patients can achieve prolonged remission with combined ARV and chemotherapy (one study showed a five 5-survival of around 35%), the diagnosis remain poor, with median survival being around 1-2 years of treatment.
The advent of ARVs have really changed the spectrum of disease we see in HIV-AIDS, but the Bronx still carries a significant portion of poorly managed AIDS patients. So, for us, knowledge about these otherwise uncommon infectious issues is still very important. Keep on reading!!

 

 

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