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castlemans disease
Aug 13, 2008

my son is hiv pos. and he has castlemans disease with kaposi sarcoma.can the virus be spread through kissing from the saliva?ihave grandchildren who he makes a fuss off.should i be concerned?

Response from Dr. Frascino

Hello,

Castleman's disease and Kaposi's sarcoma are two different illnesses, but both are caused by human herpes virus type 8 (HHV-8). HHV-8 is present in saliva. The mode of transmission of HHV-8 remains a topic of debate. I'll reprint some information about Castleman's disease below that addresses your concerns.

Dr. Bob

Incidence Is Rising Among HIV-Infected Patients An Interview With Mark Bower, Ph.D., F.R.C.P.

By Terri Wilder

August 4, 2008

This is Terri Wilder with The Body, and I've just finished watching a presentation by Professor Mark Bower of Chelsea and Westminster Hospital in the United Kingdom. He presented information on Castleman's disease in persons living with HIV.

Could you please tell us what Castleman's disease is

Castleman's disease is a rare lymphoproliferative disorder, which is monotypic -- that is, lambda light chain restricted -- but is not monoclonal. So it's a polyclonal illness. It's really a form of pre-lymphoma, if you like, driven by the human herpesvirus-8 [HHV-8], the same virus that causes Kaposi's sarcoma.

How is it diagnosed?

This is the real problem with Castleman's disease. Even in the best centers, it often takes many months before the diagnosis is made, because people who have HIV and Castleman's disease present with very nonspecific symptoms and signs. They usually have intermittent high fevers and night sweats. They usually have lymph gland enlargement and splenomegaly, and they often have anemia, low albumens and polyclonal hypogammaglobulinemia. None of these individual signs or symptoms is sufficient to establish the diagnosis, and there's a wide differential diagnosis. The only way that you can really make the diagnosis is by doing either a lymph node excisional biopsy, or a splenectomy, if that's the only site of disease. That's why it so frequently takes a long time for the diagnosis to be established in people with HIV.

What is the treatment plan for the person who has been diagnosed with Castleman's disease and HIV?

Following the establishment of a diagnosis of Castleman's disease, there is, as yet, no gold standard best-established treatment. There are no head-to-head, randomized studies of what are the best and most effective agents in the treatment of HIV-associated multicentric Castleman's disease, and the majority of the information on the management comes from relatively small published series from two or three centers, to be honest.1

It does appear, though, if you talk to most of the clinicians treating a sizable number of patients with Castleman's disease, that the optimal treatment involves a combination of single-agent chemotherapy, usually with an agent called etopocide, and monoclonal antibody therapy with anti-CD20 monoclonal antibody, known as rituximab [brand name: Rituxan]. In addition, there is also some data to suggest that where the spleen is massively enlarged, removing the spleen surgically improves the outcome.2,3

Following that sort of treatment, the patient should achieve a clinical remission, where all their symptoms have gone. There is some debate as to whether additional treatment at that time can reduce the risk of relapse. Some centers have tried using maintenance rituximab monoclonal antibody therapy,4 and other centers have tried using anti-HHV-8 (anti-herpesvirus) agents, like ganciclovir [brand name: Cytovene] and valganciclovir [brand name: Valcyte], both as treatment and, more recently, as maintenance therapy.5 But really, there's no established best treatment at present.

What is the percentage of people living with HIV who have been diagnosed with Castleman's disease?

All I can tell you about is the incidence of Castleman's within our cohort at Chelsea and Westminster Hospital.6 That's the only data there is about incidence of Castleman's disease. That's a prospective cohort of 11,000 patients, 52,000 patient-years of follow-up. So it's probably the second largest, or perhaps the largest, HIV single-center cohort in Europe. We have looked at the incidence of Castleman's disease in that cohort over the last 25 years, and the overall incidence is 4 per 10,000 patient-years. Now, let's just compare that so that you've got an idea: That's about 1/50 of the incidence of Kaposi's sarcoma, which is the disease caused by the same virus.

What is the prognosis for patients living with HIV when they are diagnosed with Castleman's disease?

Until perhaps the turn of this millennium, the best data on that was from Eric Oksenhendler's group in Paris, which suggested that the median survival following a diagnosis of HIV-associated Castleman's disease was 14 months.7 However, there have been recent dramatic improvements in the therapy of Castleman's with the recognition of the need to give chemotherapy and immunotherapy. In most more recent studies, the survival rates are very, very much higher than that. For example, there is a study that we published recently in the Annals of Internal Medicine, of 20-ish patients treated with rituximab at the first diagnosis of Castleman's disease, and the two-year survival was 95%.8 Only a single patient had passed away, and actually, that patient was already on intensive care by the time the diagnosis was established.

What I suspect, although I cannot quote you a manuscript showing it, is that the majority of patients who achieve a remission of their Castleman's disease will, at some point in the future, relapse. So unlike most HIV-associated cancers, this is a disease that keeps coming back and will need retreatment. Often the treatment-free intervals are several years, but I think these patients need very careful monitoring, particularly with HHV-8 viral loads, to look for early relapses, so that we don't spend six months establishing the diagnosis of relapse, in the way that we spend six months establishing the initial diagnosis.

Is Castleman's disease sexually transmitted?

The transmission of the virus, Kaposi's sarcoma herpesvirus, between individuals, is an area of some debate. If you look at studies from Africa, it's clear that a small percentage of infants under the age of 3 have acquired this virus, and it is suggested that some of that may be vertical transmission, mother-to-child transmission, of HHV-8.9,10 There's then some horizontal nonsexual transmission, particularly amongst young children and, later on, one suspects, sexual transmission.11

Now, then, let's look at which body fluids this virus is most prevalent in. By far, the highest levels are present in the saliva. A bit like Epstein-Barr virus, this is a virus that's probably transmitted in nurseries and crèches, what with children dribbling and all the rest, and also, subsequently, through saliva exchange in kissing. So just like Epstein-Barr virus. Yes, you could say that kissing was a sex act, but not always, perhaps.

Thank you so much for your time.

This transcript has been lightly edited for clarity. \ References

Newlon JL, Couch M, Brennan J. Castleman's disease: three case reports and a review of the literature. Ear Nose Throat J. July 2007;86(7):414-418.

Waterston A, Bower M. Fifty years of multicentric Castleman's disease. Acta Oncol. December 2004;43(8):698-704.

Lerza R, Castello G, Truini M, et al. Splenectomy induced complete remission in a patient with multicentric Castleman's disease and autoimmune hemolytic anemia. Ann Hematol. April 1999;78(4):193-196.

Gérard L, Bérezné A, Galicier L, et al. Prospective study of rituximab in chemotherapy-dependent human immunodeficiency virus-associated multicentric Castleman's disease: ANRS 117 CastlemaB Trial. J Clin Oncol. August 1, 2007;25(22):3350-3356.

Stebbing J, Pantanowitz L, Dayyani F, Sullivan RJ, Bower M, Dezube BJ. HIV-associated multicentric Castleman's disease. Am J Hematol. June 2008;83(6):498-503.

Krell J, Tuthill M, Campbell V, et al. The incidence of HIV-associated multicentric Castlemans disease. In: Program and abstracts of the XVII International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract MOAX0102.

Oksenhendler E, Duarte M, Soulier J, et al. Multicentric Castleman's disease in HIV infection: a clinical and pathological study of 20 patients. AIDS. January 1996;10(1):61-68.

Bower M, Powles T, Williams S, et al. Brief communication: rituximab in HIV-associated multicentric Castleman disease. Ann Intern Med. December 18, 2007;147(12):836-839.

Malope BI, Pfeiffer RM, Mbisa G, et al. Transmission of Kaposi sarcoma-associated herpesvirus between mothers and children in a South African population. J Acquir Immune Defic Syndr. March 1, 2007;44(3):351-355.

Mbulaiteye S, Marshall V, Bagni RK, et al. Molecular evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus in Uganda and K1 gene evolution within the host. J Infect Dis. May 1, 2006;193(9):1250-1257.

Pica F, Volpi A. Transmission of human herpesvirus 8: an update. Curr Opin Infect Dis. April 2007;20(2):152-156.

-------------------------------------------------------------------------------- This article was provided by The Body PRO, and is a part of the publication The XVII International AIDS Conference.



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