S178 Epidemiology of opportunistic infection in Europe

Symposia

-

HIV - Prophylaxis

and Treatment

can influence FcsRIol-dependent antigen presentation, we made the striking observation that significant basophil histamine release was elicited selectively by autoAb-containing CU sera. As a consequence, therapeutic efforts in CU patients should aim to alter the quality of the anti-FcsRIa immune response occurring in this disease. I S174 Immunotherapy of chronic urticaria B.F. O’Donnell. St John’s Institute of Dermatology, St. Thomas

’ Hospital,

London,

England

During active disease 60% of patients with chronic “idiopathic” urticaria (CIU) have circulating histamine releasing-activity (HRA). HRA is due to IgG autoanti-bodies directed against the high-affinity IgE receptor, FceRl (23% of patients) or against IgE (5.5%). A further subset of patients has a mast cell-specific HRA’ . The beneficial effect experienced by patients following plasmapheresis was associated with a reduction in HRA2. Patients with severe CIU and HRA whose disease was poorly responsive to antihistamines were selected for treatment by immunomodulation. A single course of intravenous immunoglobulin (0.4 g/kg per day x 5 days) in 20 patients was followed by complete remission (n = 8) and improvement in disease activity (n = 9). A randomised, double-blind trial of cyclosporin 4 mg/kg per day for 4 weeks showed a significant improvement in u&aria activity (P < 0.000) and visual analogue scores (P = 0.007), in the cyclosporin treated group compared to the placebo group. Immunotherapy is a option in patients with recalcitrant CIU in association with HRA. References [l] Niimi N et al. Jlnvest Dermatol 1996; 106: 100-6. [2] Grattan CEH et al. Lancer 1992; 339: 1078-80.

I S175 Drug therapy for urticaria L. Juhlin. Department of Dermatology, University Uppsala,

Hospital,

Sweden

The less or non-sedative antihistamines are today the most important drugs for the treatment of most types of u&aria where histamine is the main mediator. Their effects and safety profile will be reviewed. Corticosteroids can be used in certain cases. In some physical and chronic urticaria other drugs have been added with variable effect. They include Hz receptor antagonists, calcium channel blockers, anabolic steroids, anticoagulants, B-blockers and antimicrobial drugs. I S176

Inflammatory cells and CD34 expression in chronic urticaria

Gino A. Vena. Postgraduate University

of Bari,

Medical

School

of Dermatology,

Italy

CD34 is a surface protein expressed by hematopoietic stem cells. Several studies have demonstrated that this antigen is also expressed by developing endothelial cells and may be related to angiogenesis. Moreover, it has been hypothesized that it can also act as an adhesion molecule. In non-lesional skin of patients with chronic urticaria (CU)

of Opportunistic

s41

Infections

we described the presence of high amounts of microvessels showing a significant positivity to anti-CD34 monoclonal antibodies, and of inflammatory cells (mast cells, mononuclear and polymorphonuclear cells) at perivascular level. These results might support the existence of a subclinical condition, a sort of status urticariosus, responsible for an aspecific skin hyperreactivity sustained by a decrease of the threshold to stimuli. This hypothesis may be somehow supported by the fact that clinical effects of cyclosporin A, a well-established therapeutical approach to CU, parallel the disappearance of the above mentioned histological and immunohistochemical findings.

HIV - Prophylaxis and I’reatment of Opportunistic Infections S177 El

Advances in the prevention and treatment of cytomegalovirus (CMV) disease

B. Polsky. Memorial NI:

Sloan-Kettering

Cancer

Centel;

New

York,

USA

Cytomegalovirus (CMV) end-organ disease has become one of the most common HIV-associated opportunistic infections, affecting over 40% of HIV-infected individuals at some point during their illness. Although the currently approved drugs (ganciclovir, foscamet and cidofovir) are effective in controlling end-organ disease, relapse is universal, leading to impaired vision and, in some cases, dissemination to the central nervous system. Recent developments in the use of surrogate markers have altered our approach to CMV management, allowing treatment of individuals at highest risk for development of end-organ disease (pre-emptive therapy), rather than waiting for such disease to become clinically apparent, adopting an approach used successfully in transplant patients. Newer, orally bioavailable agents, such as the prodrugs of ganciclovir and cidofovir, lobucavir, and the benzimidazole compound 1263W94, promise to open the way to effective oral therapy for CMV disease. Finally, the recent elucidation of the 3-dimensional structure of the CMV protease opens the prospect of combination therapy aimed at multiple sites in the virus life cycle.

IS178

Epidemiology of opportunistic Europe

Thomas L. Benfield. EuroSIDA Department Hvidovre,

of Infectious Denmark

Diseases,

Coordinating Hvidovre

infection in Centre, Hospital,

2650

In the first decade, Pneumocystis carinii pneumonia was a more frequent diagnosis in northern Europe compared with other regions of Europe. In recent years, the incidence has declined, and regional variations are no longer evident. The main reason being the wide-spread use of effective prophylaxis. Similarly, the incidence of cerebral toxoplasmosis has declined dramatically in recent years. Tuberculosis remains a prominent problem in Spain and Portugal, whereas this infection is under reasonable control in other parts of Europe. In contrast, the prevalence of Mycobac-

S42

Symposia

-

Rosacea

terium avium infection was high in northern Europe but very low in southern Europe throughout the 1980’s. Incidence rates has increased, particularly in patients with CD4 count ~30 cellslul. There is an increasing incidence of Kaposi’s sarcoma from south to north Europe Cytomegalovirus, cryptosporidiosis, cryptosporidiosis and malignant lymphoma show no remarkable regional differences. In conclusion, there are regional differences in disease presentation among HIV-infected patients in Europe, and the epidemiology for several of the complications have changed over time. Sponsored by the Commission of the European Union. I S179 Fungial infections in AIDS William G. Powderly. Washington University, Missouri,

St. Louis

USA

Fungal infections are and important complication of HIV infection and AIDS, varying in their severity from mild disease with mucosal Candida infections to life-threatening fungal meningitis. An important emerging problem has been the appearance of fluconazole-refractory candidiasis in patients with very advanced AIDS. Cryptococcal infection, usually causing meningitis, is the most common invasive fungal infection. Recent trials have established initial amphotericin B plus flucytosine for 2-3 weeks followed by life-long fluconazole as the therapy of choice. The endemic mycoses (histoplasmosis, coccidioidomycosis and penicilliosis) are frequent AIDS-related problems in patients living in these areas, and are also seen in persons who have lived there previously or in HIV-infected patients who travel to the endemic areas. Amphoteticin B remains the initial therapy for the endemic mycosis with the azoles, especially itraconazole, as the suppressive treatment of choice. Although the azole antifungals have been shown to be very effective in preventing fungal infection, their routine use as prophylaxis remains controversial and is not generally recommended. ElSl80

University

of Liverpool,

of Pharmacology UK

USA

Pneumocystis carinii pneumonia (PCP) is still one of the most common life-threatening complications of AIDS. In North America and Western Europe, the incidence of PCP has fallen dramatically in the past 24 months as a result of improved treatment strategies for therapy of HIV infection. In a recently completed study in American patients at high risk for PCP, the event rate decreased approximately 5 fold during the past 2 years. The event rates of other opportunistic infections decreased similarly. Regardless of the dose, trimethoprim-sulfamethoxazole is the superior regimen for prophylaxis of PCP; however, due to high rates of drug intolerance, finding the optimal strategy for PCP prophylaxis remains problematic. Prophylaxis with dapsone and atovaquone, although effective second line agents, is not well tolerated, with fewer than half being able to tolerate these medications for greater than one year. Aerosolized pentamidine remains a third line PCP prophylaxis therapy, primarily because of its limited efficacy and inadequate effect on toxoplasmosis. Newer agents such as dications (pentamidine analogues) need to be developed if their safety and tolerance profile are acceptable.

Rosacea- Recent Advances

Dublin

Abstract not available.

M. Barry. Department

I S182 Update on pneumocystosis R.L. Murphy. Northwestern University, Chicago,

EC. Powell. Mater

Mark Nelson. England

of pharmacoklnetics management of HIV patients

saquinavir, indinavir) would be expected to interact with other drugs, particularly those metabolised by hepatic cytochrome P450 3A e.g. antifungals and macrolide antibiotics. Drugs used to treat 0.1. e.g. rifampicin (T.B.), rifabutin (MAC) may also affect metabolism of the protease inhibitors as a result of enzyme induction. Therefore an appreciation of pharmacokinetics will be required in the treatment of 0.1. in this clinical setting.

I S183 Current concepts of rosacea pathogenesis

Treatment and prophylaxis of Mycobacterium Avium Complex

I S181 Application

- Recent Advances

in the

& Therapeutics,

Treatment of opportunistic infections (0.1.) in HIV patients receiving combination antiretroviral therapy may result in significant drug interactions. Alteration of the pharmocokinetics of the antiretroviral agent(s) and/or the drug(s) used to treat the 0.1. may occur. These kinetic changes will largely result from enzyme induction or enzyme inhibition. For the nucleoside analogues (e.g. zidovudine, lamivudine) few significant interactions will occur and there is no evidence of an effect on the phosphorylation of other antivirals e.g. ganciclovir (CMV) or acyclovir (HSV). The protease inhibitors (e.g. ritonavir,

Misericordiae

Hospital,

Eccles

Street,

7, Ireland

Rosacea is a common dermatosis in which a genetic predisposition is indicated by its frequency in fair skinned Celts. A role for ultra violet light seems apparent from its distribution on contex facial skin and the bald scalp, but recent studies of ultraviolet sensitivity have failed to show specific abnormalities. Demodex Folliculorum thrive on rosacea skin, but successful treatment of rosacea is not paralleled by a decline in the Demodex population. Initial studies appeared to show a higher frequency Helicobacter Pylori infection in rosacea patients, but recent investigation has failed to support this or the release of vasoactive intestinal peptides as pathologic factors. The search continues for the etiology of this facial eruption ElS184 Flushing and rosacea J.K. Wilkin. Rockville, Maryland, USA There is an increased frequency of flushing with rosacea. There is a correlation between severity of ocular rosacea and a ten-