Syndromes de reconstitution immunologique au cours des mycoses systémiques chez les patients infectés par le VIH

Abstract

Antiretroviral treatment of immunodeficiency virus (HIV) infection induces the restoration of immune responses and has led to a decrease in mortality and in the frequency of opportunistic infections. However, restoration is sometimes deleterious and the cause of the immune reconstitution syndrome (IRS). This syndrome includes all unusual manifestations related to excessive immune response against antigens of an infectious or non infectious agent. Signs and symptoms of IRS are polymorphous. Their diagnosis is difficult as there is no absolute criterion and all other possible etiologies have to be ruled out, such as a relapse of infection, intolerance to drugs, other infections and poor compliance to treatment. Pathogenesis was partially elucidated; it combines a reconstitution of both acquired and innate immune responses and inflammatory phenomena which are under the control the of host's genetic polymorphism. Two different forms of IRS can be seen, they share the clinical manifestations of inflammation. One is the excessive immune response against a micro-organism diagnosed and controlled by an anti-infectious treatment, with a paradoxical recurrence or aggravation of signs and symptoms of the disease being treated. The other form is an excessive immune response against an infectious agent, which is viable but quiescent, revealing a latent infection, which was not previously diagnosed. The occurrence of an IRS after introduction of antiretroviral treatment is well known particularly with tuberculosis, atypical mycobacterial infections and cytomegalovirus infections. It is not uncommon in fungal infections particularly in cryptococcosis; its occurrence in histoplasmosis is less frequent. In fungal infections the most common presentation of IRS is the paradoxical aggravation of lesions after introduction of antiretroviral treatment despite an efficacious antifungal treatment. In one study the incidence of IRS in cryptococcosis was 28%. Among the main manifestations of IRS in cryptococcosis the most frequent are aseptic meningitis, inflammatory or necrotic adenopathies, often mediastinal — with fever in half the cases—; pulmonary, cerebral intramedullary and subcutaneous abscesses have been reported. Manifestations of IRS occur with a median time of 3 months after starting antiretroviral treatment. In histoplasmosis the main manifestations are inflammatory adenopathies, occasionally liver abscesses; uveitis and arthritis have been reported. The diagnosis of IRS relies on negative culture of clinical samples for fungi, a marked increase in the CD4 lymphocyte cell count (close to 200/mm 3), a HIV viral load which is often undetectable and lack of other etiology. Pathologic aspects in favor of IRS are epithelioid granulomas with giant cells and rare intracellular fungal elements. These features are usually observed in immunocompetent hosts and thus confirm the functional reconstitution of immune response. There is no consensus regarding the management of IRS. Immune reconstitution being the goal of therapy, if possible antiretroviral treatment should not be stopped. Spontaneous outcome is favorable in about half the cases. The use of anti-inflammatory drugs may be necessary, particularly corticosteroids, which allow rapid clearance of symptoms. The benefit of corticosteroids must be weighted against the risk of opportunistic infections in immuno-suppressed patients. Surgical treatment of abscesses may be needed. The main risk factors for IRS in cryptococcosis are dissemination of the infection at diagnosis and the introduction of antiretroviral treatment less than one month after initiation of antifungal treatment. A delay in initiation of antiretroviral treatment may decrease the incidence of IRS; however this strategy may facilitate the emergence of opportunistic infections and be hazardous, particularly for the most severely immuno-suppressed patients. IRS makes the management of HIV infection more difficult. A better knowledge of this syndrome should improve the prognosis and allow a strategy for its prevention.