Treatment of severe forms of paracoccidioidomycosis: is there a role for corticosteroids?

Abstract

Despite their immunosuppressive effects, corticosteroids have long been used as adjunct therapy (aCST) in the treatment of infectious diseases. The rationale is that in certain infections it is necessary to decrease the exacerbated host's inflammatory response, which can otherwise result in tissue damage and organ dysfunction. In fact, a major concern in treating paracoccidioidomycosis (PCM) is the host's intense inflammatory response to Paracoccidioides brasiliensis, which can be further intensified by antifungal therapy. Depending on its localization, this immunological phenomenon may be life threatening or result in permanent sequels, as is the case for some patients with cerebral or laryngeal involvement. However, the literature on aCST in paracoccidioidomycosis treatment is scarce and as a result we present our recent experience in the management of four patients with severe PCM manifestations, i.e., cerebral paracoccidioidal granuloma, laryngeal stenosis, compressive abdominal mass, and exacerbated inflammatory response with tissue destruction. In addition to the antifungal therapy, these patients required aCST, which probably promoted their clinical improvement and/or prevented serious complications. We suggest that aCST: (a) can potentially help in the management of selected cases of severe forms of PCM, particularly when there is a risk of acute complications, and (b) that it can be used safely provided that the risk-benefit ratio is carefully weighed. Well-controlled, prospective studies of aCST in the treatment of severe cases of paracoccidioidomycosis are needed to better define its role in the management of PCM.

Brazilian guidelines for the clinical management of paracoccidioidomycosis

“…Although scarce, there is evidence in the literature that some patients with PCM may benefit from the use of corticosteroids concomitantly with antifungal treatment 98 . Patients that have been shown to benefit from this approach often have intense inflammation, either in the ganglia or central nervous system, serious lesions of the larynx or trachea, and lung lesions resulting in respiratory insufficiency.…”

Paracoccidioidomycosis

“…Although the mycosis develops mainly in patients with low CD4 + lymphocyte counts (< 200 cells/μl), response to antifungal therapy is, in general, similar to that observed in non-immunocompromised patients with PCM [12,29,57]. Additionally, in severe cases, corticosteroids appear beneficial [71]. Despite the immunodeficiency, specific antibodies are detected in over 70 % of the cases [72].…”

“…In severe cases, particularly in those with the acute type disease, the antifungal agents may not have sufficient time to act and thus fatalities can occur [1,26,57,59]. Use of corticosteroids has been advocated in the presence of important tissue inflammation [71].…”

Cyclopalladated Compound 7a Induces Apoptosis- and Autophagy-Like Mechanisms in Paracoccidioides and Is a Candidate for Paracoccidioidomycosis Treatment

“…Although there are some therapeutic options available for PCM treatment, which include sulfone derivatives, amphotericin B, azoles, and terbinafine, the optimal treatment for patients with severe and disseminated forms of the disease is amphotericin B, despite its known toxic adverse effects, mainly nephrotoxicity (1). During usually long antifungal therapies, tissue damage, fibrosis, and impairment of organ functions are intensified (46), with high rates of noncompliance, relapses, and sequelae. Although alternative therapeutic approaches have been described, such as DNA vaccine (47) and nanostructured drug formulations (48), there is still a need for new drugs that are able to decrease the treatment time, toxic side effects, and sequelae.…”