Isolated Nocardiosis, an Unrecognized Primary Immunodeficiency?

Abstract

Nocardiosis is an infectious disease caused by the gram-positive bacterium Nocardia spp. Although it is commonly accepted that exposure to Nocardia is almost universal, only a small fraction of exposed individuals develop the disease, while the vast majority remain healthy. Nocardiosis has been described as an "opportunistic" disease of immunocompromised patients, suggesting that exposure to the pathogen is necessary, but a host predisposition is also required. Interestingly, increasing numbers of nocardiosis cases in individuals without any detected risk factors, i.e., without overt immunodeficiency, are being reported. Furthermore, a growing body of evidence have shown that selective susceptibility to a specific pathogen can be caused by a primary immunodeficiency (PID). This raises the question of whether an undiagnosed PID may cause nocardiosis affecting otherwise healthy individuals. This review summarizes the specific clinical and microbiological characteristics of patients with isolated nocardiosis published during the past 30 years. Furthermore, it gives an overview of the known human immune mechanisms to fend off Nocardia spp. obtained from the study of PIDs and patients under immunomodulatory therapies.

Keywords: Nocardia; PID; immune response; infection; isolated nocardiosis; nocardiosis; primary immunodeficiencies.

Figure 1

Date, gender, age, and geographical distribution of patients with isolated nocardiosis. (A) Year of publication of patients with isolated nocardiosis since 1987. Around 2010 the number of case series published increased in detriment of individual case reports. In most of those case series, we could not extract the data from individual patients so we excluded them from our analysis. Therefore, the number of cases continuously increases with time despite the graph shows a decrease after 2010. (B) Countries where patients from A were reported. (C) Gender distribution of patients with isolated nocardiosis. (D) Age distribution of patients with isolated nocardiosis published since 1987. The information for these figures was obtained from the references (–297).

Figure 2

Microbiology, treatment, and kind of infection in patients with isolated nocardiosis. (A) Type of infection of patients with isolated nocardiosis published since 1987. Unknown represent patients with disseminated nocardiosis in which the primary site of infection was not identified. (B,C) Organs, where the disease disseminated in patients with cutaneous nocardiosis in (B) and pulmonary nocardiosis in (C). Others, represent organs with a frequency of <5% in this group. (D) Distribution of Nocardia species in the different types of nocardiosis at a frequency of <5%. Others represent the species present. (E) Primary treatment of patients with isolated nocardiosis. (F) Therapy that was used in combination with TMP-SMX. Others represent the use of drugs at a frequency of <5%. The information for these figures was obtained from the references (–297).