The case of a 40-year old woman with pleuropericarditis associated with prior C. pneumoniae CAP has been described. Cardiac complications after or during Chlamydia infection (either C. pneumoniae, psittaci or trachomatis) have been described through the literature, though cases are rare, and mechanisms understudied. Most data are derived from non-human studies [12], while the association of Chlamydia infection with cardiac complications has been based mainly on cross-sectional studies with single antibody measurements, rather than multiple follow-up antibody titers and kinetics, like in our case [18, 19]. Cardiac involvement seems to be even rarer when it comes to C. pneumoniae infection [2,3,4,5,6,7,8,9,10,11]. Previous reports associated with M. pneumoniae atypical CAP have also been reported and seem to be more common through the literature [20].
A systematic review of the literature was conducted independently by two investigators (GED, EF) to detect similar cases. Search algorithm and flowchart of included studies are shown in Fig. 2. Similar case reports are rare in the literature. Five studies have been identified [7,8,9,10,11]. Main characteristics of included studies are described in Table 1. The origin of the studies was Europe and Asia, while the prognosis of patients involved was good in most cases. The study by Oztek Celebi et al. [7] was the only one where more than one antibody measurements were ordered (two in total), in order to investigate a similar case involving a 13-year-old boy with pericardial and bilateral pleural effusions. However, antibody titers did not clearly follow the expected kinetics. Our study is unique in this context as more measurements of chlamydial antibodies were ordered (three in total) with typical fluctuations indicating past infection. Regarding treatment choices among the similar studies identified, most patients have been treated mainly with macrolides but there seems to be a lack of evidence regarding the use of colchicine and/or corticosteroids in their treatment (Table 1).
In our case the patient presented to our hospital with pleuropericarditis five weeks after hospitalization for CAP in another hospital, where she was treated with ceftriaxone and moxifloxacin without any report on causative pathogen. The kinetics of the IgM and IgG antibodies against C. pneumoniae indicated the latter as the causative microorganism (Fig. 1, Additional File 1). The patient was administered moxifloxacin in her first hospitalization. This is considered as an acceptable first-line empiric treatment for most patients with community-acquired pneumonia since the etiology is usually unknown at the time of diagnosis. The patient responded and was discharged. However, macrolides represent the first-line option for C. pneumoniae [21]. Whether an initial course with macrolides could avert the subsequent pericarditis is not known. So far, the documentation and diagnosis of C. pneumoniae infection are often suboptimal in terms of standardization and methodological validation. Respiratory tract samples cultures and polymerase chain reaction (PCR) seem to be the most accurate methods, yet high cost and practical problems render them not widely applicable. In the present case, PCR or cultures of the respiratory tract samples would have not probably contributed to the diagnosis due to the delayed occurrence of the serositis after CAP. The delayed emergence of serositis after the infection could indicate indirect (namely autoimmune) mechanisms. Serologic evaluation is the most frequently used method, either by microimmunofluorescence or ELISA. Standard diagnostic criteria for serologic methods apply, such as the fourfold increase of antibody titers within 4–6 weeks after symptoms onset [1, 22]. Unfortunately, we did not have baseline values at symptoms onset and during her first hospitalization. However, the patient’s C. pneumoniae antibodies kinetics seem to be in line with our assumption of a recent C. pneumoniae CAP. IgM titers presented a peak in our first measurement and then followed a gradual decline, while IgG titers continued to increase within the next 4–6 weeks. (Fig. 1) [1, 22, 23].
Multiple possible mechanisms of cardiac damage have been suggested and could be divided into non-autoimmune and autoimmune mediated pathways [12, 14, 24, 25]. Concerning non-autoimmune pathways, C. pneumoniae-infected macrophages seem to present greater adherence to the endothelium and tend to degenerate easier to foam cells in the presence of LDL cholesterol [14, 23]. This suggested mechanism implicates that Chlamydia infection could play a role as a cardiovascular disease (CVD) risk factor for atherosclerosis [14, 24]. Autoimmune mechanisms on the other side have been reported to act mainly via molecular mimicry phenomenon [12, 25]. In this case, chlamydial proteins mimic host self-proteins and may trigger systematic autoimmune reactions [12, 25]. The impressive clinical and biochemistry patient’s response to corticosteroids and the lack of any clinical or laboratory response whenever antibiotics were initiated, is indicative of an autoimmune pathogenetic mechanism.
Our study presents several limitations regarding the diagnostic documentation of patient’s prior chlamydial infection. Appropriate diagnostic evaluation during the patient’s first hospitalization, including PCR/cultures of respiratory tract samples, as well as baseline antibody titers, was unavailable; however, such a diagnostic work-up is not routinely recommended for uncomplicated CAP. It should be mentioned that the patient presented a rather late serositis a few weeks after her discharge and remission of her initial symptoms. Indeed, similar limitations have been encountered in all relevant published studies (Table 1) [7,8,9,10,11]. These ‘inevitable’ limitations are somewhat expected in the setting of everyday clinical practice and real-world medicine. Assessment of antibody kinetics in this study might at least partly counteract some of these limitations. In fact, the etiology of polyserositis was determined on the basis of dynamic changes in antibody levels, the clinical course and the response of the patient to steroid and colchicine therapy, and the exclusion of other etiologies. It should be taken into consideration that the aim of this case presentation was to describe a probable rather than definite causative relation of chlamydial infection and pericarditis, and most importantly to raise awareness among doctors regarding the early consideration of this entity in differential diagnosis of similar cases.
In conclusion, C. pneumoniae-associated CVD or autoimmune implications may be more frequent and important than generally thought. Clinicians should be aware of atypical causes in the absence of profound and obvious explanations. Nonsteroidal anti-inflammatory drugs and colchicine constitute the mainstay of therapy in cases of pericarditis. Corticosteroids should be considered in cases of contraindications and/or failure of the above-mentioned regimens or in cases of autoimmune-related serositis.
