Pathogenesis of extrapulmonary manifestations of Mycoplasma pneumoniae infection with special reference to pneumonia

Although pneumonia has been a hallmark of Mycoplasma pneumoniae infection, it has been revealed that this infection can cause a number of extrapulmonary manifestations in the absence of pneumonia. While the host immune response has been implicated in the pathomechanism of pneumonia, the pathomechanisms of extrapulmonary manifestations remain largely unknown. It is proposed in this review that extrapulmonary manifestations due to M. pneumoniae infection can be classified into three categories; the first is a direct type in which inflammatory cytokines locally induced by lipoproteins contained in the bacterial cell membrane must play a role, the second is an indirect type in which immune modulation such as autoimmunity through cross-reaction between the bacterial cell components and human cells must play a role, and the third is a vascular occlusion type in which vasculitis and/or thrombosis with or without systemic hypercoagulable state induced by the bacterium must play a role. Based on this classification, a literature review was carried out for extrapulmonary manifestations due to M. pneumoniae infection with special reference to pneumonia, including cardiovascular, dermatological, digestive organ, hematological/hematopoietic system, musculoskeletal, sensory organ, and urogenital tract manifestations. Consequently, most extrapulmonary manifestations due to M. pneumoniae infection can be reasonably classified into and explained by one of the three types of pathomechanisms mentioned above. Noticeably in this review, Kawasaki disease and infectious mononucleosis in association with M. pneumoniae infection, which are not unusual in Japan but have seldom been reported from Western countries, are included in the panel of extrapulmonary manifestations due to M. pneumoniae infection.