Mycoplasma pneumoniae (M. pneumoniae) is a significant cause of pulmonary and extrapulmonary infections in children and adults. Before its identification, M. pneumoniae was the subject of numerous studies by Eaton et al. in which they concluded that an “Eaton agent” was the cause of primary atypical pneumonia, distinct from pneumococcal pneumonia [1]. Today, M. pneumoniae is a principal cause of community-acquired pneumonia, characteristically causing alveolar infiltrates with neutrophils and lymphocytes [2].

In addition to its established role in the pathogenesis of pneumonia, M. pneumoniae is responsible for several extrapulmonary manifestations, even when pneumonia is not present. These extrapulmonary manifestations include cardiovascular, dermatological, gastrointestinal, hematologic, musculoskeletal, urogenital, and ophthalmologic disease [3,4]. Narita et al. proposed that the pathogenesis of these manifestations may occur through three mechanisms: (a) direct, in which the bacterium induces upregulation of cytokines, including IL-18 (a regulator of T helper cells) and IL-8 (a mediator of neutrophilic inflammation); (b) indirect, in which the bacterium induces autoimmunity through cross-reaction between bacterial antigens and self-antigens; or (c) vasculopathy involving thrombosis or the development of immune complex-mediated vasculitis, with or without systemic hypercoagulability [4,5].

Previously, M. pneumoniae induced rash and mucositis (MIRM) was understood to be on a spectrum of mucocutaneous diseases including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and erythema multiforme (EM) [[6], [7], [8], [9]]. In 2015, Canavan et al. were the first to make a distinction between MIRM and SJS/TEN or EM [10]. In that systematic review of 95 articles with 202 cases of MIRM, the authors identified near universality of oral mucositis (94%) and the presence of ocular mucositis in 82% of cases. Their study distinguished MIRM from SJS/TEN as having (a) a younger age predominance, (b) predominance of mucosal involvement with a characteristic vesiculobullous and/or targetoid eruption, (c) variable though relatively sparse cutaneous involvement, and (d) excellent prognosis. The prevailing hypothesis is that MIRM is caused by cloning of B cells which thereafter produce immunoglobulins that lead to cutaneous immune complex deposition, promoting activation of the complement cascade [11]. This mechanism is distinct from that of EM and SJS/TEN, which are type IV hypersensitivity reactions and mediated by Fas-ligand cytotoxicity. Of note, EM and SJS/TEN are also clinically distinct entities from each other [12].

Although ophthalmologic findings have been reported as a manifestation in MIRM, the literature is somewhat sparse in reports and discussion around the ocular presentation and consequences of MIRM. After analyzing 36 studies of 99 patients, in this systematic review, we discuss the clinical presentation, disease course, and outcomes of MIRM with ophthalmologic involvement and synthesize a treatment approach based on current evidence and experience.