RESUMO
OBJECTIVES: Whipple's disease (WD) results from infection of the bacteria Tropheryma whipplei (TW). This disease is characterized by macrophage infiltration of intestinal mucosa and primarily affects Caucasian males. Genetic studies of host susceptibility are scarce. Nucleotide-binding oligomerization domain containing protein 2 (NOD2) is an innate immune sensor, resides mainly in monocytes/macrophages and contributes to defense against infection and inflammatory regulation. NOD2 mutations are associated with autoinflammatory diseases. We report the association of NOD2 mutations with TW and WD for the first time. METHODS: A multicenter, retrospective study of three patients with WD was conducted. Patients received extensive multidisciplinary evaluations and were cared for by the authors. NOD2 and its association with infection and inflammation were schematically represented. RESULTS: All patients were Caucasian men and presented with years of autoinflammatory phenotypes, including recurrent fever, rash, inflammatory arthritis, gastrointestinal symptoms, and elevated inflammatory markers. All patients underwent molecular testing using a gene panel for periodic fever syndromes and were identified to carry NOD2 mutations associated with NOD2-associated autoinflammatory disease. Despite initially negative gastrointestinal evaluations, repeat endoscopy with duodenal tissue biopsy ultimately confirmed WD. After initial ceftriaxone and maintenance with doxycycline and/or hydroxychloroquine, symptoms were largely controlled, though mild relapses occurred in follow up. CONCLUSION: Both NOD2 and TW/WD are intensively involved in monocytes/macrophages. WD is regarded as a macrophage disease. NOD2 leucin rich repeat-associated mutations in monocytes/macrophages cause functional impairment of these cells and consequently may make the host susceptible for TW infection and WD, especially in the setting of immunosuppression.
RESUMO
Anti-MDA5 (Melanoma differentiation-associated protein 5) myositis is a rare subtype of dermatomyositis (DM) characterized by distinct ulcerative, erythematous cutaneous lesions and a high risk of rapidly progressive interstitial lung disease (RP-ILD). It has been shown that SARS-CoV-2 (COVID-19) replicates rapidly in lung and skin epithelial cells, which is sensed by the cytosolic RNA-sensor MDA5. MDA5 then triggers type 1 interferon (IFN) production, and thus downstream inflammatory mediators (EMBO J 40(15):e107826, 2021); (J Virol, 2021, https://doi.org/10.1128/JVI.00862-21 ); (Cell Rep 34(2):108628, 2021); (Sci Rep 11(1):13638, 2021); (Trends Microbiol 27(1):75-85, 2019). It has also been shown that MDA5 is triggered by the mRNA COVID-19 vaccine with resultant activated dendritic cells (Nat Rev Immunol 21(4):195-197, 2021). Our literature review identified one reported case of MDA5-DM from the COVID-19 vaccine (Chest J, 2021, https://doi.org/10.1016/j.chest.2021.07.646 ). We present six additional cases of MDA5-DM that developed shortly after the administration of different kinds of COVID-19 vaccines. A review of other similar cases of myositis developing from the COVID-19 vaccine was also done. We aim to explore and discuss the evidence around recent speculations of a possible relation of MDA5-DM to COVID-19 infection and vaccine. The importance of vaccination during a worldwide pandemic should be maintained and our findings are not intended to discourage individuals from receiving the COVID-19 vaccine.
