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Abstract A three‐year‐old boy presented with fever, maculopapular rash involving palms and soles, and hyponatremia two weeks following a tick bite. Empiric doxycycline that he was on was discontinued following negative initial rickettsial serology based on the non‐endemicity of Rocky Mountain spotted fever (RMSF) in Northeast Ohio. He demonstrated high inflammatory markers and met the criteria for hemophagocytic lymphohistiocytosis (HLH). With a working diagnosis of macrophage activation syndrome secondary to presumed systemic‐onset juvenile idiopathic arthritis (soJIA), he received HLH‐directed therapy. Rising antibody titers in convalescent sera established the diagnosis of RMSF. The patient recovered completely with HLH directed therapy and re‐institution of doxycycline. This is the first pediatric case report of Rickettsia rickettsii induced HLH demonstrating a favorable outcome despite modified therapy.

With the discovery of novel diseases and pathways, as well as a new outlook on certain existing diseases, cellular trafficking disorders attract a great deal of interest and focus. Understanding the function of genes and their products in protein and lipid synthesis, cargo sorting, packaging, and delivery has allowed us to appreciate the intricate pathophysiology of these biological processes at the molecular level and the multi-system disease manifestations of these disorders. This article focuses primarily on lymphocyte intracellular trafficking diseases from a clinician’s perspective. Familial hemophagocytic lymphohistiocytosis is the prototypical disease of abnormal vesicular transport in the lymphocytes. In this review, we highlight other mechanisms involved in cellular trafficking, including membrane contact sites, autophagy, and abnormalities of cytoskeletal structures affecting the immune cell function, based on a newer classification system, along with management aspects of these conditions.

Daratumumab, a CD38 monoclonal antibody that has been FDA-approved to treat multiple myeloma, has acquired popularity and is used off-label for both auto- and alloantibody mediated disorders, particularly in refractory/resistant circumstances. Much of the published data for its use in pediatric blood disorders has been in post-transplant autoimmune cytopenias. Here we describe three patients in whom daratumumab was used outside of post-transplant autoimmune cytopenias, highlighting further potential uses of this medication.