Adult-onset Still's disease with concurrent thrombotic microangiopathy: Observations from pooled analysis for an uncommon finding.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder that is characterized by quotidian fevers, arthritis, and an evanescent rash. Occurrence of concurrent thrombotic microangiopathy (TMA) in AOSD is rare. The treatment aspects of TMA in AOSD are actively being debated. METHODS: Medline search using MeSH terms and snowballing yielded a total of 29 articles with co-occurrence of AOSD and thrombotic thrombocytopenic purpura (TTP) including our own. Pooled data were synthesized for descriptive analysis. RESULTS: Median age was 35 years with a majority of females (68.96%). A majority of these studies/patients were either Asian (34.48%) or Caucasian (31.03%). Concurrent TMA at the time of AOSD diagnosis was seen in 65.51% patients. Only 3/29 patients had ADAMTS13 level less than 10%, consistent with TTP and 3/29 were diagnosed with hemolytic uremic syndrome (HUS). The remainder were diagnosed clinically. Complication rate was high, and 15/29 (51.72%) patients died or had permanent neurological/renal/vision/gangrenous complications. Median and mean ferritin peak was observed to be higher (7458 and 12 349, respectively) in patients who either died/had partial remission, compared to those who had complete response (3257 and 10 899, respectively), p = .829. CONCLUSIONS: A majority of patients with AOSD-associated TMA either died or had permanent complications. TMA was diagnosed alongside AOSD in 65% patients, while the rest developed TMA during the course of their disease. Blurred vision may precede TMA and could help risk-stratify high-risk AOSD patients clinically. Glycosylated ferritin remains low several weeks to months after disease remission and may be used to monitor severity of disease process. Further studies are necessary to confirm the existing vascular endothelial growth factor hypothesis in AOSD-associated TMA.

Molecular classification and therapeutics in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) encompasses a wide variety of disease states that have to date been subgrouped and characterized based on immunohistochemical methods, which provide limited prognostic value to clinicians and no alteration in treatment regimen. The addition of rituximab to CHOP therapy was the last leap forward in terms of treatment, but regimens currently follow a standardized course when disease becomes refractory with no individualization based on genotype. Research groups are tentatively proposing new strategies for categorizing DLBCL based on genetic abnormalities that are frequently found together to better predict disease course following dysregulation of specific pathways and to deliver targeted treatment. Novel algorithms in combination with next-generation sequencing techniques have identified between 4 and 7 subgroups of DLBCL, depending on the research team, with potentially significant and actionable genetic alterations. Various drugs aimed at pathways including BCR signaling, NF-κB dysfunction, and epigenetic regulation have shown promise in their respective groups and may show initial utility as second or third line therapies to patients with recurrent DLBCL. Implementation of subgroups will allow collection of necessary data to determine which groups are significant, which treatments may be indicated, and will provide better insight to clinicians and patients on specific disease course.