ABSTRACT
Hemophagocytic lymphohistiocytosis (HLH) is characterized by dysregulated immune activation. Primary HLH involves hereditary deficits in cytotoxic lymphocytes while secondary HLH is triggered by extrinsic factors. The HLH-2004 criteria are widely used for clinical diagnosis, yet their specificity for HLH or their ability to differentiate primary from secondary disease is unclear, potentially leading to inappropriate treatment. We describe several cases where fulfillment of HLH-2004 criteria obscured the diagnoses of underlying malignancies and delayed curative management. These issues are remedied without waiting for genetic testing results through an alternative diagnostic approach using flow cytometry-based immunologic assays and a thorough investigation for malignancy.
Subject(s)
Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphoma/complications , Lymphoma/diagnosis , Paraneoplastic Syndromes/diagnosis , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Young AdultABSTRACT
Ankylosing spondylitis (AS) is not fully explained by inflammatory processes. Clinical, epidemiological, genetic, and course of disease features indicate additional host-related risk processes and predispositions. Collectively, the pattern of predisposition to onset in adolescent and young adult ages, male preponderance, and widely varied severity of AS is unique among rheumatic diseases. However, this pattern could reflect biomechanical and structural differences between the sexes, naturally occurring musculoskeletal changes over life cycles, and a population polymorphism. During juvenile development, the body is more flexible and weaker than during adolescent maturation and young adulthood, when strengthening and stiffening considerably increase. During middle and later ages, the musculoskeletal system again weakens. The novel concept of an innate axial myofascial hypertonicity reflects basic mechanobiological principles in human function, tissue reactivity, and pathology. However, these processes have been little studied and require critical testing. The proposed physical mechanisms likely interact with recognized immunobiological pathways. The structural biomechanical processes and tissue reactions might possibly precede initiation of other AS-related pathways. Research in the combined structural mechanobiology and immunobiology processes promises to improve understanding of the initiation and perpetuation of AS than prevailing concepts. The combined processes might better explain characteristic enthesopathic and inflammatory processes in AS.
