Serena Colafrancesco

Markedly increased IL-18 liver expression in adult-onset Still’s disease-related hepatitis

OBJECTIVES First, to investigate the prevalence of liver involvement in adult-onset Stills disease (AOSD) Italian patients; secondly, to measure serum IL-18 concentration and correlate its level to other inflammatory markers and disease activity; and thirdly to characterize the expression level and the cellular source of IL-18 in the liver of a patient with AOSD with hepatitis. METHODS The clinical charts of 41 consecutive Italian AOSD patients were evaluated with special attention to liver involvement. Serum levels of IL-18 were measured in 21 patients. Finally, the case of a 33-year-old woman with hepatitis where a liver biopsy was obtained and sections stained with antibodies against IL-18 and CD68 is described in detail. RESULTS Of the 41 AOSD patients, 32 and 39% displayed increased AST level or ALT level, respectively, generally normalizing with steroid treatment, while 41% had evidence of hepatosplenomegaly. Circulating IL-18 levels were significantly higher in those with active disease compared with 85 controls. A correlation was observed between IL-18 serum level and disease activity, serum ferritin level and neutrophil count. IL-18 concentration was markedly increased in the patient with active hepatitis. Intense IL-18 expression was detected within the liver parenchyma and double staining with IL-18 and CD68 clearly showed colocalization of the cytokine with the macrophage marker. CONCLUSION Macrophage-derived IL-18 might play a central role in the pathogenesis of AOSD. IL-18 serum level is higher in patients with active AOSD and its local, rather than systemic, expression may be responsible for tissue damage in some target organs, such as liver.

Presentation and diagnosis of adult-onset Still’s disease: the implications of current and emerging markers in overcoming the diagnostic challenge

Adult-onset Still’s disease (AOSD) is a known cause of fever of unknown origin. It is characterized by a triad of symptoms: spiking fever (>39°C), salmon-colored rash and arthritis/arthralgia. On a predisposing genetic background, several conditions may act as trigger for disease and among these, infectious agents are the most important. Nowadays, a dichotomous view of AOSD has been introduced which distinguishes this entity in two subsets according to the clinical features and laboratory aspects: systemic or articular. As AOSD is a diagnosis of exclusion, specific biomarkers able to facilitate differential diagnosis are needed. A number of possible biomarkers have been proposed that will be discussed in detail in this review: ferritin, IL-18, procalcitonin, s100 proteins and sCD163.

Cryoglobulinemia in Sjögren Syndrome: A Disease Subset that Links Higher Systemic Disease Activity, Autoimmunity, and Local B Cell Proliferation in Mucosa-associated Lymphoid Tissue

Objective. To compare systemic disease activity by validated tools, i.e., the European League Against Rheumatism Sjögren Syndrome Disease Activity Index (ESSDAI) and the Clinical ESSDAI (ClinESSDAI) scores, between primary Sjögren syndrome (pSS) with positive serum cryoglobulins and pSS without serum cryoglobulins. Methods. There were 825 consecutive patients with pSS who were retrospectively evaluated. Results. The ESSDAI and the ClinESSDAI scores were significantly higher in cryoglobulin-positive patients (p < 0.0001, for both scores). Cryoglobulinemia was significantly associated with these domains: constitutional (p = 0.003), lymphadenopathy (p = 0.007), glandular (p = 0.0002), cutaneous (p < 0.0001), peripheral nervous system (p < 0.0001), hematological (p = 0.004), and biological (p < 0.0001). Conclusion. Cryoglobulin-positive patients show the highest systemic activity in pSS.