Multiplex serum cytokine monitoring as a prognostic tool in rheumatoid arthritis.

OBJECTIVE: Early optimized therapy of rheumatoid arthritis (RA) results in improved outcomes. The initiation of optimized therapy is hindered by the difficulty of early diagnosis and the limitations of current disease activity and therapeutic response assessment tools. Identifying patients requiring early combination DMARD/biologic therapy is currently a significant clinical challenge given the lack of definitive prognostic criteria. Since cytokines are soluble intracellular signaling molecules that modulate disease pathology in RA, we tested the recent conjecture that en mass serum cyto-kine measurement and monitoring will provide a useful tool for effective therapeutic management in RA. METHODS: We assayed the levels of 16 serum cytokines in 18 RA patients treated prospectively with methotrexate and from 18 unaffected controls. Specific mechanistic aspects of inflammatory pathology in the periphery could be discerned on a patient-specific basis from patients' serum cytokine profiles, information that may aid in the design of anti-cytokine biologic therapy. A serum Cytokine Activity Index (CAI) was also created using multi-variant analysis methods. RESULTS: Distinct cytokines were significantly elevated in RA patients relative to controls, and three distinct clusters with correlations to disease activity were identified. The Cytokine Activity Index correlated well with the therapeutic res-ponse; responders and non-responders in this cohort were distinguishable as early as one month post initiation of methotrexate therapy, well before clinical assessments of response are commonly completed. CONCLUSION: Clinical assessment tools could be derived from this approach that may provide a means to continually track patients, allowing intervention strategies to be better evaluated on a patient-specific basis and to identify residual cytokine activity that could be used to guide combination therapy.

Rhabdomyolysis, acute renal failure, and disseminated intravascular coagulation in a man with sickle cell trait.

We have described a patient with sickle cell trait who, after severe exertion, had rhabdomyolysis, acute renal failure, and disseminated intravascular coagulation secondary to sickling. Autopsy showed the characteristic histopathology of sickle cell crisis and not terminal sicklemia.

Streptococcus anginosus-constellatus infection of the sternoclavicular joint.

We describe the first reported instance of sternoclavicular pyarthrosis caused by Streptococcus anginosus-constellatus. Infections caused by this organism are unusual in a nonimmunocompromised host. Common conditions predisposing to sternoclavicular joint infection were not present. A possible mechanism for the infection is offered.