RESEARCH HIGHLIGHTS Manifestations of Churg–Strauss

RESEARCH HIGHLIGHTS www.nature.com/clinicalpractice/rheum

adenovirus were reduced in size and weight patients. The authors suggest that a better (P <0.005) and contained fewer synoviocytes understanding of the pathogenetic mechanisms and mononuclear cells. The number of apoptotic behind the differences in clinical manifesta- cells in tissues treated with the FASLG adeno- tions might be useful in the development virus was increased 15–20-fold compared of future therapeutic strategies. with controls. Rebecca Doherty Although adenoviral vectors are immuno- Original article Sablé-Fourtassou R et al. (2005) genic—as evidenced by a small increase in Antineutrophil cytoplasmic antibodies and the Churg– the frequency of apoptotic cells after injection Strauss syndrome. Ann Intern Med 143: 632–638 with the control adenovirus—and, therefore, not likely to be optimal for gene transfer in humans, this study highlights the potential of Serum antibodies and mortality molec ular surgery for the successful treatment rate in patients with rheumatoid of RA and paves the way for further refinement arthritis of the technique. Rebecca Doherty Diagnosis of rheumatoid arthritis (RA) has Original article Zhang H et al. (2005) Elimination of historically depended upon clinical manifesta- rheumatoid synovium in situ using a Fas ligand ‘gene scalpel’. tions of the disease. Identification of factors Arthritis Res Ther 7: R1235–R1243 that could predict severe disease and death is a high priority, as it would enable treatment to be initiated earlier. Presence and/or serum levels Manifestations of of rheumatoid factor (RF), antineutrophil cyto- Churg–Strauss syndrome might plasmic antibodies (ANCA) and the antibody vary according to ANCA status against cyclic citrullinated peptide (anti-CCP) are all associated with disease severity; anti-CCP A prospective, multicenter study has suggested can be detected in serum even before the onset that patients with Churg–Strauss syndrome of clinical symptoms. Sihvonen et al. are the who test positive for antineutrophil cytoplasmic first to examine whether these factors are also antibodies (ANCAs) might be phenotypically associated with RA-related death. different to those who test negative for these Using baseline sera from 604 patients with RA antibodies. No previous large studies have who had participated in a 1988 Finnish study of evaluated the association of ANCA status with renal and urinary tract comorbidity, the investi- clinical characteristics and outcome of patients gators tested for the presence of RF (n = 604), with this rare, small-vessel vasculitis. RF isotypes (IgA RF, IgG RF and IgM RF, A total of 112 patients with recently diag- n = 206), anti-CCP (n = 184) and ANCA (n = 200). nosed Churg–Strauss syndrome from 63 clini- A mortality cutoff date of 31 August 1999 was cal centers in France, Belgium, Latvia and set, and government statistics revealed 160 the UK, were enrolled in a therapeutic trial of patients (26%) had died. Multivariate analysis cyclophosphamide. At study entry (between showed that positive RF status (P = 0.011) and December 1995 and December 2002), patients high levels of IgA (P = 0.003) and IgM (P = 0.006) were assessed for the presence of ANCAs RF isotypes were predictors of death, but in serum and for clinical symptoms and anti-CCP and ANCA levels were not. manifesta tions of Churg–Strauss syndrome. These results indicate that patients with RA ANCAs were identified in 43 patients (38%). who have high immunologic activity are at an When ANCA-positive patients were compared increased risk of death. As mean duration of with ANCA-negative patients, they were more RA in these patients was 15 ± 10 years when the likely to have peripheral neuropathy (84% study began, studies measuring immunologic versus 65%) and renal manifestations (35% activity at diagnosis are recommended, in order versus 4%), but were less likely to have fever to confirm the predictive value of these findings. (30% versus 55%) and cardiac manifestations Katherine Sole (12% versus 49%). Original article Sihvonen S et al. (2005) The predictive The therapeutic trial is ongoing, and there- value of rheumatoid factor isotypes, anti-cyclic citrullinated peptide antibodies, and antineutrophil cytoplasmic fore no information is yet available about the antibodies for mortality in patients with rheumatoid outcome of treatment in the two groups of arthritis. J Rheumatol 32: 2089–2094

62 NATURE CLINICAL PRACTICE RHEUMATOLOGY FEBRUARY 2006 VOL 2 NO 2