Valérie Badot

Anti DNA antibodies are not restricted to a specific pattern of fluorescence on HEp2 cells

Abstract Background: Antinuclear autoantibody determination relies on an initial screening step using immunofluorescence on HEp2 cells. This may be followed by anti-deoxyribonucleic acid (DNA) determination, if the fluorescence of nuclei is homogeneous. We assessed the validity of a restricted algorithm and compared this to a more comprehensive algorithm that accepted any nuclear pattern as a positive indicator. Methods: Our retrospective study analyzed routine results for antinuclear antibodies (ANA) and their anti-DNA identification [double stranded nuclear DNA (ds-DNA), membrane associated DNA (mDNA), nucleosomes] for 58 systemic lupus erythematosus (SLE) patients (690 sera). We included 158 patients with systemic or organ-specific autoimmune diseases (888 sera), 44 with viral disease (88 sera), 34 cancer patients (89 sera) and 111 patients with inflammation that served as controls (122 sera) for a total of 1187 samples. Results: 1) Anti DNA antibodies are not associated only with a homogeneous pattern, but can also be seen with a speckled or nucleolar pattern. 2) The observed pattern is typical for a particular patient rather than for a specific pathology. 3) A homogeneous pattern does not necessarily indicate SLE, nor does the presence of circulating anti DNA antibodies. 4) Determination of various specificities of anti DNA antibodies, whatever the immunofluorescent pattern, increases the sensitivity and specificity for SLE. Conclusions: If diagnosis is based exclusively on a homogenous pattern, preselection would have missed identification of SLE as high levels of anti DNA antibodies were also associated with speckled or nucleolar pattern. Clin Chem Lab Med 2009;47:543–9.

Hidradenitis suppurativa (HS): An unrecognized paradoxical effect of biologic agents (BA) used in chronic inflammatory diseases

BACKGROUNDnParadoxical hidradenitis suppurativa (HS) induced by biologic agents (BA) is scarcely reported.nnnOBJECTIVEnWe sought to describe the clinical characteristics and outcome of patients developing paradoxical HS under BA.nnnMETHODSnThis was a multicenter nationwide retrospective study asking physicians to report all cases of HS, confirmed by a dermatologist, occurring during treatment of an inflammatory disease by a BA.nnnRESULTSnWe included 25 patients (15 inflammatory rheumatism, 9 Crohns disease, 1 psoriasis) treated by 5 BA (adalimumabxa0=xa012, infliximabxa0=xa06, etanerceptxa0=xa04, rituximabxa0=xa02, tocilizumabxa0=xa01). Median duration of BAxa0exposure before HS onset was 12 (range 1-120) months. Patients were mostly Hurley stage I (nxa0=xa013) or II (nxa0=xa011). Simultaneously to HS or within 1xa0year, 11 patients developed additional inflammatory diseases, including paradoxical reactions (psoriasisxa0=xa09, Crohns diseasexa0=xa03, alopecia areataxa0=xa01, erythema elevatum diutinumxa0=xa01). Complete improvement of HS was more frequently obtained after BA discontinuation or switch (nxa0=xa06/10, 60%) rather than maintenance (nxa0=xa01/14, 7%). Reintroducing the same BA resulted in HS relapse in 3 of 3 patients.nnnLIMITATIONSnRetrospective nature and lack of complete follow-up for some patients are limitations.nnnCONCLUSIONnHS is a rare paradoxical adverse effect of BA, but fortuitous association cannot be excluded in some cases. We observed a trend toward better outcome when the BA was discontinued or switched.

Two years follow-up of an open-label pilot study of treatment with rituximab in patients with early diffuse cutaneous systemic sclerosis

Abstract Objectives: Following results in open-label studies of rituximab in patients with systemic sclerosis, a Belgian three-centre initiative was launched to explore safety and efficacy of rituximab in early, diffuse cutaneous systemic sclerosis (dcSSc). Methods: Open-label study of 17 patients with early dcSSc, treated with two courses of rituximab, at month 0 and 6. Clinical examination, lung function testing, echocardiography, disease activity score (DAS) and functional status were performed at baseline and over 24 months of follow-up. Results: Modified Rodnan skin score (MRSS) changed significantly over time, with a mean of 25.5 (standard deviation [SD] 6.0) at baseline to 12.6 (SD 5.1) at month 24 (Mixed Model Analysis [MMA] p < 0.0001), which is a decrease of 51% at month 24 vs. baseline. DAS showed significant decrease over the total study period, with a score of 4.1 (SD 1.7) at baseline to 1.5 (SD 1.8) at month 24 (MMA p < 0.0001). Additionally, this was significant at all time points vs. baseline, both for MRSS and DAS. Internal organ status remained clinically stable throughout the study period. No statistically significant differences compared to baseline were found at the follow-up time points. Seven serious adverse events took place, all except for one, considered unrelated to study medication. Conclusions: This is the first multicentre Belgian collaboration investigating potential efficacy of rituximab in early dcSSc. Rituximab appears to be safe and tolerable and it may have beneficial effects on skin involvement, on overall disease activity and on stabilization of internal organ status in early dcSSc.