B. Bienvenu

Diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a systematic review and meta-analysis

PurposeThe aim of this study was to conduct a systematic review and perform a meta-analysis on the diagnostic performances of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) for giant cell arteritis (GCA), with or without polymyalgia rheumatica (PMR).MethodsMEDLINE, Embase and the Cochrane Library were searched for articles in English that evaluated FDG PET in GCA or PMR. All complete studies were reviewed and qualitatively analysed. Studies that fulfilled the three following criteria were included in a meta-analysis: (1) FDG PET used as a diagnostic tool for GCA and PMR; (2) American College of Rheumatology and Healey criteria used as the reference standard for the diagnosis of GCA and PMR, respectively; and (3) the use of a control group.ResultsWe found 14 complete articles. A smooth linear or long segmental pattern of FDG uptake in the aorta and its main branches seems to be a characteristic pattern of GCA. Vessel uptake that was superior to liver uptake was considered an efficient marker for vasculitis. The meta-analysis of six selected studies (101 vasculitis and 182 controls) provided the following results: sensitivity 0.80 [95% confidence interval (CI) 0.63–0.91], specificity 0.89 (95% CI 0.78–0.94), positive predictive value 0.85 (95% CI 0.62–0.95), negative predictive value 0.88 (95% CI 0.72–0.95), positive likelihood ratio 6.73 (95% CI 3.55–12.77), negative likelihood ratio 0.25 (95% CI 0.13–0.46) and accuracy 0.84 (95% CI 0.76–0.90).ConclusionWe found overall valuable diagnostic performances for FDG PET against reference criteria. Standardized FDG uptake criteria are needed to optimize these diagnostic performances.

Risk factors for major infections in Wegener granulomatosis: analysis of 113 patients

Objective: To characterise major infectious complications and analyse potential risk factors in patients with Wegener granulomatosis (WG). Methods: Data from 113 patients with WG (69 male) followed at least once between January 1984 and March 2006 in our internal medicine department, were analysed retrospectively. Results: A total of 35 patients (mean (SD) age at WG diagnosis: 50.2 (13.05) years) developed 53 major infections. Infections were: bronchopneumonias (n = 19), herpes zoster recurrences (n = 9), cellulitis (n = 4), prostatitis (n = 4), spondylodiscitis and septic arthritis (n = 3), digestive tract infections (n = 2), Enterococcus faecalis or Staphylococcus aureus septicaemia (n = 2), viral hepatitis B reactivations (n = 2), post transfusion HIV infection with fatal cerebral toxoplasmosis, oesophageal candidiasis, disseminated herpes simplex and cytomegalovirus infection, cytomegalovirus retinitis, herpetic keratitis, herpetic stomatitis, Serratia sp. node suppuration and fever resolving under broad spectrum antibiotics (n = 1 each). Half of the major infectious episodes occurred within 3 years after WG diagnosis. Eight (7%) patients died, with two (2%) infection-related deaths. Patients diagnosed with WG before 1996 had a significantly higher rate of infection than those diagnosed later (48% vs 24%, p = 0.02). Cyclophosphamide and corticosteroids were independently associated with significantly higher risk of major infection (p<0.05 and <0.001, respectively). All patients treated since 1993 received antipneumocystosis prophylaxis. Conclusion: Cyclophosphamide and corticosteroids were associated with higher risk of infection. Despite systematic cotrimoxazole prophylaxis, major infections, mostly bronchopneumonias and herpes zoster recurrences, were still common in the course of WG.

Biotherapies in inflammatory ocular disorders: Interferons, immunoglobulins, monoclonal antibodies

Biotherapies used in clinical practice for the treatment of ophthalmologic manifestations of systemic diseases include interferons (IFN), intravenous immunoglobulins (IVIG) and monoclonal antibodies (anti-TNF, anakinra, tocilizumab and rituximab). Several open prospective studies have shown the effectiveness of IFN-α (78 to 98% complete remission) for the treatment of severe uveitis in Behcets disease. IFN is capable of inducing prolonged remission and continued after his arrest, in 20-40% of patients. Side effects (flu-like, psychological effects) limit its use in practice. Anti-TNFα (infliximab and adalimumab) represents an attractive alternative therapeutic in severe uveitis refractory to immunosuppressants, especially in Behcets disease. They are almost always (>90% of cases) and rapidly effective but their action is often suspensive. Anti-TNFα requires an extended prescription or takes over from another immunosuppressant once ocular inflammation has been controlled. IVIG are used for the treatment of Kawasaki disease and Birdshot disease. Several open or retrospective studies showed their effectiveness for the treatment of severe and refractory cicatricial pemphigoid. Tolerance of IVIG is good but their efficacy is transient. Rituximab showed an efficacy in few observations of various inflammatory eye diseases (uveitis, scleritis and idiopathic inflammatory pseudo-tumors or associated with granulomatosis with polyangiitis) and cicatricial pemphigoid. The risk of infection associated with this biotherapy limits its use in refractory diseases to conventional therapy. Anakinra (a soluble antagonist of IL-1R) showed interesting results in terms of efficiency in one small open study in Behcets disease. Its safety profile is good and with a quick action that could be interesting for the treatment of severe uveitis.

Treatment of Systemic Necrotizing Vasculitides in Patients Aged Sixty‐Five Years or Older: Results of a Multicenter, Open‐Label, Randomized Controlled Trial of Corticosteroid and Cyclophosphamide–Based Induction Therapy

To investigate a new therapeutic strategy, with rapid corticosteroid dose tapering and limited cyclophosphamide (CYC) exposure, for older patients with systemic necrotizing vasculitides (SNVs; polyarteritis nodosa [PAN], granulomatosis with polyangiitis [Wegneners] [GPA], microscopic polyangiitis [MPA], or eosinophilic GPA [Churg‐Strauss] [EGPA]).

Rheumatoid factor and disease activity are independent predictors of lymphoma in primary Sjögren's Syndrome

To define parameters predictive of lymphoma development in patients with primary Sjögrens syndrome (SS).

Antifungal Therapy of Aspergillus Invasive Otitis Externa: Efficacy of Voriconazole and Review

ABSTRACT Invasive otitis externa (IOE) due to Aspergillus is a rare, potentially life-threatening, invasive fungal infection affecting immunocompromised patients. The invasive process may lead to skull base osteomyelitis with progressive cranial nerve palsies and can result in irreversible hearing and neurological impairment. We report two cases of Aspergillus IOE treated with voriconazole alone and a literature review of antifungal therapy of Aspergillus IOE. Twenty-five patients, including the two described in the present report, were analyzed. Eighteen patients were treated with amphotericin B, and nine of them received itraconazole as an additional agent. Three patients received initial therapy with itraconazole, and one patient was treated with both voriconazole and caspofungin therapy. The two patients in the present report received voriconazole therapy alone with good clinical and biological tolerance despite prolonged treatment. The last patient did not receive antifungal therapy, as the diagnosis was made postmortem. Eighteen patients underwent an initial extensive surgical debridement. The majority of the patients had a favorable outcome, 17 patients experienced a complete recovery, and 6 showed a partial improvement. Both of the patients reported on here had favorable outcomes, and no aggressive surgical debridement was required. Although voriconazole has been shown to be effective for the treatment of invasive aspergillosis, its precise role in the management of Aspergillus IOE had not been documented. These observations demonstrate that voriconazole could be an effective and well-tolerated therapeutic option for the management of Aspergillus IOE.

Is there a place for cyclophosphamide in the treatment of giant-cell arteritis? A case series and systematic review

OBJECTIVE To report on the effectiveness of cyclophosphamide (CYC) to treat glucocorticoid (GC)-dependent giant-cell arteritis (GCA) and/or severe GC-related side effects. METHODS Fifteen patients with GCA and treated with CYC were retrieved from the computerized patient-record system. Glucocorticoid dependence was defined as a prednisone dose of >20mg/day for 6 months or >10mg/day for 1 year in order not to relapse. Response to CYC was defined as improved clinical and biological findings. Remission was defined as a sustained absence (>12 months) of active signs of vasculitis at a daily GC dose of <7.5mg. A literature review searched PubMed for all patients diagnosed with GCA and who received CYC. RESULTS Our 15 patients responded to monthly pulses of CYC, and all experienced a GC-sparing effect, including five patients who discontinued GC long term. At a median follow-up of 43 (range: 14-75) months after CYC, nine (53%) patients were still in remission and six (40%) had relapsed at 6 (3-36) months after the last CYC infusion. Twelve (80%) patients experienced side effects, leading to discontinuation of CYC in two (13%). A literature review retrieved 88 patients who received CYC: 66 for GC-dependent disease, 53 for GC toxicity, and 14 for severe organ involvement. Their median follow-up time was 24 (4-60) months. Among the 88 patients, 74 (84%) were responsive to CYC and 17 (19%) relapsed, although all were receiving a maintenance therapy with immunosuppressive agents (such as methotrexate). Twenty-nine (33%) patients experienced side effects and 11 (12.5%) discontinued treatment. CONCLUSION Cyclophosphamide is an interesting option for GCA patients with GC-dependent disease or with severe GC-related side effects, especially when conventional immunosuppressive agents have failed.

Excessive interleukin‐15 transpresentation endows NKG2D+CD4+ T cells with innate‐like capacity to lyse vascular endothelium in granulomatosis with polyangiitis (Wegener's)

OBJECTIVE Granulomatosis with polyangiitis (Wegeners) (GPA) is a rare systemic vasculitis of unknown etiology. Contribution of T cell-mediated immunity is suggested by the presence of granulomatous inflammation and T cell infiltrates in different tissues. We undertook this study to determine whether CD4+ T cells aberrantly expressing the NKG2D activating receptor might participate in the pathophysiology of the disease. METHODS We performed a detailed phenotype and functional analysis of CD4+ T cells in a cohort of 90 GPA patients (37 with localized GPA and 53 with generalized GPA) in comparison with 39 age-matched controls. RESULTS We observed circulating innate-like CD4+ T cells expressing an assortment of activating natural killer (NK) cell receptors (NKG2D, 2B4, DNAX-associated molecule 1, and some killer cell Ig-like receptors) and their signaling partners. Expansions of NKG2D+CD4+ T cells greater than a critical threshold of 3% yielded 100% specificity for generalized vasculitis versus localized granulomatosis, suggesting their participation in endothelium damage. Excessive interleukin-15 (IL-15) transpresentation through increased expression of IL-15 receptor α (IL-15Rα), together with abnormal expression of major histocompatibility complex (MHC) class I chain-related A protein on monocyte/macrophages, induced abnormal expansion of NKG2D+CD4+ T cells. These cells were primed in vivo to exert direct, MHC-independent cytotoxicity toward microvascular endothelial cells expressing the cognate ligands of NK cell receptors. CONCLUSION Our results suggest that NK cell-like CD4+ T cells might be the driving force of the vasculitis in GPA, and point to IL-15 as an important mediator in the progression of GPA toward generalized vasculitis. IL-15/IL-15Rα antagonists may thus become novel therapeutic tools to decrease the pool of NK cell receptor-positive CD4+ T cells in selected GPA patients.

Infliximab Versus Adalimumab in the Treatment of Refractory Inflammatory Uveitis: A Multicenter Study From the French Uveitis Network

To analyze the factors associated with response to anti–tumor necrosis factor (anti‐TNF) treatment and compare the efficacy and safety of infliximab (IFX) and adalimumab (ADA) in patients with refractory noninfectious uveitis.

Wegener’s Granulomatosis Strictly and Persistently Localized to One Organ Is Rare: Assessment of 16 Patients from the French Vasculitis Study Group Database

Objective. To study the frequency and characteristics of patients with Wegener’s granulomatosis (WG) strictly and persistently localized to one organ. Methods. Retrospective analysis of the French Vasculitis Study Group (FVSG) WG cohort. Results. Sixteen patients (3.2% of the cohort) were identified who had isolated lung nodules, ear-nose-throat, or ocular involvement that did not progress to systemic disease (median followup, 58 mo) over the period of observation. Ten received first-line therapy with cyclophosphamide, which was effective in 4. Cotrimoxazole alone achieved remission in one, combined with corticosteroids in 3. Eight required subsequent treatments because of first-line failure or relapse. Conclusion. Strictly and persistently localized WG is uncommon. Optimal treatment remains to be determined.