Influenza-like illness in individuals treated with immunosuppressants, biologics, and/or systemic corticosteroids for autoimmune or chronic inflammatory disease: A crowdsourced cohort study, France, 2017-2018.

BACKGROUND: Influenza-like illness (ILI) incidence estimates in individuals treated with immunosuppressants and/or biologics and/or corticosteroid for an autoimmune or chronic inflammatory disease are scarce. We compared the ILI incidence among immunocompromised population and the general population. METHOD: We conducted a prospective cohort study during the 2017-2018 seasonal influenza epidemic, on the GrippeNet.fr electronic platform, which allows the collection of epidemiological crowdsourced data on ILI, directly from the French general population. The immunocompromised population were adults treated with systemic corticosteroids, immunosuppressants, and/or biologics for an autoimmune or chronic inflammatory disease, recruited directly on GrippeNet.fr and also among patients of the departments of a single university hospital that were asked to incorporate GrippeNet.fr. The general population consisted of adults reporting none of the above treatments or diseases participating in GrippeNet.fr. The incidence of ILI was estimated on a weekly basis and compared between the immunocompromised population and the general population, during the seasonal influenza epidemic. RESULTS: Among the 318 immunocompromised patients assessed for eligibility, 177 were included. During the 2017-2018 seasonal influenza epidemic period, immunocompromised population had 1.59 (95% CI: 1.13-2.20) higher odds to experience an ILI episode, compared to the general population (N = 5358). An influenza vaccination was reported by 58% of the immunocompromised population, compared to 41% of the general population (p < 0.001). CONCLUSION: During a seasonal influenza epidemic period, the incidence of influenza-like illness was higher in patients treated with immunosuppressants, biologics, and/or corticosteroids for an autoimmune or chronic inflammatory disease, compared to the general population.

Usefulness of the QuantiFERON test for the diagnosis of tubercular uveitis and the predictions of response to antituberculosis treatment.

AIMS: Few studies have evaluated the contribution of QuantiFERON test for the diagnosis of tubercular uveitis in non-endemic countries for tuberculosis (TB). The objective of the present study was to evaluate the value of the QuantiFERON test in a large cohort of patients with uveitis for both the diagnosis of tubercular uveitis and antituberculosis treatment (ATT) response prediction. METHODS: A single-centre retrospective study including consecutive adult patients with uveitis who were prescribed a QuantiFERON test between January 2003 and December 2019 was performed. Adjusted ORs (aORs) were calculated between patients with uveitis responding and not responding to ATT according to the Collaborative Ocular Tuberculosis Study (COTS) group diagnostic criteria. Sensitivity (SE), specificity (Sp), and positive and negative predictive values of the QuantiFERON test were calculated. RESULTS: A total of 1075 patients were included in the study; 178 (16.5%) were found positive using the QuantiFERON test. Among the 178 positive patients, 62 (35%) had a diagnosis of tubercular uveitis according to the updated COTS classification; all received ATT for 6 months; and 44/62 (71%) responded to ATT. A QuantiFERON test value of >2 IU/mL was associated with a greater chance of responding to ATT (aOR=36.7, 95% CI 7.2 to 185.9, p<0.001). The optimal threshold to maximise both Sp and SE for diagnosis of TB uveitis was 4 IU/mL. CONCLUSION: One-sixth of the patients diagnosed with uveitis had a positive QuantiFERON test. The QuantiFERON threshold with the optimal SE and Sp for the diagnosis of tubercular uveitis was 4 IU/mL. TRIAL REGISTRATION NUMBER: NCT03863782.

Prevalence of Positive QuantiFERON-TB Test among Sarcoid Uveitis Patients and its Clinical Implications in a Country Non-endemic for Tuberculosis.

AIM: To report on the prevalence and clinical implications of positive QuantiFERON-TB (QFT) test results in the diagnostic evaluation of a cohort of consecutive sarcoid uveitis patients in France. DESIGN: Retrospective cross-sectional study. METHODS: This study included consecutive sarcoid uveitis patients who all underwent QFT testing. RESULTS: A total of 234 patients were included in the study, among them 28 (12%) were QFT-positive. Previously treated tuberculosis (TB) was documented in 2 patients. QFT-positive patients were older (59 ± 16 years vs. 51 ± 18 years, p = .025) and more in proportion to suffer from chronic uveitis and panuveitis compared to QFT-negative patients. Moderate and severe visual impairment were significantly more frequent in the QFT-positive group (35.7% vs. 18.9%, p = .049 and 25.0% vs. 9.2%, p = .022, respectively). CONCLUSION: The significant proportion of QFT-positive patients (12%) in this large series of sarcoid uveitis patients makes us suggest not to exclude the diagnosis of sarcoidosis in case of positive QFT in a low-endemic country for tuberculosis, and to manage these patients early by initiating without delay systemic steroids associated with latent tuberculosis therapy.

Expert opinion on the use of biological therapy in non-infectious uveitis.

INTRODUCTION: Conventional immunosuppressive drugs, anti-TNF alpha treatments and biotherapies are increasingly being used in non-infectious uveitis. AREAS COVERED: The present work was led by a multidisciplinary panel of experts, including internal medicine specialists, rheumatologists and ophthalmologists, and proposes an extensive review on the use of biological agents in non-infectious uveitis. EXPERT OPINION: In case of dependency to steroids or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or biological therapies such as anti-TNF alpha treatments (adalimumab, infliximab) can be used to achieve and maintain disease quiescence. Interferon is an efficient immunomodulatory drug that can be proposed as second-line therapy in specific indications (eg. refractory macular edema, sight-threatening Behçet's uveitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (steroids, sirolimus etc.) can be used as adjuvant therapies in case of unilateral relapse. Therapeutic response must always be evaluated by clinical examination and appropriate ancillary investigations.

Inflammatory disorders associated with trisomy 8-myelodysplastic syndromes: French retrospective case-control study.

OBJECTIVE: We report cases of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) with trisomy 8 associated with inflammatory and autoimmune diseases (IADs). METHOD: Data for 21 patients with trisomy 8-MDS/MPN and IADs were analyzed and compared to 103 patients with trisomy 8-MDS/MPN without IADs. RESULTS: The median age of MDS/MPN patients with IADs was 67 [59-80]. The IADs were Behçet's-like disease in 11 (52%) patients, inflammatory arthritis in 4 (19%) and Sjögren's syndrome, autoimmune hemolytic anemia, aseptic abscess, periarteritis nodosa, Sweet's syndrome and unclassified vasculitis in one patient each. Overall, 17/21 (81%) patients with IADs received treatment (88% with steroids), with complete and partial response in 7/17 (35%) and 8/17 (47%), respectively. The effect of MDS treatment on IADs could be assessed in seven patients receiving azacytidine: five achieved remission and two partial response. As compared with the 103 trisomy 8-MDS/MPN cases without IADs, those with IADs were more often non-European (P = 0.005) and had poor karyotype (P < 0.001). We found no difference in overall survival or acute myeloid leukemia progression between trisomy 8-associated MDS/MPN with and without IADs. CONCLUSION: The spectrum of IADs associated with trisomy 8-positive MDS/MPN is dominated by Behçet's-like disease. Steroid therapy is effective, but mostly sparing therapies are necessary. Azacytidine could be an effective alternative.

Gastrointestinal Behcet's-like disease with myelodysplastic neoplasms with trisomy 8: a French case series and literature review.

We report the 11 cases of +8-MDS/MPN associated with Behcet's-like syndrome and compare them with Behcet's disease and Crohn's disease, pool with literature cases for analysis. Data for patients with +8-MDS/MPN and Behçet's-like syndrome were collected from MINHEMON. Eleven patients had Behcet's-like syndrome and +8-MDS/MPN (median age 75 years [IQR 65-87]; M/F ratio 0.8). MDS and Behcet's-like syndrome were diagnosed at the same time (7/11, 64%). By comparison with 63 patients with idiopathic Behcet's disease without associated MDS, those with Behcet's-like syndrome and +8-MDS/MPN were older (median 75 vs 48 years; p = .0003) and had less pseudofolliculitis (11% vs 62%; p = .0045) and ocular impairment (0% vs 52%; p = .0008), but more frequent gastrointestinal involvement (60% vs 13%; p = .0005). By comparison with Crohn's disease, 39 patients with Behcet's-like syndrome and +8-MDS/MPN were significantly older (median 72 [53-78] vs 36 [27-45] years; p = .0002) and more frequently had oral aphtosis (97% vs 5%, p < .0001), skin features (50% vs 10%, p = .0005) and arthralgia (63% vs 20%, p = .03). Median survival did not differ between patients with Behcet's-like syndrome and +8-MDS/MPN and those with +8-MDS/MPN (n = 103) (47 vs 34 months, p = .61). AML-free survival did not differ between patients with MDS/MPN with and without Behcet's-like syndrome (p = .29). MDS/MPN with trisomy 8 can be associated with particular phenotype of ulcerative digestive disease resembling Behcet's or Crohn's disease and should be considered a single disease.

Superior efficacy and similar safety of double dose anakinra in Erdheim-Chester disease after single dose treatment.

Objectives. In Erdheim-Chester disease (ECD), the empirical single dose (SD, 100 mg/day) anakinra sometimes induces only partial responses. Since SD is usually well tolerated, doubling the dose might improve response while maintaining an acceptable safety profile. Methods. A retrospective analysis was performed of outcomes under double-dose (DD) of anakinra in 4 ECD patients who did not exhibit a complete response (CR) under SD treatment. Bone, retroperitoneal, neurologic/orbital, peritoneal, pericardial, right atrium, and pleural involvements were recorded. CR, partial response (PR), stable disease, progressive disease (PD) and tolerance of DD were assessed. Results. SD treatment was a second or third line treatment in three patients after interferon-therapy failure. Two patients, including one with a BRAF mutation, achieved a CR and one patient with a NRAS mutation achieved a PR with DD treatment. The fourth patient, wild-type for both genes, did not respond to a first DD treatment, but then achieved CR under SD associated with a reduced dose of vemurafenib (960 mg/d). Bone and retroperitoneal lesions partially improved on imaging with SD in all patients, but were further improved under DD with two patients achieving CR. With SD treatment, two patients with right atrial masses showed sustained CR. Under DD treatment, two patients with massive serositis refractory to SD, showed PR. Conclusion. DD improved the response to anakinra and lead to two CRs and a PR in three out of four ECD patients, with minor and comparable side-effects to those of SD, while failures were essentially related to massive serositis.

Uveitis: Diagnostic work-up. A literature review and recommendations from an expert committee.

PURPOSE: Diagnosis of uveitis is difficult. Etiologic investigations should take into account the epidemiology of uveitis and should focus on the most severe forms of the disease and those which can be treated. This study was undertaken to establish recommendations for the diagnosis of uveitis. METHODS: Recommendations were developed by a multidisciplinary panel of 14 experts, including internists, ophthalmologists, and rheumatologists, and are based on a review of the literature and the results of the ULISSE study, which was the first prospective study to assess the efficacy of a standardized strategy for the etiologic diagnosis of uveitis. The following groups of patients are not included in these recommendations: children, immunocompromised patients, patients with severe retinal vasculitis, and those with specific eye diseases diagnosed by ophthalmologic examination only. RESULTS: Diagnosis should be guided by the medical history of the patient and physical examination. Serologic screening for syphilis is appropriate in all forms of uveitis. If uveitis is not diagnosed at this stage, investigations oriented by the anatomic characteristics of uveitis are proposed. These consist of assays for HLA-B27 (in unilateral acute anterior non-granulomatous uveitis), serum angiotensin-converting enzyme, interferon-gamma release, chest computed tomography (chronic uveitis), cerebral magnetic resonance imaging and anterior chamber tap with interleukin-10 analysis (intermediate or posterior uveitis in patients >40years-old). Other investigations prescribed in the absence of orientation are usually unhelpful. CONCLUSIONS: A strategy is proposed for the etiologic diagnosis of uveitis. The benefit of more invasive investigations remains to be determined.

Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults: A national retrospective strobe-compliant study.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8-77.4) with a median serum creatinine level at 207 µmol/L (range 100-1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m (range 2-73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10-2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m (range 17-119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = -0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = -0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral corticosteroids are effective for the treatment of TINU syndrome's uveitis.

Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare histiocytic disorder that is challenging to diagnose and treat. We performed molecular analysis of BRAF in the largest cohort of ECD patients studied to date followed by N/KRAS, PIK3CA, and AKT1 mutational analysis in BRAF wild-type patients. Forty-six of 80 (57.5%) of patients were BRAFV600E-mutant. NRAS mutations were detected in 3 of 17 ECD BRAFV600E wild-type patients. PIK3CA mutations (p.E542K, p.E545K, p.A1046T, and p.H1047R) were detected in 7 of 55 patients, 4 of whom also had BRAF mutations. Mutant NRAS was present in peripheral blood CD14(+) cells, but not lymphoid cells, from an NRASQ61R mutant patient. Our results underscore the central role of RAS-RAF-MEK-ERK activation in ECD and identify an important role of activation of RAS-PI3K-AKT signaling in ECD. These results provide a rationale for targeting mutant RAS or PI3K/AKT/mTOR signaling in the subset of ECD patients with NRAS or PIK3CA mutations.

Systemic sclerosis and prevalence of monoclonal immunoglobulin.

INTRODUCTION: The purpose of this study was to estimate the prevalence of monoclonal immunoglobulin (MIg) among patients with systemic sclerosis (SSc) according to the capillary electrophoresis or immunofixation method of detection and to search for any related clinical correlations. PATIENTS AND METHODS: Retrospective multicenter comparison of capillary electrophoresis and immunofixation results in SSc patients and of the characteristics of patients with and without MIg. RESULTS: The study included 244 SSc patients (216 women and 28 men, mean age: 55±14 years). Median time since SSc diagnosis was 51 months [0-320]; disease was diffuse in 48% of cases. Ten percent of patients had cancer, including Waldenström macroglobulinemia (n=1) and multiple myeloma (n=3). Capillary electrophoresis showed a γ-globulin anomaly in 41% of cases, and immunofixation in 18%: MIg (13.5%) and restriction of heterogeneity (4.5%). Capillary electrophoresis failed to detect 60% of the 33 MIg patients. Measurable MIg concentrations were obtained from 7 patients. MIg patients were significantly older at SSc diagnosis than those without MIg (p=0.002), had a lower diffusing capacity (p=0.002), a higher prevalence of pulmonary hypertension and cancer (p=0.002) and were more frequently positive for anti-mitochondrial and anti-beta2-glycoprotein-I antibodies (p=0.03 and p=0.02, respectively). Multivariate analyses showed that only age at test [hazard ratio 1.03 (95% CI, 1.00-1.07, p=0.04)] and presence of cancer [hazard ratio 4.46 (95% CI, 1.6-12.4, p=0.004)] were associated with MIg. CONCLUSION: Immunofixation detected a high prevalence of MIg among SSc patients especially in patients aged 50-years or older. MIg was not detected by the standard capillary electrophoresis in 60% of cases and was significantly associated with cancer.

Systemic sclerosis with normal or nonspecific nailfold capillaroscopy.

BACKGROUND: In systemic sclerosis (SSc), a specific nailfold videocapillaroscopy (NVC) pattern is observed in 90% of cases and seems to be associated with severity and progression of the disease. OBJECTIVE: To describe the characteristics of SSc patients with normal or nonspecific (normal/nonspecific) NVC. METHODS: In a retrospective cohort study, clinical features and visceral involvements of 25 SSc cases with normal/nonspecific NVC were compared to 63 SSc controls with the SSc-specific NVC pattern. RESULTS: Normal/nonspecific NVC versus SSc-specific NVC pattern was significantly associated with absence of skin sclerosis (32 vs. 6.3%, p = 0.004), absence of telangiectasia (47.8 vs. 17.3%, p = 0.006) and absence of sclerodactyly (60 vs. 25.4%, p = 0.002), and less frequent severe pulmonary involvement (26.3 vs. 58.2%, p = 0.017). CONCLUSION: Normal/nonspecific NVC in SSc patients appears to be associated with less severe skin involvement and less frequent severe pulmonary involvement.

Study of anti-Müllerian hormone and its relation to the subsequent probability of pregnancy in 112 patients with systemic lupus erythematosus, exposed or not to cyclophosphamide.

CONTEXT: Cyclophosphamide is used for renal and major extrarenal involvement in systemic lupus erythematosus (SLE) and is associated with a risk of premature ovarian failure. There are no data available about the relation between anti-Müllerian hormone (AMH) serum levels and the probability of subsequent pregnancy in SLE patients. OBJECTIVE: We analyzed AMH levels and the probability of pregnancy in SLE women exposed to cyclophosphamide. DESIGN AND SETTING: We conducted a matched cohort study in referral centers for SLE. PATIENTS: Fifty-six cyclophosphamide-exposed SLE women younger than 40 years of age and 56 control SLE women matched for age within 6 months participated in the study. MAIN OUTCOME MEASURES: AMH was measured in samples from the PLUS study (ClinicalTrials.gov no. NCT00413361). All patients were interviewed in May 2012 regarding their obstetric status. RESULTS: The mean age ± SD of the 112 patients was 31.6 ± 5.8 years. The mean AMH level was low (1.21 ± 1.01 ng/mL) and was significantly lower in patients exposed to cyclophosphamide (P = .03) and in patients older than 30 years (P = .02). During a median follow-up (interval between sampling and the interview) period of 4.2 (range, 2.5-4.8) years, 38 patients sought to become pregnant, and 32 (84.2%) succeeded. In the univariate analysis, the risk of failure was associated with cumulative cyclophosphamide dose (P = .007) and older age (P = .02), but not with AMH. CONCLUSION: We confirmed that AMH levels are low in SLE patients and decrease significantly with age and cyclophosphamide exposure. Nonetheless, the risk of failure to conceive was low and was predicted by cyclophosphamide exposure and age, but not by AMH levels.

18F-fluorodeoxyglucose-positron emission tomography scanning is a useful tool for therapy evaluation of arterial aneurysm in Behçet's disease.

[(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET) has demonstrated its usefulness in giant cell arteritis, Takayasu's arteritis, and unclassified aortitis. FDG-PET imaging could be more effective than CT-scan or magnetic resonance imaging in detecting the earliest stages of vascular wall inflammation. Data are lacking regarding its accuracy for diagnosis and follow-up of vascular lesions in Behçet's disease. We report the case of a 32-year-old woman with history of Behçet's disease and fever of unknown origin revealing voluminous pulmonary arterial aneurysms. FDG-PET scan revealed a peripheral uptake of pulmonary aneurysms, underlying the inflammatory status of arterial aneurysms wall. Our patient was treated by glucocorticoids and intravenous cyclophosphamide and achieved remission of Behçet's disease. During follow-up, FDG-PET scan enabled to detect an early radiologic therapeutic response after 4 months, while CT angiography remained unchanged. We report the first evidence of usefulness of FDG-PET scan for therapeutic evaluation of arterial aneurysms in Behçet's disease. Further studies are warranted to determine the accuracy of FDG-PET scan in larger cohort of Behçet's disease patients with vascular involvement.

Activated and resting regulatory T cell exhaustion concurs with high levels of interleukin-22 expression in systemic sclerosis lesions.

OBJECTIVE: Transforming growth factor-ß is considered to play a key role in the process of fibrosis in systemic sclerosis (SSc) and in the development of regulatory T cells (Treg) and pro-inflammatory Th17 T cells producing interleukin 17 (IL-17) and IL-22. The authors therefore postulated that SSc could be characterised by a marked Treg/Th17 imbalance. Previous works did not distinguish between the different subsets of Treg and the non-regulatory FoxP3(+) cells leading to inconsistent results. METHODS: Combined phenotypic and functional analysis of Th17 cells and FoxP3(+)CD4 T cells, discriminating activated Tregs and resting Tregs from non-regulatory FoxP3(+) T cells, in blood and skin of SSc patients. RESULTS: In early disease stages, there is a decreased proportion of activated Tregs. A concomitant resting Treg deficit becomes more apparent with disease progression. Active and diffuse forms of the disease are characterised by a relatively higher proportion of all FoxP3(+) subsets, including non-regulatory T cells. No peripheral or local IL-17 amplification was observed. However, the authors found significantly increased IL-22 transcription levels in SSc lesional skin, as compared with healthy skin. Cytofluorometry confirmed the existence in SSc patients and controls of a distinct subset of T cells producing IL-22 in the absence of IL-17. CONCLUSION: SSc pathogenesis does not appear to be linked to IL-17-, but rather to IL-22-producing cells with skin-homing potential and a concomitant quantitative Treg defect. Active and diffuse forms of the disease are associated with a FoxP3 signature. Altogether, our data depict a status of regulatory/pro-inflammatory T cell imbalance in SSc.

Impaired carbon monoxide diffusing capacity as a marker of limited systemic sclerosis.

BACKGROUND: As impairment of diffusing capacity for carbon monoxide (DLCO) likely reflects underlying pulmonary vasculopathy in limited systemic sclerosis (lSSc), we examined whether DLCO could help to distinguish secondary from idiopathic Raynaud's phenomenon (iRP). METHODS: We compared pulmonary function test (PFT) results in 145 lSSc patients and 24 age- and sex-matched iRP patients. RP duration at time of PFT was similar in the two groups. RESULTS: DLCO values were low (<80% of predicted) in 106 (73%) of the 145 lSSc patients, and in 69 (71%) of the 97 patients with early lSSc. Interstitial lung disease (ILD) was found in 10% of lSSc patients. DLCO was significantly lower in lSSc than in iRP (72±15% versus 89±9%, p<0.0001). When evaluated, alveolar capillary membrane conductance (Dm) was markedly lower in lSSc patients without ILD than in iRP patients (45±12% versus 71±2.5%, p=0.003), although capillary blood volume was not different. DLCO was low in 3 iRP patients (12.5%). The sensitivity and specificity of low DLCO values for early lSSc diagnosis in patients with Raynaud's phenomenon were 71% and 87.5%, respectively. Sensitivity was similar to that of anti-centromere-antibodies (75%) and nailfold capillary abnormalities (81%). A DLCO cutoff of <70% had a sensitivity and specificity of 41% and 100%, respectively. In multivariable analysis, age and low DLCO were the only independent predictors of death; the hazard ratio for DLCO ≤50% was 7.9 (95% CI 2.3-26, p=0.0007). CONCLUSION: Isolated DLCO impairment is significantly more frequent in patients with lSSc than in patients with idiopathic iRP. DLCO measurement could be a useful diagnostic tool for lSSc.

QuantiFERON-TB gold cut-off value: implications for the management of tuberculosis-related ocular inflammation.

PURPOSE: To evaluate the accuracy of QuantiFERON-TB Gold testing in patients with presumptive tuberculosis-ocular inflammation. DESIGN: Prospective nonrandomized case series and clinical laboratory investigation. METHODS: Ninety-six consecutive patients presenting with ocular inflammation between January and October 2007 were tested using QuantiFERON-TB Gold. Positive patients received a 6-month anti-tuberculosis treatment. Patient follow-up ranged from 12 months to 24 months. Treatment was considered effective at the end of follow-up, in cases of no or a 2-point decrease of ocular inflammation (SUN criteria) and systemic corticosteroids stopped or tapered to 10 mg/day. RESULTS: Mean age was 51 ± 17 years. Types of ocular inflammation included scleritis (n = 7), panuveitis (n = 34), and posterior (n = 15), intermediate (n = 14), and anterior uveitis (n = 15). QuantiFERON-TB Gold was positive in 42 cases (44%), negative in 51 cases (53%), and undetermined in 3 cases (3%). Among positive QuantiFERON-TB Gold patients, 25 received a full anti-tuberculosis treatment, which was effective in 15 cases (60%). Associated systemic steroids were given to 6 patients and tapered to 10 mg/day or less in all cases. Median QuantiFERON-TB Gold value was significantly higher in the group with a successful therapeutic response (7.67 IU/mL [0.46 to 33.37]) compared to the group with treatment failure (1.22 IU/mL [0.61 to 4.4]), P = .026. CONCLUSION: Results of anti-tuberculosis treatment were encouraging in QuantiFERON-TB Gold-positive ocular inflammation, especially with values over 2 IU/mL in our study, suggesting that a higher cut-off value than that given by the manufacturer should be considered to better identify ocular inflammation that can benefit from full anti-tuberculosis treatment.

Potentiation of fluindione or warfarin by dexamethasone in multiple myeloma and AL amyloidosis.

OBJECTIVES: Patients with primary systemic (AL) amyloidosis or multiple myeloma are frequently treated with cyclic dexamethasone (DXM) courses and often require oral anticoagulants. We previously reported a strong potentiation of oral anticoagulants with intravenous methylprednisolone and observed a similar potentiation with DXM in 3 patients, which led us to prospectively investigate the interaction between DXM and oral anticoagulants. METHODS: Nine patients with multiple myeloma (n=6) or AL amyloidosis (n=3), including 6 prospective patients, taking fluindione (n=8) or warfarin (n=1), were studied for a total of 10 cycles. DXM (40 mg/day for 4 days every 28 days) was administered alone (n=4) or with melphalan (n=5). One patient was studied for 2 consecutive cycles after a moderate increase in the international normalized ratio (INR) during the first course of DXM. International normalized ratio (INR) was measured serially during DXM administration. Plasma oral anticoagulant concentrations were measured for 5 cycles. RESULTS: The mean INR increased from 2.75 (range: 1.80-3.6) at baseline to 5.22 (3.09-7.07) after DXM. Oral anticoagulants were transiently stopped during 8 cycles and 1 mg oral vitamin K was given during 2. No serious bleeding was observed. Plasma oral anticoagulant concentrations increased after DXM administration. In controls receiving DXM without oral anticoagulants, DXM alone did not increase prothrombin time. CONCLUSION: High dose DXM can potentiate oral anticoagulants and elevate INR substantially. INR should therefore be monitored repeatedly during concomitant administration of these 2 drugs to allow individual adaptation of oral anticoagulant doses.

Variability in the efficacy of interferon-alpha in Erdheim-Chester disease by patient and site of involvement: results in eight patients.

OBJECTIVE: Erdheim-Chester disease (ECD) is a rare, non-Langerhans form of histiocytosis of unknown origin, characterized by infiltration of tissues by spumous histiocytes. ECD features heterogeneous systemic manifestations, and the general prognosis remains poor despite various treatment options. METHODS: We treated 8 patients with multisystemic ECD with subcutaneous interferon-alpha (IFNalpha) at a dosage of 3-9 x 10(6) units 3 times weekly, for a median duration of 23 months (range 1-46 months). RESULTS: Treatment was generally well tolerated, and side effects remained limited to fever following injections. Treatment was discontinued in 1 patient, because of severe depression. During treatment, some manifestations of ECD disappeared (i.e., xanthelasma, exophthalmos, papilledema, and intracranial hypertension). The efficacy of IFNalpha on cardiovascular ECD was variable, however. Treatment resulted in partial regression of "coated aorta" in some cases and clear failure in others; 2 patients died. The level of C-reactive protein diminished sharply in 5 patients. CONCLUSION: IFNalpha might be a valuable first-line therapy for prolonged treatment of ECD. However, the efficacy of IFNalpha varies among patients and according to the sites of disease involvement, and symptoms may fail to respond to treatment, especially in patients with severe multisystemic forms of ECD with central nervous system and cardiovascular involvement.