Anne Grasland

Reliability of Tuberculin Skin Test Measurement

The tuberculin skin test has many potential sources of error and variability. Standardization of the tuberculin reagent and the meaning of the test results have been considered in some detail [1, 2], but little attention has been paid to the reading itself [3-10]. Measurement of the induration, however, is one of the most important potential sources of error. If the customary technique of palpation is used, the margins of the induration may be difficult to define. The alternative ballpoint-pen method, although advocated as more reliable than palpation [3], has not been discussed in official statements on tuberculosis [1, 2]. We investigated the reliability of the ballpoint-pen technique and compared this technique with the palpation method. Methods Patients and Procedures Patients and health care personnel who were in an internal medicine department and needed a tuberculin skin test were invited to participate. Persons who had received bacille CalmetteGurin vaccine were enrolled preferentially. Ninety-six persons who provided informed consent ultimately participated in the study. Tuberculin Skin Tests and Measurement Methods Ten units of tuberculin from Pasteur Merieux, Lyon, France (corresponding to the recommended 5 IU of purified protein derivative tuberculin), were injected intradermally on the volar surface of the forearm (Mantoux technique) [11]. Readings were done on the third day after the test was administered, and the diameter of induration was measured along the long axis of the forearm. Two experienced investigators each independently did three measurements. The first two measurements were taken with a blinded caliper using the ballpoint-pen technique [3]. With this technique, a medium-point ballpoint pen is used to draw a line starting 1 to 2 cm away from the skin reaction and moving toward its center. When the pen reaches the margin of the induration, an increased resistance to further movement is felt and the pen is lifted. The procedure is repeated on the opposite side of the skin reaction. The distance between the ends of the opposing lines at the margins of the induration is measured. In our study, the lines were erased and the measurement process was repeated. The lines were then erased again, and the third measurement was done by palpation [2]. To reproduce the usual conditions of testing, we used a flexible ruler. The data were collected during eight sessions; 11 to 14 participants were tested per session. To reduce the chance that an observer would remember previous readings, three things were done. First, the results of measures that were obtained with the blinded caliper were recorded by a third investigator. Second, the first ballpoint-pen measure was done for all participants at each session, then the second ballpoint-pen measure, and then the palpation measure. Third, before the second and third readings, the third investigator verified that no minor landmarks persisted. Statistical Analysis To analyze the reliability of quantitative data, we used statistical methods that have been described elsewhere [12]. Intraclass correlation coefficients and their 95% CIs were computed using SAS soft-ware (SAS Institute, Cary, North Carolina) [13]. Induration diameters were used to classify skin reactions as positive or negative according to the 5-, 10-, and 15-mm cutoff points that have been recommended as indicating positivity in various situations [2]. Reliability was then assessed with coefficients [14]. We also used a graphical analysis that focuses on the mean and the variation in the differences between repeated measurements [15]. Mean differences and the SD of the differences were calculated. An area of imprecision that was determined on the basis of the SD of the differences was placed around the arbitrarily chosen 10-mm cutoff value (10 mm 1.96 SD). If a first measurement fell within this area, particularly at or about the cutoff value, the likelihood that the second measurement would be sufficiently different to change the result of the tuberculin skin test from negative to positive (or vice versa) was high. Conversely, such reclassification would occur in only 5% of the cases that had values outside this area. Results Because of the study design, only 27 participants (28%) did not react to the tuberculin skin test. Reliability of the Ballpoint-Pen Technique Intraobserver Reliability In persons who had no response to the tuberculin skin test, the intraobserver reliability was perfect (intraclass correlation coefficient = 1.0). Intraclass correlation coefficients were high for both observers and decreased only slightly after the nonresponders were excluded. The coefficients also suggested good intraobserver reliability but were lower with the 10- and 15-mm cutoff values than with the 5-mm cutoff value (Table 1). Table 1. Reliability Study of the Ballpoint-Pen and Palpation Methods of Induration Measurement for the Tuberculin Skin Test The top panel of Figure 1 shows the difference between the two readings for each participant that were done by the first observer (range, 6.8 to +3.5 mm) plotted against the corresponding mean for each participant. The level of intraobserver reliability was evaluated by determining the 95% CI ( 2.68 to +2.96 mm) within which most of the differences were seen. This means that 5% of the time, the second measure of the test results done by using the ballpoint-pen method would be at least 2.7 mm less than or 3.0 mm more than the first one. This lack of reliability could lead to the reclassification of a negative tuberculin skin test result as positive or vice versa. Figure 1. Top. Middle. Bottom. As shown in the top panel of Figure 1, an area of imprecision that straddles the cutoff value (7.2 to 12.8 mm for a 10-mm cutoff value) was generated using the SD of the differences. Test results for 8 of the 69 patients (12%) were reclassified. The first measurement for 30 of the 69 patients (43.5%) fell within this area of imprecision; 7 of those 30 patients (23.3%) were among the 8 patients whose test results were reclassified. Interobserver Reliability Agreement between observers, estimated by using the intraclass correlation and coefficients, was high (Table 1). The first ballpoint-pen measures made by the two observers were used for these analyses. Differences between first measures done by the two observers were between 5.1 and +7.3 mm (Figure 1, middle). The 95% CI of the differences was 3.39 to +3.69 mm; this means that 5% of the time, the result of a second tuberculin skin test measurement by another investigator would be at least 3.4 mm more than or 3.7 mm less than that of a first investigator. As in the top panel of Figure 1, an area of imprecision (6.5 to 13.5 mm) is shown in the middle panel of Figure 1; this area is slightly broader than that calculated for intraobserver reliability. Test results for 8 of the 69 patients (12%) were reclassified. The first measurement for 40 of the 69 patients (58%) fell within this area of imprecision; 7 of those 40 patients (17.5%) were among the 8 patients whose results were reclassified. Reliability of the Palpation Technique Except for the coefficients at the 15-mm cutoff, assessment of agreement between observers showed that all reliability coefficients obtained with the palpation technique were slightly lower than those obtained with the ballpoint-pen method (Table 1). The 95% CI of the differences between the measures of the two observers was 4.6 to +5.2 mm (Figure 1, bottom). This resulted in a much broader area of imprecision for the readings (5.1 to 14.9 mm). Test results were reclassified for 12 of the 69 patients (17.4%). The first measure of 43 of the 69 patients (62.3%) fell within this area of imprecision, and the 12 patients whose test results were reclassified were among those 43 (27.9%). Agreement between Ballpoint-Pen and Palpation Methods Although all the intraclass correlation coefficients were high, the coefficients that were produced after persons with no response to the test were excluded suggested only moderate to good reliability (Table 1). The 95% CIs of the differences between the first ballpoint-pen and the palpation measures were 3.0 to +4.1 mm for readings taken by the first observer and 2.5 to +3.9 mm for readings taken by the second observer. The areas of imprecision for the measurements were from 6.4 to 13.6 mm for readings taken by the first observer and 6.8 to 13.2 mm for readings taken by the second observer. Reclassification occurred in 8 of 69 patients (12%) for both observers. Discussion In our study, the ballpoint-pen technique was reliable, as evaluated by global reliability coefficients. However, the graphical analysis provided a more meaningful representation of the level of variation. Intraobserver reliability may be the most important factor for such diagnostic tests as the tuberculin skin test, which are usually done by only one examiner for any given patient. Lack of reliability may lead to the frequent reclassification of results, particularly if readings are at or about the cutoff values. Reliability coefficients were slightly higher for the ballpoint-pen technique than for the palpation method. In addition, the 95% CI of the differences of the measures taken by the two observers was 38% broader for the palpation method than for the ballpoint-pen technique; this could result in more frequent misclassification. Only one study [10] has addressed the interobserver reliability of the ballpoint-pen technique. That study relied on simple correlation coefficients to determine reliability. Reanalysis of the data from that study provided a coefficient of 0.74 (using a cutoff point of 10 mm). Previous studies of the reliability of the palpation method [5, 6, 10] have also been restricted primarily to the assessment of interobserver agreement and have provided conflicting results. Recalculation from the data of one large survey of six studies on tuberculin skin testing [4] gave

Rituximab Maintenance Therapy for Granulomatosis with Polyangiitis and Microscopic Polyangiitis

Objective. To evaluate the efficacy compared to the relapse risk and tolerance of systematic rituximab (RTX) infusions as maintenance therapy for patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), who entered remission taking conventional immunosuppressants or RTX. Methods. A retrospective study of the main clinical characteristics, outcomes, and RTX tolerance of patients who had received ≥ 2 RTX maintenance infusions in our center, regardless of induction regimen, between 2003 and 2010. Results. We identified 28 patients [4 MPA and 24 GPA; median age 55.5 yrs (range 18–78); 17 (60%) males] who received a median of 4 (range 2–10) RTX maintenance infusions, with median followup of 38 months (range 21–97) since diagnosis or last flare. None experienced a RTX infusion-related adverse event; 15 patients (among the 21 with available data) had hypogammaglobulinemia (predominantly IgM) prior to their last RTX maintenance infusion; 3 had infectious events (1 cutaneous abscess, 1 otitis, 1 fatal H1N1 flu). Two patients suffered pulmonary relapses shortly before a planned RTX maintenance infusion (both had increased antineutrophil cytoplasmic antibody levels and 1 had CD19+ lymphocyte reconstitution). Conclusion. Rituximab maintenance therapy was well tolerated but did not completely prevent relapses and persistent “grumbling” disease. These preliminary results remain to be confirmed by a randomized controlled trial currently in progress.

Psoriasis onset with tocilizumab.

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 1 juin 2013

Maladie de Still de l'adulte après vaccination contre l'hépatite A et B?

Resume Introduction Les vaccinations contre les hepatites A et B sont generalement tres bien tolerees. Cependant, exceptionnellement, des observations darthrites ou de maladies systemiques apres vaccination contre lhepatite B ont ete rapportees. Observation Les auteurs rapportent une observation de maladie de Still de ladulte possiblement declenchee par une vaccination contre les hepatites A et B. Il sagit dune femme de 38 ans qui a presente un tableau avec fievre, eruption cutanee, arthrites, myalgies, hepatite, atteinte pulmonaire et neurologique, compatible avec le diagnostic de maladie de Still de ladulte. Commentaires Les auteurs rappellent la rarete des observations de maladies systemiques declenchees par ce type de vaccination, les liens entre le virus de lhepatite B et certaines vascularites, et discutent leventualite de declenchement de la maladie de Still par des infections virales ou bacteriennes.

Polychondrite atrophiante, thromboses et anticorps antiphospholipides

Resume Les auteurs rapportent une observation de polychondrite atrophiante se manifestant initialement par des thromboses veineuses a repetition, associees a la presence danticorps antiphospholipides. De tels anticorps ont ete rapportes dans de nombreuses maladies systemiques dont certaines peuvent sassocier a la polychondrite atrophiante;cependant, jamais ils nont ete mis en evidence au cours de cette maladie.

Cogan syndrome: Characteristics, outcome and treatment in a French nationwide retrospective study and literature review

BACKGROUNDnCogan syndrome is mainly treated with steroids. We aimed to determine the place of DMARDs and biologic-targeted treatments.nnnPATIENTS AND METHODSnWe conducted a French nationwide retrospective study of patients with Cogan syndrome (n=40) and a literature review of cases (n=22) and analyzed the efficacy of disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor α (TNF-α) antagonists.nnnRESULTSnWe included 62 patients (31 females) (median age 37years [range 2-76]. At diagnosis, 61 patients (98%) had vestibulo-auditory symptoms, particularly bilateral hearing loss in 41% and deafness in 31%. Ocular signs were present in 57 patients (92%), with interstitial keratitis in 31 (51%). The first-line treatment consisted of steroids alone (n=43; 70%) or associated with other immunosuppressive drugs (n=18; 30%). Overall, 13/43 (30%) and 4/18 (22%) patients with steroids alone and with associated immunosuppressive drugs, respectively (p=0.8), showed vestibulo-auditory response; 32/39 (82%) and 15/19 (79%) ocular response; and 23/28 (82%) and 10/14 (71%) general response. Overall 61 patients had used a total of 126 lines of treatment, consisting of steroids alone (n=51 lines), steroids with DMARDs (n=65) and infliximab (n=10). Vestibulo-auditory response was significantly more frequent with infliximab than DMARDs or steroids alone (80% vs 39% and 35%, respectively), whereas ocular, systemic and acute-phase reactant response rates were similar. Infliximab was the only significant predictor of vestibulo-auditory improvement (odds ratio 20.7 [95% confidence interval 1.65; 260], p=0.019).nnnCONCLUSIONnInfliximab could lead to vestibulo-auditory response in DMARDS and steroid-refractory Cogan syndrome, but prospective studies are necessary.

« Une sarcoïdose » qui évolue vers une diarrhée

Introduction L’infection chronique par Tropheryma whipplei (Tw) donne des atteintes systemiques (maladie de Whipple [MW]) ou isolees d’organes. Elle est plus frequente chez l’homme caucasien d’âge moyen. Les adenopathies granulomateuses au debut des atteintes systemiques sont source d’errance diagnostique avant l’apparition des troubles digestifs. Nous rapportons l’observation de la MW chez un patient africain revelee par des adenopathies 6xa0ans plus tot. Observation M. M., 50xa0ans d’origine capverdienne, conducteur d’engins et diabetique de type 2, presente en 2008, des polyarthalgies inflammatoires, une secheresse occulo-buccale associee a une poly adenopathie peripherique cervicale et profonde sus et sous-diaphragmatique. La BGSA decrit la presence de granulome sans necrose. Dans le meme temps, l’on decouvre un pic monoclonal a IgA kappa a 10xa0g/L et plus de 10xa0% de plasmocytes medullaires dystrophiques sans lesion osseuse, faisant retenir le diagnostic de myelome stade 1. Il est traite initialement par AINS au besoin et plaquenil puis a partir de 2013xa0par cortisone 20xa0mg/j baissee progressivement a 10xa0mg/j. L’evolution sur le plan articulaire est stable mais 6xa0mois plus tard surviennent une dysphagie aux solides, une diarrhee aqueuse et un amaigrissement de plus de 20xa0kg. Biologiexa0: syndrome de malabsorption, creatinine et calcemie normales, CRP a 40xa0mg/L, Hb a 9,8xa0g/dL, PCR Tw positive dans le sang, le LCR, la salive et les selles. FOGDxa0: importante et diffuse lymphangiectasie du bulbe et du duodenum. PAS et PCR Tw positifs sur la biopsie. Le diagnostic de MW est retenu. Traitementxa0: doxycycline 200xa0mg/j et plaquenil 600xa0mg/j depuis 3xa0semaines. La cortisone est arretee. Discussion Dans plus de 50xa0% des cas, la MW debute en moyenne 6xa0ans par des adenopathies granulomateuses avant l’apparition de troubles digestifs. Le traitement immunosuppresseur (cortisone dans notre cas) fait apparaitre quelques mois plus tard les troubles digestifs et l’alteration majeure de l’etat general. La sensation de gene a la deglutition semble etre en rapport avec la secheresse des muqueuses oropharyngees. Son association avec un pic monoclonal n’est pas decrite. Est-ce une association fortuite ou un pic par stimulation chroniquexa0? L’evolution du pic et de la plasmocytose medullaire sous traitement de la MW permettra de repondre a cette question. Conclusion Le diagnostic de sarcoidose doit etre regulierement reevalue dans son evolution. L’apparition de troubles digestifs dans l’evolution d’un tableau de «xa0sarcoidosexa0» doit faire evoquer la MW.

Fracture du sacrum par insuffisance osseuse chez le sujet âgé: à propos de 14 observations

We report a series of 14 elderly patients with sacral insufficiency fractures of the sacrum. All patients presented with pain in low back, pelvis or lower limb which was often misleading. Bone scintigraphy was diagnostic in all the patients. Outcome was favourable in all the cases.