Clinical interest of bone marrow aspiration in rheumatology: a practice-based observational study of 257 bone marrow aspirations.

Bone marrow aspiration (BMA) can be performed by rheumatologists for diagnostic purposes in clinical practice. The aim of the study was to assess professional practices of hospital-based rheumatologists with regard to BMA in order to identify the relevant indications. A retrospective observational study in patients hospitalised in a French university hospital was conducted between 2005 and 2011. All of the patients who had a BMA in the rheumatology department during the study period were included. Clinical indication, number and results of BMA and of bone marrow biopsy (BMB) were collected. Stage and treatment of the haematological disease implemented following the BMA were described. Two hundred fifty-seven BMAs and 79 BMBs were performed during the study period. Of the BMAs, 14.1 % were pathological: myeloma (n = 12), malignant B cell non-Hodgkin's lymphoma (n = 6), myelodysplastic syndrome (n = 6), chronic lymphoid leukaemia (n = 4), Waldenstrom's disease (n = 3), chronic myelomonocytic leukaemia (n = 2), hairy cell leukaemia (n = 1) and acute lymphoblastic leukaemia (n = 1). Eight of the 14 pathological BMBs were associated with normal BMA. BMAs were performed equally for gammaglobulin abnormalities (monoclonal peak = 45 % of indications, hypogammaglobulinemia = 6 %) and for other reasons (haemogram abnormality = 24 %, skeletal osteolysis = 6 %, unexplained inflammatory syndrome = 5 %, lymph node disease = 4 % and others). In clinical rheumatology, BMA may reveal two major types of malignant haematological diseases: myeloma with poor prognostic factors justifying polychemotherapy and autologous grafts and, in contrast, slowly evolving B cell lymphoid haemopathies. Given the additional risk in some types of chronic inflammatory rheumatism, BMB should be performed more frequently in certain specific situations (skeletal or lymph node tumour and unexplained inflammatory syndrome).

Usefulness of routine hepatitis C and hepatitis B serology in the diagnosis of recent-onset arthritis. Systematic prospective screening in all patients seen by the rheumatologists of a defined area--brief report.

OBJECTIVE: Previous studies evaluating the usefulness of systematic screening for hepatitis B and C in patients with recent-onset arthritis suffered from a major bias since they were conducted in hospitals. The objective of the present study was to evaluate the relevance of such screening, performed by hospital and office-based rheumatologists of a defined area, in the diagnosis of arthritis or inflammatory polyarthralgia of less than 1 year duration. METHODS: The CRRRI is a network which includes most hospital and office-based rheumatologists of an area with a population of 506,755 inhabitants. All patients seen by the CRRRI participants in their usual practice between March 2008 and December 2010 for inflammatory polyarthralgia, mono-, oligo-, or polyarthritis of less than 1 year duration were included. Patients' serum samples were screened for the presence of anti-hepatitis C virus (HCV) antibodies, with positive samples further evaluated for HCV-RNA with a reverse transcriptase-polymerase chain reaction, and for the presence of hepatitis B virus (HBV) infection. RESULTS: Two hundred and thirty-three patients were included (162 women, 71 men; mean age of 50.6±15.8 years). Patients were evaluated for inflammatory polyarthralgia (n=51), monoarthritis (n=21), oligoarthritis (n=35) or polyarthritis (n=126) lasting for a mean 19.8±29.8 weeks. No new HCV or HBV infection diagnosis was done. CONCLUSION: In this study not suffering from a hospital-selection bias, screening for hepatitis C and B infection was not helpful in the diagnosis process of recent-onset arthritis. KEY MESSAGES: Systematic hepatitis B and C serology is not relevant in patients with recent-onset (<1 year) arthritis.

Three-dimensional kinematics of the lower limbs in hip osteoarthritis during walking.

OBJECTIVE: To describe the kinematic adaptations of all lower limb joints in hip osteoarthritis patients during walking. METHODS: Patients with unilateral primary hip OA, without associated joint disorders were included. Normal subjects were included as controls. Gait analysis, using a 3-dimensional computerised gait analysis system was used to evaluate the usual spatiotemporal parameters, the peak motion of the hips, knees, and ankles during walking, and the intersegmental coordination of the lower limbs. RESULTS: Eleven patients, mean age =60.5 ± 7 years and nine controls, mean age=60.3 ± 7 years, were included. The gait of hip OA patients was characterised as follows: a reduced stride length, a reduced maximal flexion and extension in the OA hip, a reduced maximal contralateral hip range of motion, an increased ipsi- and contralateral ankle dorsal flexion, a decreased ipsilateral relative temporal phase between the thighs and shanks segments and an increased ipsilateral relative phase between the shanks and foot segments. CONCLUSION: The present results suggest that hip OA patients use shorter stride length, less contra lateral and especially ipsilateral hip motion, modify ankles motion, and have a different intra-limb coordination pattern compared to control subjects.

Study of professional practices among rheumatologists in Burgundy: initial corticotherapy in polymyalgia rheumatica.

To study the initial dose of corticoids prescribed by rheumatologists in the Côte d'Or, a French department of Burgundy, in the treatment of polymyalgia rheumatica (PMR), the clinical and biological data of patients who consulted rheumatologists of the Côte d'Or between March 2006 and December 2008 for PMR were collected. The statistical analyses concerned the initially prescribed dose of prednisone: the median, mean, and standard deviation were calculated cumulatively and then for individual rheumatologists; the Mann-Whitney test was used to compare the mean initial doses prescribed with regard to (a) the main practice of the practitioner (private-practice or hospital rheumatologist), (b) the presence of clinical signs of severity, (c) severity of the inflammatory syndrome, and (d) the presence of clinical relapse with the decrease in corticoids. Ninety-nine patients were included (age = 72 ± 8.6 years, 59% women). The mean dose of prednisone prescribed was 27.4 ± 12.4 mg/day. Considerable inter- and intra-individual variabilities in the doses prescribed were noted. There was no significant difference concerning the dose prescribed according to the clinical severity or the type of practice. However, the dose was significantly higher (34.3 ± 14.7 vs. 25.5 ± 11.1 mg/day) in patients with a high sedimentation rate. Clinical relapse was not statistically linked to the initial dose of corticoids. This evaluation of professional practices among French rheumatologists shows that the initial dose of prednisone prescribed in PMR varies considerably and is higher than the dose currently recommended in the literature (15 mg/day).

Diagnostic strategy for patients with hypogammaglobulinemia in rheumatology.

The discovery of hypogammaglobulinemia, which is defined as a plasmatic level of immunoglobulin (Ig) under 5 g/L is rare in clinical practice. However, the management of immunodepressed patients in rheumatology, sometimes due to the use of immunosuppressive treatments such as anti-CD20 in chronic inflammatory rheumatisms, increases the risk of being confronted to this situation. The discovery of hypogammaglobulinemia in clinical practice, sometimes by chance, must never be neglected and requires a rigorous diagnosis approach. First of all, in adults, secondary causes, in particular lymphoid hemopathies or drug-related causes (immunosuppressors, antiepileptics) must be eliminated. A renal (nephrotic syndrome) or digestive (protein-losing enteropathy) leakage of Ig is also possible. More rarely, it is due to an authentic primary immunodeficiency (PID) discovered in adulthood: common variable immunodeficiency (CVID) which is the most frequent form of PID, affects young adults between 20 and 30 years and can sometimes trigger joint symptoms similar to those in rheumatoid arthritis; or Good syndrome, which associates hypogammaglobulinemia, thymoma and recurrent infections around the age of 40 years. In most cases, after confirming hypogammaglobulinemia on a second test, biological examinations and thoracic-abdominal-pelvic CT scan will guide the diagnosis, after which the opinion of a specialist can be sought depending on the findings of the above examinations. At the end of this review, we provide a decision tree to guide the clinician confronted to an adult-onset hypogammaglobulinemia.

Severe pyogenic infections in patients taking infliximab: a regional cohort study.

OBJECTIVE: To evaluate the prevalence and risk factors of severe pyogenic infections in rheumatology patients taking infliximab in everyday practice. METHODS: Regional prospective cohort study of patients taking infliximab for rheumatoid arthritis or ankylosing spondylitis with data collection on standardized forms. The medical records of patients with severe pyogenic infections were subjected to a detailed retrospective review. Patients with and without severe pyogenic infections were compared. RESULTS: The cohort included 83 patients (55 women and 28 men). Severe pyogenic infections occurred in five (6%) patients (three women and two men), all of whom had acute or underlying risk factors. Higher values were found in these five patients for mean age (65.8 +/- 12 vs. 53.9 +/- 13 years, P = 0.04) and mean daily glucocorticoid dosage (15.5 +/- 9 vs. 6.9 +/- 7 mg/day prednisone-equivalent, P = 0.036), as compared to the other patients. CONCLUSION: Older age and high-dose glucocorticoid therapy are associated with an increased risk of severe pyogenic infection during infliximab therapy. Caution is in order when starting and monitoring infliximab therapy in patients with risk factors. Our data also emphasize the need for a careful search for risk factors before each infliximab infusion.

Tolerability of opioids in patients with acute pain due to nonmalignant musculoskeletal disease. A hospital-based observational study.

OBJECTIVE: To evaluate the prevalence of adverse effects of opioids used to treat acute nonmalignant musculoskeletal pain. METHODS: Prospective, single-center, observational study in patients admitted to a rheumatology department for a nonmalignant painful musculoskeletal condition with onset within the last 3 months and a need for WHO Class III analgesics. The following side effects were recorded daily: nausea and vomiting, constipation, pruritus, urinary retention, drowsiness, confusion, and hallucinations. RESULTS: The 75 study patients (46 women and 29 men with a mean age of 56.4 years) were admitted for nerve root pain, osteoporotic vertebral fracture, inflammatory joint disease, or other disorders. First-line treatment was sustained-release morphine sulfate in a mean starting dosage of 55.2 mg/day. The dosage was increased if needed (mean maximum dosage, 78.3 mg/day). Mean treatment duration was 8.9 days. Adverse effects were recorded in 73.3% of patients but were usually minor, requiring no change in the treatment regimen. Eight patients experienced serious adverse effects (confusion in five and urinary retention in three) that resolved with no change in treatment in two patients, after dosage reduction in two patients and after substitution of fentanyl or hydromorphone hydrochloride in four patients. Treatment discontinuation was not associated with adverse effects. CONCLUSIONS: Morphine is often responsible for adverse effects in patients with acute nonmalignant musculoskeletal pain. These effects are usually moderate and very rarely require discontinuation of the drug.

Joint symptoms in patients on bupropion therapy.

OBJECTIVE: To describe joint symptoms related to bupropion therapy. METHODS: We retrospectively reviewed adverse events in bupropion-treated patients reported to the Bourgogne Drug Surveillance Center, France, between October 2001 and December 2002. Joint symptoms classified by the causality assessment as related to bupropion were identified and examined. RESULTS: Four cases were found. Three patients had semi-delayed hypersensitivity reactions resembling serum sickness, manifesting as urticaria and arthralgia with or without a fever. The remaining patient had an unusual presentation consisting in acute monoarthritis of the wrist that started a few days after bupropion initiation. CONCLUSION: Hypersensitivity reactions to bupropion are fairly common and include rare cases of serum sickness-like reaction. Urticaria and incapacitating arthralgia are at the forefront of the clinical picture and may require a brief period of inpatient care. Antihistamines are the treatment of choice. Other manifestations such as acute monoarthritis might occur, although this awaits confirmation as we identified a single case.

Lumiracoxib does not affect methotrexate pharmacokinetics in rheumatoid arthritis patients.

BACKGROUND: Methotrexate and nonsteroidal antiinflammatory drugs are frequently coadministered in the treatment of rheumatoid arthritis (RA). OBJECTIVE: To evaluate the effect of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor, on methotrexate pharmacokinetics and short-term safety in patients with RA. METHODS: This multicenter, randomized, double-blind, placebo-controlled crossover study enrolled 18 patients (mean age 49.1 y) with stable RA. Patients were randomized to receive methotrexate 7.5-15 mg orally once weekly plus either lumiracoxib 400 mg/day or placebo for 7 days. Patients then received the other treatment combination for an additional 7 days. Serial blood and urine were collected for 24 hours after the methotrexate dose on day 1 (methotrexate alone) and days 8 and 15 (combination treatment). RESULTS: Plasma methotrexate pharmacokinetics (AUC(0-t), maximum concentration [C(max)], time to C(max)) and methotrexate protein binding were similar for methotrexate alone (108.0 ng.h/mL, 26.7 ng/mL, 1.5 h, and 57.1%, respectively), methotrexate/lumiracoxib (110.2 ng.h/mL, 27.5 ng/mL, 1.0 h, and 53.7%, respectively), and methotrexate/placebo (101.8 ng.h/mL, 22.6 ng/mL, 1.0 h, and 57.0%, respectively). Similarly, no clinically significant difference was found in the urinary excretion of methotrexate. Mean exposure to the 7-OH metabolite was lower when methotrexate was given with lumiracoxib compared with placebo, shown by a reduction in AUC and C(max), although similar amounts of the metabolite were recovered in urine following both lumiracoxib and placebo. Coadministration of methotrexate and lumiracoxib was well tolerated. CONCLUSIONS: Lumiracoxib had no significant effect on the pharmacokinetics, protein binding, or urinary excretion of coadministered methotrexate in patients with RA.

Sensitivity and specificity of thallium-201 scintigraphy for the diagnosis of malignant vertebral fractures.

OBJECTIVE: To evaluate the accuracy of thallium-201 (201TI) scintigraphy in distinguishing a benign from a malignant recent non-traumatic vertebral fracture. METHODS: STUDY DESIGN--Single center, prospective study. PARTICIPANTS--Patients hospitalized for a recent non-traumatic vertebral fracture. EVALUATION--Usual clinical, laboratory and radiological assessment; 201TI vertebral scintigraphy: patients were injected with iv 3 mCi 201TI. Early and delayed images of the fractured vertebra were obtained. DATA ANALYSIS--(1) Two examinators, unaware of the other findings, rated the images as hyperfixation or not of the fractured vertebra; (2) the ratio (average count per pixel of the fractured vertebra/normal adjacent vertebrae) were calculated. The FINAL DIAGNOSIS was established on the result of vertebral biopsy or on follow-up. RESULTS: Twenty-one patients were included. The final diagnosis was a benign vertebral fracture in 14 patients and a malignant vertebral fracture in 7. The sensitivity, specificity, positive and negative predictive values for a malignant fracture on early 201TI vertebral scintigraphy images were 28.6, 92.9, 66.6, and 72.2%, respectively, and on delayed images were 28.6, 100, 100, and 73.7%, respectively. The ratio of lesioned over normal tissue was not increased in malignant, compared with benign fractures. CONCLUSION: The weak sensitivity does not support the wide use of 201TI bone scintigraphy to distinguish a benign from a malignant recent non traumatic vertebral fracture. However, the high specificity suggests that such evaluation might be proposed prior to vertebral biopsy in some difficult cases.

Nicolau's syndrome after local glucocorticoid injection.

We report three cases of Nicolau's syndrome induced by intraarticular glucocorticoid injections. Nicolau's syndrome is defined as livedo-like dermatitis secondary to acute arterial thrombosis occurring immediately after intravascular injection of an insoluble drug substance. The cases described by Nicolau occurred in association with injections of oily bismuth suspensions. In 1970s and 1980s, cases occurred with delayed-action penicillin suspensions injected intramuscularly. Typically, the injection is followed immediately by excruciating pain in the buttock, sometimes with syncope. Cyanotic patches and a livedoid pattern develop. Rapid resolution of the pain and slower clearing of the skin changes occur in most patients. We report three typical cases with both severe pain and skin changes. In addition, two other patients had incomplete variants without skin abnormalities. Each of these five patients had received an injection in or about a joint of a glucocorticoid in a crystalline suspension. The pathophysiology of this syndrome probably involves acute vascular spasm related to penetration of microcrystals into a blood vessel.

Magnetic resonance imaging in the assessment of synovial inflammation of the hindfoot in patients with rheumatoid arthritis and other polyarthritis.

OBJECTIVES: To describe the localisation of synovitis and tenosynovitis of the hindfoot observed on magnetic resonance imaging (MRI) in patients with chronic polyarthritis, and to correlate the findings of physical examination and MRI. METHODS: Patients with chronic polyarthritis, and one or two painful hindfoot were included. On physical examination and on MRI, the tibio-talar, talo-calcaneal, and talo-navicular and calcaneo-cuboidal joints were adjudged to have or not synovitis, and the tibialis anterior and posterior, the peroneus longus and brevis, the flector digitorum and hallucis longus tendons to have or not tenosynovitis. Criteria for synovitis and tenosynovitis were a high signal intensity on T2-weighted images, a low signal intensity on T1-weighted images, and enhancement after Gd-DTPA injection, in the joint area, and around the tendon, respectively. The correlation between the findings of physical examination and those of MRI were evaluated using the Kappa statistics. RESULTS: 12 patients (three men, nine women, mean age of 55.5 years+/-11.4 S.D.) with chronic polyarthritis (rheumatoid arthritis (RA): nine, ankylosing spondylitis: one; psoriatic arthritis: one, unclassified: one) were included. All presented with one (7 patients) or two (5 patients) painful hindfeet (and swelling for 16 out of 17 hindfeet). On physical examination, 25 joints and eight tendons were adjudged to have synovitis and tenosynovitis. MRI showed synovitis in 12 out of 25 of these joints (48%), and tenosynovotis in three out of eight of these tendons (37.5%). Moreover, MRI showed ten and seven clinically unsuspected synovitis and tenosynovitis, respectively. The proportion of agreements between physical examination and MRI were 54.9% (kappa=0.1) and 88.2% (kappa=0.27) for synovitis and tenosynovitis, respectively. CONCLUSION: A weak correlation was observed between the findings of physical examination and MRI in patients with chronic polyarthritis and a painful hindfoot. MRI might be used to localise synovitis in the area before performing some intra-articular injections. However, other studies are needed to address this question.

Diagnostic usefulness of routine Lyme serology in patients with early inflammatory arthritis in nonendemic areas.

OBJECTIVE: To evaluate the diagnostic usefulness of routine Lyme serology in patients who live in nonendemic areas and present with early inflammatory joint disease. METHODS: All patients admitted to a rheumatology department of a nonendemic area of France for evaluation of joint disease with onset within the last year. The evaluation included a medical history, a thorough physical examination, an electrocardiogram, and an ELISA for antibodies to Borrelia burgdorferi. RESULTS: We included 90 patients, 51 women and 39 men, with a mean age of 48.1 +/- 17.9 years. Mean duration of joint symptoms was 4.3 +/- 4.3 months, with a median of 3 months. A patient (1.1%) reported a tick bite and no patients had a history of erythema migrans. Lyme serology was negative in all 90 patients. CONCLUSION: These results do not support routine Lyme serology in patients living in nonendemic areas and presenting with early inflammatory joint disease. However, Lyme serology remains appropriate in patients with features suggestive of Lyme disease. Given that Lyme disease is amenable to curative treatment, a larger study is in order to confirm our findings.