Bortezomib improved the joint manifestations of rheumatoid arthritis in three patients.

The proteasome inhibitor bortezomib has been proven effective in the treatment of multiple myeloma. We report on 3 patients with rheumatoid arthritis and multiple myeloma in whom bortezomib therapy was associated with improvements in the joint manifestations. The contribution to this effect of the concomitant glucocorticoid therapy is discussed.

Non-TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug: A Randomized Clinical Trial.

IMPORTANCE: One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α (TNF-α) inhibitors; little guidance on choosing the next treatment exists. OBJECTIVE: To compare the efficacy of a non-TNF-targeted biologic (non-TNF) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor. DESIGN, SETTING, AND PARTICIPANTS: A total of 300 patients (conducted between 2009-2012) with rheumatoid arthritis, with persistent disease activity (disease activity score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR] ≥ 3.2 [range, 0-9.3]) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter, pragmatic, open-label randomized clinical trial. The final follow-up date was in August 2013. INTERVENTIONS: Patients were randomly assigned (1:1) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism (EULAR) scale at week 24. Secondary outcomes included the EULAR response at weeks 12 and 52; at weeks 12, 24, and 52; DAS28ESR, low disease activity (DAS28 ≤3.2), remission (DAS28 ≤2.6); serious adverse events; and serious infections. RESULTS: Of the 300 randomized patients (243 [83.2%] women; mean [SD] age, 57.1 [12.2] years; baseline DAS28-ESR, 5.1 [1.1]), 269 (89.7%) completed the study. At week 24, 101 of 146 patients (69%) in the non-TNF group and 76 (52%) in the second anti-TNF group achieved a good or moderate EULAR response (OR, 2.06; 95% CI, 1.27-3.37; P = .004, with imputation of missing data; absolute difference, 17.2%; 95% CI, 6.2% to 28.2%). The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group (mean difference adjusted for baseline differences, -0.43; 95% CI, -0.72 to -0.14; P = .004). At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45% vs 28% at week 24; OR, 2.09; 95% CI, 1.27 to 3.43; P = .004 and 41% vs 23% at week 52; OR, 2.26; 95% CI, 1.33 to 3.86; P = .003). CONCLUSIONS AND RELEVANCE: Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01000441.

24 hours calciuria: normal values, regulations: about a cohort of 317 control subjects.

In a control population, we filed the 24-hour urinary calcium to set normal values, based on weight, BMI and menopause. By assessing calcium intake, 25OHD, PTH, CTX, GFR, we wanted to study how these could influence calcium excretion. A total of 317 subjects of 55.82 ± 12.6 years were studied: 249 women (210 were postmenopausal) and 66 men. Mean urinary calcium 24h was 4.07 ± 2.53 mmol: 3.99 ± 2.89 in men, 3.54 ± 2.44 in premenopausal women, 4.18 ± 2.42 in postmenopausal women. 24-hour urine calcium was lower in overweight subjects whether they are men or women. It was positively correlated to 25OHD, CTX, GFR, serum calcium and negatively to PTH, BMI and weight. In conclusion, urinary calcium was lower in overweight subjects, it increases after menopause. Dietary calcium intake seems little involved in explaining variations in urinary calcium which depends essentially on bone remodeling (CTX), GFR, levels of vitamin D and PTH.

[Vitamin D deficiency prediction by patient questionnaire and secondary hyperparathyroidism in a cohort of 526 healthy subjects in their fifties]. / Le déficit en vitamine D, très fréquent, n'entraîne qu'exceptionnellement une hyperparathyroïdie secondaire chez des sujets sains de la cinquantaine: cohorte de 526 sujets.

INTRODUCTION: Can vitamin D deficiency be predicted by patient questionnaire? Does it lead to secondary hyperparathyroidism that may cause excessive bone resorption? We studied non-osteoporotic subjects in their fifties, in whom vitamin D levels are often tested. PATIENTS AND METHODS: Patients hospitalised for degenerative osteoarthritis or consulting for assessment of menopause, without renal failure and not treated with vitamin D, completed a questionnaire on sun exposure and underwent measurement of serum calcium, creatinine, 25OH vitamin D, PTH and CTX. RESULTS: Five hundred and twenty-six subjects, mean age 54.6 years (71% women), were investigated throughout the year. 25OH vitamin D levels were correlated with sun exposure and varied according to the month of the year, unlike PTH and CTX levels. From November to May, over 90% of subjects had 25OH vitamin D levels<30ng/mL. Of the subjects who did not expose their face, arms and legs to the sun for at least 20min/day, 94% had 25OH vitamin D levels<30ng/mL. PTH levels were negatively correlated with those of 25OH vitamin D. Serum CTX levels were not correlated with PTH or 25OH vitamin D. Only 13% of subjects presented with secondary hyperparathyroidism, characterised by serum calcium<2.55mmol/L and PTH>65pg/mL, associated with increased CTX levels. CONCLUSION: Vitamin D deficiency can be predicted by patient questionnaire. It very rarely leads to secondary hyperparathyroidism.

Infection of the sigmoid colon during TNFα antagonist therapy for chronic inflammatory joint disease.

We report 7 cases of sigmoid colon infection in patients taking TNFα antagonist therapy to treat chronic inflammatory joint disease. There were 5 women and 2 men with a mean age of 57.5 years (range, 21-77 years). The presenting symptoms were abdominal pain, bowel habit changes, and a fever. These symptoms developed within 6 months after starting TNFα antagonist therapy in 5 of the 7 patients. Empirical antibiotic therapy was used in all 7 patients. Surgical colectomy was performed in 4 patients, including 1 who required a temporary Hartmann's procedure. The risk of infection associated with TNFα antagonist therapy is well documented. However, few cases of colon infection have been reported and little is known about this potentially severe complication. Glucocorticoids or non-steroidal anti-inflammatory drugs may worsen the infection, particularly as they can attenuate the clinical symptoms, thereby delaying the diagnosis. A history of sigmoid colon infection, diverticulosis, and/or diverticulitis must be sought before starting treatment with a biological agent. Prophylactic treatment may be considered if such a history is found. Diagnostic investigations are in order to develop a standardized management strategy in patients with a history of intestinal tract infection.

Fatty involution of the gluteus medius muscles: a late-onset girdle myopathy?

BACKGROUND: Involvement of the gluteus medius muscle has been reported in girdle myopathies or facioscapulohumeral myopathies. Camptocormia, or Bent spine syndrome, characterized by involuntary forward flexion of the trunk in the standing position, may be secondary to a late-onset myopathy essentially involving the spinal erector muscles. In this article, we report the observations of patients with severe deficiency of the gluteus medius, suggesting a late-onset myopathy. METHODS: Computed tomography and magnetic resonance imaging (MRI) were performed in 17 patients, with a mean age 76 years, 3 men and 14 women, presenting a Trendelenburg limp related to fatty infiltration of the gluteus medius muscles. Eight of these patients also had camptocormia. RESULTS: Computed tomographic scan and MRI appearance differed from that of age-matched controls and suggested myopathy. MRI excluded an inflammatory disorder or disinsertion of the gluteus medius muscle. Biopsies of gluteus medius and paravertebral muscles showed marked septal fibrosis and adiposis, whereas control biopsies were normal. Creatine phosphokinase was moderately increased in two thirds of patients. CONCLUSIONS: Involvement of the gluteus medius muscles, like involvement of the paravertebral muscles with which it is frequently associated, may be a form of late-onset girdle myopathy.

Longitudinal study of body composition of 101 HIV men with lipodystrophy: dual-energy X-ray criteria for lipodystrophy evolution.

The aim of this study was to define evolution profiles of body composition among human immunodeficiency virus (HIV)-infected men with lipodystrophy. The design is a retrospective analysis using observational data collected longitudinally. We included 101 HIV-infected men with lipodystrophy managed in routine practice and who had 2 dual energy X-ray absorptiometry scans within a minimum interval of 18 mo. Lipodystrophy was defined as a fat mass ratio (FMR, defined as the ratio of the percentage of the trunk fat mass over the percentage of the lower limbs fat mass) equal or superior to 1.5. Patients were classified in "improved" group (IG: increase of lower limbs fat mass >/= 10%) or "nonimproved" group (NIG). Body composition, immunovirological and epidemiological data were collected and compared between the 2 groups. In the whole population, over a 4-yr period, a significant increase was observed for total fat mass, trunk fat mass, and lower limbs fat mass, whereas total lean mass was stable. Total body mineral density decreased. Fifty-nine patients (IG), less exposed to zidovudine than the NIG, had an increase of lower limbs fat mass higher than 10%. But only 13 (22%) regained a normal distribution of fat mass (FMR < 1.5), showing that lipodystrophy was slowly reversible. Among the NIG, 5 patients (11.9%), less exposed to zidovudine and with a higher mean of viral load, reached an FMR below 1.5. It was mainly because of a loss of trunk fat mass, which could be the sign of a lipodystrophy worsening. Lipodystrophy improved for 58.4% of men. The improvement was very slow. Recovery was observed only in patients with an earlier intervention. No correlation was observed between lipodystrophy and total body bone mineral density. The loss of trunk fat mass without gain of lower limbs fat mass may indicate a worsening of HIV disease.

Joint pain with aromatase inhibitors: abnormal frequency of Sjögren's syndrome.

OBJECTIVE: Since the results of the ATAC study, women who have undergone surgery for breast cancer and who require adjuvant hormone therapy are often treated with aromatase inhibitors. With these treatments, joint pain is frequent (30% to 40%) and quite often disabling (5% to 10%). Our objective was to investigate the origin of the pain induced by the anti-aromatases. METHODS: Twenty-four women of mean age 59 years with joint pain of > 5/10 on a visual analog scale underwent a rheumatological consultation and systematic laboratory tests. RESULTS: In 5 patients, pain was considered to have a well defined cause: osteoarthritis, shoulder tendinitis, or paraneoplastic aponeurositis. The other 19 patients had inflammatory pain of the fingers, wrists, shoulders, forefeet, ankles, or knees, with slight synovial thickening of the PIP and MCP joints. Two had an inflammatory syndrome on laboratory tests. Nine of these patients had antinuclear antibodies (ANA > 1/160 on HEp-2 cells) and 4 had rheumatoid factors (> 20 U). Ten patients had sicca syndrome of the eyes or mouth, 7 had probable Sjögren's syndrome according to the San Diego criteria, and one had definite Sjögren's syndrome. One had rheumatoid arthritis, one had Hashimoto thyroiditis, and 2 had positive hepatitis C serology. CONCLUSION: Is the almost total estrogen depletion induced by aromatase inhibitors conducive to the development of sicca syndromes with ANA? Our results should be considered in relation to the Sjögren-like syndromes occurring in aromatase knock-out mice as recently reported.

Male osteoporosis with vertebral fractures? Look for ankylosing spondylitis! A report of 10 cases.

OBJECTIVE: Several authors have described the association of ankylosing spondylitis (AS) and osteoporosis. Usually vertebral fractures complicate severe AS. METHODS: We report a series of 10 men in whom benign spondyloarthropathy was discovered during etiological investigation for osteoporosis. Eight patients had B27+ AS and 2 had psoriatic arthritis with axial involvement. The mean number of vertebral fractures was 1.5. No patient had an appendicular fracture. RESULTS: Phosphorus and calcium levels and measurements of 25OHD3, parathyroid hormone, osteocalcin, and serum CTX were in the normal range. The decrease in bone mineral density was greater in the spine (mean T-score at L2-L4 -2.95, mean total hip T-score -1.67). CONCLUSION: Osteoporosis with fractures may reveal benign spondyloarthropathy whose clinical expression is sometimes incomplete. Our findings demonstrate that osteoporosis is not always correlated with the severity of AS.

Toxoplasmic chorioretinitis and antitumor necrosis factor treatment in rheumatoid arthritis.

OBJECTIVES: To present the data supporting the possible relationship of ocular toxoplasmosis to antitumor necrosis factor-alpha (TNF-alpha) therapy in patients with rheumatoid arthritis (RA). METHODS: A Medline search was performed using the words "toxoplasmosis, anti-TNF-alpha antagonists, chorioretinitis." We report 2 RA patients who developed ocular toxoplasmosis while receiving anti-TNF-alpha therapy. RESULTS: In addition to our patients with toxoplasmic chorioretinitis, there are 2 published cases of cerebral toxoplasmosis during treatment with anti-TNF-alpha agents. CONCLUSION: The risk of serious toxoplasmic infection during anti-TNF-alpha therapy for RA should be recognized.