Yolanda Braun-Moscovici

Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response

Objective: To assess the effect of rituximab on the efficacy and safety of influenza virus vaccine in patients with rheumatoid arthritis (RA). Methods: The study group comprised patients with RA treated with conventional disease-modifying drugs with or without rituximab. Split-virion inactivated vaccine containing 15 μg haemagglutinin/dose of B/Shanghai/361/02 (SHAN), A/New Caledonian/20/99 (NC) (H1N1) and A/California/7/04 (CAL) (H3N2) was used. Disease activity was assessed by the number of tender and swollen joints, duration of morning stiffness and evaluation of pain on the day of vaccination and 4 weeks later. CD19-positive cell levels were assessed in rituximab-treated patients. Haemagglutination inhibition (HI) antibodies were tested and response was defined as a greater than fourfold rise 4 weeks after vaccination or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). Geometric mean titres (GMT) were calculated in all subjects. Results: The participants were divided into three groups: RA (n = 29, aged 64 (12) years), rituximab-treated RA (n = 14, aged 53 (15) years) and healthy controls (n = 21, aged 58 (15) years). All baseline protective levels of HI antibodies and GMT were similar. Four weeks after vaccination, there was a significant increase in GMT for NC and CAL antigens in all subjects, but not for the SHAN antigen in the rituximab group. In rituximab-treated patients, the percentage of responders was low for all three antigens tested, achieving statistical significance for the CAL antigen. Measures of disease activity remained unchanged. Conclusion: Influenza virus vaccine generated a humoral response in all study patients with RA and controls. Although the response was significantly lower among rituximab-treated patients, treatment with rituximab does not preclude administration of vaccination against influenza.

Vitamin D, Parathyroid Hormone, and Acroosteolysis in Systemic Sclerosis

Objective Sclerodactyly with acroosteolysis (AO) and calcinosis are prominent features of systemic sclerosis (SSc), but the pathogenesis of these findings is poorly understood. Vitamin D and parathyroid hormone (PTH) have a crucial role in bone metabolism and resorption and may affect AO and calcinosis. We assessed vitamin D and PTH in patients with SSc. Methods Medical records of 134 consecutive patients with SSc (American College of Rheumatology criteria) followed at the rheumatology department during the years 2003–2006 were reviewed for clinical assessment, laboratory evaluation [including 25(OH) vitamin D, calcium, phosphorus, alkaline phosphatase, PTH, creatinine, and albumin]; imaging data confirming AO and/or calcinosis. Patients followed routinely at least once a year were included (81 patients). Of these, 60 patients’ medical records were found to have complete, relevant clinical, laboratory, and radiographic imaging. Results Thirteen patients had diffuse disease and 47 limited disease — 51 women and 9 men, 44 Jews and 16 Arabs; mean age 55 ± 14 years; disease duration 8 ± 6 years. AO with or without calcinosis was observed in 42 patients (70%). Vitamin D deficiency was found in 46% of patients (16 out of 44 Jewish patients, 10 out of 16 Arab patients). PTH was elevated in 21.7% of patients. Significant correlations were observed between acroosteolysis and PTH (p = 0.015), calcinosis (p = 0.009), and disease duration (p = 0.008), and between PTH and vitamin D levels (p = 0.01). All patients had normal serum concentrations of calcium, phosphorus, magnesium, and albumin, and liver and kidney functions. Conclusion In this group of Mediterranean patients with SSc, the incidence of vitamin D deficiency and secondary hyperparathyroidism was surprisingly high. This finding correlated with the occurrence of AO and calcinosis. Low levels of vitamin D may reflect silent malabsorption and might be a risk factor for secondary hyperparathyroidism and bone resorption. Traditional dress habits and low exposure to sun may contribute to vitamin D deficiency in an Arab population but do not explain all the findings. The pathogenesis of these findings needs to be corroborated in other SSc populations.

Vasculitis in siblings with familial Mediterranean fever: a report of three cases and review of the literature.

Familial Mediterranean Fever (FMF) is characterized by recurrent attacks of self-limited polyserositis and fever. Several types of vasculitis are associated with FMF: polyarteritis nodosa, Henoch–Schonlein purpura (HSP), and protracted febrile myalgia (PFM). We describe three cases of vasculitis in four siblings of a Sephardic Jewish family with FMF and reviewed the literature. One brother and one sister developed severe HSP with intestinal involvement while another brother developed PFM. Genetic tests in three brothers confirmed the M694V mutation on both alleles. Vasculitides may be a clinical feature of FMF with a higher familiar prevalence. MEFV mutations may act as a genetic susceptibility factor for vasculitides in FMF patients.

Immunoglobulin for rheumatic diseases in the twenty-first century: take it or leave it?

&NA; There is no simple answer to the question: intravenous immunoglobulin—take it or leave it? A thorough review of the current data on mechanisms of action, efficacy, and safety of intravenous immunoglobulins in rheumatic diseases demonstrates that the answer depends on the disease and the patients involved.

Relapse of rheumatoid arthritis after substitution of oral for parenteral administration of methotrexate

We read with interest the letters: “Is parenteral methotrexate worth trying?” by Osman and Mulherin1 and “Intramuscular methotrexate in inflammatory rheumatic disease” by Burbage, Gupta, and Lim.2 We would like to present our findings, which indicate that parenteral methotrexate (MTX) may be more efficient than oral MTX at the same dose and in the same patients with inflammatory joint disease. During the second half of 2000 we were faced with an unexpected shortage of parenteral MTX (ABIC, Israel) which lasted for more than five months, and patients were switched to oral MTX (Lederle, Germany). This gave us the opportunity to evaluate the difference in efficacy of parenteral versus oral administration of low dose MTX. Eight patients (seven female) with a mean age of 55 (38–70) years, who fulfilled the following criteria, were analysed retrospectively: ( a ) all had inflammatory joint diseases (four seropositive rheumatoid arthritis (RA), two seronegative RA (revised American Rheumatism Association criteria for RA), and two RA-like psoriatic arthropathy); ( b ) all were receiving parenteral MTX and were in complete clinical remission (fulfilling at least five of six …

Periodontal Condition of Patients With Autoimmune Diseases and the Effect of Anti-Tumor Necrosis Factor-α Therapy

BACKGROUND The aim of this study is to evaluate the effect of autoimmune diseases (AIs), as well as anti-tumor necrosis factor-α (TNF-α) therapy on the clinical and immunologic parameters of the periodontium. METHODS Thirty-six AI patients (12 rheumatoid arthritis [RA], 12 psoriatic arthritis, and 12 systemic sclerosis) were recruited together with 12 healthy (H) and 10 RA patients receiving anti-TNF-α therapy (RA+). Periodontal indices including plaque index, gingival index (GI), probing depth (PD), and bleeding on probing (BOP) were measured, and gingival crevicular fluid (GCF) was collected from five deepest pockets using papers strips. The TNF-α level was analyzed using enzyme-linked immunosorbent assay. Analysis of variance test was used for statistical comparison between groups, whereas Pearson linear correlation coefficient test was used to examine the association between TNF-α and periodontal status indices. RESULTS The three AI subgroups were very similar in clinical and immunologic parameters. GI was greater in the AI patients compared to the H and RA+ groups (1.91 ± 0.54, 1.21 ± 0.67, and 1.45 ± 0.30, respectively, P = 0.0005). AI patients exhibited significantly more BOP than H and RA+ (46.45% ± 17.08%, 30.08% ± 16.86%, and 21.13% ± 9.51%, respectively, P = 0.0002). PD in H and RA+ groups were lower than in the AI (3.47 ± 0.33, 3.22 ± 0.41, and 3.91 ± 0.49 mm, P = 0.0001). Number of sites with PD >4 mm was higher in AI patients compared to H and RA+ (42.44 ± 17.5 versus 24.33 ± 15.62 versus 33.3 ± 6.6, P = 0.0002). GCF TNF-α was higher among the AI patients (1.67 ± 0.58 ng/site) compared to 1.07 ± 0.33 ng/site for the H group and 0.97 ± 0.52 ng/site for the RA+ group (P = 0.0002). A significant positive correlation was found between PD and TNF-α levels in the GCF (r = 0.4672, P = 0.0002), BOP (r = 0.7491, P = 0.0001), and GI (r = 0.5420, P = 0.0001). CONCLUSIONS Patients with AI diseases have higher periodontal indices and higher TNF-α levels in GCF than H controls. Anti-TNF-α treatment appears to reverse this phenomenon.

Scleroderma – New aspects in pathogenesis and treatment

Systemic sclerosis (SSc) is a multisystem disease with a variable clinical course and a poor prognosis corresponding to extent of microangiopathy and skin and internal organ fibrosis. Microvascular damage provokes immune cells to produce autoantibodies, pro-inflammatory and pro-fibrotic cytokines and chemokines. The hallmark of SSc is excessive collagen production by activated fibroblasts and myofibroblasts, and its accumulation in skin and internal organs. Better understanding of SSc pathogenesis resulted in the development of drugs, such as prostanoids, endothelin-1 and phosphodiesterase inhibitors, for treatment of pulmonary arterial hypertension and digital ulcers. The use of biological therapies and anti-fibrotic agents is under investigation. Stem cell transplantation seems to be promising in restarting the immune system to diminish fibrosis and restore microvasculature. Future research will be directed at genetic factors, diagnostic and prognostic markers for fibrosis and microangiopathy, and development of drugs directed to pathogenic key cells and mediators.

Cocaine-Induced Raynaud’s Phenomenon and Ischaemic Finger Necrosis

Abstract A 37-year-old man with ischaemic finger necrosis and recent-onset Raynaud’s phenomenon associated with cocaine abuse is reported. Initial therapy with systemic vasodilators, low-molecular-weight heparin and aspirin failed. Resolution of the ischaemia and ulcer healing was rapidly achieved with intravenous infusions of the prostacyclin analogue iloprost. The mechanism of vascular ischaemic injury and the development of secondary Raynaud’s phenomenon due to cocaine use is discussed.

Pulmonary Arteries Involvement in Takayasu's Arteritis: Two Cases and Literature Review

OBJECTIVES To review pulmonary arteritis (PA) complicated by pulmonary arterial hypertension (PAH) in Takayasus arteritis (TA). METHODS Two cases of PA and PAH in TA patients and similar cases published in the Medline database from 1975 to 2009 were reviewed. RESULTS Forty-six cases (females 89.1%, Asians 65%, mean age 34.6 years) were analyzed, 42.2% of which had PAH. Isolated PA was reported in 31.8%. Respiratory symptoms were presented as dyspnea (75.5%), chest pain (48.9%), hemoptysis (42.2%), and cough (17.7%). Hypertension, vascular bruits, and diminished/absent pulses were reported in 48.9% of patients. A diagnosis of PA was based on abnormal uptake on pulmonary perfusion scan and a finding of stenosis, narrowing, occlusion, and irregularity on computed tomography or magnetic resonance imaging, and/or pulmonary angiography. Patients were treated with glucocorticoids (77.5%), disease-modified antirheumatic drugs (35%), and warfarin (20%); only a few were treated with biological agents. Vascular procedures were performed in 52.5% of cases, on pulmonary arteries in 37.5% with good results. The outcome was death in 20.5% of PA patient and 33.3% in PAH patients. CONCLUSIONS TA may be complicated by life-threatening PA and PAH. Clinical signs are not specific and may be masked by involvement of the aorta and its branches. Treatment with glucocorticoids and disease-modified antirheumatic drugs has only partial effect, which may be intensified by biological agents. Invasive procedures on pulmonary arteries may be a complementary option. PA and PAH in TA patients should be recognized early and treated promptly for prevention of irreversible vascular damage.

Pneumatosis cystoides intestinalis in scleroderma-related conditions.

Aims:  Pneumatosis cystoides intestinalis (PCI) is a rare life‐threatening gastrointestinal complication in the course of connective tissue disease (CTD). PCI is characterised by the appearance of intramural clusters of gas in the small and large bowel wall on X‐ray or computed tomography and often is accompanied by free air in the peritoneal cavity.