A high and equal prevalence of the Q703K variant in NLRP3 patients with autoinflammatory symptoms and ethnically matched controls.

OBJECTIVES: Cryopyrin associated periodic syndromes (CAPS) comprise a spectrum of autoinflammatory disorders of varying severity caused by mutations in the NLRP3 gene. The NLRP3-Q703K allele has been reported both as a functional polymorphism and as a low penetrance mutation. METHODS: To describe the clinical phenotype of subjects with the Q703K allele and to report the frequency of this allele among patients with autoinflammatory symptoms and healthy controls. To this end, a cohort of 10 ethnically-matched controls per each Q703K-carrying patient, was composed. RESULTS: Ninety patients suspected of harboring a systemic autoinflammatory disease (SAID), exclusive of FMF, were referred to our center for genotyping between 2012 and 2015. Fourteen of them (15.5%) were found to carry the Q703K allele, compared to 22 of 130 (16.9%) healthy, ethnically matched controls. CONCLUSIONS: The similar carrier rate of the NLRP3-Q703K allele among patients with manifestations of a SAID and an ethnically matched control group suggest that this variant, does not determine the clinical phenotype. This reiterates the importance of testing a control group to avoid erroneously attributing a causative role to a gene polymorphism.

MEFV mutation carriage in Israeli Jewish individuals from ethnicities with low risk for familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a disease caused by mutations in the MEditerranean FeVer gene (MEFV), and in Israel it most commonly affects Jews of North African extraction, in whom the mutation carrier rate is as high as 1 in 5. To assess the protective as well as the modulating affect of MEFV mutation carriage on various inflammatory disease states, we sought to define the frequency of MEFV mutations in Israeli Jewish individuals of various ethnicities, including those with low frequency of FMF, which were not in the focus of our attention hitherto. A total of 163 adults of Bucharian, Turkish, Georgian, Yemenite and Bulgarian origin comprised the study group. The prevalence of the most frequent MEFV mutations in the Israeli Jewish population, namely: M694V, V726A and E148Q, was assessed. The association of mutation carriage with a personal history of FMF-like phenomena, as well as various inflammatory and non-inflammatory diseases, was evaluated. A high MEFV mutation frequency was found among Jews of Bucharian, Georgian and Bulgarian origin (20%), whereas intermediate and low rates were detected in Jews of Turkish and Yemenite extraction (14 and 8%, respectively). FMF-like manifestations and related diseases were observed more often in MEFV mutation carriers than in their counterparts. MEFV mutation frequency, directly assessed by DNA analysis, exceeds the rate calculated from disease prevalence in Israeli Jewish individuals originated from ethnicities with a low prevalence of FMF. MEFV mutation carriage in this subgroup is associated with various inflammatory disorders.

Use of complementary and alternative medicine among patients attending rheumatology clinics in Israel.

BACKGROUND: Complementary and alternative medicine has recently attracted attention due to its widespread use. In a recent study in Israel, almost a half of CAM users in the general population used it for joint diseases or back pain. OBJECTIVE: To evaluate the prevalence of CAM use among patients with defined rheumatic diseases, and analyze the demographic features of CAM users, their reasons for using CAM and the use of specific CAM methods. METHODS: We conducted face-to-face structured interviews of 350 patients attending rheumatology clinics, regarding past or present use of CAM, specifying the various CAM types they used, and reasons for using CAM. Demographic data including age, gender, country of birth and origin, and level of education were also collected. RESULTS: Altogether, 148 patients reported using CAM (42%). In general, homeopathy and acupuncture were the most commonly used types (44% and 41% of the patients, respectively). The mean number of CAM methods per patient was 1.9 +/- 1.1. CAM was more commonly used by patients with advanced education (52% vs. 37% of patients with lower education, P= 0.007). Patients with rheumatoid arthritis used CAM significantly less than patients with other rheumatologic conditions (32% vs. 48%, P= 0.008). CONCLUSION: CAM use is influenced by level of education. The choice of the preferred CAM method among patients with rheumatic diseases seemed to follow the popular CAM methods in the general population, and was not specific to rheumatic diseases.

The outcome of pregnancy in the wives of men with familial mediterranean fever treated with colchicine.

OBJECTIVE: To evaluate the outcome of pregnancies of normal women married to men with familial Mediterranean fever (FMF), some of whom took colchicine during the conception with their wives. PATIENTS AND METHODS: We followed the outcome of pregnancies and deliveries of 60 wives of FMF patients; 53 of the husbands were taking colchicine during that time. As a control group we screened the outcome of pregnancy and delivery from 230 healthy women married to healthy men. RESULTS: The 60 FMF patients- wives had 222 pregnancies, of which 206 ended in term delivery with 209 live births. Sixteen pregnancies ended in spontaneous abortions (7%). Three of the newborns in the study group were born with congenital malformations. In the control group, of 788 pregnancies, 127 ended in abortions (16%). Six of the newborns were born with congenital malformations. The rate of the late abortions (second trimester) in both groups was comparable. CONCLUSIONS: The results of our study indicates that neither FMF nor colchicine increases the rate of abortions or congenital malformations. Therefore we believe that there is no need to discontinue colchicine treatment in men with FMF before the conception with their wives.

Low-dose aspirin and prevention of cranial ischemic complications in giant cell arteritis.

OBJECTIVE: Cranial ischemic complications such as cerebrovascular accidents (CVAs) and acute visual loss are among the leading causes of giant cell arteritis (GCA)-related morbidity. In this retrospective study, we evaluated the effect of treatment with low-dose aspirin on the incidence of cranial ischemic complications in GCA. METHODS: Charts of 175 consecutive patients in whom GCA was diagnosed between 1980 and 2000 were reviewed for medical data. Data for 166 patients who were followed up for at least 3 months were also available. RESULTS: At the time of the diagnosis of GCA, 36 patients (21%) had already been receiving low-dose aspirin (100 mg/day). In all cases, the indication for this treatment was ischemic heart disease. There were no significant differences between the aspirin-treated and non-aspirin-treated groups regarding the mean age of patients, the male-to-female ratio, duration of GCA-related symptoms, rates of headaches, systemic symptoms, and jaw claudication, and the mean erythrocyte sedimentation rate, hemoglobin count, and platelet count. Cerebrovascular risk factors (hypertension, hyperlipidemia, or diabetes mellitus) were more common in the aspirin-treated group (38.9% versus 20%; P= 0.03). Cranial ischemic complications were diagnosed in 43 patients at presentation: 30 patients had acute visual loss, 11 had CVAs, and 2 had both conditions simultaneously. Only 3 of the aspirin-treated patients (8%) presented with cranial ischemic complications, compared with 40 (29%) of the non-aspirin-treated patients (P = 0.01). Despite the use of steroid therapy, cranial ischemic complications developed in 14 of the 166 patients followed up for 3 months or longer. However, cranial ischemic complications developed in only 3% of the aspirin-treated patients, compared with 13% of the patients treated with prednisone only (P = 0.02). CONCLUSION: These data suggest that low-dose aspirin decreases the rate of visual loss and CVAs in patients with GCA.

Risk factors for cranial ischemic complications in giant cell arteritis.

Cranial ischemic complications (CICs) are among the presenting manifestations of giant cell arteritis (GCA). Yet patients with GCA may develop CICs at a later stage, despite steroid therapy. In the current report we delineate risk factors for CICs, both at presentation and during follow-up, and review the relevant literature. We reviewed charts of 175 patients with GCA. Follow-up data were available for 166 patients. CICs at presentation or developing within 2 weeks of GCA diagnosis were considered GCA related. CICs developing later were considered GCA related only when associated with other GCA-related manifestations or acute-phase reactions. Associations between CICs and other variables were tested by multivariate analysis. At presentation, 43 patients (24.6%) had CICs. Risk factors were transient cerebro-ophthalmic ischemic episodes (COIEs) (odds ratio [OR] 4.3) and male sex (OR 2.5), while the presence of systemic symptoms was "protective" (OR 0.3). During follow-up 8.4% of patients with GCA developed new CICs. Risk factors in these cases were previous CICs at presentation (OR 5.6) and transient COIEs developing during follow-up (OR 14.8). The use of low-dose aspirin was protective (OR 0.2). These data, together with data from the literature review, suggest that GCA patients with transient COIEs and without fever or other systemic symptoms are at increased risk of presenting with CICs. Risk factors for late-developing CICs were CICs at presentation and late-developing transient COIEs.

Intestinal protein loss and hypoalbuminemia in children with pneumonia.

BACKGROUND: Intestinal protein loss has been reported mainly in diseases affecting the gastrointestinal tract. Intestinal protein loss during pneumonia with effusion has not been reported to date. The authors attempted to assess the associations between pneumonia with effusion and intestinal protein loss and hypoalbuminemia in children. METHODS: This was a prospective consecutive case series study of in children hospitalized with pneumonia and effusion during a period of 4(1/2) years. Serum albumin, C-reactive protein (CRP), and fecal alpha-1 antitrypsin (alpha-1-AT) were measured in the first 72 hours of hospitalization. Two control groups were studied: one consisted of 50 febrile children hospitalized because of viral or mild bacterial infections, and the other consisted of 20 afebrile children hospitalized because of convulsive disorders. RESULTS: Sixty-seven children ages 4 months to 14 years hospitalized with pneumonia and effusion were enrolled in the study. Fifty-nine percent (40 children) were found to have elevated fecal alpha-1-AT excretion (range, 2-10 mg/g) compared with none in the two control groups (P < 0.000).Fifty-two percent (35 children) of the children with pneumonia and effusion had mild to moderate hypoalbuminemia (range, 22-34 g/L). Only one child (2%) in the febrile control group had a low albumin of 34 g/L; none were found in the afebrile control group. The level of fecal alpha-1-AT was inversely correlated with serum albumin level. CONCLUSIONS: Pneumonia with effusion in children is often associated with an intestinal protein loss that can be monitored by measuring gastrointestinal loss of protein, namely fecal alpha-1-AT. In most cases the development of hypoalbuminemia correlates with the development of intestinal protein loss.