Israel Medical Association Journal

Chikungunya fever (CHIK-F) has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular tourist sites.  We present three Israeli travelers who developed fever, maculopapular rash and long-standing arthralgias while visiting northern Indian states not known to be involved in the chikungunya fever epidemic. We also present an epidemiological review of the chikungunya epidemic over the past decades. Rare systemic manifestations of this disorder, like catastrophic antiphospholipid syndrome (CAPS) and adult onset still’s syndrome, are discussed. The present era of international travel poses a novel diagnostic and epidemiologic challenge and we must increase our awareness to the possibility of an exotic tropical infectious disease.

Long-term extension studies and observational drug registers have revealed an increased risk of serious infections in patients treated with anti-tumor necrosis factor agents, particularly infliximab, etanercept and adalimumab. The same may be true for the newer biological drugs rituximab, tocilizumab and abatacept, although this has yet to be confirmed by long-term observational studies. We review the risk of tuberculosis, herpes zoster and other opportunistic infections, and the recommendations for screening for tuberculosis and hepatitis B and C infections in patients affected by rheumatoid arthritis, with the aim of informing patients and encouraging greater awareness among physicians.

Behçet’s disease (BD) is a systemic inflammatory disorder characterized by a protean clinical spectrum and an enigmatic pathogenesis. After being classified as an autoimmune disorder, spondyloarthritis and vasculitis, today BD is considered at the crossroad between autoimmune and auto-inflammatory syndromes. Many pathogenetic, clinical and therapeutic clues support this recent interpretation, enabling novel treatment choices such as interleukin (IL)-1 inhibition. Thus, in the last decade the IL-1 receptor antagonist anakinra and the anti-IL-1β monoclonal antibody canakinumab were increasingly administered in BD patients resistant to standard therapies, leading to interesting results and new intriguing pathogenetic implications. However, further studies are essential to both establish how the innate and acquired immune systems interact in BD patients and identify the best way of administering anti-IL-1 agents with regard to dosage, interval of administration and organ response.

There is growing interest in the contribution of vitamin D deficiency to autoimmunity. Several studies have shown an association between low levels of vitamin D and autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes, autoimmune thyroid diseases, celiac disease, and systemic lupus erythematosus (SLE). Vitamin D receptor ligands can mediate immunosuppressive effects. It has been suggested that low levels of this hormone contribute to the immune activation in lupus and other autoimmune diseases. This review updates and summarizes the literature on the association between vitamin D and SLE, and discusses the various correlations between vitamin D and SLE activity, clinical expressions, serology, and gene polymorphisms of vitamin D receptors.

Autoimmune rheumatic diseases (ARD) affect mainly young women during their reproductive years. Fertility is usually not diminished but the time it takes to conceive is usually longer. Factors related to an ARD or to its treatment are responsible for this effect. In addition, contraception counseling is required to prevent negative fetal outcome and exacerbation of disease symptoms. In recent years, advances in therapies, clarification of risk factors for adverse pregnancy outcomes, and a multidisciplinary approach have vastly improved obstetric management, increasing the possibility of successful pregnancy with a high likelihood of favorable outcome.

Background: The role of autoimmune factors in the etiology of coronary artery disease (CAD) was suggested in numerous studies but has not been definitively determined.

Objectives: To assess the possible influence of antiphospholipid and antinuclear antibodies on atherosclerosis development in young patients after myocardial revascularization procedures.

Methods: The study group included 39 patients younger than 45 years with coronary artery disease (CAD) who underwent myocardial revascularization. Serum levels of antiphospholipid (aPL), antinuclear (ANA) and antineutrophil cytoplasmatic (ANCA) antibodies were tested within 1 month after the procedure.

Results: All three types of aPL were significantly higher in CAD patients when compared to healthy controls: anti-β2-glycoprotein I (aβ2GPI), both immunoglobulin (Ig)G and IgM classes (median 4.10 SGU, range 3.45–21.63 vs. 0.76, 0.12–6.01, P < 0.001, and 2.82 SGU, 1.44–11.70 vs. 1.08, 0.44–3.64, P < 0.001, respectively); anticardiolipin antibodies (aCL) both IgG and IgM classes (3.13 GPL, 1.32–14.03 vs. 2.42, 0.96–18.45, P = 0.0037, and 6.94 MPL, 1.90–26.40 vs. 4.32, 1.9–28.73, P < 0.008, respectively); and lupus anticoagulant (LA) (27.7% vs. 0%, P = 0.005). ANA were elevated in one patient and ANCA in 23 (60%). The levels of aPL did not correlate with the presence of a clot in a coronary vessel detected during angiography or with exacerbation of coronary artery atherosclerosis.

Conclusions: In young patients with CAD who underwent myocardial revascularization the levels of aPL were significantly higher than in young healthy subjects. Thus, besides the classic risk factors for CAD, autoimmunity may play an important role in atherosclerotic plaque formation and progression.

Behçet's disease (BD) is a multi-systemic disorder of unknown etiology characterized by relapsing oral-genital ulcers, uveitis, and involvement of the articular, gastrointestinal, neurologic, and vascular systems. The choice of treatment is based on the severity of systemic involvement, clinical presentation and the site affected, and includes corticosteroids, azathioprine, interferon, cyclophosphamide, methotrexate or tumor necrosis factor-alpha and interleukin-1 blockers. We present a case series of four refractory BD patients successfully treated with intravenous immunoglobulins (IVIG). All patients fulfilled International Study Group criteria. The patients’ mean age was 38.75 ± 12.09 years and mean disease duration 10.25 ± 8.5 years. Human leukocyte antigen B51 was positive in two of four patients. In addition to oral aphthosis, all patients suffered from genital ulcers and cutaneous BD-related manifestations; central nervous system involvement and arthralgia were found in two patients. Peripheral nervous system, gastrointestinal and eye involvement occurred in 25% of cases. In all patients, previously treated according to EULAR recommendations without reaching satisfactory results, IVIG induced immediate and sustained response over time without incurring any side effects. We propose IVIG administration as an additional effective and safe treatment option in patients with severe and resistant BD.

Background: Radiation exposure is a well-known risk factor for well-differentiated thyroid cancer (WDTC). However, disease characteristics, optimal treatment, time from exposure to disease appearance, and the effect on outcome of age at initial exposure have yet to be determined. 

Objectives: To identify the characteristics of radiation-induced thyroid carcinoma.

Methods: We retrieved the charts of all patients previously exposed to radiation who were diagnosed with WDTC between the years 1985 and 2013 in a tertiary referral center. 

Results: Forty-four patients were reviewed. Median time from radiation exposure to diagnosis was 23 years. These patients had higher rates of aerodigestive symptoms and distant metastases on presentation than seen in non-radiated patients. Patients who were exposed to radiation before age 15 years tended to develop the disease at a younger age but had a longer latency period (34.7 ± 15.3 vs. 16.3 ± 10 years, P < 0.001) and none had significantly higher rates of vocal cord palsy, hoarseness on presentation, or aggressive variants on histology compared to patients exposed to radiation at an older age. Disease-specific survival (DSS) was the same for both groups and were similar to that seen in the general population (95% 20 year DSS).

Conclusions: Radiation-induced thyroid cancer has a more aggressive presentation and the age at exposure affects the presentation of disease. Nonetheless, appropriate treatment leads to a favorable prognosis.

 

Background: Concomitant carotid artery disease (CaAD) in patients with coronary artery disease (CAD) is associated with worse cardiac and neurologic outcomes. The reported prevalence and risk factors for concomitant CaAD in CAD patients varied among previous studies. 

Objectives: To examine these factors in ambulatory patients with CAD and well-documented cholesterol levels treated with cholesterol-lowering medications. 

Methods: We retrospectively analyzed prospectively collected data from 325 unselected patients with CAD (89 women, mean age 68.8 ± 9.9 years) undergoing routine evaluation at the coronary clinic of our hospital. 

Results: The low density lipoprotein-cholesterol (LDL-C) was < 100 mg/dl in 292 patients (90%). Age at onset of CAD symptoms was 59.4 ± 10.8 years. Carotid stenosis ≥ 50% was seen in 83 patients (25.5%) and between 30% and 49% in 55 patients (17%) (duplex method). Carotid stenosis was significantly associated with hypertension (P = 0.032), peripheral arterial disease (P = 0.002) and number of coronary arteries with ≥ 50% stenosis (P = 0.002), and showed a borderline association with age at CAD onset (P = 0.062) and diabetes mellitus (P = 0.053). On linear regression analysis, independent predictors of CaAD were peripheral vascular disease (OR 3.186, 95%CI 1.403–7.236, P = 0.006), number of coronary arteries with ≥ 50% stenosis (OR 1.543, 95%CI 1.136–2.095, P = 0.005), and age at CAD onset (OR 1.028, 95%CI 1.002–1.054, P = 0.003). None of the variables studied predicted freedom from CaAD. 

Conclusions: Carotid atherosclerosis is very common in stable ambulatory patients with CAD regularly taking statins. The risk is higher in patients with peripheral arterial disease, a greater number of involved coronary arteries, and older age at onset of CAD. 

 

Background: Various vena cava filters (VCF) are designed with the ability to be retrieved percutaneously. Yet, despite this option most of them remain in the inferior vena cava (IVC). 

Objectives: To report our experience in the placement and retrieval of three different types of VCFs, and to compare the indications for their insertion and retrieval as reported in the literature.

Methods: During a 5 year period three types of retrievable VCF (ALN, OptEase, and Celect) were inserted in 306 patients at the Rabin Medical Center (Beilinson and Hasharon hospitals). Indications, retrieval rates, median time to retrieval, success and complications rate were viewed and assessed in the three groups of filter types and were compared with the data of similar studies in the literature.

Results: Of the 306 VCFs inserted, 31 (10.1%) were retrieved with equal distribution in the three groups. In most patients the reason for filter insertion was venous thromboembolic events (VTE) and contraindications to anticoagulant therapy. Mean age was 68.38 ± 17.5 years (range 18–99) and was noted to be significantly higher compared to similar studies (53–56 years) (P < 0.0001). Multi-trauma patients were significantly older (71.11 ± 14.99 years) than post-pulmonary embolism patients (48.03 ± 20.98 years, P < 0.0001) and patients with preventive indication (26.00 ± 11.31, P < 0.0001). The mean indwelling time was 100.6 ± 103.399 days. Our results are comparable with the results of other studies, and there was no difference in percentage of retrieval or complications between patients in each of the three groups. 

Conclusions: In 1 of 10 patients filters should be removed after an average of 3.5 months. All three IVC filter types used are safe to insert and retrieve.