Israel Medical Association Journal

Fibromyalgia is a pain-related condition common in women and is present in about 5% of the population [1]. Its treatment involves physical exercise, psychotherapy (mainly behavioral–cognitive therapy), and antidepressant/anticonvulsant use as class IA evidence treatments [1]. Although in several cases this treatment fails or loses effectiveness over time, necessitating novel therapeutical agents.

Naltrexone is an opioid antagonist drug used for opioid addiction therapy. It also has anti-inflammatory and analgesic properties when used in low dosages [2]. Our group recently wrote a systematic review of low-dose naltrexone (LDN) for treating rheumatic diseases, including fibromyalgia [3]. In all seven published articles on LDN for fibromyalgia, a benefit was observed in pain reduction and improvements in fibromyalgia questionnaires [3]. To the best of our knowledge, no study using LDN as the first option of treatment has been conducted. Therefore, in this study we aimed to evaluate the effects of LDN as the first line of therapy in patients with fibromyalgia.

Hearing and vestibular function may be affected by gout and/or hyperuricemia. We performed a systematic review of the literature on ear involvement in patients with gout and hyperuricemia. We selected 24 articles: 8 case reports and 16 original articles. Case reports mainly focused on the presence of tophi in the middle ear, which was resolved with surgical treatment. Seven articles studied the hearing function in relationship to serum uric acid and 10 articles studied the occurrence of vertigo, with one of them studying both aspects. Regarding results on vertigo, five studies showed an association with uric acid elevation, three with lowering of uric acid, and two found no differences. Concerning hearing loss, five studies detected poor hearing function in association with high uric acid levels while other two did not.) Most of the studies showed an association of hearing loss with high uric acid/gout. Regarding vestibular function, the results are too heterogeneous to make any conclusions.

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease characterized by synovitis leading to polyarthritis. It affects 1% of the population [1]. Genetic and environmental factors are linked to the development of RA and include the presence of HLA-DR4 and shared epitope, and smoking is the primary representative of the negative environmental factor [1].

However, RA mainly affects middle age. Late-onset RA that initiates after 60 years is sometimes named elderly onset rheumatoid arthritis (EORA) [2]. This disease's prevalence varied from 2.03% to 2.34% in a large study in the United States. EORA affects more women than men [1]. However, to the best of our knowledge, no patient description of RA initiated at 97 years of age has been described.

Background: Lumbar spinal stenosis (LSS) is a narrowing of the lumbar canal causing lower back pain, gluteal pain, and neurogenic claudication. LSS has been associated with cardiovascular co-morbidities. Metabolic syndrome (MetS), a pro-inflammatory condition involving a cluster of risk factors for cardiovascular disease and diabetes, is increasingly prevalent worldwide.

Objectives: To evaluate the prevalence of MetS in patients with LSS, compared to age- and sex-matched healthy controls, and to explore potential associations between MetS and LSS-related clinical parameters and cardiovascular risk factors.

Methods: We conducted a cross-sectional study including 64 patients diagnosed as symptomatic LSS (NASS criteria) and 32 controls. MetS was diagnosed using the 2009 Harmonizing criteria adjusted for South Americans. Multivariate logistic regression was used to identify independent risk factors for MetS. The level of statistical significance was set at 5%.

Results: The prevalence of MetS was significantly higher in the LSS group than in the control group (76.6% vs. 31.3%; P < 0.001). LSS patients displayed greater waist circumference (P = 0.003), blood glucose levels (P = 0.009) and arterial pressure (P < 0.001) than controls. The variables with independent influence on MetS in the logistic regression model were: diabetes (P = 0.008), blood glucose (P = 0.004), and body mass index (P = 0.005).

Conclusions: MetS was significantly more prevalent among LSS patients, and diabetes and elevated body mass index were found to be risk factors for MetS in these LSS patients

Background: Vitamin D deficiency and insufficiency have been reported in fibromyalgia. However, to the best of our knowledge, only one study has evaluated the role of 25-hydroxyvitamin D [25(OH)D] supplementation on fibromyalgia symptoms.

Objectives: To analyze the effects of 3 months of 25(OH)D supplementation on symptoms of fibromyalgia.

Methods: This study included 11 female patient. Demographic and clinical data, tender points, visual analog scale results, and pre- and post-serum levels of 25(OH)D supplementation were analyzed. The levels of 25(OH)D were measured by a radioimmunologic test.

Results: Patients with fibromyalgia diagnosis and 25(OH)D values ≤ 30 ng/ml were recruited to receive 50,000 IU of oral vitamin D once every week for 3 months. The disease was diagnosed based on the American College of Rheumatology criteria. The median age of all patients was 48.5 (28–67) years and 63.4% were Caucasian. Disease duration varied from 1–10 years. The 25(OH)D levels increased significantly after 3 months, 18.4 (15.5–25.8) ng/ml vs. 33.8 (28–58) ng/ml, P = 0.01. Interestingly, an improvement of visual analog scale scores was observed at 3 months, 90 (0–100) vs. 30 (0–80), P = 0.002. Eight patients (72.2%) responded that they experienced a very significant improvement in symptoms. In addition, a trend for reduction of the number of tender points was observed after 3 months, 17 (11–18) vs. 10 (0–18), P = 0.07.

Conclusions: The 25(OH)D levels and disease symptoms in patients with fibromyalgia and vitamin D deficiency/insufficiency seem to improve with vitamin D supplementation.

Smoking is a risk factor for thromboangiitis obliterans (TAO, Buerger’s disease) and arteriosclerosis, but there are few cases of coronary heart disease (CAD)-associated Buerger's disease. A literature search for articles in English, Spanish and French published between 1966 and 2012 on patients with coronary involvement and TAO revealed 12 patients. We describe an additional case with involvement of the central nervous system, myocardium and large-diameter proximal arteries. The main clinical manifestations in these 13 cases were lower limb claudication and acute thoracic pain. The histologic findings showed thrombosis with unbroken internal elastic lamina and intimal clusters of granulocytes; coronary angiography revealed predominant involvement of the left anterior descending and right coronary artery. Treatment included coronary bypass procedures, coronary angioplasty, smoking cessation, and anticoagulant therapy. A complete therapeutic response was observed in half the patients. This review of all published cases of TAO patients with coronary symptoms, together with our patient, demonstrates the rarity of this clinical association. Patients under age 40 with CAD but no prominent cardiovascular risk factors besides smoking should be evaluated for the presence of Buerger's disease.

Objectives: To describe the types of endothelial cell organelles involved in vascular permeability in drug-induced acute urticaria (DIAU).

Methods: Seven patients with DIAU were enrolled in the study. Biopsies of urticarial lesions and apparently normal skin were performed. The 14 collected fragments were processed with immunogold electron microscopy using single stains for tryptase and factor XIIIa (FXIIIa) and double immunogold labeling for both tryptase and FXIIIa.

Results: Some sections demonstrated mast cells in the degranulation process, in both anaphylactic and piecemeal degranulation. After double immunogold staining, 10 nm (FXIIIa) and 15 nm (tryptase) gold particles were both present, covering the granules in the mast cells, indicating that both tryptase and FXIIIa were localized within the granules of these cells. Interestingly, we found strong evidence of the presence of caveolae and vesico-vacuolar organelles (VVOs) in the endothelial cells of the biopsies. In addition to these findings, we were able to demonstrate the presence of tryptase and FXIIIa in the endothelial cells, in urticarial lesions and in apparently normal skin.

Conclusions: VVOs are present in the endothelial cells of post-capillary venules in DIAU. This is the first report on the expression of FXIIIa and tryptase in the cytoplasm of endothelial cells in urticaria. 

The DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), also known as DIHS (drug-induced hypersensitivity syndrome), presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, producing damage in several systems, especially kidney, heart, lungs, and pancreas. The pathogenesis is related to specific drugs (especially the aromatic anticonvulsants), altered immune response, sequential reactivation of herpes virus, and association with some HLA alleles. Glucocorticoids are the basis for the treatment of the syndrome, which may be given with intravenous immunoglobulin and, in selected cases, ganciclovir. This article reviews current concepts regarding the interaction of drugs, viruses and immune responses during this complex adverse-drug reaction.