Israel Medical Association Journal

Since 1980 dermatologists have been interested in the exceptional healing reported by patients who underwent treatments at the Dead Sea. Tens of thousands of patients have visited this area and more than 10,000 cases have been the subject of clinical and laboratory studies since this natural therapeutic option was discovered for psoriasis management. Through evaluation of the published articles on climatotherapy, we tried to reach a global assessment of the usefulness of this approach and to discover whether this treatment still can be recommended in the era of biologic treatments. I conducted a review of the available literature on clinical trials through PubMed, Medline, and Google Scholar using the terms psoriasis and Dead Sea. I found 26 studies published between 1982 and 2021. Assessment of patients showed major improvement through several selected parameters. Length of the stay and medical supervision positively influenced the major outcomes observed. Duration of improvement and possible long-term side effects of this natural treatment still need to be more precisely determined. Exposure to the unique climatic factors of the region, essentially the sun and the sea, induces fast and significant results with high clearance rates of psoriasis plaques. Dead Sea climatotherapy still has its place for the control of psoriasis symptoms.

Background: Several studies have shown that patients with fibromyalgia present with neuroendocrine, inflammatory, and coagulation features linked to cardiovascular disease development. However, the exact profile of cardiovascular risk factors and events in fibromyalgia remains to be defined.

Objectives: To compare the profile of cardiovascular risk factors and events between fibromyalgia outpatients and the general population in Italy.

Methods: Cardiovascular risk factors and events in fibromyalgia females were collected using the criteria adopted in the CUORE Project.

Results: The study comprised 62 female fibromyalgia patients and 4093 female controls from 35 to 75 years of age. The prevalence of hypertension, diabetes, atrial fibrillation, transient ischemic attack, and cardiovascular total burden was significantly higher in fibromyalgia females than in the general Italian population. No difference was found in blood fasting glucose, triglycerides, total and fractionated cholesterol levels, body mass index, and metabolic syndrome (MetS). The MetS rate was underestimated for methodological aspects.

Conclusions: Fibromyalgia is associated with an increased cardiovascular burden, probably through a specific risk factor profile.

Background: The use of oral midazolam as premedication to induce anxiolysis before surgical procedures under local anesthesia is widely accepted in plastic surgery. Rhinoplasty performed under local anesthesia is known to generate high levels of perioperative anxiety, thus the use of appropriate premedication is important. Oral midazolam has been shown to be safe in various procedures. However, the safety of oral midazolam before rhinoplasty has not been evaluated.

Objectives: To evaluate the safety of premedication with oral midazolam prior to rhinoplasty by analyzing the intraoperative blood oxygen saturation levels as predictors of adverse respiratory events.

Methods: We retrospectively reviewed the anesthesia records of 62 patients who underwent rhinoplasty under local anesthesia and received premedication with oral midazolam for anxiolysis between March 2017 and December 2017. The median age of the patients was 25.4 years, and they were all classified as American Society of Anesthesiologists class 1. The patients received 10 mg midazolam hydrochloride orally 1 hour prior to the procedure. Oxygen blood saturation was monitored using a pulse oximeter and recorded every 15 minutes.

Results: All the patients maintained blood oxygen saturation levels above 95% (median peripheral capillary oxygen saturation 99%) on room air, and they did not require supplemental intraoperative oxygen. There were no transient hypoxemic events during and following the procedure.

Conclusions: Our study confirmed the safety of oral midazolam premedication to reduce perioperative anxiety when performing rhinoplasty under local anesthesia.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive death of motor neurons leading to fatal paralysis. The causes of ALS remain unknown; however, evidence supports the presence of autoimmune mechanisms contributing to pathogenesis. Although several environmental factors have been proposed, the only established risk factors are older age, male gender, and a family history of ALS. To date, there are no diagnostic test for ALS, and clinicians rely on the combination of upper motor neuron and lower motor neuron signs in the same body region. The aim of this paper was to provide a comprehensive review of current clinical literature with special focus on the role of autoimmunity in ALS, differential diagnosis, and available therapeutic approaches. Current evidence suggests a contribution of the innate immune system in ALS, with a role of microglial cell activation at the sites of neurodegeneration. The median time from symptom onset to diagnosis of ALS is 14 months, and this time estimate is mainly based on specific clinical signs and exclusion of ALS-like conditions. Several therapeutic approaches have been proposed, including immunosuppressive drugs, to reduce disease progression. Riluzole has been established as the only, although modestly effective, disease modifying therapy, extending mean patient survival by 3to 6 months. Recent advances in understanding the pathophysiology mechanisms of ALS encourage realistic hope for new treatment approaches. To date, the cornerstones of the management of patients with ALS are focused on symptom control, maintaining quality of life and improving survival.

Background: Multidisciplinary biopsychosocial rehabilitation for patients presenting with rheumatic diseases has been shown to produce better results in a warm climate. Dead Sea Climatotherapy (DSC) has been successfully used for decades to treat many patients with rheumatic diseases.

Objectives: To evaluate the short-term improvement of Norwegian patients who presented with chronic pain following a multidisciplinary biopsychosocial approach to treatment combined with DSC. Both objective and subjective clinical parameters were evaluated.

Methods: This retrospective study included a statistical analysis of 938 patients presenting with rheumatoid arthritis and ankylosing spondylitis (n=105), osteoarthritis (n=342), fibromyalgia (n=374), and other orthopedic conditions (n=117). Clinical assessments were conducted before and after a 3 week treatment program at the Dead Sea.

Results: Six parameters improved significantly in the rheumatoid arthritis and ankylosing spondylitis group as well as in the osteoarthritis group. Five parameters in the fibromyalgia group improved, while two improved in the orthopedic conditions group. Overall, major significant changes occurred in the pain self-assessment, joint motility, and daily activities scores.

Conclusions: A 3-week multidisciplinary biopsychosocial program combined with DSC induced positive changes in the clinical parameters of Norwegian patients presenting with chronic musculoskeletal pain.

Background: Behçet’s disease (BD) is an inflammatory disorder potentially leading to life- and sight-threatening complications. No laboratory marker correlating with disease activity or predicting the occurrence of disease manifestations is currently available.

Objectives: To determine an association between serum amyloid-A (SAA) levels and disease activity via the BD Current Activity Form (BDCAF), to evaluate disease activity in relation to different SAA thresholds, to examine the association between single organ involvement and the overall major organ involvement with different SAA thresholds, and to assess the influence of biologic therapy on SAA levels.

Methods: We collected 95 serum samples from 64 BD patients. Related demographic, clinical, and therapeutic data were retrospectively gathered.

Results: No association was identified between SAA levels and BD disease activity (Spearman's rho = 0.085, P = 0.411). A significant difference was found in the mean BDCAF score between patients presenting with SAA levels < 200 mg/L and those with SAA levels > 200 mg/L (P = 0.027). SAA levels > 200 mg/L were associated with major organ involvement (P = 0.008). A significant association was found between SAA levels > 150 mg/dl and ocular (P = 0.008), skin (P = 0.002), and mucosal (P = 0.012) manifestations. Patients undergoing biologic therapies displayed more frequently SAA levels < 200 mg/L vs. patients who were not undergoing biologic therapies (P = 0.012).

Conclusions: Although SAA level does not represent a biomarker for disease activity, it might be a predictor of major organ involvement and ocular disease relapse at certain thresholds in patients with BD.

Background: Type 2 diabetes mellitus is a multifactorial disease in which genetic susceptibility and environmental factors induce pancreatic β-cell dysfunction and insulin resistance. Additional factors such as hyperglycemia and hyperlipidemia have roles in β-cell dysfunction and disease progression. The phenomenon of lipid-induced pancreatic β-dysfunction, designated as lipotoxicity, has been observed in several in vitro and in vivo experiments; however, there is still no solid evidence for the occurrence of this event in humans. The toxic effect of high lipid levels on β-cell function consists of impaired insulin gene expression, apoptosis, and reduced glucose-stimulated insulin secretion.

Objectives: To demonstrate the importance of treating hypertriglyceridemia in reducing glucose intolerance and the need for insulin therapy in hospitalized diabetic patients.

Methods: We evaluated five clinical case reports and conducted a detailed literature review via the PubMed search engine.

Results: Reduction in elevated blood triglyceride and glucose levels in hospitalized diabetic patients resulted in a rapid decline in glucose levels and in the need for insulin therapy.

Conclusions: A decrease in high triglyceride levels in “lipotoxic” diabetic patients may improve insulin intolerance and glucose homeostasis and reduce the need for insulin therapy.

Background: The goals of treatment for rheumatoid arthritis (RA) are remission and low disease activity (LDA). However, many patients do not reach or maintain these targets with regard to disease control. 

Objective: To identify predictive factors of remission/LDA in a cohort of RA patients who started treatment with first line tumor necrosis factor-inhibitors (TNF-i). 

Methods: We included 308 RA patients treated with first line TNF-i for 2 years to evaluate remission/LDA based on the 28-joint disease activity score (DAS28). Predictive factors considered for achievement of remission/LDA were: gender, age at the time of TNF-i treatment, early arthritis, baseline C-reactive protein (CRP) and erythrocyte sedimentation rate levels, RF/anti-citrullinated protein antibody positivity, good/moderate European League Against Rheumatism response at 6 months, co-morbidities, and concomitant disease modifying antirheumatic drugs (DMARDs). Intention to treat, receiver operating characteristic curve, and univariate and multivariate analyses by logistic regression were performed. 

Results: Positive predictors of remission/LDA in both the univariate and the multivariate analyses were: male gender, age at the time of TNF-i treatment ≤ 54 years, negative baseline CRP, and concomitant DMARDs. The presence of any co-morbidity resulted to be a negative predictor of remission/LDA in both the univariate and the multivariate analyses. 

Conclusions: Demographic and clinical features were identified as reliable predictors of both the achievement and the maintenance of treatment targets in a cohort of RA patients treated for 2 years with first line TNF-i. 

 

Background: Non-infectious uveitis (NIU) leads to severe visual impairment, potentially impacting on health-related quality of life (QoL). 

Objectives: To investigate the impact of NIU on QoL.

Methods: Eighty NIU patients and 23 healthy controls completed the 36-item Short-Form Health Survey (SF)-36. The SF-36 values were statistically analyzed to evaluate differences between patients and healthy controls and to identify correlations between SF-36 subscores and clinical/demographic data. 

Results: NIU patients showed a decrease in the physical component summary score (P < 0.0001) compared to healthy controls, while no difference was highlighted in the mental component summary score (P = 0.97). NIU patients showed a decrease in physical functioning (P = 0.008), role-physical (P = 0.003), bodily pain (P = 0.0001), general health (P < 0.0001), and social functioning (P = 0.01). Physical functioning was lower in patients with acute anterior uveitis (AAU) than in those with panuveitis (P = 0.003). No differences were found between patients with bilateral or unilateral NIU, isolated NIU, or NIU associated with systemic diseases and with or without ocular activity. No correlations were identified between best-corrected visual acuity and SF-36 subscores. Physical functioning (P = 0.02), bodily pain (P = 0.004), and social functioning (P = 0.02) were reduced in males versus females. 

Conclusions: QoL is impaired in individuals with NIU, particularly in the physical domains, general health, and social functioning. AAU affects physical functioning more than panuveitis. NIU seems to affect per se QoL disregarding inflammatory activity, visual impairment, and presence of associated systemic diseases.

 

Background: The evidence on the use of dexamethasone implants in the treatment of Behçet’s disease (BD)-related uveitis is limited to a few cases. 

Objectives: To evaluate the efficacy of dexamethasone implants on ocular functional, morphological, and clinical parameters in BD patients with severe refractory uveitis. 

Methods: Five eyes from five BD patients were enrolled. A single intravitreal dexamethasone injection was applied to each eye. Best corrected visual acuity (BCVA), central macular thickness (CMT) assessed with optical coherence tomography, retinal vasculitis assessed by fluorescein angiography, vitreous haze score (Nussenblatt scale), intraocular pressure (IOP), and lens status (LOCS III, Lens Opacities Classification System III) were recorded at baseline and at 1, 3, and 6 month follow-up visits.

Results: At baseline, all eyes showed marked macular edema and 4/5 had concomitant active retinal vasculitis. Mean BCVA was increased from baseline at each control visit with a mean improvement of 0.26 ± 0.18 lines at 6 months follow-up. Mean CMT decreased from baseline at each control visit with a mean improvement at 6 months follow-up of 198.80 ± 80.08 µm. At the end of the study, none of the eyes showed macular edema and the mean CMT was 276.80 ± 24.94 µm. Retinal vasculitis resolved in all eyes. One eye experienced an IOP spike during treatment that resolved spontaneously, and one eye developed a clinically significant lens opacity at 6 months follow-up. 

Conclusions: Treatment with a dexamethasone implant in BD-uveitis and inflammatory macular edema was safe and effective as an additional treatment combined with systemic immunomodulatory drugs.

 

Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that it is very difficult to diagnose in the early phase, resulting in a critical delay in therapy which is often begun when internal organ involvement is already irreversible. The ACR or LeRoy criteria have a low sensitivity for the early phases; these criteria were replaced by the ACR/EULAR 2013 criteria which improved the disease classification. Therefore, the SSc diagnosis may be delayed for several years after the onset of Raynaud’s phenomenon (RP) and even after the onset of the first non-RP symptom. RP, antinuclear antibodies (ANA) positivity, and puffy fingers were recently indicated as “red flags” (by the VEDOSS project) – that is, the main elements for suspicion of SSc in the very early phase of the disease. Confirming the diagnosis requires further tests, particularly nailfold videocapillaroscopy and evaluation of specific disease antibodies (anti-centromere and anti-topoisomerase I). In this way, the VEDOSS project identified patients in the very early phase of disease enabling a ‘‘window of opportunity’’ whereby the physician can act with effective drugs to block or at least slow the progression of the disease. The principal challenge in the fight against SSc is to detect valid predictors of disease evolution in order to treat patients in the early stage of disease. While waiting to find valid predictors, a close follow-up of the patients with the VEDOSS red flags is essential, as is a close collaboration between rheumatologists and general practitioners in order to identify all potential SSc patients as soon as possible.