Israel Medical Association Journal

Background: Eosinophilic fasciitis (EF) is a rare disease characterized by scleroderma-like skin, inflammation of deep muscle fascia, hypergammaglobulinemia, peripheral eosinophilia, and elevated erythrocyte sedimentation rate.

Objectives: To present our experience in diagnosis and treatment of seven biopsy-proven EF patients in a large tertiary medical center.

Methods: We screened all patients who were admitted to our tertiary medical center and diagnosed with EF by tissue biopsies from January 2000 to January 2016. We analyzed relevant patient files regarding diagnosis, treatment, and outcome parameters. A comprehensive framework was presented based on the results of our observations and the corresponding literature.

Results: We identified seven patients (six males; one child). Mean age at diagnosis was 37.4 years (range 10–67 years). Underlying autoimmune disorders were observed in three patients (42.8 %). Disease anatomical distribution was noted in lower and upper limbs (85.7% and 57.1%, respectively) as well as neck and shoulders (14.3% each). Three patients (42.8%) had a history of initial misdiagnosis. The mean time period from first clinical presentation to histopathological diagnosis was 150.3 days (range 16–602 days). Treatment included oral glucocorticoids (71.4%), pulse methylprednisolone (14.2%), and methotrexate (42.8%). Recovery from symptoms related to EF was observed in six patients.

Conclusions: Diagnosis of EF is primarily based on clinical and histopathological findings. As eradication of this disease can be expedited with early treatment, it is important to increase awareness in the medical community.

Background: Magnetic resonance imaging (MRI) is the most sensitive imaging modality for the detection of sacroiliitis. Diagnosing sacroiliitis on MRI is not always straightforward and can be challenging in some cases.

Objectives: To evaluate the prevalence of alternative diagnoses suggested by MRI and characterize the MR appearance of the most common ones.

Methods: Consecutive MRI examinations of the sacroiliac joints (SIJ) performed between 2005 and 2012 were retrospectively evaluated for the presence of structural and active sacroiliitis findings according to the Assessment of SpondyloArthritis International Society guidelines. Alternative diagnoses, including degenerative changes, diffuse idiopathic skeletal hyperostosis (DISH), Osteitis condensans ilii (OCI), septic sacroiliitis/discitis, stress reaction as well as anatomic variants, were registered

Results: We evaluated 281 MRI examinations, 116 males, 165 females, average age 44 ± 15 years. Sacroiliitis was found in 71 examinations (25%) and alternative diagnoses were suggested in 87 (31%) (OCI 8.9%, anatomic variants 5.3%, septic sacroiliitis 5.3%, degenerative findings 4.3%, diffuse idiopathic skeletal hyperostosis [DISH] 1.5%, stress reaction 0.7%, tumor 0.3%). A normal examination was found in the remaining 123 examinations. Patients with alternative diagnoses were older than those with sacroiliitis (62 vs. 47 years of age, respectively, P > 0.05). Alternative pathologies in the SIJ were significantly more common in females (66) than males (21), P < 0.05.

Conclusions: A substantial proportion of patients with suspected sacroiliitis had normal SIJ while the rest were more commonly diagnosed with other pathologies. A referral by an experienced rheumatologist may improve the sensitivity and specificity of this important examination.

Axial spondyloarthritis (axSpA) covers the stage of non-radiographic axial spondyloarthritis (nr-axSpA) and classic ankylosing spondylitis. The pathognomonic findings of axSpA are mainly inflammatory and osteoproliferative changes in the sacroiliac joints (SIJ) and the spine. Various imaging techniques are being used in daily practice for assessment of disease-specific changes, such as periarticular bone marrow edema, erosions, sclerosis, fat metaplasia and ankylosis in the SIJ or spondylitis, spondylodiscitis, facet joint involvement, or syndesmophytes in the spine of patients with axSpA. Conventional radiographs are still considered the gold standard for assessment of structural changes, while the method of for detection of inflammatory changes is magnetic resonance imaging (MRI).

A result for an MRI in the SIJ is considered positive for axSpA when more than one lesion is present on one MRI slice, If there is one lesion only, this should be present on at least two consecutive slices. For the spine, inflammatory lesions should preferably be located in the corner of the vertebral bodies, while occurrence of spondylitis in three or more vertebral corners is considered highly suggestive of axSpA.

This review gives a detailed overview about the benefits and limitations of all available imaging techniques in patients with axSpA, explains the usage of imaging techniques in the context of diagnosis and differential diagnosis of the disease, and reports on the potential future trends in the area of imaging of the axial skeleton in patients who are suspicious for this diagnosis.

Background: Medication reconciliation (MR) at hospital admission, transfer, and discharge has been designated as a required hospital practice to reduce adverse drug events.

Objectives: To perform MR among elderly patients admitted to the hospital and to determine factors that influence differences between the various lists of prescribed drugs as well as their actual consumption.

Methods: We studied patients aged 65 years and older who had been admitted to the hospital and were taking at least one prescription drug.

Results: The medication evaluation and recording was performed within 24 hours of admission (94%). The mean number of medications was 7.8 per patients, 86% consumed 5 or more medications. Mismatching between medication prescribed by a primary care physician (PCP) and by real medication use (RMU) was found in 82% of patients. In PCP the most common mismatched medications were cardiovascular drugs (39%) followed by those affecting the alimentary tract, metabolism (24%), and the nervous (12%) system. In RMU, the most commonly mismatched medications were those affecting the alimentary tract and metabolism (36%). Among all causes of mismatched medications, discrepancies in one drug were found in 67%, in two drugs in 21%, and in three drugs in 13%. The mismatching was more common in females (85%) than in males (46%, P = 0.042).

Conclusions: This study provided evidence in a small sample of patients on differences of drug prescription and their use on admission and on discharge from hospital. MR processes have a high potential to identify clinically important discrepancies for all patients.

Background: Postpericardiotomy syndrome (PPS) is characterized by pleuro-pericardial inflammation, which occurs in patients undergoing surgical procedures involving the pleura, pericardium, or both. The syndrome is considered to be immune mediated. However, its pathogenesis is not fully understood. It has previously been demonstrated that the Mediterranean Fever (MEFV) gene, which is associated with familial Mediterranean fever (FMF), has a role in the activation and expression of several inflammatory diseases.

Objectives: To investigate whether carriage of the MEFV mutation may precipitate PPS or affect its phenotype.

Methods: The study population included 45 patients who underwent cardiac surgery and developed PPS. The control group was comprised of 41 patients who did not develop PPS. Clinical and demographic data was collected. The severity of PPS was evaluated. Genetic analysis to determine the carriage of one the three most common MEFV gene mutations (M694V, V726A, E148Q) was performed. The carriage rate of MEFV mutations in patients with and without PPS was compared. Association between MEFV mutation carriage and severity of PPS was evaluated. 

Results: The rate of mutation carriage in the MEFV gene was similar in patients with and without PPS (15.6% in the study groups vs. 29.3% in the control group, P = 0.1937). The rate of mutation carriage in the MEFV gene was significantly lower among patients with severe PPS as compared to patients with mild-moderate PPS (4.8% vs. 25%, P < 0.05).

Conclusions: Carriage of mutations in the MEFV gene is not associated with development of PPS; however, it may affect PPS severity.

 

Background: Abatacept acts as a co-stimulation modulator preventing activation of T cells. Although it is approved for the treatment of rheumatoid arthritis (RA), its effects on adaptive immune response have not been fully elucidated. 

Objectives: To observe, in a cohort study, based on a clinical practice setting, the variation of peripheral blood T cells, immunoglobulin levels, and autoantibodies in the serum of RA patients during abatacept therapy. 

Methods: Our study comprised 48 RA patients treated with abatacept. All clinical data were collected at baseline and after 3 months of treatment. Clinical and laboratory tests included erythrocyte sedimentation rate, C-reactive protein, 28-joint disease activity score, RF, anti-citrullinated protein antibody, total immunoglobulins, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and lymphocyte sub-population. 

Results: Total immunoglobulin serum levels significantly decreased after 3 months of treatment and correlated positively with disease activity both at baseline and after 3 months of abatacept treatment. A reduction of serum IgM, IgG, IgA and RF was also demonstrated. The absolute number and percentage of cytotoxic (CD8+) T cells significantly decreased after 3 months of abatacept treatment, in particular the percentage of cytotoxic (CD8+) T cells significantly decreased only in patients responding to the treatment.

Conclusions: Our results highlight a different role of abatacept in the modulation of the adaptive immune response in RA by the reduction of polyclonal B-cell activation and cytotoxic T cells. 

 

Background: Holocaust survivors report a much higher prevalence of osteoporosis and fracture in the hip joint compared to those who were not Holocaust survivors.

Objective: To evaluate whether being a Holocaust survivor could affect the functional outcome of hip fracture in patients 64 years of age and older undergoing rehabilitation.

Methods: A retrospective cohort study compromising 140 consecutive hip fracture patients was conducted in a geriatric and rehabilitation department of a university-affiliated hospital. Being a Holocaust survivor was based on registry data. Functional outcome was assessed by the Functional Independence Measure (FIM)TM at admission and discharge from the rehabilitation ward. Data were analyzed by t-test, chi-square test, and linear regression analysis. 

Results: Total and motor FIM scores at admission (P = 0.004 and P = 0.006, respectively) and total and motor FIM gain scores at discharge (P = 0.008 and P = 0.004 respectively) were significantly higher in non-Holocaust survivors compared with Holocaust survivors. A linear regression analysis showed that being a Holocaust survivor was predictive of lower total FIM scores at discharge (β = -0.17, P = 0.004).

Conclusion: Hip fracture in Holocaust survivors showed lower total, motor FIM and gain scores at discharge compared to non-Holocaust survivor patients. These results suggest that being a Holocaust survivor could adversely affect the rehabilitation outcome following fracture of the hip and internal fixation. 

 

Background: During 2013–2014 Israel experienced a continuous circulation of wild poliovirus type 1 (WPV1) but with no clinical cases. WPV1 circulation was gradually terminated following a national vaccination campaign of bivalent oral poliovirus vaccine (bOPV) for 943,587 children < 10 years. Four cases of children with neurological manifestations that appeared following bOPV vaccinations were reported during the campaign: three of Guillain-Barré syndrome (GBS) and one of acute disseminated encephalomyelitis (ADEM). 

Objectives: To present an analysis of these cases, the rapid response and the transparent publication of the results of this analysis. 

Methods: The clinical, laboratory and epidemiological data of these four patients were available during the analysis. In addition, data regarding the incidence of GBS and ADEM during previous years, and reported cases of acute flaccid paralysis (AFP) and the incidence of Campylobacter jejuni enteritis were collected from the Epidemiology Department of the Israel Ministry of Health.

Results: The incidence of GBS among bOPV-vaccinated children was not higher than among bOPV-unvaccinated children. For all the cases reviewed the "incubation period" from vaccination to the event was longer than expected and other more plausible causes for the neurologic manifestations were found. There is no evidence in the literature of a causal relationship between bOPV and ADEM. 

Conclusions: There was no association between the bOPV vaccine and the reported neurological manifestations. We believe that our experience may assist other public health professionals when confronting a similar problem of alleged side effects during a mass medical intervention.

 

Background: Antiphospholipid antibodies (aPL) have been advocated as potential mediators of unexplained female infertility, but no evidence has yet been raised to support such an association.

Objectives: To test the hypothesis that aPL might interfere with uterine decidualization, a gene expression study was performed on decidual stromal cells treated with different aPL preparations.

Methods: Decidual stromal cells were isolated from first-trimester deciduas obtained from two women undergoing elective abortion, and treated with: (i) a β2GPI-dependent aPL monoclonal antibody (IS3); (ii) IS3 plus TIFI, a synthetic peptide mimicking PL-binding region of β2GPI; and (iii) IgG from healthy subjects (NHS). Gene expression data were acquired using human HT-12 v3 beadchip arrays (Illumina). Differential expression analysis was performed by fitting a gene-wise linear model using the treatment group and decidual source as covariates.

Results: In the comparison of IS3 versus IgG NHS-treated decidual cells, gene ontology (GO) enrichment was expressed in terms relating to well-characterized aPL-mediated cellular effects: “inflammatory response,” “immune response,” “response to stress,” “oxydoreductase activity,” “metalloendopeptidase activity,” and “cytokine/chemokine activity.” As expected, almost all genes were up-regulated by IS3 treatment. The same GO categories appeared to be differentially expressed when IS3 treatment was compared to IS3 + TIFI, but with most genes being down-regulated.

Conclusions: Given the inflammatory response evinced at gene expression analysis on decidual stromal cells treated with a β2GPI -dependent aPL monoclonal antibody, it is feasible that aPL might interfere with uterine decidualization, affecting the early stages of implantation and ultimately resulting in female infertility.