Israel Medical Association Journal

Background: Anti-glomerular basement membrane (GBM) antibody disease, or Goodpasture’s disease, is the clinical manifestation of the production of anti-GBM antibodies, which causes rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Anti-GBM antibody detection is mandatory for the diagnosis of Goodpasture’s disease either from the serum or kidney biopsy. Renal biopsy is necessary for disease confirmation; however, in cases in which renal biopsy is not possible or is delayed, serum detection of anti-GBM antibody is the only way for diagnosis.

Objectives: To assess the predictive value of positive anti-GBM antibodies in a clinical setting. 

Methods: Data from anti-GBM antibody tests performed at one medical center between 2006 and 2016 were systematically and retrospectively retrieved. We recruited 1914 patients for the study. Continuous variables were computed as mean ± standard deviation, while categorical variables were recorded as percentages where appropriate. Sensitivity and specificity of anti-GBM titers were calculated. Kaplan–Meyer analysis was performed, stratifying survival according to the anti-GBM antibody titers.

Results: Of the 1914 anti-GBM test results detected, 42 were positive, 23 were borderline, 142 were excluded, and 1707 results were negative. Male-to-female ratio was 1:1.2. Sensitivity of anti-GBM test was 41.2% while specificity was 85.4%. Concerning the Kaplan–Meyer analysis, overall survival was 1163.36 ± 180.32 days (median 1058 days). 

Conclusions: Our study highlights the lack of sensitivity of serological testing of anti-GBM titers. Comparing survival curves, the survival correlated with anti-GBM titer only in a borderline way. Because highly sensitive bioassays are not routinely used in clinics, renal biopsy is still pivotal for Goodpasture’s disease diagnosis.

 

Background: Arthritis and arthralgia are painful symptoms experienced by many elderly patients during hospitalization. Crystal-induced arthritis (CIA) is one of the most common causes of arthritis worldwide and represents the most common cause of acute arthritis in the elderly.  

Objective: To determine the incidence of both acute new onset or acute exacerbation of CIA among elderly patients hospitalized due to an acute medical illness.

Method: This study comprised 85 patients. Patients aged 70 years and older who complained of any articular pain were included in the study. Exclusion criteria were signs of septic arthritis, chronic use of steroids or non-steroidal anti-inflammatory drugs, or admission to the hospital due to an acute attack of CIA. 

Results: Synovial aspiration was performed in 76 patients (89%). Joint aspiration yielded a diagnosis in 67 of them (79%). The predominant type of crystal was calcium pyrophosphate dehydrate (68%) followed by monosodium urate (20%). The main causes of hospitalization were acute infectious disease (57%) followed by neurologic and cardiac diseases, 14% and 9% respectively, and orthopedic problems (6%). Among patients with acute infectious disease, the main causes were pulmonary (57%) and gastrointestinal (22%) infections. In 9 patients (12%) who underwent synovial aspiration, visible crystals were identified without a definite diagnosis.

Conclusion: Our study showed that hospitalization could be a risk factor for the development of CIA, and the time to diagnose CIA is during hospitalization for other acute illnesses.

 

Background: Early prenatal ultrasound is an important part of prenatal screening in Israel. No studies have described the rate of trisomy 21 [T21] identification at 14–17 weeks gestation.

Objectives: To describe the rate of T21 identification by transvaginal sonograms (TVS) at 14–17 weeks gestation. 

Methods: We conducted a historical prospective study. Since 1986, early TVS of 72,000 fetuses at 14–17 weeks gestation have been prospectively recorded together with prenatal screening data at a private ultrasound center (AL-KOL, Haifa). We calculated the fraction of T21 cases by dividing the total number of cases with abnormal sonographic findings by the total number of diagnosed T21 cases. We also examined the percentage of verified T21 cases that had completely normal prenatal screening tests prior to the early prenatal TVS, thus revealing the contribution of this examination to the existing prenatal screening. Fisher’s exact test was used to calculate odds ratios for each sonographic marker. 

Results: Of 137 T21 fetuses, 123 had sonographic markers on early TVS, yielding a prediction capability of at least 89.87%. Of all T21 cases, 14% had completely normal nuchal translucency/first-trimester screening prior to the abnormal 14–17 week TVS findings. Isolated abnormal sonographic findings, which were found to increase the risk for T21, were common atrioventricular septal canal (odds ratio 88.88), duodenal atresia (OR 88.23), nuchal edema (OR 39.14), and hydrocephalus (OR 15.78). Fetal hydronephrosis/pyelectasis was non-significant when isolated (OR 1), and cardiac echogenic focus was associated with a decreased risk (OR 0.13).

Conclusions: Early prenatal TVS at 14–17 weeks may identify almost 90% of T21 and adds 14% to the identification rate at the first-trimester screening.

 

Background: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. 

Objectives: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009.

Methods: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009–2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method.

Results: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2–69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47–69%) and local control was 88% (95%CI 78–94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1–2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%.

Conclusions: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

 

Sjögren’s syndrome (SS), a chronic systemic autoimmune inflammatory condition involving the exocrine glands, has been suggested to be part of the spectrum of the “Autoimmune/inflammatory Syndrome Induced by Adjuvants” (ASIA). ASIA incorporates an umbrella of clinical conditions including siliconosis, macrophage myofasciitis syndrome, and post-vaccination phenomena that occur after the exposure to a substance, namely the adjuvant. Interestingly, SS and ASIA share several common features. Firstly, a shared pathogenic mechanism involving a disruption of the immune system balance, with B cell proliferation, cytokine production and tissue infiltration, have been proposed. Patients with ASIA often present clinical features resembling those of SS; dry mouth and dry eyes have also been included in the proposed classification criteria for ASIA. Finally, several case reports have suggested that both vaccines and silicone may trigger the development of SS. Unveiling these common pathways will contribute considerably to our understanding and managing of both conditions.

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.

Sarcoidosis is a chronic multisystem disease with variable course resulting from the interaction between environmental factors and the immune system of individuals genetically predisposed. The evidence linking sarcoidosis with environmental triggers such as metals is increasing. We describe the case of a 44 year old female with a history of smoking since age 30 and previous mercury dental filling who presented at physical examination with numerous subcutaneous nodules. Laboratory data showed accelerated erythrocyte sedimentation rate and high titer of anti-U1 ribonucleoprotein antibodies (U1-RNP). Skin biopsy and chest X-ray suggested the diagnosis of sarcoidosis. In this report we illustrate the different causes involved in the onset of sarcoidosis.