Elena De Santis PhD, Alessandra Melegari PhD, Chiara Bonaguri PhD , Gilda Sandri MD, Maria Teresa Mascia MD, Federica Gaiani MD, Valentina Pecoraro PhD , Gianluigi De Angelis MD and Tommaso Trenti MD
Background: Biological agents for anti-tumor necrosis factor-α therapy have revolutionized treatments for autoimmune diseases; however, approximately 20% of rheumatology and 40% of gastroenterology patients do not respond to the therapy, or they show reduced drug efficacy because of anti-drug antibody (ADA) formation.
Objectives: To evaluate laboratory tools for individual monitoring of infliximab therapy and the relationship between ADA and infliximab serum levels, ADA and clinical response, and ADA and autoantibodies.
Methods: Our study comprised patients treated with infliximab and affected by selected rheumatology and gastroenterology diseases. Sera were analyzed for infliximab, total-anti-drug antibodies (Total-ADA), and free-anti-drug antibodies (Free-ADA) serum levels and for the detection of specific autoantibodies.
Results: We analyzed 73 patients. Total-ADA were detected in 26 rheumatology and 21 gastroenterology patients. Serum infliximab levels were significantly lower in Total-ADA positive patients (P = 0.01 for rheumatology group, P = 0.02 for gastroenterology group). A lack of response was observed in 7 rheumatology and 15 gastroenterology samples. Total-ADA serum levels were statistically significantly higher in patients with treatment failure in both groups (P = 0.01 and P = 0.001, respectively). There was no significant association between the presence of Total-ADA and other autoantibodies. Free-ADA were detected in only 27 rheumatology patients. Results showed a significant correlation with clinical outcome (P = 0.006).
Conclusions: The correlation with clinical response suggests that the presence of ADA could interfere with efficacy of therapy. The tests for monitoring therapy may be an important tool to assist clinicians in early detection and prevention of therapy failure.
Oded Shamriz MD, Mariana Druker Bsc, Tzahi Neuman MD MHA, Zvi Dranitzki MD and Yuval Tal MD PhD
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.
Ori Eyal MD, Asaf Oren MD, Dganit Almasi-Wolker MD, Yardena Tenenbaum-Rakover MD, Marianna Rachmiel MD and Naomi Weintrob MD
Background: Diabetic ketoacidosis (DKA) as the first presentation of type 1 diabetes mellitus (T1DM) is a serious complication that is preventable.
Objectives: To identify risk factors for DKA at presentation of T1DM to delineate high-risk Israeli populations that could benefit from preventative measures.
Methods: Data for this multicenter retrospective study were collected from the medical files of three pediatric diabetes centers representing three districts in Israel. Inclusion criteria were diagnosis of T1DM, age at diagnosis ≤ 17 years, permanent residency in Israel, and documentation of the presence or absence of DKA at presentation.
Results: The study population included 607 patients of whom 438 met the inclusion criteria. The mean age at diagnosis was 9.1 ± 4.5 years. DKA was present at diagnosis in 156/438 patients (35.6%). The incidence of DKA was different among the three diabetes centers (P = 0.04). The DKA group was significantly younger than the non-DKA group (8.4 ± 4.5 vs. 9.5 ± 4.4, respectively, P = 0.008). DKA was significantly associated with maternal origin (Ashkenazi Jewish origin [lower] vs. non-Ashkenazi, P = 0.04) and with paternal education level (academic [lower] vs. non-academic education, P = 0.04). Stepwise logistic regression showed that maternal Ashkenazi Jewish origin has a protective effect on DKA (odds ratio [OR] 0.4, 95% confidence interval [95%CI] 0.21–0.74, P = 0.004) and that younger age is an independent risk factor (OR 1.06, 95%CI 1.01–1.1, P = 0.02).
Conclusions: A diabetes educational program targeting high-risk population groups may reduce the prevalence of DKA nationwide.
Maurizio Benucci MD, Arianna Damiani MD, Francesca Bandinelli MD, Valentina Grossi MD, Maria Infantino MD, Mariangela Manfredi MD, Francesca Li Gobbi MD, Piercarlo Sarzi-Puttini MD and Fabiola Atzeni MD PhD
Igal Kushnir MD, Viacheslav Soyfer MD and Ofer Merimsky MD