Keren Mahlab-Guri

Angiotensin-converting enzyme inhibitor-induced angioedema.

Angiotensin-converting enzyme inhibitors (ACE-I) are widely used, effective, and well-tolerated antihypertensive agents. The mechanisms by which those agents act can cause side effects such as decreased blood pressure, hyperkalemia, and impaired renal function. ACE-I can induce cough in 5%-35% and angioedema in up to 0.7% of treated patients. Because cough and angioedema are considered class adverse effects, switching treatment to other ACE-I agents is not recommended. Angioedema due to ACE-I has a low fatality rate, although deaths have been reported when the angioedema involves the airways. Here, we review the role of bradykinin in the development of angioedema in patients treated with ACE-I, as well as the incidence, risk factors, clinical presentation, and available treatments for ACE-I-induced angioedema. We also discuss the risk for recurrence of angioedema after switching from ACE-I to angiotensin receptor blockers treatment.

Inhaled Fluticasone Causes Iatrogenic Cushing’s Syndrome in Patients Treated with Ritonavir

Introduction: Ritonavir, a protease inhibitor (PI), is commonly used in the treatment of HIV-1 infection. It is a potent inhibitor of the hepatic cytochrome P450 superfamily. Therefore, its usage with other PI medications leads to significant increases in the levels of the latter PI, which allows a reduction in pill burden. Intranasal and inhaled corticosteroids are widely used for the treatment of allergic rhinitis and asthma. Inhaled steroids do not usually lead to systemic adverse events, since their plasma concentrations are quite low due to extensive first-pass metabolism and clearance by CYP3A4. However, the coadministration of Ritonavir with inhaled (or intranasal) corticosteroids may result in an increase in the plasma corticosteroid levels due to the potent CYP3A4 inhibition by Ritonavir. This may cause Cushing’s syndrome (laboratory and clinical) with adrenal suppression. Methods: Plasma cortisol and urinary-free cortisol levels were determined using immunoassays. In the Synacthen test, plasma cortisol levels were measured at time 0 as well as at times 60, 120, and 150 minutes following an intramuscular injection of 0.25 mg Synacthen. Results: We present here three HIV-1 female patients aged 12, 55 and 65 years who developed iatrogenic Cushing’s syndrome with adrenal suppression following the coadministration of Ritonavir and inhaled Fluticasone, both at the standard recommended doses. Conclusions: The coadministration of Ritonavir and Fluticasone at the recommended doses caused, in our three patients, iatrogenic Cushing’s syndrome with adrenal suppression. We suggest that this adverse event is underdiagnosed and high clinical suspicion is needed for early diagnosis and prenention of Addisonian crises. Thus, Fluticasone treatment should be avoided in patients who are treated with Ritonavir. Alternative therapeutic options for asthma control such as oral Montelukast or bronchodilators alone should be considered.

Omalizumab for severe chronic spontaneous urticaria: Real-life experiences of 280 patients

Omalizumab for severe chronic spontaneous urticaria: Real-life experiences of 280 patients Zahava Vadasz, MD, PhD, Yuval Tal, MD, Menachem Rotem, MD, Vered Shichter-Confino, MD, Keren Mahlab-Guri, MD, Yael Graif, MD, Aharon Kessel, MD, Nancy Agmon-Levin, MD, Ramit Maoz-Segal, MD, Shmuel Kivity, MD, Shira Benor, MD, Idit Lachover-Roth, MD, Yuri Zeldin, MD, Migel Stein, MD, Ori Toker, MD, Gamal Hassoun, MD, Shira Bezalel-Rosenberg, MD, Elias Toubi, MD, Ilan Asher, MD*, and Zev Sthoeger, MD*; for The Israeli Forum for investigating and treating Chronic Spontaneous Urticaria (CSU)

Hospitalizations of HIV patients in a major Israeli HIV/AIDS center during the years 2000 to 2012

Abstract To evaluate hospitalization rates and causes among human immunodeficiency virus (HIV) patients in the late highly active antiretroviral therapy (HAART) era. Data during the years 2000 to 2012 were obtained from hospital/clinical charts. Hospitalizations were defined as a ≥24 hours hospital admission. Obstetric admissions were excluded. Causes of hospitalizations were defined as acquired immune deficiency syndrome (AIDS)-defining illnesses, AIDS-related diseases (HAART adverse events, metabolic complications and non-AIDS-defining tumors/infections), and non-HIV-related diseases. Hospitalization rates are presented as admissions per 100 patient years. The number of HIV patients (58% males) in our center increased from 521 in 2000 to 1169 in 2012. 1676 hospital admissions (in 557 patients) were observed during the years of the study. The mean number of admissions per hospitalized patient was 3 ± 3.39. Hospitalization rates of HIV patients declined significantly (18.4/100 in 2000, 9/100 patient years in 2012; P = .0001), but it was higher than the rates reported in the Israeli general population (X8.76 in 2000, X6.04 in 2012). Furthermore, hospitalizations for AIDS-defining illness declined (from 46.9% to 16.1%) whereas non-HIV-related hospitalizations increased (from 31.3% to 60.1%). Lower cluster of differentiation 4 (CD4) cell counts and older age, at the time of HIV diagnosis, were associated with higher rates of admissions (especially for AIDS-defining illnesses) and mortality. Hospitalization rates of HIV patients, especially for AIDS-defining illness, continue to decline in the late HAART era despite the increasing age of the patients, though it is still higher than that of the general population. Low CD4 cell counts and older age, at the time of HIV diagnosis, are associated with readmissions and mortality.

Low levels of the immunoregulator Semaphorin 4D (CD100) in sera of HIV patients

INTRODUCTION Semaphorin-4D (CD100), generated by CD4/CD8 T-cells and its receptor on B cells - CD72, play a role in immune regulation. Both have soluble forms - sCD100/sCD72. METHODS sCD100 and sCD72 levels were determined by ELISA (MyBioSource, USA). RESULTS 28 chronic HIV patients and 50 matched healthy volunteers participated in our study. Before treatment, CD4 T-cells counts were 267 ± 216 cells/mcl and viral load (VL) was 586,675 ± 1897,431 copies/ml. Two years following HAART, CD4 T-cells counts rose to 475 ± 264 cells/mcl and VL dropped to 2050 ± 10,539 copies/ml. CD8 T-cells counts were stable. sCD72 levels prior (4.13 ± 2.03 ng/ml) and following HAART (3.53 ± 2.01 ng/ml) were similar to control levels (4.51 ± 2.66 ng/ml). sCD100 levels before (40.47 ± 31.4 ng/ml) and following HAART (37.68 ± 29.44 ng/ml) were significantly lower compared to controls (99.67 ± 36.72 ng/ml) despite the significant increase in CD4 T-cells counts. CONCLUSIONS The permanent low levels of the immunoregulator sCD100 suggest a role for CD100 in the immune dysfunction and T cells exhaustion of HIV.

Two case reports of severe myocarditis associated with the initiation of dolutegravir treatment in HIV patients.

Rationale:The integrase inhibitor dolutegravir is now recommended as first-line treatment for HIV. A single case of myocarditis after treatment with dolutegravir was reported in the FLAMINGO trial. We present here 2 cases of severe myocarditis that occurred shortly after the initiation of dolutegravir treatment. Patients concerns:The first case is a 45-year-old female who developed severe congestive heart failure and died, weeks after the initiation of dolutegravir treatment (for simplification of her antiretroviral regimen). The second case was a 51-year-old male who presented with effort dyspnea 3 weeks after the initiation of dolutegravir treatment and was later diagnosed as severe congestive heart failure. The treatment was changed and the patient survived, but he still suffers from severe heart failure with functional impairment. Diagnosis and Outcome:Patient 1 died, patient 2 suffers from severe heart failure. Lessons:We discuss here the possible relationship between the initiation of dolutegravir treatment and the development of lymphocytic myocarditis in our patients, and we suggest a possible mechanism.