Otologic evaluation of patients with primary antibody deficiency.

Common variable immunodeficiency (CVID) represents the most frequent primary immunodeficiency, often encountered in the ENT clinical practice. The clinical spectrum of CVID is quite broad, but otitis media are certainly among the most common clinical manifestations. This prospective study enrolled 60 patients (34 males, 26 females) with a previous diagnosis of CVID with the aim of performing an otologic evaluation and a more precision characterization of incidence, diagnosis, and treatment of otitis media in this group of patients. In consideration that Eustachian tube dysfunction (ETD) could be the 'primum movens' of otitis media, we wanted to assess whether a Eustachian tube dysfunction was present in these patients. Besides, we propose a possible diagnostic algorithm of middle ear pathologies to use in all cases of primary antibody deficiency patients. Results of our otologic examination showed that: 5 % of patients had chronic suppurative otitis media, 25 % bilateral otitis media with effusion and 10 % reported unilateral OME with associated contralateral ETD. There was bilateral isolated ETD and unilateral isolated ETD in 5 and 15 % of patients, respectively. All patients with unilateral OME had associated contralateral ETD. Finally, 40 % of patients were bilaterally negative at otoscopic examination and all otologic tests.

Hemolysis in patients with antibody deficiencies on immunoglobulin replacement treatment.

BACKGROUND: Immunoglobulin (Ig)G replacement with intravenous or subcutaneous immunoglobulins is a lifelong substitutive therapy in patients with primary antibody deficiencies (PADs). Hemolysis after immunoglobulin therapy was described in patients receiving high immunoglobulin dosages. The issue of hemolysis after immunoglobulin administration at replacement doses has been considered of little clinical significance. STUDY DESIGN AND METHODS: This was a single-center observational study over a 2-year period on immunoglobulin-induced hemolysis in a cohort of 162 patients with PADs treated with immunoglobulin administered at replacement dosages. RESULTS: Six patients had signs and symptoms of immunoglobulin-induced hemolysis. Two additional asymptomatic patients were identified by a short-term study run on 16 randomly selected asymptomatic patients. Alloantibodies eluted from patients' red blood cells (RBCs) had anti-A and Rh specificities (anti-D and anti-C). The immunoglobulins contained alloantibodies with the same specificities of the antibodies eluted from patients' RBCs. CONCLUSION: Hemolysis occurred in patients receiving immunoglobulin at replacement dosages. Polyvalent immunoglobulin preparations contained multiple clinically significant antibodies that could have unexpected hemolytic consequences, as anti-C whose research and titration are not required by the European Pharmacopoeia. The issue of hemolysis in long-term recipients of immunoglobulin treatment administered at replacement dosages should be more widely recognized.

Clitoral blood flow in systemic sclerosis women: correlation with disease clinical variables and female sexual dysfunction.

OBJECTIVES: The objectives of this study were to investigate clitoral blood flow in SSc women compared with healthy controls and to correlate it with microvascular damage and disease clinical variables. We also evaluated the correlation between clitoral blood flow and sexual dysfunction. METHODS: Twenty-two SSc women and 20 healthy controls matched for sex and age were enrolled in this study. Baseline Doppler indices of the clitoral artery were measured. Peak systolic velocity, end diastolic velocity, resistive index (RI), pulsatile index (PI) and systolic/diastolic (S/D) ratio were measured. The female sexual function index (FSFI) was used to assess sexual function. RESULTS: The RI and S/D ratio were higher (P < 0.0001) in SSc women compared with healthy controls. The PI, RI and S/D ratio increased with progression of capillaroscopic damage. The RI and S/D ratio were higher (P < 0.01) in women with digital ulcers than in women without digital ulcers. No correlation exists between Doppler indices of the clitoral artery and age or clinical variables of disease. The FSFI was reduced in 7 (32%) of 22 SSc women. A negative correlation was observed between both the FSFI and RI (R = -0.74, P < 0.0001) and the S/D ratio (R = -0.68, P < 0.0001). A negative correlation exists between the RI and all domains of the FSFI score except for desire. CONCLUSION: Clitoral blood flow was reduced in SSc women compared with healthy controls. Clitoral blood flow was reduced in SSc women with digital ulcers and it correlated with capillaroscopic damage progression. A negative correlation exists between the RI and S/D ratio and all domains of the FSFI score except for desire.

On the dark side of therapies with immunoglobulin concentrates: the adverse events.

Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.

Longitudinal study on health-related quality of life in a cohort of 96 patients with common variable immune deficiencies.

Health-related quality of life (HRQoL) in common variable immunodeficiency diseases (CVID) was evaluated by different tools, which were mainly used to compare different schedules of immunoglobulins administration in cross-sectional or short-term longitudinal studies. We assessed the HRQoL and psychological status of CVID patients in a longitudinal study over a 6-year period by a generic, non-disease-specific instrument (SF-36), and by a General Health Questionnaire (GHQ-12) for the risk of depression/anxiety. At baseline, 96 patients were enrolled. After 1 year, a second assessment was performed on 92 patients and, after 6 years, a third assessment was performed on 66 patients. Eighteen patients died during the study time. HRQoL was low, with mental health scales less affected than physical scales. A decline in the score on SF-36 scales was observed between the first and the third assessment for the Physical Functioning, Body Pain, General Health, Social Functioning, and Role-Emotional scales. The General Health scale showed a lower score in these patients, when compared to patients with other chronic diseases. Approximately one-third of the patients were at risk of anxiety/depression at all observation times, a percentage that reached two thirds of the patients, considering only the group of females. Over the 6 years of the study, the health condition of 11/66 patients worsened, passing from "GHQ-negative" to "GHQ-positive"; their score on SF-36 scales also decreased. A decrement of one point in each of the Physical Functioning, Vitality, Social Functioning, and Mental Health SF-36 scales increased the risk of developing anxiety/depression from three to five percent. A negative variation of the Physical Functioning score increased the risk of psychological distress. In a survival analysis with dichotomized variables, Physical Functioning scores <50 were associated with a relative risk (RR) of 4.4, whereas Social Functioning scores <37.5 were associated with a RR of 10.0. In our study, it was the clinical condition, as opposed to the different treatment strategies with immunoglobulins, which had a major role on the deterioration of HRQoL. Moreover, in a quality-of-life evaluation, disorders such as anxiety/depression should be assessed, as they yet often go unrecognized. Our results might be helpful in the interpretation of currently available data on quality of life in CVID patients.