How to manage hypersensitivity reactions to biological agents?

Biological agents induce cutaneous adverse drug reactions (CADR) different from those observed with xenobiotics. Type alpha is the cytokine release syndrome, type beta are hypersensitivity reactions and type gamma is a cytokine imbalance syndrome. Infusion-reactions, anaphylactoid reactions occur with various biological agents administered intravenously. In non-severe cases the infusion rate has to be reduced, in severe reactions, the treatment must be stopped and resuscitation carried out with corticosteroids and epinephrine. Reactions may be due to an alpha syndrome but a true allergy could be involved as demonstrated in some patients with IgE antibodies to the galactose-alpha-1,3-galactose portion of the cetuximab or anti infliximab-IgE. Some desensitisation protocols have been published. Non allergic itching and eczema-like lesions are frequent with epidermal growth factor receptor inhibitors. Rash or desquamation was observed in 40% of cases with antiangiogenic agents, 90% of patients treated with imatinib have rashes, oedema or pruritus and a non-allergic periorbital oedema. Severe CADR, such as Stevens-Johnson syndrome, can be provoked. Delayed readings of intradermal tests could be of value in managing patients with a maculopapular rash due to interferon. Anaphylaxis attributed to omalizumab seems to be rare (0.2%) and skin rashes occur in 7% of cases. Anaphylactoid reactions occur in 1% of patients treated with natalizumab. In the case of anti-natalizumab antibody-mediated reactions, treatment should be stopped. These allergic-like side effects of new biological agents must be known and reported to Pharmacovigilance agency networks.

Arterial stiffness predicts severe progression in systemic sclerosis: the ERAMS study.

OBJECTIVE: The ERAMS study addressed the value of arterial stiffness in predicting the severity of systemic sclerosis. METHODS: ERAMS was a prospective multicentre cohort study including patients with definite systemic sclerosis. Arterial stiffness was measured by the standardized non-invasive QKd 100-60 method. Clinical evaluation, biological measurements, functional respiratory tests and cardiac Doppler echography were performed at inclusion then each year until 3 years' follow-up was completed. Progression was defined as mild (articulations, muscle, oesophagus or skin involvement) or severe (lung, heart or kidney involvement) by a critical event committee. The prediction of severe progression was studied for QKd 100-60 as well as clinical and biological data at baseline by univariate and multivariate analysis. RESULTS: Ninety-nine patients were included (81 women, 18 men, mean age 57 years, standard deviation 12.5). Although their blood pressure profile was normal, half the patients had increased arterial stiffness (QKd 100-60<200 ms). There was a significant relationship between age-adjusted arterial stiffness and decrease in carbon dioxide diffusion (P<0.03) or haemoglobin rate (P<0.01). By univariate analysis, severe progression after 3 years was predicted by age (P=0.04), lung involvement (P=0.04), diffusion of lung carbon oxide (DLCO) (P<0.01), skin score (P=0.02), haemoglobin (P<0.01) and baseline Qkd 100-60 divided into two classes according to the median (P<0.01). By multivariate analysis, only haemoglobin rate [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.2-0.9] and QKd 100-60 (OR 19.6, 95% CI 1.2-308.2) predicted severe progression of systemic sclerosis. CONCLUSION: The measurement of arterial stiffness by the QKd method is a useful objective method for assessing the prognosis of systemic sclerosis independently from other data.