Dottorato in TECNOLOGIE INNOVATIVE NELLE MALATTIE DELLO SCHELETRO,
DELLA CUTE E DEL DISTRETTO ORO-CRANIO-FACCIALE

Titolo della tesi: Dupilumab e colonizzazione microbica cutanea: analisi fenotipica e molecolare di Staphylococcus aureus e di stafilococchi coagulasi negativi in pazienti affetti da dermatite atopica

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease whose pathogenesis is still not completely understood. Recent evidences suggest that impaired barrier integrity associated with dysbiosis play a key role in AD. Staphylococcus aureus colonization has been associated with increased inflammation and disease severity. The aim of the study is to characterize S. aureus strains involved in the acute phase of the disease and to isolate and identify Coagulase Negative Staphylococci (CoNS) able to control/inhibit the skin colonization by S. aureus. Methods: In this prospective study 20 adult Caucasian with moderate to severe AD patients and 20 healthy controls will be enrolled. For each patient, three swabs collected from nose, lesional and nonlesional skin were performed before start treatment with dupilumab (flare phase) and at the clinical remission (post-flare) of disease in order to perform phenotypical and molecular analyses (cultural examination; Maldi-Tof mass spectrometry; RAPD-PCR) of resident microbial species. Results: We report preliminary results of the study. S. aureus was hydentified in all AD patients, and only in 10% oh healty controls. At flare phase, high load of S. aureus (104-105 UFC/mL) strong biofilm producers has been in all samples collected by lesional skin, significantly higer when compared to non lesional skin and to healty controls (103 UFC/ml, p<0.05). At post-flare, a significantly lower S. aureus load has been found in all samples associated with higher load of S. epidermidis capable of inhibiting S. aureus biofilm production. Conclusion: In acute AD patients there is a high bacterial load of S. aureus which also has a strong production of biofilm that offers the microorganism the ability to cooperate and adapt to a hostile and highly competitive environment. Dupilumab therapy, while improving the clinical signs of the disease, does not allow the complete eradication of S. aureus, however it is associated with a recolonization with new strains, especially of S. epidermidis.