After the epidemic of Coronavirus associated disease (COVID-19) sustained by SARS-CoV-2 in Wuhan (China), the first case of COVID-19 in Lombardy, a region in Northern Italy, was reported on 20th February 2020. In the following weeks this region rapidly became the most affected area in the world [1], causing great difficulty in the management of patients with chronic illnesses, including rheumatic diseases such as Systemic Sclerosis (SSc). The number of new COVID-19 cases in Lombardy peaked on 15th March and slowly decreased thereafter [2].
Immediately after the first report of a COVID-19 case, therapies for rheumatic outpatients in our University Hospital (ASST Spedali Civili of Brescia, Lombardy), serving an area of nearly one million people, were centralized in a Clinic having a separate entry. Patients were allowed to access this area only after having undergone a triage and received personal protective equipment.
Here we report the follow-up of patients with SSc who were receiving periodic intravenous iloprost infusions (or, in 3 patients with iloprost intolerance, alprostadil infusions) in our outpatient clinic in February 2020. Iloprost is recommended used for treatment of digital ulcers (DU) in patients with SSc [3]. Main demographic and clinical characteristics of these patients are reported in Table 1. All patients were regularly contacted by telephone before the scheduled access, to assess their health status, particularly focusing on the presence of flu-like symptoms and on DU, which were assessed with the DU Clinical Assessment Score (DUCAS) [4]. When necessary, photos and other files were received from the patients, and diagnostic and therapeutic prescriptions were sent electronically.
Even if infusive therapies with iloprost were never interrupted at our Hospital, between 20th February and 31st May, 47 of 64 SSc patients (73%) did not receive at least one of the scheduled infusions. The main cause of therapy discontinuation was patients concern related to Hospital access and/or logistical difficulties (43/64, 91%), while in 2 cases therapy was interrupted because of COVID-19, and in other 2 cases for other concomitant diseases. The mean length of time of therapy discontinuation was 2.4 months.
Baseline DUCAS (at the last infusion before 20th February) was not different between patients who discontinued prostanoid infusion (group 1) and never discontinued it (group 2; p= 0.09 Mann-Whitney test). During the period considered, 12 of 63 evaluable patients (19%) had new DU (observed directly or via images sent by e-mail); this was similar in group 1 (9/46; 20%) and group 2 (3/17; 18%). However, in group 1 DUCAS score slightly increased during therapy discontinuation, and then decreased once therapy was resumed (Table 2). In one patient with multiple DU at baseline, despite therapy with iloprost and bosentan, after COVID-19, sub-amputation of the 2nd right fingertip was necessary. An 85-year-old patient with severe neoplastic and cardiovascular comorbidities died of complications related to COVID-19.
In summary, although the iloprost infusion activity was never suspended by our Hospital during the COVID-19 emergency, the majority of SSc patients briefly discontinued the therapy. The regular telephonic contact with them allowed a good control of the symptoms. Although not optimal, this management was tailored on individual needs, thereby optimizing the timing of iloprost therapy restart. In fact, patients who discontinued the therapy did not experience an increase in the number of new DU, but a slight increase of their severity. While this observation reflects the importance of therapeutic continuity, it should be noted that the optimal regimen (dosage, duration and frequency) of iloprost infusions is not yet fully defined [5]. DUCAS proved to be a useful tool for the rheumatologist in evaluating DU.
COVID-19 had serious consequences in the two SSc patients of this cohort who suffer it. The impact of COVID-19 on SSc patients is still not defined [6-8] and strategies to improve their management have been suggested [6, 9-10].