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Background. Environmental factors such as infections and vaccines are known to trigger dermatomyositis (DM), and during the recent SARS-CoV-2 pandemic this has become even clearer. SARS-CoV-2 infection may share features with anti-MDA5 DM, such as rapidly progressive lung involvement, cutaneous lesions and cytokine release syndrome. A few case reports of DM following SARSCoV-2 vaccination have been published, suggesting the onset of an aberrant immune response leading to DM with specific autoantibody signatures and severe organ impairment. Methods. Clinical and laboratory data of the 2 case reports were obtained from electronic clinical charts in Humanitas Research Hospital (Rozzano, Milan, Italy). Autoantibody analysis was performed by protein-immunoprecipitation for anti-MDA5 and immunoblot for anti-Ro52 and TIF1gamma antibodies as per protocol. Results. Case report 1 is a 71-year-old woman who developed fever, cough, and anosmia, which resolved spontaneously in two weeks, but did not undergo a nasopharyngeal swab, while her relatives were diagnosed with SARS-CoV-2 infection. When symptoms improved, she developed arthralgia and skin lesions on her face, chest, and hands for which she started topical treatment, with negative SARSCoV-2 nasopharyngeal swab and positive serum test for IgG against SARS-CoV-2 spike protein. For the persistence of the skin rash and arthralgia, she was admitted to our Department in March 2021. Blood tests showed mild elevation of C reactive protein (2.1 mg/L -normal value NV<5), aspartate (84 UI/L) and alanine aminotransferase (133 UI/L -NV<35), ferritin (595 ng/ml -NV<306), troponin I (19 ng/L -NV<14), and BNP (251 pg/ml -NV<100) with normal complete blood cell count, creatine kinase, C3 and C4. IgG antibodies for SARS-CoV-2 spike protein were confirmed to be elevated (96 AU/ml -NV<15). Autoantibodies associated with connective tissue diseases were tested and only anti-MDA5 antibodies were positive at immunoprecipitation. A punch biopsy of a Gottron-like lesion on the left hand showed leukocytoclastic vasculitis. We observed reduced capillary density with neoangiogenesis and ectasic capillaries at the nailfold capillaroscopy. EKG and ecocardiography were normal, while cardiac magnetic resonance detected abnormalities in the parametric sequences, consistent with signs of previous myocarditis. A lung CT scan revealed pulmonary emphysema while respiratory function tests demonstrated reduced volumes (FVC 82%, FEV1 64%, inadequate compliance CO diffusion test). Based on the biochemical and clinical findings, a diagnosis of anti-MDA5-associated DM with skin and heart involvement was made and treatment with low-dose methylprednisolone (0.25 mg/kg daily) and azathioprine 100 mg was started, then switched to mycophenolate because not effective on skin lesions. Case report 2 is an 84-year-old woman with history of colon cancer (surgical treatment) and oral lichen treated with low doses steroids in the last 2 years. After the 2nd dose of SARS-CoV-2 mRNA vaccination, in March 2021 she developed skin rash with V-sign, Gottron's papules, periungueal ulcers, muscle weakness and fatigue, thus she performed a rheumatologic evaluation. Blood tests showed mild elevation of creatine kinase (484 UI/L, NV <167), CK-MB (9.6ng/ml, NV <3.4), BNP (215 pg/ml -NV<100) with normal values of complete blood cell count, C3 and C4. Anti-Ro52kDa and TIF1gamma were positive at immunoblot, thus we confirmed a diagnosis of DM. The clinical evaluation also showed active scleroderma pattern at nailfold capillaroscopy, normal echocardiography, bronchiectasia but not interstitial lung disease at lung CT, and normal respiratory function tests (FVC 99%, FEV1 99%, DLCO 63%, DLCO/VA 81%). A PET-CT scan was performed to exclude paraneoplastic DM, and treatment with steroids and mycophenolate was started. Conclusions. SARS-CoV-2 may induce mechanisms for escaping the innate immunity surveillance and causing autoimmune diseases, but more clinical and functional studies are needed to demonstrate this possible association.
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Case report: A 63 y.o. man with known allergic rhinoconjunctivitis and mild asthma, sensitized to house dust mites, cat dander and grass and pellitory pollens, presented at the Emergency Department (ED) of our Hospital for diplopia, left temporo-parietal headache, fleeting knurled scotoma, and impaired color vision, associated with dry cough, occurring the day after the booster dose of the anti-SARS- CoV- 2 vaccine (mRNA-1273). Collecting clinical history, it emerged that 6 months before, just after the first vaccine dose (BNT162b2), he developed a progressive worsening of asthma, becoming severe and uncontrolled despite high dose inhaled corticosteroids plus long-acting beta2-agonists, montelukast and tiotropium bromide, and requiring maintenance oral corticosteroid treatment: any attempt to withdraw systemic corticosteroid was associated with exacerbations of asthma. During the access to the emergency room and the subsequent hospitalization, the following emerged: severe hypereosinophilia (12400 cells/mcl), left third cranial nerve palsy, elevated serum troponin, echocardiographic signs of acute myopericarditis with interventricular septal thickening, MRI signs of cardiac interventricular septal hypokinesia, and multiple pulmonary consolidations on CT scan. Serum ANCA was negative. The clinical presentation (asthma, third cranial nerve mononeuropathy, myopericarditis with signs of interventricular septal distress, typical lung involvement) associated with the finding of severe hypereosinophilia was suggestive of eosinophilic granulomatosis with polyagioitis (EGPA). Already in the emergency room, the patient was promptly treated with 3 boluses of methylprednisolone 1 g i.v. (1 bolus per dey). During the hospitalization he underwent the first cycle (out of 6 planned) of i.v. cyclophosphamide 1000 mg and initiated therapy with oral prednisone 75 mg/day (1 mg/kg/day). After the initiation of systemic corticosteroid therapy there was depletion of blood eosinophils, progressive reduction of serum troponin, resolution of cough and almost complete regression of 3rd cranial nerve palsy. At the time of submission, the patient was discharged and taken on an outpatient basis to continue therapy with cyclophosphamide and possibly associate mepolizumab as a steroid-sparing strategy. In conclusion, this is a case of EGPA arising after SARS-CoV- 2 vaccination. It has been described that vasculitis can be triggered by infectious episodes or vaccinations: to date only two other EGPA cases likely induced by anti-SARS- CoV- 2 mRNA vaccines have been described in the literature.
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Background: Studies evaluating COVID-19 in cancer patients beyond the effects of the infection itself are generally from single institutions, voluntary surveillance registries, or surveys. To extend the limited evidence available, we analyzed both the incidence and one-year mortality of breast cancer (BC) female patients at a population level in Lombardy, the first Italian region affected by the pandemic and the most populous one. Method(s): The regional COVID-19 database, including all SARS-CoV2 cases based on a positive swab result, was integrated with the Regional Health Information System, collecting data from 10 million habitants on primary medical care;hospitalization;pharmaceuticals;and survival status. From the database, we extracted data of newly-diagnosed not previously treated BC patients, including patient characteristics and comorbidities (respiratory insufficiency, diabetes, chronic kidney disease, cerebral vasculopathy, hypertension and cardiovascular disease), BC stage, and treatment. Result(s): The study population consisted of 12912 newlydiagnosed/ not previously treated BC patients, 7349 in 2019 and 5563 in 2020. There were two drops of newly diagnosed cases, one in the first wave (March-May 2020;-37.2%), the other in the second wave (October-December 2020;-15.8%). No major differences were found between characteristics of cases occurring in 2019 and 2020;with the exception of a reduced use of both chemotherapy (86.2% vs 53.4%) and radiotherapy (65.7% vs 42.1%) in 2020. One-year overall survival was 97.6% in 2020 vs 98.3% in 2019, Hazard Ratio [HR] (95% Confidence Interval [95%CI]): 1.51 (1.18-1.93);p=0.0010 at univariate analysis;HR 0.91 (0.71-1.17), p= 0.47, after adjusting for age, stage, BC treatment and comorbidities at multivariable analysis. COVID-19 occurred in 250 of 5563 (4.5%) newly-diagnosed BC cases in 2020. Notably, the time-dependent COVID-19 effect was significantly associated with mortality (multivariable Cox analysis HR 2.25 (1.35-3.74);p=0.0018) even after adjusting for age, stage, treatment and comorbidities. Conclusion(s): Breast cancer incidence and survival were both reduced in 2020, and COVID-19 was an independent predictor of death in BC patients. While follow-up is ongoing to assess long sequelae of COVID-19, these results encourage prevention of infection regardless of BC stage;and at the same time warn against suboptimal treatment and overlooking new diagnoses to ensure a favourable prognostic outcome.
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Background: Patients with autoimmune systemic diseases (ASDs) can be counted among frail populations as regards the predisposition to COVID-19 due to the frequent visceral organ involvement and comorbidities, as well as the ongoing immunomodulating treatments. Objectives: Our long-term multicenter telephone survey prospectively investigated the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients during the frst 3 pandemic waves. Methods: A large series of 3,918 ASD patients (815 M, 3103 F;mean age 59±12SD years) was consecutively recruited at the 36 referral centers of COVID-19 & ASD Italian Study Group. In particular, ASD series encompassed the following conditions: rheumatoid arthritis (n: 981), psoriatic arthritis (n: 471), ankylosing spondylitis (n: 159), systemic sclerosis (n: 1,738), systemic lupus (172), systemic vasculitis (n: 219), and a miscellany of other ASDs (n: 178). The development of COVID-19 was recorded by means of telephone survey using standardized symptom-assessment questionnaire (1). Results: A signifcantly increased prevalence of COVID-19 (8.37% vs 6.49%;p<0.0001) was observed in our ASD patients, while the cumulative death rate revealed statistically comparable to the Italian general population (3.65% vs 2.95%;p: ns). In particular, among the 328 ASD patients complicated by COVID-19, 57 (17%) needed hospitalization, while mild-moderate manifestations were observed in the large majority of individuals (83%). In addition, 12/57 hospitalized patients died due to severe interstitial pneumonia and/or cardiovascular manifestations. Interestingly, a signifcantly higher COVID-19-related death rate was observed in systemic sclerosis patients compared to the Italian general population (6.29% vs 2.95%;p=0.018). Other adverse prognostic factors to develop COVID-19 were the patients' older age, male gender, pre-existing ASD-related interstitial lung involvement, and chronic steroid treatment. Conversely, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a signifcantly lower prevalence of COVID-19 compared to those without (3.58% vs 46.99%;p=0.000), as well as the chronic administration of low dose aspirin in a subgroup of SSc patients (with 5.57% vs without 27.84%;p=0.000). Conclusion: The cumulative impact of COVID-19 on ASD patients after the frst 3 pandemic waves revealed less severe than that observed during the frst phase of pandemic (1), especially with regards to the death rate that was comparable to the Italian general population in spite of the increased prevalence of complicating COVID-19 in the same ASD series. Ongoing long-term treatments, mainly csDMARDs, might usefully contribute to generally positive outcomes of in this frail patients' population. Of note, a signifcantly increased COVID-19-related mortality was recorded in only SSc patients' subgroup, possibly favored by pre-existing lung fbrosis. Among different ASD, SSc deserves special attention, since it shares the main pathological alterations with COVID-19, namely the interstitial lung involvement and the endothelial injury responsible for diffuse microangiopathy. Besides SSc, the patients' subgroups characterized by older age, chronic steroid treatment, pre-existing interstitial lung disease, and/or impaired COVID-19 vaccine response (1-3), may deserve well-designed prevention and management strategies.
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Background-Physical distancing for COVID-19 led to decreased in-person patient follow up assessments and delayed imaging appointments. Herein we describe for the first time the impact of delays in diagnostic investigations of patients with an history of early-stage breast cancer (BC) in the largest public cancer center of Lombardy, the Italian region most affected by the pandemic. Methods-This single-institution retrospective study included three observational periods. The first pandemic peak period (March-April 2020) corresponding to the interruption of follow up imaging;the post-peak period (May-December 2020);the pre-pandemic period represented by the five previous years (January 2015-December 2019) as control. The flow of diagnostic activities was compared among the different years. Moreover, the number and characteristics of recurrent BC cases (rBC) diagnosed in the post-peak period were compared to the figures observed in pre-pandemic years, when imaging was regularly carried out, using descriptive statistics. A further comparison was performed between the characteristics of scheduled and delayed rBC diagnosed after the first peak. Results-During the first pandemic peak, diagnostic investigations declined by 81.2% (from 1032 in January-February to 194 in March-April), a drop which was not identified in the same period of the pre-pandemic years, before rebounding to 1065 in May-June, 832 July-August (reflecting the Ssummer physiological drop), 1334 September-October, and 879 November-December. The average number of rBC cases of 16 (range 12-25) in March-April of the pre-pandemic period declined to a value as low as 4 during the first pandemic peak. Thereafter, the number of rBC cases began a steady increase, until reaching a total of 27 in September-October 2020, almost doubling the mean of 14.8 (range 11-21) achieved in the corresponding months of 2015-2019. As a result, the absolute number of rBC cases was 76 in 2020 and on average 78.4 (range 70-95) in pre-pandemic years, and the rBC proportion of 1.42% (76/5336;95% exact confidence interval, CI: 1.12-1.78%) in 2020 was slightly higher than the average proportion of 1.26% of the five previous years, though the latter being well included in the CI of the 2020 proportion. No difference in primary tumor presentation and age at initial diagnosis was found among recurrent patients before and after the pandemic. Of the rBC cases reported during 2020, 10 were from 513 patients with postponed follow up who were finally diagnosed between September-December. As compared to patients on schedule, delayed rBC cases did not present with ductal carcinoma in situ, and reported a median tumor size of 18 mm (range 4.3-90 mm), which was 20% higher than the median of 15 mm (3.1-34) observed for scheduled patients. Distribution of luminal-like, triple negative and HER2-overexpressing BC subtypes among evaluable rBC cases was 75%, 12.5%, 12.5% in scheduled and 66%, 11% and 22% in delayed cases, respectively. Conclusions-Our data showed a slight decrease in the absolute number of rBC during 2020 despite a rebound of examinations, and an increased size of invasive recurrence following the 2-month stop of the first pandemic peak. The full impact of the COVID-19 pandemic on recurrent cancer diagnosis will be known when national population-based data become available in the coming years.
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Background: SARS-CoV-2 infection poses a serious challenge for patients with rheumatic autoimmune systemic diseases (ASD), characterized by marked immune-system dysregulation and frequent visceral organ involvement. Objectives: To evaluate the impact of COVID-19 pandemic in a large series of Italian patients with ASD. Methods: Our multicenter telephone survey (8-week period, March-April 2020) included a large series of 2,994 patients (584 M, 2,410 F, mean age 58.9±13.4SD years) with ASD followed at 34 tertiary referral centers of 14 regions of northern, central, and southern Italian macro areas, characterized by different prevalence of SARS-CoV-2 infection. According to currently used criteria, COVID-19 was classified as definite COVID-19 (signs or symptoms of COVID-19 confirmed by positive oral/nasopharyngeal swabs at PCR testing) or highly suspected COVID-19 (signs or symptoms highly suggestive of Covid-19, but not confirmed by PCR testing due to limited availability of virological tests in that period). The results were analyzed performing the Odds Ratio by Java-Stat 2-way Contingency Table Analysis. Results: The main findings of the survey study revealed a significantly increased prevalence of COVID-19 in: a.the whole series of ASD patients (definite Covid-19: 22/2994, 0.73%;p=0.0007;definite COVID-19 plus highly suspected Covid-19: 74/2,994, 2.47%;p<0.0001) when compared to Italian general population of COVID-19 infected individuals (349/100000 = 0.34%;data from Italian Superior Institute of Health;h t t p s : / / w w w . e p i c e n t r o . i s s . i t / e n / c o r o n a v i r u s / sars-cov-2-national-surveillance-system). b.the subgroup of patients with connective tissue diseases or systemic vasculitis (n = 1,901) compared to the subgroup of inflammatory arthritis (n = 1,093), namely rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (definite Covid-19: 19/1,901, 0.99%, vs 3/1,093, 0.27%;p=0.036;definite COVID-19 plus highly suspected Covid-19: 69/1,901, 3.6%, vs 5/1,093, 0.45%;p<0.0001) c.the subgroup of patients with pre-existing interstitial lung involvement (n = 526) compared to those without (n = 2,468) (definite Covid-19: 10/526, 1.90%, vs 12/2,468, 0.48%;p=0.0015;definite COVID-19 plus highly suspected Covid-19: 33/526, 6.27%, vs 41/2,468, 1.66%;p<0.0001). Of interest, the prevalence of COVID-19 did not correlate with presence/absence of different comorbidities, mainly diabetes, cardio-vascular and/or renal disorders, as well as of ongoing treatments with biological DMARDs;while patients treated with conventional DMARDs showed a significantly lower prevalence of COVID-19 compared to those without. COVID-19 was more frequently observed in the patients' populations from northern and central compared to southern Italian macro area with lower diffusion of pandemic. Clinical manifestations of Covid-19, observed in 74 patients, were generally mild or moderate;4/9 individuals requiring hospital admission died for severe pneumonia. Conclusion: The prevalence of COVID-19 observed in ASD patients during the first wave of pandemic was significantly higher than that observed in Italian general population;moreover, the actual prevalence of COVID-19 might be underestimated due to the high number of mild variants as well as the possible clinical overlapping between these two conditions. Patients with ASD should be invariably regarded as 'frail patients' during the pandemic course, considering the risk of worse outcome in the acute phase of Covid-19, as well as the potential long-term effects of viral infection. The statistically significant association of COVID-19 with connective tissue diseases/ systemic vasculitis, as well as with pre-existing interstitial lung involvement, suggests the presence of distinct clinico-pathological ASD subsets, characterized by markedly different patients' vulnerability to SARS-CoV-2 infection.
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Background: Coronavirus disease-19 (COVID-19) has been a major clinical challenge worldwide. Sex, age and comorbidities have been associated with worse outcome in the general population. Systemic sclerosis (SSc) is a severe, autoimmune disease with frequent multi-organ involvement. Objectives: To assess the impact of COVID-19 and to determine factors associated with worse outcome in SSc patients from the European Scleroderma Trial and Research (EUSTAR) database. Methods: SSc patients from the EUSTAR database with COVID-19 were prospectively collected between 15.03.-31.12.2020. Two outcomes were chosen: (1) hospitalization;and (2) severe outcome defined as either non-invasive ventilation, mechanical ventilation/extracorporeal membrane oxygenation (ECMO) or death. General risk factors assessed were sex, age and number of comorbidities. SSc related risk factors were SSc subtype, autoantibodies, disease duration, SSc associated organ manifestations including interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), cardiac, gastrointestinal (GI), and musculoskeletal involvement;digital ulcers (DU), CRP at last visit, renal disease (scleroderma renal crisis and SSc associated renal insufficiency), modified Rodnan skin score (mRSS) and immunosuppressive treatment. Descriptive statistics and logistic regression models were applied. Results: In total, 178 European SSc patients with COVID-19 were registered with a median observation time of 5.5 weeks (Table 1). 95 patients (53%) could recall SAR-Cov-2 contact, while 47 (26%) had no contact. 156 (88%) were symptomatic at COVID-19 onset with fever, cough, malaise and dyspnea being most prevalent. Over the disease course, 63 (36%) developed pneumonia. In total, 67/176 (38%) were hospitalized which were in 84% due to COVID-19. 41/170 (24%) had a severe outcome including 21 (12%) deaths. 128 (72%) recovered completely, while 14 (8%) complained of sequela, with 7 (50%) stating respiratory complications. Age, non-SSc comorbidities, presence of ILD, PAH and SSc associated renal or cardiac disease were numerically associated with hospitalization and severe outcome (Table 1). Univariable logistic analyses for hospitalization and severe outcome are shown in Figure 1. In multivariable logistic regression, age (OR 1.03, 95%CI 1.01-1.07, p=0.019), presence of non-SSc comorbidities (OR 2.52, 95%CI 1.16-5.47, p=0.019) and SSc-related renal disease (predicting success perfectly) were associated with hospitalization and for severe outcome age (OR 1.05, 95%CI 1.01-1.08). Conclusion: SSc patients at older age, with non-SSc comorbidities, SSc related renal disease or ILD are at risk of a more severe outcome and should follow precautions to avoid COVID-19 infections and need careful monitoring in case of COVID-19.
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Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by a novel SARS-CoV-2 pathogen. Its capacity for human-to-human transmission through respiratory droplets, coupled with a high-level of population mobility, has resulted in a rapid dissemination worldwide. Healthcare workers have been particularly exposed to the risk of infection and represent a significant proportion of COVID-19 cases in the worst affected regions of Europe. Like other open airway procedures or aerosol-generating procedures, bronchoscopy poses a significant risk of spreading contaminated droplets, and medical workers must adapt the procedures to ensure safety of both patients and staff. Several recommendation documents were published at the beginning of the pandemic, but as the situation evolves, our thoughts should not only focus on the present, but should also reflect on how we are going to deal with the presence of the virus in the community until there is a vaccine or specific treatment available. It is in this sense that this document aims to guide interventional pulmonology throughout this period, providing a set of recommendations on how to perform bronchoscopy or pleural procedures safely and efficiently.