Glomerulonephritis associated with systemic sclerosis: a case report.

BACKGROUND: Systemic sclerosis is a multiorgan autoimmune disease that can overlap with other rheumatologic disorders; however, co-occurrence with antineutrophil cytoplasmic antibody-associated vasculitis is rare. CASE PRESENTATION: A 39-year-old Persian female patient with systemic sclerosis according to American College of Rheumatology/European League Against Rheumatism 2013 criteria with a disease duration of 6 years was admitted to the hospital due to a rise in creatinine level in July 2021. She had complaints of nasal speech and feeling of nasal perforation. The first symptoms of antineutrophil cytoplasmic antibody-associated vasculitis had started 5 years earlier with palpable purpura in the lower limbs, hemoptysis, and positive perinuclear (p)-antibody-associated vasculitis level (> 300 AU/mL). Still, the diagnosis was not achieved due to the patient's reluctance to undergo a biopsy. She was treated with azathioprine (150 mg/day) and prednisolone (10 mg/day) during the 5-year follow-up. Her renal biopsy results showed cortical renal tissue with a cellular crescent in more than 50% of the specimen, rupture of the Bowman capsule and the glomerular basement membrane, peri-glomerular inflammation, and mild tubular atrophy in microscopic examinations. The immunofluorescence study resulted in a granular pattern of immune deposits along the glomerular basement membrane, mesangial tissue, and tubular basement membranes. CONCLUSION: We reported a rare case of comorbid systemic sclerosis and antineutrophil cytoplasmic antibody-associated vasculitis with nasal perforation. Her renal biopsy showed immune deposits along the glomerular basement membrane, mesangial tissue, and tubular basement membranes. Overlapping with other collagen vascular diseases can occur in rheumatology patients with uncommon manifestations. In systemic sclerosis, renal involvement in the form of glomerulonephritis is infrequent, and comorbid systemic lupus erythematosus or antineutrophil cytoplasmic antibody-associated vasculitis should be considered.

Systemic sclerosis following COVID-19 infection with recurrent corticosteroid-induced scleroderma renal crisis.

Systemic sclerosis is a complex multisystem connective tissue disease resulting in fibrosis of the skin and internal organs. Exposure to corticosteroids can trigger scleroderma renal crisis, a life-threatening complication of the disease. Autoimmune disease following infection with COVID-19 is being increasingly recognised. The mechanisms of post-COVID-19 autoimmunity are likely multifactorial, involving immune dysregulation, molecular mimicry and the development of cross-reactive antibodies. There are currently only two reported cases of systemic sclerosis occurring post-COVID-19 infection.We present the case of a female patient who developed systemic sclerosis post-COVID-19 infection. Following exposure to corticosteroids, the patient developed scleroderma renal crisis complicated by thrombotic microangiopathy, seizures and acute renal failure. Despite an antibody profile not typically associated with renal crisis (anti-topoisomerase positive, anti-RNA-polymerase III negative), the patient developed recurrent renal crisis with repeated exposure to corticosteroid therapy, highlighting the risk of steroid use in all patients with systemic sclerosis.

Acute limb ischemia in an adolescent with COVID-19 and systemic scleroderma: a case report.

BACKGROUND: Juvenile Scleroderma is a rare autoimmune disease of the connective tissue. Its concurrence with COVID-19 can lead to limb ischemia as both disease entities are pro-inflammatory and pro-thrombotic. To date, there is no case report describing the symptomatology and course of disease in patients with juvenile Scleroderma and COVID-19. CASE PRESENTATION: An adolescent with acute limb ischemia presented with a history of generalized hypo-and-hyperpigmented skin lesions and mild, non-productive cough. She tested positive for SARS-CoV-2 on nasopharyngeal swab RT-PCR. Further work-up revealed elevated anti-phospholipid antibodies, anti-nuclear antibody, and D-dimer; low Protein S activity; and evidence of peripheral arterial disease on imaging studies. She was started on peripheral vasodilators, Methotrexate, and anticoagulation. Close monitoring of the affected limbs and other organs involved was done. Control of limb ischemia was achieved after 4 months of regular Cyclophosphamide infusion. Continued multi-disciplinary care was ensured for this patient. CONCLUSION: There is evolving knowledge about the interplay of COVID-19 hyperinflammatory state and rheumatologic disorders. COVID-19 is thought to exacerbate cutaneous manifestations of autoimmune disorders via antigen protein mimicry and cytokine imbalance. Moreover, COVID-19 is characterized by complex hematopathologic processes that put a patient in a hypercoagulable state. Elevated D-dimer can be seen in both COVID-19 and systemic sclerosis owing to their pro-thrombotic sequela. There is scarcity of data on the association of Protein S activity with COVID-19 and systemic sclerosis. More studies need to be carried out to ultimately arrive at a consensus on thrombosis prophylaxis for patients with Scleroderma and COVID-19.

Sudden winter iloprost withdrawal in scleroderma patients during COVID-19 pandemic.

INTRODUCTION: Intravenous iloprost is currently recommended in the treatment of Raynaud's phenomenon (RP) refractory to oral therapy and of digital ulcers (DUs) related to systemic sclerosis (SSc). In real-life practice there is a huge heterogeneity about the Iloprost regimens used. METHODS: A survey was carried out on SSc patients that interrupted Iloprost infusion to compare acral vascular symptoms just before Iloprost withdrawal and just after the missed infusion. Severity, and frequency of RP, new DUs onset or aggravation of those pre-existing were reported. Last available capillaroscopic images were also evaluated. RESULTS: The analysis includes 50 patients. After iloprost withdrawal, 11 patients reported a RP worsening because of enhanced intensity (p = 0.007). Only 8 patients of them also complained of an increased frequency (p = 0.07). None of the patients experienced digital ulcers for the first-time during quarantine. Among the 27 patients with a history of digital ulcers, 9 reported worsening and 7 recurrence of DUs. Overall, 17 patients (34.0 %) complained of a worsening of SSc vascular acral manifestations, namely RP or DUs. Reduced capillary density was associated with RP worsening, in particular, each unit increase of capillary density corresponds to an average 44 % decrease in the odds of RP worsening (OR 0.56, CI 95 % 0.36-0.97, p = 0.037). As for RP worsening, the aggravation of DU was associated with a lower capillary density. CONCLUSIONS: Low capillary density can predict a worsening of both RP and DUs in controlled quarantine conditions within a month after iloprost discontinuation in SSc patients.

Severity and mortality of COVID-19 in patients with systemic sclerosis: a Brazilian multicenter study.

INTRODUCTION: COVID-19 may be associated with greater severity and mortality in patients with systemic sclerosis (SSc). The present study aimed to evaluate the prevalence, severity and mortality of COVID-19 in a Brazilian cohort of SSc patients. METHODS: This multicenter, retrospective, observational study included 1,042 SSc patients followed in four centers of São Paulo between March 2020 and June 2021. Diagnosis of COVID-19 was established by proper positive RT-PCR testing or by highly suspicious infection. Patients were grouped into mild (outpatient setting treatment and no need for oxygen support) and moderate-to-severe (hospitalization and/or need for oxygen support) COVID-19. RESULTS: Of the 1,042 SSc patients, 118 patients were diagnosed with COVID-19. Interstitial lung disease (SSc-ILD) was present in 65.6% of the total cohort and in 46.3% of SSc patients with COVID-19. There were 78 (66.1%) cases of mild COVID-19, and 40 (33.9%) cases of moderate-to-severe disease, with 6 (5.1%) deaths. By univariate analysis, pulmonary arterial hypertension (OR 9.50, p=0.006), SSc-ILD (OR 3.90, p=0.007), FVC <80% (OR 2.90, p=0.01), cardiac involvement (OR 5.53, p=0.003), and use of rituximab (OR 3.92, p=0.039), but not age, gender, comorbidities or use of corticosteroids, were predictors of worse outcome for COVID-19. Using multivariate analysis, only SSc-ILD was significantly associated to a higher risk of moderate-to-severe COVID-19 (OR 2.73, 95% CI 1.12-6.69, p=0.02). Forty percent of the patients remained with symptoms after presenting COVID-19, predominantly dyspnea and/or cough (17%). CONCLUSION: In this cohort of patients with SSc, those with SSc-ILD were highly impacted by COVID-19, with a higher risk of moderate-to-severe COVID-19 infection and death.

From Raynaud Phenomenon to Systemic Sclerosis in COVID-19: A Case Report.

ABSTRACT: In 2019, the novel SARS-CoV-2 infection emerged, causing the disease called COVID-19, which primarily affects the respiratory tract and lung at alveolar and interstitial levels. Systemic sclerosis (SSc) is an autoimmune connective disease characterized by vascular abnormalities and diffuse and progressive fibrosis of the skin and internal organs. Raynaud phenomenon (RP) occurs in virtually all patients affected by SSc and, in most cases, is an onset symptom of the disease; that is, RP may appear several years before overt illness. Although the exact pathophysiologic pathways leading to RP and SSc are still unknown, several infectious agents, especially viruses, have been suggested as possible triggering factors. Here, the authors describe the first case of RP secondary to SSc following SARS-CoV-2 infection.

The role of chest CT in deciphering interstitial lung involvement: systemic sclerosis versus COVID-19.

OBJECTIVE: The aim of this study was to identify the main CT features that may help in distinguishing a progression of interstitial lung disease (ILD) secondary to SSc from COVID-19 pneumonia. METHODS: This multicentric study included 22 international readers grouped into a radiologist group (RADs) and a non-radiologist group (nRADs). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. RESULTS: Fibrosis inside focal ground-glass opacities (GGOs) in the upper lobes; fibrosis in the lower lobe GGOs; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONs in the lower lobes (P < 0.0001) and signs of fibrosis in GGOs in the lower lobes (P < 0.0001) remained independently associated with COVID-19 pneumonia and SSc-ILD, respectively. A predictive score was created that was positively associated with COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity). CONCLUSION: CT diagnosis differentiating between COVID-19 pneumonia and SSc-ILD is possible through a combination of the proposed score and radiologic expertise. The presence of consolidation in the lower lobes may suggest COVID-19 pneumonia, while the presence of fibrosis inside GGOs may indicate SSc-ILD.

Patient Perspectives on the Effect of the SARS-CoV-2 Pandemic on Patients With Systemic Sclerosis: An International Patient Survey.

BACKGROUND: The coronavirus disease (COVID-19) pandemic and its subsequent effects on health care systems have significantly impacted the management of chronic rheumatic diseases, including systemic sclerosis (SSc). METHODS: In this context, a 25-item anonymized e-survey was posted on the Twitter and Facebook e-groups and pages of various scleroderma organizations and patient communities to assess the problems faced by patients with SSc during the pandemic, with a focus on effects on the disease, drug procurance, continuity of medical care, and prevalent fears among patients. RESULTS: Of the 291 participants (median age of 55 [43.5-63] years, 93.8% females), limited systemic sclerosis was the most common diagnosis (42.3%). Many patients experienced problems attributable to the COVID-19 pandemic (119, 40.9%), of which 46 (38.7%) required an increase in medicines, and 12 (10.1%) of these needed hospitalizations for disease-related complications. More than one-third (36.4%) were on glucocorticoids or had underlying cardiovascular risks (39%) that would predispose them to severe COVID-19.A significant proportion (38.1%) faced hurdles in procuring medicines or experienced disruption in physiotherapy sessions (24.7%). One-quarter (24.1%) felt it was difficult to contact their specialist, whereas another 7.2% were unable to do so. Contracting COVID-19 was the most prevalent fear (71.5%), followed by infection in the family (61.9%), and a flare of the disease (45.4%). Most respondents preferred teleconsultations (55.7%) over hospital visits in the pandemic period. CONCLUSION: The results of the patient survey suggest that the COVID-19 pandemic has affected many patients with SSc and may translate to poorer outcomes in this population in the postpandemic period.

Hydroxychloroquine and maintenance immunosuppression use in kidney transplant recipients: Analysis of linked US registry and claims data.

Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory effects used to treat systemic lupus erythematosus (SLE) and scleroderma. The antiviral effects of HCQ have raised attention in the context of the COVID-19 pandemic, although safety is controversial. We examined linkages of national transplant registry data with pharmaceutical claims and Medicare billing claims to study HCQ use among Medicare-insured kidney transplant recipients with SLE or scleroderma (2008-2017; N = 1820). We compared three groups based on immunosuppression regimen 7 months-to-1 year post transplant: (a) tacrolimus (Tac) + mycophenolic acid (MPA) + prednisone (Pred) (referent group, 77.7%); (b) Tac + MPA + Pred + HCQ (16.5%); or (c) other immunosuppression + HCQ (5.7%). Compared to the referent group, recipients treated with other immunosuppression + HCQ had a 2-fold increased risk of abnormal ECG or QT prolongation (18.9% vs. 10.7%; aHR,1.12 1.963.42 , p = .02) and ventricular arrhythmias (15.2% vs. 11.4%; aHR,1.00 1.813.29 , p = .05) in the >1-to-3 years post-transplant. Tac + MPA + Pred + HCQ was associated with increased risk of ventricular arrhythmias (13.5% vs. 11.4%; aHR,1.02 1.542.31 , p = .04) and pancytopenia (35.9% vs. 31.4%; aHR,1.03 1.311.68 , p = .03) compared to triple immunosuppression without HCQ. However, HCQ-containing regimens were not associated with an increased risk of death or graft failure. HCQ may be used safely in selected kidney transplant recipients in addition to their maintenance immunosuppression, although attention to arrhythmias is warranted.

National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 in Germany (ReCoVery): a valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV-2 infections in patients with IRD.

OBJECTIVES: Patients with inflammatory rheumatic diseases (IRD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be at risk to develop a severe course of COVID-19. The influence of immunomodulating drugs on the course of COVID-19 is unknown. To gather knowledge about SARS-CoV-2 infections in patients with IRD, we established a registry shortly after the beginning of the pandemic in Germany. METHODS: Using an online questionnaire (www.COVID19-rheuma.de), a nationwide database was launched on 30 March 2020, with appropriate ethical and data protection approval to collect data of patients with IRD infected with SARS-CoV-2. In this registry, key clinical and epidemiological parameters-for example, diagnosis of IRD, antirheumatic therapies, comorbidities and course of the infection-are documented. RESULTS: Until 25 April 2020, data from 104 patients with IRD infected with SARS-CoV-2 were reported (40 males; 63 females; 1 diverse). Most of them (45%) were diagnosed with rheumatoid arthritis, 59% had one or more comorbidities and 42% were treated with biological disease-modifying antirheumatic drugs. Hospitalisation was reported in 32% of the patients. Two-thirds of the patients already recovered. Unfortunately, 6 patients had a fatal course. CONCLUSIONS: In a short time, a national registry for SARS-CoV2-infected patients with IRD was established. Within 4 weeks, 104 cases were documented. The registry enables to generate data rapidly in this emerging situation and to gain a better understanding of the course of SARS-CoV2-infection in patients with IRD, with a distinct focus on their immunomodulatory therapies. This knowledge is valuable for timely information of physicians and patients with IRD, and shall also serve for the development of guidance for the management of patients with IRD during this pandemic.