Scleroderma renal crisis following Covid-19 infection.

To describe a series of systemic sclerosis (SSc) patients with the unusual combination of scleroderma renal crisis (SRC) and pulmonary hypertension (PHT) without interstitial lung disease. The medical records of 2,459 SSc patients in the University of Pittsburgh Scleroderma Databank first evaluated between 1972 and 1999 were reviewed. Eleven patients (0.45%) had both SRC and PHT. All had been evaluated since 1979, when angiotensin-converting enzyme (ACE) inhibitor therapy for SRC became available. Seven had SSc with limited cutaneous involvement, and 4 had SSc with diffuse cutaneous involvement. SRC occurred first in all patients except 1, in whom the onsets of SRC and PHT were simultaneous. SRC preceded PHT by a mean of 4.3 years. Four patients had anti-Th/To antibody, 5 had anti-RNA polymerase III antibody, 2 had anti-U3 RNP antibody, and none had anticentromere or antitopoisomerase I antibody. Ten of the 11 patients died, 8 from PHT. Ten patients were being treated with ACE inhibitor drugs when PHT developed. In SSc, SRC and PHT are not mutually exclusive complications. SSc patients surviving SRC who have serum antibodies to Th/To, RNA polymerase III, or U3 RNP are at increased risk to develop PHT. ACE inhibitor therapy did not prevent the development of PHT.

To characterise the clinical features, predictors, and prognosis of patients with systemic sclerosis (SSc) who had both scleroderma renal crisis (SRC) and pulmonary arterial hypertension (PAH). In this retrospective cohort study, we reviewed 234 patients diagnosed with SSc at our institute between January 2013 and April 2024. Clinical characteristics and prognosis were compared among patients with both SRC and PAH, PAH alone, SRC alone, and neither PAH nor SRC. Predictors of the coexistence of PAH and SRC were identified using multivariate logistic regression analysis. Among the 234 patients with SSc, 17 (7.3%) had both PAH and SRC. PAH preceded SRC in five patients, followed SRC in three, and occurred simultaneously in nine. Compared with patients with SRC alone, those with both SRC and PAH had a higher prevalence of interstitial lung disease, a higher rate of gastrointestinal bleeding (GIB), and lower serum albumin levels. GIB (OR=9.545, 95%CI: 1.679, 54.264; p=0.011) was independently associated with the coexistence of PAH and SRC compared with SRC alone, whereas older age at disease onset (OR=1.200, 95%CI: 1.014, 1.420; p=0.033) and elevated NT-proBNP (OR=1.001, 95%CI: 1.000, 1.001; p=0.030) were independently associated with the coexistence of PAH and SRC compared with PAH alone. PAH may precede, follow, or coincide with SRC. Patients with both SRC and PAH had a significantly higher risk of GIB. Older age and elevated NT-proBNP were independent factors associated with the coexistence of SRC and PAH.

Background:Systemic sclerosis (SSc) is characterized by progressive fibrosis and microvascular dysfunction that involves multiple organ systems, including kidneys. Kidney involvement, beyond the scleroderma renal crisis (SRC), is often asymptomatic and...

POS0054 THE IMPACT AND OUTCOME OF COVID-19 ON SYSTEMIC SCLEROSIS PATIENTS FROM THE EUROPEAN SCLERODERMA TRIAL AND RESEARCH GROUP (EUSTAR)

Angiotensin-converting enzyme inhibitors (ACEIs) are widely used in the treatment of scleroderma renal crisis (SRC), and their use prior to the onset of SRC in patients with systemic sclerosis (SSc) has received wide attention in recent years. We undertook an evidence-based approach to identify whether the use of ACEIs prior to the onset of SRC is beneficial for patients with SSc. We searched PubMed and Embase for any published studies produced between database inception and 22 October 2021. Articles obtained after using appropriate keywords were selected independently by two reviewers according to the established inclusion and exclusion criteria. Nine studies were included. Pooled results indicated that using ACEIs prior to SRC was associated with a higher incidence of SRC than no ACEIs prior to SRC (RR 2.05, 95% confidence interval 1.08-3.91, p=0.03). Compared with patients who did not use ACEIs prior to the onset of SRC, a higher proportion of patients with SRC who used ACEIs prior to its onset had a poorer prognosis (RR 1.46, 95% confidence interval 1.20-1.78, p<0.01). The difference in mortality between patients who used ACEIs prior to SRC onset and those who did not was not statistically significant (RR 1.12, 95% confidence interval 0.76-1.65, p=0.57). We recommend against using ACEIs prior to SRC in SSc patients. The use of ACEIs prior to SRC is associated with a higher incidence of SRC and poorer prognosis, especially in patients with progressive SSc or SSc-related renal vasculopathy (SSc-related hypertension and proteinuria).

The increased awareness of systemic sclerosis (SS) and its pathogenetic background made the management of this disease more amenable than previously thought. However, scleroderma renal crisis (SRC) is a rarely seen as an associated disorder that may involve 2%-15% of SS patients. Patients presented with earlier, rapidly progressing, diffuse cutaneous SS disease, mostly in the first 3-5 years after non-Raynaud clinical manifestations, are more vulnerable to develop SRC. SRC comprises a collection of acute, mostly symptomatic rise in blood pressure, elevation in serum creatinine concentrations, oliguria and thrombotic microangiopathy in almost 50% of cases. The advent of the antihypertensive angiotensin converting enzyme inhibitors in 1980 was associated with significant improvement in SRC prognosis. In a scleroderma patient maintained on regular dialysis; every effort should be exerted to declare any possible evidence of renal recovery. A given period of almost two years has been suggested prior to proceeding in a kidney transplant (KTx). Of note, SS patients on dialysis have the highest opportunity of renal recovery and withdrawal from dialysis as compared to other causes of end-stage renal disease (ESRD). KTx that is the best well-known therapeutic option for ESRD patients can also be offered to SS patients. Compared to other primary renal diseases, SS-related ESRD was considered for a long period of poor patient and allograft survivals. Pulmonary involvement in an SS patient is considered a strong post-transplant independent risk factor of death. Recurrence of SRC after transplantation has been observed in some patients. However, an excellent post-transplant patient and graft outcome have been recently reported. Consequently, the absence of extrarenal manifestations in an SS-induced ESRD patient can be accepted as a robust indicator for a successful KTx.

The renin-angiotensin-aldosterone system (RAAS) and glucocorticoids (GCs) are involved in vascular remodeling and fibrosis but have not been extensively studied in systemic sclerosis (SSc). Our aim was to investigate the RAAS and GC hormones in SSc patients. Serum levels of renin (dosage and activity), aldosterone and its precursors (DOC, B, 18-OH-DOC, 18-OH-B), and GCs (cortisol, cortisone, 11-deoxycortisol, 18-OH-F) were assessed in 122 SSc patients and 52 healthy controls. After applying stringent inclusion criteria aimed at ensuring accurate hormone assessments (exclusion of interfering drugs, strict sampling conditions), we analysed RAAS hormones in 61 patients, and GCs in 96 patients. Hormone levels were compared between patients and controls; and associations with disease characteristics were assessed in patients. Regarding RAAS hormones, SSc patients displayed significantly lower aldosterone levels (although within normal range), similar renin levels, and higher B levels than controls. Abnormal RAAS hormone levels were associated with a more severe SSc phenotype (lung and skin fibrosis, heart and pulmonary vascular involvements, inflammation). Regarding GC hormones, SSc patients had higher levels of cortisol, 11-desoxycortisol (precursor) and 18-OH-F (metabolite) but lower levels of cortisone (inactive counterpart) than controls. RAAS hormone levels were assessed in five SSc patients before and during scleroderma renal crisis (SRC): concentrations varied considerably between patients, but consistently included normal/increased aldosterone levels and elevated renin levels. RAAS and GC hormones are abnormally produced in SSc patients, especially in patients with severe SSc and during SRC. This could suggest a participation of these hormonal systems in SSc pathogenesis.

Mortality and risk factors of scleroderma renal crisis: a French retrospective study of 50 patients

To determine whether the initiation of corticosteroids or other types of therapy affects the development of scleroderma renal crisis (SRC). Using a case-control study, 110 patients with systemic sclerosis who developed SRC between 1981 and 1993 were closely matched with controls on sex, race, age, disease duration, skin score, levels of creatine phosphokinase, and presence of tendon friction rubs. Corticosteroid use was determined prior to the onset of SRC in cases or prior to the first visit in controls. Cases were compared with matched controls using McNemar's matched-pair analysis and conditional logistic regression analysis. The effects of other drugs, including D-penicillamine, nonsteroidal antiinflammatory drugs (NSAIDs), calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors, were also evaluated. In the 6 months prior to SRC onset or to the first visit, high-dose corticosteroids (> or =15 mg/day prednisone or equivalent) were administered significantly more frequently in SRC patients (36%) than in the controls (12%) (McNemar's odds ratio 4.37, 95% confidence interval 2.03-9.43, P < 0.0001). New use of low-dose steroids, continuous use of any steroid dose, NSAIDs, calcium channel blockers, and ACE inhibitors were not associated with an increased risk of SRC. Antecedent D-penicillamine therapy may have been protective against the development of SRC in controls. This retrospective case-control study has shown a significant association between antecedent high-dose corticosteroid therapy and the development of SRC. These results should discourage the use of high-dose corticosteroids in patients with early diffuse scleroderma who are at increased risk of developing SRC.

Scleroderma renal crisis (SRC) is a major complication in patients with systemic sclerosis (SSc). SRC occurs during the first 4 years of disease evolution in more than 75% of the cases, almost exclusively in patients with diffuse SSc. Other risk factors, including preceding corticosteroid therapy, have been associated with an increased occurrence of SRC. Prior to the late 1970s, SRC was a major cause of death in SSc patients. However, the prognosis has dramatically improved with the introduction of angiotensin-converting enzyme inhibitors. Thus, prompt diagnosis and early initiation of angiotensin-converting enzyme inhibitors therapy will improve the outcome. Nevertheless, additional antihypertensive treatments are often needed. Quite a large proportion of patients require dialysis, although this therapy may be stopped in approximately one-third of patients. Patients remaining on dialysis after 2 years can be proposed for a renal transplantation.

To identify indications for which different dosages of glucocorticoids (GCs) have been prescribed in systemic sclerosis (SSc), and to assess the efficacy and safety of GCs in SSc. A literature search focusing on experimental studies, observational studies, and case reports describing GC use in SSc was conducted using PubMed, EMBASE and Cochrane databases. Information about the study population, GC therapy and its effects was recorded. Available data have been summarised, and efficacy and safety of GCs have been assessed for different indications and dosages. Forty-four studies and 93 case reports were included in this review. GCs were applied in the treatment of interstitial lung disease (ILD), diffuse cutaneous disease, myopathy, painful hands and cardiac involvement, or accompanying anti-thymocyte globulin to prevent serum sickness in the context of stem cell transplantation. GCs were used in different dosages, predominantly in combination with other immunosuppressive treatments. Monotherapy with GCs led to inconsistent results. Most adverse events recorded were infections. Twenty-three cases of scleroderma renal crisis (SRC) have been reported, mainly in patients with early diffuse disease (n=10) or with anti-thymocyte treatment (n=10). These patients were treated with low to medium dose GCs (n=10), high-dose GCs (n=11) and pulse therapy (n=2). Evidence of a beneficial role of GCs in SSc is limited. GCs have been part of the therapeutic strategy in the management of ILD, diffuse cutaneous disease or myositis. Awareness for the risk of SRC should persist, especially in patients with diffuse disease who are also treated with possibly nephrotoxic drugs.

A 46-year-old man was diagnosed with anti jo-1 antibody-positive dermatomyositis 11years ago and had been treated with prednisolone and tacrolimus. In the present case, after contracting SARS-CoV-2 virus infection, his dyspnoea rapidly worsened, and he presented with renal and cardiac failure. Based on the biopsy results of the same area and anti-U1-RNP antibody positivity, he was diagnosed with systemic sclerosis and scleroderma renal crisis and required haemodialysis. A renal biopsy performed later showed tubular atrophy, intratubular cell debris, and endothelial cell damage, consistent with scleroderma renal crisis. Although rapid skin hardening and high-dose glucocorticoid use are known risks for scleroderma renal crisis, scleroderma renal crisis triggered by novel SARS-CoV-2 virus infection has never been reported before and is very rare. It is crucial to identify the relationship between the scleroderma renal crisis and SARS-CoV-2 virus infection. This relationship can be explained through the RAS system, which is believed to play a role in the development of both.

Background:Systemic sclerosis (SSc) manifests through a diverse interplay of inflammatory, fibrotic, and vascular alterations, intricately entwined in its pathogenesis, which encompasses immune system dysregulation, tissue fibrosis, and vascular dysfunction. While...

Background:LL37 is a human cathelicidin peptide reported to have antimicrobial and immunomodulatory activity. Excess levels of LL37 are thought to correlate with enhanced local inflammation in various diseases, including rheumatoid...

Antinuclear antibody-negative systemic sclerosis