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Objectives To evaluate the effectiveness of early initiation of angiotensin-converting enzyme inhibitor (ACEi) in patients with scleroderma renal crisis (SRC). Methods This was a retrospective cohort study using a nationwide inpatient database in Japan from July 2010 to March 2020. All hospitalized patients with SRC were divided into those who received ACEi within 2 days of admission (early ACEi group) and those who did not (control group). Propensity-score overlap weighting analysis was performed to adjust for confounding factors. The primary outcome was the composite of in-hospital mortality or haemodialysis dependence at discharge. Results Of the 475 eligible patients, 248 (52.2%) were in the early ACEi group and 227 (47.8%) were in the control group. After overlap weighting, the primary outcome was significantly lower in the early ACEi group than in the control group (40.1% vs 49.0%; odds ratio, 0.69; 95% CI: 0.48, 1.00; P  = 0.049). Conclusions The present study showed that early initiation of ACEi was associated with lower composite outcome of in-hospital mortality or haemodialysis dependence at discharge in patients with SRC. Further prospective studies are warranted to verify the present findings. [ABSTRACT FROM AUTHOR]

We present the case of a 63-year-old female diagnosed with atypical SSc in the setting of acute SRC. She was undergoing work-up for progressive dyspnoea in the outpatient setting when she was found to have newly diagnosed restrictive lung pathology and worsening renal function, thus prompting acute hospital admission. Given multisystem involvement of the pulmonary and renal systems, the differential diagnosis included autoimmune and connective tissue disorders. Although serologies were non-specific, renal biopsy confirmed scleroderma renal disease, and she was started on treatment with captopril. This case highlights the importance of clinical judgment and timely diagnosis, even when laboratory data might indicate otherwise.

Abstract Background The kidney biopsy is a routine procedure. Once an indication has been established, the benefit–risk balance may be considered. Sometimes, even with effective treatment, a severe complication may develop. Case presentation We present the case of a Caucasian 20-year-old young woman admitted to investigating and treating acute kidney injury. Renal involvement was characterized by kidney damage requiring hemodialysis treatment, positive immunologic testing, 0.5 g/day proteinuria, and microscopic hematuria. Contraindications were excluded, so an ultrasound-guided kidney biopsy was performed. To reduce the bleeding complication, Octostim (desmopressin) was administered. There were no direct complications following the kidney biopsy, so we continued the immunosuppressive treatment. Histologically founded thrombotic microangiopathy. However, 1 week later, severe bleeding developed with the need for urgent surgical left kidney removal. Conclusion Kidney biopsy can be considered a routine procedure, and various bleeding episodes are most common in terms of complications, the detection of which is essential. Delayed bleeding complications are rare and can be caused by minor injuries. Our young patient had no injury during the hospitalization. We hypothesized that the developed serious and delayed bleeding complication resulted from effective immunosuppressive treatment. To the best of our knowledge, this is the first such case to date. However, renal biopsy in the case of thrombotic microangiopathy requires caution.

Background: The kidney biopsy is a routine procedure. Once an indication has been established, the benefit–risk balance may be considered. Sometimes, even with effective treatment, a severe complication may develop. Case presentation: We present the case of a Caucasian 20-year-old young woman admitted to investigating and treating acute kidney injury. Renal involvement was characterized by kidney damage requiring hemodialysis treatment, positive immunologic testing, 0.5 g/day proteinuria, and microscopic hematuria. Contraindications were excluded, so an ultrasound-guided kidney biopsy was performed. To reduce the bleeding complication, Octostim (desmopressin) was administered. There were no direct complications following the kidney biopsy, so we continued the immunosuppressive treatment. Histologically founded thrombotic microangiopathy. However, 1 week later, severe bleeding developed with the need for urgent surgical left kidney removal. Conclusion: Kidney biopsy can be considered a routine procedure, and various bleeding episodes are most common in terms of complications, the detection of which is essential. Delayed bleeding complications are rare and can be caused by minor injuries. Our young patient had no injury during the hospitalization. We hypothesized that the developed serious and delayed bleeding complication resulted from effective immunosuppressive treatment. To the best of our knowledge, this is the first such case to date. However, renal biopsy in the case of thrombotic microangiopathy requires caution. [ABSTRACT FROM AUTHOR]

Abstract Background Scleroderma renal crisis (SRC) is a critical kidney involvement of systemic sclerosis (SSc), often resulting in end-stage renal disease. Although the recurrence of SRC in the allograft has been reported, the development of de novo SRC after kidney transplantation has not been reported. Furthermore, normotensive SRC, which rarely occurs, makes prompt diagnosis more challenging. This fact should be recognized widely among nephrologists. Case presentation We report a 37-year-old Japanese man with overlapping SSc/systemic lupus erythematous syndrome who developed normotensive SRC in the transplanted kidney shortly after glucocorticoid escalation. Six years prior to admission, he underwent an ABO-compatible living donor kidney transplantation because of lupus nephritis. He was admitted to our hospital for gradually worsening kidney dysfunction. A kidney biopsy showed idiopathic granulomatous interstitial nephritis and high-dose prednisolone was prescribed. Although renal function improved tentatively, it deteriorated again a week later. A secondary kidney biopsy revealed acute thrombotic microangiopathy, leading to the diagnosis of normotensive SRC because all other causes were excluded, and blood pressure was within normal range. Adding an angiotensin-converting enzyme inhibitor and tapering glucocorticoid slowed the speed of deterioration of his kidney function, but he finally required hemodialysis induction. Conclusions SRC can newly develop even in the transplanted kidney, especially when high-dose glucocorticoid is administered. Normotensive SRC makes the diagnosis challenging, so nephrologists should carefully monitor patients with SSc and transplanted kidneys to treat SRC promptly.

Background: Scleroderma renal crisis (SRC) is a critical kidney involvement of systemic sclerosis (SSc), often resulting in end-stage renal disease. Although the recurrence of SRC in the allograft has been reported, the development of de novo SRC after kidney transplantation has not been reported. Furthermore, normotensive SRC, which rarely occurs, makes prompt diagnosis more challenging. This fact should be recognized widely among nephrologists. Case presentation: We report a 37-year-old Japanese man with overlapping SSc/systemic lupus erythematous syndrome who developed normotensive SRC in the transplanted kidney shortly after glucocorticoid escalation. Six years prior to admission, he underwent an ABO-compatible living donor kidney transplantation because of lupus nephritis. He was admitted to our hospital for gradually worsening kidney dysfunction. A kidney biopsy showed idiopathic granulomatous interstitial nephritis and high-dose prednisolone was prescribed. Although renal function improved tentatively, it deteriorated again a week later. A secondary kidney biopsy revealed acute thrombotic microangiopathy, leading to the diagnosis of normotensive SRC because all other causes were excluded, and blood pressure was within normal range. Adding an angiotensin-converting enzyme inhibitor and tapering glucocorticoid slowed the speed of deterioration of his kidney function, but he finally required hemodialysis induction. Conclusions: SRC can newly develop even in the transplanted kidney, especially when high-dose glucocorticoid is administered. Normotensive SRC makes the diagnosis challenging, so nephrologists should carefully monitor patients with SSc and transplanted kidneys to treat SRC promptly. [ABSTRACT FROM AUTHOR]

La crise rénale sclérodermique (CRS) est une urgence diagnostique et thérapeutique. Elle se manifeste le plus souvent par la survenue de novo d'une hypertension artérielle (HTA) qui peut être maligne chez un patient ayant une sclérodermie systémique (ScS) cutanée le plus souvent diffuse évoluant depuis moins de 5 ans. Cependant, la CRS peut également survenir au cours des formes cutanées limitées de ScS. La présence d'anticorps anti-ARN polymérase 3 constitue un sur-risque de CRS mais les patients avec anticorps antitopoisomérases I (ou anti-Scl70) et anticentromères ne sont pas à l'abri. Dans 10 % des cas environ, la CRS est normotensive. Les signes d'alerte sont alors une augmentation inexpliquée de la créatininémie, la survenue d'une thrombopénie, d'une hémolyse, et/ou d'une protéinurie. La prévention de la CRS repose sur 3 principes : identifier les patients à risque, reconnaître les facteurs précipitants afin de les éviter, et l'éducation thérapeutique du patient. L'exposition aux corticoïdes constitue un facteur de risque majeur (risque × 2 à 5). Il est aujourd'hui bien admis qu'il faut éviter au maximum chez les patients ScS toute prescription de corticoïdes à une dose > 15 mg/j d'équivalent de prednisone. L'intégration du patient à risque dans un programme d'éducation thérapeutique doit le sensibiliser à l'autosurveillance de la pression artérielle et aux manifestations cliniques évocatrices (céphalées...). On recommande aussi chez les patients les plus à risque une surveillance biologique régulière de la numération formule sanguine avec recherche de schizocytes, réticulocytes, haptoglobinémie et créatininémie. Les inhibiteurs de l'enzyme de conversion (IEC) doivent être prescrits en urgence une fois le diagnostic posé, quel que soit le taux de créatininémie et la dialyse sera discutée en fonction des menaces métaboliques ou volémiques. En cas de CRS avec signes de microangiopathie thrombotique mettant en jeu le pronostic vital, les échanges plasmatiques peuvent se discuter ainsi que l'utilisation précoce de l'éculizumab. Scleroderma renal crisis (SRC) is a diagnostic and therapeutic emergency. It usually consists of a novel onset of high blood pressure that may be malignant in a patient with mostly diffuse cutaneous systemic sclerosis (SSc) evolving for less than 5 years. However, SRC can occur during limited cutaneous SSc. The presence of anti-RNA polymerase 3 antibodies is a major risk factor for SRC, but patients with anti-topoisomerase I (or anti-Scl70) and anti-centromere antibodies are also at risk. In about 10 % of SRC cases, blood pressure is normal. The warning signs are an increase of creatinine, the occurrence of thrombocytopenia, hemolysis and/or proteinuria. Prevention of SRC is based on three principles: identifying patients at risk, recognizing precipitating factors in order to avoid them, and patient therapeutic education. Exposure to corticosteroids is a major risk factor (risk × 2 to 5). It is now well accepted that SSc patients should not be prescribed corticosteroids at a dose > 15 mg/day of prednisone equivalent. Participation in a therapeutic education program can raise patient awareness of self-monitoring of blood pressure and recognition of clinical warning signs (headache). Regular monitoring of blood count with schistocytes, reticulocytes, haptoglobin and creatinine is also recommended. Angiotensin-converting enzyme inhibitors should be prescribed urgently no matter the creatinine value. Dialysis will be discussed depending on metabolic threat and circulatory overload. In case of SRC with signs of life-threatening thrombotic microangiopathy, plasma exchanges may be discussed as well as the early use of eculizumab. [ABSTRACT FROM AUTHOR]

A Black woman in her 40s with past medical history significant for obesity treated with Roux-en-Y bypass surgery and a history of Raynaud’s phenomenon, presented with acute pulmonary edema secondary to severe malignant hypertension and critically accelerated acute kidney injury, with evidence of systemic microangiopathic hemolytic anemia in the setting of clinical suspicion of systemic sclerosis sine scleroderma. Renin-angiotensin system blockade (angiotensin-converting enzyme inhibitor) was immediately started at the maximum possible dose in the setting of scleroderma renal crisis. Despite better control of blood pressure and volume status, kidney function continued to rapidly decline, thus a decision was made to go ahead with a kidney biopsy on day 3 of admission, which revealed severe features of scleroderma renal crisis with active thrombotic microangiopathy. The multidisciplinary team elected to treat the patient with terminal complement blockade using eculizumab in addition to high dose lisinopril and blood pressure control. Her serum creatinine peaked at 9.3 mg/dL shortly after eculizumab initiation, but improved soon after, dropping to 2.8 mg/dL after completion of the final eculizumab dose and 1.8 mg/dL 3 years later.

Objective(s): Systemic sclerosis (SSc) is an autoimmune disease of unknown etiology with a high mortality rate. Renal crisis has been reported as one of the predictors of early mortality in these patients. The present study was performed to evaluate bleomycin-induced SSc using an osmotic minipump as a possible model for the analysis of renal damage in SSc.Materials and Methods: Male CD1 mice were implanted with osmotic minipumps loaded with saline or bleomycin and sacrificed at 6 and 14 days. Histopathological analysis was performed through hematoxylin and eosin (H&E) and Masson’s trichrome staining. The expression of endothelin 1 (ET-1), inducible nitric oxide synthase (iNOS), transforming growth factor β (TGF-β), and 8-hydroxy-2-deoxyguanosine (8-OHdG) was also evaluated by immunohistochemistry.Results: The administration of bleomycin induced a decrease in the length of Bowman’s space (3.6 μm, P

Objective(s): Systemic sclerosis (SSc) is an autoimmune disease of unknown etiology with a high mortality rate. Renal crisis has been reported as one of the predictors of early mortality in these patients. The present study was performed to evaluate bleomycin-induced SSc using an osmotic minipump as a possible model for the analysis of renal damage in SSc. Materials and Methods: Male CD1 mice were implanted with osmotic minipumps loaded with saline or bleomycin and sacrificed at 6 and 14 days. Histopathological analysis was performed through hematoxylin and eosin (H&E) and Masson's trichrome staining. The expression of endothelin 1 (ET-1), inducible nitric oxide synthase (iNOS), transforming growth factor ß (TGF-ß), and 8-hydroxy-2-deoxyguanosine (8-OHdG) was also evaluated by immunohistochemistry. Results: The administration of bleomycin induced a decrease in the length of Bowman's space (3.6 µm, P<0.001); an increase in collagen deposition (14.6%, P<0.0001); and an increase in the expression of ET-1 (7.5%, P<0.0001), iNOS (10.8%, P<0.0001), 8-OHdG (161 nuclei, P<0.0001), and TGF-ß (2.4% µm, P<0.0001) on Day 6. On Day 14, a decrease in the length of Bowman's space (2.6 µm, P<0.0001); increased collagen deposition (13.4%, P<0.0001); and increased expression of ET-1 (2.7%, P<0.001), iNOS (10.1%, P<0.0001), 8-OHdG (133 nuclei, P<0.001), and TGF-ß (0.6%, P<0.0001) were also observed. Conclusion: Systemic administration of bleomycin via an osmotic minipump produces histopathological changes in the kidneys, similar to kidney damage in SSc. Therefore, this model would allow the study of molecular alterations associated with SSc-related renal damage. [ABSTRACT FROM AUTHOR]

Objectives Scleroderma renal crisis (SRC) is a rare vascular complication of systemic sclerosis with substantial risks for end-stage renal disease and premature death. Activating autoantibodies (Abs) targeting the angiotensin II type 1 (AT1R) and the endothelin-1 type A receptor (ETAR) have been identified as predictors for SRC. Here, we sought to determine their pathogenic significance for acute renal vascular injury potentially triggering kidney failure and malignant hypertension. Methods IgG from patients with SRC was studied for AT1R and ETAR dependent biologic effects on isolated rat renal interlobar arteries and vascular cells including contraction, signalling and mechanisms of receptor activation. Results In myography experiments, patient IgG exerted vasoconstriction sensitive to inhibition of AT1R and ETAR. This relied on MEK-ERK signalling indicating functional relevance of anti-AT1R and anti-ETAR Abs. The contractile response to angiotensin II and endothelin-1 was amplified by patient IgG containing anti-AT1R and anti-ETAR Abs with substantial crosstalk between both receptors implicating autoimmune receptor hypersensitization. Co-immunoprecipitation experiments indicated heterodimerization between both receptor types which may enable the observed functional interrelation by direct structural interactions. Conclusion We provide experimental evidence that agonistic Abs may contribute to SRC. This effect is presumably related to direct receptor stimulation and additional allosteric effects, at least in heterodimeric receptor constellations. Novel therapies targeted at autoimmune hyperactivation of AT1R and ETAR might improve outcomes in severe cases of SRC. [ABSTRACT FROM AUTHOR]

Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality in scleroderma (SSc), it remains a serious complication, often necessitating level three care for patients affected. Whilst renal outcomes have significantly improved following the advent of angiotensin-converting enzyme inhibitor (ACEi) therapy, SRC remains a precarious challenge for clinicians, due to lack of preventative measures and the fact that patients can rapidly decline despite best medical management. Large cohort studies spanning decades have allowed clear identification of phenotypes particularly at risk of developing SRC thus allowing enhanced monitoring and early identification in those individuals. Novel urinary biomarkers for renal disease in SSc may offer a new window for early identification of SRC patients and response to treatment. Multiple studies have demonstrated increased activity of complement pathways in SRC with some anecdotal cases exhibiting serological response to treatment with eculizumab where ACEi and therapeutic plasma exchange (TPE) were not successful. Endothelin-1 blockade, a therapeutic strategy in other SSc vasculopathies, has shown potential as a target but clinical trials are yet to show a clear treatment benefit. Clear guidelines for the management of SRC are in place to standardise care and facilitate early collaboration between rheumatology and renal physicians. Outcomes following renal transplant have improved but the mortality of SRC remains high, indicating the need for continued exploration of the mechanisms precipitating and exacerbating SRC in order to develop novel therapies. [ABSTRACT FROM AUTHOR]

Scleroderma renal crisis is a serious complication that can develop in certain patients with systemic sclerosis. Some risks have been identified as potential triggers of scleroderma renal crisis, including the high-dose oral corticosteroids. Here, we present a patient who developed clinically severe systemic sclerosis and scleroderma renal crisis after exposure to oral corticosteroids and intravitreal vascular endothelial growth factor blockade with bevacizumab for cotton wool spots. The patient's scleroderma renal crisis was severe, progressive, and refractory to the standard of care therapy: oral captopril. Biopsy showed a diffuse thrombotic microangiopathy and findings consistent with scleroderma renal crisis. We hypothesize that depletion of systemic vascular endothelial growth factor with intravitreal anti-vascular endothelial growth factor injections likely contributed to the particularly severe presentation seen in this case. Though the finding of a monoclonal gammopathy of undetermined significance is another complicating factor, this case suggests that vascular endothelial growth factor inhibition may be a newly recognized trigger of scleroderma renal crisis.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is the diagnosis that rheumatologists most often need to consider when a patient with lupus presents with neurologic symptoms. However, neurological involvement is rare in systemic sclerosis (SSc), and high doses of steroids tend to trigger scleroderma renal crisis (SRC). When a patient with SSc overlapping SLE presents with epilepsy and renal crisis, the exact diagnosis and whether to initiate high-dose glucocorticoid therapy are questions to ponder. Here, we report a patient with overlap syndrome (SSc overlapping SLE), who developed CNS symptoms, and improved after treatment against SRC after excluding NPSLE. We report this case with the aim of arousing the attention of rheumatologists to SSc and SRC-related encephalopathy when SSc was overlapped with SLE.

Introduction/objectives: Scleroderma is a rare complication in taxanes therapy. Although individual cases of taxanes-induced scleroderma have been reported, the clinical manifestation and treatment outcomes were reviewed and summarized rarely. This study reported a patient who developed diffuse scleroderma and possible scleroderma renal crisis after paclitaxel therapy for ureter cancer. Method: A PubMed literature review on published cases of taxanes-induced scleroderma up until April 2022 was included for analysis. Results: The search identified 27 patients with adequate information for analysis. Of the 28 patients, including the one presented here, 22 were female. Peripheral edema was the most common symptom in all but one patient, and often accompanied by erythema in 11. Symptoms usually occurred in half of the patients within the 4th course of treatment. Skin lesions gradually progressed to skin fibrosis, and extended proximally. Internal organ involvements were uncommon. Antinuclear antibody tests were positive occasionally, but anti-Scl70 and anti-centromere usually were negative. Taxanes therapy was discontinued, continued and unavailable in 21, 3, and 4 patients, respectively. Corticosteroids for skin lesions with or without immunosuppressive drugs were given to 15 patients. Of 25 patients with available skin outcomes, 19 improved. There was no significant skin improvement between those who did or did not receive skin treatment (62.5% vs. 75.0%, p = 0.37). Skin usually improved after discontinuing taxanes. Conclusion: Taxanes-induced scleroderma is different from idiopathic scleroderma. Physicians should be aware of this condition in order to provide early diagnosis and apply appropriate management in order to avoid serious complications from severe skin sclerosis. Key Points • Scleroderma is a rare but unique and serious complication of taxanes therapy • Skin manifestations and distribution are similar to idiopathic scleroderma, but vascular phenomenon, internal organ involvement and scleroderma-associated auto-antibodies are presented rarely. Skin improvement usually occurs shortly after discontinuing taxanes • The role of immunosuppressive therapy in treating taxanes-induced scleroderma is not clear [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate association of autoantibodies with scleroderma renal crisis (SRC) among Japanese patients. Methods The clinical characteristics and mortality of 330 patients with sytemic screlosis (SSc) at Kyoto University Hospital were retrospectively analysed, focusing on possible association with anti-topoisomerase I (anti-topo I), anti-centromere (ACA), anti-RNA polymerase III (RNAPIII) and/or anti-U1-RNP. Logistic regression analyses were performed to reveal any association of these autoantibodies with the development and mortality of SRC. Results SRC was observed in 24 out of 330 SSc patients, including patients with anti-topo I (n  = 12/24, 50%), anti-RNAPIII (n  = 7/24, 29%), anti-U1-RNP (n  = 5/24, 21%) and ACA (n  = 3/24, 13%). Anti-U1-RNP [odds ratio (95% CI), 3.63 (1.11, 10.2)], anti-topo I [3.22 (1.37, 7.57)] and anti-RNAPIII (3.29 [1.16, 8.70]) were associated with the development of SRC. Furthermore, anti-topo I [6.00 (1.11, 41.1)] was associated with 1-year mortality of SRC. The 1-year survival rate after the onset of SRC among all patients and among those positive for anti-topo I was 54% and 33%, respectively. In contrast, the survival rate in patients negative for anti-topo I was 75%, of which the survival rate of patients positive for anti-RNAPIII and ACA was 83% and 100%, respectively. Conclusion Specific SSc-related autoantibodies were associated with the morbidity and mortality of SRC. [ABSTRACT FROM AUTHOR]

Abstract Background Systemic sclerosis (SSc) may overlap with other connective tissue diseases, which is named overlap syndrome. Scleroderma renal crisis (SRC) is a rare but severe complication of SSc. SSc related thrombotic microangiopathy (SSc-TMA) is an infrequent pathology type of SRC, while SSc-TMA accompanied by overlap syndrome is very rare. Case presentation This study reported a case of acute kidney injury (AKI) accompanied with overlap syndrome of SSc, systemic lupus erythematosus (SLE) and polymyositis (PM). The renal pathology supported the diagnosis of SSc-TMA but not SLE or PM-related renal injury, characterized by renal arteriolar thrombosis, endothelial cells edema, little cast in tubules and mild immune complex deposition. The primary TMA related factors (ADAMTS13 and complement H factor) were normal. Thus, this case was diagnosed as secondary TMA associated with SSc. The patient was treated with renin angiotensin system inhibitors, sildenafil, supportive plasma exchange/dialysis, and rituximab combined with glucocorticoids. After 2 months of peritoneal dialysis treatment, her renal function recovered and dialysis was stopped. Conclusion This study presented a case of SSc-TMA with overlap syndrome. Rituximab can be used as a treatment option in patients with high SRC risk or already manifesting SRC.

Kidney injury is a common pathology in the group of patients with systemic sclerosis. At least half of the patients show histological signs of it. Acute condition is known as scleroderma renal crisis. Although discussions regarding the risk factors for scleroderma renal crisis are open, most researchers consider the following factors: female sex, previous proteinuria and hypertension, the presence of anti-RNA polymerase III antibodies, and a decrease in lung diffusion capacity ≤75%. Diagnostic criteria for scleroderma renal crisis include an acute increase in blood pressure, accompanied by acute renal failure and abnormalities in the urinary sediment, anemia, and thrombocytopenia. Treatment of scleroderma renal crisis entails decreasing blood pressure, mainly with short-acting angiotensin-converting enzyme inhibitors, followed by selecting effective antihypertensive therapy. Further research of new treatment approaches is being carried on: the use of endothelin receptor antagonists (bosentan), monoclonal antibodies against the complement component 5 (eculizumab). Despite the approved strategies for identifying risk factors for scleroderma renal crisis development and treatment approaches, this group of patients is still characterized by high rates of mortality, the need for renal replacement therapy, and kidney transplantation. Thus, the problem of kidney injury in systemic sclerosis remains relevant.

Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis, and inflammation. Renal disease occurring in patients with SSc may have a variable clinicopathological picture. However, the most specific renal condition associated with this disease is the scleroderma renal crisis (SRC), characterized by acute onset of renal failure and severe hypertension. SRC develops in about 20% of cases of SSc, especially in those patients with diffuse cutaneous disease. The prognosis of this condition is often negative, with a rapid progression to end-stage renal disease (ESRD). The advent of the antihypertensive angiotensin-converting enzyme inhibitors in 1980 was associated with a significant improvement in patients' survival and recovery of renal function. However, the prognosis of these patients can still be improved. The dialytic condition is associated with early death, and mortality is significantly higher than among patients undergoing renal replacement therapy (RRT) due to other conditions. Patients with SRC who show no signs of renal functional recovery despite timely blood pressure control are candidates for kidney transplantation (KT). In this review, we reported the most recent advances in KT in patients with ESRD due to SSc, with a particular overview of the risk of disease recurrence after transplantation and the evolution of other disease manifestations. [ABSTRACT FROM AUTHOR]

Background: Systemic sclerosis is a chronic multisystem autoimmune disease, characterized by diffuse fibrosis and abnormalities of microcirculation and small arterioles in the skin, joints and visceral organs. Material and Methods: We searched for the relevant articles on systemic sclerosis and kidney involvement in systemic sclerosis in the NIH library of medicine, transplant, rheumatologic and nephrological journals. Results: Half of patients with systemic sclerosis have clinical evidence of kidney involvement. Scleroderma renal crisis represents the most specific and serious renal event associated with this condition. It is characterized by an abrupt onset of moderate to marked hypertension and kidney failure. Early and aggressive treatment is mandatory to prevent irreversible organ damage and death. The advent of ACE-inhibitors revolutionized the management of scleroderma renal crisis. However, the outcomes of this serious complication are still poor, and between 20 to 50% of patients progress to end stage renal disease. Conclusions: Scleroderma renal crisis still represents a serious and life-threatening event. Thus, further studies on its prevention and on new therapeutic strategies should be encouraged. [ABSTRACT FROM AUTHOR]

Objectives Vascular disease in SSc is associated with significant morbidity and mortality. Preliminary data may lead to the suggestion of a modifiable unified-vascular endophenotype. Our aim was to determine whether the prevalence, mortality and severity of SSc-vascular disease have changed over time. Methods We performed a systematic review and meta-analysis of the literature in PubMed 1950–2019 related to SSc-digital ulcers (DUs), pulmonary artery hypertension (PAH) and scleroderma renal crisis (SRC). We included full-text articles and extracted study characteristics and assessed risk of bias/quality. We examined the prevalence, mortality and surrogate measures of SSc-associated vascular disease severity. Results We included 55 studies in our meta-analysis. The pooled prevalence of DUs (41.0%), PAH (9.5%) and SRC (4.9%) remained largely stable over time. There was significant improvement in PAH 1-year (P  = 0.001) and SRC mortality (P  < 0.001), but not PAH 3-year (P  = 0.312) or 5-year (P  = 0.686) mortality. The prevalence of DU healing did not significantly change (P  = 0.265). There was a trend (all P  = ∼0.1) towards improvement in PAH surrogates: mean pulmonary artery pressure, pulmonary vascular resistance and right atrial pressure. For SRC, there was evidence that the overall frequency of dialysis (66.7%, P  = 0.297) and permanent dialysis (35.4%, P  = 0.036) increased over time. Conclusion Despite the heterogeneity and scarcity of the disease, there have been major improvements obtained in the various vascular complications in SSc leading to benefit in survival. This is supported by a trend towards improvement in several surrogate markers and demonstrates that progress in vascular management translates into major patient benefit. [ABSTRACT FROM AUTHOR]

A middle-aged woman presented with hypertensive emergency after corticosteroid treatment for Sjögren syndrome-associated multiple mononeuropathy with suspected systemic sclerosis. Hypertensive heart failure with hyperreninemia improved with antihypertensives, including aliskiren; however, she became hemodialysis-dependent. Clinical findings and biopsy-proven thrombotic microangiopathy indicated conditions resembling scleroderma renal crisis (SRC). Severe hypertension and heart failure with hyperreninemia occurred after stopping aliskiren for hypotension due to diverticular bleeding, which improved after the reintroduction of aliskiren. Aliskiren appears to be effective in managing hypertensive heart failure in patients with SRC. Nevertheless, hemodialysis remained necessary in our case, and whether or not aliskiren can restore the renal function is unclear.

We present the case of a 63-year-old female diagnosed with atypical SSc in the setting of acute SRC. She was undergoing work-up for progressive dyspnoea in the outpatient setting when she was found to have newly diagnosed restrictive lung pathology and worsening renal function, thus prompting acute hospital admission. Given multisystem involvement of the pulmonary and renal systems, the differential diagnosis included autoimmune and connective tissue disorders. Although serologies were non-specific, renal biopsy confirmed scleroderma renal disease, and she was started on treatment with captopril. This case highlights the importance of clinical judgment and timely diagnosis, even when laboratory data might indicate otherwise., Learning Points: Scleroderma renal crisis (SRC) remains an important cause of morbidity and mortality in systemic sclerosis (SSc), and clinicians should have a high index of suspicion to diagnose it.The absence of specific serologic markers makes SSc diagnosis challenging and necessitates reliance on clinical findings and additional diagnostic tools such as imaging studies and tissue sampling., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis, and inflammation. Renal disease occurring in patients with SSc may have a variable clinicopathological picture. However, the most specific renal condition associated with this disease is the scleroderma renal crisis (SRC), characterized by acute onset of renal failure and severe hypertension. SRC develops in about 20% of cases of SSc, especially in those patients with diffuse cutaneous disease. The prognosis of this condition is often negative, with a rapid progression to end-stage renal disease (ESRD). The advent of the antihypertensive angiotensin-converting enzyme inhibitors in 1980 was associated with a significant improvement in patients’ survival and recovery of renal function. However, the prognosis of these patients can still be improved. The dialytic condition is associated with early death, and mortality is significantly higher than among patients undergoing renal replacement therapy (RRT) due to other conditions. Patients with SRC who show no signs of renal functional recovery despite timely blood pressure control are candidates for kidney transplantation (KT). In this review, we reported the most recent advances in KT in patients with ESRD due to SSc, with a particular overview of the risk of disease recurrence after transplantation and the evolution of other disease manifestations.

What is known and objective: 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. Methods: 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. Results: 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). What is new and conclusions: 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). [ABSTRACT FROM AUTHOR]

Systemic sclerosis is a chronic autoimmune disorder characterized by multiorgan involvement, most notably of the skin through fibrosis and vasculopathy. One of its most feared complications requiring rapid intervention is scleroderma renal crisis, as it can be fatal in the absence of prompt treatment. A 34-year old woman presents with a history of acute renal failure and malignant hypertension occurring one month postpartum and no other scleroderma feature in the following 5 years. Eventually, skin, heart and lung involvement is observed, positive anti-ARN III polymerase antibodies and suggestive capillaroscopic findings. Immunosuppressive therapy with mycophenolate mofetil is initiated and later switched to off-label Rituximab, with significant improvement of disease manifestations. Regular patient monitoring for novel symptom occurrence and appropriate treatment adjustment is essential for optimal management of scleroderma.

Background: Systemic sclerosis (SSc) may overlap with other connective tissue diseases, which is named overlap syndrome. Scleroderma renal crisis (SRC) is a rare but severe complication of SSc. SSc related thrombotic microangiopathy (SSc-TMA) is an infrequent pathology type of SRC, while SSc-TMA accompanied by overlap syndrome is very rare.Case Presentation: This study reported a case of acute kidney injury (AKI) accompanied with overlap syndrome of SSc, systemic lupus erythematosus (SLE) and polymyositis (PM). The renal pathology supported the diagnosis of SSc-TMA but not SLE or PM-related renal injury, characterized by renal arteriolar thrombosis, endothelial cells edema, little cast in tubules and mild immune complex deposition. The primary TMA related factors (ADAMTS13 and complement H factor) were normal. Thus, this case was diagnosed as secondary TMA associated with SSc. The patient was treated with renin angiotensin system inhibitors, sildenafil, supportive plasma exchange/dialysis, and rituximab combined with glucocorticoids. After 2 months of peritoneal dialysis treatment, her renal function recovered and dialysis was stopped.Conclusion: This study presented a case of SSc-TMA with overlap syndrome. Rituximab can be used as a treatment option in patients with high SRC risk or already manifesting SRC. [ABSTRACT FROM AUTHOR]

Objectives The study aim was to evaluate the estimated glomerular filtration rate (eGFR), its association with clinical disease and its predictive ability with respect to mortality in SSc patients from the European Scleroderma Trials and Research Group (EUSTAR) database. Methods SSc patients from the EUSTAR database who had items required for the calculation of eGFR at a baseline visit and a second follow-up visit available were included. A cut-off eGFR value of 60 ml/min was chosen for all SSc patients, and 30 ml/min for those with scleroderma renal crisis (SRC). Cox regression and competing risk analysis were performed to evaluate the use of eGFR as a predictive factor of mortality. Results A total of 3650 SSc patients were included in this study. The median serum level of creatinine and the mean of eGFR were 0.8 mg/dl (interquartile range = 0.6–0.9) and 86.6 ± 23.7 ml/min, respectively. The eGFR was significantly lower in patients with pulmonary hypertension. Overall survival (OS) was significantly reduced in SSc patients with eGFR < 60 ml/min compared with patients with eGFR ≥ 60 ml/min [OS at 5 years 0.763 (95% CI: 0.700, 0.814) vs 0.903 (95% CI: 0.883, 0.919; P  < 0.001)]. In multivariable analysis, OS was associated with male gender (P  < 0.01), systolic pulmonary arterial pressure (sPAP) (P  < 0.001) and eGFR (P  < 0.001). The cumulative incidence of deaths due to SSc was associated with increased sPAP (P  < 0.001) and reduced eGFR (P  < 0.05). The OS at 5 years of 53 SRC patients was not significantly different between SSc patients with eGFR > 30 ml/min and those with eGFR <30 ml/min. Conclusion eGFR represents a predictive risk factor for overall survival in SSc. The eGFR, however, does not represent a risk factor for death in SRC. [ABSTRACT FROM AUTHOR]

Background: Systemic sclerosis is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis and autoimmune phenomena. Summary: Renal disease occurring in patients with systemic sclerosis may have a variable clinicopathological picture. The most specific renal condition associated with systemic sclerosis is scleroderma renal crisis, characterized by acute onset of renal failure and severe hypertension. Although the management of scleroderma renal crisis was revolutionized by the introduction of angiotensin-converting enzyme inhibitors, there is still a significant proportion of patients with poor outcomes. Therefore, research on establishing disease markers (clinical, ultrasonographical and serological) and clear diagnostic criteria, which could limit the risk of developing scleroderma renal crisis and facilitate diagnosis of this complication, is ongoing. Other forms of renal involvement in systemic sclerosis include vasculitis, an isolated reduced glomerular filtration rate in systemic sclerosis, antiphospholipid-associated nephropathy, high intrarenal arterial stiffness and proteinuria. Key Messages: Scleroderma renal crisis is the most specific and life-threatening renal presentation of systemic sclerosis, albeit with declining prevalence. In patients with scleroderma renal crisis, it is mandatory to control blood pressure early with increasing doses of angiotensin-converting enzyme inhibitors, along with other antihypertensive drugs if necessary. There is a strong association between renal involvement and patients’ outcomes in systemic sclerosis; consequently, it becomes mandatory to find markers that may be used to identify patients with an especially high risk of scleroderma renal crisis.

Abstract Objectives To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06–4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65–3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29–3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32–2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC—mostly in daily dosages below 15 mg of prednisolone—did not influence the hazard for SRC. Conclusions ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.

This case report details a rare presentation of diffuse scleroderma, where a 38-year-old female developed hypertensive encephalopathy due to scleroderma renal crisis (SRC). SRC, characterized by sudden severe hypertension and renal failure, poses a life-threatening emergency. The patient's clinical features, including skin changes and abnormalities on nailfold capillaroscopy, facilitated the diagnosis of diffuse scleroderma. Comprehensive diagnostic investigations revealed multisystem involvement. Management involved angiotensin-converting enzyme inhibitors, hydroxychloroquine, and packed red cell transfusions, highlighting a holistic therapeutic approach. This case underscores the importance of recognizing diverse scleroderma manifestations in hypertensive emergencies for timely intervention and improved outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Raut et al.)

To date, scleroderma renal crisis (SRC) remains a life-threatening complication in patients affected by systemic sclerosis (SSc), with high morbidity and mortality. In the last few years, some studies have tried to more precisely identify predictors of SRC and clarify the role of previous drug exposure--in particular, angiotensin-converting enzyme (ACE) inhibitors and corticosteroids--in patients with SSc presenting other well-known risk factors for SRC. Different from the findings of previous reports, more recent findings suggest that the presence of chronic kidney disease, systemic arterial hypertension, and proteinuria might all be predictors of SRC. Moreover, because about 40 to 50% of SRC cases can present signs of microangiopathy, a recent study has proposed SSc thrombotic microangiopathy (SSc-TMA) as a clinically and pathophysiologically different entity from narrowly defined SRC. Even though such clear distinction may not always be applicable/feasible in clinical practice, it highlights that complement pathway dysregulation may play a key pathogenetic role in SRC presenting as TMA. Thus, plasma exchange may be considered in severe refractory cases. Nevertheless, ACE inhibitors and prompt achievement of blood pressure control (to rapidly improve ongoing renal ischemia) remain to date the cornerstone of SRC treatment. Here, we report the cases of three SSc patients with SRC followed at our rheumatology units. While describing these patients' risk factors, clinical presentation, and therapy, we aim to discuss the state of the art in SRC and highlight critical issues. [ABSTRACT FROM AUTHOR]

Background: Systemic sclerosis is a chronic multisystem autoimmune disease, characterized by diffuse fibrosis and abnormalities of microcirculation and small arterioles in the skin, joints and visceral organs. Material and Methods: We searched for the relevant articles on systemic sclerosis and kidney involvement in systemic sclerosis in the NIH library of medicine, transplant, rheumatologic and nephrological journals. Results: Half of patients with systemic sclerosis have clinical evidence of kidney involvement. Scleroderma renal crisis represents the most specific and serious renal event associated with this condition. It is characterized by an abrupt onset of moderate to marked hypertension and kidney failure. Early and aggressive treatment is mandatory to prevent irreversible organ damage and death. The advent of ACE-inhibitors revolutionized the management of scleroderma renal crisis. However, the outcomes of this serious complication are still poor, and between 20 to 50% of patients progress to end stage renal disease. Conclusions: Scleroderma renal crisis still represents a serious and life-threatening event. Thus, further studies on its prevention and on new therapeutic strategies should be encouraged.

Systemic sclerosis is a chronic autoimmune disorder characterized by multiorgan involvement, most notably of the skin through fibrosis and vasculopathy. One of its most feared complications requiring rapid intervention is scleroderma renal crisis, as it can be fatal in the absence of prompt treatment. A 34-year old woman presents with a history of acute renal failure and malignant hypertension occurring one month postpartum and no other scleroderma feature in the following 5 years. Eventually, skin, heart and lung involvement is observed, positive anti-ARN III polymerase antibodies and suggestive capillaroscopic findings. Immunosuppressive therapy with mycophenolate mofetil is initiated and later switched to off-label Rituximab, with significant improvement of disease manifestations. Regular patient monitoring for novel symptom occurrence and appropriate treatment adjustment is essential for optimal management of scleroderma. [ABSTRACT FROM AUTHOR]

Pantipa Tonsawan,1 Komkid Talabthong,1 Anucha Puapairoj,2 Chingching Foocharoen11Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 2Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandCorrespondence: Chingching FoocharoenDepartment of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002 ThailandTel +66 4 336 3746Email fching@kku.ac.thBackground: The information guiding the treatment decision(s) for renal diseases in systemic sclerosis (SSc) is the renal pathological finding. This study aimed to evaluate the renal pathological diagnosis and its clinical feature among SSc.Method: A historical cohort study was performed on adult Thai SSc patients who underwent renal biopsy during January 2005–December 2016. The renal pathologic findings and patient clinical characteristics were reviewed. Chi-square or Fisher’s exact test was applied to analyze the association between clinical manifestation and renal pathology.Results: Of the 26 SSc patients identified (77% female), 46% had the diffuse cutaneous SSc subtype. The mean age at the time of biopsy was 53.2±14.4 years and median duration of disease was 2.4 years (IQR 0.5–7.0). Rapidly progressive glomerulonephritis (RPGN) was the most common renal manifestation (53.9%) followed by nephrotic syndrome (19.2%) and nephritis (11.5%). The pathological diagnosis included lupus nephritis (LN) class IV (26.9%), LN class V (19.2%), scleroderma renal crisis (SRC; 19.3%), progressive renal disease in scleroderma (7.7%), and IgA nephropathy (7.7%). The nephrotic syndrome was the most common renal feature among LN class V patients, whereas RPGN was the commonest renal presentation among LN class IV and SRC patients (p=0.001). Dialysis treatment at the time of kidney biopsy was significantly higher in SRC patients than in the other groups (p

Abstract Background Scleroderma Renal Crisis (SRC) is associated with significant morbidity and mortality. While prednisone is strongly associated with SRC, there are no previous large cohort studies that have evaluated ace inhibitor (ACEi) calcium channel blocker (CCB), angiotensin receptor blocker (ARB), endothelin receptor blocker (ERB), non-steroidal anti-inflammatory drug (NSAID), fluticasone, or mycophenolate mofetil (MMF) use in systemic sclerosis (SSc) and the risk of SRC. Methods In this retrospective cohort study of the entire military electronic medical record between 2005 and 2016, we compared the use of ACEi, ARB, CCB, NSAID, ERB, fluticasone, and MMF after SSc diagnosis for 31 cases who subsequently developed SRC to 322 SSc without SRC disease controls. Results ACEi was associated with an increased risk for SRC adjusted for age, race, and prednisone use [odds ratio (OR) 4.1, 95% confidence interval (CI) 1.6–10.2, P = 0.003]. On stratified analyses, ACEi was only associated with SRC in the presence [OR 5.3, 95% CI 1.1–29.2, p = 0.03], and not the absence of proteinuria. In addition, a doubling of ACEi dose [61% vs. 12%, p

Connective tissue diseases (CTDs) are a heterogeneous group of disorders that have certain clinical presentations and a disturbed immunoregulation, leading to autoantibody production. Subclinical or overt renal manifestations are frequently observed and complicate the clinical course of CTDs. Lesion of kidney function are typical for such CTDs as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Sjogren syndrome, autoimmune myopathies (dermatomyositis and polymyositis). At the present stage, considering the availability of many diagnostic manipulations and the possibility of etiopathogenetic treatment, therapists, rheumatologists and nephrologists must suspect in advance the presence of kidney disease in patients with CTD and assume measures for diagnosis and treatment. In systemic lupus erythematosus, renal prognosis is significantly improved based on specific classification and treatment strategies adjusted to kidney biopsy findings. One of the most severe kidney lesions is scleroderma renal crisis, which is usually characterized by severe hypertension, progressive decline of renal function and thrombotic microangiopathy. Early administration of angiotensin-converting enzyme inhibitors in these patients shows a significant benefit in particular and strict blood pressure control in general. Treatment of the underlying autoimmune disorder or discontinuation of specific therapeutic agents improves kidney function in most patients with Sjogren syndrome, autoimmune myopathies, and rheumatoid arthritis. On the other hand, chronic use of immunosuppressive agents and non-steroidal anti-inflammatory drugs, as well as comorbidities, such as diabetes, hypertension, and cardiovascular complications, are the main causes of renal involvement in patients with rheumatic diseases. Apart from this, long-standing primary kidney disease can lead to manifestations simulating primary rheumatologic disorders. In this review, we focus on impairment of renal function in relation to underlying disease or adverse drug effects and implications on treatment decisions.

Scleroderma renal crisis (SRC) is a major complication in patients with systemic sclerosis. SRC occurs in about 5–25 % of all patients with scleroderma. It is characterized by malignant hypertension and olig-/anuric acute renal failure. Around 10 % of SRC cases may present with normal blood pressure, termed normotensive renal crisis. The etiopathogenesis is presumed to be a series of insults to the kidneys resulting in endothelial injury, intimal proliferation, and narrowing of renal arterioles leading to decreased blood flow, hyperplasia of the juxtaglomerular apparatus, hyperreninemia, and accelerated hypertension. SRC is often triggered by nephrotoxic drugs and/or intravascular volume depletion. SRC occurs particularly in the first years of disease and in its diffuse form. The occurrence of SRC is more common in patients treated with glucocorticoids, the risk increases with increasing dose. Left ventricular insufficiency and hypertensive encephalopathy are typical clinical features. Thrombotic microangiopathy is detected in 43 % of the cases. Anti-RNA-polymerase III antibodies are present in one third of patients who develop SRC. Renal biopsy is not necessary if SRC presents with classical features. However, it can help to establish prognosis and approaches to the treatment in atypical forms. The prognosis of SRC has dramatically improved with the introduction of angiotensin-converting enzyme inhibitors. However, 5-year survival in patients with systemic sclerosis who develop the full picture of SRC remains low (65 %). The treatment of SRC is based on aggressive control of blood pressure with angiotensin-converting enzyme inhibitors, if needed, in combination with other types of antihypertensive drugs. Dialysis is frequently indicated, but can be stopped in approximately half of patients, mainly in those with good control of blood pressure. Patients who need dialysis for more than 2 years qualify for renal transplantation. SRC still remains an important cause of morbidity and mortality in scleroderma. Prompt diagnosis and treatment may help prevent adverse outcomes and improve survival.

Introduction Endothelin antagonist receptors (ERAs) and phosphodiesterase-5 inhibitors (PDE5i) are beneficial in pulmonary arterial hypertension (PAH) and digital ulcers (DU) and prevent from DU recurrences. Our study aimed to determine the difference in the incidence rate of PAH and scleroderma renal crisis (SRC) in patients with SSc and DU (SSc-DU) under ERAs/PDE5i or without treatment. Methods We conducted a retrospective cohort study including SSc-DU patients from the Spanish Scleroderma Registry (RESCLE). The primary outcome was the incidence rate of PAH and SRC in patients under ERAs/PDE5i or not. Results Some 544 patients out of 1817 (29.9%) in the RESCLE database had DU, 221 (40.6%) under ERAs/PDE5i and 323 (59.4%) not. The incidence rate (95% CI) difference between patients under treatment or not under did not reach statistical significance in PAH [−0.1 (−4.8, 4.69), P  = 0.988] or in SRC [0.7 (−2.2, 3.7), P  = 0.620]. However, the time from the first DU to the diagnosis of SRC was delayed in treated patients [mean (s. d.) 7.6 (5.8) years vs 2.9  (5.3); P  = 0.021]. The dcSSc subset was more prevalent in the treatment group (36 vs 26%; P  = 0.018), along with anti-topoisomerase I antibodies (34 vs 18%; P  < 0.001) and tendon friction rubs (12 vs 6%; P  = 0.038), whereas the lcSSc subset was more prevalent in the no-treatment group (57 vs 66%; P  = 0.031) along with ACA (37 vs 46%; P  = 0.031). Conclusion There was no difference in the incidence rate of PAH and SRC between groups. However, treatment with ERAs and/or PDE5i appeared to delay the occurrence of SRC. [ABSTRACT FROM AUTHOR]

Background: Scleroderma renal crisis (SRC) is a rare but feared complication with high morbidity and mortality. Its aetiopathogenesis is unclear. Aim: To investigate epidemiological, serologic and clinical features of all patients with SRC listed on the population‐based South Australian Scleroderma Register and to examine possible factors in aetiopathogenesis. Method: A case note review was performed on all SRC patients with relevant data extracted to determine incidence, clinical phenotype, presence of autoantibodies and survival. Possible precipitating and aetiopathogenic factors were also examined. Data from the South Australian Scleroderma Register and Australia Bureau of Statistics was sourced for comparative purposes. Results: Over the 34‐year period (1985–2018), 30 patients (21 females, 9 males) presented with SRC giving a South Australian mean annual incidence of 0.58/million/year (95% CI 0.39–0.89). Twenty‐eight of these patients had diffuse cutaneous scleroderma and two with limited cutaneous scleroderma. The mean age at first symptom of scleroderma was 51.2 ± 15.9 (mean ± SD) years with SRC occurring 4.6 years later (median = 3.0 years, range 0.1–20 years). Possible precipitating factors for SRC included high dose steroids in five patients. Twelve patients were anti‐ RNA polymerase3 (RNAPol3) positive and two were anti‐topoisomerase 1 (Topo1) positive. Renal outcome was poor with 13 patients requiring renal replacement therapy and two proceeding to renal transplantation. The mean age at death was 61.2 ± 11.6 years with SRC patient survival being significantly shorter than patients with diffuse scleroderma without renal involvement (P = 0.002). There was no significant difference in survival between the 1985–2002 and the 2003–2018 SRC cohorts (P = 0.2). Nailfold capillaroscopy performed in 10 patients revealed extensive microvascular damage with prominent capillary drop out. Conclusion: SRC is a rare occurrence with an incidence of 0.58/million/year in South Australia. This frequency has not changed over time. It continues to have a severe adverse outcome with frequent requirement for renal replacement therapy and poor survival. Nailfold capillaroscopy revealed evidence of extensive capillary damage. No improvement in survival was observed over the 34‐year study period. [ABSTRACT FROM AUTHOR]