-
Clinical Rheumatology Dec 2022Scleroderma is a rare complication in taxanes therapy. Although individual cases of taxanes-induced scleroderma have been reported, the clinical manifestation and... (Review)
Review
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 4 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.
Topics: Humans; Female; Male; Paclitaxel; Scleroderma, Diffuse; Taxoids; Scleroderma, Localized; Scleroderma, Systemic; Acute Kidney Injury; Erythema
PubMed: 36085204
DOI: 10.1007/s10067-022-06364-z -
Indian Journal of Dermatology,... 2010Scleroderma is a set of rare connective tissue diseases of unknown etiology. It is characterized by thickening and hardening of the skin. Scleroderma is divided into two... (Review)
Review
Scleroderma is a set of rare connective tissue diseases of unknown etiology. It is characterized by thickening and hardening of the skin. Scleroderma is divided into two main subgroups: systemic and localized. The systemic form, also known as systemic sclerosis, involves diffuse skin involvement associated with fibrotic changes in internal organs. Juvenile localized scleroderma is a more common entity and is usually confined to a specific region of the body with no internal organ involvement. Therapeutics are divided into three main subgroups for juvenile systemic sclerosis: antifibrotics, anti-inflammatories, and vasodilators. For localized disease, anti-inflammatories, vitamin D analogues, and UV irradiation have been investigated. The rarity of scleroderma in children and the self-limiting nature of the disease together make randomized controlled trials very difficult. Therefore, most data on therapeutic modalities for this condition have to be extrapolated from studies conducted on adults. International cooperation, following a standardized operation protocol, is needed to validate these and future interventions such as autologous stem cell transplant and cytokine-directed therapies.
Topics: Child; Dermatology; Humans; Pediatrics; Scleroderma, Limited; Scleroderma, Systemic
PubMed: 20657114
DOI: 10.4103/0378-6323.66578 -
Nature Reviews. Rheumatology May 2022Diffuse cutaneous systemic sclerosis (dcSSc) is associated with high mortality resulting from early internal-organ involvement. Clinicians therefore tend to focus on... (Review)
Review
Diffuse cutaneous systemic sclerosis (dcSSc) is associated with high mortality resulting from early internal-organ involvement. Clinicians therefore tend to focus on early diagnosis and treatment of potentially life-threatening cardiorespiratory and renal disease. However, the rapidly progressive painful, itchy skin tightening that characterizes dcSSc is the symptom that has the greatest effect on patients' quality of life, and there is currently no effective disease-modifying treatment for it. Considerable advances have been made in predicting the extent and rate of skin-disease progression (which vary between patients), including the development of techniques such as molecular analysis of skin biopsy samples. Risk stratification for progressive skin disease is especially relevant now that haematopoietic stem-cell transplantation is a treatment option, because stratification will inform the balance of risk versus benefit for each patient. Measurement of skin disease is a major challenge. Results from clinical trials have highlighted limitations of the modified Rodnan skin score (the current gold standard). Alternative patient-reported and other potential outcome measures have been and are being developed. Patients with early dcSSc should be referred to specialist centres to ensure best-practice management, including the management of their skin disease, and to maximize opportunities for inclusion in clinical trials.
Topics: Disease Progression; Humans; Quality of Life; Scleroderma, Diffuse; Skin; Skin Diseases
PubMed: 35292731
DOI: 10.1038/s41584-022-00765-9 -
Rheumatology (Oxford, England) Nov 2022Cardiac complications of SSc are a leading cause of SSc-associated death. Cardiac imaging for identifying substrate abnormality may be useful in predicting risk of...
OBJECTIVES
Cardiac complications of SSc are a leading cause of SSc-associated death. Cardiac imaging for identifying substrate abnormality may be useful in predicting risk of cardiac arrhythmias or future cardiac failure. The aim of this study was to quantify the burden of asymptomatic fibro-inflammatory myocardial disease using cardiac magnetic resonance imaging (CMR) and assess the relationship between asymptomatic myocardial fibrosis and cardiac arrhythmias in SSc.
METHODS
Thirty-two patients with SSc with no documented history of pulmonary vascular or heart disease underwent CMR with gadolinium and 24-h ambulatory ECG. Focal myocardial fibrosis was assessed using post-gadolinium imaging and diffuse fibro-inflammatory myocardial disease quantified using T1- and T2-mapping. CMR results were compared with an age- and sex-matched control group.
RESULTS
Post-gadolinium focal fibrosis was prevalent in SSc but not controls (30% vs 0%, p < 0.01).. T1-mapping values (as a marker of diffuse fibrosis) were greater in SSc than controls [saturated recovery single-shot acquisition (SASHA): 1584 ms vs 1515 ms, P < 0.001; shortened Modified look locker sequence (ShMOLLI): 1218 ms vs 1138 ms, p < 0.001]. More than one-fifth (22.6%) of the participants had ventricular arrhythmias on ambulatory ECG, but no associations between focal or diffuse myocardial fibrosis and arrhythmias were evident.
CONCLUSION
In SSc patients without evidence of overt cardiac disease, a high burden of myocardial fibrosis and arrhythmias was identified. However, there was no clear association between focal or diffuse myocardial fibrosis and arrhythmias, suggesting CMR may have limited use as a screening tool to identify SSc patients at risk of future significant arrhythmias.
Topics: Humans; Gadolinium; Cardiomyopathies; Fibrosis; Scleroderma, Systemic; Myocardium; Myocarditis; Arrhythmias, Cardiac; Magnetic Resonance Imaging; Magnetic Resonance Imaging, Cine
PubMed: 35136975
DOI: 10.1093/rheumatology/keac065 -
Rheumatic Diseases Clinics of North... Nov 1996Raynaud's phenomenon is a common clinical problem occurring in 3% to 5% of the general population. The first symptom of scleroderma is often Raynaud's phenomenon, which... (Review)
Review
Raynaud's phenomenon is a common clinical problem occurring in 3% to 5% of the general population. The first symptom of scleroderma is often Raynaud's phenomenon, which is associated with a diffuse small vessel vasculopathy and ischemia and reperfusion injury to skin and other organs targeted in this disease. Current studies support the concept that Raynaud's phenomenon is secondary to a local defect in the regulation of regional blood flow. New evidence demonstrates that there is a profound sensitivity to alpha 2-adrenoceptors mediated vasoconstriction in scleroderma vessels. Traditional treatment of Raynaud's phenomenon is cold avoidance and the use of vasodilators. Oral prostaglandins have shown promise as therapeutic agents.
Topics: Clinical Trials as Topic; Humans; Microcirculation; Prostaglandins; Raynaud Disease; Scleroderma, Systemic
PubMed: 8923595
DOI: 10.1016/s0889-857x(05)70300-8 -
Arthritis Research & Therapy 2007The precise aetiology of systemic sclerosis (SSc) remains elusive, but significant advances over the past few years have improved our understanding of the underlying... (Review)
Review
The precise aetiology of systemic sclerosis (SSc) remains elusive, but significant advances over the past few years have improved our understanding of the underlying pathogenic processes and identified key pathways and mediators that are potential therapeutic targets. The situation is complicated by the clinical heterogeneity of SSc and the differential pathogenesis that underlies the two commonest subsets, namely diffuse and limited cutaneous disease. However, there are common mediators that could be targeted to provide clinical benefit in both types of disease. To date, clinical success with therapies directed against logical profibrotic mediators, such as connective tissue growth factor and transforming growth factor-beta, is yet to be reported, although studies are ongoing. More promising clinical results have been obtained with the dual endothelin receptor antagonist bosentan, which has been shown to manage two vascular complications of SSc effectively: pulmonary arterial hypertension and digital ulceration. It remains to be determined whether the identification of additional mediators merely furthers our knowledge of the natural history of SSc or presents targets that can be manipulated to manage SSc patients effectively.
Topics: Animals; Drug Delivery Systems; Humans; Scleroderma, Systemic
PubMed: 17767744
DOI: 10.1186/ar2190 -
Postgraduate Medical Journal Feb 1988Difficulty in the diagnosis of the disease scleroderma may occur at the early stage prior to the development of obvious skin sclerosis. A presumptive diagnosis may be... (Review)
Review
Difficulty in the diagnosis of the disease scleroderma may occur at the early stage prior to the development of obvious skin sclerosis. A presumptive diagnosis may be made if Raynaud's phenomenon is accompanied by a positive 'neck test', 'scleroderma' capillary changes in the nailfolds or antinuclear antibodies. Definitive diagnosis may have to be delayed for several years from the onset of Raynaud's phenomenon until definite characteristic skin changes are seen. Ten cases in which an earlier diagnosis of scleroderma was not substantiated are listed. The earlier incorrect diagnosis would have been avoided by use of the methods described in this paper. Various terms have been used to denote subdivisions of scleroderma. These include acrosclerosis, diffuse scleroderma and CREST. We have used the terms Type 1, Type 2 and Type 3 based on the early extent of the skin sclerosis where Type 1 (limited extent) indicates sclerodactyly only, Type 2 (moderate extent) indicates sclerosis proximal to the metacarpophalangeal joints but excluding the trunk and Type 3 (extensive) indicates diffuse skin sclerosis including the trunk. The clinical value of this simple classification is reviewed and contrasted to other classifications which appear to be poorly defined and of limited use.
Topics: Adult; Female; Humans; Male; Scleroderma, Systemic
PubMed: 3050937
DOI: 10.1136/pgmj.64.748.121 -
Journal of Cardiology Aug 2023Systemic sclerosis (SSc) is divided into diffuse and limited cutaneous SSc (dcSSc and lcSSc). The dcSSc subtype has more severe internal organ damage. This study aimed...
BACKGROUND
Systemic sclerosis (SSc) is divided into diffuse and limited cutaneous SSc (dcSSc and lcSSc). The dcSSc subtype has more severe internal organ damage. This study aimed to assess whether cardiovascular magnetic resonance (CMR) parametric mapping could detect early cardiac involvement and evaluate differences between these two subtypes.
METHODS
Eighty SSc patients (37 dcSSc and 43 lcSSc) underwent CMR at 3.0 T (Philips Healthcare, Best, The Netherlands) in our hospital between July 2018 and July 2021. We analyzed myocardial damage by CMR parametric mapping and compared it with clinical data.
RESULTS
The median duration of the disease was 10.2 months. The left ventricular ejection fraction was preserved in both groups. DcSSc had significantly higher native T1 (1333.4 ± 71.2 ms vs. 1295.0 ± 42.7 ms, p = 0.006) and extracellular volume fraction (32.6 ± 4.1 % vs. 30.3 ± 4.0 %, p = 0.018) in the mid-ventricular septum as compared to lcSSc, although there were no differences in T2 values. Native T1 values were positively correlated with the E/e' ratio and left atrial volume indices evaluated by transthoracic echocardiography in overall SSc and dcSSc, but not in lcSSc. Logistic regression analysis revealed that native T1 was an independent predictor of left ventricular diastolic dysfunction in SSc patients (odds ratio, 1.194; 95 % confidence interval, 1.021-1.396; p = 0.026). Native T1 was higher in SSc patients with progressive skin lesions. Additionally, there were positive correlations between brain natriuretic peptide, New York Heart Association functional classification, and native T1.
CONCLUSIONS
CMR parametric mapping is a useful tool for detecting myocardial changes. Native T1 was the most sensitive parameter for identifying diffuse myocardial changes in the early stages of SSc and was associated with left ventricular diastolic function. DcSSc had more severe myocardial involvement than lcSSc; therefore, the use of CMR parametric mapping may aid in its prediction.
Topics: Humans; Stroke Volume; Ventricular Function, Left; Scleroderma, Systemic; Myocardium; Heart
PubMed: 36921691
DOI: 10.1016/j.jjcc.2023.03.003 -
Medicine Jul 2013Experience suggests that African Americans may express autoimmune disease differently than other racial groups. In the context of systemic sclerosis (scleroderma), we... (Review)
Review
Experience suggests that African Americans may express autoimmune disease differently than other racial groups. In the context of systemic sclerosis (scleroderma), we sought to determine whether race was related to a more adverse expression of disease. Between January 1, 1990, and December 31, 2009, a total of 409 African American and 1808 white patients with scleroderma were evaluated at a single university medical center. While the distribution by sex was virtually identical in both groups, at 82% female, African American patients presented to the center at a younger mean age than white patients (47 vs. 53 yr; p < 0.001). Two-thirds of white patients manifested the limited cutaneous subset of disease, whereas the majority of African American patients manifested the diffuse cutaneous subset (p < 0.001). The proportion seropositive for anticentromere antibody was nearly 3-fold greater among white patients, at 34%, compared to African American patients (12%; p < 0.001). Nearly a third of African American (31%) patients had autoantibodies to topoisomerase, compared to 19% of white patients (p = 0.001). Notably, African American patients experienced an increase in prevalence of cardiac (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-2.2), renal (OR, 1.6; 95% CI, 1.2-2.1), digital ischemia (OR, 1.5; 95% CI, 1.4-2.2), muscle (OR, 1.7; 95% CI, 1.3-2.3), and restrictive lung (OR, 6.9; 95% CI, 5.1-9.4) disease. Overall, 700 (32%) patients died (159 African American; 541 white). The cumulative incidence of mortality at 10 years was 43% among African American patients compared to 35% among white patients (log-rank p = 0.0011). Compared to white patients, African American patients experienced an 80% increase in risk of mortality (relative risk [RR], 1.8; 95% CI, 1.4-2.2), after adjustment for age at disease onset and disease duration. Further adjustment by sex, disease subtype, and scleroderma-specific autoantibody status, and for the socioeconomic measures of educational attainment and health insurance status, diminished these risk estimates (RR, 1.3; 95% CI, 1.0-1.6). The heightened risk of mortality persisted in strata defined by age at disease onset, diffuse cutaneous disease, anticentromere seropositivity, decade of care at the center, and among women. These findings support the notion that race is related to a distinct phenotypic profile in scleroderma, and a more unfavorable prognosis among African Americans, warranting heightened diagnostic evaluation and vigilant care of these patients. Further, we provide a chronologic review of the literature regarding race, organ system involvement, and mortality in scleroderma; we furnish synopses of relevant reports, and summarize findings.
Topics: Black or African American; Female; Humans; Lung; Male; Middle Aged; Multivariate Analysis; Risk Assessment; Scleroderma, Diffuse; Scleroderma, Localized; Scleroderma, Systemic; Social Class; Survival Analysis; United States
PubMed: 23793108
DOI: 10.1097/MD.0b013e31829be125 -
Rheumatic Diseases Clinics of North... Nov 1996Renal crisis occurs in systemic sclerosis patients with rapidly progressive diffuse cutaneous thickening early in their disease. SRC is characterized by malignant... (Review)
Review
Renal crisis occurs in systemic sclerosis patients with rapidly progressive diffuse cutaneous thickening early in their disease. SRC is characterized by malignant hypertension, hyperreninemia, azotemia, microangiopathic hemolytic anemia, and renal failure. This complication, which in the past has been almost uniformly fatal, is now successfully treated in most cases with ACE inhibitors. This therapy has improved survival, reduced requirement for dialysis, and in those on dialysis has often allowed discontinuation of this procedure 6 to 18 months later. Prompt diagnosis and early, aggressive initiation of therapy with ACE inhibitors will result in the most optimal outcome. Chronic nonrenal crisis renal insufficiency is unusual and rarely progresses to significant renal dysfunction.
Topics: Humans; Kidney Diseases; Scleroderma, Systemic
PubMed: 8923600
DOI: 10.1016/s0889-857x(05)70305-7