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Pediatric Rheumatology Online Journal Aug 2022Rapidly progressive (RP) interstitial lung disease (ILD) is a life-threatening complication of juvenile dermatomyositis (JDM); however, it is generally refractory to... (Review)
Review
Successful rituximab treatment for severe rapidly progressive interstitial lung disease with anti-MDA5 antibody-positive juvenile dermatomyositis: a case report and literature review.
BACKGROUND
Rapidly progressive (RP) interstitial lung disease (ILD) is a life-threatening complication of juvenile dermatomyositis (JDM); however, it is generally refractory to treatment; to the best of our knowledge, no evidence-based treatment has been established for RP-ILD yet. We present the case of a 2-year-old girl with RP-ILD who showed resistance to treatment with methylprednisolone, cyclosporine A, cyclophosphamide, immunoglobulin, and plasma exchange (PE) and was finally treated with extracorporeal membrane oxygenation. We further present a literature review of 18 cases of JDM with RP-ILD.
CASE PRESENTATION
A 2-year-old girl presented with malar rash, mild muscle weakness, and weight loss for a few months before admission. She had a history of dry cough and dyspnea for a few days, followed by rapid respiratory failure. The patient was diagnosed with JDM with RP-ILD through physical examination (malar rashes and Gottron's sign) and based on the finding of myositis on femoral magnetic resonance imaging, elevated levels of serum muscle enzymes, positive anti-melanoma differentiation-association gene 5 (MDA5) antibody (> 7,500 index), elevated level of Krebs von den Lungen-6 glycoprotein (KL-6; 3,420 U/mL), and extensive ground-glass opacities with consolidation in the bilateral lungs on chest high-resolution computed tomography. She received combination therapy, including methylprednisolone pulse therapy, followed by oral prednisolone and intravenous cyclosporine A, cyclophosphamide, and immunoglobulin. On day 11 of hospitalization, she was placed on ventilation support and PE was initiated. However, her respiratory condition continued to deteriorate and veno-venous extracorporeal membrane oxygenation was started on day 24 of hospitalization. Rituximab was administered on day 28. After 2 weeks of rituximab therapy initiation, her respiratory condition showed gradual improvements. Eventually, on day 52 of hospitalization, the patient could be weaned off extracorporeal membrane oxygenation. Finally, she was discharged with minimal ventilation support and no neurological complications 11 months after admission.
CONCLUSIONS
Our literature review suggest that JDM with RP-ILD has a high mortality rate. In JDM, rituximab may be a promising treatment option for RP-ILD. In the future, the efficacy of rituximab in the early phases of ILD should be investigated.
Topics: Autoantibodies; Child, Preschool; Cyclophosphamide; Cyclosporine; Dermatomyositis; Disease Progression; Female; Humans; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Methylprednisolone; Rituximab
PubMed: 35927666
DOI: 10.1186/s12969-022-00723-5 -
Journal of Clinical Medicine Apr 2024Lupus erythematosus (LE) is an autoimmune inflammatory disease with complex etiology. LE may present as a systemic disorder affecting multiple organs or be limited... (Review)
Review
Lupus erythematosus (LE) is an autoimmune inflammatory disease with complex etiology. LE may present as a systemic disorder affecting multiple organs or be limited solely to the skin. Cutaneous LE (CLE) manifests with a wide range of skin lesions divided into acute, subacute and chronic subtypes. Despite classic forms of CLE, such as malar rash or discoid LE, little-known variants may occur, for instance hypertrophic LE, chilblain LE and lupus panniculitis. There are also numerous non-specific manifestations including vascular abnormalities, alopecia, pigmentation and nail abnormalities or rheumatoid nodules. Particular cutaneous manifestations correlate with disease activity and thus have great diagnostic value. However, diversity of the clinical picture and resemblance to certain entities delay making an accurate diagnosis The aim of this review is to discuss the variety of cutaneous manifestations and indicate the clinical features of particular CLE types which facilitate differential diagnosis with other dermatoses. Although in diagnostically difficult cases histopathological examination plays a key role in the differential diagnosis of LE, quick and accurate diagnosis ensures adequate therapy implementation and high quality of life for patients. Cooperation between physicians of various specialties is therefore crucial in the management of patients with uncommon and photosensitive skin lesions.
PubMed: 38673692
DOI: 10.3390/jcm13082419 -
Clinical and Experimental Rheumatology Jan 2023Several studies show that age at onset has an impact on the clinical-serological presentation, comorbidities and disease course of patients with systemic lupus...
OBJECTIVES
Several studies show that age at onset has an impact on the clinical-serological presentation, comorbidities and disease course of patients with systemic lupus erythematosus (SLE). We evaluated whether, in patients with recent onset SLE, the age at onset correlates with clinical-serological manifestations and with comorbidities.
METHODS
We analysed 171 patients with a SLE diagnosis obtained within 12 months of diagnosis enrolled in the Early Lupus project. Based on the age of onset of the first disease symptom, they were stratified into 2 groups: early onset (18-45 years) and late onset (>45 years). The analysis was replicated by stratifying patients based on age at diagnosis (fulfillment of ACR classification criteria). Each comparison was made at baseline and at 36 months of follow-up.
RESULTS
Baseline: patients with late onset displayed comorbidities (hypertension, dyslipidemia and osteoporosis) more frequently than early onset group. 11.4% of late onset patients had a malignancy in medical history, not recorded in the early onset cohort. The two groups differed neither in organ involvement (domain BILAG) nor in disease activity (ECLAM). Patients with early onset showed a disease with signs of higher serologic activity (higher frequency of anti-dsDNA positivity and lower mean C3 and C4 levels) and had malar rash more frequently than the late onset group (36.2% vs. 18.2%, p=0.042). Similar results were obtained by stratifying patients by age of diagnosis (18-45 years and >45 years), except for the higher frequency of discoid rash in the group with age at diagnosis >45 years (18% vs. 6.6%, p=0.045). 36 months: the 2 groups of patients independently of the stratification applied did not differ in the accumulation of damage, but showed a different pattern of 8 organ involvement. Musculoskeletal involvement was more frequent both in the late onset group (18.6% vs. 7.3%, p=0.043) and in the group with age at diagnosis >45 years (20.4% vs. 5.9%, p=0.009) compared to their counterparts, while renal involvement was more frequent in the group with age at diagnosis 18-45 years (21.4% vs. 6.1%, p=0.03).A sub analysis at 36 months on patients without hypertension and osteoporosis at enrollment showed that patients with older age at onset had a higher frequency of these comorbidities, compared to their counterparts.
CONCLUSIONS
In our cohort, younger disease SLE onset seems to correlate with a more active immunological profile, while late onset with a higher incidence of comorbidities.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Age of Onset; Lupus Erythematosus, Systemic; Hypertension; Osteoporosis
PubMed: 35894063
DOI: 10.55563/clinexprheumatol/oo5ymg -
BMJ Case Reports May 2017
Topics: Cheek; Child; Facial Dermatoses; Female; Homocystinuria; Humans; Intellectual Disability; Vision Disorders
PubMed: 28473367
DOI: 10.1136/bcr-2017-220296 -
Medicine Jul 2016Systemic lupus erythematosus (SLE) is a chronic autoimmune multiorgan disorder of unknown etiology. It affects both men and women, but with different disease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Systemic lupus erythematosus (SLE) is a chronic autoimmune multiorgan disorder of unknown etiology. It affects both men and women, but with different disease manifestations of differing disease severity and in varying proportion, with a female predominance of approximately 90%. There have been numerous studies addressing this issue, especially its implications in relation to optimal sex-tailored treatment and improvement of survival rate; however, further research is warranted. A meta-analysis of studies was performed to compare the impact of sex on the clinical outcomes of SLE in different populations.
METHODS
A literature search of the MEDLINE/PubMed and EMBASE databases (until January 2016) was conducted to identify relevant articles. Clinical manifestations reported in these patients were considered as endpoints for this meta-analysis. Two independent reviewers determined eligibility criteria. A fixed-effect model has been used where a small heterogeneity was observed, or else, a random-effect model has been used among the studies. Odd ratio (OR) with 95% confidence interval (CI) was used to express the pooled effect on dichotomous variables, and the pooled analyses were performed with RevMan 5.3.
RESULTS
Sixteen studies consisting of a total of 11,934 SLE patients (10,331 females and 1603 males) have been included in this meta-analysis. The average female-to-male ratio of all the included studies is around 9.3:1. Several statistically significant differences were found: alopecia, photosensitivity, and oral ulcers were significantly higher in female patients (OR 0.36, 95% CI 0.29-0.46, P < 0.00001; OR 0.72, 95% CI 0.63-0.83, P < 0.00001; and OR 0.70, 95% CI 0.60-0.82, P < 0.00001, respectively). Malar rash was significantly higher in female patients (OR 0.68, 95% CI 0.53-0.88, P = 0.003), and arthritis was significantly lower in male patients (OR 0.72, 95% CI 1.25-1.84, P < 0.00001). However, serositis and pleurisies were significantly higher in female patients (OR 1.52, 95% CI 1.25-1.84 P < 0.0001; and OR 1.26, 95% CI 1.07-1.48, P = 0.006, respectively). Renal involvement was higher in male patients (OR 1.51, 95% CI 1.31-1.75, P < 0.00001).
CONCLUSION
The results of this meta-analysis suggest that alopecia, photosensitivity, oral ulcers, arthritis, malar rash, lupus anticoagulant level, and low level of C3 were significantly higher in female lupus patients, whereas renal involvement, serositis and pleurisies, thrombocytopenia, and anti-double stranded deoxyribonucleic acid level were predominant in male patients.
Topics: Female; Humans; Lupus Erythematosus, Systemic; Male; Precision Medicine; Sex Characteristics; Treatment Outcome
PubMed: 27442661
DOI: 10.1097/MD.0000000000004272 -
Acta Medica Portuguesa 1998We report the case of a sixteen year old female patient, admitted to a general hospital due to fever, poliarthritis, malar rash and vasculitis. Diagnostic studies...
We report the case of a sixteen year old female patient, admitted to a general hospital due to fever, poliarthritis, malar rash and vasculitis. Diagnostic studies confirmed the existence of Systemic Lupus Erythematosus. Shortly after admission, the patient was transferred to an intensive care unit due to severe acute pancreatitis. In spite of its infrequency, the diagnosis of acute pancreatitis must always be considered whenever a patient with SLE presents abdominal pain. The authors emphasise the importance of an early diagnosis of this rare complication, with high mortality rates, and present a brief review of the international literature.
Topics: Acute Disease; Adolescent; Female; Humans; Intensive Care Units; Lupus Erythematosus, Systemic; Pancreatitis
PubMed: 9951072
DOI: No ID Found -
Hematology. American Society of... Dec 2016A 35-year-old man presents with an acute unprovoked deep vein thrombosis of the left lower extremity. He is treated with anticoagulation and elects to discontinue... (Review)
Review
A 35-year-old man presents with an acute unprovoked deep vein thrombosis of the left lower extremity. He is treated with anticoagulation and elects to discontinue treatment after 6 months. He subsequently develops polyarthralgias, fatigue, and a malar rash, and a diagnosis of systemic lupus erythematosus is made based on laboratory and clinical findings. Additional laboratory testing reveals persistent triple positive antiphospholipid antibodies, including lupus anticoagulant, high titer anticardiolipin antibodies, and anti-β-glycoprotein I antibodies. The patient is reinitiated on anticoagulation, and the patient's rheumatologist inquires if the addition of hydroxychloroquine could help to prevent recurrent thrombosis.
Topics: Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Humans; Hydroxychloroquine; Male; Venous Thrombosis
PubMed: 27913551
DOI: 10.1182/asheducation-2016.1.714 -
American Journal of Human Genetics Aug 2018Bloom syndrome, caused by biallelic mutations in BLM, is characterized by prenatal-onset growth deficiency, short stature, an erythematous photosensitive malar rash, and...
Bloom syndrome, caused by biallelic mutations in BLM, is characterized by prenatal-onset growth deficiency, short stature, an erythematous photosensitive malar rash, and increased cancer predisposition. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges (SCEs) on cytogenetic testing. Here, we describe biallelic mutations in TOP3A in ten individuals with prenatal-onset growth restriction and microcephaly. TOP3A encodes topoisomerase III alpha (TopIIIα), which binds to BLM as part of the BTRR complex, and promotes dissolution of double Holliday junctions arising during homologous recombination. We also identify a homozygous truncating variant in RMI1, which encodes another component of the BTRR complex, in two individuals with microcephalic dwarfism. The TOP3A mutations substantially reduce cellular levels of TopIIIα, and consequently subjects' cells demonstrate elevated rates of SCE. Unresolved DNA recombination and/or replication intermediates persist into mitosis, leading to chromosome segregation defects and genome instability that most likely explain the growth restriction seen in these subjects and in Bloom syndrome. Clinical features of mitochondrial dysfunction are evident in several individuals with biallelic TOP3A mutations, consistent with the recently reported additional function of TopIIIα in mitochondrial DNA decatenation. In summary, our findings establish TOP3A mutations as an additional cause of prenatal-onset short stature with increased cytogenetic SCEs and implicate the decatenation activity of the BTRR complex in their pathogenesis.
PubMed: 30057030
DOI: 10.1016/j.ajhg.2018.07.001 -
Biology of Sex Differences Dec 2019Systemic lupus erythematosus (SLE) predominantly affects women, but previous studies suggest that men with SLE present a more severe disease phenotype. In this study, we...
OBJECTIVE
Systemic lupus erythematosus (SLE) predominantly affects women, but previous studies suggest that men with SLE present a more severe disease phenotype. In this study, we investigated a large and well-characterized patient group with the aim of identifying sex differences in disease manifestations, with a special focus on renal involvement.
METHODS
We studied a Swedish multi-center SLE cohort including 1226 patients (1060 women and 166 men) with a mean follow-up time of 15.8 ± 13.4 years. Demographic data, disease manifestations including ACR criteria, serology and renal histopathology were investigated. Renal outcome and mortality were analyzed in subcohorts.
RESULTS
Female SLE patients presented more often with malar rash (p < 0.0001), photosensitivity (p < 0.0001), oral ulcers (p = 0.01), and arthritis (p = 0.007). Male patients on the other hand presented more often with serositis (p = 0.0003), renal disorder (p < 0.0001), and immunologic disorder (p = 0.04) by the ACR definitions. With regard to renal involvement, women were diagnosed with nephritis at an earlier age (p = 0.006), while men with SLE had an overall higher risk for progression into end-stage renal disease (ESRD) with a hazard ratio (HR) of 5.1 (95% CI, 2.1-12.5). The mortality rate among men with SLE and nephritis compared with women was HR 1.7 (95% CI, 0.8-3.8).
CONCLUSION
SLE shows significant sex-specific features, whereby men are affected by a more severe disease with regard to both renal and extra-renal manifestations. Additionally, men are at a higher risk of developing ESRD which may require an increased awareness and monitoring in clinical practice.
Topics: Adult; Disease Progression; Female; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Male; Middle Aged; Pericarditis; Pleurisy; Serositis; Severity of Illness Index; Sex Characteristics; Sweden; Young Adult
PubMed: 31843005
DOI: 10.1186/s13293-019-0274-2 -
European Journal of Rheumatology Jan 2022Systemic lupus erythematosus (SLE) is a complex heterogenous autoimmune disease that can affect multiple organs. We performed clinical clustering analysis to describe a...
OBJECTIVE
Systemic lupus erythematosus (SLE) is a complex heterogenous autoimmune disease that can affect multiple organs. We performed clinical clustering analysis to describe a lupus cohort from the University of Pittsburgh Medical Center.
METHODS
A total of 724 patients who met the American College of Rheumatology (ACR) classification criteria for SLE were included in this study. Clustering was performed using the ACR classification criteria and the partitioning around medoid method. Correlation analysis was performed using the Spearman's Rho test.
RESULTS
Patients with SLE in our cohort identify three district clinical disease subsets. Patients in cluster 1 were significantly more likely to develop renal and hematologic involvement, and had overrepresentation in African-American and male lupus patients. Clusters 2 and 3 identified a milder disease, with a significantly less likelihood of organ complications. Patients in cluster 2 are characterized by malar rash and photosensitivity, while patients in cluster 3 are characterized by oral ulcers, which is present in ~90% of patients within this cluster. The presence of photosensitivity or oral ulcers appears to be protective against the development of lupus nephritis in our cohort.
CONCLUSION
We describe a large cohort of SLE from Western Pennsylvania and identify three distinct clinical disease subgroups. Clustering analysis might help to better manage and predict disease complications in heterogenous diseases like lupus.
PubMed: 34554910
DOI: 10.5152/eurjrheum.2020.21225