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de Oliveira Rocha AM, Ribeiro GF, Silva JC. Immunobiologics in juvenile dermatomyositis: a systematic review of promising therapeutic advances. Reumatologia 2024; 62:447-455. [PMID: 39866309 PMCID: PMC11758102 DOI: 10.5114/reum/195799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 11/10/2024] [Indexed: 01/28/2025] Open
Abstract
Introduction To identify the most effective treatment for juvenile dermatomyositis (JDM), considering efficacy, safety, impact on patients and improvement in their quality of life. Material and methods A systematic review was carried out comparing known treatments and immunobiological therapies, evaluating clinical improvement, adverse events and prognosis. The MEDLINE, PubMed, LILACS and Cochrane Library databases were used with children aged 0 to 18 diagnosed with JDM. The PRISMA 2020 statement was followed throughout the process. Results The immunobiologics studied were rituximab (RTX) and anti-tumor necrosis factor drugs and used the Disease Activity Score to skin, Childhood Myositis Assessment Scale and Manual Muscle Testing tools. There was no difference in the response when RTX was used (early or late). The anti-TNF studies were carried out in a population that was refractory to the initial treatment and showed a significant improvement in muscle and skin disease activity. Conclusions For severe or refractory disease, biologics tend to be the medication with the best therapeutic response.
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Mehta P, Lawrence A, Gupta L, Misra DP, Agarwal V, Misra R, Aggarwal A. Long-standing and poorly controlled disease in juvenile dermatomyositis is associated with calcinosis: a real-world experience from a low-middle income country. Rheumatol Int 2024; 44:3035-3040. [PMID: 37405442 DOI: 10.1007/s00296-023-05377-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 06/16/2023] [Indexed: 07/06/2023]
Abstract
To study the prevalence and predictors of calcinosis in Juvenile Dermatomyositis (JDM). Medical records over 20 years at a tertiary care rheumatology center in Northern India were reviewed to identify patients with JDM and clinical details were recorded. The frequency of calcinosis, predictors, specific treatment, and its outcomes were studied. Data are expressed as median and interquartile range. In eighty-six patients (median age 10) of JDM, the frequency of calcinosis was 18.2% (8.5% at presentation). Younger age at presentation, longer follow-up, heliotrope rash [Odds Ratio (95% confidence interval), 11.4 (1.4-92.12)], chronic or polycyclic course [4.4 (1.2-15.5)] and cyclophosphamide use [8.2 (1.6-41.9)] were associated with calcinosis. Dysphagia [0.14 (0.02-1.2)] and elevated muscle enzymes [0.14 (0.04-0.5)] were negatively associated with calcinosis. Treatment with pamidronate had a good to moderate response to calcinosis in five of seven children. Calcinosis in JDM is associated with long-standing, poorly controlled disease, and the use of bisphosphonates like pamidronate offer promise in the future for its treatment.
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Affiliation(s)
- Pankti Mehta
- Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
- Department of Clinical Immunology & Rheumatology, King George Medical University, Lucknow, India
| | - Able Lawrence
- Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Latika Gupta
- Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
- Department of Rheumatology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, WV10 0QP, UK
- Division of Musculoskeletal and Dermatological Sciences, Centre for Musculoskeletal Research, School of Biological Sciences, The University of Manchester, Manchester, UK
- Department of Rheumatology, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
| | - Durga P Misra
- Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Vikas Agarwal
- Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Ramnath Misra
- Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
- Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, Bhubhaneshwar, India
| | - Amita Aggarwal
- Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
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3
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Yi BY, Marrs J, Acharya P, Sura A, Cidon M. Risk factors for developing calcinosis in juvenile dermatomyositis: subcutaneous and myofascial edema in initial magnetic resonance imaging. Rheumatol Int 2024; 44:2577-2582. [PMID: 37432516 DOI: 10.1007/s00296-023-05385-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 06/28/2023] [Indexed: 07/12/2023]
Abstract
Calcinosis is a sequela of Juvenile Dermatomyositis (JDM) with significant morbidity. A retrospective study observing risk factors for JDM calcinosis, including a possible association between higher intensity of subcutaneous and myofascial edema in initial magnetic resonance imaging (MRI) and development of calcinosis was performed at a tertiary pediatric medical center. Data from the past 20 years on JDM patients with MRIs at the time of JDM diagnosis were obtained. MRIs were individually evaluated by two pediatric musculoskeletal radiologists who blindly graded the intensity of edema on a 0-4 Likert scale. Clinical data and edema scores were compared between patients who developed calcinosis and who did not. Forty-three patients (14 with calcinosis and 29 without calcinosis) were identified. The calcinosis group contained more racial and ethnic minorities, younger ages of JDM onset and longer time to reach JDM diagnosis. Muscle enzyme levels at JDM diagnosis were lower in the calcinosis group, especially Creatinine Kinase (CK) (p = 0.047) and Alanine Aminotransferase (ALT) (p = 0.015). The median score for edema in both groups was 3 (p = 0.39) with an inter-rater reliability of 95%. There was no association between increased subcutaneous and myofascial edema in MRIs at the time of JDM diagnosis and development of calcinosis. Earlier age of JDM onset, racial and ethnic minority, and delay in JDM diagnosis could be risks for developing calcinosis. The calcinosis group presented with lower muscle enzyme levels at the time of JDM diagnosis, especially CK and ALT with statistical significance. This could reflect delay in diagnosis and treatment.
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Affiliation(s)
- Belina Y Yi
- Division of Rheumatology, Children's Hospital Los Angeles, Los Angeles, CA, USA.
| | - Joshua Marrs
- Department of Pediatrics, Los Angeles General Medical Center, Los Angeles, CA, USA
| | - Patricia Acharya
- Department of Radiology, Keck School of Medicine, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA, USA
| | - Amit Sura
- Department of Radiology, Keck School of Medicine, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA, USA
| | - Michal Cidon
- Division of Rheumatology, Keck School of Medicine, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA, USA
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4
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Lau CB, Smith GP. Treatment of calcinosis cutis associated with autoimmune connective tissue diseases. Arch Dermatol Res 2024; 316:390. [PMID: 38878086 DOI: 10.1007/s00403-024-03148-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 11/02/2023] [Accepted: 05/18/2024] [Indexed: 09/11/2024]
Abstract
Calcinosis cutis is a condition that is commonly associated with autoimmune connective tissue diseases. It is characterized by the deposition of insoluble calcium salts in the skin and subcutaneous tissue, which can cause pain, impair function, and have significant impacts on quality of life. Calcinosis cutis is difficult to manage because there is no generally accepted treatment: evidence supporting treatments is mostly comprised of case reports and case series, sometimes yielding mixed findings. Both pharmacologic and procedural interventions have been proposed to improve calcinosis cutis, and each may be suited to different clinical scenarios. This review summarizes current treatment options for calcinosis cutis, with discussion of recommendations based on patient-specific factors and disease severity.
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Affiliation(s)
- Charles B Lau
- Department of Dermatology, Massachusetts General Hospital, 50 Staniford Street, Suite 200, Boston, MA, 02114, USA.
- Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
| | - Gideon P Smith
- Department of Dermatology, Massachusetts General Hospital, 50 Staniford Street, Suite 200, Boston, MA, 02114, USA
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Achieng S, Harris J, Samaranayaka M, Herrick AL. A rare form of calcinosis in patients with systemic sclerosis-myositis overlap: report of four cases. Rheumatol Adv Pract 2024; 8:rkae011. [PMID: 38420189 PMCID: PMC10901148 DOI: 10.1093/rap/rkae011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 01/04/2024] [Indexed: 03/02/2024] Open
Abstract
Objectives Calcinosis is a well-described entity that occurs in patients with systemic sclerosis (SSc) and dermatomyositis (DM). Calcinosis in SSc typically occurs over pressure points and is usually nodular. We present a case series of four patients with SSc with a much rarer, diffuse form of calcinosis to illustrate this poorly recognized pattern of extensive and debilitating disease. Methods Four patients with SSc and extensive calcinosis were identified from patients attending a tertiary rheumatology centre in the preceding 3 years. Their electronic case notes, radiographic images and medical photographs were reviewed. Results All four patients had the diffuse cutaneous subtype of SSc (dcSSc) and additionally a myositis overlap. This was in the context of 102 of 461 (22%) patients with SSc whose clinical details had been recorded in the preceding 3 years having dcSSc. Their ages at diagnosis ranged from 27 to 65 years. Three were female, two were anti-Scl70 antibody positive, and two were anti-PMScl antibody positive. Development of calcinosis occurred between 1 and 6 years after onset of SSc. Plain radiography showed very extensive calcinosis in various sites, distributed in a pattern akin to sheets of calcium-containing deposits in the skin and subcutaneous tissue. Conclusions Although calcinosis is common in SSc, extensive sheet-like calcinosis is very rare. Our experience suggests that when this form of calcinosis does occur, this is in the context of the diffuse cutaneous subtype of disease and with myositis overlap. The four cases described should raise awareness of this unusual and extensive pattern of disease.
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Affiliation(s)
- Sheilla Achieng
- School of Biological Sciences, Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
- Department of Rheumatology, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Manchester, UK
| | - Jonathan Harris
- Department of Radiology, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Manchester, UK
| | - Muditha Samaranayaka
- Department of Rheumatology, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Manchester, UK
| | - Ariane L Herrick
- School of Biological Sciences, Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
- Department of Rheumatology, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Manchester, UK
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Shiari R, Khalili M, Zeinali V, Shashaani N, Samami M, Moghaddamemami FH. Local injection of infliximab into calcinosis lesions in patients with juvenile dermatomyositis (JDM): a clinical trial. Pediatr Rheumatol Online J 2024; 22:2. [PMID: 38166943 PMCID: PMC10759742 DOI: 10.1186/s12969-023-00941-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 12/08/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND Juvenile Dermatomyositis (JDM) is a rare autoimmune disorder that primarily affects muscles and skin. One of the severe complications associated with JDM is calcinosis, and treating this condition presents significant challenges. This study aimed to evaluate the efficacy and safety of local injection of infliximab into calcinosis lesions in patients with JDM. METHODS In this clinical trial, five patients diagnosed with JDM and calcinosis lesions were enrolled. The primary treatment consisted of weekly infliximab injections for 16 weeks, targeting all four sides of each lesion. Lesion dimensions, including length and width, were documented and monitored weekly. Before the intervention, patients underwent radiographic imaging. After the final injection in week 16, a follow-up radiographic assessment was performed. Data were analyzed using the Generalized Estimating Equation (GEE) method. RESULTS The lesions' size significantly decreased in both length and width during each visit. On average, the lesion length reduced by 2.66%, and the width shrank by 3.32% per visit. Based on radiographic findings, the average length and width of lesions at the initial visit were 12.09 ± 5.05 mm (range: 6.00-25.50 mm) and 6.35 ± 3.00 mm (range: 2.00-16.00 mm), respectively. The average length and width at the last visit were 5.59 ± 7.05 mm (range: 0-23.00 mm) and 3.41 ± 4.05 mm (range: 0-13.00 mm), respectively. No specific side effects related to the treatment were reported. CONCLUSIONS The results suggest that the direct administration of infliximab into the calcinosis lesions of patients with JDM could be a safe and effective treatment approach. TRIAL REGISTRATION Name of the registry: The effect of infliximab injection into calcinosis lesions on patients with juvenile dermatomyositis (JDM), Trial registration number: IRCT20210808052107N1, Registration date: 2022-07-22, URL of trial registry record: https://en.irct.ir/trial/58329 .
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Affiliation(s)
- Reza Shiari
- Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mitra Khalili
- Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Vahide Zeinali
- Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Niloufar Shashaani
- Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Samami
- Dental Sciences Research Center, Department of Oral and Maxillofacial Medicine, School of Dentistry, Guilan University of Medical Sciences, Rasht, Iran
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Sherman MA, Pak K, Pinal-Fernandez I, Flegel WA, Targoff IN, Miller FW, Rider LG, Mammen AL. Autoantibodies Recognizing Specificity Protein 4 Co-occur With Anti-Transcription Intermediary Factor 1 and Are Associated With Distinct Clinical Features and Immunogenetic Risk Factors in Juvenile Myositis. Arthritis Rheumatol 2023; 75:1668-1677. [PMID: 36996276 PMCID: PMC10524257 DOI: 10.1002/art.42512] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 03/17/2023] [Accepted: 03/28/2023] [Indexed: 04/01/2023]
Abstract
OBJECTIVE Autoantibodies recognizing specificity protein 4 (Sp4) were recently discovered in adults with idiopathic inflammatory myopathies (IIM). Anti-Sp4 autoantibodies co-occurred in patients with anti-transcription intermediary factor 1 (anti-TIF1) autoantibody-positive dermatomyositis (DM) and were associated with a reduced risk of cancer. In the present study, the prevalence and clinical features associated with anti-Sp4 autoantibodies in juvenile-onset IIM were investigated. METHODS Serum samples from 336 patients with juvenile myositis in a cross-sectional cohort and 91 healthy controls were screened for anti-Sp4 autoantibodies using enzyme-linked immunosorbent assay. Clinical characteristics, outcomes, and HLA alleles of those with and those without anti-Sp4 autoantibodies were compared. RESULTS Anti-Sp4 autoantibodies were present in 23 patients (7%) with juvenile myositis and were not present in any of the controls. Anti-Sp4 autoantibodies were found among each clinical myositis subgroup. The frequency of TIF1 autoantibody positivity was significantly higher among those with anti-Sp4 autoantibodies (21 [91%] versus 92 [30%], P < 0.001). In the anti-TIF1 autoantibody-positive subgroup, Raynaud's phenomenon (8 [38%] versus 2 [2%], P < 0.001) was more common and peak aspartate aminotransferase was significantly lower in those with anti-Sp4 autoantibodies. None of the patients with anti-Sp4 autoantibodies required a wheelchair. Among White patients, DQA1*04 and DRB1*08 were associated with anti-Sp4 autoantibodies. CONCLUSION Anti-Sp4 autoantibodies were found in patients with juvenile-onset IIM, predominantly those with coexisting anti-TIF1 autoantibodies. Patients with anti-Sp4 autoantibodies represent a phenotypic subset of anti-TIF1 autoantibody-positive myositis characterized by frequent Raynaud's phenomenon and less pronounced muscle involvement, similar to adults with these autoantibodies. Novel immunogenetic risk factors for White patients with IIM were identified among juveniles with anti-Sp4 autoantibodies.
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Affiliation(s)
- Matthew A. Sherman
- Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Katherine Pak
- Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Iago Pinal-Fernandez
- Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Willy A. Flegel
- Department of Transfusion Medicine, National Institutes of Health Clinical Center, National Institutes of Health (NIH), Bethesda, MD, USA
| | - Ira N. Targoff
- Veteran’s Affairs Medical Center, University of Oklahoma Health Sciences Center, and Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
| | - Frederick W. Miller
- Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland, USA
| | - Lisa G. Rider
- Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland, USA
| | - Andrew L. Mammen
- Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Papadopoulou C, Chew C, Wilkinson MGL, McCann L, Wedderburn LR. Juvenile idiopathic inflammatory myositis: an update on pathophysiology and clinical care. Nat Rev Rheumatol 2023; 19:343-362. [PMID: 37188756 PMCID: PMC10184643 DOI: 10.1038/s41584-023-00967-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2023] [Indexed: 05/17/2023]
Abstract
The childhood-onset or juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogenous group of rare and serious autoimmune diseases of children and young people that predominantly affect the muscles and skin but can also involve other organs, including the lungs, gut, joints, heart and central nervous system. Different myositis-specific autoantibodies have been identified that are associated with different muscle biopsy features, as well as with different clinical characteristics, prognoses and treatment responses. Thus, myositis-specific autoantibodies can be used to subset JIIMs into sub-phenotypes; some of these sub-phenotypes parallel disease seen in adults, whereas others are distinct from adult-onset idiopathic inflammatory myopathies. Although treatments and management have much improved over the past decade, evidence is still lacking for many of the current treatments and few validated prognostic biomarkers are available with which to predict response to treatment, comorbidities (such as calcinosis) or outcome. Emerging data on the pathogenesis of the JIIMs are leading to proposals for new trials and tools for monitoring disease.
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Affiliation(s)
- Charalampia Papadopoulou
- Department of Paediatric Rheumatology, Great Ormond Street Hospital for Children NHS Foundation Trust (GOSH), London, UK
- Rare Diseases Theme NIHR Biomedical Research Centre at GOSH, London, UK
| | - Christine Chew
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - Meredyth G Ll Wilkinson
- Rare Diseases Theme NIHR Biomedical Research Centre at GOSH, London, UK
- Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH, London, UK
- Infection Immunity and Inflammation Research and Teaching Department, UCL GOS Institute of Child Health, London, UK
| | - Liza McCann
- Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK
| | - Lucy R Wedderburn
- Department of Paediatric Rheumatology, Great Ormond Street Hospital for Children NHS Foundation Trust (GOSH), London, UK.
- Rare Diseases Theme NIHR Biomedical Research Centre at GOSH, London, UK.
- Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH, London, UK.
- Infection Immunity and Inflammation Research and Teaching Department, UCL GOS Institute of Child Health, London, UK.
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Mormile I, Mosella F, Turco P, Napolitano F, de Paulis A, Rossi FW. Calcinosis Cutis and Calciphylaxis in Autoimmune Connective Tissue Diseases. Vaccines (Basel) 2023; 11:vaccines11050898. [PMID: 37243003 DOI: 10.3390/vaccines11050898] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/21/2023] [Accepted: 04/23/2023] [Indexed: 05/28/2023] Open
Abstract
Calcinosis represents a severe complication of several autoimmune disorders. Soft-tissue calcifications have been classified into five major types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Autoimmune diseases are usually associated with dystrophic calcifications, including calcinosis cutis, occurring in damaged or devitalized tissues in the presence of normal serum levels of calcium and phosphate. In particular, calcinosis cutis has been described in dermatomyositis, polymyositis, juvenile dermatomyositis, systemic sclerosis, systemic lupus erythematosus, primary Sjögren's syndrome, overlap syndrome, mixed connective tissue disease, and rheumatoid arthritis. Calciphylaxis, a severe and life-threatening syndrome presenting with vascular calcifications and thrombosis, has also been associated with some autoimmune conditions. Due to the potentially disabling character of calcinosis cutis and calciphylaxis, physicians' awareness about the clinical presentation and management of these diseases should be increased to select the most appropriate treatment option and avoid long-term complications. In this review, we aim to analyze the clinical features of calcinosis cutis and calciphylaxis associated with autoimmune diseases, and the main treatment strategies evaluated up to now for treating this potentially disabling disease.
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Affiliation(s)
- Ilaria Mormile
- Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Francesca Mosella
- Department of Plastic and Reconstructive Surgery, University of Naples Federico II, 80131 Naples, Italy
| | - Piergiorgio Turco
- Department of Plastic and Reconstructive Surgery, University of Naples Federico II, 80131 Naples, Italy
| | - Filomena Napolitano
- Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy
| | - Amato de Paulis
- Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy
- WAO Center of Excellence, 80131 Naples, Italy
| | - Francesca Wanda Rossi
- Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy
- WAO Center of Excellence, 80131 Naples, Italy
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Lin TW, Hu YC, Chiang BL. Characterization of the biomarkers related to the clinical course and outcomes of juvenile dermatomyositis. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:416-423. [PMID: 36572597 DOI: 10.1016/j.jmii.2022.12.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 12/05/2022] [Accepted: 12/10/2022] [Indexed: 12/23/2022]
Abstract
OBJECTIVE This study aimed to evaluate the clinical characteristics of children diagnosed with juvenile dermatomyositis (JDM) in a tertiary medical centre in Taiwan and to identify important biomarkers for predicting the disease course and outcomes of JDM. METHODS We retrospectively reviewed patients with JDM diagnosed at the National Taiwan University Hospital between 1 January 2001 and 31 December 2021. The endpoints for disease assessment included complete clinical response or remission. The JDM courses were divided into monocyclic, polycyclic, and chronic continuous statuses. The significant relationship between the predictors and outcomes was further analysed. RESULTS A total of 47 patients were included in this study. The mean age at disease onset was 7.5 years. The female-to-male ratio was 1.35. The most common initial presentations were Gottron's sign (74%), followed by muscle weakness (66%) and facial rash (66%). Among all included patients, 35 (74.5%) patients achieved complete clinical remission, 15 (31.9%) had a monocyclic course, six (12.7%) had a polycyclic course, and 24 (51.1%) had a chronic continuous course. Negative facial rash and arthralgia were favourable factors for achieving complete clinical remission. Muscle weakness, higher lactate dehydrogenase (LDH), and higher erythrocyte sedimentation rate (ESR) at disease onset were related to the chronic continuous course. The most common long-term complication was calcinosis (29.8%). CONCLUSION Juvenile dermatomyositis is a rare disease, and only a few studies have been conducted in Asia. Our results identified the important predictors of the disease course and outcomes. The chronic continuous course requires more attention and aggressive treatment.
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Affiliation(s)
- Ting-Wei Lin
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Ya-Chiao Hu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Bor-Luen Chiang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
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11
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Fernández T, Ganau S. Dermatomyositis-associated Calcinosis Cutis on Digital Breast Tomosynthesis. Radiology 2023; 307:e222173. [PMID: 36809216 DOI: 10.1148/radiol.222173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2023]
Abstract
Supplemental material is available for this article.
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Affiliation(s)
- Tomás Fernández
- From the Department of Radiology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain
| | - Sergi Ganau
- From the Department of Radiology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain
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12
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Agud-Dios M, Arroyo-Andres J, Rubio-Muñiz C, Zarco-Olivo C, Calleja-Algarra A, de Inocencio J, Perez SIP. Juvenile dermatomyositis-associated calcinosis successfully treated with combined immunosuppressive, bisphosphonate, oral baricitinib and physical therapy. Dermatol Ther 2022; 35:e15960. [PMID: 36286617 PMCID: PMC10078250 DOI: 10.1111/dth.15960] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 10/08/2022] [Accepted: 10/23/2022] [Indexed: 11/28/2022]
Affiliation(s)
- Manuel Agud-Dios
- Department of Dermatology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Jorge Arroyo-Andres
- Department of Dermatology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Carmen Rubio-Muñiz
- Department of Dermatology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Carlos Zarco-Olivo
- Department of Dermatology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | - Jaime de Inocencio
- Department of Pediatric Rheumatology, Hospital Universitario 12 de Octubre, Madrid, Spain
- Department of Public Health & Maternal and Child Health, Complutense University of Madrid, Madrid, Spain
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13
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Janarthanan M, Mohan M, Murali A. Bisphosphonate therapy for juvenile dermatomyositis-associated calcinosis and metaphyseal zebra lines. BMJ Case Rep 2022; 15:e252814. [PMID: 36343985 PMCID: PMC9644302 DOI: 10.1136/bcr-2022-252814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/28/2022] [Indexed: 11/09/2022] Open
Affiliation(s)
- Mahesh Janarthanan
- Rheumatology, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India
| | - Meenakshi Mohan
- Pediatrics, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India
| | - Arunan Murali
- Radiology, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India
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14
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Karasawa R, Yudoh K, Sato T, Tanaka M, Tamaki M, Sabbagh SE, O’Hanlon TP, Noroozi-Farhadi P, Targoff IN, Flegel WA, Mammen AL, Miller FW, Hicar MD, Rider LG, Jarvis JN. Association of anti-HSC70 autoantibodies with cutaneous ulceration and severe disease in juvenile dermatomyositis. Rheumatology (Oxford) 2022; 61:2969-2977. [PMID: 34791087 PMCID: PMC9258543 DOI: 10.1093/rheumatology/keab846] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 11/06/2021] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVES JDM is an inflammatory myopathy characterized by prominent vasculopathy. AECAs are frequently detected in inflammatory and autoimmune diseases. We sought to determine whether AECAs correlate with clinical features of JDM, and thus serve as biomarkers to guide therapy or predict outcome. METHODS Plasma samples from 63 patients with JDM, 49 patients with polyarticular JIA and 40 juvenile healthy controls were used to detect anti-heat shock cognate 71 kDa protein (HSC70) autoantibodies, a newly identified AECA, in ELISA assays. Clinical features were compared between JDM patients with and without anti-HSC70 autoantibodies. RESULTS Anti-HSC70 autoantibodies were detected in 35% of patients with JDM, in 0% of patients with JIA (P < 0.0001) and in 0% of healthy donors (P < 0.0001). Both the presence of cutaneous ulcers (59% vs 17%, P < 0.002) and the use of wheelchairs and/or assistive devices (64% vs 27%, P < 0.007) were strongly associated with anti-HSC70 autoantibodies in JDM. High scores on the severity of myositis damage measures at the time of measurement of anti-HSC70 autoantibodies and an increased number of hospitalizations were also associated with anti-HSC70 autoantibodies. Intravenous immunoglobulin therapy was used more often in anti-HSC70 autoantibody-positive patients. CONCLUSION Anti-HCS70 autoantibodies are detected frequently in children with JDM and are novel myositis-associated autoantibodies correlating with disease severity.
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Affiliation(s)
- Rie Karasawa
- Department of Frontier Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Kazuo Yudoh
- Department of Frontier Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Toshiko Sato
- Department of Frontier Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Megumi Tanaka
- Department of Frontier Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Mayumi Tamaki
- Department of Frontier Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Sara E Sabbagh
- Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, MD
- Division of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI
| | - Terrance P O’Hanlon
- Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Bethesda, MD
| | - Payam Noroozi-Farhadi
- Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Bethesda, MD
| | - Ira N Targoff
- Oklahoma City VA Health Care System, University of Oklahoma Health Sciences Center, and Oklahoma Medical Research Foundation, Oklahoma City, OK
| | - Willy A Flegel
- Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health (NIH), Bethesda, MD
| | - Andrew L Mammen
- Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, MD
| | - Frederick W Miller
- Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Bethesda, MD
| | - Mark D Hicar
- Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences
| | - Lisa G Rider
- Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Bethesda, MD
| | - James N Jarvis
- Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences
- Genetics, Genomics, & Bioinformatics Program, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA
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15
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Davuluri S, Duvvuri B, Lood C, Faghihi-Kashani S, Chung L. Calcinosis in dermatomyositis: Origins and possible therapeutic avenues. Best Pract Res Clin Rheumatol 2022; 36:101768. [PMID: 35803868 DOI: 10.1016/j.berh.2022.101768] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Calcinosis, insoluble calcium compounds deposited in skin and other tissues, is a crippling sequela of dermatomyositis. Prolonged disease associated with ongoing inflammation, ischemia, repetitive trauma, and certain autoantibodies are associated with calcinosis. Herein, we describe potential pathogenic mechanisms including the role of mitochondrial calcification. There are no widely effective treatments for calcinosis. We review available pharmacologic therapies for calcinosis including those targeting calcium and phosphorus metabolism; immunosuppressive/anti-inflammatory therapies; and vasodilators. Mounting evidence supports the use of various formulations of sodium thiosulfate in the treatment of calcinosis. Although the early institution of aggressive immunosuppression may prevent calcinosis in juvenile dermatomyositis, only limited data support improvement once it has developed. Minocycline can be useful particularly for lesions associated with surrounding inflammation. Powerful vasodilators, such as prostacyclin analogs, may have promise in the treatment of calcinosis, but further studies are necessary. Surgical removal of lesions when amenable is our treatment of choice.
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Affiliation(s)
- Srijana Davuluri
- Stanford School of Medicine, Division of Immunology &Rheumatology, 1000 Welch Road, Suite 204, Palo Alto, 94304, California, USA.
| | - Bhargavi Duvvuri
- University of Washington, Department of Medicine, Division of Rheumatology, 750 Republican Street, Seattle, WA, 98109, USA.
| | - Christian Lood
- University of Washington, Division of Rheumatology, 750 Republican Street, Room E-545, Seattle, WA, 98109, USA.
| | - Sara Faghihi-Kashani
- Stanford School of Medicine, Division of Immunology &Rheumatology, 1000 Welch Road, Suite 204, Palo Alto, 94304, California, USA.
| | - Lorinda Chung
- Stanford School of Medicine & Palo Alto VA Health Care System, Division of Immunology &Rheumatology, 1000 Welch Road, Suite 203, Palo Alto, 94304, California, USA.
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16
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Dressler F, Maurer B. [Dermatomyositis and juvenile dermatomyositis]. Z Rheumatol 2022; 82:233-245. [PMID: 35486206 DOI: 10.1007/s00393-022-01205-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/17/2022] [Indexed: 11/29/2022]
Abstract
Dermatomyositis (DM) is an inflammatory multisystem disease of unknown etiology, which can already occur in children but first onset can also be in older adulthood. Myalgia and muscle weakness can occur later in the course of the disease or even be completely absent in some forms. Classical signs on the skin include heliotrope rash, facial erythema, Gottron's papules and nailfold capillary abnormalities. For the diagnosis, screening for the presence of myositis-specific autoantibodies has become increasingly more relevant. Muscle enzymes may be elevated but not in approximately one third of patients. In the absence of typical clinical or serologic findings, additional examination methods such as nailfold capillaroscopy, magnetic resonance imaging, electromyography, skin or muscle biopsies may help to establish the diagnosis. Depending on the clinical and serological subtype, additional screening for gastrointestinal or cardiopulmonary involvement should be considered. In adults, an age-appropriate tumor screening should also be performed. Apart from corticosteroids as induction therapy, biologics and small molecule inhibitors are gaining in importance in addition to conventional disease-modifying anti-rheumatic drugs and intravenous immunoglobulins. The prognosis for DM and juvenile DM (JDM) has improved. Most patients recover at least to some extent; however, a few patients die and a minority develop persisting muscle atrophy or severe calcinosis.
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Affiliation(s)
- Frank Dressler
- Kinderklinik, Medizinische Hochschule Hannover, 30623, Hannover, Deutschland.
| | - Britta Maurer
- Universitätsklinik für Rheumatologie und Immunologie, Inselspital Bern, 3010, Bern, Schweiz.
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17
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Wang YT, Zhang Y, Tang T, Luo C, Liu MY, Xu L, Wang L, Tang XM. Anti-nuclear matrix protein 2+ juvenile dermatomyositis with severe skin ulcer and infection: A case report and literature review. World J Clin Cases 2022; 10:3579-3586. [PMID: 35611208 PMCID: PMC9048553 DOI: 10.12998/wjcc.v10.i11.3579] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/07/2022] [Accepted: 02/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Juvenile dermatomyositis (JDM) is an idiopathic inflammatory myopathy that occurs in childhood. It is characterized by muscle weakness and a characteristic rash. Previous literature reports have rarely described JDM with severe skin ulcers and infections.
CASE SUMMARY Herein, we describe a case of a 2-year-old female patient who suffered from JDM, whose myositis-specific autoantibodies were positive for anti-nuclear matrix protein 2 antibody, with progressively worsening skin ulcers and severe infections. The patient was treated with glucocorticoids and various immunosuppressants. Nevertheless, further progression of the disease and the combination of primary disease and severe infection in the later period were fatal.
CONCLUSION In children, anti-nuclear matrix protein 2+ JDM combined with skin ulcers often indicates severe disease. In such cases, personalized treatment for the primary disease and infection prevention and control are essential.
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Affiliation(s)
- Ya-Ting Wang
- Department of Rheumatology and Immunology; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation base of Child Development and Critical Disorders; Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
- Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Yu Zhang
- Department of Rheumatology and Immunology; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation base of Child Development and Critical Disorders; Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
- Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Tao Tang
- Department of Rheumatology and Immunology; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation base of Child Development and Critical Disorders; Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
- Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Chong Luo
- Department of Rheumatology and Immunology; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation base of Child Development and Critical Disorders; Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
- Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Ming-Yue Liu
- Department of Rheumatology and Immunology; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation base of Child Development and Critical Disorders; Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
- Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Li Xu
- Department of Rheumatology and Immunology; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation base of Child Development and Critical Disorders; Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
- Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Li Wang
- Department of Rheumatology and Immunology; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation base of Child Development and Critical Disorders; Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
- Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Xue-Mei Tang
- Department of Rheumatology and Immunology; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation base of Child Development and Critical Disorders; Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
- Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
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18
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Valenzuela A, Chung L. Subcutaneous calcinosis: Is it different between systemic sclerosis and dermatomyositis? JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2022; 7:7-23. [PMID: 35386947 PMCID: PMC8922676 DOI: 10.1177/23971983211053245] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 09/27/2021] [Indexed: 02/03/2023]
Abstract
Calcinosis cutis is the deposition of insoluble calcium in the skin and subcutaneous tissues. It is a manifestation of several autoimmune connective tissue diseases, most frequently with systemic sclerosis and juvenile dermatomyositis, followed by adult dermatomyositis. Autoimmune connective tissue disease-associated calcinosis is of the dystrophic subtype, which occurs at sites of damaged tissue in the setting of normal serum calcium and phosphate levels. In juvenile dermatomyositis, calcinosis is considered a marker of ongoing disease activity and possibly inadequate treatment, while in adult dermatomyositis, it is a hallmark of skin damage due to chronic rather than active disease. Calcinosis is associated with long disease duration in systemic sclerosis and dermatomyositis, anti-polymyositis/sclerosis autoantibodies in systemic sclerosis and NXP-2 and melanoma differentiation-associated gene 5 in dermatomyositis. Calcinosis in systemic sclerosis occurs most frequently in the hands, particularly the fingers, whereas in dermatomyositis, it affects mainly the trunk and extremities. The primary mineral component of calcinosis is hydroxyapatite in systemic sclerosis and carbonate apatite in dermatomyositis. Calcinosis in dermatomyositis and systemic sclerosis share some pathogenic mechanisms, but vascular hypoxia seems to play a more important role in systemic sclerosis, whereas the release of calcium from mitochondria in muscle cells damaged by myopathy may be a primary mechanism contributing to dermatomyositis-related calcinosis. Multiple treatment strategies for dermatomyositis and systemic sclerosis-related calcinosis have been used with variable results. Early aggressive treatment of underlying myositis in patients with dermatomyositis may improve long-term outcomes of calcinosis. A better understanding of the pathogenesis of calcinosis is needed to improve treatment options.
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Affiliation(s)
- Antonia Valenzuela
- Division of Clinical Immunology and Rheumatology, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Lorinda Chung
- Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA,Division of Immunology and Rheumatology, VA Palo Alto Health Care System, Palo Alto, CA, USA,Lorinda Chung, Division of Immunology and Rheumatology, Stanford University School of Medicine, 1000 Welch Rd Ste 203, MC 5755, Palo Alto, CA 94304, USA.
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19
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Kassamali B, Mazori DR, LaChance AH, Christopher-Stine L. Exploring Dermatomyositis through an Interdisciplinary Lens: Pearls from Dermatology and Rheumatology. Int J Womens Dermatol 2022; 7:576-582. [PMID: 35005177 PMCID: PMC8721135 DOI: 10.1016/j.ijwd.2021.09.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 09/14/2021] [Accepted: 09/19/2021] [Indexed: 11/30/2022] Open
Affiliation(s)
- Bina Kassamali
- Department of Dermatology, Brigham and Women's Hospital, Boston, MA.,Harvard Medical School, Boston, MA
| | - Daniel R Mazori
- Department of Dermatology, Brigham and Women's Hospital, Boston, MA.,Harvard Medical School, Boston, MA
| | - Avery H LaChance
- Department of Dermatology, Brigham and Women's Hospital, Boston, MA.,Harvard Medical School, Boston, MA
| | - Lisa Christopher-Stine
- Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD
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20
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Yildirim DG, Akdulum İ, Talim B, Demir E, Buyan N, Bakkaloğlu SA. Milk of calcium: A rare manifestation of juvenile dermatomyositis. Arch Rheumatol 2021; 36:302-304. [PMID: 34527937 PMCID: PMC8418756 DOI: 10.46497/archrheumatol.2021.8197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 06/25/2020] [Indexed: 12/05/2022] Open
Affiliation(s)
- Deniz Gezgin Yildirim
- Department of Pediatrics, Division of Pediatric Rheumatology, Gazi University, Faculty of Medicine, Ankara, Turkey
| | - İsmail Akdulum
- Department of Radiology, Division of Pediatric Radiology, Gazi University, Faculty of Medicine, Ankara, Turkey
| | - Beril Talim
- Department of Pathology Unit, Hacettepe University, Faculty of Medicine, Ankara, Turkey
| | - Ercan Demir
- Department of Pediatrics, Division of Pediatric Neurology, Gazi University, Faculty of Medicine, Ankara, Turkey
| | - Necla Buyan
- Department of Pediatrics, Division of Pediatric Rheumatology, Gazi University, Faculty of Medicine, Ankara, Turkey
| | - Sevcan A Bakkaloğlu
- Department of Pediatrics, Division of Pediatric Rheumatology, Gazi University, Faculty of Medicine, Ankara, Turkey
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21
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Taneja N, Gupta S, Patel U, Arava S, Gupta V. Diffuse Lacy Reticular Calcinosis in Juvenile Dermatomyositis. J Clin Rheumatol 2021; 27:e232-e233. [PMID: 32251056 DOI: 10.1097/rhu.0000000000001369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Neha Taneja
- From the Departments of Dermatology and Venereology
| | | | - Utpal Patel
- From the Departments of Dermatology and Venereology
| | - Sudheer Arava
- Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Vishal Gupta
- From the Departments of Dermatology and Venereology
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22
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Orandi AB, Fotis L, Lai J, Morris H, White AJ, French AR, Baszis KW. Favorable outcomes with reduced steroid use in juvenile dermatomyositis. Pediatr Rheumatol Online J 2021; 19:127. [PMID: 34404425 PMCID: PMC8369654 DOI: 10.1186/s12969-021-00615-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 06/14/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis but are associated with several adverse side-effects. Evidence-based treatment guidelines from North American and European pediatric rheumatology research societies both advocate induction with intravenous pulse steroids followed by high dose oral steroids (2 mg/kg/day), which are then tapered. This study reports the time to disease control with reduced glucocorticoid dosing. METHODS We retrospectively reviewed the records at a single tertiary-care children's hospital of patients diagnosed with Juvenile Dermatomyositis between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure was time to control of muscle and skin disease. Additional outcome measures included glucocorticoid dosing, effect of treatment on height, frequency of calcinosis, and complications from treatment. RESULTS Of the 69 patients followed during the study period, 31 fulfilled inclusion criteria. Median length of follow-up was 4.58 years, (IQR 3-7.5). Myositis control was achieved in a median of 7.1 months (IQR 0.9-63.4). Cutaneous disease control was achieved in a median of 16.7 months (IQR 4.3-89.5). The median starting dose of glucocorticoids was 0.85 mg/kg/day, (IQR 0.5-1.74). The median duration of steroid treatment was 9.1 months, (IQR 4.7-17.4), while the median duration of any pharmacotherapy was 29.2 months (IQR 10.4 to 121.3). Sustained disease control off medications was achieved in 21/31 (68%) patients by the end of review. Persistent calcinosis was identified in only one patient (3%). CONCLUSION Current accepted treatment paradigms for Juvenile Dermatomyositis include oral glucocorticoids beginning at 2 mg/kg/day and reduced over a prolonged time period. However, our results suggest that treatment using reduced doses and duration with early use of steroid-sparing agents is comparably effective in achieving favorable outcomes in Juvenile Dermatomyositis.
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Affiliation(s)
- Amir B. Orandi
- grid.4367.60000 0001 2355 7002Division of Pediatric Rheumatology/Immunology, Washington University of School of Medicine, St Louis, MO USA ,grid.66875.3a0000 0004 0459 167XPresent Address: Department of Pediatric and Adolescent Medicine, Division of Pediatric Rheumatology, Mayo Clinic, Rochester, MN USA
| | - Lampros Fotis
- grid.4367.60000 0001 2355 7002Division of Pediatric Rheumatology/Immunology, Washington University of School of Medicine, St Louis, MO USA ,grid.5216.00000 0001 2155 0800Present Address: Department of Pediatrics, Division of Pediatric Rheumatology, National and Kapodistrian University of Athens, Athens, Greece
| | - Jamie Lai
- grid.4367.60000 0001 2355 7002Department of Pediatrics, Washington University School of Medicine, St. Louis, MO USA ,grid.39382.330000 0001 2160 926XPresent Address: Department of Pediatrics, Division of Pediatric Rheumatology, Baylor College of Medicine, Houston, TX USA
| | - Hallie Morris
- grid.4367.60000 0001 2355 7002Department of Pediatrics, Washington University School of Medicine, St. Louis, MO USA ,grid.253615.60000 0004 1936 9510Present Address: Division of Neonatology, George Washington University School of Medicine and Health Science, Washington, D.C, USA
| | - Andrew J. White
- grid.4367.60000 0001 2355 7002Division of Pediatric Rheumatology/Immunology, Washington University of School of Medicine, St Louis, MO USA
| | - Anthony R. French
- grid.4367.60000 0001 2355 7002Division of Pediatric Rheumatology/Immunology, Washington University of School of Medicine, St Louis, MO USA
| | - Kevin W. Baszis
- grid.4367.60000 0001 2355 7002Division of Pediatric Rheumatology/Immunology, Washington University of School of Medicine, St Louis, MO USA
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23
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Jiang W, Yang H, Li S, Tian X, Wang G. Clinical features, treatments and outcomes of calcinosis in adult patients with dermatomyositis: a single cohort study. Rheumatology (Oxford) 2021; 60:2958-2962. [PMID: 33249499 DOI: 10.1093/rheumatology/keaa618] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 08/23/2020] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVE The occurrence of calcinosis cutis as a clinical feature of dermatomyositis in adult patients is not well understood. Cohort studies of adult patients with calcinosis are rare. We systematically describe the clinical features, treatments and outcomes of adult patients with calcinosis. METHODS We initially enrolled 627 adult DM patients. Of those enrolled, 35 (5.6%) were found to have calcinosis. We analysed the clinical features associated with calcinosis in this subgroup. The risk factors associated with calcinosis were analysed using the Poisson regression model. RESULTS Multivariate analysis showed that a younger age at disease onset [odds ratio (OR) = 0.945, 95% CI 0.925, 0.966, P < 0.001], dysphagia (OR = 2.609, 95% CI 1.189, 5.728, P = 0.017), skin ulcer (OR = 5.705, 95% CI 3.041, 10.705, P < 0.001) and the presence of anti-nuclear matrix protein 2 antibody (OR = 5.917, 95% CI 2.754, 12.714, P < 0.001) were independently associated with calcinosis. In both the low- and high-dose prednisone treatment groups, no difference in treatment response was seen between the bisphosphonate treatment group and the group not receiving bisphosphonate treatment (P = 1.000 and P = 0.375, respectively). A follow-up study revealed that the mortality rate of the calcinosis group was 5.7%. Additionally, 60.6% of the cases had a chronic polycyclic disease course and 17.1% had mild complications secondary to calcinosis. CONCLUSION Calcinosis is an uncommon, but significant clinical feature in adult patients with DM. Bisphosphonates were not found to effectively treat calcinosis, however, the overall health outcomes of adult DM patients with calcinosis were favourable.
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Affiliation(s)
- Wei Jiang
- Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China
| | - Hanbo Yang
- Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China
| | - Sizhao Li
- Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China
| | - Xiaolan Tian
- Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China
| | - Guochun Wang
- Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China
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24
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Sangeetha G, Dhanabal D, Mouttou Prebagarane S, Janarthanan M. Juvenile dermatomyositis: a case of delayed recognition with unusual complication of nephrocalcinosis. BMJ Case Rep 2021; 14:14/4/e241152. [PMID: 33795282 DOI: 10.1136/bcr-2020-241152] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in children and is characterised by the presence of proximal muscle weakness, heliotrope dermatitis, Gottron's papules and occasionally auto antibodies. The disease primarily affects skin and muscles, but can also affect other organs. Renal manifestations though common in autoimmune conditions like lupus are rare in JDM. We describe a child whose presenting complaint was extensive calcinosis cutis. Subtle features of proximal muscle weakness were detected on examination. MRI of thighs and a muscle biopsy confirmed myositis. Nephrocalcinosis was found during routine ultrasound screening. We report the first case of a child presenting with rare association of dermatomyositis, calcinosis cutis and bilateral medullary nephrocalcinosis.
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Affiliation(s)
- Geminiganesan Sangeetha
- Pediatric Nephrology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamilnadu, India
| | - Divya Dhanabal
- Pathology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
| | | | - Mahesh Janarthanan
- Pediatric Rheumatology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
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Castillo RL, Femia AN. Covert clues: the non-hallmark cutaneous manifestations of dermatomyositis. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:436. [PMID: 33842657 PMCID: PMC8033358 DOI: 10.21037/atm-20-5252] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Dermatomyositis (DM) is a strikingly heterogenous disease characterized by a broad and ever-evolving spectrum of cutaneous manifestations that transcend the classic “hallmarks” defined by Peter and Bohan in 1975. Despite the increasing preponderance and ubiquity of autoantibody, radiologic, and electrophysiologic testing, the diagnosis of DM still hinges largely on prompt detection of cutaneous manifestations of this condition. While pathognomonic cutaneous features of DM are more readily recognizable, many patients present with subtle and/or atypical skin manifestations, and diagnosis of DM may require clinician identification of these cutaneous clues. In this review, we highlight several of the lesser-known skin manifestations of DM, specifically, panniculitis, diffuse subcutaneous edema, erythroderma, calcinosis, ulceration, flagellate erythema, Wong-type DM, gingival telangiectasias, and the ovoid palatal patch. We describe the clinical and histopathologic presentation of these cutaneous findings. While manifesting less frequently than the heliotrope rash, Gottron’s papules, and Gottron’s sign, these cutaneous clues are equally important for clinicians to recognize in order to facilitate timely diagnosis and early intervention.
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Affiliation(s)
- Rochelle L Castillo
- Department of Medicine, Division of Rheumatology, NYU Grossman School of Medicine, New York, NY, USA
| | - Alisa N Femia
- Ronald O. Perelman Department of Dermatology, NYU Grossman School of Medicine, New York, NY, USA
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Kul Cinar O, Papadopoulou C, Pilkington CA. Treatment of Calcinosis in Juvenile Dermatomyositis. Curr Rheumatol Rep 2021; 23:13. [PMID: 33555459 DOI: 10.1007/s11926-020-00974-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/08/2020] [Indexed: 10/22/2022]
Abstract
PURPOSE OF REVIEW Juvenile dermatomyositis (JDM) is a rare autoimmune disease characterised by muscle and skin involvement. Calcinosis is a debilitating complication of JDM which is difficult to treat and may cause long-term morbidity. The purpose of this review is to provide an update for the treatment of JDM-associated calcinosis based on previously published studies. RECENT FINDINGS Evidence-based studies are lacking for the management of calcinosis, and current treatment modalities have been largely based on case reports, case series, cohort studies, limited controlled studies and anecdotal clinical experience. The use of early aggressive therapy for resistant cases is strongly suggested to halt persistent disease activity which may help in reducing steroid use and their associated complications. Recent insights into disease pathogenesis, myositis-specific antibodies and genetic associations have led to identification of novel therapeutic targets such as Janus kinase (JAK) 1/2. Different treatment regimens with variable outcomes are in use for the treatment of refractory calcinosis; nevertheless, the level of evidence is not sufficient to propose specific guidelines. Recently, JAK 1/2 inhibitors have shown to be effective as an emerging therapeutic option highlighting that translational and clinical research is crucial to develop targeted treatment for JDM-associated calcinosis.
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Affiliation(s)
- Ovgu Kul Cinar
- Paediatric Rheumatology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH, UK. .,Division of Infection and Immunity, University College London, London, WC1E 6BT, UK.
| | - Charalampia Papadopoulou
- Paediatric Rheumatology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH, UK.,Infection, Inflammation and Rheumatology Section, University College London Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK
| | - Clarissa A Pilkington
- Paediatric Rheumatology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH, UK.,NIHR Biomedical Research Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
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Abstract
One of the most fascinating aspects of mitochondria is their remarkable ability to accumulate and store large amounts of calcium in the presence of phosphate leading to mitochondrial calcification. In this paper, we briefly address the mechanisms that regulate mitochondrial calcium homeostasis followed by the extensive review on the formation and characterization of intramitochondrial calcium phosphate granules leading to mitochondrial calcification and its relevance to physiological and pathological calcifications of body tissues.
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Affiliation(s)
- Bhargavi Duvvuri
- Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA 98195, USA
| | - Christian Lood
- Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA 98195, USA
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Chandrasekaran AC, Fu Z, Kraniski R, Wilson FP, Teaw S, Cheng M, Wang A, Ren S, Omar IM, Hinchcliff ME. Computer vision applied to dual-energy computed tomography images for precise calcinosis cutis quantification in patients with systemic sclerosis. Arthritis Res Ther 2021; 23:6. [PMID: 33407814 PMCID: PMC7788847 DOI: 10.1186/s13075-020-02392-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 12/09/2020] [Indexed: 01/12/2023] Open
Abstract
Background Although treatments have been proposed for calcinosis cutis (CC) in patients with systemic sclerosis (SSc), a standardized and validated method for CC burden quantification is necessary to enable valid clinical trials. We tested the hypothesis that computer vision applied to dual-energy computed tomography (DECT) finger images is a useful approach for precise and accurate CC quantification in SSc patients. Methods De-identified 2-dimensional (2D) DECT images from SSc patients with clinically evident lesser finger CC lesions were obtained. An expert musculoskeletal radiologist confirmed accurate manual segmentation (subtraction) of the phalanges for each image as a gold standard, and a U-Net Convolutional Neural Network (CNN) computer vision model for segmentation of healthy phalanges was developed and tested. A validation study was performed in an independent dataset whereby two independent radiologists manually measured the longest length and perpendicular short axis of each lesion and then calculated an estimated area by assuming the lesion was elliptical using the formula long axis/2 × short axis/2 × π, and a computer scientist used a region growing technique to calculate the area of CC lesions. Spearman’s correlation coefficient, Lin’s concordance correlation coefficient with 95% confidence intervals (CI), and a Bland-Altman plot (Stata V 15.1, College Station, TX) were used to test for equivalence between the radiologists’ and the CNN algorithm-generated area estimates. Results Forty de-identified 2D DECT images from SSc patients with clinically evident finger CC lesions were obtained and divided into training (N = 30 with image rotation × 3 to expand the set to N = 120) and test sets (N = 10). In the training set, five hundred epochs (iterations) were required to train the CNN algorithm to segment phalanges from adjacent CC, and accurate segmentation was evaluated using the ten held-out images. To test model performance, CC lesional area estimates calculated by two independent radiologists and a computer scientist were compared (radiologist 1 vs. radiologist 2 and radiologist 1 vs. computer vision approach) using an independent test dataset comprised of 31 images (8 index finger and 23 other fingers). For the two radiologists’, and the radiologist vs. computer vision measurements, Spearman’s rho was 0.91 and 0.94, respectively, both p < 0.0001; Lin’s concordance correlation coefficient was 0.91 (95% CI 0.85–0.98, p < 0.001) and 0.95 (95% CI 0.91–0.99, p < 0.001); and Bland-Altman plots demonstrated a mean difference between radiologist vs. radiologist, and radiologist vs. computer vision area estimates of − 0.5 mm2 (95% limits of agreement − 10.0–9.0 mm2) and 1.7 mm2 (95% limits of agreement − 6.0–9.5 mm2, respectively. Conclusions We demonstrate that CNN quantification has a high degree of correlation with expert radiologist measurement of finger CC area measurements. Future work will include segmentation of 3-dimensional (3D) images for volumetric and density quantification, as well as validation in larger, independent cohorts.
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Affiliation(s)
- Anita C Chandrasekaran
- Yale School of Medicine, Section of Rheumatology, Allergy & Immunology, The Anlyan Center, 300 Cedar Street, PO BOX 208031, New Haven, CT, 06520, USA
| | - Zhicheng Fu
- Department of Computer Science, Illinois Institute of Technology, 10 W 31st St, Chicago, IL, 60616, USA.,Motorola Mobility LLC, 222 W Merchandise Mart Plaza #1800, Chicago, IL, 60654, USA
| | - Reid Kraniski
- Department of Radiology, Yale School of Medicine, 330 Cedar St, New Haven, CT, 06520, USA
| | - F Perry Wilson
- Clinical and Translational Research Accelerator, Department of Medicine, Yale School of Medicine, Temple Medical Center, 60 Temple Street Suite 6C, New Haven, CT, 06510, USA
| | - Shannon Teaw
- Yale School of Medicine, Section of Rheumatology, Allergy & Immunology, The Anlyan Center, 300 Cedar Street, PO BOX 208031, New Haven, CT, 06520, USA
| | - Michelle Cheng
- Yale School of Medicine, Section of Rheumatology, Allergy & Immunology, The Anlyan Center, 300 Cedar Street, PO BOX 208031, New Haven, CT, 06520, USA
| | - Annie Wang
- Department of Radiology, Yale School of Medicine, 330 Cedar St, New Haven, CT, 06520, USA
| | - Shangping Ren
- Department of Computer Science, Illinois Institute of Technology, 10 W 31st St, Chicago, IL, 60616, USA.,Department of Computer Science, San Diego State University, 5500 Campanile Drive, San Diego, CA, 92182, USA
| | - Imran M Omar
- Department of Radiology, Northwestern University Feinberg School of Medicine, 676 N St Clair St, Chicago, IL, 60611, USA
| | - Monique E Hinchcliff
- Yale School of Medicine, Section of Rheumatology, Allergy & Immunology, The Anlyan Center, 300 Cedar Street, PO BOX 208031, New Haven, CT, 06520, USA. .,Clinical and Translational Research Accelerator, Department of Medicine, Yale School of Medicine, Temple Medical Center, 60 Temple Street Suite 6C, New Haven, CT, 06510, USA. .,Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine, 240 E. Huron Street, Suite M-300, Chicago, IL, 60611, USA.
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Toplak N, Pimpale Chavan P, Rosina S, Dallos T, Rotem Semo O, Aguiar CL, Khubchandani R, Ravelli A, Patwardhan A. Is Anti-NXP2 Autoantibody a Risk Factor for Calcinosis and Poor Outcome in Juvenile Dermatomyositis Patients? Case Series. Front Pediatr 2021; 9:810785. [PMID: 35280444 PMCID: PMC8904416 DOI: 10.3389/fped.2021.810785] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 12/20/2021] [Indexed: 11/27/2022] Open
Abstract
Juvenile dermatomyositis (JDM) has a wide spectrum of clinical presentations. In the last decade, several myositis-specific antibodies have been identified in patients with JDM and connected with specific organ involvement or specific clinical picture. It has been published that the presence of anti-NXP2 autoantibodies presents a risk for calcinosis in patients with JDM. We aimed to investigate the prevalence of calcinosis and response to the treatment in JDM patients with anti-NXP2. In a retrospective, multinational, multicenter study, data on 26 JDM (19 F, 7 M) patients with positive anti-NXP2 were collected. The mean age at disease presentation was 6.5 years (SD 3.7), the median diagnosis delay was 4 months (range 0.5-27 months). Patients were divided into two groups (A and B) based on the presence of calcinosis, which occurred in 42% of anti-NXP2 positive JDM patients (group A). Four patients already had calcinosis at presentation, one developed calcinosis after 4 months, and 6 developed calcinosis later in the disease course (median 2 years, range 0.8-7.8). The differences in laboratory results were not statistically significant between the groups. The mean age at disease presentation (5.2/7.5 years) trended toward being younger in group A. Children with calcinosis were treated with several combinations of drugs. In four cases, rituximab and, in one case, anti-TNF alpha agents were used successfully. Disease outcome (by evaluation of the treating physician) was excellent in four, good in two, stable in two, and poor in three patients. None of the patients from group B had a poor disease outcome. In conclusion, JDM patients with anti-NXP2 are prone to develop calcinosis, especially if they present with the disease early, before 5 years of age. The development of calcinosis is associated with worse disease outcomes. The combination of several immunomodulatory drugs and biologic drugs can stop calcinosis progression; however, there are no evidence-based therapies for treating calcinosis in JDM patients.
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Affiliation(s)
- Natasa Toplak
- Department of Allergology, Rheumatology and Clinical Immunology, Faculty of Medicine, University Children's Hospital, University Medical Centre, Ljubljana, Slovenia
| | | | - Silvia Rosina
- Pediatric Rheumatology, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Tomas Dallos
- Department of Paediatrics, Comenius University Medical School, National Institute of Children's Diseases, Bratislava, Slovakia
| | - Oz Rotem Semo
- Section of Pediatric Rheumatology, University of Chicago Medical Center, Chicago, IL, United States
| | - Cassyanne L Aguiar
- Pediatric Rheumatology, Eastern Virginia Medical School (EVMS), Children's Hospital of The King's Daughters, Norfolk, VA, United States
| | | | - Angelo Ravelli
- Direzione Scientifica, IRCCS Istituto Giannina Gaslini, Genoa, Italy.,Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Universita Degli Studi di Genova, Genoa, Italy
| | - Anjali Patwardhan
- Pediatric Rheumatology, University of Missouri, School of Medicine, Columbia, MO, United States
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31
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Wang A, Morgan GA, Paller AS, Pachman LM. Skin disease is more recalcitrant than muscle disease: A long-term prospective study of 184 children with juvenile dermatomyositis. J Am Acad Dermatol 2020; 84:1610-1618. [PMID: 33359787 DOI: 10.1016/j.jaad.2020.12.032] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 12/05/2020] [Accepted: 12/13/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND Persistent skin manifestations, especially calcinoses, contribute to morbidity in children with juvenile dermatomyositis. OBJECTIVE To compare the course of skin and muscle involvement and document frequency of calcinosis in juvenile dermatomyositis. METHODS Prospective cohort study of 184 untreated children with juvenile dermatomyositis (July 1971 to May 2019) at a single children's hospital. RESULTS Disease Activity Scores (DASs) were persistently higher for skin versus muscle at all points; clinical inactivity (DAS ≤2) occurred earlier for muscle than skin. Among vascular features for DAS for skin, eyelid margin capillary dilatation was most frequent (54.3%) and persisted longest. Intravenous methylprednisolone reduced DAS for skin more than oral prednisone at 12 months (P = .04). Overall, 16.8% of patients (n = 31) had calcifications, with 4.9% at enrollment. Despite therapy, 25.0% of calcifications recurred and 22.6% failed to resolve; of the latter, 71.4% (n = 5) were present at enrollment. Children with persistent calcifications had longer duration of untreated disease than those whose calcifications resolved (mean 12.5 months) (P < .001). Hydroxychloroquine did not improve DAS for skin (P = .89). LIMITATIONS DAS does not quantify nailfold capillary dropout. CONCLUSIONS In juvenile dermatomyositis, skin disease presents with greater activity and is more recalcitrant to therapies than muscle disease. Early and aggressive treatment can limit the severity and persistence of calcifications identified later in the disease course.
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Affiliation(s)
- Andi Wang
- Division of Pediatric Rheumatology, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Gabrielle A Morgan
- Cure JM Center of Excellence in Juvenile Dermatomyositis Care and Research, Stanley Manne Children's Research Institute; and The Ann and Robert H. Lurie Children's Hospital of Chicago Research Center, Cure JM Myositis Center, Chicago, Illinois
| | - Amy S Paller
- Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Lauren M Pachman
- Division of Pediatric Rheumatology, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cure JM Center of Excellence in Juvenile Dermatomyositis Care and Research, Stanley Manne Children's Research Institute; and The Ann and Robert H. Lurie Children's Hospital of Chicago Research Center, Cure JM Myositis Center, Chicago, Illinois.
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Vargas Lebrón C, Ruiz Montesino MD, Moreira Navarrete V, Toyos Sainz de Miera FJ. Treatment With Rituximab in Juvenile Dermatomyositis: Effect on Calcinosis. REUMATOLOGIA CLINICA 2020; 16:368-370. [PMID: 30054253 DOI: 10.1016/j.reuma.2018.06.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 05/31/2018] [Accepted: 06/19/2018] [Indexed: 05/28/2023]
Affiliation(s)
- Carmen Vargas Lebrón
- Servicio de Reumatología, Hospital Universitario Virgen Macarena, Sevilla, España
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Chung MP, Richardson C, Kirakossian D, Orandi AB, Saketkoo LA, Rider LG, Schiffenbauer A, von Mühlen CA, Chung L. Calcinosis Biomarkers in Adult and Juvenile Dermatomyositis. Autoimmun Rev 2020; 19:102533. [PMID: 32234404 PMCID: PMC7225028 DOI: 10.1016/j.autrev.2020.102533] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 12/13/2019] [Indexed: 02/06/2023]
Abstract
Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy characterized by muscle weakness and cutaneous manifestations in adults and children. Calcinosis, a complication of DM, is the abnormal deposition of insoluble calcium salts in tissues, including skin, subcutaneous tissue, tendons, fascia, and muscle. Calcinosis is more commonly seen in juvenile DM (JDM), but also develops in adult DM. Although the mechanism of calcinosis remains unclear, several pathogenic hypotheses have been proposed, including intracellular accumulation of calcium secondary to an alteration of the cellular membrane by trauma and inflammation, local vascular ischemia, dysregulation of mechanisms controlling the deposition and solubility of calcium and phosphate, and mitochondrial damage of muscle cells. Identifying calcinosis biomarkers is important for early disease detection and risk assessment, and may lead to novel therapeutic targets for the prevention and treatment of DM-associated calcinosis. In this review, we summarize myositis autoantibodies associated with calcinosis in DM, histopathology and chemical composition of calcinosis, genetic and inflammatory markers that have been studied in adult DM and JDM-associated calcinosis, as well as potential novel biomarkers.
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Affiliation(s)
- Melody P Chung
- Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Carrie Richardson
- Division of Rheumatology, Rush University Medical Center, Chicago, IL, USA
| | - David Kirakossian
- Department of Internal Medicine, Kaiser Permanente Santa Clara, Santa Clara, CA, USA
| | - Amir B Orandi
- Division of Pediatric Rheumatology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
| | - Lesley A Saketkoo
- Louisiana State University School of Medicine, Tulane University School of Medicine, New Orleans Scleroderma and Sarcoidosis Patient Care and Research Center, New Orleans, LA, USA
| | - Lisa G Rider
- Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD, USA
| | - Adam Schiffenbauer
- Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD, USA
| | - Carlos A von Mühlen
- Consultant in Rheumatology and Clinical Pathology, San Diego, USA; Brazilian Society of Autoimmunity, Porto Alegre, Brazil
| | - Lorinda Chung
- Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA.
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Sukumaran S, Vijayan V. Abatacept in the Treatment of Juvenile Dermatomyositis-Associated Calcifications in a 16-Year-Old Girl. Case Rep Rheumatol 2020; 2020:4073879. [PMID: 32550037 PMCID: PMC7275234 DOI: 10.1155/2020/4073879] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 05/19/2020] [Indexed: 02/03/2023] Open
Abstract
Calcinosis is a feared complication of JDM that may be seen in up to 40% of children with JDM. It is associated with negative impact on the patients' quality of life due to weakness, functional disability, joint contractures, muscle atrophy, skin ulcers, and secondary infections. Calcinosis can present as superficial nodules or plaques, larger nodular deposits extending into deeper tissue layers, accumulation of calcifications along the fascial planes of muscles or tendons, or an exoskeleton of calcium leading to limitations in mobility and joint contractures. Currently, there are no known effective treatments for calcinosis and current therapy is based on anecdotal retrospective studies and cases series. We report the case of a child with JDM-associated calcinosis with extensive intramuscular calcifications who failed conventional therapies but demonstrated improvement as evident by decrease in calcinosis and improved physical function with use of abatacept. We found that use of abatacept was associated with improvement in functional outcome and recurrence did not occur. This case suggests use of abatacept as a safe and effective treatment option for calcinosis due to JDM. Furthermore, large-scale clinical studies are needed to validate our findings and to evaluate the long-term outcomes.
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Affiliation(s)
- Sukesh Sukumaran
- Division of Rheumatology, Department of Pediatrics, Valley Children's Hospital, Madera, CA, USA
| | - Vini Vijayan
- Division of Infectious Diseases, Department of Pediatrics, Valley Children's Hospital, Madera, CA, USA
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35
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Schempp CM, Schauer F, Huhn CK, Venhoff N, Finzel S. Skin inflammation associated with arthritis, synovitis and enthesitis. Part 2: rheumatoid arthritis, reactive arthritis, Reiter's syndrome, Lyme borreliosis, dermatomyositis and lupus erythematosus. J Dtsch Dermatol Ges 2020; 17:167-181. [PMID: 30762968 DOI: 10.1111/ddg.13761] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 01/16/2019] [Indexed: 11/30/2022]
Abstract
Syndromes associated with concurrent skin and joint inflammation frequently pose a therapeutic challenge for both dermatologists and rheumatologists. In part 1 of this review, we discussed psoriatic arthritis as well as the autoinflammatory disorders SAPHO syndrome, Still's disease and Behçet's disease. Part 2 will address rheumatoid arthritis, reactive arthritis, Reiter's syndrome and Lyme borreliosis. In addition, we will discuss dermatomyositis and lupus erythematosus, two common autoimmune disorders that frequently present with both cutaneous and joint involvement. For each of the aforementioned disorders, we will highlight aspects of epidemiology, pathogenesis, clinical presentation, diagnosis and treatment.
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Affiliation(s)
- Christoph M Schempp
- Department of Dermatology and Venereology, Freiburg University Medical Center, Medical Faculty, Albert Ludwigs University, Freiburg, Germany
| | - Franziska Schauer
- Department of Dermatology and Venereology, Freiburg University Medical Center, Medical Faculty, Albert Ludwigs University, Freiburg, Germany
| | - Christian K Huhn
- Department of Dermatology and Venereology, Freiburg University Medical Center, Medical Faculty, Albert Ludwigs University, Freiburg, Germany
| | - Nils Venhoff
- Department of Rheumatology and clinical Immunology, Freiburg University Medical Center, Medical Faculty, Albert Ludwigs University, Freiburg, Germany
| | - Stephanie Finzel
- Department of Rheumatology and clinical Immunology, Freiburg University Medical Center, Medical Faculty, Albert Ludwigs University, Freiburg, Germany
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Zhong D, Wu C, Bai J, Xu D, Zeng X, Wang Q. Co-expression network analysis reveals the pivotal role of mitochondrial dysfunction and interferon signature in juvenile dermatomyositis. PeerJ 2020; 8:e8611. [PMID: 32110496 PMCID: PMC7034382 DOI: 10.7717/peerj.8611] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 01/21/2020] [Indexed: 12/14/2022] Open
Abstract
Background Juvenile dermatomyositis (JDM) is an immune-mediated disease characterized by chronic organ inflammation. The pathogenic mechanisms remain ill-defined. Methods Raw microarray data of JDM were obtained from the gene expression omnibus (GEO) database. Based on the GSE3307 dataset with 39 samples, weighted correlation network analysis (WGCNA) was performed to identify key modules associated with pathological state. Functional enrichment analyses were conducted to identify potential mechanisms. Based on the criteria of high connectivity and module membership, candidate hub genes were selected. A protein-protein interaction network was constructed to identify hub genes. Another dataset (GSE11971) was used for the validation of real hub genes. Finally, the real hub genes were used to screen out small-molecule compounds via the Connectivity map database. Results Three modules were considered as key modules for the pathological state of JDM. Functional enrichment analysis indicated that responses to interferon and metabolism were dysregulated. A total of 45 candidate hub genes were selected according to the pre-established criteria, and 20 genes could differentiate JDM from normal controls by validation of another external dataset (GSE11971). These real hub genes suggested the pivotal role of mitochondrial dysfunction and interferon signature in JDM. Furthermore, drug repositioning highlighted the importance of acacetin, helveticoside, lanatoside C, deferoxamine, LY-294002, tanespimycin and L01AD from downregulated genes with the potential to perturb the development of JDM, while betonicine, felodipine, valproic acid, trichostatin A and sirolimus from upregulated genes provided potentially therapeutic goals for JDM. Conclusions There are 20 real hub genes associated with the pathological state of JDM, suggesting the pivotal role of mitochondrial dysfunction and interferon signature in JDM. This analysis predicted several kinds of small-molecule compounds to treat JDM.
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Affiliation(s)
- Danli Zhong
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.,Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Chanyuan Wu
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.,Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Jingjing Bai
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.,Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Dong Xu
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.,Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.,Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Qian Wang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China.,Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
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Wu JQ, Lu MP, Reed AM. Juvenile dermatomyositis: advances in clinical presentation, myositis-specific antibodies and treatment. World J Pediatr 2020; 16:31-43. [PMID: 31556011 DOI: 10.1007/s12519-019-00313-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 08/29/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Juvenile dermatomyositis (JDM) is a chronic autoimmune disease characteristic by inflammation of small vessels within the skin, muscle and vital organs. But the clinical features and treatment of JDM have not been fully clarified. DATA SOURCES Databases underwent through PubMed for articles about the clinical features, myositis-specific antibodies of JDM and its treatment, and we selected publications written in English which were relevant to the topic of this review. RESULTS Clinical features and myositis-specific antibodies may predict the severity and prognosis of disease. Although the mortality rate has been lower with traditional treatments, such as corticosteroid, intravenous immunoglobulin, and disease-modifying anti-rheumatic drugs such as methotrexate, their usages are variable. Novel biological therapies seem to be effective for refractory JDM patients, but more clinical trials are necessary. CONCLUSIONS JDM is a sever disease of childhood. We need to better understand recent advances of JDM in the context of clinical features including skin manifestations, muscle weakness and organ damage, myositis-specific antibodies and their associated outcomes and the treatment of disease.
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Affiliation(s)
- Jian-Qiang Wu
- Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Mei-Ping Lu
- Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Ann M Reed
- Department of Pediatrics, Division of Pediatric Rheumatology, Duke University School of Medicine, Durham, 27710, USA.
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Chung M, Chung L. Management of Calcinosis Associated with Dermatomyositis. CURRENT TREATMENT OPTIONS IN RHEUMATOLOGY 2019. [DOI: 10.1007/s40674-019-00134-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Eleryan MG, Awosika O, Akhiyat S, Qureshi A, Rengifo-Pardo M, Curiel R, Rider LG, Ehrlich A. Treatment of calcinosis associated with adult and juvenile dermatomyositis using topical sodium thiosulfate via fractionated CO2 laser treatment. Clin Exp Rheumatol 2019; 37:1092-1093. [PMID: 31796160 PMCID: PMC7108296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Accepted: 06/11/2018] [Indexed: 06/10/2023]
Affiliation(s)
- Misty G Eleryan
- The George Washington University School of Medicine and Health Sciences, and Department of Dermatology, George Washington Medical Faculty Associates, Washington DC, USA
| | - Olabola Awosika
- Department of Dermatology, George Washington Medical Faculty Associates, Washington DC, USA
| | - Sophia Akhiyat
- The George Washington University School of Medicine and Health Sciences, Washington DC, USA
| | - Azam Qureshi
- Department of Dermatology, George Washington Medical Faculty Associates, Washington DC, USA
| | - Monica Rengifo-Pardo
- The George Washington University School of Medicine and Health Sciences, and Department of Dermatology, George Washington Medical Faculty Associates, Washington DC, USA
| | - Rodolfo Curiel
- The George Washington University School of Medicine and Health Sciences, and Department of Dermatology, George Washington Medical Faculty Associates, Washington DC, USA
| | - Lisa G Rider
- Department of Dermatology and Division of Rheumatology, Department of Medicine, George Washington Medical Faculty Associates, Washington DC, USA
| | - Alison Ehrlich
- The George Washington University School of Medicine and Health Sciences, Washington DC, USA.
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40
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Neely J, Long CS, Sturrock H, Kim S. Association of Short-Term Ultraviolet Radiation Exposure and Disease Severity in Juvenile Dermatomyositis: Results From the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry. Arthritis Care Res (Hoboken) 2019; 71:1600-1605. [PMID: 30714338 DOI: 10.1002/acr.23840] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 01/29/2019] [Indexed: 01/06/2023]
Abstract
OBJECTIVE Ultraviolet (UV) radiation is considered to be an important environmental factor in the clinical course of children with juvenile dermatomyositis (DM). We aimed to evaluate the association between UV radiation and severe disease outcomes in juvenile DM. METHODS This is a cross-sectional study of patients with juvenile DM enrolled in the US multicenter Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry from 2010 to 2015. The mean UV index (UVI) in the calendar month prior to symptom onset in each subject's zip code was calculated from daily satellite solar noon measurements. Multivariable logistic regression was used to model the relationship between the mean UVI and calcinosis as well as other outcomes of severe disease. Covariates included sex, race, age, time to diagnosis, disease duration, and latitude. RESULTS In a multivariable model, there was no association between the mean UVI and calcinosis. African American race was associated with a 3-fold greater odds of calcinosis. However, there was a significant statistical interaction between race and mean UVI. Accounting for this interaction, the odds of calcinosis markedly decreased in African American subjects and steadily increased in non-African American subjects over a range of increasing the mean UVI. Higher mean UVI was associated with decreased odds of using biologics or nonmethotrexate disease-modifying antirheumatic drugs and skin ulceration. CONCLUSION We described a novel association between UV radiation, calcinosis, and race in a large cohort of patients with juvenile DM. This study furthers our knowledge of the role of UV radiation in the clinical course of juvenile DM and highlights the complex interplay between genes and environment in the clinical phenotypes and development of calcinosis in children with juvenile DM.
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Affiliation(s)
| | - Craig S Long
- National Oceanic and Atmospheric Administration, College Park, Maryland
| | | | - Susan Kim
- University of California, San Francisco
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Key Words
- CREST
- CREST, calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia
- IL, interleukin
- PDE-4, phosphodiesterase 4
- PTH, parathyroid hormone
- RA, rheumatoid arthritis
- apremilast
- cAMP, cyclic adenosine monophosphate
- calcinosis cutis
- dystrophic calcification
- limited scleroderma
- morphea
- persistent
- potential
- therapeutic substance
- treatment
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Affiliation(s)
- Sultan H Qiblawi
- Michigan State University College of Human Medicine, St. Joseph Mercy Health System Dermatology Residency Program, Ann Arbor, Michigan
| | - David P Fivenson
- Michigan State University College of Human Medicine, St. Joseph Mercy Health System Dermatology Residency Program, Ann Arbor, Michigan
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42
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Wakiguchi H. Multispecialty approach for improving outcomes in juvenile dermatomyositis. J Multidiscip Healthc 2019; 12:387-394. [PMID: 31213823 PMCID: PMC6549682 DOI: 10.2147/jmdh.s171095] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Accepted: 04/11/2019] [Indexed: 11/23/2022] Open
Abstract
Juvenile dermatomyositis (JDM) is a pediatric rheumatic disease characterized by inflammation of the muscle and skin. Prognosis of JDM in children has improved in general owing to medical progress; however, pathogenesis and management of JDM in children and prognosis in refractory JDM remain challenging. For elucidation of JDM pathophysiology and establishment of appropriate treatment for JDM, pediatric rheumatologists need to adopt a multispecialty approach that involves experts in genetics, immunology, pathology, musculoskeletal medicine, dermatology, pulmonology, cardiology, hematology, gastroenterology, endocrinology, ophthalmology, psychology, radiology, pharmacology, physiotherapy, surgery, preventive medicine, and adult rheumatology. Such collaborations will potentially lead to improved outcomes in children with JDM.
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Affiliation(s)
- Hiroyuki Wakiguchi
- Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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43
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Ciurtin C, Sin F, Hall-Craggs M, Sen D. Hard lumps under the skin. Assoc Med J 2019. [DOI: 10.1136/bmj.l2291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Baenas DF, Pirola JP, Benzaquén NR, Caeiro F, Álvarez AC, Saurit V, Retamozo S, Alvarellos A. Extensive calcinosis in adult dermatomyositis. REUMATOLOGIA CLINICA 2019; 15:121-123. [PMID: 28396153 DOI: 10.1016/j.reuma.2017.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Revised: 02/13/2017] [Accepted: 03/03/2017] [Indexed: 06/07/2023]
Affiliation(s)
- Diego Federico Baenas
- Servicio de Reumatología. Hospital Privado Universitario de Córdoba, Córdoba, Argentina.
| | - Juan Pablo Pirola
- Servicio de Reumatología. Hospital Privado Universitario de Córdoba, Córdoba, Argentina
| | | | - Francisco Caeiro
- Servicio de Reumatología. Hospital Privado Universitario de Córdoba, Córdoba, Argentina
| | - Ana Cecilia Álvarez
- Servicio de Reumatología. Hospital Privado Universitario de Córdoba, Córdoba, Argentina
| | - Verónica Saurit
- Servicio de Reumatología. Hospital Privado Universitario de Córdoba, Córdoba, Argentina
| | - Soledad Retamozo
- Servicio de Reumatología. Hospital Privado Universitario de Córdoba, Córdoba, Argentina
| | - Alejandro Alvarellos
- Servicio de Reumatología. Hospital Privado Universitario de Córdoba, Córdoba, Argentina
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Schempp CM, Schauer F, Huhn CK, Venhoff N, Finzel S. Hautentzündungen mit Arthritis, Synovitis und Enthesitis. Teil 2: Rheumatoide Arthritis, reaktive Arthritis, Morbus Reiter, Lyme-Borreliose, Dermatomyositis und Lupus erythematodes. J Dtsch Dermatol Ges 2019; 17:167-182. [DOI: 10.1111/ddg.13761_g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 01/16/2019] [Indexed: 11/29/2022]
Affiliation(s)
- Christoph M. Schempp
- Klinik für Dermatologie und Venerologie; Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
| | - Franziska Schauer
- Klinik für Dermatologie und Venerologie; Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
| | - Christian K. Huhn
- Klinik für Dermatologie und Venerologie; Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
| | - Nils Venhoff
- Klinik für Rheumatologie und klinische Immunologie; Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
| | - Stephanie Finzel
- Klinik für Rheumatologie und klinische Immunologie; Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg
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Zhong L, Yu Z, Song H. Association of anti-nuclear matrix protein 2 antibody with complications in patients with idiopathic inflammatory myopathies: A meta-analysis of 20 cohorts. Clin Immunol 2019; 198:11-18. [DOI: 10.1016/j.clim.2018.11.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 10/10/2018] [Accepted: 11/11/2018] [Indexed: 12/31/2022]
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Orandi AB, Dharnidharka VR, Al-Hammadi N, Baszis KW. Clinical phenotypes and biologic treatment use in juvenile dermatomyositis-associated calcinosis. Pediatr Rheumatol Online J 2018; 16:84. [PMID: 30594206 PMCID: PMC6311016 DOI: 10.1186/s12969-018-0299-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 12/10/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Few risk factors have been identified for the development of calcinosis among patients with Juvenile Dermatomyositis, and currently no clinical phenotype has been associated with its development. We analyzed a large database of patients to further elucidate any relationships among patients with and without calcinosis. METHOD The CARRA legacy registry recruited pediatric rheumatology patients from 55 centers across North America from 2010 through 2014, including over 650 subjects with Juvenile Dermatomyositis. We compared the demographic characteristics, clinical disease features and treatment histories of those with and without calcinosis using univariate and multivariate logistic regression. RESULTS Of the 631 patients included in the analysis, 84 (13%) had a current or prior history of calcinosis. These patients were statistically more likely to have longer durations of disease prior to diagnosis and treatment, have lipodystrophy and joint contractures, and to have received intravenous immune globulin or rituximab as treatments. CONCLUSIONS Calcinosis is found more often in patients with prolonged active disease, severe disease, and certain clinical features such as lipodystrophy and joint contractures. When these factors are combined with other known associations and predictors, groups of at-risk patients can be more effectively identified, treated and studied to improve overall outcomes.
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Affiliation(s)
- Amir B. Orandi
- 0000 0004 0459 167Xgrid.66875.3aDivision of Pediatric Rheumatology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55902 USA ,Division of Pediatric Rheumatology, Department of Pediatrics, St. Louis, MO USA
| | | | - Noor Al-Hammadi
- 0000 0001 2355 7002grid.4367.6Division of Biostatistics, Washington University School of Medicine, St. Louis, MO USA
| | - Kevin W. Baszis
- Division of Pediatric Rheumatology, Department of Pediatrics, St. Louis, MO USA
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Abstract
The juvenile idiopathic inflammatory myopathies (JIIM) are a group of rare, chronic, autoimmune illnesses that affect muscle and, to a lesser extent, skin. The presence of new-onset weakness and, in juvenile dermatomyositis, typical rahes, should lead to consideration of these diagnoses. Careful evaluation to exclude alternative diagnoses is needed. Investigations include a variety of blood tests, imaging, and possibly muscle biopsy. Validated clinical assessments are available for monitoring. Standard treatment includes corticosteroids and methotrexate and often extends beyond 1 year. Outcomes are generally good, but disease persistence remains problematic. Early involvement of providers with expertise in JIIM is essential.
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Affiliation(s)
- Adam M Huber
- Division of Pediatric Rheumatology, IWK Health Centre, Dalhousie University, 5850 University Avenue, Halifax, Nova Scotia B3K 6R8, Canada.
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49
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Radke J, Koll R, Preuße C, Pehl D, Todorova K, Schönemann C, Allenbach Y, Aronica E, de Visser M, Heppner FL, Weis J, Doostkam S, Maisonobe T, Benveniste O, Goebel HH, Stenzel W. Architectural B-cell organization in skeletal muscle identifies subtypes of dermatomyositis. NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION 2018. [PMID: 29520367 PMCID: PMC5840889 DOI: 10.1212/nxi.0000000000000451] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Objective To study the B-cell content, organization, and existence of distinct B-cell subpopulations in relation to the expression of type 1 interferon signature related genes in dermatomyositis (DM). Methods Evaluation of skeletal muscle biopsies from patients with adult DM (aDM) and juvenile DM (jDM) by histology, immunohistochemistry, electron microscopy, and quantitative reverse-transcription PCR. Results We defined 3 aDM subgroups—classic (containing occasional B cells without clusters), B-cell–rich, and follicle-like aDM—further elucidating IM B-lymphocyte maturation and immunity. The quantity of B cells and formation of ectopic lymphoid structures in a subset of patients with aDM were associated with a specific profile of cytokines and chemokines involved in lymphoid neogenesis. Levels of type 1 interferon signature related gene expression paralleled B-cell content and architectural organization and link B-cell immunity to the interferon type I signature. Conclusion These data corroborate the important role of B cells in DM, highlighting the direct link between humoral mechanisms as key players in B-cell immunity and the role of type I interferon–related immunity.
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Affiliation(s)
- Josefine Radke
- Author affiliations are provided at the end of the article
| | - Randi Koll
- Author affiliations are provided at the end of the article
| | - Corinna Preuße
- Author affiliations are provided at the end of the article
| | - Debora Pehl
- Author affiliations are provided at the end of the article
| | | | | | - Yves Allenbach
- Author affiliations are provided at the end of the article
| | | | | | | | - Joachim Weis
- Author affiliations are provided at the end of the article
| | | | | | | | | | - Werner Stenzel
- Author affiliations are provided at the end of the article
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Abstract
Juvenile dermatomyositis (JDM) is a rare autoimmune disease mainly characterized by muscle and skin involvement. Vasculopathy is considered central to the pathogenesis of the disease. The exact nature of vasculopathy is not yet understood but it is a complex process with both an inflammatory and a non-inflammatory, occlusive component. Impaired function of JDM vasculature includes immune complex deposition, altered expression of cell adhesion molecules predominantly inducing Th17 cell infiltration, and endothelial cell dysfunction. Development of vasculopathy is associated with the severe extra-muscular manifestations of JDM, such as gastrointestinal and cardiac manifestations, interstitial lung disease, ulcerative skin disease or development of calcinosis, and portends a poor prognosis. Correlation of histopathological findings, autoantibodies, and extensive diagnostic workup represent key elements to the early detection of vasculopathic features and early aggressive treatment. Monitoring of vasculopathy remains challenging due to the lack of non-invasive biomarkers. Current treatment approaches provide variable benefit, but better understanding of the essential pathogenic mechanisms should help lead to improved outcomes. Whilst acknowledging that evidence is limited, this review aims to describe the vasculopathy of JDM in the context of pathophysiology, clinical features, and treatment of disease.
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Affiliation(s)
- Charalampia Papadopoulou
- Infection, Inflammation, and Rheumatology Section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.,Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom
| | - Liza J McCann
- Department of Pediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom
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