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Xu XM, Ye S, Jin YY, Liu CX, Bao SF, Huang H, Ding F, Yang Z, Jin YL. Anti-nuclear matrix protein 2 antibody-associated juvenile dermatomyositis with gastrointestinal perforations was successfully treated with traditional therapeutic drugs combined with vedolizumab: a case report after a long-term follow-up and a review of the literature. Front Pediatr 2025; 12:1522559. [PMID: 39902228 PMCID: PMC11788329 DOI: 10.3389/fped.2024.1522559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 12/26/2024] [Indexed: 02/05/2025] Open
Abstract
Gastrointestinal perforation in patients with juvenile dermatomyositis has been reported as a life-threatening complication in the literature. However, effective treatment of juvenile dermatomyositis with gastrointestinal perforation remains challenging. We report the case of a patient who developed intestinal perforation 5 months after being diagnosed with anti-nuclear matrix protein 2 antibody-positive juvenile dermatomyositis. We systematically reviewed the literature on the medical and/or surgical treatment of gastrointestinal perforation in juvenile dermatomyositis. In addition to our case, as of October 2023, we identified 29 cases of gastrointestinal perforation in patients with juvenile dermatomyositis. Current treatment options for gastrointestinal perforation in juvenile dermatomyositis mainly include corticosteroids, methylprednisolone pulses, rituximab, intravenous immunoglobulin, cyclophosphamide, methotrexate, cyclosporine A, mycophenolate mofetil, and other traditional disease-modifying anti-rheumatic drugs. Notably, juvenile dermatomyositis complicated by gastrointestinal perforation is always associated with disease severity and activity. However, these are extremely severe patients who may not respond to treatment with methylprednisolone pulses and rituximab. Given the limited efficacy of conventional high-intensity systemic immunosuppressive therapy for juvenile dermatomyositis with gastrointestinal perforation, there is an urgent need to explore novel therapeutic approaches. We report on the successful use of vedolizumab in combination with corticosteroids, cyclophosphamide, and intravenous immunoglobulin as a novel therapeutic strategy for treating juvenile dermatomyositis complicated by gastrointestinal perforation. Importantly, up to now, there has been no report of juvenile dermatomyositis with gastrointestinal perforation treated with vedolizumab combined with traditional disease-modifying anti-rheumatic drugs in children.
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Affiliation(s)
- Xue-mei Xu
- Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Shuang Ye
- Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
| | - Ying-ying Jin
- Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chen-xi Liu
- Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Sheng-fang Bao
- Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hua Huang
- Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Fei Ding
- Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhen Yang
- Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yan-liang Jin
- Department of Rheumatology and Immunology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Adeva-Andany MM, Adeva-Contreras L, Fernandez-Fernandez C, Vila-Altesor M, Castro-Quintela E, Funcasta-Calderon R. Interferon Causes Endothelial Injury in Humans. Curr Rev Clin Exp Pharmacol 2025; 20:122-139. [PMID: 40326264 DOI: 10.2174/0127724328322183240922153629] [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: 05/07/2024] [Revised: 08/04/2024] [Accepted: 08/08/2024] [Indexed: 05/07/2025]
Abstract
Therapy with exogenous interferon and human conditions that feature endogenous interferon upregulation may be associated with endothelial damage that primarily involves small blood vessels. Endothelial injury associated with interferon may display different clinical expression, including thrombotic microangiopathy, Raynaud's phenomenon, vasculopathy of dermatomyositis and atrophic papulosis, interferon-associated skin angiopathy, systemic capillary leak syndrome, collapsing glomerulopathy, interstitial lung disease, pulmonary hypertension, and retinopathy. Interferon- induced endothelial damage involves complement-mediated injury, although pathogenic mechanisms by which interferon promote abnormal complement activation on endothelial cells are not fully understood. Human interferon-γ (type II interferon) binds to heparan sulfate on the endothelial surface, suggesting that overproduction of interferon-γ may hinder factor H attachment to the same location. Absence of factor H on self surfaces promotes activation of the alternative pathway of complement and complement-mediated endothelial damage. Type I interferon typically induces the generation of antibodies. Type I interferon upregulation may elicit the formation of autoantibodies against factor H. These autoantibodies block factor H binding to endothelial surfaces, abolishing the protective effect of factor H on complement-mediated damage. In addition, interferon induces insulin resistance which is associated with reduced heparan sulfate in the extracellular matrix, including the endothelial surface. Decreased amount of heparan sulfate suppresses factor H attachment, promoting activation of the alternative pathway of complement. Complement blockade with eculizumab (a monoclonal antibody against C5) improves endothelial damage in patients with thrombotic microangiopathy and other situations associated with interferon upregulation and interferon-induced endothelial injury, suggesting that complement-mediated injury is clinically relevant under conditions that feature interferon overproduction.
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Affiliation(s)
- Maria M Adeva-Andany
- Department of Internal Medicine, Hospital General Juan Cardona, c/ Pardo Bazán, s/n, Ferrol 15406, Spain
| | - Lucía Adeva-Contreras
- School of Medicine, Santiago de Compostela University, Santiago de Compostela, Spain
| | - Carlos Fernandez-Fernandez
- Department of Internal Medicine, Hospital General Juan Cardona, c/ Pardo Bazán, s/n, Ferrol 15406, Spain
| | - Matilde Vila-Altesor
- Department of Internal Medicine, Hospital General Juan Cardona, c/ Pardo Bazán, s/n, Ferrol 15406, Spain
| | - Elvira Castro-Quintela
- Department of Internal Medicine, Hospital General Juan Cardona, c/ Pardo Bazán, s/n, Ferrol 15406, Spain
| | - Raquel Funcasta-Calderon
- Department of Internal Medicine, Hospital General Juan Cardona, c/ Pardo Bazán, s/n, Ferrol 15406, Spain
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Xiangyuan C, Xiaoling Z, Guangchao S, Huasong Z, Dexin L. Juvenile dermatomyositis complications: navigating gastrointestinal perforations and treatment challenges, a case report. Front Pediatr 2024; 12:1419355. [PMID: 39070551 PMCID: PMC11272553 DOI: 10.3389/fped.2024.1419355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 07/01/2024] [Indexed: 07/30/2024] Open
Abstract
Juvenile dermatomyositis (JDM) is a rare autoimmune disorder with multi-system involvement, often presenting with a heliotrope rash, Gottron's papules, and proximal muscle weakness. JDM patients with anti-nuclear matrix protein 2 (anti-NXP2) positivity tend to have more severe manifestations, including a higher risk of gastrointestinal (GI) complications such as dysphagia, intestinal motility changes, edema, malabsorption, ulcers, and perforations. These complications are associated with poor outcomes and high mortality rates, particularly in patients with anti-NXP2 positivity. A case is presented of a 12-year-old girl with JDM who developed multiple GI perforations after being treated with high-dose methylprednisolone. Despite multiple surgical attempts, the patient experienced continued leakage and new perforations. The treatment approach was shifted to include jejunostomy, plasma exchanges, fresh frozen plasma support, and tofacitinib, leading to gradual improvement in muscle strength and reduction in inflammation. GI involvement in JDM is a significant concern due to its association with poor prognosis and high mortality. The use of high-dose glucocorticoids must be carefully considered in JDM patients with GI involvement, as they may contribute to the development of perforations and complicate treatment. A combination of plasma exchange, fresh frozen plasma support, low-dose glucocorticoids, and Janus kinase inhibitors may offer a safer treatment strategy for managing refractory JDM with GI complications. The case highlights the importance of a multidisciplinary approach to treatment and the need for further research to determine the necessity of high-dose glucocorticoid therapy following GI involvement in JDM.
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Affiliation(s)
- Chen Xiangyuan
- Department of Allergy, Immunology and Rheumatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Zeng Xiaoling
- Department of Allergy, Immunology and Rheumatology, Liuzhou Hospital, Guangzhou Women and Children’s Medical Center, Liuzhou, China
| | - Sun Guangchao
- Department of Allergy, Immunology and Rheumatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Zeng Huasong
- Department of Allergy, Immunology and Rheumatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Liu Dexin
- Department of Allergy, Immunology and Rheumatology, Liuzhou Hospital, Guangzhou Women and Children’s Medical Center, Liuzhou, China
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Ma O, Day J. Case report: Pneumatosis coli in an anti-TIF1-ɣ-positive dermatomyositis patient. Int J Rheum Dis 2024; 27:e15245. [PMID: 38937988 DOI: 10.1111/1756-185x.15245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 06/18/2024] [Indexed: 06/29/2024]
Affiliation(s)
- Ocean Ma
- Melbourne University, Parkville, Melbourne, Victoria, Australia
| | - Jessica Day
- Melbourne University, Parkville, Melbourne, Victoria, Australia
- Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia
- Walter and Eliza Hall Medical Research Institute, Parkville, Melbourne, Victoria, Australia
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Li ZG, Zhou JM, Li L, Wang XD. Malignant atrophic papulosis: Two case reports. World J Clin Cases 2022; 10:12971-12979. [PMID: 36569027 PMCID: PMC9782946 DOI: 10.12998/wjcc.v10.i35.12971] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 08/16/2022] [Accepted: 11/18/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Malignant atrophic papulosis is a rare and potentially lethal thrombo-occlusive microvasculopathy characterized by cutaneous papules and gastrointestinal perforation. The precise pathogenesis of this disease remains obscure.
CASE SUMMARY We describe the case of a 67-year-old male patient who initially presented with cutaneous aubergine papules and dull pain in the epigastrium. One week after symptom onset, he was admitted to the hospital for worsening abdominal pain. Exploratory laparotomy showed patchy necrosis and subserosal white plaque lesions on the small intestinal wall, along with multiple perforations. Histological examination of the small intestine showed extensive hyperemia, edema, necrosis with varying degrees of inflammatory reactions in the small bowel wall, small vasculitis with fibrinoid necrosis and intraluminal thrombosis in the mesothelium. Based on the mentioned evidence, a diagnosis of malignant atrophic papulosis was made. We also present the case of a 46-year-old man with known cutaneous manifestations, abdominal pain, nausea and vomiting. His physical examination showed positive rebound tenderness. A computed tomography scan revealed free intraperitoneal air. He required surgical intervention on admission and then developed an esophageal perforation. He ultimately died of a massive hemorrhage.
CONCLUSION In previously published cases of this disease, the cutaneous lesions initially appeared as small erythematous papules. Subsequently, the papules became porcelain-white atrophic depression lesions with a pink, telangiectatic peripheral rim. In one of the patients, the cutaneous lesions appeared as aubergine papules. The other patient developed multiple perforations in the gastrointestinal tract. Due to malignant atrophic papulosis affecting multiple organs, many authors speculated that it is not a specific entity. This case series serves as additional evidence for our hypothesis.
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Affiliation(s)
- Zhi-Gui Li
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Ming Zhou
- Department of Clinical Medicine, West China School of Medicine, Sichuan University, Chengdu 610207, Sichuan Province, China
| | - Li Li
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Dong Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Ai W, Liang Z, Li F, Yu H. Degos disease with multiple intestinal perforations: A missed-opportunity case report and literature review. Front Cardiovasc Med 2022; 9:910288. [PMID: 36324742 PMCID: PMC9618646 DOI: 10.3389/fcvm.2022.910288] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 09/30/2022] [Indexed: 11/13/2022] Open
Abstract
Introduction Degos disease, also known as malignant atrophic papulosis (MAP), is a rare systemic obstructive vascular disease with unknown pathophysiology, which can affect multiple systems, especially gastrointestinal tract and central nervous system. Intestinal perforations with MAP is associated with high mortality rate and ambiguous treatment outcomes. Case presentation Here we report a missed-opportunity case of Degos disease characterized by generalized skin eruption and multiple intestinal perforations. Definite diagnosis of Degos disease was finally concluded after two exploratory laparotomy operations and skin biopsies. Due to the delayed diagnosis and treatment, the patient died after being discharged automatically in spite of application of aspirin and low-dose subcutaneous heparin. In view of such circumstances, we searched the Pubmed using “Degos [Title] OR Malignant Atrophic Papulosis [Title]” AND “perforation [Title] OR perforations [Title]” and make a detailed analysis of the result. Conclusions Degos disease is a rare systemic obstructive vascular disease with unknown pathologic mechanism and unavailable treatment methods. Diagnosis is usually based on the presence of pathognomonic skin lesions and tissue biopsy. Gastrointestinal involvement can cause serious and lethal conditions with high mortality. Currently, how to achieve a satisfying prognosis of MAP with intestinal perforations becomes the most urgent problem in front of medical staff.
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Gastrointestinal Involvement in Dermatomyositis. Diagnostics (Basel) 2022; 12:diagnostics12051200. [PMID: 35626355 PMCID: PMC9139828 DOI: 10.3390/diagnostics12051200] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/27/2022] [Accepted: 05/09/2022] [Indexed: 01/27/2023] Open
Abstract
Dermatomyositis is a systemic vasculopathy mainly affecting skin, muscle and lung, but may affect the gastrointestinal tract. We aim to describe clinical characteristics of patients with severe gastrointestinal involvement related to dermatomyositis in our center and medical literature. We retrospectively analysed these patients in our center, including cases of erosions/ulcers, perforation or digestive bleeding. Reported cases from April 1990 to April 2021 were reviewed through PubMed and Cochrane. From our cohort (n = 188), only 3 presented gastrointestinal compromise. All were women (10, 46 and 68 years). The initial symptom was abdominal pain and all had ≥2 episodes of digestive bleeding. All died due to complications of gastrointestinal involvement. Available pathological samples showed vascular ectasia. From the literature review (n = 50), 77% were women with a mean age of 49 years and the main symptom was abdominal pain (65%). All presented active muscular and cutaneous involvement at complication diagnosis. Mortality was 41.7%. The underlying lesion was perforation or ulcer (n = 22), intestinal wall thickening (n = 2), macroscopic inflammation (n = 2) or intestinal pneumatosis (n = 15). In 13 cases, vasculitis was described. Gastrointestinal involvement in dermatomyositis denotes severity, so an early intensive treatment is recommended. Pathological findings suggest that the underlying pathophysiological mechanism is a vasculopathy and not a true vasculitis.
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Huang J, Huang J, Li Y, Wang Y, Wang F, Qiu X, Liu X, Li H. Sodium Alginate Modulates Immunity, Intestinal Mucosal Barrier Function, and Gut Microbiota in Cyclophosphamide-Induced Immunosuppressed BALB/c Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:7064-7073. [PMID: 34152142 DOI: 10.1021/acs.jafc.1c02294] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/19/2023]
Abstract
This study investigated the protective effects of sodium alginate (SA) on the gut microbiota, immunity, and intestinal mucosal barrier function in cyclophosphamide-induced immunosuppressed BALB/c mice. SA alleviated spleen tissue damage and restored impaired immune functions, such as increasing the immune organ index, decreasing splenic T lymphocytes, and markedly increasing the secretion of serum immunoglobulins and cytokines in immunosuppressed mice. In addition, SA reversed the intestinal mucosal injury and increased the intestinal permeability by upregulating the expression of tight junction proteins. Moreover, SA decreased gut inflammation by reducing serum d-lactic acid (D-LA) and lipopolysaccharide (LPS) concentrations and downregulating toll-like receptor 4 (Tlr4) and mitogen-activated protein kinase (Mapk) pathway expression. Furthermore, SA significantly increased the abundance of beneficial bacteria (Lactobacillus, Roseburia, and Lachnospiraceae NK4A136) and decreased pathogenic bacteria (Helicobacter, Peptococcus, and Tyzzerella) in the intestine as determined by 16S rRNA gene high-throughput sequencing. In conclusion, our study provides a scientific basis for SA as a functional food in modulating gut microbiota and protecting against intestinal mucosal injury and indicates that SA has potential application for enhancing immunity.
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Affiliation(s)
- Juan Huang
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, 116044 Dalian, PR China
| | - Jinli Huang
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, 116044 Dalian, PR China
| | - Yao Li
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, 116044 Dalian, PR China
| | - Yilu Wang
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, 116044 Dalian, PR China
| | - Fahe Wang
- State Key Laboratory of Bioactive Seaweed Substances, Qingdao Bright Moon Seaweed Group Co.,, Ltd., 266400 Qingdao, PR China
| | - Xia Qiu
- State Key Laboratory of Bioactive Seaweed Substances, Qingdao Bright Moon Seaweed Group Co.,, Ltd., 266400 Qingdao, PR China
| | - Xvliang Liu
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, 116044 Dalian, PR China
| | - Huajun Li
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, 116044 Dalian, PR China
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Doudouliaki T, Papadopoulou C, Deakin CT. Use of Rescue Therapy with IVIG or Cyclophosphamide in Juvenile Myositis. Curr Rheumatol Rep 2021; 23:24. [PMID: 33686540 DOI: 10.1007/s11926-021-00990-3] [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] [Accepted: 01/20/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW This review aims to present the literature available to date on the use of intravenous immunoglobulin and cyclophosphamide for juvenile patients with inflammatory myopathies, to evaluate the strength of the evidence so far for both these medications, and to reach conclusions about their efficacy. RECENT FINDINGS Juvenile idiopathic inflammatory myopathies, mainly represented by juvenile dermatomyositis (JDM), are rare diseases but quite debilitating for the patients. JDM is an autoimmune condition with predominantly muscle and skin involvement but also systemic features affecting the cardiovascular, respiratory, and gastrointestinal systems. The mainstay therapy is based on corticosteroids and methotrexate, but often other therapeutic alternatives are sought for patients with severe or refractory disease. The rarity of these conditions makes research for new medications even more challenging. Innovative trial designs or statistical methods can be used to emulate a randomized study and investigate drug effectiveness. Despite the lack of Level I evidence on the use and efficacy of intravenous immunoglobulin and cyclophosphamide, their use is advocated by a substantial number of case reports and case series as well as analyses using marginal structural models.
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Affiliation(s)
- Theonymfi Doudouliaki
- Department of Rheumatology, Great Ormond Street Hospital NHS Foundation Trust, London, UK
| | - Charalampia Papadopoulou
- Department of Rheumatology, Great Ormond Street Hospital NHS Foundation Trust, London, UK
- Infection, Immunity and Inflammation Research and Teaching Department, UCL, Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
| | - Claire T Deakin
- Infection, Immunity and Inflammation Research and Teaching Department, UCL, Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
- Centre for Adolescent Rheumatology Versus Arthritis at UCL, UCLH and GOSH, London, UK.
- NIHR Biomedical Research Centre at Great Ormond Street Hospital, London, UK.
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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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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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