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1
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Rose J. Autoimmune Connective Tissue Diseases: Systemic Lupus Erythematosus and Rheumatoid Arthritis. Rheum Dis Clin North Am 2025; 51:347-359. [PMID: 40246444 DOI: 10.1016/j.rdc.2025.01.008] [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] [Indexed: 04/19/2025]
Abstract
Systemic lupus erythematosus and rheumatoid arthritis are just 2 of several autoimmune connective tissue diseases that are primarily chronic in nature but can present to the emergency department by virtue of an acute exacerbation of disease. Beyond an acute exacerbation of disease, their predilection for invading multiple organ systems lends itself to the potential for patients presenting to the emergency department with either a single or isolated symptom or a myriad of signs and/or symptoms indicative of a degree of disease complexity and severity that warrant timely recognition and resuscitation.
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Affiliation(s)
- Jonathan Rose
- Department of Emergency Medicine, Memorial Healthcare System, Memorial Hospital West, 703 N Flamingo Road, Pembroke Pines, FL 33028, USA.
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2
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Saeki K, Nakagama H, Tanaka Y, Goto Y, Kaneshiro K, Kono H, Yanai K, Yamamoto H, Yoneda R, Shimakawa T, Ueki T. Rectum necrosis in a patient with severe COVID19 infection after CAR-T therapy: a case report. Surg Case Rep 2024; 10:227. [PMID: 39325308 PMCID: PMC11427651 DOI: 10.1186/s40792-024-02026-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 09/14/2024] [Indexed: 09/27/2024] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID19) can cause gastrointestinal complications as well as respiratory tract disease. Coagulation abnormalities and thrombosis frequently occur in COVID19, especially in cases with severe clinical outcome. The relationship between gastrointestinal perforation and coagulopathy due to COVID19 remains unclear. CASE PRESENTATION A 49-year-old female received Chimeric antigen receptor T (CAR-T) therapy for an early recurrence of diffuse large B-cell lymphoma (DLBCL) that was refractory to chemotherapy. She was diagnosed with cytokine release syndrome (CRS) because of a fever and oxygen desaturation, and administered tocilizumab. Forty days after completing CAR-T therapy, she was infected with COVID19 and transferred to our hospital. Her general condition worsened and she developed COVID19 pneumonia, and then steroid pulse therapy was started. While her respiratory condition improved, she experienced pain in the anal region and computed tomography (CT) revealed a rectal perforation. An emergency surgery was undertaken, and the lower rectum wall was found to be completely necrotic. Removal of the necrotic part of the rectum tissue, and drainage and lavage of necrotic tissue in the pelvic cavity were performed. The remaining rectum was resected with partial sigmoidectomy, but we could not make the anal stump closed. In addition, an end colostomy in the sigmoid colon was performed. Histopathological findings showed thromboses in the rectal mesentery veins. After the first surgery, the pelvic abscess cavity persisted and her high-grade fever continued. Reoperation was laparoscopically performed, and she underwent a resection of anal canal with residual necrotic rectal and mesorectal tissue, and a drainage of the pelvic abscess. After the reoperation, her general condition improved and CT showed that the abscess cavity had significantly improved. CONCLUSIONS Gastrointestinal perforation, especially rectal necrosis due to coagulopathy caused by severe COVID19 infection, is a rare but life-threatening complication. Physicians should have a high degree of clinical suspicion for timely diagnosis and management, and surgical intervention is necessary in cases of rectal necrosis.
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Affiliation(s)
- Kiyoshi Saeki
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan.
| | - Hidenobu Nakagama
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Yuichi Tanaka
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Yoshitaka Goto
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Kazuhisa Kaneshiro
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Hiroshi Kono
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Kosuke Yanai
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Hirofumi Yamamoto
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
| | - Reiko Yoneda
- Department of Pathology, Hamanomachi General Hospital, Fukuoka, Japan
| | - Takashi Shimakawa
- Department of Hematology, Hamanomachi General Hospital, Fukuoka, Japan
| | - Takashi Ueki
- Department of Surgery, Hamanomachi General Hospital, 3-3-1, Nagahama, Fukuoka, 810-8539, Japan
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Hoisnard L, Meyer A, Dray-Spira R, Weill A, Zureik M, Sbidian E. Risk of Gastrointestinal Perforation in Patients With Rheumatic Diseases Exposed to Janus Kinase Inhibitors Versus Adalimumab: A Nationwide Cohort Study. Arthritis Rheumatol 2024; 76:1364-1376. [PMID: 38699822 DOI: 10.1002/art.42862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 03/20/2024] [Accepted: 04/11/2024] [Indexed: 05/05/2024]
Abstract
OBJECTIVE To compare the risk of gastrointestinal perforation (GIP), a rare but serious adverse event, in patients who a JAK inhibitor (JAKi; tofacitinib, baricitinib, upadacitinib, or filgotinib) versus adalimumab (tumor necrosis factor inhibitor) among a comprehensive real-world population of patients with rheumatic diseases. METHODS We conducted a nationwide population-based cohort study of the French national health data system, the exposed group that received a JAKi and the comparison group adalimumab. We included all individuals with a rheumatic disease who had their first dispensation of these treatments from July 2017 to December 2021. The primary endpoint was the occurrence of GIP (end of follow-up May 2022). Weighted hazard ratios (wHRs) were estimated with the inverse probability of treatment weighting method to account for confounding factors. Concomitant administration of systemic glucocorticoids, nonsteroidal anti-inflammatory drugs, and proton-pump inhibitors were time-varying variables. RESULTS The cohort included 39,758 patients: 12,335 and 27,423 in the groups that received a JAKi and adalimumab (mean age 58.2 and 47.3 years; female 76% and 58%; rheumatoid arthritis 85.3% and 27.3%, and psoriatic arthritis/axial spondyloarthritis 14.7% and 72.7%), respectively. During follow-up, 38 and 42 GIPs occurred in the groups that received a JAKi and adalimumab groups; incidence rates were 2.1 (95% confidence interval [CI] 1.5-2.8) and 1.1 (95% CI 0.8-1.5) per 1,000 person-years, respectively. Rates of GIP did not differ between the groups that received a JAKi and adalimumab: wHR 1.1 (95% CI 0.7-1.9; P = 0.65). Despite the lack of power in some subgroup analyses, results were consistent whatever the subgroup of a type of JAKi received or subgroup with a type of rheumatic disease. CONCLUSION In this nationwide cohort study, the rates of GIPs did not differ between groups of patients who received JAKi and adalimumab treatment. These results need to be confirmed in other observational studies.
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Affiliation(s)
- Lea Hoisnard
- Henri Mondor Hospital, INSERM, and Paris Est Créteil University, Créteil, France
| | - Antoine Meyer
- French National Agency for Medicines and Health Products Safety, Saint-Denis, France, and Bicêtre University Hospital, Paris-Saclay University, Le Kremlin Bicêtre, France
| | - Rosemary Dray-Spira
- French National Agency for Medicines and Health Products Safety, Saint-Denis, France
| | - Alain Weill
- French National Agency for Medicines and Health Products Safety, Saint-Denis, France
| | - Mahmoud Zureik
- French National Agency for Medicines and Health Products Safety, Saint-Denis, France
| | - Emilie Sbidian
- Henri Mondor Hospital, Créteil, France, INSERM, Créteil, France, Paris Est Créteil University, Créteil, France, French National Agency for Medicines and Health Products Safety, Saint-Denis, France, Le Kremlin Bicêtre, France
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Fujimoto S, Eriguchi Y, Nakamura R, Kamikawa S, Yonekawa A, Miyake N, Ono N, Niiro H. Streptococcal toxic shock syndrome due to Streptococcus dysgalactiae subsp. equisimilis from retroperitoneal panniculitis during the treatment with anti-IL-6 receptor antibody: A case report. Mod Rheumatol Case Rep 2024; 8:255-258. [PMID: 38217091 DOI: 10.1093/mrcr/rxae001] [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: 10/26/2023] [Revised: 12/18/2023] [Accepted: 12/28/2023] [Indexed: 01/15/2024]
Abstract
A 53-year-old man with adult-onset Still's disease developed severe streptococcal toxic shock syndrome (STSS) due to Streptococcus dysgalactiae subsp. equisimilis (SDSE), following retroperitoneal panniculitis. He was receiving tocilizumab (TCZ), an interleukin-6 receptor inhibitor. The modifying effect of TCZ on the immune response and the pathophysiology of SDSE infection may have led to retroperitoneal panniculitis and atypical STSS with delayed shock and flare of soft tissue inflammation.
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MESH Headings
- Humans
- Shock, Septic/etiology
- Shock, Septic/drug therapy
- Shock, Septic/diagnosis
- Shock, Septic/microbiology
- Male
- Middle Aged
- Streptococcal Infections/diagnosis
- Streptococcal Infections/drug therapy
- Streptococcal Infections/complications
- Streptococcal Infections/microbiology
- Panniculitis/diagnosis
- Panniculitis/etiology
- Panniculitis/microbiology
- Panniculitis/drug therapy
- Streptococcus/immunology
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antibodies, Monoclonal, Humanized/adverse effects
- Still's Disease, Adult-Onset/diagnosis
- Still's Disease, Adult-Onset/complications
- Still's Disease, Adult-Onset/drug therapy
- Receptors, Interleukin-6/antagonists & inhibitors
- Treatment Outcome
- Retroperitoneal Space
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Affiliation(s)
- Sho Fujimoto
- Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital, Fukuoka, Japan
| | - Yoshihiro Eriguchi
- Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital, Fukuoka, Japan
| | - Rinto Nakamura
- Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital, Fukuoka, Japan
| | - Sota Kamikawa
- Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital, Fukuoka, Japan
| | - Akiko Yonekawa
- Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital, Fukuoka, Japan
| | - Noriko Miyake
- Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital, Fukuoka, Japan
| | - Nobuyuki Ono
- Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University Hospital, Fukuoka, Japan
| | - Hiroaki Niiro
- Department of Medical Education, Faculty of Medical Sciences, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
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5
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Xu JB. Correlation between fasting time and bleeding, infection, and perforation after high-frequency electroresection of polyps under colonoscopy. Shijie Huaren Xiaohua Zazhi 2023; 31:973-980. [DOI: 10.11569/wcjd.v31.i23.973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/14/2023] [Accepted: 11/27/2023] [Indexed: 12/08/2023] Open
Abstract
BACKGROUND Endoscopic mucosal resection (EMR) is a common method for treating colorectal polyps. The duration of fasting after the operation has been the focus of clinical attention. However, there is currently a lack of research on the correlation between fasting duration and the occurrence of bleeding, infection, and perforation.
AIM To explore the relationship between fasting time and bleeding, infection, and perforation after colonoscopic electro-resection of polyps to provide guidance on fasting strategies for postoperative patients.
METHODS In a cohort of 14857 colorectal polyp patients admitted to the Second People's Hospital of Luqiao District from 2000 to 2023, a case-control study design with matching propensity scores was used to evaluate the risk of bleeding and perforation after polypectomy in adults aged 40 years and older; 3505 patients with short-term postoperative fasting and 9669 patients with prolonged postoperative fasting met the study criteria. A total of 2560 patients in each group were matched for further analysis. The postoperative fasting time of the experimental group was 2 h, and the postoperative fasting time of the control group was 24 h. The liquid food was gradually replaced with semi-liquid food and ordinary food according to the size of the incision and the effect of the operation. The postoperative follow-up duration was 1 mo, and the incidence of postoperative bleeding, infection, and perforation in both groups was recorded.
RESULTS In the short fasting group, the rates of bleeding, infection, and perforation were 0.64%, 0.07%, and 0.07%, respectively. In the long fasting group, the rates of bleeding, infection, and perforation were 0.40%, 0.04%, and 0.04%, respectively. There was no significant difference between the two groups in terms of the rates of bleeding, infection, and perforation.
CONCLUSION Based on these results, it can be preliminarily concluded that the duration of postoperative fasting may not have a significant effect on the incidence of bleeding, infection, and perforation after colonoscopic high-frequency electroresection of polyps. For choosing fasting time, strategies can be developed according to the specific situation and actual needs of the patient. However, it is important to note that this is only a retrospective study and more clinical studies are needed to further validate our findings and explore other possible influencing factors.
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Affiliation(s)
- Jun-Bin Xu
- Department of Gastroenterology, The Second People's Hospital of Luqiao District, Taizhou 318058, Zhejiang Province, China
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6
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Rose J. Autoimmune Connective Tissue Diseases: Systemic Lupus Erythematosus and Rheumatoid Arthritis. Immunol Allergy Clin North Am 2023; 43:613-625. [PMID: 37394263 DOI: 10.1016/j.iac.2022.10.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/04/2023]
Abstract
Systemic lupus erythematosus and rheumatoid arthritis are just 2 of several autoimmune connective tissue diseases that are primarily chronic in nature but can present to the emergency department by virtue of an acute exacerbation of disease. Beyond an acute exacerbation of disease, their predilection for invading multiple organ systems lends itself to the potential for patients presenting to the emergency department with either a single or isolated symptom or a myriad of signs and/or symptoms indicative of a degree of disease complexity and severity that warrant timely recognition and resuscitation.
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Affiliation(s)
- Jonathan Rose
- Department of Emergency Medicine, Memorial Healthcare System, Memorial Hospital West, 703 N Flamingo Road, Pembroke Pines, FL 33028, USA.
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7
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Brooks SN, Brown T, Yeary C. Extrapulmonary COVID-19 Presents As Spontaneous Small Bowel Perforation. Cureus 2023; 15:e35524. [PMID: 37007414 PMCID: PMC10054185 DOI: 10.7759/cureus.35524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/26/2023] [Indexed: 03/02/2023] Open
Abstract
SARS-CoV2 is a well-recognized pathogen with a myriad of presenting symptoms. Well-documented pulmonary, neurological, gastrointestinal, and hematologic complications have occurred during the global COVID-19 pandemic. While gastrointestinal symptoms are the most commonly reported extrapulmonary symptom of COVID-19, the incidence of primary perforation has not been widely reported. In this case report, we describe a spontaneous small bowel perforation in a patient who was incidentally found to be COVID-19 positive. This peculiar case underlies the continued evolution of SARS-CoV2 understanding and potential unknown complications of the virus.
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8
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Moroz EV, Popkova TV, Moroz AE. Manifestations of the gastrointestinal tract in systemic rheumatic diseases: A narrative review. RHEUMATOLOGY SCIENCE AND PRACTICE 2022. [DOI: 10.47360/1995-4484-2022-578-586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Gastrointestinal disorders are important place among the visceral manifestations of systemic autoimmune and immunoinflammatory rheumatic diseases (RD). Pathology of the esophagus, stomach, small and large intestine can vary from moderate functional disorders to the development of severe chronic inflammation with metaplasia and dysplasia of the mucous membrane, the formation of multiple erosions, hemorrhages and deep ulcers. Complications of gastrointestinal pathology in RD, such as bleeding, perforations and strictures, can cause death. This review examines the main clinical manifestations, possibilities of diagnosis and treatment of gastrointestinal lesions in systemic scleroderma, idiopathic inflammatory myopathies, systemic vasculitis, Sjogren’s syndrome and disease, as well as systemic lupus erythematosus.
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Affiliation(s)
- E. V. Moroz
- Main Military Clinical Hospital named after N.N. Burdenko
| | | | - A. E. Moroz
- V.A. Nasonova Research Institute of Rheumatology
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9
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Chang TC, Kan WC, Cheng KC, Ho CH, Chen YC, Chu CC, Hsu CC, Kuo HT, Lin HJ, Huang CC. Comparison of the risk of gastrointestinal perforation between patients with and without rheumatoid arthritis: A nationwide cohort study in Asia. Front Med (Lausanne) 2022; 9:974328. [PMID: 36250072 PMCID: PMC9556734 DOI: 10.3389/fmed.2022.974328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 09/13/2022] [Indexed: 11/24/2022] Open
Abstract
Objectives Patients with rheumatoid arthritis (RA) may have an increased risk for gastrointestinal perforation (GIP) caused by medications or chronic inflammation. However, the risk of GIP between patients with and without RA remains unclear. Therefore, we conducted this study to clarify it. Methods Using the Taiwan National Health Insurance Research Database, we identified patients with and without RA matched at 1:1 ratio by age, sex, and index date between 2000 and 2013 for this study. Comparison of the risk of GIP between the two cohorts was performed by following up until 2014 using Cox proportional hazard regression analyses. Results In total, 11,666 patients with RA and an identical number of patients without RA were identified for this study. The mean age (±standard deviation) and female ratio were 55.3 (±15.2) years and 67.6% in both cohorts. Patients with RA had a trend of increased risk for GIP than patients without RA after adjusting for underlying comorbidities, medications, and monthly income [adjusted hazard ratio (AHR) 1.42; 95% confidence interval (CI) 0.99–2.04, p = 0.055]. Stratified analyses showed that the increased risk was significant in the female population (AHR 2.06; 95% CI 1.24–3.42, p = 0.005). Older age, malignancy, chronic obstructive pulmonary disease, and alcohol abuse were independent predictors of GIP; however, NSAIDs, systemic steroids, and DMARDs were not. Conclusion RA may increase the risk of GIP, particularly in female patients. More attention should be paid in female population and those with independent predictors above for prevention of GIP.
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Affiliation(s)
- Ting-Chia Chang
- Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Wei-Chih Kan
- Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan
| | - Kuo-Chen Cheng
- Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Chung-Han Ho
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
- Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan
| | - Yi-Chen Chen
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Chin-Chen Chu
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Chien-Chin Hsu
- Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Hsing-Tao Kuo
- Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Hung-Jung Lin
- Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan
- Department of Emergency Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chien-Cheng Huang
- Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan
- Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- *Correspondence: Chien-Cheng Huang
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10
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Chaugale SB, Singhal V, Kapoor D, Singh A. Gastrointestinal complications (gangrene or perforation) after corona virus disease 2019 - A series of ten patients. Indian J Gastroenterol 2022; 41:307-312. [PMID: 35471720 PMCID: PMC9038998 DOI: 10.1007/s12664-021-01218-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 08/19/2021] [Indexed: 02/04/2023]
Abstract
During the recent second wave of corona virus disease 2019 (COVID-19) pandemic in India, we managed a series of gastrointestinal complications in patients with COVID-19. We aim to highlight the key presentation and clinical course and emphasize the lessons we learnt from our series of such patients. A case review of ten consecutive patients with either bowel gangrene or perforation who were managed at our centre from March 20, 2021 to June 10, 2021. Clinical-demographic details, possible etiology, radiological findings, management and outcomes have been described. Of the 10 patients, 2 presented with bowel gangrene and 8 with perforation. In our series, all these patients were diagnosed with the help of computed tomography (CT) abdomen during the 3rd week after diagnosis of COVID-19. All had received steroid medication. Both patients with bowel gangrene and 4 of 8 patients with perforation underwent surgery, while 4 were managed non-operatively. Barring one patient, all the operated patients succumbed within 5 days of surgery after rapid clinical deterioration. Non-operative management in selected patients with perforation including placement of percutaneous drains, bowel rest and antibiotics was successful. Emergency surgery for COVID-19 related intestinal gangrene or perforation was associated with high mortality in our series. Non-operative management which avoids the added stress of a major emergency surgery particularly in patients just recovering from COVID-19 may be considered in stable patients in whom perforation appears to be contained.
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Affiliation(s)
- Sudarshan B. Chaugale
- Department of GI Surgery, GI Oncology, Minimal Access and Bariatric Surgery, Medanta Medicity Hospital, Sector 38, Islampur, 122 001 Gurugram, India
| | - Vikas Singhal
- Department of GI Surgery, GI Oncology, Minimal Access and Bariatric Surgery, Medanta Medicity Hospital, Sector 38, Islampur, 122 001 Gurugram, India
| | - Deeksha Kapoor
- Department of GI Surgery, GI Oncology, Minimal Access and Bariatric Surgery, Medanta Medicity Hospital, Sector 38, Islampur, 122 001 Gurugram, India
| | - Amanjeet Singh
- Department of GI Surgery, GI Oncology, Minimal Access and Bariatric Surgery, Medanta Medicity Hospital, Sector 38, Islampur, 122 001 Gurugram, India
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11
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Adamski J, Jäschke B, Nieminen T, Weigl W. Bowel Perforation During Haemophagocytic Lymphohistiocytosis Treatment with Corticosteroids and Anakinra. Eur J Case Rep Intern Med 2021; 8:002759. [PMID: 34790620 DOI: 10.12890/2021_002842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 09/06/2021] [Indexed: 11/05/2022] Open
Abstract
We report the use of anakinra to treat a case of a 64-year-old man diagnosed with haemophagocytic lymphohistiocytosis (HLH) with neurological involvement. After the administration of intravenous pulse corticosteroid therapy, immunoglobulin and anakinra the patient showed neurological recovery. However, the recovery was complicated by the perforation of a pre-existing bowel diverticulum. The effect of anakinra on bowel inflammation has not yet been clearly established. It can potentially augment bowel inflammation and contribute to the risk of bowel perforation associated with the concomitant use of corticosteroids. LEARNING POINTS Anakinra can potentially augment bowel inflammation.The concomitant use of anakinra and corticosteroids may increase the risk of bowel perforation.Use of anakinra and corticosteroids in patients with pre-existing gastrointestinal diseases requires vigilant observation for abdominal symptoms.
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Affiliation(s)
- Jan Adamski
- Department of Anaesthesiology and Intensive Care, Faculty of Medical Sciences, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland
| | - Björn Jäschke
- Department of Anaesthesiology and Intensive Care, Satakunta Central Hospital, Pori, Finland
| | - Tuomas Nieminen
- Department of Infectious Diseases, Satakunta Central Hospital, Pori, Finland
| | - Wojciech Weigl
- Anaesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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12
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Rose J. Autoimmune Connective Tissue Diseases: Systemic Lupus Erythematosus and Rheumatoid Arthritis. Emerg Med Clin North Am 2021; 40:179-191. [PMID: 34782087 DOI: 10.1016/j.emc.2021.09.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Systemic lupus erythematosus and rheumatoid arthritis are just 2 of several autoimmune connective tissue diseases that are primarily chronic in nature but can present to the emergency department by virtue of an acute exacerbation of disease. Beyond an acute exacerbation of disease, their predilection for invading multiple organ systems lends itself to the potential for patients presenting to the emergency department with either a single or isolated symptom or a myriad of signs and/or symptoms indicative of a degree of disease complexity and severity that warrant timely recognition and resuscitation.
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Affiliation(s)
- Jonathan Rose
- Department of Emergency Medicine, Memorial Healthcare System, Memorial Hospital West, 703 N Flamingo Road, Pembroke Pines, FL 33028, USA.
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13
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Garrido I, Lopes S, Macedo G. Hit the Road JAK! The Role of New Oral Treatment in Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:2010-2022. [PMID: 33742651 DOI: 10.1093/ibd/izab037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Indexed: 02/07/2023]
Abstract
Crohn disease (CD) and ulcerative colitis (UC) are considered chronic disorders of the gastrointestinal tract, lifelong medication often being necessary. Furthermore, they have significant implications on the quality of life. In the past few years, major advances have been achieved concerning the treatment of inflammatory bowel disease. These advances are expanding the possibilities for managing these patients. Janus kinase (JAK) inhibitors represent the most auspicious treatment to date because they consist of drugs that are orally administered, with a short half-life and low antigenicity. In addition, they seem to concurrently lessen various proinflammatory routes. In fact, tofacitinib has already been approved in patients with UC, both naïve and with prior exposure to tumor necrosis factor inhibitors. In CD, the results with tofacitinib have been less impressive. Several other JAK inhibitors are currently being investigated. However, given the wide spectrum of immunosuppressive effects, special attention has been given to the safety profile of these drugs, namely with regard to the occurrence of thromboembolic events, opportunistic infections, and malignancy. In this article, we review key evidence on the efficacy and safety of JAK inhibitors concerning both UC and CD.
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Affiliation(s)
- Isabel Garrido
- Gastroenterology and Hepatology Department, Centro Hospitalar Universitário de São João, Porto, Portugal.,World Gastroenterology Organization Porto Training Center, Porto, Portugal
| | - Susana Lopes
- Gastroenterology and Hepatology Department, Centro Hospitalar Universitário de São João, Porto, Portugal.,World Gastroenterology Organization Porto Training Center, Porto, Portugal
| | - Guilherme Macedo
- Gastroenterology and Hepatology Department, Centro Hospitalar Universitário de São João, Porto, Portugal.,World Gastroenterology Organization Porto Training Center, Porto, Portugal
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Luo Y, Alexander M, Gadina M, O'Shea JJ, Meylan F, Schwartz DM. JAK-STAT signaling in human disease: From genetic syndromes to clinical inhibition. J Allergy Clin Immunol 2021; 148:911-925. [PMID: 34625141 PMCID: PMC8514054 DOI: 10.1016/j.jaci.2021.08.004] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 08/04/2021] [Accepted: 08/09/2021] [Indexed: 12/18/2022]
Abstract
Since its discovery, the Janus kinase-signal transduction and activation of transcription (JAK-STAT) pathway has become recognized as a central mediator of widespread and varied human physiological processes. The field of JAK-STAT biology, particularly its clinical relevance, continues to be shaped by 2 important advances. First, the increased use of genomic sequencing has led to the discovery of novel clinical syndromes caused by mutations in JAK and STAT genes. This has provided insights regarding the consequences of aberrant JAK-STAT signaling for immunity, lymphoproliferation, and malignancy. In addition, since the approval of ruxolitinib and tofacitinib, the therapeutic use of JAK inhibitors (jakinibs) has expanded to include a large spectrum of diseases. Efficacy and safety data from over a decade of clinical studies have provided additional mechanistic insights while improving the care of patients with inflammatory and neoplastic conditions. This review discusses major advances in the field, focusing on updates in genetic diseases and in studies of clinical jakinibs in human disease.
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Affiliation(s)
- Yiming Luo
- Vasculitis Translational Research Program, Systemic Autoimmunity Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Md
| | - Madison Alexander
- Translational Immunology Section, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Md
| | - Massimo Gadina
- Office of Science and Technology, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Md
| | - John J O'Shea
- Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Md
| | - Francoise Meylan
- Office of Science and Technology, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Md
| | - Daniella M Schwartz
- Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
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15
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Barbulescu A, Delcoigne B, Askling J, Frisell T. Gastrointestinal perforations in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs in Sweden: a nationwide cohort study. RMD Open 2021; 6:rmdopen-2020-001201. [PMID: 32669452 PMCID: PMC7425111 DOI: 10.1136/rmdopen-2020-001201] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 04/07/2020] [Accepted: 06/25/2020] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVES To compare incidence rates of gastrointestinal (GI) perforations between patients with RA and the general population, and between patients treated with tumour necrosis factor inhibitors (TNFi) and non-TNFi biologics. METHODS In this nationwide cohort study, a total of 63 532 patients with RA, with 26 050 biological treatment episodes (TNFi, rituximab, abatacept or tocilizumab) and 76 304 general population controls, were followed between 2009 and 2017 until the first outcome event. The main outcome was hospitalisation or death due to lower GI perforations, identified according to a prespecified list of ICD-10 (International Classification of Diseases, 10th revision) codes. Inverse probability of treatment weighting was used for adjustment. RESULTS The sex-standardised and age-standardised incidence rates of lower GI perforations were 1.1 (95% CI 1.0 to 1.3) events per 1000 person-years among general population controls, 1.6 (1.5-1.7) among bionaïve patients and ranged from 1.8 (1.4-3.6) (TNFi) to 4.5 (2.7-10.4) (tocilizumab) among biologics-treated patients. After adjustment for glucocorticoid use, the risk in bionaïve, TNFi-treated, abatacept-treated or rituximab-treated patients with RA was no longer different from the general population, while for tocilizumab it remained significantly higher. Comparing tocilizumab to TNFi, the adjusted HR for lower GI perforations was 2.2 (1.3-3.8), corresponding to one additional GI perforation per 451 patient-years treated with tocilizumab instead of TNFi. CONCLUSION Tocilizumab was associated with a higher risk of lower GI perforations compared with alternative biologics. In absolute numbers, the risk remained low on all biologics commonly used to treat RA, but the accumulated evidence across settings and outcome definitions supports that this risk should be considered in treatment guidelines for RA.
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Affiliation(s)
- Andrei Barbulescu
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | | | - Johan Askling
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Thomas Frisell
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
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16
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Damsky W, Peterson D, Ramseier J, Al-Bawardy B, Chun H, Proctor D, Strand V, Flavell RA, King B. The emerging role of Janus kinase inhibitors in the treatment of autoimmune and inflammatory diseases. J Allergy Clin Immunol 2020; 147:814-826. [PMID: 33129886 DOI: 10.1016/j.jaci.2020.10.022] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 10/01/2020] [Accepted: 10/05/2020] [Indexed: 12/26/2022]
Abstract
Autoimmune and inflammatory diseases are common and diverse, and they can affect nearly any organ system. Much of the pathogenesis of these diseases is related to dysregulated cytokine activity. Historically, autoimmune and inflammatory diseases have been treated with medications that nonspecifically suppress the immune system. mAbs that block the action of pathogenic cytokines emerged 2 decades ago and have become widely useful. More recently, agents that simultaneously block multiple pathogenic cytokines via inhibition of the downstream Janus kinase (JAK)-signal transducer and activator of transcription pathway have emerged and are becoming increasingly important. These small-molecule inhibitors, collectively termed JAK inhibitors, are US Food and Drug Administration-approved in a few autoimmune/inflammatory disorders and are being evaluated in many others. Here, we review the biology of the JAK-signal transducer and activator of transcription pathway and the use of JAK inhibitors to treat autoimmune and inflammatory diseases across medical subspecialties.
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Affiliation(s)
- William Damsky
- Department of Dermatology, Yale University School of Medicine, New Haven, Conn.
| | - Danielle Peterson
- Department of Dermatology, Yale University School of Medicine, New Haven, Conn
| | - Julie Ramseier
- Department of Dermatology, Yale University School of Medicine, New Haven, Conn
| | - Badr Al-Bawardy
- Division of Digestive Diseases, Yale University School of Medicine, New Haven, Conn
| | - Hyung Chun
- Division of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn
| | - Deborah Proctor
- Division of Digestive Diseases, Yale University School of Medicine, New Haven, Conn
| | - Vibeke Strand
- Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, Calif
| | - Richard A Flavell
- Department of Immunobiology, Yale University School of Medicine, New Haven, Conn; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Conn
| | - Brett King
- Department of Dermatology, Yale University School of Medicine, New Haven, Conn.
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17
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Schwab K, Hamidi S, Chung A, Lim RJ, Khanlou N, Hoesterey D, Dumitras C, Adeyiga OB, Phan-Tang M, Wang TS, Saggar R, Goldstein J, Belperio JA, Dubinett SM, Kim JT, Salehi-Rad R. Occult Colonic Perforation in a Patient With Coronavirus Disease 2019 After Interleukin-6 Receptor Antagonist Therapy. Open Forum Infect Dis 2020; 7:ofaa424. [PMID: 33204749 PMCID: PMC7543619 DOI: 10.1093/ofid/ofaa424] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 09/09/2020] [Indexed: 12/21/2022] Open
Abstract
Background Interleukin-6 blockade (IL-6) has become a focus of therapeutic investigation for the coronavirus disease 2019 (COVID-19). Methods We report a case of a 34-year-old with COVID-19 pneumonia receiving an IL-6 receptor antagonist (IL-6Ra) who developed spontaneous colonic perforation. This perforation occurred despite a benign abdominal exam and in the absence of other known risk factors associated with colonic perforation. Results Examination of the colon by electron microscopy revealed numerous intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions abutting the microvilli of the colonic mucosa. Multiplex immunofluorescent staining revealed the presence of the SARS-CoV-2 spike protein on the brush borders of colonic enterocytes that expressed angiotensin-converting enzyme 2. However, no viral particles were observed within the enterocytes to suggest direct viral injury as the cause of colonic perforation. Conclusions These data and absence of known risk factors for spontaneous colonic perforation implicate IL-6Ra therapy as the potential mediator of colonic injury in this case. Furthermore, this report provides the first in situ visual evidence of the virus in the colon of a patient presenting with colonic perforation adding to growing evidence that intact infectious virus can be present in the stool.
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Affiliation(s)
- Kristin Schwab
- Division of Pulmonary and Critical Care, Department of Medicine at University of California, Los Angeles, California, USA
| | - Sepehr Hamidi
- Department of Pathology and Laboratory Medicine at University of California, Los Angeles, California, USA
| | - Augustine Chung
- Division of Pulmonary and Critical Care, Department of Medicine at University of California, Los Angeles, California, USA
| | - Raymond J Lim
- Department of Molecular and Medical Pharmacology at University of California, Los Angeles, California, USA
| | - Negar Khanlou
- Department of Pathology and Laboratory Medicine at University of California, Los Angeles, California, USA
| | - Daniel Hoesterey
- Department of Medicine at University of California, Los Angeles, California, USA
| | - Camelia Dumitras
- Division of Pulmonary and Critical Care, Department of Medicine at University of California, Los Angeles, California, USA
| | - Oladunni B Adeyiga
- Division of Infectious Diseases, Department of Medicine at University of California, Los Angeles, California, USA
| | - Michelle Phan-Tang
- Department of Pathology and Laboratory Medicine at University of California, Los Angeles, California, USA
| | - Tisha S Wang
- Division of Pulmonary and Critical Care, Department of Medicine at University of California, Los Angeles, California, USA
| | - Rajan Saggar
- Division of Pulmonary and Critical Care, Department of Medicine at University of California, Los Angeles, California, USA
| | - Jeffrey Goldstein
- Department of Pathology and Laboratory Medicine at University of California, Los Angeles, California, USA
| | - John A Belperio
- Division of Pulmonary and Critical Care, Department of Medicine at University of California, Los Angeles, California, USA
| | - Steven M Dubinett
- Division of Pulmonary and Critical Care, Department of Medicine at University of California, Los Angeles, California, USA.,Department of Pathology and Laboratory Medicine at University of California, Los Angeles, California, USA.,Department of Molecular and Medical Pharmacology at University of California, Los Angeles, California, USA.,Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California, USA.,Jonsson Comprehensive Cancer Center at University of California, Los Angeles, California, USA
| | - Jocelyn T Kim
- Division of Infectious Diseases, Department of Medicine at University of California, Los Angeles, California, USA
| | - Ramin Salehi-Rad
- Division of Pulmonary and Critical Care, Department of Medicine at University of California, Los Angeles, California, USA.,Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California, USA
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A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Giant Cell Arteritis. Rheumatol Ther 2020; 7:793-810. [PMID: 32844378 PMCID: PMC7695797 DOI: 10.1007/s40744-020-00227-2] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION To evaluate the efficacy and safety of sirukumab in giant cell arteritis (GCA). METHODS In this multicentre, randomised, double-blind, placebo-controlled, two-part phase 3 trial (NCT02531633; Part A [52-week double-blind treatment]; Part B [104-week follow-up]), patients with GCA were randomised (3:3:2:2:2) to sirukumab 100 mg every 2 weeks plus 6-month or 3-month prednisone taper, sirukumab 50 mg every 4 weeks plus 6-month prednisone taper, or placebo every 2 weeks plus 6-month or 12-month prednisone taper. The primary endpoint was the proportion of patients in sustained remission at week 52. Secondary endpoints included disease flare and safety. The study was terminated early (October 2017; sponsor decision). RESULTS Of 161 patients randomised (sirukumab: n = 107; placebo: n = 54), 28 (17.4%) completed week 52 (median treatment duration: 24-30 weeks). In a revised intent-to-treat (ITT) subgroup (completed week 52 or discontinued before study termination [n = 55]); six patients (all receiving sirukumab) achieved the primary endpoint. In the ITT population (n = 161), the proportion of patients with flares (week 2-52) was lower with sirukumab (18.4-30.8%) than placebo (37.0-40.0%). The proportion of patients with flares (week 2-12) was highest with sirukumab 100 mg every 2 weeks plus 3-month prednisone taper (23.1%). In Part A, 94.4% of patients reported ≥ 1 treatment-emergent adverse event (TEAE); 19.3% reported serious TEAEs. The proportions of patients with TEAEs were generally similar across treatment arms. No deaths occurred. CONCLUSIONS Although data were limited due to early termination and shortened treatment duration, sirukumab treatment resulted in numerically lower proportions of patients with flare by week 52 versus placebo, with no unexpected safety findings. TRIAL REGISTRATION Clinicaltrials.gov: NCT02531633.
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Ucar O. Delivering Precision Medicine and Patient-Centred Care Through a Multidisciplinary Approach. EUROPEAN MEDICAL JOURNAL 2018. [DOI: 10.33590/emj/10313695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
The current treatment strategy for patients with inflammatory bowel disease (IBD) aims to enable physicians to deliver optimal care and to improve the role that patients play in treatment decisions. The multidisciplinary team (MDT) approach integrates the patient’s perspective and sees the discussion of treatment options with both gastroenterologists and surgeons as early as possible. The MDT approach is also vital in managing the risk of IBD and cardiovascular-related comorbidities in patients with psoriasis (PsO) and psoriatic arthritis (PsA), where selection of appropriate medication may affect both the rheumatic condition and the associated comorbidity. Close interdisciplinary interactions between gastroenterologists, rheumatologists, and/or dermatologists are vital, and the ensuing knowledge transfer facilitates the provision of optimal patient care. Personalised medicine will have a profound impact on future treatment algorithms in IBD and other chronic inflammatory conditions. Owing to the complexity of these diseases, a novel approach is urgently needed that will aggregate data from multiple systems and integrate it into a so-called ‘IBD interactome’. This may help identify and target the key molecular components responsible for inflammation. Future treatment practices will also address the psychosocial aspects of IBD by empowering patients and integrating their perspective into the shared treatment decision-making process early on.
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