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Rathi H, Patra T, Poojary I, Pathak PR, Haley H. Idiopathic Mixed Cryoglobulinemia: A Diagnostic Challenge. Cureus 2024; 16:e70069. [PMID: 39449949 PMCID: PMC11499966 DOI: 10.7759/cureus.70069] [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] [Accepted: 09/23/2024] [Indexed: 10/26/2024] Open
Abstract
Mixed cryoglobulinemia (MC) is commonly associated with chronic hepatitis C infection. Symptoms usually present as a clinical triad of purpuric rash, arthralgia, and generalized weakness. There have been several case reports establishing the relationship between hepatitis C and MC. Here, we report a case of a 22-year-old female presenting with bilateral lower extremity and facial swelling with no history of hepatitis C developing idiopathic mixed cryoglobulinemia. She was treated with intravenous steroids, rituximab, and plasmapheresis, resulting in improvement with outpatient nephrology and oncology follow-ups.
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Affiliation(s)
- Hinal Rathi
- Internal Medicine, University of Alabama Heersink School of Medicine Huntsville Regional Campus, Huntsville, USA
| | - Tumpa Patra
- Internal Medicine, Crestwood Medical Center, Huntsville, USA
| | - Indira Poojary
- Internal Medicine, Crestwood Medical Center, Huntsville, USA
| | - Prutha R Pathak
- Internal Medicine, North Alabama Medical Center, Florence, USA
| | - Heather Haley
- Nephrology, Huntsville Renal Clinic, Huntsville, USA
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Reinberg C, Vingerhoets S, Pavlova O, Guenova E, Papadimitriou-Olivgeris M, Comte D. Cryoglobulinemic vasculitis triggered by Staphylococcus aureus endocarditis with chronic hepatitis C virus co-infection: a case report and literature review. Front Immunol 2024; 15:1385086. [PMID: 39076993 PMCID: PMC11284083 DOI: 10.3389/fimmu.2024.1385086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Accepted: 06/25/2024] [Indexed: 07/31/2024] Open
Abstract
Infective endocarditis is a rare but life-threatening condition, occasionally linked to diverse immunologic manifestations, including mixed cryoglobulinemia. This can lead to cryoglobulinemic vasculitis, which has the potential for widespread organ damage. Although some cases have highlighted the relationship between infective endocarditis and cryoglobulinemic vasculitis, no comprehensive epidemiological evaluation or optimal treatment strategies have been advanced for such a combination. We present a case of methicillin-sensitive Staphylococcus aureus infective endocarditis associated with cryoglobulinemic vasculitis and conduct a literature review to compare management and outcomes in similar cases. Our patient presented with classical Meltzer's triad and mild renal involvement. Cryoimmunofixation confirmed type III cryoglobulinemia, and serum cytokines showed elevated IL-6 levels. The differential diagnosis included infective endocarditis and chronic active hepatitis C virus infection. Rapid symptom resolution after antibiotic treatment identified infective endocarditis as the likely cause of cryoglobulinemic vasculitis. Our case and review of the literature highlight that early identification of the cause of cryoglobulinemic vasculitis is crucial for selecting appropriate treatment and preventing recurrence or morbidity.
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Affiliation(s)
- Céline Reinberg
- Service of Internal Medicine, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Sébastien Vingerhoets
- Service of Infectious Diseases, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Olesya Pavlova
- Service of Dermatology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Emmanuella Guenova
- Service of Dermatology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | | | - Denis Comte
- Service of Internal Medicine, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
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Zhang R, Wei M, Zhou J, Yang Z, Xiao M, Du L, Bao M, Ju J, Dong C, Zheng Y, Bao H. Effects of organic trace minerals chelated with oligosaccharides on growth performance, blood parameters, slaughter performance and meat quality in sheep. Front Vet Sci 2024; 11:1366314. [PMID: 38577544 PMCID: PMC10993154 DOI: 10.3389/fvets.2024.1366314] [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: 01/06/2024] [Accepted: 03/05/2024] [Indexed: 04/06/2024] Open
Abstract
The present study assessed the effects of oligosaccharide-chelated organic trace minerals (OTM) on the growth performance, digestive enzyme activity, blood parameters, slaughter performance, and meat quality indexes of mutton sheep. A total of 60 East Ujumuqin × small-tailed Han crossbred mutton sheep were assigned to two groups (10 duplicates per group) by body weight (26.12 ± 3.22 kg) according to a completely randomized design. Compared to the CON group, the results of the OTM group showed: (1) no significant changes in the initial body weight, final body weight, dry matter intake, average daily gain, and feed conversion ratio (p > 0.05); (2) the activities of trypsin, lipase, and amylase in the jejunum were significantly increased (p < 0.05); (3) serum total protein, albumin, and globulin of the blood were significantly increased (p < 0.05), and the growth factor interleukin IL-10 was significantly higher (p < 0.05), while IL-2, IL-6, and γ-interferon were significantly lower (p < 0.05). Immunoglobulins A, M, and G were significantly higher (p < 0.05); (4) the live weight before slaughter, carcass weights, dressing percentage, eye muscle areas, and GR values did not differ significantly (p > 0.05); (5) shear force of mutton was significantly lower (p < 0.05), while the pH45min, pH24h, drip loss, and cooking loss did not show a significant difference (p > 0.05). The content of crude protein was significantly higher (p < 0.05), while the ether extract content was significantly reduced (p < 0.05), but no significant difference was detected between moisture and ash content; (6) the total amino acids, essential amino acids, semi-essential amino acids, and umami amino acids were significantly increased (p < 0.05). Although umami amino acids were not significant, the total volume increased (p > 0.05). Among these, the essential amino acids, threonine, valine, leucine, lysine in essential amino acids and arginine were significantly increased (p < 0.05). Also, non-essential amino acids, glycine, serine, proline, tyrosine, cysteine, and aspartic acid, were significantly higher (p < 0.05). The content of alanine, aspartate, glutamic acid, phenylalanine, and tyrosine in umami amino acids was significantly higher (p < 0.05).
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Affiliation(s)
- Runze Zhang
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China
| | - Manlin Wei
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China
| | - Jianqun Zhou
- Nanning Zeweier Feed Limited Liability Company, Nanning, China
| | - Zaibin Yang
- College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China
| | - Ming Xiao
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China
| | - Liu Du
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China
| | - Meili Bao
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China
| | - Ji Ju
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China
| | - Chenyang Dong
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China
| | - Yongjie Zheng
- College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, China
| | - Hailin Bao
- Horqin Left Wing Rear Banner National Vocational and Technical School, Tongliao, China
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Verheyden MJ, Yu SP. A rare entity: Progressive multisystem involvement in type 1 cryoglobulinaemia. Australas J Dermatol 2024; 65:85-87. [PMID: 37997690 DOI: 10.1111/ajd.14191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/29/2023] [Accepted: 11/09/2023] [Indexed: 11/25/2023]
Affiliation(s)
- Matthew J Verheyden
- Department of Rheumatology, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
| | - Shirley P Yu
- Department of Rheumatology, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, School of Medicine, Sydney Musculoskeletal Health, The Kolling Institute, University of Sydney, Sydney, New South Wales, Australia
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Treppo E, Quartuccio L, De Vita S. Recent updates in the diagnosis and management of cryoglobulinemic vasculitis. Expert Rev Clin Immunol 2023; 19:1457-1467. [PMID: 37698547 DOI: 10.1080/1744666x.2023.2249609] [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: 04/27/2023] [Accepted: 08/15/2023] [Indexed: 09/13/2023]
Abstract
INTRODUCTION Cryoglobulinemic vasculitis (CV), also known as mixed cryoglobulinemic syndrome (MCS), is a systemic vasculitis that affects small blood vessels. It exhibits a wide range of clinical manifestations, making its treatment a continuing challenge for physicians. AREAS COVERED We conducted a comprehensive review to evaluate the current status of diagnosis, management, and treatment of mixed cryoglobulinemia (MC). The accurate clinical and serological evaluation plays a vital role in diagnosing MC, identifying potential comorbidities, and monitoring its main manifestations and complications. Treatment strategies should be individualized based on the underlying etiopathogenesis, the severity of organ involvement, and the associated underlying disease. At present, the two mainstays of CV treatment are direct antiviral agents (for HCV-related CV) and B-cell-targeted therapy. EXPERT OPINION MC remains one of the few autoimmune diseases where the etiology is known, at least for the majority of patients. Its pathogenetic mechanism offers a unique opportunity to investigate the interplay between infections and the immune system. Moving forward, the primary challenge will continue to lie in the treatment of resistant or refractory cases of CV, particularly those associated with autoimmune diseases, or cases classified as 'essential' CV.
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Affiliation(s)
- Elena Treppo
- Rheumatology Unit, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria del Friuli Centrale (ASUFC), Udine, Italy
| | - Luca Quartuccio
- Rheumatology Unit, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria del Friuli Centrale (ASUFC), Udine, Italy
| | - Salvatore De Vita
- Rheumatology Unit, Department of Medicine, University of Udine, Azienda Sanitaria Universitaria del Friuli Centrale (ASUFC), Udine, Italy
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Sugihara A, Ureshino H, Yamasaki M, Fukuda M, Yoshihara M, Nonaka E, Miyazaki M, Fujita M, Ishii K, Kamachi K, Sano H, Okamoto S, Itamura H, Yoshimura M, Katsuya H, Ando T, Aoki S, Ubara Y, Kimura S. Type II Cryoglobulinemic Membranoproliferative Glomerulonephritis Caused by Mucosa-associated Lymphoid Tissue Lymphoma. Intern Med 2023; 62:1983-1988. [PMID: 37394661 PMCID: PMC10372288 DOI: 10.2169/internalmedicine.0756-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/04/2023] Open
Abstract
A 67-year-old man complained of lower limb edema with a purpuric skin rash. Laboratory tests revealed proteinuria, elevated serum creatinine levels, and low serum albumin levels. The patient was also positive for cryoglobulin in serum, immunoglobulin (Ig) M gammopathy, hypocomplementemia, and rheumatoid factor. He was negative for anti-hepatitis C virus antibodies. A pathological analysis of the renal tissue revealed membranoproliferative glomerulonephritis, common histological features of cryoglobulinemic vasculitis (CV), and mucosa-associated lymphoid tissue lymphoma invasion. Although hematologic malignancy is a rare cause of type II CV, these clinical findings suggest that mucosa-associated lymphoid tissue lymphoma (MALT) lymphoma may have been the cause in the present case.
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Affiliation(s)
- Ayano Sugihara
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Hiroshi Ureshino
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
- Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Japan
| | - Masatora Yamasaki
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Makoto Fukuda
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Maki Yoshihara
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Eriko Nonaka
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Mariko Miyazaki
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Mai Fujita
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Keitaro Ishii
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Kazuharu Kamachi
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Haruhiko Sano
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Sho Okamoto
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Hidekazu Itamura
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Mariko Yoshimura
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Hiroo Katsuya
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Toshihiko Ando
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Shigehisa Aoki
- Division of Pathology, Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Japan
| | | | - Shinya Kimura
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
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Alsaidi Y, Thompson A, Spilchuk V, House RA, Adisesh A. Cryoglobulins and cold agglutinins for hand arm vibration syndrome. Occup Med (Lond) 2022; 72:609-613. [PMID: 36179074 DOI: 10.1093/occmed/kqac083] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Hand arm vibration syndrome (HAVS) is a condition caused by hand transmitted vibration from the use of hand-held vibrating tools or workpieces. The disease affects the vascular, neurological and musculoskeletal systems. The vascular component of HAVS is a form of secondary Raynaud's phenomenon. Other causes of disease must be excluded before attributing the cause to hand transmitted vibration. AIMS To evaluate the prevalence, and utility of testing for, cryoglobulins and cold agglutinins in patients with HAVS symptoms. METHODS A retrospective cohort study of 1183 patients referred for HAVS clinical assessment at St. Michael's Hospital, Toronto, Canada, between 2014 and 2020. The standard operating procedure at the clinic includes a detailed clinical and exposure history, physical examination, objective investigations and blood tests. Data were retrieved from patient chart review and laboratory investigation results for all cases with cryoglobulin and cold agglutinin testing. RESULTS A total of 1183 patients had a serum cryoglobulin measurement. Eleven patients (1%) were positive. Seven positive results were 'low titre' (1% positive) and the other four results were 2%, 6%, 9% and 18%. The patient with a 9% positive cryoglobulin titre had previously diagnosed Sjögren's syndrome. There were no positive cold agglutinin tests in the 795 patients tested. CONCLUSIONS Routine testing for cryoglobulins and cold agglutinins in patients with HAVS symptoms is not recommended because test positivity rates are negligible. Testing may be considered if the clinical history or routine blood investigations suggest evidence of underlying cryoglobulinaemia or cold agglutinin disease.
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Affiliation(s)
- Y Alsaidi
- Division of Occupational Medicine, Department of Medicine, University of Toronto and St. Michael's Hospital, Toronto, Canada
| | - A Thompson
- Division of Occupational Medicine, Department of Medicine, University of Toronto and St. Michael's Hospital, Toronto, Canada
| | - V Spilchuk
- Division of Occupational Medicine, Department of Medicine, University of Toronto and St. Michael's Hospital, Toronto, Canada
| | - R A House
- Division of Occupational Medicine, Department of Medicine, University of Toronto and St. Michael's Hospital, Toronto, Canada
| | - A Adisesh
- Division of Occupational Medicine, Department of Medicine, University of Toronto and St. Michael's Hospital, Toronto, Canada
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Fenoglio R, Sciascia S, Rossi D, Naretto C, Alpa M, Roccatello D. Non HCV-Related Mixed Cryoglobulinemic Vasculitis With Biopsy-Proven Renal Involvement: The Effects of Rituximab. Front Med (Lausanne) 2022; 9:819320. [PMID: 35419372 PMCID: PMC8995745 DOI: 10.3389/fmed.2022.819320] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 03/03/2022] [Indexed: 11/17/2022] Open
Abstract
In the countries where HCV infection is still endemic, about 90% of subjects with mixed cryoglobulinemia had previously been infected with HCV and about 80% are RNA positive. Remarkable results in severe HCV-related cryoglobulinemic vasculitis have been obtained with Rituximab. Details of the clinical characteristics and effective treatment of non HCV-related cryogloulinemic syndromes are presently lacking. This paper reports on a prospective single-Center open study aimed at evaluating the clinical presentation and effects of Rituximab administered alone in patients with severe non HCV-related cryoglobulinemic syndrome. The study group included 11 patients followed for at least 6 months. Three patients had type I cryoglobulinemia, 6 had type II and the remaining 2 patients had type III. Mean cryocrit was 2.5%. Four out of 11 patients had symptomatic sicca complex with anti-SSA (Ro)/anti SSB (La) antibodies. All 11 patients presented with biopsy-proven renal involvement, 4 out of 11 with leukocytoclastic vasculitis, and 8 with involvement of the peripheral nervous system. Renal biopsy revealed diffuse membranoproliferative glomerulonephritis (MPGN) in 9 out of 11 patients. Extracapillary proliferation and necrosis of the glomerular tuft was observed in 1 of these 9 cases. Interstitial nephritis together with mesangial expansion and capillary immune deposits were observed in 1 patient. Prevalent interstitial fibrosis and glomerular sclerosis were detected in the remaining case. Patients underwent treatment with rituximab alone. After 6 months we observed a remarkable improvement in the necrotizing skin ulcers and a substantial amelioration of the electrophysiological parameters of motor and sensory peripheral neuropathy. Improvement in both renal function (from 2.8 to 1.4 mg/dl, p < 0.001) and proteinuria (from 4.2 g/24 to 0.4 g/24 h, p < 0.001) was found in 10 out of 11 patients, while 1 could not be fully treated because of a severe infusion reaction and sudden development of anti-Rituximab antibodies. Good renal response was confirmed at the end of follow-up (38.4 months). Three patients had a relapse at 6, 12, and 48 months, respectively. In our cohort the administration of 4 once-weekly infusions of Rituximab followed by 2 more infusions after 1 and 2 months proved to be effective in the management of these rare patients.
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Affiliation(s)
- Roberta Fenoglio
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
| | - Savino Sciascia
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
| | - Daniela Rossi
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
| | - Carla Naretto
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
| | - Mirella Alpa
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
| | - Dario Roccatello
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
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Secular trends in cryoglobulinemia mortality in the USA in the era of direct-acting antivirals. Arthritis Res Ther 2022; 24:41. [PMID: 35151354 PMCID: PMC8840313 DOI: 10.1186/s13075-022-02720-1] [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: 08/17/2021] [Accepted: 01/13/2022] [Indexed: 11/10/2022] Open
Abstract
Background Hepatitis C virus (HCV) is the main etiology of cryoglobulinemia with mortality around 25%. Little is known on the changes in cryoglobulinemia mortality after the introduction of direct-acting antivirals (DAA) for treatment of HCV in 2014 in the USA. Methods We used the multiple-cause mortality files compiled by the National Center for Health Statistics to calculate cryoglobulinemia mortality from 1999 to 2018. The proportionate mortality ratio (PMR) of cryoglobulinemia cases with HCV and those with autoimmune diseases was computed to assess the impact of introduction of DAA. Results We identified 1299 people aged ≥ 20 years who died with cryoglobulinemia between 1999 and 2018. The cryoglobulinemia mortality (deaths per million) declined from 1999 (0.4) to 2010 (0.22) and mildly increased to 2014 (0.26), and then decreased abruptly from 2014 to 2018 (0.19) with annual percent change of − 14.3%. The proportion of cryoglobulinemia patients with HCV was 39% (118/302) in 2009–2013 and 26% (81/310) in 2014–2018, with a PMR of 0.67 (95% CI 0.50–0.89). By contrast, the proportion of cryoglobulinemia patients with systemic autoimmune diseases was 2.6% (8/302) in 2009–2013 and 4.2% (13/310) in 2014–2018, with a PMR of 1.58 (95% CI 0.66–3.82). Conclusion The changes in cryoglobulinemia mortality during the past two decades are mainly related to the aging and dying of the “baby boomer” cohort who had a high HCV prevalence and to the introduction of a DAA in 2014.
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Carmona-Rocha E, Iznardo H, Puig L. Retiform purpura in an 80-year-old woman. Int J Dermatol 2022; 61:1225-1226. [PMID: 35106756 DOI: 10.1111/ijd.16120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 01/06/2022] [Accepted: 01/11/2022] [Indexed: 11/30/2022]
Affiliation(s)
- Elena Carmona-Rocha
- Dermatology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, España
| | - Helena Iznardo
- Dermatology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, España
| | - Lluís Puig
- Dermatology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, España
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Gragnani L, Lorini S, Martini L, Stasi C, Visentini M, Petraccia L, Marello N, Monti M, Marri S, Madia F, Ricca V, Zignego AL. Rapid improvement of psychiatric stigmata after IFN-free treatment in HCV patients with and without cryoglobulinemic vasculitis. Clin Rheumatol 2022; 41:147-157. [PMID: 34409558 PMCID: PMC8724104 DOI: 10.1007/s10067-021-05877-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 07/30/2021] [Accepted: 07/30/2021] [Indexed: 10/29/2022]
Abstract
OBJECTIVE Hepatitis C virus (HCV) causes neuropsychiatric disorders and quality of life impairment, especially in patients with cryoglobulinemic vasculitis (CV). Direct acting antivirals (DAAs) are effective in most extrahepatic HCV diseases, but limited information exists regarding the outcome of psychiatric disorders in patients with and without CV, after therapy. We aimed to evaluate psychiatric outcomes, in HCV-patients with and without CV, before and after successful DAA therapy. METHODS We prospectively studied DAA-treated HCV-patients, stratified into presence (CV) or absence of CV (NON-CV). Four psychometric scales were administered to assess depression (HAM-D and MADRS), anxiety (HAM-A), and mania (MRS). Short-Form-36 questionnaires evaluated quality of life. RESULTS Seventy-six patients were recruited, and 47 CV and 29 NON-CV were treated with antivirals. At baseline, depression and anxiety, from mild to severe, were frequently shown, with the most advanced cases in thee CV group; no patients achieved the scores for mania. A significant improvement emerged for all the psychometric scales in the entire population and in the subgroups, after viral eradication even in the short-term outcome. The Short-Form-36 summary components showed benefits. CONCLUSIONS After HCV eradication, the depression and anxiety scores significantly improved and severity grade generally lowered. DAA-positive effects on mental disorders should be considered part of the therapy outcome, being beneficial especially in CV patients who usually have worse baseline mental scores. Key Points • HCV frequently causes psychiatric disorders and an often-invalidating autoimmune/lymphoproliferative disease called cryoglobulinemic vasculitis. • The new direct acting antivirals (DAAs) are very effective and well tolerated by HCV-patients. • This study shows DAA-induced benefits on depression and anxiety in HCV-patients that are especially evident in CV patients who usually have worse baseline mental scores. • DAA-induced benefits are observed in the short-term post-therapy follow-up, in contrast with data previously obtained in HCV patients treated with IFN-based anti-HCV therapy.
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Affiliation(s)
- Laura Gragnani
- MASVE Interdepartmental Hepatology Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, Largo Brambilla 3, 50134, Firenze, Italy
| | - Serena Lorini
- MASVE Interdepartmental Hepatology Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, Largo Brambilla 3, 50134, Firenze, Italy
| | - Lorenzo Martini
- MASVE Interdepartmental Hepatology Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, Largo Brambilla 3, 50134, Firenze, Italy
| | - Cristina Stasi
- MASVE Interdepartmental Hepatology Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, Largo Brambilla 3, 50134, Firenze, Italy
| | - Marcella Visentini
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185, Rome, Italy
| | - Luisa Petraccia
- MASVE Interdepartmental Hepatology Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, Largo Brambilla 3, 50134, Firenze, Italy
| | - Niccolò Marello
- MASVE Interdepartmental Hepatology Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, Largo Brambilla 3, 50134, Firenze, Italy
| | - Monica Monti
- MASVE Interdepartmental Hepatology Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, Largo Brambilla 3, 50134, Firenze, Italy
| | - Silvia Marri
- MASVE Interdepartmental Hepatology Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, Largo Brambilla 3, 50134, Firenze, Italy
| | - Francesco Madia
- MASVE Interdepartmental Hepatology Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, Largo Brambilla 3, 50134, Firenze, Italy
| | - Valdo Ricca
- Department of Health Sciences, Psychiatry Unit, University of Florence, 50134, Florence, Italy
| | - Anna Linda Zignego
- MASVE Interdepartmental Hepatology Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, Largo Brambilla 3, 50134, Firenze, Italy.
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Maslennikov R, Ivashkin V, Efremova I, Shirokova E. Immune disorders and rheumatologic manifestations of viral hepatitis. World J Gastroenterol 2021; 27:2073-2089. [PMID: 34025065 PMCID: PMC8117740 DOI: 10.3748/wjg.v27.i18.2073] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 02/28/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
Abstract
Infection with hepatotropic viruses is not limited to the liver and can lead to the development of various immunological disorders (the formation of cryoglobulins, rheumatoid factor, antinuclear antibodies, autoantibodies specific for autoimmune hepatitis and primary biliary cholangitis, and others), which can manifest as glomerulonephritis, arthritis, uveitis, vasculitis (cryoglobulinemic vasculitis, polyarteritis nodosa, Henoch-Schonlein purpura, isolated cutaneous necrotizing vasculitis), and other rheumatologic disorders, and be a trigger for the subsequent development of autoimmune hepatitis and primary biliary cholangitis. A further study of the association between autoimmune liver diseases and hepatotropic virus infection would be useful to assess the results of treatment of these associated diseases with antiviral drugs. The relationship of these immune disorders and their manifestations with hepatotropic viruses is best studied for chronic hepatitis B and C. Only isolated cases of these associations are described for hepatitis A. These links are least studied, and are often controversial for hepatitis E, possibly due to their relatively rare diagnoses. Patients with uveitis, glomerulonephritis, arthritis, vasculitis, autoimmune liver diseases should be tested for biomarkers of viral hepatitis, and if present, these patients should be treated with antiviral drugs.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119435, Russia
- Department of Internal Medicine 1, Сonsultative and Diagnostic Center 2 of the Moscow City Health Department, Moscow 107564, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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Fung WWS, Yip TCF, Wong VWS, Chow KM, Wong GLH, Szeto CC. Clinical Spectrum and Renal Outcome of Cryoglobulinemia in Hong Kong. KIDNEY360 2021; 2:721-728. [PMID: 35373043 PMCID: PMC8791315 DOI: 10.34067/kid.0007532020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 02/17/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Cryoglobulinemia is a systemic disease and the clinical involvement is variable. The long-term renal outcome of cryoglobulinemia remains unclear, and most published series are from the Western world, with a high proportion of chronic hepatitis C. The objective is to determine the prevalence, causes, and renal outcome of cryoglobulinemia in Hong Kong. METHODS We reviewed 289 patients with cryoglobulinemia in the public hospital database of Hong Kong between 2000 and 2019. The renal event-free survival, dialysis-free survival, and overall survival were analyzed according to the underlying etiologies, and compared with 7483 patients who tested negative for cryoglobulinemia during the same period. RESULTS Among the patients with cryoglobulinemia, 68 (24%) had chronic hepatitis B, 69 (24%) had hepatitis C, and 14 (5%) paraproteinemia. They were followed for 62.7±58.0 months. The 5-year dialysis-free survival was 68%, 70%, 67%, and 83% for patients with cryoglobulinemia attributed to hepatitis B, hepatitis C, paraproteinemia, and unknown etiology, respectively (P=0.05), and their 5-year overall survival was 61%, 58%, 22%, and 72%, respectively (P=0.002). Among patients with hepatitis B, the group with cryoglobulin had a worse renal event-free survival than those without (36% versus 43%, P=0.005), although their dialysis-free survival and all-cause mortality were similar. For patients with hepatitis C or paraproteinemia, the presence of cryoglobulin did not affect the renal outcome. CONCLUSIONS Hepatitis B is a common cause of cryoglobulinemia in southeast Asia, and the presence of cryoglobulinemia is associated with a worse renal event-free survival. The renal prognosis of cryoglobulinemia appears to be affected by the underlying cause, with hepatitis B having a worse renal outcome and patients with paraproteinemia having a worse overall survival than those with other causes of cryoglobulinemia.
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Affiliation(s)
- Winston Wing-Shing Fung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Kai-Ming Chow
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Cheuk-Chun Szeto
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
- Department of Nephrology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China
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14
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Cardinale V, Capurso G, Ianiro G, Gasbarrini A, Arcidiacono PG, Alvaro D. Intestinal permeability changes with bacterial translocation as key events modulating systemic host immune response to SARS-CoV-2: A working hypothesis. Dig Liver Dis 2020; 52:1383-1389. [PMID: 33023827 PMCID: PMC7494274 DOI: 10.1016/j.dld.2020.09.009] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 08/16/2020] [Accepted: 09/02/2020] [Indexed: 12/15/2022]
Abstract
The microbiota-gut-liver-lung axis plays a bidirectional role in the pathophysiology of a number of infectious diseases. During the course of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and 2 (SARS-CoV-2) infection, this pathway is unbalanced due to intestinal involvement and systemic inflammatory response. Moreover, there is convincing preliminary evidence linking microbiota-gut-liver axis perturbations, proinflammatory status, and endothelial damage in noncommunicable preventable diseases with coronavirus disease 2019 (Covid-19) severity. Intestinal damage due to SARS-CoV-2 infection, systemic inflammation-induced dysfunction, and IL-6-mediated diffuse vascular damage may increase intestinal permeability and precipitate bacterial translocation. The systemic release of damage- and pathogen-associated molecular patterns (e.g. lipopolysaccharides) and consequent immune-activation may in turn auto-fuel vicious cycles of systemic inflammation and tissue damage. Thus, intestinal bacterial translocation may play an additive/synergistic role in the cytokine release syndrome in Covid-19. This review provides evidence on gut-liver axis involvement in Covid-19 as well as insights into the hypothesis that intestinal endotheliitis and permeability changes with bacterial translocation are key pathophysiologic events modulating systemic inflammatory response. Moreover, it presents an overview of readily applicable measures for the modulation of the gut-liver axis and microbiota in clinical practice.
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Affiliation(s)
- Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Viale dell'Università 37, Rome 00185, Italy.
| | - Gabriele Capurso
- Pancreato-biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Sacred Heart, Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Sacred Heart, Rome, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreato-biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Università 37, Rome 00185, Italy
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15
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Mazzaro C, Dal Maso L, Mauro E, Visentini M, Tonizzo M, Gattei V, Andreone P, Pozzato G. Hepatitis C virus- related cryoglobulinemic vasculitis: A review of the role of the new direct antiviral agents (DAAs) therapy. Autoimmun Rev 2020; 19:102589. [PMID: 32540448 DOI: 10.1016/j.autrev.2020.102589] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 03/02/2020] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) infection affects about 70 million people worldwide. HCV is responsible for both hepatitis and extra-hepatic manifestations. Chronic infection has been shown to develop in about 70% of cases and can progress to cirrhosis or hepatocellular carcinoma. Ten percent of HCV patients may develop extra-hepatic manifestations, including mixed cryoglobulinemia (MC) and non-Hodgkin lymphomas. Many studies have demonstrated that, after antiviral therapy, MC can disappear along with HCV eradication. After the introduction of the new direct antiviral agents (DAAs), the combination of pegylated interferon and ribavirin has been abandoned. Several studies on new DAAs have reported remarkable 90% to 100% eradication rates, regardless of HCV genotype. Treatment with DAAs has comparable efficacy on viral eradication in patients with MC, but definite clinical improvements of vasculitis can be observed only in half the patients. On the contrary, the regression of renal disease and lympho-proliferative disorders, induced by HCV, appears to have a lower remission rate after viral eradication with DAAs and most cases need immunosuppressive treatments. In HCV related CV, the main clinical goal must be early eradication of HCV, to avoid organ complication and manifestation of lympho-proliferative diseases. This review focuses on the role of DAAs in treatment of HCV-related cryoglobulinemic vasculitis.
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Affiliation(s)
- Cesare Mazzaro
- Clinical of Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, PN, Italy.
| | - Luigino Dal Maso
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, PN, Italy.
| | - Endri Mauro
- Dipartimento di medicina interna, unità di ematologia, Ospedale Cà Foncello Treviso, Italy
| | - Marcella Visentini
- Depatment of Clinical Medicine, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Roma, Italy
| | - Maurizio Tonizzo
- Department of Internal Medicine, Pordenone General Hospital, Pordenone,Italy
| | - Valter Gattei
- Clinical of Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, PN, Italy
| | - Pietro Andreone
- Department of SMECHIMAI, University of Modena and Reggio Emilia, Modena, Italy
| | - Gabriele Pozzato
- Clinical and Surgical Sciences, University of Trieste, Trieste, Italy
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