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Balavoine AS, Glinoer D, Dubucquoi S, Wémeau JL. Antineutrophil Cytoplasmic Antibody-Positive Small-Vessel Vasculitis Associated with Antithyroid Drug Therapy: How Significant Is the Clinical Problem? Thyroid 2015; 25:1273-81. [PMID: 26414658 DOI: 10.1089/thy.2014.0603] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND The aim of this review was to delineate the characteristics of antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis associated with antithyroid drugs (ATD). A PubMed search was made for English language articles using the search terms antithyroid drugs AND ANCA OR ANCA-associated vasculitis. SUMMARY The literature includes approximately 260 case reports of ANCA-associated small-vessel vasculitis related to ATD, with 75% of these associated with thiouracil derivatives (propylthiouracil [PTU]) and 25% with methyl-mercapto-imidazole derivatives (MMI/TMZ). The prevalence of ANCA-positive cases caused by ATD varied between 4% and 64% with PTU (median 30%), and 0% and 16% with MMI/TMZ (median 6%). Young age and the duration of ATD therapy were the main factors contributing to the emergence of ANCA positivity. Before ATD therapy initiation, the prevalence of ANCA-positive patients was 0-13%. During ATD administration, 20% of patients were found to be positive for ANCA. Only 15% of ANCA-positive patients treated with ATD exhibited clinical evidence of vasculitis, corresponding to 3% of all patients who received ATD. Clinical manifestations of ANCA-associated vasculitis related to ATD were extremely heterogeneous. When vasculitis occurred, ATD withdrawal was usually followed by rapid clinical improvement and a favorable prognosis. CONCLUSIONS ANCA screening is not systematically recommended for individuals on ATD therapy, particularly given the decreasing use of PTU in favor of TMZ/MMI. Particular attention should be given to the pediatric population with Graves' disease who receive ATD, as well as patients treated with thiouracil derivatives and those on long-term ATD therapy.
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Affiliation(s)
| | - Daniel Glinoer
- 2 Department of Internal Medicine, Division of Endocrinology, University Hospital Saint Pierre , Brussels, Belgium
| | | | - Jean-Louis Wémeau
- 1 Service of Endocrinology and Metabolic Diseases, CHRU de Lille , Lille, France
- 3 Institut d'Immunologie, CHRU de Lille , Lille, France
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Antineutrophilic Cytoplasmic Antibody Positive Vasculitis Associated with Methimazole Use. Case Rep Endocrinol 2015; 2015:530319. [PMID: 26060588 PMCID: PMC4427812 DOI: 10.1155/2015/530319] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Accepted: 04/16/2015] [Indexed: 11/24/2022] Open
Abstract
ANCA-associated vasculitis (AAV) is a rare and potentially life threatening complication associated with antithyroid drug use. It is more commonly reported with propylthiouracil, with fewer cases reported with methimazole use. We present the case of a 55-year-old man with toxic multinodular goiter which was treated with methimazole for 6 months. He developed ANCA positive leukocytoclastic vasculitis with hemorrhagic and necrotic bullous lesions of lower extremities. The vasculitis was initially thought to be secondary to recent cephalosporin use; however, the skin lesions progressed despite stopping the cephalosporin and treatment with steroids, and he developed osteomyelitis. His vasculitis resolved after cessation of methimazole use. This case highlights the importance of careful monitoring for variable manifestations of AAV in patients treated with methimazole.
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Vascularite cutanée à anticorps anti-cytoplasme des polynucléaires neutrophiles induite par le benzylthio-uracile : à propos d’un cas et revue de la littérature. Rev Med Interne 2013; 34:561-4. [DOI: 10.1016/j.revmed.2013.05.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2012] [Revised: 05/06/2013] [Accepted: 05/27/2013] [Indexed: 11/22/2022]
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Sue M, Akama T, Kawashima A, Nakamura H, Hara T, Tanigawa K, Wu H, Yoshihara A, Ishido Y, Hiroi N, Yoshino G, Kohn LD, Ishii N, Suzuki K. Propylthiouracil increases sodium/iodide symporter gene expression and iodide uptake in rat thyroid cells in the absence of TSH. Thyroid 2012; 22:844-52. [PMID: 22853729 PMCID: PMC3407387 DOI: 10.1089/thy.2011.0290] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Propylthiouracil (PTU) and methimazole (MMI) are drugs that are widely used to treat Graves' disease. Although both exert an antithyroid effect primarily by blocking thyroid peroxidase activity, their molecular structure and other actions are different. We hypothesized that PTU and MMI may have differential effects on thyroid-specific gene expression and function. METHODS The effects of PTU and MMI on thyroid-specific gene expression and function were examined in rat thyroid FRTL-5 cells using DNA microarray, reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blot, immunohistochemistry, and radioiodine uptake studies. RESULTS DNA microarray analysis showed a marked increase in sodium/iodide symporter (NIS) gene expression after PTU treatment, whereas MMI had no effect. RT-PCR and real-time PCR analysis revealed that PTU-induced NIS mRNA levels were comparable to those elicited by thyroid-stimulating hormone (TSH). PTU increased 5'-1880-bp and 5'-1052-bp activity of the rat NIS promoter. While PTU treatment also increased NIS protein levels, the size of the induced protein was smaller than that induced by TSH, and the protein localized predominantly in the cytoplasm rather than the plasma membrane. Accumulation of (125)I in FRTL-5 cells was increased by PTU stimulation, but this effect was weaker than that produced by TSH. CONCLUSIONS We found that PTU induces NIS expression and iodide uptake in rat thyroid FRTL-5 cells in the absence of TSH. Although PTU and MMI share similar antithyroid activity, their effects on other thyroid functions appear to be quite different, which could affect their therapeutic effectiveness.
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Affiliation(s)
- Mariko Sue
- Laboratory of Molecular Diagnostics, Department of Mycobacteriology, National Institute of Infectious Diseases, Tokyo, Japan
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine (Omori), Toho University School of Medicine, Tokyo, Japan
| | - Takeshi Akama
- Laboratory of Molecular Diagnostics, Department of Mycobacteriology, National Institute of Infectious Diseases, Tokyo, Japan
| | - Akira Kawashima
- Laboratory of Molecular Diagnostics, Department of Mycobacteriology, National Institute of Infectious Diseases, Tokyo, Japan
| | - Hannah Nakamura
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine (Omori), Toho University School of Medicine, Tokyo, Japan
- Cell Regulation Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - Takeshi Hara
- Laboratory of Molecular Diagnostics, Department of Mycobacteriology, National Institute of Infectious Diseases, Tokyo, Japan
| | - Kazunari Tanigawa
- Laboratory of Molecular Diagnostics, Department of Mycobacteriology, National Institute of Infectious Diseases, Tokyo, Japan
| | - Huhehasi Wu
- Laboratory of Molecular Diagnostics, Department of Mycobacteriology, National Institute of Infectious Diseases, Tokyo, Japan
| | - Aya Yoshihara
- Laboratory of Molecular Diagnostics, Department of Mycobacteriology, National Institute of Infectious Diseases, Tokyo, Japan
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine (Omori), Toho University School of Medicine, Tokyo, Japan
| | - Yuko Ishido
- Laboratory of Molecular Diagnostics, Department of Mycobacteriology, National Institute of Infectious Diseases, Tokyo, Japan
| | - Naoki Hiroi
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine (Omori), Toho University School of Medicine, Tokyo, Japan
| | - Gen Yoshino
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine (Omori), Toho University School of Medicine, Tokyo, Japan
| | - Leonard D. Kohn
- Cell Regulation Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
- Department of Biomedical Sciences, Edison Biotechnology Institute, College of Osteopathic Medicine, Ohio University, Athens, Ohio
| | - Norihisa Ishii
- Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan
| | - Koichi Suzuki
- Laboratory of Molecular Diagnostics, Department of Mycobacteriology, National Institute of Infectious Diseases, Tokyo, Japan
- Cell Regulation Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
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Wakabayashi K, Kadowaki T. [A case of alveolar hemorrhage 35 years after propylthiouracil treatment]. Nihon Ronen Igakkai Zasshi 2012; 49:612-616. [PMID: 23459653 DOI: 10.3143/geriatrics.49.612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
A 69-year-old woman had received oral treatment of propylthiouracil (PTU) under a diagnosis of hyperthyroidism for 35 years. In the first 10 days of January 2009, she noticed the development of a cough. In February of the same year, she consulted a clinic with bloody sputum. Chest X-ray films revealed diffuse infiltration in both lungs, and she came to our hospital for further examination. An alveolar hemorrhage was identified by bronchial alveolar lavage testing. Because the cough was relieved by stopping PTU administration and there has been no relapse during 2-year follow-up, this case was diagnosed as PTU-induced diffuse alveolar hemorrhage. Her myeloperoxidase (MPO) -anti-neutrophil cytoplasmic antibody (ANCA) level was 55 EU, suggesting ANCA-associated angitis. However, as a drug lymphocyte stimulation test to PTU was also positive and her MPO-ANCA level was not elevated, the onset mechanism of this case was unclear.
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Affiliation(s)
- Kiryo Wakabayashi
- Department of Pulmonary Medicine, National Hospital Organization Matsue Medical Center
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Lee JH, Kim MS, Lee JG, Kim DS, Yang HJ, Kang KW. A Case of Diffuse Alveolar Hemorrhage with Glomerulonephritis after Propylthiouracil Treatment. Tuberc Respir Dis (Seoul) 2012. [DOI: 10.4046/trd.2012.72.1.93] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
- Ji Hyun Lee
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Min Su Kim
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Jae Gon Lee
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Dae Sik Kim
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Hae Jin Yang
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Kyung Woo Kang
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
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Sato H, Minagawa M, Sasaki N, Sugihara S, Kazukawa I, Minamitani K, Wataki K, Konda S, Inomata H, Sanayama K, Kohno Y. Comparison of methimazole and propylthiouracil in the management of children and adolescents with Graves' disease: efficacy and adverse reactions during initial treatment and long-term outcome. J Pediatr Endocrinol Metab 2011; 24:257-63. [PMID: 21823520 DOI: 10.1515/jpem.2011.194] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE The aim of this study was to compare the efficacy and adverse reactions during initial treatment and long-term outcome between children and adolescents with Graves' disease (GD) treated with propylthiouracil (PTU) and those treated with methimazole (MMI). DESIGN, SETTING AND PARTICIPANTS Retrospective and collaborative study. Children and adolescents with GD were divided into group M (MMI: n=64) and group P (PTU: n=69) and into four subgroups by initial dose: group M1 (<0.75 mg/kg of MMI, n=34), group M2 (> or = 0.75 mg/kg, n=30), group P1 (<7.5 mg/kg of PTU, n=24) and group P2 (> or = 7.5 mg/kg, n=45). MAIN OUTCOME MEASURES The duration for normalization of serum T4 on initial treatment, the incidence of adverse effects for one year and outcomes at 10 years after were compared. RESULTS Mean durations for normalization of T4 (+/- SD) were 1.7 +/- 1.0 months in group M and 2.3 +/- 2.4 in group P [not significant (NS)], while the mean duration in group P1 (3.1 +/- 3.3) was significantly longer than those in the other subgroups (M1: 1.9 +/- 1.2; M2: 1.4 +/- 0.7; P2; 1.7 +/- 1.3). No major adverse reaction was observed. Minor adverse effects occurred in 25.0% of cases in group M and 31.9% in group P (NS). The incidence in group P2 (44.4%) was significantly higher than those in group M1 (20.6%) and group P1 (8.3%). Remission rates did not differ between the MMI-treated group (35.0%, n=20) and PTU-treated group (50.0%, n=40). CONCLUSIONS PTU may not be suitable for initial use in children and adolescents with GD, even with the risk of major adverse reactions such as liver failure excluded.
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Carrion AF, Czul F, Arosemena LR, Selvaggi G, Garcia MT, Tekin A, Tzakis AG, Martin P, Ghanta RK. Propylthiouracil-induced acute liver failure: role of liver transplantation. Int J Endocrinol 2010; 2010:910636. [PMID: 21234410 PMCID: PMC3014703 DOI: 10.1155/2010/910636] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2010] [Accepted: 11/30/2010] [Indexed: 11/18/2022] Open
Abstract
Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death.
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Affiliation(s)
- Andres F. Carrion
- Department of Medicine, University of Miami Leonard M. Miller School of Medicine, 185 SW 7th Street, Unit 1510, Miami, FL 33130, USA
| | - Frank Czul
- Department of Medicine, University of Miami Leonard M. Miller School of Medicine, 185 SW 7th Street, Unit 1510, Miami, FL 33130, USA
| | - Leopoldo R. Arosemena
- Division of Hepatology, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33130, USA
| | - Gennaro Selvaggi
- Division of Liver and Gastrointestinal Transplantation, Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33130, USA
| | - Monica T. Garcia
- Department of Pathology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33130, USA
| | - Akin Tekin
- Division of Liver and Gastrointestinal Transplantation, Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33130, USA
| | - Andreas G. Tzakis
- Division of Liver and Gastrointestinal Transplantation, Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33130, USA
| | - Paul Martin
- Divisions of Hepatology and Liver and Gastrointestinal Transplantation, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33130, USA
| | - Ravi K. Ghanta
- Division of Gastroenterology, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33130, USA
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Calhan T, Senateş E, Cebeci E, Zuhur SS, Ozbakır F, Görpe U. A comparison of antineutrophil cytoplasmic antibody prevalence in patients treated and untreated for hyperthyroidism. Endocrine 2010; 38:199-205. [PMID: 21046481 DOI: 10.1007/s12020-010-9373-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2010] [Accepted: 07/01/2010] [Indexed: 12/16/2022]
Abstract
We aimed to compare the prevalence of antineutrophil cytoplasmic antibody (ANCA) and its subgroups between on-treatment (with anti-thyroid drugs; propylthiouracil, methimazole) and untreated patients with hyperthyroidism in our unit. Overall 78 consecutive patients were enrolled in the study; 45 patients were on-treatment (female/male 31:14) and 33 were newly diagnosed (female/male 20:13). We have studied ANCA, perinuclear-ANCA (p-ANCA), cytoplasmic-ANCA (c-ANCA), myeloperoxidase-ANCA (mpo-ANCA), and proteinase 3-ANCA (pr3-ANCA) in sera of all the patients. The data about clinical status, laboratory tests, and physical examination and mean duration of treatment in treated group were recorded. There was no statistically significant difference between the two groups for ANCA, c-ANCA, and pr3-ANCA (P=0.13, P=0.07, and P=0.63 respectively). p-ANCA and mpo-ANCA prevalences were significantly higher in on-treatment group than in untreated group (P=0.04 and P=0.01, respectively). The mean duration of treatment was 17 months in on-treatment group. The use of antithyroid drugs (propylthiouracil, methimazole) seems to be correlated with increased prevalence of ANCA. These drugs may especially increase p-ANCA and mpo-ANCA positivity.
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Affiliation(s)
- Turan Calhan
- Internal Medicine Department, Istanbul University Cerrahpaşa Faculty of Medicine, Istanbul, Turkey
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Servonnet A, Garcia-Hejl C, Banal F, Ramirez J, Fontan E. Anticorps anticytoplasme des polynucléaires neutrophiles multispécifiques induits par le propylthiouracile. Rev Med Interne 2010; 31:e9-e10. [DOI: 10.1016/j.revmed.2009.08.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2009] [Revised: 07/02/2009] [Accepted: 08/18/2009] [Indexed: 11/28/2022]
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Pasquet F, Pavic M, Mounier C, Karkowski L, Colle B. Vascularite avec anticorps anticytoplasme des polynucléaires neutrophiles : une complication rare du propylthiouracile. Rev Med Interne 2009; 30:882-5. [DOI: 10.1016/j.revmed.2009.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2008] [Revised: 02/01/2009] [Accepted: 04/05/2009] [Indexed: 10/20/2022]
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Benzylthiouracil-induced glomerulonephritis. Case Rep Med 2009; 2009:687285. [PMID: 19721711 PMCID: PMC2729276 DOI: 10.1155/2009/687285] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2009] [Accepted: 06/05/2009] [Indexed: 12/03/2022] Open
Abstract
Vasculitis is a rare complication of antithyroid drugs (ATDs). It was first described with Propylthiouracil (PTU). We report a new case of antineutrophil cytoplasmic antibody (ANCA) vasculitis with glomerulonephritis induced by Benzylthiouracile (BTU). A 50-year-old man with Graves disease treated with BTU developed general malaise and haematuria without skin rash or respiratory involvement. Laboratory data revealed acute renal failure with proteinuria and haematuria. An indirect immunofluorescence test for ANCA was positive, showing a perinuclear pattern with specificity antimyeloperoxidase (MPO). A renal biopsy was performed and revealed pauci-immune extracapillary glomerular nephropathy and necrotic vasculitis lesions. Based on these findings we concluded to the diagnosis of rapidly progressive glomerulonephritis associated with ANCA induced by BTU therapy. The drug was therefore discontinued and the patient was treated with steroids and immunosuppressive treatment during 3 months. Renal failure, proteinuria and haematuria significantly improved within 2 months. However, P-ANCA remained positive until 10 months after drug withdrawal. Thyroid function was kept within normal range using iodine solution. We demonstrated clearly that BTU may induce severe forms of vasculitis with glomerulonephritis. Thus, the ANCA must be measured when confronted to systemic manifestation during treatment.
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Churg-Strauss Syndrome following PTU Treatment. Int J Rheumatol 2009; 2009:504105. [PMID: 20107567 PMCID: PMC2809019 DOI: 10.1155/2009/504105] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2008] [Accepted: 02/16/2009] [Indexed: 11/17/2022] Open
Abstract
Propylthiouracil (PTU) is a frequently prescribed drug in the treatment of hyperthyroidism. The use of PTU is, however, accompanied by numerous potentially serious side effects including vasculitis. PTU-related vasculitides can present as haematuria, pulmonary haemorrhage, or cutaneous lesion together with aspecific symptoms such as fever, myalgia, arthralgia, and fatigue. Cerebral involvement is seldom observed. We present a 49-year-old female with Graves' disease and asthma, who developed paresis of the proximal extremities, eosinophilia, pulmonary, and cutaneous lesions following treatment with PTU. A cerebral vasculitis consistent with Churg-Strauss syndrome (CSS) was suspected. Although cerebral involvement is seldom observed with PTU treatment, cerebral vasculitis should be considered in patients developing CNS symptoms.
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Tripodi PF, Ruggeri RM, Campennì A, Cucinotta M, Mirto A, Lo Gullo R, Baldari S, Trimarchi F, Cucinotta D, Russo GT. Central nervous system vasculitis after starting methimazole in a woman with Graves' disease. Thyroid 2008; 18:1011-3. [PMID: 18788922 DOI: 10.1089/thy.2008.0121] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Graves' disease (GD), a prototypical autoimmune disorder, is associated with other autoimmune diseases, including vasculitis. Antithyroid drugs, despite their postulated immunosuppressive effects, may cause several autoimmune disorders. Here we describe the first patient with central nervous system (CNS) vasculitis that developed shortly after the start of methimazole (MMI) treatment for GD. PATIENT FINDINGS CNS vasculitis was suspected on the basis of the clinical features and neurologic examination, showing a reinforcement of deep reflexes, especially of the left knee and Achilles reflexes. The diagnosis was confirmed by a brain magnetic resonance imaging (MRI), which showed some hyperintensive spots in the subcortical substantia alba and in the parietal area bilaterally, and by a single-photon emission computed tomography (SPECT) imaging, which showed a nonhomogenous distribution of the blood flow in the brain, with a reduced perfusion on the left side of the frontotemporal and parietal regions, and on the right side of the frontotemporal area. MMI was stopped before total thyroidectomy, and symptoms resolved in the next 5 weeks. Six months after MMI was stopped, the brain MRI and SPECT had become normal. SUMMARY To our knowledge, this is the first report of CNS vasculitis related to MMI therapy.
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Gao Y, Chen M, Ye H, Yu F, Guo XH, Zhao MH. Long-term outcomes of patients with propylthiouracil-induced anti-neutrophil cytoplasmic auto-antibody-associated vasculitis. Rheumatology (Oxford) 2008; 47:1515-20. [DOI: 10.1093/rheumatology/ken321] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Une complication rare du propylthio-uracile au cours d’une maladie de Basedow. Rev Med Interne 2008. [DOI: 10.1016/j.revmed.2008.03.225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Hachicha M, Kammoun T, Ben Romdhane W, Ben Abdallah R, Mahfoudh A, Kammoun K, Hachicha J, Triki A. Vascularite avec atteinte rénale et anticorps anticytoplasme des polynucléaires neutrophiles (ANCA) après prise de benzylthio-uracile chez l'enfant. Nephrol Ther 2007; 3:147-51. [PMID: 17658441 DOI: 10.1016/j.nephro.2007.04.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2006] [Revised: 03/26/2007] [Accepted: 04/11/2007] [Indexed: 11/15/2022]
Abstract
Vasculitis associated to antineutrophil cytoplasmic antibodies (ANCA) is a rare complication of therapy with antithyroid medication. They were mainly described in patients treated with propylthiouracil (PTU), carbimazole, methimazole and rarely by benzylthiouracil (Basden). We report a case of 12-years-old girl treated by benzylthiouracil for Grave's disease who developed after 2 years vasculitis associated with cutaneous involvement (generalized ulcer necrotic purpura) and glomerulonephritis with proteinuria of 24 hours at 26 mg/kg/day, microscopic hematuria and renal failure with creatinemia level at 135 micromol/l. The ANCA type antiMPO (myeloperoxidase) was positive. The histology study of the renal needle biopsy was in favour with focal necrotizing glomerulonephritisand crescents with different evolutive stages. The discontinuation of benzylthiouracil and the treatment by the corticoids involved a disappearance of cutaneous lesions, a negative result of proteinuria, a normalization of the renal function (creatinemia=84 micromol/l) and a disappearance of hematuria and ANCA. These results permitted to announce hypothesis that benzylthiouracil was implicated in development of vasculitis associated to ANCA.
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Gao Y, Chen M, Ye H, Guo XH, Zhao MH, Wang HY. Follow-up of avidity and titre of anti-myeloperoxidase antibodies in sera from patients with propylthiouracil-induced vasculitis. Clin Endocrinol (Oxf) 2007; 66:543-7. [PMID: 17371473 DOI: 10.1111/j.1365-2265.2007.02770.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE Propylthiouracil (PTU) has been known to induce myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positive vasculitis. Our previous study indicated that the increase of avidity of MPO-ANCA might be associated with the occurrence of clinical vasculitis in patients with PTU-induced ANCA. The current study aimed to follow-up the avidity and titre of anti-MPO antibodies in sequential sera from patients with PTU-induced ANCA-associated systemic vasculitis (AASV). METHODS Six patients with PTU-induced vasculitis were enrolled in the current study. Serial sera in both active phase and in remission were collected. MPO-ANCA avidity was assessed by antigen-inhibition enzyme-linked immunosorbent assays (ELISAs), and avidity constant (aK) was determined as the reciprocal value of the MPO molar concentration in the liquid phase resulting in 50% inhibition of anti-MPO antibody binding to MPO in solid phase ELISA. Titres of MPO-ANCA were determined by using serial serum dilutions in MPO-ELISA. RESULTS After cessation of PTU and initiation of immunosuppressive therapy, the avidity and titre of MPO-ANCA decreased significantly during follow-up in sera from all the patients, and the avidity decreased much more quickly than the titres. CONCLUSION Our study indicates that avidity of anti-MPO antibodies might be more closely associated with clinical vasculitis than titre.
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Affiliation(s)
- Ying Gao
- Department of Nephrology, Peking University first Hospital, Beijing, China
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19
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Sato H, Harada S, Yokoya S, Tanaka T, Asayama K, Mori M, Sasaki N. Treatment for childhood-onset Graves' disease in Japan: results of a nationwide questionnaire survey of pediatric endocrinologists and thyroidologists. Thyroid 2007; 17:67-72. [PMID: 17274753 DOI: 10.1089/thy.2006.0193] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE AND DESIGN To determine the present condition of treatment of childhood-onset Graves' disease in Japan, a nationwide questionnaire survey was conducted among councilors of the Japanese Society for Pediatric Endocrinology and the Japan Thyroid Association. MAIN OUTCOME Responses were received from 125 individuals, and the rate of collection of questionnaires was 47%. Methimazole was selected for first-line initial antithyroid drug therapy by 92% of respondents. Antithyroid drugs tended to be given at larger initial doses and over longer periods of time to childhood-onset patients than to adult patients, and these tendencies were more pronounced for pediatric endocrinologists. Combination therapy with an antithyroid drug and thyroxine was used more frequently by pediatric endocrinologists. Thyroidologists had more experience with radioiodine therapy than pediatric endocrinologists. Opinions regarding preparation of guidelines for the initial dose of methimazole in childhood-onset Graves' disease were almost equally divided among the following: the dose of methimazole should be adjusted according to the severity of disease as in adult cases, methimazole should be started at a dose of 1mg/kg per day in all patients, and the dose should be determined based on results of a randomized study. CONCLUSIONS The present condition of treatment of childhood-onset Graves' disease in Japan was clarified.
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20
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Bilu Martin D, Deng A, Gaspari A, Pearson F. Perinuclear antineutrophil cytoplasmic antibody-associated vasculitis in a patient with Graves' disease treated with methimazole. Skinmed 2006; 5:302-5. [PMID: 17086001 DOI: 10.1111/j.1540-9740.2006.05350.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
A 15- year-old Caucasian girl presented with a 1-week history of necrotic ulcers on her bilateral lower extremities, associated with fever and malaise. She had had similar ulcerations on and off over the past 3 years. She had a medical history of Graves' disease, diagnosed in 1999, for which she was taking methimazole (MMI). On physical examination, there were multiple necrotic ulcers with elevated, inflamed borders and an overlying eschar on the bilateral distal extremities (Figure 1). There was one hemorrhagic, flaccid bulla on the lateral aspect of the ankle. Her complete blood count, comprehensive metabolic panel, prothrombin time, and international normalized ratio were within normal limits. Histopathology revealed a neutrophilic vasculitis involving small as well as medium-sized blood vessels. The overlying epidermis and upper dermis showed necrosis (Figure 2). Antinuclear antibody (ANA) was positive at 1:160. Perinuclear (p-) antineutrophil cytoplasmic antibody (ANCA) was positive at 1:320. Cytoplasmic ANCA was negative. The patient did not meet any clinical criteria for a diagnosis of lupus erythematosus. Direct immunofluorescence revealed IgM, complement C3, and fibrin in small- and medium-caliber blood vessels in the dermis, consistent with a leukocytoclastic vasculitis of small- and medium-caliber blood vessels (Figure 3). MMI was stopped and the patient was given prednisone, tapered over 5 days. Her thyroid function remained stable, and she did not develop new necrotic ulcers. One month later, the patient developed urticarial lesions on her lower extremities. Histopathology revealed a lymphocytic vascular reaction. No eosinophils or neutrophils were seen. These newer urticarial lesions resolved. The patient underwent debridement of the thick, necrotic ulcerative eschars. To date, her lesions have resolved (Figure 4). An ANA drawn 5 months after withdrawal of MMI was negative, and p-ANCA was 1:67.
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MESH Headings
- Adolescent
- Antibodies, Antineutrophil Cytoplasmic
- Antithyroid Agents/adverse effects
- Diagnosis, Differential
- Female
- Graves Disease/drug therapy
- Humans
- Leg Ulcer/chemically induced
- Leg Ulcer/diagnosis
- Leg Ulcer/immunology
- Leg Ulcer/pathology
- Methimazole/adverse effects
- Vasculitis, Leukocytoclastic, Cutaneous/diagnosis
- Vasculitis, Leukocytoclastic, Cutaneous/etiology
- Vasculitis, Leukocytoclastic, Cutaneous/immunology
- Vasculitis, Leukocytoclastic, Cutaneous/pathology
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Affiliation(s)
- Donna Bilu Martin
- Department of Dermatology, University of Maryland Medical System, Baltimore, MD, USA.
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Benyounes M, Sempoux C, Daumerie C, Rahier J, Geubel AP. Propylthiouracyl-induced severe liver toxicity: An indication for alanine aminotransferase monitoring? World J Gastroenterol 2006; 12:6232-4. [PMID: 17036403 PMCID: PMC4088125 DOI: 10.3748/wjg.v12.i38.6232] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Propylthiouracyl (PTU)-related liver toxicity is likely to occur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced subacute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the underestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotransferase monitoring, at least during the first six months of therapy.
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Affiliation(s)
- M Benyounes
- Department of Gastroenterology, St Luc University Hospital, Université Catholique de Louvain, Brussels 1200, Belgium
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22
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Aloush V, Litinsky I, Caspi D, Elkayam O. Propylthiouracil-Induced Autoimmune Syndromes: Two Distinct Clinical Presentations with Different Course and Management. Semin Arthritis Rheum 2006; 36:4-9. [PMID: 16887463 DOI: 10.1016/j.semarthrit.2006.03.003] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
OBJECTIVES To report 4 cases of propythiouracil (PTU)-induced lupus or vasculitis and to review the literature on that subject. METHODS We describe the clinical presentation, course, and outcome of 4 patients and review the medical literature registered in the Medline PubMed database from 1966 to 2004 by using the keywords: Graves, thyrotoxicosis, propylthiouracil, lupus, vasculitis, arthritis, rash, ANA, and ANCA. Cases were classified into drug-induced lupus (DIL) or vasculitis using accepted definitions and evaluated with emphasis on gender, age, origin, duration of treatment, delay in diagnosis, clinical and serological features, and outcome. RESULTS We described our 4 patients and analyzed 42 well-documented cases of DIL- and PTU-induced vasculitis (30 had vasculitis and 12 fulfilled the classification criteria of DIL). Patients with vasculitis were significantly older (mean 43 versus 22 years) and had a longer duration of treatment in comparison with DIL (35 versus 24 weeks). Musculoskeletal symptoms were prominent in DIL, while renal and pulmonary involvement was found in a significantly higher proportion of PTU-induced vasculitis. ANA, anti-DNA, and anti-histone were predominantly found in DIL, while p-ANCA was found in a similar proportion of patients in both groups. c-ANCA was detected only in patients with vasculitis. All patients with DIL completely recovered (most after stopping PTU), while about 50% of PTU-induced vasculitis needed steroids or immunosuppressive drugs, including cyclophosphamide and plasmapheresis. CONCLUSIONS Most of the cases of PTU-induced autoimmune phenomena are due to vasculitis. Despite the common presence of p-ANCA in both DIL- and PTU-induced vasculitis, substantial differences in demographic, clinical, and outcome features of these entities allow an accurate diagnosis and consequent management.
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Affiliation(s)
- Valerie Aloush
- Trainee in Rheumatology, Department of Rheumatology, Tel Aviv Medical Center and the Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel
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Affiliation(s)
- David S Cooper
- Division of Endocrinology, Sinai Hospital of Baltimore, the Johns Hopkins University School of Medicine, Baltimore 21215, USA.
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Calañas-Continente A, Espinosa M, Manzano-García G, Santamaría R, Lopez-Rubio F, Aljama P. Necrotizing glomerulonephritis and pulmonary hemorrhage associated with carbimazole therapy. Thyroid 2005; 15:286-8. [PMID: 15785249 DOI: 10.1089/thy.2005.15.286] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Methimazole, carbimazole, and propylthiouracil (PTU) are the mainstays of antithyroid drug therapy. Adverse effects of these drugs have been documented in less than 15% of patients undergoing treatment for hyperthyroidism. Common problems include fever, skin rash, urticaria, arthralgias, and arthritis. Vasculitis associated with antineutrophil anticytoplasmic antibodies (ANCA) has been reported on several occasions following treatment with PTU. However, vasculitis rarely appears to be associated with carbimazole. We report the clinical history of a woman with a necrotizing glomerulonephritis and pulmonary hemorrhage associated with carbimazole therapy.
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Boulenger-Vazel A, Kupfer-Bessaguet I, Gouedard C, Leberre R, Leroy JP, Sonnet E, Desvignes O, Misery L, Sassolas B. Dermatose neutrophilique associée à des anticorps anticytoplasme des polynucléaires neutrophiles (p-ANCA) induits par le propylthiouracil. Ann Dermatol Venereol 2005; 132:27-31. [PMID: 15746603 DOI: 10.1016/s0151-9638(05)79191-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION We report on a patient who progressively developed polymorphic expressions of neutrophilic dermatosis (Sneddon-Wilkinson subcorneal pustulosis and pyoderma gangrenosum) associated with p-antineutrophil cytoplasmic antibodies (p-ANCA), while receiving propylthiouracil for hyperthyroidism. To our knowledge, such associations have never been published so far. CASE-REPORT A 40 year-old woman was treated with propylthiouracil for Graves'disease. After 16 months of therapy, she noted flares of pustular lesions surrounded with erythematous halo mainly localized on the trunk. The lesions became chronic, and were not improved by potent topical corticosteroids. When first seen in our department in February 2003, the eruption was typical of Sneddon-Wilkinson subcorneal pustulosis. This diagnosis was confirmed by the histological examination of a skin biopsy of a pustule. One month later, she developed an inflammatory progressively ulcerative lesion on the right ankle, typical of pyoderma gangrenosum. The diagnosis was confirmed by the histological examination of a skin biopsy taken on the evolving border of the lesion and showed polynuclear neutrophilic infiltration without vasculitis. Direct immunofluorescence was negative. The presence of serum anti-myeloperoxydase p-ANCA was known for this patient since October 2002. No IgA monoclonal gammapathy was revealed on extensive biological check-up. Systemic oral corticosteroid therapy (1 mg/kg/day) dramatically improved skin lesions with complete healing within 8 weeks. DISCUSSION Propylthiouracil is well known to induce the occurrence of ANCA in 20 to 64p. 100 of patients treated for Graves'disease. The mechanisms involved are badly recognized so far. Cutaneous vasculitis, glomerulonephritis and polychondritis may be clinically associated with those antibodies. Rare observations of neutrophilic dermatosis, mostly Sweet's syndrome, have been described in patients with propylthiouracil-induced ANCA. One case-report described a 44 year-old woman who developed pyoderma gangrenosum associated with propylthiouracil-induced p-ANCA. These manifestations usually appear within 2 years, as our patient. The data in the literature, allows us to report the polymorphic expressions of neutrophilic dermatosis in this patient with p-ANCA which could be related to propylthiouracil. Such association of Sneddon-Wilkinson subcorneal pustulosis and pyoderma gangrenosum with p-ANCA has never been described in this endocrinologic context so far. Furthermore we propose that neutrophilic dermatosis should be inscribed in the list of side effects induced by propylthiouracil therapy.
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Vanek C, Samuels MH. Central nervous system vasculitis caused by propylthiouracil therapy: a case report and literature review. Thyroid 2005; 15:80-4. [PMID: 15687828 DOI: 10.1089/thy.2005.15.80] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Antineutrophil cytoplasmic antibodies (ANCA) are associated with vasculitis, including vasculitis induced by drugs such as the thionamides. The affected organ systems in thionamide-induced vasculitis have been primarily renal, musculoskeletal, and dermatologic. We describe the first case of thionamide-induced central nervous system vasculitis presenting as confusion, with complete resolution after discontinuation of propylthiouracil. We review the literature and summarize 42 additional cases of thionamide-induced ANCA-positive vasculitis since 1992. Propylthiouracil was responsible in 93% of cases and the predominant ANCA pattern on immunofluorescent staining was perinuclear (p-ANCA). Clinical improvement occurred after drug discontinuation in 93%, steroid therapy was used in some cases. The mean duration of treatment with thionamides was 35 months prior to presentation. Long-term medical treatment with thionamides for hyperthyroidism may increase the risk of this severe side effect.
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Affiliation(s)
- C Vanek
- Oregon Health and Science University, Divison of Endocrinology, Diabetes, and Clinical Nutrition, Portland, OR 97239-3098, USA
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27
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Abstract
Rheumatic syndromes related to drug therapies have been described for decades. The introduction of many new therapeutic agents in recent years has been accompanied by an increase in such reported associations. By definition, drug-induced syndromes are temporally related to starting a drug, and the symptoms and signs generally regress with its discontinuation. The classic and still most common cases resemble systemic lupus erythematosus or scleroderma. Some newer agents appear related to myositis or vasculitis. The origins of most of these syndromes remain obscure.
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Affiliation(s)
- Beth L Brogan
- Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232-2681, USA
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Tieulie N, Huong DLT, Andreu M, Wechsler B, Mercadal L, Beaufils H, Diermert MC, Piette JC. [ANCA associated glomerulonephritis related to benzylthiouracil]. Rev Med Interne 2002; 23:853-6. [PMID: 12428489 DOI: 10.1016/s0248-8663(02)00694-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
INTRODUCTION Vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) have been reported in patients suffering from Graves' disease treated with anti-thyroid drugs and especially propylthiouracil (PTU). EXEGESIS We report a case of Graves' disease treated with benzylthiouracil (Basdène). This therapy was complicated by acute renal insufficiency due to crescentic glomerulonephritis associated with pANCA. After benzylthiouracil withdrawal and under corticosteroids, renal insufficiency, biological inflammation and pANCA levels decreased. CONCLUSION Similar vasculitis associated with pANCA secondary to anti-thyroid drugs, especially propylthiouracil, were described. This suggests a causal relation between drug and vasculitis. To our best knowledge, it is the first case of vasculitis secondary to benzylthiouracil.
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Affiliation(s)
- N Tieulie
- Service de médecine interne, groupe hospitalier Pitié-Salpêtrière, 47, boulevard de l'Hôpital, 75651 Paris, France
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Wada N, Mukai M, Kohno M, Notoya A, Ito T, Yoshioka N. Prevalence of serum anti-myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) in patients with Graves' disease treated with propylthiouracil and thiamazole. Endocr J 2002; 49:329-34. [PMID: 12201217 DOI: 10.1507/endocrj.49.329] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Patients with Graves' disease (n = 61) treated with propylthiouracil (PTU) or thiamazole (MMI) were studied retrospectively to investigate differences in the prevalence of anti-myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) in relation to treatment with anti-thyroid drugs. The patients were divided into two groups: PTU-treated group (n = 32) and MMI-treated group (n = 29). There were no significant differences between the two groups in terms of age, gender distribution, or duration of treatment. In the PTU group, 8/32 (25%) patients were positive for MPO-ANCA, whereas in the MMI group, 1/29 (3.4%) patients were positive. There were no significant differences in age, duration, or dosage between the MPO-ANCA positive and negative patients. Most of the MPO-ANCA positive patients were asymptomatic, except for two patients in whom rheumatic arthritis or membranous glomerulonephritis developed. None of the MPO-ANCA positive patients were diagnosed as having classical ANCA-associated vasculitis. Thus, there is a high frequency of MPO-ANCA in patients with Graves' disease treated with PTU, compared with patients treated with MMI, although classical ANCA-associated vasculitis develops in only a few MPO-ANCA positive patients.
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Affiliation(s)
- Norio Wada
- Division of Endocrinology and Metabolism, Department of Medicine, Sapporo City General Hospital, Kita-11, Nishi-13, Chuo-Ku, Sapporo 060-8604, Japan
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Fujieda M, Hattori M, Kurayama H, Koitabashi Y. Clinical features and outcomes in children with antineutrophil cytoplasmic autoantibody-positive glomerulonephritis associated with propylthiouracil treatment. J Am Soc Nephrol 2002; 13:437-445. [PMID: 11805173 DOI: 10.1681/asn.v132437] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A retrospective investigation was conducted by members of the Japanese Society for Pediatric Nephrology from 1990 to 1997 to define the clinical features and outcomes in children with antineutrophil cytoplasmic autoantibody (ANCA)-positive glomerulonephritis associated with propylthiouracil treatment. Seven Japanese pediatric patients who had myeloperoxidase-specific ANCA-positive biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis associated with propylthiouracil administration were entered in the study. Three patients had nephritis alone, and four had nephritis and extrarenal organ system vasculitis. Females predominated, and the mean age at onset was 14 yr. Propylthiouracil was reduced or discontinued in all patients and was switched to methimazole in three patients. For the treatment of nephritis, five patients received corticosteroids; three had pulse methylprednisolone, one had plasma exchange, and one had plasma exchange and pulse methylprednisolone before initiating oral prednisolone. The remaining two patients received cyclophosphamide and corticosteroids, one of whom had pulse methylprednisolone before initiating oral prednisolone and cyclophosphamide. All patients achieved remission. In general, ANCA titers correlated with the response to treatment and disease activity, with some exceptions. No patient progressed to end-stage renal disease, renal dysfunction, or death during the follow-up period (58 +/- 25 mo; range, 32 to 108 mo). All but one patient remained euthyroid. In conclusion, this experience suggests that the clinical disease spectrum of ANCA-positive disease associated with propylthiouracil treatment is similar in pediatric and adult patients and that the overall prognosis may be better than that in the non-drug-induced ANCA-positive disease.
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Affiliation(s)
- Mikiya Fujieda
- *Department of Pediatrics, Kochi Medical School, Kochi; Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo; Department of Pediatrics, National Chiba Higashi Hospital, Chiba; and Department of Pediatrics, St. Marianna University, School of Medicine, Kawasaki, Japan
| | - Motoshi Hattori
- *Department of Pediatrics, Kochi Medical School, Kochi; Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo; Department of Pediatrics, National Chiba Higashi Hospital, Chiba; and Department of Pediatrics, St. Marianna University, School of Medicine, Kawasaki, Japan
| | - Hideaki Kurayama
- *Department of Pediatrics, Kochi Medical School, Kochi; Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo; Department of Pediatrics, National Chiba Higashi Hospital, Chiba; and Department of Pediatrics, St. Marianna University, School of Medicine, Kawasaki, Japan
| | - Yasushi Koitabashi
- *Department of Pediatrics, Kochi Medical School, Kochi; Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo; Department of Pediatrics, National Chiba Higashi Hospital, Chiba; and Department of Pediatrics, St. Marianna University, School of Medicine, Kawasaki, Japan
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Dysseleer A, Buysschaert M, Fonck C, Van Ginder Deuren K, Jadoul M, Tennstedt D, Cosyns JP, Daumerie C. Acute interstitial nephritis and fatal Stevens-Johnson syndrome after propylthiouracil therapy. Thyroid 2000; 10:713-6. [PMID: 11014318 DOI: 10.1089/10507250050137815] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
We report a case of acute interstitial nephritis and fatal Stevens-Johnson syndrome in a 90-year-old woman with amiodarone-induced hyperthyroidism, who had been treated for 5 weeks with propylthiouracil (PTU). On admission, the patient exhibited acute renal failure and generalized macular purpuric eruption. Acute interstitial nephritis and Stevens-Johnson syndrome were diagnosed and PTU withdrawn. Although renal function recovered after PTU withdrawal and corticosteroid therapy, the patient's condition worsened, and she died after developing multiple organ failure. Acute interstitial nephritis seems to be rarely associated with PTU therapy. Moreover, a literature review suggested that this could represent the first published report of a Stevens-Johnson syndrome developing during PTU therapy.
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Affiliation(s)
- A Dysseleer
- Department of Endocrinology, Université Catholique de Louvain, Cliniques Universitaires St. Luc, Brussels, Belgium
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