propylthiouracil and Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) refers to a group of potentially life-threatening autoimmune diseases. A recent development in this field is the recognition that certain drugs can induce AAV. Among these agents, the drug most often implicated in causing disease is the commonly used antithyroid agent propylthiouracil (PTU). This Review provides an update on PTU-induced AAV. Clinical characteristics of PTU-induced AAV are similar to that of primary AAV, but usually have a milder course and better prognosis, provided early cessation of the disease-causing drug. PTU-induced ANCAs usually react to several components of myeloid granules, which is helpful in differentiating PTU-induced AAV from primary AAV. Early cessation of PTU is crucial in the treatment of PTU-induced AAV. The duration of immunosuppressive therapy might be shorter than in primary AAV, depending on the severity of organ damage, and maintenance therapy is not always necessary.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoimmune Diseases; Glucocorticoids; Humans; Immunosuppressive Agents; Plasmapheresis; Prognosis; Propylthiouracil; Risk Factors; Vasculitis

Propylthiouracil (PTU), methimazole (MMI) and carbimazole are indicated for the treatment of hyperthyroidism in adult and pediatric patients. The aim of this review is to present all the relevant information regarding the use of antithyroid drugs (ATD) in pediatric thyrotoxic cases, the pediatric toxicology of ATD and the warning which has recently been issued for PTU by the FDA.. Epidemiology, diagnosis and treatment of pediatric thyrotoxicosis are all presented in this article. The authors also extensively discuss the details regarding the pharmacology, bioactivation, biodisposition, bioavailability and pharmacokinetic properties of the two main ATD (MMI and PTU).. The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.

Topics: Agranulocytosis; Animals; Antithyroid Agents; Carbimazole; Child; Child, Preschool; Evidence-Based Medicine; Female; Graves Disease; Humans; Hyperthyroidism; Liver Failure; Methimazole; Pregnancy; Propylthiouracil; Randomized Controlled Trials as Topic; Thyrotoxicosis; Vasculitis

A recent development in the field of vasculitis is the increasing recognition that certain medications such as propylthiouracil can induce anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). This review focuses on the data on causal drugs, possible pathogenesis, clinical description, diagnosis, treatment and prognosis of patients with drug-induced AAV. The pathogenesis of drug-induced AAV might be multifactorial. The clinical manifestations are similar to those of primary AAV, but ANCA with multi-antigenicity may help to differentiate it from primary AAV. The diagnosis of drug-induced AAV is based on the temporal relationship between clinically evident vasculitis and administration of the offending drugs, and excluding medical conditions that mimic vasculitis and other definable types of vasculitis. After the diagnosis of drug-induced AAV was made, the offending drugs should be withdrawn immediately, and appropriate immunosuppressive therapy should be administered only for patients with vital organ involvement. The duration of immunosuppressive therapy should be much shorter than that in primary AAV and long-term maintenance therapy might not be necessary. The prognosis of patients with drug-induced AAV is good as long as the offending drug is discontinued in time.

Topics: Animals; Antibodies, Antineutrophil Cytoplasmic; Humans; Leukotriene Antagonists; Peroxidase; Prognosis; Propylthiouracil; Vasculitis

Recent studies provided new insights into the pathogenesis of vasculitides associated with antineutrophil cytoplasm antibodies (ANCA). They yield more information about the pathogenic role of ANCA, the initiation of the immune response against proteinase 3, the expression of ANCA target antigens on neutrophil surfaces, endothelial damage and the mechanisms of vasculitis associated with propylthiouracil. The pathogenic role of antimyeloperoxidase antibodies has been established in vitro and in vivo in animal models and in human. A pathogenic role for antiproteinase 3 antibodies has not yet been clearly established in vivo although it is well documented in vitro.

Topics: Adult; Animals; Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Chemokines; Churg-Strauss Syndrome; Dendritic Cells; Disease Models, Animal; Epitopes; Female; Granulomatosis with Polyangiitis; Humans; Infant, Newborn; Male; Mice; Myeloblastin; Peroxidase; Polymorphism, Genetic; Propylthiouracil; Rats; Rats, Inbred WKY; Risk; Vasculitis

Antithyroid drugs sometimes cause severe complications. Propylthiouracil (PTU) can be associated to ANCA positive vasculitis, most often related to myeloperoxidase subtype (ANCA-MPO). Our objective is to describe a female patient with Graves' disease, who developed PTU induced-autoimmune disease, with cutaneous, pulmonary, and renal lesions, associated with ANCA. Histopathological examination revealed diffuse pulmonary hemorrhage, and focal segmental glomerulosclerosis at the kidney biopsy. She was treated with systemic corticosteroid therapy and cyclophosphamide, with clinical improvement. This case highlights the need for greater awareness of this relatively rare adverse effect of propylthiouracil.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoimmune Diseases; Female; Graves Disease; Humans; Immunologic Factors; Peroxidase; Propylthiouracil; Vasculitis

Topics: Alleles; alpha 1-Antitrypsin; Animals; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal; Antithyroid Agents; gamma-Globulins; Glomerulonephritis; HLA Antigens; Humans; Immunosuppressive Agents; Infliximab; Lipopolysaccharides; Mycophenolic Acid; Neutrophil Activation; Propylthiouracil; Silicon Dioxide; Staphylococcus aureus; Vasculitis

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.

Topics: Central Nervous System Diseases; Confusion; Female; Graves Disease; Humans; Middle Aged; Propylthiouracil; Vasculitis

A 50-year-old woman was admitted because of severe exophthalmos associated with Graves disease. She underwent methimazole (MMI) and methylprednisolone pulse therapy against exophthalmos. She noticed photophobia and blurred vision 3 weeks after the start of pulse therapy and she was diagnosed as having uveitis. Methylprednisolone pulse therapy was performed again for both exophthalmos and uveitis, followed by daily administration of 20 mg of prednisolone and instillation of betamethasone for 2 weeks and the uveitis was improved. Western blot analysis confirmed that human T lymphotropic virus type 1 (HTLV-1) antibody was present in her serum. Propylthiouracil was substituted for MMI and HTLV-1-associated uveitis (HAU) has not recurred. Six months after the beginning of administration of PTU, anti-neutrophil cytoplasmic antibody-related vasculitis developed in the patient. We review 43 cases of HAU with Graves disease, including the present case, in the literature. Only 2 of 27 cases (except unknown cases) (7.4%) had Graves ophthalmopathy. To the best of our knowledge, there has been no investigation of HAU and Graves ophthalmopathy.

Topics: Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; HTLV-I Infections; Humans; Magnetic Resonance Imaging; Methimazole; Methylprednisolone; Middle Aged; Prednisolone; Propylthiouracil; Severity of Illness Index; Thyroid Hormones; Time Factors; Treatment Outcome; Uveitis; Vasculitis

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Humans; Middle Aged; Peroxidase; Propylthiouracil; Vasculitis

We report a case of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis induced by propylthiouracil (PTU), and review the literature concerning to anti-thyroid drug-induced ANCA-associated vasculitis. A 45-year-old man treated with PTU developed fever and arthralgia without pulmonary, skin or eye involvement. These symptoms persisted for a long period without specific symptom, sign or laboratory data of other arthritis. Laboratory findings of urine and blood were normal, except for positive MPO-ANCA (191EU) and PR3-ANCA (37EU) findings. After PTU was discontinued without steroids or immune modulating drugs, both symptoms disappeared. Our patient had a high titer of MPO-ANCA. Moreover, titers of ANCA fell in correlation with the course of symptoms after the cessation of PTU, and we diagnosed PTU-induced ANCA-associated vasculitis. Most patients with pulmonary renal syndrome receive anti-thyroid drugs over a prolonged period, but the duration of our case was shorter than those of these patients. It is suggested that our patient was diagnosed at an early stage of ANCA-associated vasculitis before the start of pulmonary or renal involvement.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Humans; Japan; Male; Middle Aged; Propylthiouracil; Vasculitis

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Female; Glomerulonephritis; Hemorrhage; Humans; Propylthiouracil; Pulmonary Circulation; Radiography, Thoracic; Vasculitis

A 39-year-old Japanese woman had been receiving propylthiouracil for 5 years for hyperthyroidism when she developed myalgia, scleritis, proteinuria, fever, and inflammation of the nose. Examination of a renal biopsy specimen showed focal segmental necrotizing glomerulonephritis. Indirect immunofluorescent staining showed a highly positive perinuclear pattern of anti-neutrophil cytoplasmic antibody (ANCA) in her serum. Enzyme-linked immunosorbent assay (ELISA) of the ANCA showed positivity for anti-proteinase 3, anti-myeloperoxidase, anti-leukocyte elastase, and anti-lactoferrin, but anti-cathepsin G and anti-lysozyme were negative. Because ELISA showed the titer of anti-leukocyte elastase antibody to be markedly elevated, we challenged this data by performing dot blot analysis. The patient's serum reacted with the native form, but not with denatured leukocyte elastase. Propylthiouracil-induced vasculitis was suspected. Symptoms abated within 2 weeks and all values of ANCA were reduced after the drug was withdrawn. Vasculitis is a rare side-effect of propylthiouracil therapy. Recently it was reported in association with ANCA. We present the findings of this patient and compare them with those described in 19 published cases of propylthiouracil-induced vasculitis associated with ANCA.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Humans; Hyperthyroidism; Leukocyte Elastase; Propylthiouracil; Vasculitis

Topics: Agranulocytosis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Humans; Propylthiouracil; Vasculitis

Topics: Adult; Antithyroid Agents; Cheek; Female; Graves Disease; Humans; Propylthiouracil; Purpura; Vasculitis

Topics: Antibodies, Antineutrophil Cytoplasmic; Humans; Propylthiouracil; Vasculitis

Topics: Adrenal Cortex Hormones; Antithyroid Agents; Diagnosis, Differential; Disease Progression; Female; Humans; Immunosuppressive Agents; Middle Aged; Necrosis; Predictive Value of Tests; Propylthiouracil; Skin; Time Factors; Treatment Outcome; Vasculitis; Wound Healing

The authors present the case history of a patient suffering from hyperthyroidism. The diagnostic procedures revealed the presence of propylthiouracyl induced vasculitis with renal involvement, that recovered completely after the withdrawal of propylthiouracyl and corticosteroid treatment. Thereafter, the patient was treated with thiamasol, that caused agranulocytosis with fever. After transient litium carbonate therapy a succesful thyreoidectomy was performed. Cumulative serious side effects of antithyroid drugs are rare. This case highlights some of the challenges and complications encountered in the management of hyperthyroidism.

Topics: Adult; Antithyroid Agents; Febrile Neutropenia; Female; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Thyroidectomy; Vasculitis

Propylthiouracil is the most common drug used to treat hyperthyroidism. However, this drug could cause a severe disease, antineutrophilic cytoplasmic antibody-associated vasculitis (AAV), which was usually misdiagnosed.. We reported a 60-year-old woman of propylthiouracil-induced AAV manifested as blood coagulation disorders. The patient was admitted because of hyperthyroidism and leukopenia. At the time of hospitalization, she suffered from dry cough, erythema and knee joints ache, and gradually became febrile. And then BP decreased and PLT was reduced with coagulation disorders. ANCA: c-ANCA positive (1:100), p-ANCA positive (1:320), MPO-IgG positive, PR3-IgG positive, GBM-IgG negative. Erythrocyte sedimentation rate and C-reactive protein increased markedly. Chest high-resolution computed tomography (HRCT) showed that scattered spots, patch and ground-glass opacity.. Finally, we made a terminal diagnosis of PTU-induced AAV possibly. After drug withdrawal and use of steroid, the patient recovered well and then accepted RAI therapy. As the patient was given imipenem-cilastatin before the reduction of PLT and coagulation disorders, we considered that the hematologic disorders might be caused by antibiotics or a clinical presentation of the vasculitis itself.. Drug-induced vasculitis is relatively good prognosis, but early diagnosis and timely withdrawal of associated drugs are the key to the treatment.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antimetabolites; Blood Coagulation Disorders; Diagnosis, Differential; Female; Graves Disease; Humans; Middle Aged; Propylthiouracil; Tomography, X-Ray Computed; Vasculitis

Propylthiouracil (PTU)-associated vasculitis is a potentially life-threatening disease with a recent increase in the reported cases in the medical literature. This increase may suggest that some earlier cases have been unrecognized or assigned to an alternative nosology category. Although the skin can be the only organ affected by PTU-associated vasculitis, there are many reports with multiple-system involvement. Classically, the symptoms appear under a tetrad of fever, sore throat, arthralgia, and skin lesions. Cutaneous lesions in reported cases of PTU vasculitis have most commonly consisted of retiform acral, purpuric plaques, or nodules. We report a case of perinuclear antineutrophil cytoplasmic antibody-associated vasculitis developed during treatment with PTU for Grave's disease.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biopsy; Female; Graves Disease; Humans; Propylthiouracil; Vasculitis

Propylthiouracil is a drug used to treat hyperthyroidism. It can cause several side effects including pulmonary disorders that, although rare, can be severe. The authors describe the case of a woman treated with propylthiouracil who developed diffuse alveolar haemorrhage with severe respiratory failure and anaemia, which improved with discontinuation of the antithyroid drug and on starting systemic corticosteroid therapy.

Topics: Aged; Antithyroid Agents; Diagnosis, Differential; Female; Hemorrhage; Humans; Hyperthyroidism; Lung Diseases; Propylthiouracil; Pulmonary Alveoli; Tomography, X-Ray Computed; Treatment Outcome; Vasculitis

Topics: Cryoglobulinemia; Female; Humans; Middle Aged; Propylthiouracil; Vasculitis

Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Female; Humans; Middle Aged; Propylthiouracil; Vasculitis

The objective of this study was to report 11 cases of propylthiouracil (PTU)-induced autoimmune syndromes. We describe the clinical presentation, course, and outcome of 11 patients and compare clinical features between PTU-induced lupus and PTU-induced vasculitis. Of our 11 patients, 7 patients had vasculitis and 4 patients had lupus. Patients with vasculitis were older and had a longer duration of treatment in comparison with lupus. P-ANCA were predominantly found in PTU-induced vasculitis, but also found in lupus, while ANA and anti-dsDNA were often found in lupus. Some difference of renal and pulmonary involvement was often found between PTU-induced vasculitis and lupus. Most of patients needed steroids or immunosuppressive drugs. Vasculitis in the cases of PTU-induced autoimmune phenomena is often found than lupus. P-ANCA in both PTU-induced lupus and vasculitis can all present, but there are differences in clinical and outcome features to diagnosis.

Topics: Adolescent; Adult; Age Factors; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Kidney; Lung; Lupus Erythematosus, Systemic; Middle Aged; Propylthiouracil; Therapeutics; Treatment Outcome; Vasculitis; Young Adult

To report the first case of concomitant drug- and infection-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in a patient treated with propylthiouracil (PTU) and suffering from tuberculosis.. A 28-year-old woman with PTU-treated hyperthyroidism presented with fever, purpura, pulmonary cavitations and ANCA to myeloperoxidase, bactericidal/permeability-increasing protein (BPI), proteinase-3 and elastase. Skin histopathology confirmed vasculitis. However, sputum examination revealed Mycobacterium tuberculosis. Remission was achieved after PTU withdrawal and treatment with antituberculosis drugs.. Our case confirmed that BPI-ANCA are elevated in active tuberculosis. Multispecific ANCA were helpful for the diagnosis of concomitant PTU- and M. tuberculosis-induced AAV.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Antitubercular Agents; Female; Humans; Hyperthyroidism; Propylthiouracil; Tuberculosis, Pulmonary; Vasculitis

We report the case of a 28-year-old woman who presented with arthralgia during a treatment with propylthiouracil (PTU) for hyperthyroidism. Detection of antineutrophil cytoplasmic antibodies (ANCA) against myeloperoxidase, proteinase 3 and elastase led to suspect PTU induced vasculitis.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Humans; Propylthiouracil; Vasculitis

A 34-year-old woman who had been treated with propylthiouracil (PTU) for hyperthyroidism, was admitted because of bloody sputum and pyrexia. The chest CT scan showed some nodules in both lung fields. The serum level of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was high, but proteinase-3 antineutrophil cytoplasmic antibody (PR-3 ANCA) was negative. A limited form of Wegener's granulomatosis without PR-3 ANCA was ruled out, because of the absence of abnormalities in the upper airway and kidney. No lesions other than the multiple pulmonary nodules of the lung were detected. We diagnosed MPO-ANCA associated vasculitis induced by PTU. After the termination of PTU, bloody sputum, pyrexia, and pulmonary nodules improved spontaneously and the serum level of MPO-ANCA returned to normal gradually. The case of MPO-ANCA positive vasculitis associated with multiple pulmonary nodules following propylthiouracil treatment is very rare.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Humans; Hyperthyroidism; Multiple Pulmonary Nodules; Peroxidase; Propylthiouracil; Vasculitis

Topics: Antithyroid Agents; Exanthema; Female; Fever; Graves Disease; Humans; Middle Aged; Oral Ulcer; Propylthiouracil; Vasculitis

Topics: Antithyroid Agents; Child, Preschool; Female; Humans; Lung Diseases; Propylthiouracil; Pulmonary Alveoli; Purpura; Vasculitis

Topics: Adult; Agranulocytosis; Antibodies, Antineutrophil Cytoplasmic; Bone Marrow Diseases; Female; Graves Disease; Humans; Plasma Cells; Propylthiouracil; Vasculitis

Agranulocytosis or allergic skin reactions are common side effects of antithyroid drugs. Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis is very uncommon.. We report a 29-year-old woman treated with propylthiouracil for Graves' disease who developed a vasculitic skin involvement. ANCA with antimyeloperoxidase specificity were documented. Symptoms resolved after discontinuation of the drug.. ANCA associated vasculitis is an unusual complication of propylthiouracil. Prognosis is conditioned by renal and pulmonary involvement.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Humans; Propylthiouracil; Vasculitis

The patient was a 62-year-old female. In June 1999, thiamazole (MMI) was orally administered under a diagnosis of hyperthyroidism. However, drug exanthema developed. In July, oral administration of propylthiouracil (PTU) was started. On October 20, 2005, palpitation and exertional dyspnea occurred. On November 1, bloody sputum was noted, and the patient consulted our hospital on November 8. In addition to severe anemia, chest X-ray and CT revealed diffuse infiltration in the bilateral lungs. The patient was admitted for detailed examination and treatment. After admission, the myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) level was 390 EU, suggesting ANCA-associated angitis. PTU was discontinued, and steroid pulse therapy resulted in the disappearance of alveolar hemorrhage and hematuria. Transbronchial lung biopsy suggested alveolar hemorrhage, and kidney biopsy showed glomerular necrosis and interstitial infiltration of inflammatory cells, suggesting PTU-induced ANCA-associated angitis. Posttreatment with prednisolone at 30 mg/day gradually decreased the MPO-ANCA level. There has been no relapse during the 2-years follow-up.

Topics: Antibodies, Antineutrophil Cytoplasmic; Female; Glomerulonephritis; Hemorrhage; Humans; Middle Aged; Peroxidase; Propylthiouracil; Pulmonary Alveoli; Vasculitis

Topics: Acute Disease; Adult; Antithyroid Agents; Hemoptysis; Humans; Lung Diseases; Male; Propylthiouracil; Pulmonary Alveoli; Vasculitis

It was well known that propylthiouracil (PTU) could induce ANCA-associated vasculitis (AAV) and clinical evident vasculitis could resolve after cessation of PTU with or without immunosuppressive therapy. However, the treatment strategy for patients with PTU-induced AAV remained inconclusive and their long-term outcomes were lacking. The aim of our study was to summarize these data.. Fifteen patients with PTU-induced AAV, receiving immunosuppressive agents for <12 months and following over 24 months, were selected in the current study. The clinical and pathological data, including treatment protocols and outcomes, were retrospectively investigated.. All the patients were followed for a mean of 55.0 (25-98) months. PTU was discontinued upon diagnosis of PTU-induced AAV. Immunosuppressive therapy was administrated only for patients with vital organ involvements, such as lung and kidney, and lasted only 7.9 +/- 3.3 (0.27-12) months. No relapse of vasculitis occurred during follow-up, even after withdrawal of immunosuppressive therapy. Twelve (80%) patients remained in complete remission and one patient remained in partial remission at the latest follow-up. Two patients were treatment resistant due to late referral and late withdrawal of PTU, both of them progressed to end-stage renal disease. For uncontrolled hyperthyroidism on presentation, six patients switched to methimazole and none of them experienced relapse of vasculitis.. The long-term outcomes of patients with PTU-induced AAV were relatively good. PTU should be discontinued immediately after diagnosis. Immunosuppressive therapy may be only used in patients with vital organ involvements, and a long-term maintenance therapy may not be necessary.

Topics: Adolescent; Adult; Algorithms; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoimmune Diseases; Child; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Humans; Hyperthyroidism; Immunosuppressive Agents; Male; Middle Aged; Prognosis; Propylthiouracil; Retrospective Studies; Treatment Outcome; Vasculitis

Propylthiouracil (PTU) can induce anti-myeloperoxidase (MPO-ANCA) positive vasculitis. We performed a cross-sectional study to estimate the prevalence of MPO-ANCA in patients with childhood onset Graves' disease (GD) receiving PTU and to assess the relationship between ANCA and clinical manifestations of vasculitis. We studied 60 patients (59 girls and one boy) between 7.3 and 25.0 years of age (mean +/- SD, 14.71 +/- 4.49). GD, diagnosed at the age of 3.0 to 14.5 years (11.3 +/- 2.48), was designated as: newly diagnosed, on PTU therapy, and after PTU discontinuation in 4, 50 and 6 patients, respectively. Manifestations of vasculitis were noted and the patients were tested for MPO-ANCA, antinuclear antibodies, blood urea nitrogen, creatinine and urine analysis. Twenty-six patients (43.3%) reacted positively for MPO-ANCA, 23 were on PTU therapy (0.42 to 6.00, median 3.00 years) and three had discontinued PTU. There were 34 (56.7%) ANCA-negative patients and 27 patients on PTU therapy (0.25 to 5.17, median 1.00 years, p = 0.012). Vasculitis presented in 16 patients (26.7%), all of whom were receiving PTU at the time of the study. The percentage of vasculitis among MPO-ANCA positive patients was 27.6% more than in the negative group, p = 0.017. PTU was discontinued in patients with vasculitis and positive for MPO-ANCA. Our findings show a high prevalence of MPO-ANCA positivity and a significantly higher percentage of vasculitis among these patients, suggesting that patients taking PTU should be closely observed for the appearance of MPO-ANCA and signs of vasculitis, especially patients GD who have been treated for a long time.

Topics: Adolescent; Adult; Age of Onset; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Female; Graves Disease; Humans; Male; Prevalence; Propylthiouracil; Vasculitis

Antineutrophil cytoplasmic antibody (ANCA) has been well documented in association with propylthiouracil (PTU), and some patients with PTU-induced ANCA also develop clinical vasculitis. The aim of the current study was to detect ANCA specificities in sera from patients with PTU-induced ANCA with and without clinical vasculitis.. Sera from 65 patients with PTU-induced ANCA were collected, and 27 of these patients were diagnosed with PTU-induced ANCA associated systemic vasculitis (AASV). Indirect immunofluorescence assay and antigen-specific ELISAs were used to detect ANCA and their antigen specificities. The seven known target antigens included myeloperoxidase (MPO), proteinase 3, human leukocyte elastase, lactoferrin, cathepsin G, azurocidin and bactericidal/permeability-increasing protein (BPI).. In IIF assay, P-ANCA was found in 58/65 (89.2%) sera, C-ANCA in two, both P-ANCA and C-ANCA in five, respectively. MPO (60%) and lactoferrin (63.1%) were the two most common target antigens detected in sera from all the patients. 25/27 sera from patients with PTU-induced AASV recognized multiple target antigens, which was significantly higher than those (13/38) from patients without (P<0.001). Except anti-BPI antibodies, the prevalence of antibodies against the other six target antigens was significantly higher in patients with clinical vasculitis than that in patients without (P<0.05, respectively).. Antibodies against multiple ANCA specific antigens, especially the antigens rather than MPO and PR3, might be the characteristic of PTU-induced ANCA. Patients with antibodies against more ANCA specific antigens might be at increased risk of developing overt clinical vasculitis. The mechanism of ANCA production in PTU-induced cases was different from that in primary AASV.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antigens; Antithyroid Agents; Child; Female; Humans; Male; Middle Aged; Propylthiouracil; Vasculitis

Propylthiouracil is a drug used in the treatment of hyperthyroidism for more than 60 years. Adverse side effects are seen in 1-5% of patients. Renal complications of the drug including glomerulonephritis and vasculitis are rarely seen. Cases of propylthiouracil-induced rapidly progressive glomerulonephritis and vasculitis are reported in association with antineutrophil cytoplasmic autoantibodies. Here we report a case of positive antineutrophil cytoplasmic autoantibodies rapidly progressive glomerulonephritis (RPGN) associated with propylthiouracil treatment.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Antineutrophil Cytoplasmic; Atrophy; Humans; Hyperthyroidism; Kidney; Kidney Glomerulus; Male; Propranolol; Propylthiouracil; Ramipril; Vasculitis

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).. 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.. 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.. Our study indicates that avidity of anti-MPO antibodies might be more closely associated with clinical vasculitis than titre.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Antibody Affinity; Antigen-Antibody Reactions; Antithyroid Agents; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Glomerulonephritis; Graves Disease; Humans; Peroxidase; Propylthiouracil; Vasculitis; Withholding Treatment

The kidney is one of the organs affected in patients with propylthiouracil (PTU)-associated antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. We present a series of Chinese patients with renal involvement in PTU-associated ANCA-positive vasculitis and describe their clinical and pathological characteristics.. Clinical and pathological data from patients with PTU-associated ANCA-positive vasculitis with renal involvement, diagnosed in Peking University First Hospital, were collected and analyzed retrospectively.. Nineteen patients with PTU-associated ANCA-positive vasculitis were treated at Peking University First Hospital between December 1999 and December 2005, and 15 of them had renal involvement. Of the 15 patients, 13 were female and 2 were male, with an average age of 26.3 +/- 11.8 years. All 15 patients were perinuclear ANCA positive with specificities to myeloperoxidase (15 of 15), cathepsin G (9 of 15), human leukocyte elastase (8 of 15), lactoferrin (7 of 15), azurocidin (5 of 15), and proteinase 3 (4 of 15). Duration of PTU administration was 43.0 +/- 31.2 months. All 15 patients had clinical markers of renal involvement, including hematuria (100%), proteinuria (100%), and renal function abnormality (47%). All 15 patients underwent percutaneous renal biopsy. Ten patients had necrotizing crescentic glomerulonephritis, and 7 of these 10 patients had immune complex deposition. Three patients had minimal involvement, 2 patients had immunoglobulin A nephropathy, and 2 patients had membranous nephropathy. PTU treatment was discontinued in all 15 patients. All except 2 patients with minimal renal involvement received immunosuppressive treatment. Eleven of 15 patients achieved complete clinical remission.. Renal involvement in our case series of patients with PTU-associated ANCA-positive vasculitis was heterogeneous, and nearly half our patients had renal immune complex deposition.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Child; Female; Humans; Immune Complex Diseases; Immunosuppressive Agents; Kidney; Kidney Diseases; Male; Middle Aged; Propylthiouracil; Retrospective Studies; Vasculitis

To investigate the features, followup data, and outcomes of patients with propylthiouracil (PTU)-associated antineutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis.. Nineteen patients with PTU-associated ANCA-positive vasculitis diagnosed in our hospital from 2000 to 2006 were analyzed retrospectively.. Our data showed a female predominance among the patients. Eleven patients had involvement of more than one organ. Renal involvement was the most common manifestation. Fourteen patients underwent renal biopsy. Four patients had focal proliferative glomerulonephritis with crescent formation. Two had necrotizing glomerulonephritis with crescent formation. Two patients had minor glomerular abnormalities, 2 had IgA nephropathy, one had membranous nephropathy, one had focal proliferative glomerulonephritis, one had granulomatous interstitial nephritis, and the remaining one had focal segmental glomerular sclerosis. Immune complex glomerulonephritis was found in 3 patients. On indirect immunofluorescence, 17 patients were perinuclear-pattern ANCA-positive, one was positive for atypical ANCA, and one was positive for cytoplasmic-pattern-ANCA. By ELISA, 4 patients were positive for both myeloperoxidase (MPO)-ANCA and proteinase-3 (PR3)-ANCA, one was positive for PR3-ANCA only, and the others were positive for MPO-ANCA only. For the treatment of vasculitis, 5 patients received prednisone alone, 10 received prednisone and cyclophosphamide, and the remaining 4 did not receive prednisone or cyclophosphamide. During followup, 15 patients achieved remission, 3 patients died, and one patient depended on dialysis. In general, MPO-ANCA concentration did not correlate with disease progression, and a delayed decrease of MPO-ANCA concentration was found in most patients who achieved remission.. Most patients with PTU-associated ANCA-positive vasculitis had good outcomes; however, severe cases existed. We suggest early recognition and adequate treatment are necessary to improve outcome.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antimetabolites; Female; Humans; Kidney Diseases; Male; Middle Aged; Propylthiouracil; Retrospective Studies; Treatment Outcome; Vasculitis

We report a 16 year-old girl with propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-positive glomerulonephritis combined with Henoch-Schönlein purpura nephritis (HSPN) and antiphospholipid syndrome (APS).. The patient had Graves' disease and had been treated with PTU for about 6 years. She complained of arthralgia, epigastralgia, purpura of the lower extremities, anemia, and abnormal urinalysis. Lupus anticoagulant was positive. Additionally, a high level of anti-myeloperoxidase (MPO) antibodies (IgG) and a low level of coagulation factor XIII were recognized. She had several complications including lung bleeding, lacuna infarctions of the right frontal and parietal brain lobes, and deep vein thrombosis of the left lower extremity. We studied tissue histology and carried out MPO-ANCA subtype analysis by immunofluorescence and flow cytometry and MPO-ANCA epitope analysis.. Histologically, purpura showed leukocytoclastic vasculitis with perivascular depositions of IgA and complement C3. Renal biopsy showed necrotizing glomerulonephritis with crescents and mesangial IgA deposits. Notably, IgG, IgM, and IgA ANCA were detected in the patient's serum by flow cytometry and immunofluorescence. We diagnosed an overlap syndrome of ANCA-positive vasculitis, HSPN, and APS. A change in the reactivity of MPO-ANCA from recognition of only the Hg epitope in the C-terminal region to recognition of multiple MPO epitopes was accompanied by a remission of symptoms.. This report may provide a very rare description of an overlap syndrome of PTU-induced ANCA vasculitis, HSPN, and APS in which not only IgG ANCA but also IgA and IgM ANCA were found. Epitope analysis may be a useful marker for disease-monitoring of PTU-induced ANCA-positive vasculitis. This case may provide insight into the pathological mechanism underlying each of these diseases.

Topics: Antibodies, Antineutrophil Cytoplasmic; Child; Epitopes; Female; Flow Cytometry; Fluorescent Antibody Technique, Indirect; Humans; Kidney Glomerulus; Peroxidase; Propylthiouracil; Vasculitis

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; Humans; Middle Aged; Oral Ulcer; Propylthiouracil; Vasculitis

Palpable purpura is a concerning clinical finding in pediatric patients and can have many causes, including infectious and autoimmune processes. A rare cause, drug-induced vasculitis, may result from the production of antineutrophil cytoplasmic antibodies (ANCAs) in response to a medication. We report a girl with Turner syndrome and Graves' disease who presented with palpable purpuric lesions. The diagnosis of propylthiouracil (PTU)-associated vasculitis was made by observation of consistent clinical features, the detection of elevated ANA and ANCA in the blood, and the observed clinical resolution of symptoms following withdrawal of PTU. Subsequent treatment of persistent hyperthyroidism with radioablation did not result in an exacerbation of the vasculitis, a complication described in prior case reports.

Topics: Antithyroid Agents; Child; Female; Graves Disease; Humans; Propylthiouracil; Thyroxine; Turner Syndrome; Vasculitis

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Biopsy; Female; Follow-Up Studies; Glomerulonephritis; Humans; Hyperthyroidism; Necrosis; Plasmapheresis; Propylthiouracil; Radiography, Thoracic; Time Factors; Treatment Outcome; Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis is an uncommon complication of the use of propylthiouracil. When it occurs, it affects multiple organs as any systemic vasculitis. We report three females and one male, aged 30, 40, 43 and 41 years respectively, that after a lapse of 12 to 28 months of propylthiouracil use, presented clinical signs of vasculitis. All had high titers of ANCA against myeloperoxidase. In three patients, a skin biopsy confirmed the diagnosis. The condition subsided when propylthiouracil was discontinued, but one female patient required the use of prednisone.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biomarkers; Biopsy; Female; Humans; Hyperthyroidism; Male; Propylthiouracil; Vasculitis

Topics: Animals; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoimmunity; Disease Models, Animal; Graves Disease; Humans; Male; Middle Aged; Peroxidase; Propylthiouracil; Vasculitis

A 60-year-old man with a history of Graves' disease, treated with propylthiouracil (PTU), presented with a rash, pancytopenia, and lymphadenopathy. The patient subsequently developed acute renal failure and diffuse alveolar hemorrhage. Despite discontinuation of PTU and aggressive therapy including high-dose steroids, cyclophosphamide, and plasma exchange, the patient died. PTU-induced antineutrophilic cytoplasmic antibody (ANCA)-positive vasculitis has been well described in the literature. Patients with this condition are almost always positive for pANCA or anti-myeloperoxidase (MPO). Patients can have varying presentations, and symptoms usually resolve with discontinuation of the drug. Some patients, however, require high-dose steroids, immunosuppressives, or plasmapheresis. Rarely, fatalities can occur from this condition. The mechanism of PTU-induced vasculitis is not well understood.

Topics: Antibodies, Antineutrophil Cytoplasmic; Fatal Outcome; Humans; Male; Middle Aged; Propylthiouracil; Vasculitis

Increasing evidence has demonstrated that propylthiouracil (PTU) could induce ANCA positive vasculitis. However, our previous work has suggested that only one-fifth of the PTU-induced ANCA positive patients had clinical vasculitis and so the mechanism is not clear. Anti-endothelial cell antibodies (AECA) have been implicated in the pathogenesis of various vasculitides, including primary ANCA positive systemic vasculitis. The purpose of this study is to investigate the prevalence of AECA and their possible role in the pathogenesis of patients with PTU-induced ANCA positive vasculitis. Sera from 11 patients with PTU-induced ANCA positive vasculitis at both active and quiescent phases, and sera from 10 patients with PTU-induced ANCA but without clinical vasculitis, were studied. Sera from 30 healthy blood donors were collected as normal controls. Soluble proteins from 1% Triton-100 extracted in vitro cultured human umbilical vein endothelial cells were used as antigens and an immunoblotting technique was performed to determine the presence of AECA, and their specific target antigens were identified. In patients with PTU-induced ANCA positive vasculitis, 10 of the 11 patients in an active phase of disease were serum IgG-AECA positive and six protein bands of endothelial antigens could be blotted (61 kD, 69 kD, 77 kD, 85 kD, 91 kD and 97 kD). However, in the quiescent phase, seven of the 10 positive sera turned negative. None of the ANCA positive but vasculitis negative patients or normal controls were AECA positive. In conclusion, AECA could be found in sera from patients with PTU-induced ANCA positive vasculitis and were associated more closely with vasculitic disease activity.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Blotting, Western; Case-Control Studies; Cell Culture Techniques; Chi-Square Distribution; Endothelial Cells; Female; Humans; Male; Middle Aged; Propylthiouracil; Vasculitis

A 48 year old white woman was admitted to the hospital because of several bouts of migratory polyarthritis, weight loss, fever, and abdominal pain over a period of 15 months. She had been taking propylthiouracil 100 mg daily for three years for hyperthyroidism treatment. A test for antineutrophil cytoplasmic autoantibodies (ANCA) was positive with a perinuclear pattern of staining. Antiphospholipid antibodies were also detected. Colonoscopy showed several ulcers on intestinal mucosa and the biopsy specimen showed intense microscopic vasculitis. The patient is well after methylprednisolone pulse therapy and eight months of oral azathioprine. A surveillance colonoscopy showed complete healing of intestinal ulcers. No recurrence of symptoms has occurred and autoantibodies are negative, 10 months after treatment finished. The sequence of events suggests a propylthiouracil induced vasculitis p-ANCA positive and an antiphospholipid syndrome. This is the first report of colonic ulcers diagnosed and successfully treated in such circumstances.

Topics: Antiphospholipid Syndrome; Antithyroid Agents; Colonic Diseases; Female; Humans; Hyperthyroidism; Middle Aged; Propylthiouracil; Ulcer; Vasculitis

Propylthiouracil (PTU) could induce MPO-ANCA-positive vasculitis. The aim of this study was to compare the IgG subclass distribution and avidity of MPO-ANCA in sera from patients with primary ANCA-associated vasculitis (AASV) and PTU-induced vasculitis.. Nineteen patients with primary AASV with MPO-ANCA and thirteen patients with PTU-induced vasculitis were enrolled in the current study. Sera in both active phase and remission were collected. Anti-MPO IgG subclasses were detected by antigen specific ELISAs using specific monoclonal antibodies as second antibodies, and MPO-ANCA avidity was assessed by antigen-inhibition ELISAs.. In primary AASV, all four anti-MPO IgG subclasses could be detected in active phase with IgG1 (100%), IgG2 (73.7%), IgG3 (63.2%) and IgG4 (94.7%), and in remission, IgG1 and IgG4 subclasses in most patients remained positive. However, in PTU-induced vasculitis, anti-MPO IgG3 subclass could not be detected, the anti-MPO IgG subclasses in active phase were IgG1 (100%), IgG2 (61.5%) and IgG4 (46.2%). Furthermore, five out of the six patients (88.8%) with PTU-induced vasculitis with positive IgG4 subclass in active phase turned to negative in remission, however, only eight out of the fourteen patients (57.1%) with primary AASV turned to negative. The median avidity constant of MPO-ANCA was 56 (8.96 to >140) x 10(7) mol/l for patients with primary AASV and 0.7 (<0.28 to >140) x 10(7) mol/l for patients with PTU-induced vasculitis respectively. Furthermore, the relative levels of MPO-ANCA avidity were associated with elevation of ESR in primary AASV and were associated with BVAS scores in patients with PTU-induced vasculitis, respectively.. MPO-ANCA IgG subclass distribution and avidity were different between patients with primary AASV and PTU-induced vasculitis. It was suggested that the mechanism of ANCA production in PTU-induced vasculitis was different from that in primary AASV, and the avidity of MPO-ANCA might be associated with disease activity.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antibody Affinity; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin G; Male; Middle Aged; Peroxidase; Propylthiouracil; Vasculitis

To investigate the prevalence of anti-endothelial cell antibodies(AECA) and its possible role in the pathogenesis of propylthiouracil (PTU) induced ANCA positive vasculitis.. Sera from 11 patients with PTU induced ANCA positive vasculitis and 10 patients with PTU induced ANCA but without clinical vasculitis were studied. Soluble proteins from in vitro cultured human umbilical vein endothelial cells were used as antigens and immunoblotting technique was performed to identify the specific target antigens.. In patients with PTU induced ANCA positive vasculitis group, 10 of the 11 patients in active phase were AECA positive and 7 of the 10 patients turned to negative in remission. AECA consisted of a group of heterogeneous antibodies. In patients with ANCA positive but without vasculitis, none was AECA positive.. AECAs recognizing a variety of antigens could be found in sera from patients with PTU induced ANCA positive vasculitis and they had a much closer association with vasculitic disease activity compared with ANCA.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Female; Humans; Male; Middle Aged; Propylthiouracil; Vasculitis

Substantial evidences suggested that propylthiouracil (PTU) could induced anti-myeloperoxidase (MPO) antibodies in sera from patients with hyperthyroidism, however, only a subgroup of the PTU-induced anti-MPO antibody positive patients developed clinical evident vasculitis. The aim of this study is to compare the titres and affinities of PTU induced anti-MPO antibodies in sera from patients with hyperthyroidism with and without clinical vasculitis. Anti-MPO antibody positive sera from patients diagnosed hyperthyroidism with (n = 13) and without (n = 14) clinical evident vasculitis were collected. The titre was determined by MPO-ELISA and expressed as logarithm value (lgT). The affinity constant (aK) of anti-MPO IgG was measured by antigen inhibition assay. The titre and aK values were compared between patients with and without vasculitis. In patients with vasculitis, the mean lgT of anti-MPO antibodies was 3.62 +/- 0.66; the median aK was 4.47 x 10(7)M(-1). In patients without vasculitis, the mean lgT was 2.54 +/- 0.29; the median aK was 0.14 x 10(7)M(-1), and both were significant lower than those in patients with vasculitis (t = 5.464; P = 0.000 & z = -4.373; P = 0.000, respectively). We concluded that the titre and affinity of anti-MPO antibodies might be associated with the development of clinical vasculitis in patients with PTU-induced ANCA.

Topics: Adolescent; Adult; Antibodies; Antibody Affinity; Child; Female; Humans; Hyperthyroidism; Immunoglobulin G; Male; Middle Aged; Peroxidase; Propylthiouracil; Vasculitis

Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (alpha1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low alpha1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antibody Specificity; Antithyroid Agents; Autoantigens; Autoimmune Diseases; Churg-Strauss Syndrome; Cyclophosphamide; Female; Fluorescent Antibody Technique, Indirect; Follow-Up Studies; Granulomatosis with Polyangiitis; Graves Disease; Hashimoto Disease; Humans; Hyperthyroidism; Immunoprecipitation; Kidney; Lung; Male; Methimazole; Middle Aged; Myeloblastin; Nephelometry and Turbidimetry; Peroxidase; Polyarteritis Nodosa; Prednisone; Pregnancy; Pregnancy Complications; Propylthiouracil; Retrospective Studies; Serine Endopeptidases; Skin; Vasculitis; Vasculitis, Leukocytoclastic, Cutaneous

To analyze the clinical features and outcomes of hyperthyroidism patients positive in propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA).. The clinical data, including the clinical manifestations, treatment, and outcomes of 45 PTU-induced ANCA positive patients with hyperthyroidism were prospectively studied.. Seventeen of the 45 patients had clinically evident vasculitis and 28 of the 45 patients were not complicated by vasculitis. In the vasculitis group, 13 patients (76.5%) had renal involvement manifested by hematuria, proteinuria, and renal insufficiency. 7 of them (41.2%) had lung involvement and 6 of them had hemoptysis. Perinuclear ANCA (p-ANCA) was detected in all 17 patients and 16 of them (94.1%) were anti-myeloperoxidase antibodies (MPO-ANCA) positive. PTU was discontinued in all 17 patients and the treatment was switched over to methimazole (MMI) in 6 patients. Four patients with severe organ involvement received prednisone and immunosuppressant for 6 to 12 months. No relapse or death occurred during the follow-up period (8 to 60 months with a median of 30 months). All the 17 patients achieved clinical remission except for two that developed end stage renal disease due to late diagnosis. 27 of the 28 patients without vasculitis (96.4%) were p-ANCA positive and 14 of them (50.0%) were MPO-ANCA positive. PTU treatment was discontinued in 24 patients and switched over to MMI treatment in 15 patients, and 4 patients continued to take low dose PTU. No vasculitis manifestation occurred during the follow-up period (3 to 36 months with a median of 20 months). However, the ANCA titer declined slowly in most patients in both groups.. PTU treatment should be discontinued without delay in the PTU-induced ANCA positive patients with hyperthyroidism. Treatment can be switched over to MMI when necessary. Patients with severe organ involvement should receive prednisone and immunosuppressant. No vasculitis relapse is found during the follow-up after withdrawal of PTU. However, ANCA may keep positive for a long time.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Child; Female; Follow-Up Studies; Humans; Hyperparathyroidism, Secondary; Male; Middle Aged; Propylthiouracil; Prospective Studies; Recurrence; Vasculitis

This paper describes a patient treated for 12 months with propylthiouracil for multinodular toxic goiter who developed vasculitis. The clinical picture consisted of nasal septal necrosis, pulmonary infiltrations and skin rash. Patient's serum were positive for anti neutrophil cytoplasmatic antibodies (c-ANCA). Histopathological examination revealed the presence of small vessel vasculitis without granuloma formation. This condition resulted in patient's critical state with respiratory failure and severe cardiovascular complications. The article also contains a brief review of available literature concerning this very rare complication. Conclusion. Propylthiouracil, a widely-used medicine, can cause severe life-threatening complication. It is associated with propylthiouracil-induced immunological disturbances.

Topics: Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Goiter, Nodular; Humans; Methylprednisolone; Middle Aged; Prednisone; Propylthiouracil; Severity of Illness Index; Vasculitis

A 50-year-old woman had been treated with propylthiouracil (PTU) for hyperthyroidism. She was admitted to our hospital because of hemosputum, and severe hypoxemia developed. The CT scan showed diffuse infiltration in both lung fields, bronchoalveolar lavage fluid revealed diffuse alveolar hemorrhage, and the level of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was high; and therefore diffuse alveolar hemorrhage associated with MPO-ANCA positive vasculitis induced by PTU was diagnosed. Following corticosteroid therapy initiated after the termination of PTU, the pulmonary infiltration rapidly improved and the patient's MPO-ANCA level returned to normal. Recrudescence of diffuse alveolar hemorrhage occurred following a reduction in steroids, but no recurrence was found after cyclophosphamide therapy was combined with steroid therapy. During the course of therapy, various cardiac conducting system abnormalities which correlate with the course of steroid therapy were found, indicating that cardiac conducting system abnormalities may be associated with MPO-ANCA-positive vasculitis.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Bundle-Branch Block; Female; Heart Block; Hemorrhage; Humans; Hyperthyroidism; Lung Diseases; Middle Aged; Peroxidase; Propylthiouracil; Pulmonary Alveoli; Vasculitis

Propylthiouracil (PTU) as a drug used during the treatment of hyperthyroidism could induce antineutrophil cytoplasmic autoantibody-positive vasculitis. Here the author reported a childhood case of antineutrophil cytoplasmic autoantibody-positive vasculitis induced by PTU, which is rarely described.. The diagnosis was made according to the symptoms, signs, serum markers and renal biopsy, and the relevant literature was reviewed.. The 12-year-old girl presented with gross hematuria, proteinuria, renal function damage [Ccr 52.46 ml/(min. 1.73 m(2))], positive antineutrophil cytoplasmic autoantibody (ANCA-MPO) (MPO ELISA 140%) and a vasculitis lesion in the renal biopsy sample. She had been treated with PTU for 5 years because of Graves disease. After the diagnosis, the PTU was withdrawn, and prednisone (40 mg/d) and cyclophosphamide (25 mg, Bid) were applied. Three weeks after the therapy with prednisone and cyclophosphamide the gross hematuria disappeared. Three months after the treatment the renal function returned to normal [Ccr 124 mg/(min.1.73 m(2))], and the titer of ANCA-MPO decreased from 140% to 57%.. PTU may induce antineutrophil cytoplasmic autoantibody positive vasculitis. A right diagnosis and treatment can improve its prognosis of the disease.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Prognosis; Propylthiouracil; Treatment Outcome; Vasculitis

Myeloperoxidase (MPO) is one of the major target antigens of antineutrophil cytoplasmic antibodies (ANCA) in primary systemic vasculitis. It is known that propylthiouracil (PTU) could induce MPO-ANCA-positive vasculitis. The production of anti-MPO antibodies in patients with PTU-induced vasculitis may be different from that in patients with primary microscopic polyangiitis (MPA). One possible reason for this may be differences in epitope recognition. The aim of this study is to compare the epitopes of antibodies to MPO in sera from patients with PTU-induced vasculitis (n = 10) and MPA (n = 10). The sera were collected and used to inhibit monoclonal antibodies against human MPO (3D8 and 6B9) and affinity purified, horseradish peroxidase conjugated human anti-MPO antibodies (Pab1-HRP, Pab2-HRP) in a competitive inhibition enzyme-linked immunosorbent assay (ELISA) system using soluble human MPO as solid phase ligand. The Pab1-HRP and Pab2-HRP were affinity purified from plasma exchanges of a patient with PTU-induced vasculitis and a patient with MPA, respectively. The inhibition rates were evaluated and compared between the PTU and primary MPA groups. In the PTU group all 10 sera could inhibit 3D8: the average inhibition rate was 44.7% +/- 5.0%; 9/10 sera could inhibit 6B9: the average inhibition rate was 35.6% +/- 6.0%. However, in the MPA group all 10 sera could inhibit 3D8 and 6B9; the average inhibition rates were 68.4% +/- 16.1% (P < 0.01) and 62.2% +/- 17.2% (P < 0.01), respectively. Sera in both the PTU and MPA groups could inhibit Pab1-HRP and the inhibition rates were 81.4% +/- 9.4%versus 86.6% +/- 17.2% (P > 0.05). However, the average inhibition rate for Pab2-HRP in the MPA group was significantly higher than that in the PTU group (76.3% +/- 7.8%versus 58.9% +/- 15.5%, P < 0.01). We conclude that anti-MPO antibodies from patients with PTU-induced vasculitis and from patients with primary MPA could recognize more than one epitope on the native MPO molecule. Although the epitopes overlapped between the two groups, the epitopes of anti-MPO antibodies from patients with PTU-induced vasculitis might be more restricted.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal; Antibody Affinity; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Horseradish Peroxidase; Humans; Male; Middle Aged; Peroxidase; Propylthiouracil; Vasculitis

To investigate the distribution of IgG subclass of anti-myeloperoxidase (MPO) antibodies, a kind of antineutrophil cytoplasmic autoantibody (ANCA), in sera from patients with propylthiouracil (PIU)-induced vasculitis.. Serum samples were collected from 12 patients with PIU-induced MPO ANCA positive vasculitis, both sera of active and remission phases were collected from 10 of which, and only serum of active phase was collected from 2 of which. Anti-MPO IgG subclasses were detected by antigen-specific ELISA. The distribution of anti-MPO IgG subclasses in PIU-induced vasculitis was compared with that in primary vasculitis.. Anti-MPO IgG3 subclass was not detected in the sera from both active and remission phases of PIU-induced vasculitis. In the active phase the following anti-MPO IgG subclasses were found: IgG1 (12/12, 100%), IgG2 (1/12, 66.7%), and IgG4 (7/12, 58.3%). In the remission phase, the following anti-MPO IgG subclasses were found: IgG1 (9/10, 90%), IgG2 (4/10, 40%), and IgG4 (2/10, 20%). The titer of anti-MPO IgG4 subclass remained high in the remission phase in primary vasculitis; however, it decreased significantly after the cessation of PIU use in PIU-induced vasculitis.. The distribution of anti-MPO IgG subclasses in the sera of the patients with PIU-induced vasculitis is different from that of the patients with primary vasculitis. The higher titer pf MPO-ANCA in the sera of the patients with PIU-induced vasculitis may be associated with the repeated PIU stimulation.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Child; Female; Humans; Immunoglobulin G; Male; Middle Aged; Propylthiouracil; Vasculitis

To study the clinical characteristics of propylthiouracil (PTU) induced antineutrophil cytoplasmic antibodies (ANCA) positive cases and increase the awareness of PTU induced ANCA positive vasculitis (APV).. The clinical data of nine cases with positive ANCA induced by PTU in Peking Union hospital since 2000 were analyzed and literature review was conducted.. (1) Nine patients with hyperthyroidism, at a mean age of 33.1 (16 approximately 51), who were treated with PTU for a mean period of 32.4 months (3 approximately 84); (2) Sera from nine cases were ANCA positive, and autoantibodies from six tested cases could recognize not only MPO, but also PR3, HLE, BPI and LF; (3) Six cases with high titer perinuclear ANGA (pANCA) (> or = 1:1280) were diagnosed APV and all had renal involvement (five confirmed by renal biopsies), three cases with low titer pANCA (< or = 1:320) had little clinical manifestations of vasculitis; (4) Eight patients stopped taking PTU when positive ANCA were noted. One case with APV got remission after stopping PTU, the other three APV were treated with glucocorticosteroid and immunosuppressive agents at meanwhile. Only one patient kept taking PTU for eighteen months without an increased titer of ANCA.. PTU could induce production of ANCA. High titer of ANCA might suggest existence of APV and the titer would be associated with status of APV. Early withdrawal of PTU and administration of glucocorticosteroid and immunosuppressive agents based on renal pathology will greatly improve the prognosis.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Female; Humans; Hyperthyroidism; Immunosuppressive Agents; Male; Methylprednisolone; Middle Aged; Propylthiouracil; Vasculitis

To compare the epitopes of antibodies for myeloperoxidase (MPO) in the serum from patients with propylthiouracil (PTU) induced vasculitis and microscopic polyangiitis (MPA).. Serum samples from patients with PTU-induced vasculitis (n = 10) and MPA (n = 10) were collected and used to inhibit monoclonal antibodies against human MPO 3D8 and 6B9 and then affinity was purified, horseradish peroxidase conjugated and human MPO antibodies determined (Pab1-HRP, Pab2-HRP) in a competitive inhibition ELISA system using soluble human MPO as solid phase ligands. The Pab1-HRP and Pab2-HRP were affinity purified from plasma exchanges of a patient with PTU-induced vasculitis and a patient with MPA. The inhibition rates were evaluated and compared between PTU group and primary MPA group.. In PTU group, all the 10 serum samples could inhibit 3D8; the average inhibition rate was 44.7%, 9/10 of the serum samples could inhibit 6B9; the average inhibition rate was 35.6%; In MPA group, all 10 serum samples could inhibit 3D8 and 6B9; the average inhibition rates were 68.4% and 62.2%. Serum in both groups could inhibit Pab1-HRP and the inhibition rates were both more than 80%; the average inhibition rate for Pab2-HRP in MPA group was significantly higher than that in PTU group (76.3% vs 58.9%, P < 0.01).. MPO antibodies from patients with PTU-induced vasculitis and patients with primary MPA could recognize more than one epitopes on native MPO molecule. Although the epitopes were overlapping between the two groups, the epitopes of MPO antibodies from patients with PTU-induced vasculitis might be more restricted.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antibody Affinity; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Female; Humans; Male; Middle Aged; Peroxidase; Propylthiouracil; Vasculitis

Topics: Antibodies, Antineutrophil Cytoplasmic; Follow-Up Studies; Graves Disease; Humans; Propylthiouracil; Risk Assessment; Vasculitis

A 54-year-old woman had been administered propylthiouracil (PTU) for Graves' disease for 4 years. Recently, she complained of hemoptysis due to pulmonary alveolar hemorrhage causing anemia, and also had microhematuria. Antineutrophil cytoplasmic antibody against myeloperoxidase (MPO-ANCA) was positive, and she was diagnosed with PTU-induced vasculitis. Cessation of PTU and the administration of corticosteroids ameliorated these manifestations.

Topics: Antibodies, Antineutrophil Cytoplasmic; Blood Chemical Analysis; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Graves Disease; Humans; Middle Aged; Peroxidase; Propylthiouracil; Risk Assessment; Severity of Illness Index; Thyroid Function Tests; Tomography, X-Ray Computed; Vasculitis

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Arthritis; Diagnosis, Differential; Food Hypersensitivity; Foot Diseases; Hematologic Tests; Humans; Hyperthyroidism; Male; Propylthiouracil; Vasculitis

To study the clinicopathological manifestations and target antigens of propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA) positive vasculitis.. Four hospitalized patients with PTU-induced ANCA positive vasculitis in recent two years were studied. Target antigens and antibody titers were investigated with ELISA using seven highly purified known ANCA antigens as solid phase ligands. The known antigens included proteinase 3 (PR3), myeloperoxidase (MPO), human leukocyte elastase (HLE), lactoferrin (LF), cathepsinG (CG), bactericidal/permeability-increasing protein (BPI) and azurocidin (AZU).. Four patients with Grave's disease, 2 female and 2 male with a mean age of 30 (11 approximately 57) years who had been treated with PTU for 7 approximately 60 months suffered from ANCA positive vasculitis. All the 4 patients had renal, lung, skin, joint, muscle and hematological involvement. Sera from all the 4 patients were ANCA positive and recognized MPO, LF and CG. Sera from 3 patients recognized HLE and AZU and 2 recognized PR3. None of the sera recognized BPI. The majority of the autoantibodies had high titers >/= 1:25 600. All the sera from 30 patients with Grave's disease and PTU treatment but without vasculitis were ANCA negative. All the 4 patients had pauci- immune glomerular lesions in renal biopsy; 2 had crescentic glomerulonephritis and the remaining 2 had minor glomerular abnormalities. All the 4 patients responded to withdrawal of propylthiouracil; 3 patients were treated with immunosuppressive agents. All the patients achieved clinical remission. However, one patient with crescentic glomerulonephritis was dialysis dependent. After withdrawal of PTU and administration of immunosuppressants, ANCA titres declined, but did not turn to negative in 1-6 months in most of the patients.. PTU can induce ANCA positive vasculitis. The autoantibodies were polyclonal and recognized multiple target antigens of neutrophil cytoplasm. Early withdrawal of PTU and administration of immunosuppressive agents might improve the prognosis.

Topics: Adolescent; Adult; Antibodies, Antineutrophil Cytoplasmic; Child; Female; Graves Disease; Humans; Immunosuppressive Agents; Male; Middle Aged; Propylthiouracil; Vasculitis

Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Hemorrhage; Humans; Hyperthyroidism; Lung Diseases; Propylthiouracil; Pulmonary Alveoli; Vasculitis

A 30-year-old female patient, diagnosed as having Graves' disease in 1996, was treated with propylthiouracil (PTU) for 4 years. She developed a low-grade fever from December 1999. As myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) vasculitis is one of the adverse effects of PTU, we examined serum MPO-ANCA level and found it was positive, but cytoplasmic-ANCA (c-ANCA) was negative. There were no symptoms that indicated other diseases associated with MPO-ANCA. She was confirmed to be at 6 weeks gestation, and thyroid hormone levels were elevated at that time. We discontinued PTU and gave methyl-mercaptoimidazole (MMI), and the titer of MPO-ANCA fell along with fever. Therefore we estimated the case as probable MPO-ANCA positive vasculitis induced by PTU. MMI was also suspended because of the development of hepatic dysfunction. After thyroid function was normalized by administration of potassium iodide, she underwent subtotal thyroidectomy, and delivered a 2350 g infant at 38 weeks' gestation, which was less than the normal birth weight of 2400 g. MPO-ANCA is considered to be one reason of low birth weight infant including hyperthyroidism. It is necessary to consider the appearance of the possibility of MPO-ANCA positive vasculitis in patients who are treated with PTU.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Female; Graves Disease; Humans; Infant, Low Birth Weight; Infant, Newborn; Methimazole; Peroxidase; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Thyroidectomy; Vasculitis

Topics: Adult; Antithyroid Agents; Female; Graves Disease; Humans; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Propylthiouracil; Vasculitis

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive vasculitis has been reported in patients with Graves' disease who were treated with propylthiouracil (PTU). The appearance of MPO-ANCA in these cases was suspected of being related to PTU because the titres of MPO-ANCA decreased when PTU was stopped. Nevertheless, there have been no studies on the temporal relationship between the appearance of MPO-ANCA and vasculitis during PTU therapy, or on the incidence of MPO-ANCA in untreated Graves' disease patients. Therefore, we sought to address these parameters in patients with Graves' disease.. We investigated 102 untreated patients with hyperthyroidism due to Graves' disease for the presence of MPO-ANCA, and for the development vasculitis after starting PTU therapy. Twenty-nine of them were later excluded because of adverse effects of PTU or because the observation period was less than 3 months. The remaining 73 patients (55 women and 18 men), all of whom were examined for more than 3 months, were adopted as the subjects of the investigation. The median observation period was 23.6 months (range: 3-37 months).. MPO-ANCA was measured at intervals of 2-6 months.. Before treatment, the MPO-ANCA titres of all 102 untreated Graves' disease patients were within the reference range (below 10 U/ml). Three (4.1%) of the 73 patients were positive for MPO-ANCA at 13, 16 and 17 months, respectively, after the start of PTU therapy. In two of them, the MPO-ANCA titres transiently increased to 12.8 and 15.0 U/ml, respectively, despite continued PTU therapy, but no vasculitic disorders developed. In the third patient, the MPO-ANCA titre increased to 204 U/ml and she developed a higher fever, oral ulcers and polyarthralgia, but the symptoms resolved 2 weeks after stopping PTU therapy, and the MPO-ANCA titre decreased to 20.7 U/ml by 4 months after discontinuing PTU.. PTU therapy may be related to the appearance of MPO-ANCA, but MPO-ANCA does not appear to be closely related to vasculitis.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biomarkers; Child; Female; Graves Disease; Humans; Male; Middle Aged; Peroxidase; Propylthiouracil; Time Factors; Vasculitis

Topics: Adult; Antithyroid Agents; Disseminated Intravascular Coagulation; Female; Humans; Propylthiouracil; Vasculitis

The triggers that induce antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis (APV) are largely unknown. However, there have been reports suggesting that hydralazine, propylthiouracil, and several other drugs may cause some cases of APV, and the majority of these cases have been associated with antimyeloperoxidase (anti-MPO) ANCA. Our experience led us to hypothesize that cases of high titers of anti-MPO antibodies are often drug-associated.. In this study, we determined the prevalence of exposure to hydralazine, propylthiouracil, and other drugs previously implicated in APV among 30 patients with vasculitis and the highest titers of anti-MPO antibodies newly detected in our laboratory between 1994 and 1998. The clinical, histologic, and other serologic features of these 30 patients were also examined.. The 30 study patients accounted for 12% of the 250 new patients with APV and anti-MPO who were tested during the study period. All 30 study subjects had anti-MPO titers that were more than 12 times the median titer of the 250 patients. Ten (33%) of the 30 patients had been exposed to hydralazine and 3 (10%) had been exposed to propylthiouracil. An additional 5 patients (17%) had been exposed to 1 of the other previously reported candidate drugs: 2 to penicillamine, 2 to allopurinol, and 1 to sulfasalazine. One of the patients exposed to hydralazine had also been exposed to allopurinol. In all cases, the clinical and histologic findings were typical of APV. There was a strong association between the presence of antielastase and/ or antilactoferrin antibodies and exposure to candidate drugs.. These data suggest that a sizable proportion of cases of APV with high titers of anti-MPO antibodies are drug-associated, especially following exposure to hydralazine or propylthiouracil. We recommend that the use of these drugs should be sought in cases of anti-MPO-positive vasculitis, particularly among patients with high titers of these antibodies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Antibodies; Antibodies, Antineutrophil Cytoplasmic; Female; Humans; Hydralazine; Male; Middle Aged; Penicillamine; Peroxidase; Propylthiouracil; Sulfasalazine; Vasculitis

Topics: Administration, Oral; Adolescent; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Glucocorticoids; Humans; Peroxidase; Prednisolone; Propylthiouracil; Vasculitis

A 62-year-old woman had been treated with propylthiouracil(PTU) for hyperthyroidism. Because bloody sputum, dyspnea, and severe hypoxemia developed, the patient was admitted to our hospital. Chest X-ray and chest computed tomographic (CT) films disclosed diffuse infiltrative shadows in both lung fields. Bronchoalveolar lavage revealed abundant hemosiderin-laden macrophages. Alveolar hemorrhage associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positive vasculitis syndrome was diagnosed because of the high serum level of MPO-ANCA. After the initiation of steroid therapy and termination of PTU, the infiltrative shadows in both lung fields disappeared, PaO2 improved, and MPO-ANCA decreased. There have been some reports of MPO-ANCA positive vasculitis syndrome developing during PTU therapy, but most were concerned with renal disease. We concluded that PTU and similar agents should be given consideration as one of the possible causes of MPO-ANCA-induced alveolar hemorrhage.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Hemorrhage; Humans; Hyperthyroidism; Lung Diseases; Middle Aged; Peroxidase; Propylthiouracil; Pulmonary Alveoli; Syndrome; Vasculitis

Propylthiouracil (PTU), a drug commonly used for treatment of hyperthyroidism, is associated with various rare side effects. Antineutrophil cytoplasm antibody (ANCA)-positive vasculitis is a relatively unusual complication among them. The pathogenesis of ANCA-positive vasculitis during PTU therapy is still obscure. We present the case of a 12-year-old boy who developed ANCA-positive vasculitis during PTU therapy for Graves' disease. His symptoms and signs were indistinguishable from anaphylactoid purpura, a common small-vessel vasculitis in children. The clinical manifestations improved after discontinuation of PTU and immunosuppressant treatment. He remained symptom-free at 11-months follow-up.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Graves Disease; Humans; IgA Vasculitis; Male; Propylthiouracil; Vasculitis

Antithyroid drugs adverse effects are varied and rare. Autoimmune disorders (vasculitis, lupus erythematosus, polyarthritis...) are unusual and serious complications of antithyroid drugs. Since 1945, fewer than 100 cases of systemic manifestations related to antithyroid drugs have been reported in the literature, most frequently with propylthiouracil. The outcome is usually good after drug discontinuation, but some fatal cases have been reported. Because possible cross-sensitivity with other antithyroid drugs, the appropriate treatment for hyperthyroidism relapse if a patient has had an antithyroid drug adverse reaction, should be 131I-Iodine or surgery. We report four new cases of systemic manifestations during propylthiouracil therapy.

Topics: Adult; Antithyroid Agents; Arthritis; Diagnosis, Differential; Female; Follow-Up Studies; Graves Disease; Humans; Lupus Erythematosus, Systemic; Middle Aged; Propylthiouracil; Recurrence; Thyroidectomy; Vasculitis

Propylthiouracil (PTU) has recently been observed to be associated with antineutrophil cytoplasmic antibody (ANCA)-positive small vessel vasculitis, resulting in crescentic glomerulonephritis and, infrequently, diffuse alveolar hemorrhage (DAH). We describe a case of a 23-year-old pregnant woman who developed a perinuclear ANCA and antimyeloperoxidase-positive small vessel vasculitis manifesting as DAH and crescentic glomerulonephritis after she began taking PTU. An open lung biopsy was consistent with pulmonary capillaritis. She responded to corticosteroid therapy and discontinuation of PTU. DAH can be caused by pulmonary capillaritis, bland hemorrhage, or diffuse alveolar damage. To our knowledge, this represents the first documentation of an underlying pulmonary capillaritis in a case of PTU-induced DAH.

Topics: Adult; Antimetabolites; Biopsy; Capillaries; Female; Glucocorticoids; Hemorrhage; Humans; Hyperthyroidism; Lung; Lung Diseases; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, First; Propylthiouracil; Pulmonary Alveoli; Radiography, Thoracic; Vasculitis

Two cases of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis following treatment with propylthiouracil and carbimazole are described. Both patients had crescentic glomerulonephritis proven by renal biopsy and responded to immunosuppressive therapy and withdrawal of the anti-thyroid drugs. Though systemic vasculitis associated with propylthiouracil is reported, this is the first report to our knowledge of renal biopsy-proven vasculitis associated with either of these drugs.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Carbimazole; Glomerulonephritis; Humans; Hyperthyroidism; Kidney; Male; Middle Aged; Propylthiouracil; Thyrotoxicosis; Vasculitis

Vasculitis is a rare complication of propylthiouracil therapy. Antineutrophil cytoplasmic antibodies (ANCA) have been described in association with several vasculitic disorders. We report detection of ANCA against human neutrophil elastase, proteinase 3, and myeloperoxidase in serum from six patients who developed evidence of vasculitis during propylthiouracil treatment of hyperthyroidism. On withdrawal of the drug ANCA concentrations fell and clinical symptoms resolved completely.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Biomarkers; Female; Humans; Hyperthyroidism; Immunoglobulin G; Middle Aged; Propylthiouracil; Vasculitis

Aiming to know the incidence and evolution of major adverse reactions to propylthiouracil in patients with hyperthyroidism, we performed a retrospective analysis of 586 patients treated between 1982 and 1992. All known complications associated to the use of propylthiouracil were considered major adverse reactions, when other causes were discarded. Eight patients (1.4% of the sample) had major adverse reactions: three had agranulocytosis, 3 hepatitis, 1 cholestasis and 1 vasculitis. All had a good evolution after discontinuing the drug. The patients with agranulocytosis were treated with antibiotics and the patient with cholestasis received prednisone. We conclude that major adverse reactions to propylthiouracil are infrequent, that they occur preferentially during the first months of treatment, earlier after reexposure and that there was no associated mortality.

Topics: Adolescent; Adult; Agranulocytosis; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Humans; Hyperthyroidism; Male; Middle Aged; Propylthiouracil; Retrospective Studies; Vasculitis

Topics: Agranulocytosis; Drug Hypersensitivity; Female; Humans; Middle Aged; Plasmapheresis; Propylthiouracil; Vasculitis

Topics: Adult; Female; Fever; Humans; Immune Complex Diseases; Leg Ulcer; Lung Diseases; Propylthiouracil; Purpura; Skin Transplantation; Transplantation, Autologous; Vasculitis