thiouracil and Vasculitis

Vasculitis is a rare complication of antithyroid drugs reported with propylthiouracil, carbimazole, methimazole and we describe the first case with benzylthyouracil. Renal involvement during thyroid auto-immune diseases and during vasculitis as complication of antithyroid drugs will be discussed.. We present a case study of 28-year-old female patient with Graves' disease diagnosed in 1996 and treated by benzylthiouracil for 2 years. The thyroid function was poorly controlled, so surgical treatment was indicated in May 1998. One month later, she developed vasculitis with pulmonary and renal involvement. Her renal function deteriorated rapidly. On admission, the additional laboratory findings showed hematuria, proteinuria of 1.44 g/day and serum creatinine level at 1000 mumol/l. She had myeloperoxidase-anti neutrophil cytoplasmic antibody, antithyroglobulin and antimicrosome antibodies. A renal biopsy revealed pauci-immune crescentic glomerulonephritis with 75% sclerous crescents. Chest-X-ray showed unilateral alveolar shadowing and a bronchio-alveolar lavage revealed lymphocytic alveolitis. She was treated with high dose of prednisolone and cyclophosphamide. After a follow-up of 18 months, the serum creatinine level decreased at 186 mumol/l and chest-X-ray returned to normal.. Some cases of vasculitis associated with anti-thyroid drug treatment are reported.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Female; Glomerulonephritis; Graves Disease; Humans; Lung Diseases, Interstitial; Thiouracil; Vasculitis

In adults, anti-neutrophil cytoplasmic antibodies (ANCA) are considered as serological markers of several diseases, especially vasculitis and glomerulonephritis. Since ANCA are rarely positive in children, few data about the clinical relevance of these auto-antibodies in pediatric population have been reported. Therefore, our study aims to describe the spectrum of disorders associated with positive ANCA in Tunisian children. This study had been carried out over a period of 12 years and a half. All patients under the age of 15 for whom ANCA screening was performed in our laboratory were included. Clinical data were collected retrospectively. Indirect immunofluorescence (IFI) technique for ANCA detection was performed using PNN smears fixed with ethanol, formalin and, if necessary, methanol. Positive results were tested using immunodot to characterize the antigenic targets (myeloperoxydase (MPO) and proteinase 3 (PR3)). Our results showed that 410/5,990 (6.8%) laboratory requests for ANCA screening were for children. Forty (9.7%) requests were positive (24 children). Clinical data were available for 19 patients only. Sex-ratio (F/M) was 1.25. The mean age was 9 years and a half (3-15 years). The most frequent IIF patterns were x-ANCA (n=12) and p-ANCA (n=7). In our patients, the most frequent conditions associated to ANCA were treatment with benzylthiouracil for hypothyroidism (n=6), inflammatory bowel disease (n=4) and hemolytic anemia (n=4). In conclusion, the positivity of ANCA in children seems to be a rare event. Associated conditions include clinical disorders specific to the pediatric population. Treatment with benzylthiouracil is an etiology to be taken into consideration.

Topics: Adolescent; Anemia, Hemolytic; Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Blood Chemical Analysis; Child; Child, Preschool; Female; Fluorescent Antibody Technique, Indirect; Glomerulonephritis; Humans; Hypothyroidism; Inflammatory Bowel Diseases; Male; Prevalence; Retrospective Studies; Seroepidemiologic Studies; Thiouracil; Vasculitis

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

Antineutrophil cytoplasmic antibodies are classical serological markers of small-vessels vasculitis. However, they have been described in many other pathological situations. The aim of this study was to determine through our experience, the main antineutrophil cytoplasmic antibodies-associated diseases and to investigate antigen targets of these antibodies. Forty complete observations of antineutrophil cytoplasmic antibodies (ANCA) positive patients either by indirect immunofluorescence or by enzyme immunoassay were analysed. Only five (12.5%) patients have small-vessels vasculitis. Among these, antineutrophil cytoplasmic antibodies were detected only by Elisa in one patient and they were exclusively directed against bactericidal permeability increasing protein in another one. Our study confirms the presence of antineutrophil cytoplasmic antibodies in different diseases. It demonstrates that antineutrophil cytoplasmic antibodies should be investigated by Elisa when indirect immunofluorescence is negative. In small-vessels vasculitis, Proteinase 3 and myeloperoxidase are mainly but not exclusively the antigenic targets of antineutrophil cytoplasmic antibodies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Autoantigens; Autoimmune Diseases; Child; Connective Tissue Diseases; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Humans; Infections; Inflammation; Male; Mass Screening; Middle Aged; Myeloblastin; Peroxidase; Thiouracil; Vasculitis; Young Adult

Drug induced antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis is a rare complication associated especially with propylthiouracil (PTU). Prevalence of ANCA in patients receiving PTU is well established. Few cases of vasculitis were also reported with benzylthiouracil (BTU). The objective of this study is to clarify the prevalence of ANCA in patients receiving BTU.. ANCA were investigated by indirect immunofluoresence and enzyme linked immunosorbant assay in 159 patients with Graves' disease (86 untreated and 73 treated with BTU).. ANCA were positive in three (3.5%) untreated patients and 27 (37%) treated ones. Titres of ANCA varied between 1:20 and 1:200. There was a significant association between BTU treatment and ANCA (p<0.001). ANCA were directed against myeloperoxidase (MPO) in 28 (93.3%) patients. Median treatment duration was 24 months (ranges 0.5 to 144 months). There was no significant association between treatment duration and ANCA. Vasculitis was found in two (2.7%) treated patients. One patient has developed isolated cutaneous vasculitis and the other one a pulmonary vasculitis with diffuse alveolar haemorrhage.. BTU therapy is characterised by a high prevalence of ANCA mainly but not exclusively directed against MPO. However, vasculitis remains a rare complication.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantigens; Autoimmune Diseases; Child; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Graves Disease; Humans; Male; Middle Aged; Peroxidase; Thiouracil; Vasculitis; Young Adult

Vasculitis with antineutrophilic cytoplasmic antibodies (ANCA) have been reported in patients treated with anti-thyroid drugs, especially propylthiouracil. Benzylthiouracil, which exhibits similar structural likeness with propylthiouracil, has been recently observed to be associated with Anca-positive vasculitis.. We present a study of three women with Grave's disease aged 21, 37 and 40 years, who were treated with benzylthiouracil. These patients developed vasculitis characterized by constitutional symptoms (two patients), joint pain (two patients), renal involvement (two patients), pulmonary hemorrhage (one patient) and multiple neuropathy (one patient). All patients presented p-ANCA with anti-MPO pattern. Discontinuation of benzylthiouracil and treatment with corticosteroids improved systemic involvement in all patients.. Much like other anti-thyroid drugs, benzylthiouracil can be associated with ANCA-positive vasculitis. Because of the gravity of this complication, clinical monitoring is recommended in patients taking benzylthiouracil. If vasculitis develops, the anti-thyroid drug should be discontinued and corticosteroid treatment, with immunosuppressors in some cases, is initiated.

Topics: Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Antibodies; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Enzyme-Linked Immunosorbent Assay; Female; Graves Disease; Humans; Immunosuppressive Agents; Myelography; Peroxidase; Thiouracil; Vasculitis; Young Adult

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.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Female; Graves Disease; Hematuria; Humans; Kidney Diseases; Thiouracil; Treatment Outcome; Uridine Phosphorylase; Vasculitis

Benzylthiouracil has been recently observed to be associated with antineutrophil cytoplasmic antibody-positive vasculitis, resulting in crescentic glomerulonephritis. We report an 8-year-old girl treated with benzylthiouracil for Graves's disease who developed an ANCA-positive vasculitis with pulmonary hemorrhage. She responded to corticosteroids and discontinuation of benzylthiouracil. This represents the first pediatric case of benzylthiouracil-induced diffuse alveolar hemorrhage.

Topics: Antibodies, Antineutrophil Cytoplasmic; Child; Female; Graves Disease; Hemorrhage; Humans; Lung Diseases; Thiouracil; Vasculitis

Several cases of vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) have been reported in patients treated with synthetic anti-thyroid drugs but only 2 cases have incriminated benzylthiouracil.. A 36 year-old woman, 3 years after treatment with benzylthiouracil, rapidly developed progressive kidney failure, related to a pauci-immune extra-capillary glomerular nephropathy and necrotic vasculitis lesions. The search for p-ANCA was positive with anti-myeloperoxidase specificity. She was treated with corticosteroids and 6 monthly intravenous pulses of cyclophosphamide substituted by azathioprine. Renal failure and proteinuria significantly improved. However the high level of p-ANCA.. ANCA vascularities are a rare but serious complication of treatment with synthetic thiouracile-type anti-thyroid drugs. The ANCA must be measured when confronted with a systemic manifestation during treatment.

Topics: Adrenal Cortex Hormones; Adult; Antibodies, Antinuclear; Female; Humans; Hyperthyroidism; Thiouracil; Uridine Phosphorylase; Vasculitis

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).. 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.. 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.

Topics: Antibodies, Antineutrophil Cytoplasmic; Glomerulonephritis; Graves Disease; Humans; Male; Middle Aged; Thiouracil; Uridine Phosphorylase; Vasculitis