Antineutrophil cytoplasmic antibodies

The inflammatory response in UC is propagated by atypical type 2 helper T cells that produce proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF).7 As discussed previously, a genetic predisposition to UC may partially explain the development of excessive colonic and rectal inflammation. The finding of positive perinuclear antineutrophil cytoplasmic antibodies (pANCA) in association with the human leukocyte antigen (HLA)-DR2 allele in a large percentage of patients with UC supports this theory.4,12... 

Ulcerative colitis Leukocytosis, decreased hematocrit/hemoglobin, elevated erythrocyte sedimentation rate (ESR), guaiac-positive stool, (+) perinuclear antineutrophil cytoplasmic antibodies (pANCA up to 70% of patients)... 

Shapiro, L.E., Uetrecht, J., and Shear, N.H. Minocycline, perinuclear antineutrophilic cytoplasmic antibody and pigment The biochemical basis, J. Amer. Acad. Dermatol., 45, 787, 2001... 

Pelletier, F. et al, Minocycline-induced cutaneous polyarteritis nodosa with antineutrophil cytoplasmic antibodies, Em J. Dermatol., 13, 396, 2003. 

Ototoxicity has rarely been attributed to antithyroid drugs (13). In one case progressive bilateral sensorineural hearing loss attributed to propylthiouracil was associated with myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) (14). 

Of 14 cases of suspected drug-induced liver disease presenting to a gastroenterology department over a 3-year period, one was thought to be related to thiamazole, with a hepatitic pattern of liver function tests in a 39-year-old woman 6 days after the start of therapy recovery was swift and complete (48). Delayed cholestatic hepatitis without antineutrophil cytoplasmic antibodies has been reported (49), and there have been fatal cases of hepatic necrosis (SEDA-21, 438) (7). 

Acute pancreatitis and parotitis without antineutrophil cytoplasmic antibodies has been attributed to thiamazole (53). 

Antithyroid drugs, especially propylthiouracil, can be associated with the development of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis, often manifesting as renal disease. Atypical presentations, with pulmonary capillaritis (58) and lupus-like syndrome (59), have been described in individual cases. Furthermore, two cases of vasculitis have been associated with carbimazole, one presenting with eosinophilic granulomatous vasculitis localized to the stomach (60) and another with p-ANCA positive vasculitis causing simultaneous acute renal insufficiency and massive pulmonary hemorrhage (61). 

Slot MC, Links TP, Stegeman CA, Tervaert JW. Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients with hyperthyroidism treated with antithyroid drugs a long-term followup study. Arthritis Rheum 2005 53(1) 108-13. 

Gao Y, Ye H, Yu F, Guo XH, Zhao MH. Anti-myeloper-oxidase IgG subclass distribution and avidity in sera from patients with propylthiouracil-induced antineutrophil cytoplasmic antibodies associated vasculitis. Clin Immunol 2005 117(l) 87-93. 

Choi HK, Merkel PA, Walker AM, Niles JL. Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis prevalence among patients with high titers of antimyeloperoxidase antibodies. Arthritis Rheum 2000 43(2) 405-13. 

Sera N, Yokoyama N, Abe Y, Ide A, Usa T, Tominaga T, Ejima E, Kawakami A, Ashizawa K, Eguchi K. Antineutrophil cytoplasmic antibody-associated vasculitis complicating Graves disease report of two adult cases. Acta Med Nagasaki 2000 45 33-6. 

Otsuka S, Kinebuchi A, Tabata H, Yamakage A, Yamazaki S. Myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis following propylthiouracil therapy. Br J Dermatol 2000 142(4) 828-30. 

Matsubara K, Nigami H, Harigaya H, Osaki M, Baba K. Myeloperoxidase antineutrophil cytoplasmic antibody positive vasculitis during propylthiouracil treatment successful management with oral corticosteroids. Pediatr Int 2000 42(2) 170-3. 

Antineutrophil cytoplasmic antibody (ANCA)-positive cutaneous leucocytoclastic vasculitis associated with antithyroid therapy in Graves disease. Australas J Dermatol 1998 39(2) 96-9. 

Gunton JE, Stiel J, Caterson RJ, McElduff A. Clinical case seminar anti-thyroid drugs and antineutrophil cytoplasmic antibody positive vasculitis. A case report and... 

Miller RM, Darben TA, Nedwich J, Savige J. Propylthiouracil-induced antineutrophil cytoplasmic antibodies in a patient with Graves disease and a neutrophilic dermatosis. Br J Dermatol 1999 141(5) 943-4. 

Wada N, Mukai M, Kohno M, Notoya A, Ito T, Yoshioka N. Prevalence of serum anti-myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) in patients with Graves disease treated with propylthiouracil and thiamazole. Endocr J 2002 49(3) 329-34. 

Katayama K, Hata C, Kagawa K, Noda M, Nakamura K, Shimizu H, Fujimoto M. Diffuse alveolar hemorrhage associated with myeloperoxidase-antineutrophil cytoplasmic antibody induced by propylthiouracil therapy. Respiration 2002 69(5) 473. 

Hong SB, Lee MH. A case of propylthiouracil-induced pyoderma gangrenosum associated with antineutrophil cytoplasmic antibody. Dermatology 2004 208(4) 339-41. 

Harper L, Chin L, Daykin J, Allahabadia A, Heward J, Gough SC, Savage CO, Franklyn JA. Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves disease. Clin Endocrinol (Oxf) 2004 60(6) 671-5. 

ACE = angiotensin-converting enzyme ANA = antinuclear antibody ANCA = antineutrophil cytoplasmic antibody BUN = blood urea nitrogen CBC = complete blood count ELISA = enzyme-Mnked immunoassay assay ESR = erythrocyte sedimentation rate FTA-ABS = fluorescent treponemal antibody absorption HLA = human lymphocyte antigen MHA-TP = micro-hemagglutination-7re/ OMew pallidum-, PPD = purified protein derivative RPR = rapid plasma reagin VDRL = venereal disease reference laboratory. 

Haubitz M, ScheUong S, Gobel U, Schurek HI, Schaumann D, Koch KM, Brunkhorst R. Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vascuhtis and renal involvement a prospective, randomized study. Arthritis Rheum 1998 41(10) 1835 4. 

Five of 160 children with nephrotic syndrome developed distinctive vascular purpura (45). They had taken levamisole for a mean of 24 months when they developed purpuric erythematous macules, which evolved to ecchy-motic and necrotic purpura. The lesions were mostly on the external ear. Biopsies obtained from the ear lesions in four patients showed vasculopathic reaction patterns, ranging from leukocytoclastic and thrombotic vasculitis to vascular occlusive disease without true vasculitis. There were anticardiolipin, antinuclear, and/or antineutrophil cytoplasmic antibodies in four patients. The lesions resolved within 2-3 weeks after levamisole withdrawal, whereas anticardiolipin and antineutrophil cytoplasmic antibodies disappeared after 2-14 months only. A direct effect of levamisole on the endothehal cells or levamisole-induced or unmasked latent immunological abnormalities was suspected. 

Two cases of biopsy-proven cutaneous polyarteritis nodosa with positive perinuclear antineutrophilic cytoplasmic antibodies have been reported with long-term use of minocycline for acne vulgaris (50-100 mg/day for 44 months and 100 mg/day for 65 months) (52). In one of the cases, involvement was not restricted to medium-size vessels alone. In both cases the vasculitis disappeared after a short course of prednisone (40 mg/day) and withdrawal of minocycline. Rechallenge was not performed. P-ANCA is usually found in microscopic poly angiitis, a vasculitis of smaller arteries, and its significance in polyarteritis nodosa is not clear. 

Schaffer JV, Davidson DM, McNiff JM, Bolognia JL. Perinuclear antineutrophilic cytoplasmic antibody-positive cutaneous polyarteritis nodosa associated with minocychne therapy for acne vulgaris. J Am Acad Dermatol 2001 44(2) 198-206. 

Aguilera CR, Garcia-De La Torre 1. Diffuse alveolar hemorrhage in limited cutaneous systemic sclerosis with positive perinuclear antineutrophil cytoplasmic antibodies. J Rheumatol 1996 23(10) 1821-3. 

Keogh KA, Wylam ME, Stone JH, Specks U. Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005 52(l) 262-8. 

Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis is a well-described complication, particularly with propylthiouracil and to a lesser extent with carbimazole, and has been most often described in patients with Graves disease. The possible drug-induced causes of ANCA-positive vasculitis with high titers of antimyeloperoxidase antibodies in 30 new patients have been reviewed (47). The findings illustrated that this type of vasculitis is a predominantly drug-induced disorder. Only 12 of the 30 cases were not related to a drug. The most frequently implicated drug was hydralazine (n = 10) the remainder involved propylthiouracil n — 3), penicillamine (n = 2), allopurinol n = 2), and sulfasalazine (n = 1). 

---