minocycline and Anti-Neutrophil-Cytoplasmic-Antibody-Associated-Vasculitis

Antineutrophil cytoplasmic autoantibody (ANCA) vasculitis is a systemic autoimmune disease resulting in small-vessel inflammation caused by pathogenic autoantibodies directed against proteinase 3 or myeloperoxidase. Legal drug culprits have been implicated as causative agents in secondary forms of disease, and a recent burst of reports also implicate levamisole-adulterated cocaine as a culprit.. Here, we briefly discuss all drug culprits associated with ANCA vasculitis and then focus on clinical, serologic, therapeutic and mechanistic aspects of four main drug culprits receiving attention of late, namely hydralazine, minocycline, propylthiouracil (PTU) and levamisole-adulterated cocaine.. Hydralazine, minocycline, propylthiouracil and levamisole-adulterated cocaine use should be closely considered in any patient where ANCA vasculitis is entertained given the wide use of these drugs in the community. Furthermore, medical practitioners should test urine for the presence of cocaine in any patient with presumed ANCA vasculitis, and if positive, then urine should also be tested for levamisole. Clinical features can be severe requiring not only drug cessation and supportive care, but also immunosuppression, plasma exchange in severe cases and dialysis as needed. Clinical trial investigators should strongly consider excluding patients with drug-induced forms of disease and mechanistic inroads are greatly needed in these secondary forms of disease to help elucidate the underlying cause and pathogenesis of ANCA vasculitis.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cocaine; Cocaine-Related Disorders; Drug Contamination; Humans; Hydralazine; Levamisole; Minocycline; Propylthiouracil

We report two cases of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) that developed after long-term oral administration of minocycline and consider the contribution of human leukocyte antigen (HLA)-DRB 1 * 09: 01 allele to its development. Case 1; A 47-year-old man receiving minocycline for palmoplantar pustulosis for 24 months developed fever, arthralgia, and irregular livedo on the bilateral lower legs. Skin biopsy demonstrated vasculitis, while a blood test showed positivity of myeloperoxidase (MPO)-ANCA. Discontinuation of minocycline and oral administration of prednisolone relieved the symptoms promptly. Case 2; A 53-year-old woman developed reddish-brown livedo reticularis with tenderness on the bilateral lower legs after administration of minocycline to treat palmoplantar pustulosis for 24 months. Although skin biopsy did not demonstrate vasculitis, a blood test showed MPO-ANCA positivity. Cessation of minocycline resulted in rapid improvement of the cutaneous lesions and constitutional symptoms. We diagnosed both cases as having Drug-associated ANCA-associated Vasculitis (DAV) caused by minocycline according to the diagnostic criteria proposed by Cluver et al. Further examination revealed the presence of HLA-DRB1 * 09:01 allele in both cases. This allele has been implicated in the genetic background of idiopathic microscopic polyangiitis (MPA) in the Japanese population. Our finding suggests a relationship between the development of MPO-ANCA or DAV caused by minocycline and HLA-DRB1 * 09:01 allele, but will have to confirmed by further studies with larger numbers of patients.

Topics: Alleles; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Biomarkers; Biopsy; Disease Susceptibility; Female; Genetic Predisposition to Disease; HLA-DRB1 Chains; Humans; Male; Middle Aged; Minocycline