Drug-induced anca-positive vasculitis I77.6

Drug-induced ANCA+ vasculitis (see also overview - ANCA-positive vasculitis) can affect several organs, but preferably the skin. Symptoms appear on average around 2 weeks after taking the medication. The diseases are often mild, especially when the causative medication is discontinued.

A clinical subgroup of drug-induced ANCA-positive vasculitis is cocaine levamisole-induced vasculopathy syndrome , which can be severe and fatal (Agdamag AC et al. 2018).

ANCA-positive drug-induced vasculitis was triggered by propylthiouracil, minocycline and hydralazine. Other triggers include amoxicillin, metamizole, pristinamycin, rifampicin, fluconazole, metformin, glimepiride, phenobarbital, gabapentin, fenofibrate, ibuprofen, allopurinol, rituximab and tinzaparin.

A clinical subgroup of drug-induced ANCA-positive vasculitis is the cocaine-levamisole-induced vasculopathy syndrome, which occurs after ingestion of cocaine laced with levamisole. The patient collective is relatively young (45 years +/- 12 years).

Typical are pronounced vasculitic symptoms with a p-NCA-positive leukocytoclastic vasculitis of the skin (palpable purpura), frequently also with multiple painful ulcers of the skin (82% skin infestation, especially lower extremity), more rarely also of the oral mucosa.

Furthermore, arthralgias (71%) and acute arthritides (33%) occur.

Further vasculitic system involvement (lungs, kidneys) is possible, but rather rare. In addition to isolated skin involvement, other monoorganic involvement patterns can also occur, such as ANCA-positive, chronic inflammatory deforming arthritis (typically: rheumatoid factor and anti-cyclic citrullinated antibody-negative, HLA-B27 negative; Emil NS et al. 2018).

BSG↑↑, ANCAs↑↑ (86% p-ANCA and 14% c-ANCA - Emil NS et al. 2018); furthermore neutropenia (18%), C3↓ decreased (27%), antiphospholipid antibodies ↑ (50%)

Image of leukocytoclastic vasculitis

• Occurrence of c-ANCA-positive granulomatosis with polyangiitis (GPA) in a patient treated with an“anti-programmed death protein-1 (PD-1) antibody” for advanced non-small cell lung cancer (C34.9) (NSCLC). Vasculitic symptoms, including myositis and skin lesions, combined with a high c-ANCA titer, appeared in this patient as early as after the first single dose (Sibille A et al. 2019).
• In a 50-year-old man with hypertension and sarcoidosis, drug-induced systemic lupus erythematosus combined with high-titer ANCAs developed following treatment of hypertension and heart failure with hydralazine(Watanabe-Kusunoki K et al. (2019).
• A 19-year-old female patient with Graves’ disease suddenly developed fever, polyarthralgia, and pulmonary hemorrhage with a high titer of MPO-ANCA (p-ANCA). Treatment consisted of propylthiouracil (PTU). Following discontinuation of PTU therapy and treatment with immunosuppressants and plasmapheresis, there was a prompt reduction in pathogenic autoantibodies. (Fathallah N et al. 2019)
• Marquez J et al. (2017) reported cases of p-ANCA-positive granulomatous vasculitis with predominant cutaneous symptoms (palpable purpura) following ingestion of a cocaine-levamisole drug mixture.
• Agdamag AC et al. (2018) reported on a 51-year-old woman with chronic cocaine-levamisole abuse and a high p-ANCA titer, who initially developed multiple skin ulcers and later experienced pulmonary and renal involvement. In this case as well, systemic immunosuppressive therapy was necessary.
• Hacking S et al. (2019) reported a fatal case of ANCA-associated vasculitis caused by metamizole in a 64-year-old woman. She was initially admitted to the hospital for abdominal pain and suspected colitis and subsequently developed hematuria, renal failure, and hemoptysis. Serological testing revealed positive antinuclear antibodies (ANAs) and p-ANCA titers. A subsequent autopsy revealed severe rapid-onset progressive glomerulonephritis (type 3 RPGN; ICD: NO1.9), diffuse pulmonary alveolar hemorrhage with pericarditis, and focal coronary vasculitis.
• Jin Q et al. (2018) reported on a 46-year-old woman with a history of cocaine (and levamisole) use who suffered from a recurrent ANCA-positive hemorrhagic rash on her extremities and face.

1. Agdamag AC et al (2018) Multiple cutaneous and mucosal lesions in a patient with cocaine-levamisole-induced vasculopathy syndrome.Proc Bayl Univ Med Cent 32:93-95.
2. Emil NS et al (2018) Atypical Chronic Inflammatory ANCA-Positive Deforming Arthritis After Cocaine-Levamisole Exposure.J Clin Rheumatol doi: 10.1097/RHU.
3. Espinosa MC et al (2019) A simultaneous presentation of drug-induced lupus with drug-induced ANCA vasculitis secondary to hydralazine use in a patient with sarcoidosis. Proc (Bayl Univ Med Cent)32:231-234.
4. Fathallah N et al (2019) Drug-induced vasculitis. Therapy 74:347-354.
5. Hacking S et al (2019) Systemic p-ANCA vasculitis with fatal outcome, arising in the setting of methimazole use. Clin Nephrol Case Studies 7:23-26.
6. Jin Q et al (2018) Levamisole adulterated cocaine associated ANCA vasculitis: review of literature and update on pathogenesis. J Community Hosp Intern Med Perspect 8:339-344.
7. Marquez J et al (2017) Cocaine-Levamisole-Induced Vasculitis/Vasculopathy Syndrome. Curr Rheumatol Rep 19:36.
8. Nguyen V et al (2019) Levamisole-Induced Vasculitis in the Lower Extremities: A Case Report. J Am Podiatr Med Assoc 109:150-154.
9. Sibille A et al (2019) Granulomatosis With Polyangiitis in a Patient on Programmed Death-1 Inhibitor for Advanced Non-small-cell Lung Cancer. Front Oncol 9:478.
10. Watanabe-Kusunoki K et al. (2019) A case report dysregulated neutrophil extracellular traps in a patient with propylthiouracil-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. Medicine (Baltimore) 98:e15328.