Drug-induced anca-positive vasculitis I77.6

Drug-induced ANCA+ vasculitis can affect several organs, but preferably the skin. The symptoms appear on average about 2 weeks after taking the medication. The disease often progresses mildly, especially when the causative medication is discontinued.

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

ANCA-positive drug-induced vasculitides have been induced by propylthiouracil, minocycline, hydralazine. Other triggers include amoxicillin, metamizole, pristinamycin, rifampicin, fluconazole, metformin, glimepiride, phenobarbital, gabapentin, fenofibrate, ibuprofen, allopurinol, rituximab and tinzaparin, cocaine levamisole.

A clinical subgroup of drug-induced ANCA-positive vasculitis is cocaine levamisole-induced vasculopathy syndrome, which occurs after ingestion of cocaine laced with levamisole. The patient population is relatively young (45 years +/- 12 years). Typical are pronounced vasculitic symptoms with a p-NCA-positive leukocytoclastic vasculitis of the skin (palpable purpura), often also with multiple painful ulcers of the skin (82% skin involvement especially lower extremity), more rarely also of the oral mucosa. Furthermore, arthralgias (71%) and acute arthritides (33%) occur. Further systemic involvement (lungs, kidneys) is possible but rather rare. In addition to isolated skin involvement, other monoorganic patterns of involvement may occur such as ANCA-positive chronic inflammatory deforming arthritis (typically: rheumatoid factor and anti-cyclic citrillinated 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" in advanced non-small cell lung cancer (C34.9) (NSCLC). The vasculitic symptoms with myositis and skin lesions combined with a high c-ANCA titer occurred in this patient after the first single dose (Sibille A et al.2019).

• In a 50-year-old man with hypertension and sarcoidosis, drug-induced lupus erythematosus combined with high titre ANCAs occurred after 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 high titers of MPO-ANCA (p-ANCA). Treatment was propylthiouracil (PTU). After interruption of PTU therapy and treatment with immunosuppressive drugs and plasmapheresis, there was a prompt reduction of pathogenic autoantibodies. (Fathallah N et al. 2019)
• Marquez J et al (2017) reported cases of p-ANCA-positive granulomatous vasculitis with leading integumentary symptoms (palpable purpura) after ingestion of a cocaine-levamisole drug mixture.
• Agdamag AC et al. (2018) reported a 51-year-old woman with chronic cocaine-levamisole abusus and high titre p-ANCA, titer, who first had multiple skin ulcers and later lung and kidney involvement. Also in this case an immunosuppressive systemic therapy was necessary.
• Hacking S et al (2019) reported a fatal case of ANCA-associated vasculitis due to metamizole in a 64-year-old woman. She was initially hospitalized for abdominal pain and questionable colitis and subsequently developed hematuria, renal failure and hemoptysis. Serological workup revealed positive antinuclear antibodies (ANAs) and p-ANCAs. A subsequent autopsy revealed severe rapid progressive glomerulonephritis (type 3 of RPGN; ICD: NO1.9), diffuse pulmonary alveolar hemorrhage; as well as pericarditis and focal vasculitis of the coronary arteries.
• Jin Q et al (2018) reported a 46-year-old woman with cocaine (-levamisol) drug use who suffered from a recurrent ANCA-positive hemorrhagic exanthema of the 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.