Cocaine- and Levamisole-Induced Vasculitis: Defining the Spectrum of Autoimmune Manifestations

Abstract

Drug-induced or associated vasculitis is a prevalent form of vasculitis that resembles primary idiopathic antineutrophil cytoplasmic autoantibody (ANCA) vasculitis (AAV). Cocaine is a diffuse psychostimulant drug and levamisole is a synthetic compound used to cut cocaine. Their abuse may result in a spectrum of autoimmune manifestations which could be categorized into three overlapping clinical pictures: cocaine-induced midline destructive lesion (CIMDL), levamisole-adulterated cocaine (LAC) vasculopathy/vasculitis, and cocaine-induced vasculitis (CIV). The mechanisms by which cocaine use leads to disorders resembling AAV are not well understood. Cocaine can cause autoimmune manifestations ranging from localized nasal lesions to systemic diseases, with neutrophils playing a key role through NETosis and ANCA development, which exacerbates immune responses and tissue damage. Diagnosing and treating these conditions becomes challenging when cocaine and levamisole abuse is not suspected, due to the differences and overlaps in clinical, diagnostic, therapeutic, and prognostic aspects compared to primary idiopathic vasculitides.

Keywords: ANCA; CIMDL; CIV; LAC vasculopathy/vasculitis; antineutrophil cytoplasmic autoantibody; cocaine; cocaine-induced midline destructive lesion; cocaine-induced vasculitis; levamisole; levamisole-adulterated cocaine; vasculitis.

Figure 1

A model of the immunopathogenesis underlying damage to local nasal structures and autoimmune reactions in cocaine and levamisole-induced vasculitis (Created with www.app.biorender.com accessed on 25 May 2024). ANCAs: anti-neutrophils cytoplasmatic antibodies; APC: antigen-presenting cell; MPO: myeloperoxidase; NETs: neutrophil extracellular traps; PR3: proteinase 3.

Figure 2

(A) External endoscopic view of a right paralatero–nasal cutaneous fistula in a patient with history of cocaine abuse. (B) The same cutaneous defect is visible in a 3D-rendering based on CT scan.

Figure 3

(A) Nasal endoscopy with a 30-degree endoscope shows a large hard- and soft-palate defect with evidence of oral cavity and laryngopharyngeal structures such as oral tongue, base of the tongue with hypertrophic lingual tonsils, free margin of the epiglottis, laryngeal vestibule, arytenoids, and retrocricoid space. A cluster of three ulcerated lesions of the posterior wall of the nasopharynx is visible. (B) Endoscopic view with a 30-degree endoscope from the oral cavity in the same patient revealed an anterior hard-palate fistula, and a larger hard- and soft-palate defect.

Figure 4

CT scan of a patient with a history of cocaine abuse, showing in the axial scans (A,B) a complete erosion of the nasal septum and bony limits of the paranasal sinuses, with right paralatero–nasal fistula and hyperostosis of the residual left maxillary-sinus bony walls. This is more evident in the coronal scan (C), where an oronasal fistulation of the hard palate is visible. The ethmoidal cells are obliterated, as well as the frontal and sphenoid sinuses (D).

Figure 5

The abuse of cocaine may result in a “spectrum of autoimmune manifestations” in predisposed individuals, ranging from localized to systemic effects. These manifestations, which may partially overlap, can ultimately be classified into three clinical entities: cocaine-induced midline destructive lesion (CIMDL), levamisole-adulterated cocaine (LAC) vasculopathy/vasculitis, and cocaine-induced vasculitis (CIV). AAV: ANCA-associated vasculitis; ANCA: anti-neutrophil cytoplasmatic antibody; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; HNE: human neutrophilic elastase; MPO: myeloperoxidase; p-ANCA: perinuclear-ANCA, PR3 proteinase 3.