French Multicenter Retrospective Study of Patients with Cocaine- and/or Levamisole-induced Vasculitis and Vasculopathy

Kevin Chevalier¹, François Chasset², Yoann Zerbib³, Pierre-André Jarrot⁴, Romain Muller⁴, Thomas Pires⁵, Saroumadi Adavane⁶, Didier Bessis⁷, Alban Deroux⁸, Vincent Descamps⁹, Fanny Domont¹⁰, Joëlle Faddoul¹⁰, Pierre-Edouard gavand¹¹, Tiphaine Goulenok¹², Baptiste Gramont¹³, Vincent Jachiet¹⁴, Gaëlle Leroux¹⁵, Matthieu Mahevas¹⁶, Julie Merindol¹⁷, Loïc Meudec¹⁸, Martin Michaud¹⁹, Morgane Mourguet²⁰, Héloïse Munos pons²¹, Yann Nguyen²², Bénédicte Oules²³, Thomas Papo²⁴, Jacques Pouchot²⁵, Sébastien Rivière¹⁴, Oscar Robert²⁶, Charles ronsin²⁷, Benjamin Rossi²⁸, Delphine Staumont-salle²⁹, Benjamin Terrier³⁰, Nathalie Tieule³¹, Vollmer Olivier³², Pierre Wolkenstein³³, Xavier Puéchal³⁴, Jean-David Bouaziz³⁵, Nicolas Dupin²³, Gilles Peytavin³⁶, Jean-Claude Alvarez³⁷, Luc Mouthon³⁸ and Alexis Régent³⁴, ¹Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France, Paris, France, ²Dermatology, Hôpital Tenon, Paris, France, ³Medical Intensive Care Unit and MP3CV-EA7517, Amiens University Hospital, Amiens, France, Amiens, France, ⁴Service de Médecine Interne et Immunologie Clinique, Hôpital de La Conception, Marseille, Marseille, France, ⁵Department of Internal Medicine, CHU Bordeaux, Bordeaux, France., Bordeaux, France, ⁶Service de Cardiologie, Hôpitaux Saint-Antoine and Tenon, AP-HP, 75012 Paris, France., Paris, France, ⁷Department of Dermatology and Reference Center for Rare Skin Diseases (MAGEC), Saint-Eloi Hospital, University of Montpellier and INSERM U1058, Montpellier, France., Montpellier, France, ⁸Clinique Universitaire de Médecine Interne, Department of Internal Medicine, Grenoble University Hospital, Grenoble, France, ⁹Department of Dermatology, APHP, Bichat Hospital, Paris, France., Paris, France, ¹⁰AP-HP. Centre de Référence des Maladies Auto-Immunes Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose Inflammatoire, F-75013 Paris, France., Paris, France, ¹¹Department of Internal Medicine, Clinique Rhena, Strasbourg, France., Strasbourg, France, ¹²Assistance Publique Hôpitaux de Paris, Paris, France, ¹³Internal Medicine Departement, Saint Etienne, Saint Etienne, France, ¹⁴Service de médecine interne, AP-HP, Hôpital Saint Antoine, Sorbonne Universite, Paris, France., Paris, France, ¹⁵Service de Médecine Interne, AP-HP Hôpital Pitié-Salpêtrière, Paris, France., Paris, France, ¹⁶Department of Internal Medicine, APHP, Mondor Hospital, Paris, France., Créteil, France, ¹⁷Internal Medicine Department, University Hospital of Nice, Côte d'Azur University, Nice, Provence-Alpes-Côte d'Azur, France., Nice, France, ¹⁸Department of Rheumatology, Université Paris-Saclay, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France., Kremlin Bicêtre, France, ¹⁹Department of Internal Medicine, Clinique Saint-Exupery, Toulouse, France., Toulouse, France, ²⁰service de médecine interne CHU Toulouse RANGUEIL, Toulouse, France, ²¹Department of Internal Medicine, Saint-Etienne University Hospital, Saint-Etienne, France., Saint Etienne, France, ²²Université Paris Saclay, Clichy, Ile-de-France, France, ²³Dermatology Department, Cochin Hospital, Paris, France., Paris, France, ²⁴Université Paris Cité, Paris, France, ²⁵Service de médecine Interne, Centre National de Référence des syndromes drépanocytaires majeurs de l'adulte, AP-HP, Hôpital Européen Georges Pompidou, Paris, France, Paris, France, ²⁶Groupe Hospitalier Pitié Salpêtrière, Assistance Publique Hopitaux de Paris, Service de Pneumologie et Réanimation Médicale, Paris, France; [email protected]., Paris, France, ²⁷cHD Vendée, La Roche sur Yon, La Roche sur Yon, France, ²⁸Service de médecine interne, maladies infectieuses, Centre hospitalier intercommunal de Robert Ballenger, Aulnay-sous-bois, France., Aulnay-sous-bois, France, ²⁹Service de dermatologie, CHU de Lille, université de Lille, 59000 Lille, France., Lille, France, ³⁰Service de Médecine interne, Hôpital Cochin, AP-HP, Paris, Ile-de-France, France, ³¹Rhumatologie, Centre Hospitalier Universitaire Nice, Hôpital Pasteur, Nice, France, ³²Department of Immunology and Internal Medicine, Strasbourg University Hospital, Strasbourg, France., Strasbourg, France, ³³Department of Dermatology, National Referral Center for Neurofibromatosis, Henri Mondor University Hospital, Assistance Publique- Hôpitaux de Paris, Creteil, France., Créteil, France, ³⁴National Referral Center For Rare Systemic Autoimmune Diseases, Paris, France, ³⁵Dermatology, Hopital Saint-Louis, Paris, Île-de-France, France., Paris, France, ³⁶Service de Pharmacologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France., Paris, France, ³⁷Service de Pharmacologie‑Toxicologie, Hôpital Raymond Poincaré, Groupe Hospitalier Universitaires AP-HP.Paris-Saclay, Garches, 92380, France, Paris, France, ³⁸Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes et Autoinflammatoires Rares d'Ile de France de l’Est et de l’Ouest, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France

Meeting: ACR Convergence 2024

Keywords: ANCA, skin, Vasculitis

Session Information

Date: Monday, November 18, 2024

Title: Vasculitis – Non-ANCA-Associated & Related Disorders Poster III

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: Levamisole, an imidazothiazole formerly used as an anthelmintic, is also used as a cutting agent to enhance the effects and duration of cocaine. In recent years, levamisole has been implicated in cases of vasculitis and/or thrombotic vasculopathy, particularly in the context of adulterated cocaine use. In addition, cocaine itself has significant vascular effects. We decided to describe a large series of patients with vasculopathy/vasculitis induced by levamisole and/or cocaine.

Methods: We conducted a retrospective multicenter observational study in France. Patients were recruited by a call for observations on behalf of the French Vasculitis Study Group (FVSG) and by screening data from toxicology laboratories.

Patients were included if they had 1) a documented or reported cocaine use regardless of the type of use and 2) vasculitis and/or vasculopathy symptoms after exclusion of other causes, ANCA positivity was not an exclusion criterion. We collected data using a standardized form, including age, sex, past medical history, clinical manifestations, biological and immunological characteristics, pathological data, treatment and outcome.

Results: A total of 63 patients were included, most of them male (58.7%), with a median age of 40 [35-47] years. The main characteristics of the patients are shown in Table 1. The main manifestations were skin (n=34, 54%) with purpura (n=13, 38.2%), necrosis (n=17, 50%) and erythematous plaques (n=14, 41.2%) mainly localized to the extremities, ear-nose and throat (ENT) symptoms (n=40, 63.5%) including sinusitis (n=27, 67.5%), nasal crusts (n=27, 67.5%), epistaxis (n=16, 40%) and saddle nasal deformity (n=28, 70%).

Patients with a positive ANCA test by ELISA (ANCA+) including 16 patients with PR3-ANCA, 3 with MPO-ANCA and 7 with both, were more likely to have ENT involvement than patients with a negative ANCA test (ANCA-) (Table 2). Of the 40 patients (63.5%) with histological results, ENT (n=20, 50%) and skin (n=18, 45%) were the preferred biopsy sites. Necrosis (n=13, 65%) and granuloma (n=6, 20%) were commonly described in ENT biopsies, whereas vasculitis (n=9, 50%) and thrombosis (n=6, 33%) were commonly identified in skin biopsies.

At disease onset, 24 patients (38.1%) were able to stop using cocaine. Of the 63 patients, 24 patients (38.1%) received glucocorticoids, 9 patients (14.3%) received methotrexate and 8 patients (12.7%) received rituximab. Treatment details and therapeutic sequences are summarized in Figure 1.

At the last follow-up, 37 patients (58.7%) were in remission and 7 (11.1%) had died. Twenty-four patients (38.1%) had relapsed. Patients who had been weaned from cocaine were more likely to be in remission (p< 0.0001) and had significantly fewer relapses (p=0.04) than other patients.

Conclusion: Cocaine/levamisole-induced vasculitis/vasculopathy frequently affects the skin (with a histological pattern of vasculitis and thrombosis) and ENT (with a histological pattern of necrosis). ANCA positivity does not appear to influence the clinical phenotype or the clinical course of the disease. Cocaine withdrawal significantly improves the prognosis of these patients.

Table 1 – Clinical characteristics of patients with cocaine/levamisole induced vasculitis/vasculopathy at the time of diagnosis

Table 2 – Comparison of main characteristics between patients with ANCA in ELISA (ANCA+) and patients without ANCA (ANCA-)

Figure 1 – Sunburst representation of treatment combinations at disease onset (baseline) or at first and second relapse according to disease severity
Patients’ manifestations were classified according to their functional or life-threatening consequences as minor organ involvement (i.e. skin, ear-nose-throat or musculoskeletal) or major organ involvement (i.e. lung, kidney, peripheral or central nervous system and heart).
DMARD stands for disease-modifying anti-rheumatic drugs and includes azathioprine, methotrexate, and mycophenolate mofetil. IS stands for immunosuppressive treatments and includes cyclophosphamide and rituximab.
GC: glucocorticoids

Disclosures: K. Chevalier: None; F. Chasset: AstraZeneca, 1, 2, 4, 5, Biogen, 12, National coordinator of clinical trial, BMS, 6, 12, National coordinator of clinical trial, GSK, 1, 4, 5, HorizonTherapeutics, 1, 4, Merck, 1, 4, PrincipaBio, 1; Y. Zerbib: None; P. Jarrot: None; R. Muller: None; T. Pires: None; S. Adavane: None; D. Bessis: None; A. Deroux: None; V. Descamps: None; F. Domont: None; J. Faddoul: None; P. gavand: None; T. Goulenok: None; B. Gramont: None; V. Jachiet: None; G. Leroux: None; M. Mahevas: None; J. Merindol: None; L. Meudec: None; M. Michaud: None; M. Mourguet: None; H. Munos pons: None; Y. Nguyen: None; B. Oules: None; T. Papo: None; J. Pouchot: None; S. Rivière: None; O. Robert: None; C. ronsin: None; B. Rossi: None; D. Staumont-salle: None; B. Terrier: AstraZeneca, 2, GlaxoSmithKline, 2, Novartis, 2, Vifor Pharma, 2; N. Tieule: None; V. Olivier: None; P. Wolkenstein: None; X. Puéchal: None; J. Bouaziz: None; N. Dupin: None; G. Peytavin: None; J. Alvarez: None; L. Mouthon: None; A. Régent: None.

To cite this abstract in AMA style:

Chevalier K, Chasset F, Zerbib Y, Jarrot P, Muller R, Pires T, Adavane S, Bessis D, Deroux A, Descamps V, Domont F, Faddoul J, gavand P, Goulenok T, Gramont B, Jachiet V, Leroux G, Mahevas M, Merindol J, Meudec L, Michaud M, Mourguet M, Munos pons H, Nguyen Y, Oules B, Papo T, Pouchot J, Rivière S, Robert O, ronsin C, Rossi B, Staumont-salle D, Terrier B, Tieule N, Olivier V, Wolkenstein P, Puéchal X, Bouaziz J, Dupin N, Peytavin G, Alvarez J, Mouthon L, Régent A. French Multicenter Retrospective Study of Patients with Cocaine- and/or Levamisole-induced Vasculitis and Vasculopathy [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/french-multicenter-retrospective-study-of-patients-with-cocaine-and-or-levamisole-induced-vasculitis-and-vasculopathy/. Accessed .

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