Search Results (7)

Background and Clinical Significance: Cocaine-induced vasculitis (CIV), especially when associated with PR3-ANCA positivity, can be very similar both clinically and serologically to idiopathic granulomatosis with polyangiitis (GPA). The distinction between these entities is crucial due to the different etiologies, treatment strategies, and prognoses. We present a unique case of CIV that manifested exclusively in a previously dissected neck area—an example of the locus minoris resistance phenomenon—and was initially misinterpreted as skin melanoma recurrence. Case presentation: A 59-year-old man with a history of skin melanoma (pT4b, left pectoral region) and a previous modified radical neck dissection presented in 2024 with new onset of painful subcutaneous nodules and ulcerative lesions at the surgical site. The imaging procedures (CT and PET-CT) raised the suspicion of locoregional malignant recurrence. However, histology revealed necrotizing granulomatous inflammation without tumor cells. Extensive infectious and autoimmune investigations ruled out alternative causes. Subsequently, the patient developed a perforation of the nasal septum and ulcers on the oral mucosa. PR3-ANCA was strongly positive (up to 49 U/mL). Urine toxicology revealed intranasal cocaine use. A diagnosis of cocaine-induced PR3-ANCA vasculitis was made. After immunosuppressive therapy (high-dose glucocorticoids and methotrexate) and substance withdrawal counseling, the patient showed significant clinical improvement. Conclusions: This case highlights the importance of including CIV in the differential diagnosis of granulomatous or ulcerative lesions, especially when they are localized to previous surgical sites. The presentation illustrates the concept of locus minoris resistentiae and highlights the role of toxicological testing in atypical ANCA-positive disease. Full article

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. Full article

Levamisole is an anti-helminthic drug with immunomodulatory properties that is added to cocaine to increase its potency and weight. Levamisole-adulterated cocaine (LAC) may cause an antineutrophil cytoplasmic antibody (ANCA)-associated systemic small vessel vasculitis (AAV). We aimed to characterize the phenotype of persons developing pulmonary-renal syndrome (PRS) in LAC-induced AAV and summarize its treatment and outcomes. Pubmed and Web of Science were searched (until September 2022). Reports that described co-existing diffuse alveolar hemorrhage and glomerulonephritis in an adult (age ≥ 18) with confirmed or suspected LAC exposure were included. Reports, demographics, clinical and serologic features, treatment and outcome characteristics were extracted. Of the 280 records identified, eight met the inclusion criteria, including eight unique cases. Persons were aged 22–58 years, and 50% were women. Cutaneous involvement occurred in only half of the cases. Other associated vasculitis findings and serologies were heterogeneous. All patients received immunosuppression with steroids, with cyclophosphamide and rituximab commonly added. We concluded that PRS could occur from LAC-induced AAV. Distinguishing LAC-induced AAV from primary AAV is challenging as clinical and serologic presentations overlap. Asking about cocaine use is requisite in persons presenting with PRS to guide diagnosis and appropriately counsel on cocaine cessation in conjunction with immunosuppression as treatment. Full article

Adulteration is a well-known practice of drug manufacturers at different stages of drug production. The intentional addition of active ingredients to adulterate the primary drug may enhance or mask pharmacological effects or may produce more potent drugs to increase the number of available doses and the dealer’s profit. Adulterants found in different drugs change over time in response to different factors. A systematic literature search in PubMed and Scopus databases and official international organizations’ websites according to PRISMA guidelines was performed. A total of 724 studies were initially screened, with 145 articles from PubMed and 462 from Scopus excluded according to the criteria described in the Method Section. The remaining 117 records were further assessed for eligibility to exclude articles without sufficient data. Finally, 79 studies were classified as “non-biological” (n = 35) or “biological” (n = 35 case reports; n = 9 case series) according to the samples investigated. Although the seized samples analyses revealed the presence of well-established adulterants such as levamisole for cocaine or paracetamol/acetaminophen for heroin, the reported data disclosed new adulteration practices, such as the use of NPS as cutting agents for classic drugs of abuse and other NPS. For example, heroin adulterated with synthetic cannabinoids or cocaine adulterated with fentanyl/fentalogues raised particular concern. Notably, adulterants play a role in some adverse effects commonly associated with the primary drug, such as levamisole-adulterated cocaine that may induce vasculitis via an autoimmune process. It is essential to constantly monitor adulterants due to their changing availability that may threaten drug consumers’ health. Full article

The use of levamisole as the most frequent adulterant of cocaine has merged in previously unknown toxicities, notably a disease entity called cocaine/levamisole-associated autoimmune syndrome (CLAAS). Clinically, CLAAS can manifest with diverse cutaneous and extracutaneous features sharing common laboratory findings (neutropenia, autoantibody patterns). We report the case of a cocaine-abusing female patient with relapsing episodes of painful ulcers, worsening and expanding over a three-year period. The case exhibited all features of a drug-induced, skin-limited, ANCA-associated vasculitis, evolving over time to PG-like findings. In both disease stages, the patient responded well to the cessation of cocaine exposure and systemic glucocorticosteroids. This case demonstrates the continuous nature of cutaneous CLAAS manifestations in a single patient. CLAAS has become a major public health issue in the at-risk group of cocaine users, and clinicians should be alert of this condition when treating cocaine users presenting with single or multiple skin ulcerations. Full article

Levamisole is effectively used in steroid-dependent nephrotic syndrome and the more frequent side effects reported are cytopenia and liver enzymes alterations. Several studies have demonstrated that this drug can induce high titers of circulating perinuclear antineutrophil cytoplasmic autoantibodies (ANCA) and vasculitis, most of them occurring in the case of prolonged use. A four-year-old boy that was affected with steroid-dependent nephrotic syndrome was treated with Levamisole as a steroid-sparing agent at a dose of 2 mg/kg/48 h. After initiation of the treatment, the number of relapses drastically decreased, enabling a significant reduction in the cumulative steroid dose. Levamisole was well tolerated, and was therefore administered for several years. At the age of 15, he was also diagnosed with celiac disease. After nine years of continuous Levamisole treatment, he presented with a high fever, hand and foot joint arthritis, and increased levels of total and direct bilirubin. Since the symptoms started two days after the injection of the second dose of the COVID-19 vaccine, it was initially concluded that these manifestations were rare vaccination side effects. Therefore, he did not receive any specific treatments, and Levamisole was continued at the same dose. After an initial improvement, two months later, the patient presented with the same symptoms. Suspecting Levamisole-induced vasculitis, an ANCA titer was measured and this returned positive. Clinical manifestations and double positivity for both myeloperoxidase (MPO) and anti-proteinase 3 (PR3) antibodies argued against the fact that that these findings were secondary to vaccination, cocaine abuse, or celiac disease. Assuming that we were facing a rare drug reaction, Levamisole was promptly interrupted. This resulted in a rapid remission of fever and arthritis improvement, and a decrease in ANCA titers. By reporting this case, we want to raise awareness among clinicians regarding a rare complication of treatment with Levamisole that is often misdiagnosed due to the fact that the current literature lacks univocal guidelines regarding the precise timing of ANCA titrations and the duration of the treatment. Full article

Background: Since 2006 there have been increased reports of severe agranulocytosis and vasculitis associated with levamisole use. Historically, levamisole was an immunomodulatory agent used in various cancer treatments in the United States. Currently the drug is used as an antihelminthic veterinary medication, but it is also used as an additive in freebase cocaine. There are multiple reports of levamisole-induced vasculitis in the head and neck but limited reported cases in the lower extremities. This article describes a 60-year-old woman who presented to the emergency department with multiple painful lower-extremity ulcerations. Results: Radiographs, laboratory studies, and punch biopsy were performed. Physical examination findings and laboratory results were negative for signs of infection. Treatment included local wound care and education on cocaine cessation, and the patient was transferred to a skilled nursing facility. Her continued use of cocaine, however, prevented her ulcers from healing. Conclusions: Local wound care and cocaine cessation is the optimal treatment for levamisole-induced lesions. With the increase in the number of patients with levamisole-induced vasculitis, podiatric physicians and surgeons would benefit from the immediate identification of these ulcerations, as their appearance alone can be distinct and pathognomonic. Early identification of levamisole-induced ulcers is important for favorable treatment outcomes. A complete medical and social history is necessary for physicians to treat these lesions with local wound care and provide therapy for patients with addictions. (J Am Podiatr Med Assoc 109(2): 150-154, 2019) Full article