Cocaine is a tropane alkaloid and one of 14 alkaloids derived from the leaves of two coca plant species: Erythroxylum coca and Erythroxylum novogranatense [1]. The Incas chewed coca leaves mixed with ashes or lime to reduce hunger, thirst, and fatigue, as well as to cope with cold temperatures and high altitudes. These leaves contain low concentrations of cocaine and are not addictive. Over time, more potent and highly addictive derivatives have been developed at different stages of processing, including cocaine paste (PBC), cocaine hydrochloride, and freebase cocaine, also known as “crack”. Cocaine hydrochloride is usually snorted or injected when mixed with water, while PBC and freebase cocaine are typically smoked [2].

Its effects induce euphoria and heightened activity by blocking the reuptake of catecholamines. Street cocaine, commonly used by addicts, is often adulterated with various substances (“cutting agents”), which may include amphetamines, antihistamines, benzocaine, inositol, lactose, lidocaine, mannitol, opioids, phencyclidine, procaine, sugars, tetracaine, and occasionally arsenic, caffeine, quinidine, or even flour and talc [1]. Cocaine is the second most used illicit drug in Europe as of 2024 with approximately 2.5 million 15- to 34-year-olds using it last year [3].

The use of the terms dermatitis and mucositis is extremely common to refer to conditions in relation to inflammation of the skin and mucosa, respectively. However, the term dermatomucositis as an entity is rarely used in scientific literature and it has been applied for several reactions related to inflammation of skin and mucosa due to different causes such as corticosteroids [4], Lortat–Jacob bullous muco-synechial and atrophic dermatitis [5], fatal dermatomucositis due to an adenoidal-pharyngeal-conjunctival virus [6], and recently by Fernández-Flores et al. who defended the term in the full sense in relation to the use of cocaine [7].

Dermatological findings related to cocaine use have been extensively reported in the literature as different entities. They appear in approximately 0.5–3% of people who use cocaine and they might be present as early as 24 h after use. Lesions occur more frequently in women with an average age of 42.7 years [8].

One of the skin manifestations that has been associated with cocaine use is the drug-induced variant of erythema multiforme major known as Stevens–Johnson syndrome, an entity that tends to lack targetoid-like skin lesions but more mucosal involvement than erythema multiforme [9]. The effects of cocaine on the skin extend beyond Stevens–Johnson syndrome; cocaine has been assumed to be the culprit of other manifestations such as drug reaction with eosinophilia and systemic response (DRESS) syndrome [10], eosinophilic granulomatosis with polyangiitis [11], pseudovasculitis [12], Raynaud’s phenomenon and ischemic finger necrosis [13], urticarial vasculitis [14], thromboangiitis obliterans [8], acute generalized exanthematous pustulosis [15], IgA vasculitis [16], fixed drug eruption, retiform purpura, bullous diseases (pemphigus vegetans and pemphigus vulgaris), anetoderma [17], perniosis, pulp artophy [18], and systemic scleroderma [2].

Snorting cocaine can lead to various nasal complications specifically, including intranasal viral warts (“snorters’ warts”), crusting inside and around the nose, nosebleeds, and asymmetry of the nostrils. On the other hand, high-temperature smoke when smoking cocaine contains toxic and irritating substances that can burn the lips and facial skin, lead to eyelash loss, and accelerate skin aging [2].

Sometimes a variety of cocaine-induced effects on nasal structures lead to the formation a particular entity known as cocaine-induced midline destructive lesions (CIMDL), a condition that resembles systemic diseases associated with positive anti-neutrophil cytoplasmic antibodies (ANCA). It is estimated to affect approximately 4.8% of cocaine users. Symptoms include hyposmia, facial pain, crusting, ulcers, perforation of the nasal septum and palate, sinus wall destruction, orbital damage, and erosion of the anterior skull base. A key characteristic of CIMDL is the presence of ANCAs targeting human neutrophil elastase (HNE) and other neutrophil antigens, such as lactoferrin and cathepsin G [2, 19].

Levamisole, a synthetic anthelmintic once used for its immune-modulating effects in cancer and autoimmune treatments, was discontinued in human medicine because of serious side effects, including vasculitis (levamisole-induced vasculitis, LIV), agranulocytosis, thrombocytopenia, and arthritis. Notably, levamisole is a common adulterant in cocaine, particularly in Europe, where it is used to increase product volume and dealer profits. It is believed that levamisole enhances cocaine’s effects by inhibiting monoamine oxidase and catechol-O-methyl transferase, prolonging catecholamine activity in synapses [20].

LIV has been associated with the appearance of purpuric lesions in different parts of the body. Additionally, LIV has been reported in association with ocular cicatricial pemphigoid and its positivity to ANCA, making the differential diagnosis with granulomatosis with polyangiitis challenging [20, 21]. It must be noted, however, that Kunzler et al. described 10 cases in previous literature with ANCA-negative LIV [22].

In our practice, we received a case of a woman with cocaine-induced dermatomucositis and an anomalous high IgG4 expression, a manifestation not previously reported in the literature to be associated with cocaine-induced dermatomucositis. In fact, it had even been used to rule out this disease. We decided to review the scarce literature on cocaine- and/or levamisole-induced lesions as well as IgG4-related disease in the hope of better understanding the pathophysiology of these diseases, provide a comprehensive differential diagnosis for these entities, and ultimately to incorporate this new finding in our case to cocaine-induced dermatomucositis differential diagnosis and expected histological manifestations.

The procedures followed here were in accordance with the ethical standards of the committee responsible for human experimentation and with the 1975 Helsinki Declaration, revised in 1983. Informed consent was obtained from the patient for this study and its publication. We have not used patients’ names, initials, or hospital numbers.