A survey conducted in 2012 found that approximately 9.2% of the American population aged 12 and older had used an illicit substance in the last month [1]. Clinicians often find it difficult to detect these dangerous practices, likely from lack of self-reporting, which frequently stems from fear of discrimination and disdain by others. Consequently, clinicians should be able to recognize the cutaneous signs of substance abuse in order to more effectively diagnose and treat patients. In this review, we provide an overview of key dermatologic symptoms of various abusive and addictive substances.

Stigmata of injection drug use (IDU)

Perhaps the most notorious sign of intravenous drug abuse is injection marks, also called “track marks”. These linear marks represent post-inflammatory hyperpigmentation at the injection site, resulting from damage and consequent sclerosis of the underlying veins [2,3]. The antecubital fossa of the non-dominant arm is the site that is most commonly affected, as it is easily accessible and often disguisable with long-sleeved clothing [4]. Nevertheless, drug abusers have been reported to inject into more obvious veins, such as those in the neck, as well as more concealed veins such as the popliteal vein, inguinal veins, and dorsal veins of the feet [3,4].

Once the veins become sclerotic and inaccessible, drug users often resort to intradermal, subcutaneous, and sometimes intramuscular drug administration, also known as “skin-popping.” This method of drug administration usually results in deep, circular, punched-out looking atrophic scars; however, hypertrophic scars and keloids have also been reported. They are frequently indicative of scar formation from prior small abscesses, but abscess formation does not necessarily arise from skin-popping [2-4].

Eventually, drug users resort to injection of drugs with a hot needle. This results in “sooting” tattoos which are marks represent inadvertent entry and accumulation of carbon and soot into the dermis. Drug users will often acquire commercial tattoos in order to disguise these scars [3-5].

Skin and soft tissue infections (SSTI) are among the most common infectious complications of injection drug abuse, comprising the majority of emergency department visits by injection drug users (IDU) [2,3,6]. Abscesses and cellulitis include the most common SSTI affecting IDU [4,7]. There are several independent risk factors for developing SSTI in injection drug abusers, the most important being skin-popping [8]. Skin-popping causes tissue trauma and introduces bacteria into the skin. It may also introduce adulterant substances, which can concentrate locally and irritate the skin. Injection drug users who skin-pop are five times more likely to develop an abscess or cellulitis [9]. Other independent risk factors include the use of nonsterile needles and injecting “speedball,” a combination of cocaine and heroin [3,4,10]. The most common pathogens isolated are Staphylococcus aureus , streptococcal species, and oral bacteria, such as Eikenella corrodens . Inoculation with oral pathogens is usually the result of IDU “cleaning” their needles with saliva prior to injection [3,11-13].

SSTI with uncommon pathogens, such as the spore-forming Clostridium species, have been reported in IDU who skin-pop with black tar heroin [2,4]. Black tar heroin is often cut with dirt that may be contaminated with heat-resistant spores. It is often injected into the subcutaneous tissue or dermis, an anaerobic environment where the spores are able to germinate and release exotoxin into the surrounding tissues. Wound botulism, tetanus, and necrotizing fasciitis due to the toxins of C. botulinum , C. tetani, and C. perfringens , respectively, have reported in skin-poppers [2,4,8,14-19].

A study conducted by Pieper et al. found that 88% of IDU in the study had chronic venous insufficiency (CVI) [4]. Important contributors to CVI in IDUs included venous damage from repeated needle-sticks, thrombophlebitis, and deep venous thrombosis. Repeated infections also lead to damage to lymphatic vessels, which impairs lymphatic drainage. Chronic lower extremity edema often results from the combination of lymphatic obstruction and venous insufficiency [4, 20,21].

Intra-arterial injection of drugs, unintentional or purposeful, frequently results in ischemic complications and is thought to be due to a combination of the effects of the drug and its adulterant, which is a non-specific term for an additive commonly included in drug preparations. For example, cocaine is a potent vasoconstrictor that can also induce vasospasm. Adulterant particles are often locally injurious, causing thromboembolism and vasospasm that may result in compartment syndrome. Acute, drug-induced thrombosis is marked by intense burning and pain immediately following intra-arterial injection of the drug. Ensuing edema develops, followed by cyanosis [4,22-24]. In severe cases, skin necrosis can develop, such as scrotal necrosis due to pudendal artery thrombosis [25,26]. A case of scalp necrosis was reported in a patient secondary to heroin injection into the external carotid artery [27]. Reports of penile ulcers following heroin injection into the dorsal penile vein have also been described [28,29]. Digital veins and the ventral tongue are other bizarre injection sites that have the potential to develop ulcerations. Necrotic ulcerations in unusual sites should prompt clinicians to consider IV drug use in the differential [30]. Intravenous cocaine use has also been associated with necrotic skin ulcers and digital necrosis in in addition to secondary Raynaud’s phenomenon and infarction to end-organs, such as the liver and kidney [31-33].

Occasionally, pseudoaneurysms and mycotic aneurysms, can develop as a result of vascular injuries due to IDU and bacterial infection of the arterial wall, respectively. They are characterized by pulsatile masses in the distribution of major arteries. Non-pulsatile aneurysms may be mistaken for abscesses, which can lead to catastrophic outcomes if they are wrongfully incised [22,34,35]. Mycotic aneurysms are commonly caused by S. aureus and often involve the femoral artery due to drug injection in the groin. More unusual organisms, such as Candida albicans , have also been reported to cause mycotic aneurysms [36]. Management of pseudoaneurysms and mycotic aneurysms are challenging and may involve resection of the aneurysm or surgical debridement of the infected artery and revascularization by grafting or re-anastomosis [37-40].

Cocaineis an alkaloid compound extracted from the South American coca plant known to create euphoria, pleasure, and increased libido. In addition, a systemic “fight or flight” response, consisting of tachycardia, vasoconstriction, hypertension, and mydriasis may occur [3,8,41]. The stimulant effects of cocaine stem from its dual mechanisms: as a sympathomimetic and an inhibitor of norepinephrine, dopamine, and serotonin reuptake [8,42]. Cocaine increases dopamine concentrations in reward centers of the brain, creating sustained and dose-dependent feelings of euphoria [42]. Long-term alterations in the neuronal pathways in these reward centers ultimately leads to addiction [42,43].

Cocaine hydrochloride is a crystalline white powder produced by adding hydrochloric acid to coca leaf paste. Nasal inhalation of the powder can cause necrosis and midline perforation of the nasal septum and oral palate, secondary to vasoconstriction in mucus membranes [8,44,45]. “Snorter” warts, or intranasal human papillomavirus (HPV)- related warts, have also been reported in cocaine snorters, especially among those who share paraphernalia contaminated with HPV [3,46].

Crack cocaine is produced from neutralizing aqueous cocaine hydrochloride with baking soda or another alkaline compound and heating the mixture until rock-like pellets form [47]. Crack cocaine is cheaper and more potent than cocaine hydrochloride, and is subsequently more prevalent within lower socioeconomic groups [48]. Crack cocaine is often smoked through a glass pipe, and users may have burns and cuts on their hands from holding broken pipes [3,44]. Loss of lateral eyebrows, or madarosis, has also been noted in users as a result of hot fumes contacting the face [3,49]. “Crack hands” or black, hyperkeratotic, punctate lesions over the dorsal and palmar aspects of the hands are other indicators of crack cocaine use [47,50].

Cocaine use by various methods has been associated with endorgan damage secondary to vasoconstriction and ischemia. Caramelo et al. reported renal infarction in a cocaine “mule” secondary to systemic absorption from the intestines [51]. Lower extremity ischemic phenomenon similar to that of Buerger’s disease was reported by Denegri et al. in a long-term user of cocaine via inhalation method [52].

Cocaine is also associated with vasculitides, such as urticarial vasculitis [53], retiform purpura [54], scleroderma [32,55], Raynaud’s phenomenon [56], Churg-Strauss [57], and a P-ANCA positive Wegener granulomatosis-like syndrome [58,59]. P-ANCA specifically against human neutrophil elastase distinguishes cocaine-induced dermatologic and rheumatologic diseases from primary autoimmune diseases [59].

Levamisole is an adulterant particle commonly added to powder cocaine in order to minimize the proportion of cocaine in the drug mixture being sold [60]. Levamisole-related complications from cocaine are also becoming increasingly common with the rise in levamisole-contaminated cocaine in the United States. In 2009, the U.S. Drug Enforcement Administration estimated that nearly 70% of the cocaine entering the United States was contaminated with levamisole [61]. Hemorrhagic bullae or necrosis of the bilateral cheeks and helices of the ears are common vascular complications associated with levamisole. Similar lesions on the chest, back, abdomen, legs, and buttocks have also been reported [62]. The pathogenesis of cutaneous levamisole toxicity remains unclear and may involve a true or immune-mediated vasculitis [63-65].

General excoriations of the body can result from cocaine abuse as it is known to cause formication and delusions of parasitosis, in which the user reports tactile hallucinations of insects crawling under their skin [66].

Heroin is the acetylated opioid product of morphine, a naturally occurring opiate extracted from poppy seeds. Acetylation increases lipid solubility, allowing the compound to rapidly penetrate the blood brain barrier. This property along with heroin’s high potency at muopioid receptors gives users immediate euphoria and pain relief, making heroin a highly addictive drug [8,67]. The principal forms of heroin sold in the US drug market are white powder and black tar heroin. Due to its purity, white powder heroin can be snorted, smoked, or injected. Black tar heroin is an impure, gummy substance that is typically dissolved and injected intravenously (IV) or intramuscularly [67]. While heroin abuse used to predominate in urban areas, there has been a upward trend of use in some suburban and rural areas of the Midwestern United States since 2007 [68].

A common dermatologic complaint among heroin users is a pruritic urticarial rash of the body or genitalia due to mast cell degranulation and histamine release. Intense pruritus occurs immediately following injection with duration lasting up to several days [3, 69,70]. Cases of morbilliform eruptions in users have also been described, although the etiology remains indistinguishable between an adulterant or heroin itself [71]. Less commonly, glucagonoma-like syndrome of necrolytic migratory erythema as well as acanthosis nigricans have also been associated with heroin use [70,72,73].

Marijuana is a psychoactive drug derived from the hemp plant, Cannabis sativa. As of April 2015, cannabis remains illegal in the United States except in 23 states and Washington D.C. Marijuana remains the most popular illicit substance used in the United States with an increase in use [74]. Typically marijuana leaves are dried and rolled into cigarettes, or “joints,” for smoking. The leaves can also be steeped into teas and added to foods for consumption [74,75]. Marijuana contains delta-9-tetrahydrocannabinol (THC) among other compounds, which target cannabinoid receptors in the brain to produce effects such as euphoria, heightened senses, and a slowed perception of time. Activation of cannabinoid receptors produces systemic vasoconstrictions secondary to decreased production of nitric oxide and is responsible for the cutaneous manifestations of marijuana [76].

Common skin manifestations include premature aging such as periorbital darkening, hair loss and graying of hair. Some other skin manifestations include cannabis induced arteritis. This is a serious condition affecting marijuana users and is often misdiagnosed as atherosclerosis. Similarities in clinical presentation and arteriography exist between cannabis arteritis and thromboangiitis obliterans (TOA); cannabis arteritis may be considered a subtype of TOA [77]. In a retrospective study of peripheral vascular disease (PVD) in under the age of 50%, 20% of cases were due to TOA and cannabis use was more frequent among these patients [76,78]. The condition may present as Raynaud’s phenomenon, ulceration, or necrosis in distal extremities or digits. Cannabis arteritis can be discerned from atherosclerosis via Duplex ultrasonography showing patent arteries. Treatment involves cessation of marijuana and antiplatelet therapy with low-dose aspirin to promote revascularization [77,79]. It is imperative that clinicians consider cannabis use in young patients presenting with PVD.

A report of recurrent migratory superficial thrombophlebitis was also described in a chronic cannabis user in the lower extremities, hand, and groin. The patient’s condition resolved after cessation of marijuana use [80].

Interestingly, marijuana may provide benefits to the skin. A recent study by Olah et al. showed that cannabidiol (CBD), a nonpsychotropic phytocannabinoid derived from Cannabis sativa might, in fact, improve acne vulgaris through a sebostatic mechanism, among others. [81]. The study found that CBD had antiproliferative effects on both keratinocytes and sebocytes, thus decreasing formation of comedones and production of sebum. Furthermore, CBD has demonstrated antimicrobial activity, although activity against Propionibacterium acnes has not yet been determined [82,83]. CBD also has antiinflammatory properties, owing to its inhibition of NF-κB signaling. Collectively, the effects exerted by CBD exemplify its pharmacologic potential in the treatment of acne vulgaris [81,84].

Methamphetamine or “meth” is a CNS stimulant manufactured from pseudoephedrine and ephedrine (ingredients of common decongestants) in addition to toxic chemicals such as acetone, ammonia (fertilizer), battery acid, ethylene glycol (antifreeze), and ether. The resulting product can be smoked, inhaled, injected, or ingested. Smoking and injecting are the most common modes of abuse, as they produce rapid-onset euphoria. Chronic users may exhibit aggression, anxiety, mood instability, and psychosis [85].

Dental decay, also known as “meth mouth”, is one of the most common findings among meth abusers, due to a combination of methamphetamine-mediated vasoconstriction of oral mucosal vasculature, poor hygiene of the user, and chemical properties of the drug. Furthermore, meth intoxication increases dopamine levels, which can decrease saliva production, increase sugar consumption, and cause bruxism [44,86]. Methamphetamine also causes xerostomia, or dry mouth, which contributes to dental decay in meth users similar to that in Sjögren's syndrome [87]. Malnutrition, weight loss, and premature aging are other notable effects of methamphetamine. Finally, users can develop neurotic excoriations with subsequent abscess formation over the extremities due to the intense pruritus caused by delusions of parasitosis, or “meth mites” [88,89].

Ethanol (ethyl alcohol) is the intoxicating agent found in alcoholic beverages produced through fermentation of sugars and starches using yeast. Alcohol is a CNS depressant, impairing motor function and coordination, decision-making and judgment, and memory. Highly intoxicating doses can lead to respiratory depression and death [90]. The DSM-V classifies alcohol abuse and dependence as an alcohol use disorder (AUD). In 2012, approximately 17 million US adults and more than 800,000 US youths (ages 12-17) suffered from an AUD [91,92]. Long-term alcohol abuse is often associated with dermatologic stigmata of liver disease. While some findings may be nonspecific to alcoholism, alcohol abuse is among one of the leading cause of cirrhosis and should be considered in patients with cutaneous findings of liver disease [93].

There are multiple cutaneous findings in alcoholic liver disease. Superficial erythematous macule with radiating arterioles called spider angiomas are common. They classically appear in the regions of the hands, upper chest, neck, and face. They are a nonspecific finding in alcoholic liver disease and found in pregnant women, alcoholics without liver disease, and healthy individuals. Alcohol-induced vasodilation or elevated estrogen levels have been implicated as cause of these lesions [94]. Additionally, caput medusa or dilated periumbilical veins may occur in alcoholics and is an indicator of severe liver disease and portal hypertension [88].

Jaundice is a yellow discoloration of the skin and mucus membranes due to elevated serum bilirubin. Scleral icterus, or yellowing of the sclera, results when bilirubin levels reach 2.5 mg/dL. Jaundice is a nonspecific indicator of many types of liver disease. Hyperbilirubinemia seen in alcoholic liver disease is specifically caused by hepatocellular dysfunction in bilirubin conjugation and excretion [95].

Porphyria cutanea tarda (PCT) is a condition characterized by hemorrhagic bullae, crusting, and scarring in sun-exposed areas often accompanied by facial hypertrichosis. It is caused by a defect in uroporphyirinogen decarboxylase, an enzyme in the heme biosynthesis pathway, that leads to an accumulation of porphyrins, which cause photosensitivity [96]. Alcohol was shown to increase the activity of earlier enzymes in this pathway, which leads to further accumulation of porphyrins and worsens the condition in patients with preexisting PCT. Agents or conditions that adversely affect the liver, such as alcohol abuse and/or hepatitis C, can lead to acquired PCT [97]. Newonset PCT in patients with other stigmata of alcoholic liver disease should alert clinicians of possible alcohol abuse.

Psoriasis in alcohol abusers arises in a distinct distribution of flat, hyperkeratotic, erythematous plaques over the acral surfaces [88,94]. Increased skin-surface involvement and diminished treatment responsiveness in alcohol abusers may be evidence that alcohol exacerbates psoriasis [98,99]. Other dermatologic disorders associated with alcohol abuse include rosacea, nummular eczema [96], and seborrheic dermatitis [100].

Anabolic-androgenic steroids (AAS) are synthetic androgenic steroids similar to testosterone. As their name suggests, they stimulate growth of bone and skeletal muscle. Akin to male sex hormones, anabolic steroids produce virilization in abusers. Medical indications of these compounds include delayed puberty, impotence, and muscle wasting seen in HIV or malignancy [101]. Because of their growth stimulating properties, bodybuilders and athletes are known to abuse these steroids to improve athletic performance. Illicit anabolic steroids have been sold at competitions and gyms as well as smuggled into the US from countries in which prescriptions are not required to obtain steroids. They are typically injected intramuscularly, ingested orally, or applied to the skin with a topical creams or gels, and abusers have been known to use 10-100 times medically indicated dosages [102].

Physicians should be aware of the skin manifestations of steroid abuse in order to recognize the clinical signs of this unhealthy practice in athletic patients. AAS stimulate the sebaceous gland unit, causing it to enlarge. High doses lead to increases in sebum production, skinsurface lipids, and Propionibacterium acnes population [103,104]. This effect most commonly manifests in patients as acne vulgaris. The classic distribution is on the face, shoulders, upper chest, and back. AAS can cause new-onset acne vulgaris or exacerbate pre-existing acne vulgaris into severe forms that are resistant to treatment, such as acne conglobata. With continued steroid use, acne vulgaris can progress to acne fulminans [104,105]. Recalcitrant acne vulgaris in athletic patients should alert physicians to include anabolic steroid use in their differential diagnosis. Enlargement of the sebaceous gland also leads to increased incidence of rosacea, seborrheic dermatitis, and oily hair and skin [106]. AAS also cause rapid increases in muscle mass, which can lead to linear striae resulting from the disproportionate rate of expansion of the skin to the underlying skeletal muscle. Areas in which the striae are most pronounced include the neck, trunk, shoulders, and upper arms, as the upper body has the most substantial increase in muscle mass [107]. While discontinuation of steroid use causes reduction in muscle size, striae are permanent [106]. Hair growth is also affected by use of AAS, resulting in androgenic alopecia of the scalp and hirsutism of the face and body. These effects are most apparent in female users of AAS but can also be seen in male abusers [104,106].

The incidence of melanoma and non-melanoma skin cancers continues to rise. Ultraviolet (UV) radiation accounts for up to 90% of these cancers and is the only known modifiable risk factor associated with skin cancers [108-110]. While the importance of sun-protection is well recognized, excessive sunbathing and the overuse of tanning beds remains in our society. Tanning addiction is a developing phenomenon, as many behaviors associated with addiction are consistent with those of many frequent tanners [111]. Such behaviors include continuing to sunbathe despite knowledge of negative consequences (example: development of skin cancer), failure to discontinue tanning despite previous attempts to quit, impairment of interpersonal relationships, and neglect of personal responsibilities. A study conducted by Harrington et al. reported that 41% of indoor tanners surveyed met DSM-IV criteria for addictive behavior [111,112]. There has been debate as to whether the etiology of tanning addiction is neurobiological or based on cosmetic desire for tanned skin [113]. Recent evidence supports a biological etiology. Fell et al. reported that mice repeatedly exposed to UV light developed an endogenous opioid-dependent state secondary to increased release of endogenous β-endorphins and opioid receptor signaling. Furthermore, opioid withdrawal was precipitated in these mice by treatment with naloxone, an opioid receptor antagonist [114].

It is important that dermatologists are able recognize the psychological as well as cutaneous signs of tanning addiction. Perhaps the most significant change resulting from chronic UV light exposure is premature aging, or photoaging of the skin, which is distinct from natural skin aging. Unlike photoaging, physiologic skin aging is characterized by fine lines and moderate skin laxity. Photoaging results in dry, leathery skin with deep wrinkles, blotchy pigmentation (resembling lentigines), and yellow hues known as solar elastosis. Telangiectasias and precancerous lesions, including actinic keratoses are also common [109,115]. In regards to the development of nonmelanoma skin cancer, a study conducted by Karagas et al. showed that tanning bed users were 2.5 more likely to develop SCC and 1.5 times more likely to develop BCC [116]. Another study showed that patients with early-onset BCC (onset prior to age 50) were 1.6 times more likely to report the use of indoor tanning beds. This study also noted a strong association between tanning bed usage and early-onset BCC of the trunk and extremities, sites that normally receive less exposure to natural UV light [117]. Thus, BCC in patients under the age of 50 or unusual sites should prompt physicians to question patients about UV exposure. Melanomas in normally non-sun exposed areas, such as the breast and genitals, may also be indicative of excessive tanning bed use [118]. An increased number of seborrheic keratoses in a sun-exposed distribution were noted in an Australian population, suggesting UV light might increase the frequency of seborrheic keratoses in chronically sun-exposed and predisposed individuals [119].

Drug abuse and addictive behavior are commonly encountered issues in clinical dermatology practice. These behaviors can often produce cutaneous manifestations. It is important that dermatologists are able to recognize these presentations, as they provide clinical clues that are relevant to the diagnosis and management in this patient population. While this review is not exhaustive, it provides a concise and high-yield overview of the major addictive substances and their associated cutaneous findings.