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Official websites use. Share sensitive information only on official, secure websites. Correspondence: Alysse G. This comprehensive review of infectious and noninfectious syndromes associated with illicit drug use focuses on underrecognized complications of common illicit drugs and constellations of syndromes associated with emerging illicit drugs. Keywords: illicit drug use, injection drug use, skin and soft-tissue infections, altered mental status, substance abuse. Illicit drug use can result in a wide range of medical complications. As the availability, synthesis, and popularity of illicit drugs evolve over time, new syndromes associated with their use may mimic infections. Some of these symptoms are anticipated drug effects, and others are complications of adulterants mixed with drugs or complications from the method of using drugs. Some illicit drugs are associated with rare infections, which are difficult to diagnosis with standard microbiological techniques. The goal of this review is to orient a wide range of clinicians—including general practitioners, emergency medicine providers, and infectious diseases specialists—to complications of illicit drug use that may be underrecognized. Improving awareness of infectious and noninfectious complications of illicit drug can expedite diagnosis and medical treatment of persons who use drugs and facilitate targeted harm reduction counseling to prevent future complications. In , an estimated Rates of morbidity and mortality associated with illicit drug use especially from use of opiates and heroin, is increasing in the United States \[ 2 , 3 \]. In contrast to demographics of drug use from 10 years ago, the most dramatic increases in illicit drug use have been recorded among young white persons living in rural areas \[ 4 , 5 \]. There are several well-known infectious complications of injection drug use, including tissue and bloodstream infections, bacterial endocarditis, human immunodeficiency virus HIV , and viral hepatitis \[ 6 \]. There are also underrecognized and some newly emerging complications of commonly used illicit drugs, including cocaine and marijuana, which can cause patterns of multisystem organ dysfunction similar to infectious syndromes. Diagnosis and treatment of clinical syndromes related to illicit drug use are hampered by lack of validated toxicology screens, in addition to reluctance of persons who use drugs PWUD to report their drug use history and lack of knowledge among providers that these new illicit drugs and syndromes exist. The goal of this review is to give clinicians a foundation of knowledge to inform future clinical assessments and decision making in PWUD who present for medical care. Through out this paper we use the term illicit drug use because it is widely accepted and commonly used in the litera ture, but it does have negative connotations; providers should be aware of this and try to decrease stigmatization in patient interactions. We developed a search strategy for Medical Subject Heading MeSH terms and free text key words relevant to illicit drug use, including the following terms: drug abuse, illicit drug use, endocarditis, polysubstance abuse, emerging drugs of abuse, rare complications, toxicities, novel psychoactive substances, bath salts, synthetic cathinones, synthetic cannabinoids, jelling-up, crush-resistant, krokodil, cocaine, heroin, marijuana, methamphetamine, adulterants, levamisole, black tar heroin, anthrax, and tetanus. We searched the PubMed database for all relevant articles, published until June containing individual key words and combinations of above key words. Before discussing the presenting symptoms that may be seen in PWUD, it is important to review some of the emerging illicit drugs and adulterants. Details about their history, methods of use, mechanisms of action, desired effects, and adverse effects are provided in Table 1. Table 2 summarizes the complications of illicit drug use that can mimic infectious syndromes. Injection drug use is a common cause of skin and soft-tissue infections with both gram-positive skin flora and gram-negative enteric flora, dependent on the materials used to process and use the drug. Gram-positive infections from Staphlococcus aureus and Streptococcus pyogenes are the most common and result from introduction of skin flora past the epidermis into deeper tissues discussed below in Sepsis-Like Syndromes. Any clinical encounter with a PWUD should incorporate a review of harm reduction techniques, including cleaning the skin with alcohol before injecting and using bleach and water to disinfect syringes. Two less common causes of severe skin-based infection are clostridial infections and anthrax. Clostridial infections can progress rapidly from cellulitis to necrotizing fasciitis or gas gangrene. Clostridial spores are introduced when black tar heroin is cut with brown material eg, shoe polish, wood pulp, coffee grounds, or dirt to increase bulk. Typically heroin is heated and dissolved in water before use, but clostridial spores can survive this process and even begin germination \[ 6 \]. The most commonly involved clostridial species is Clostridium botulinum also discussed below in the section below on neurological manifestations , but gangrene has also been reported from Clostridium perfringens, Clostridium sordellii, and Clostridium novyi \[ 36 , 37 , 44 — 48 \]. Biopsy of the infected area can reveal black tar deposits in the tissue Figure 1. Injectional anthrax infection was first described in Norway in in a group of PWUD who injected heroin subcutaneously. There have been 2 subsequent outbreaks, one in in the United Kingdom and another in in Northern Europe, Germany, and the United Kingdom \[ 49 , 50 \]. Although injectional anthrax can progress to secondary bacteremia, the initial presentation is a unique clinical syndrome lacking the classic black-crusted painless eschar of traditional cutaneous anthrax. Presenting symptoms are significant edema, necrosis, and blistering, potentially leading to compartment syndrome or necrotizing fasciitis. Imaging and soft-tissue exploration show edematous muscle and subcutaneous tissue with or without necrosis and without collections or abscesses. Other symptoms include nausea, vomiting, abdominal pain, and variable neurological syndromes, including meningitis and intracranial hemorrhage \[ 49 \]. Two emerging illicit drugs should be considered when evaluating a PWUD with skin or soft-tissue symptoms. Tissue damage results from contamination with substances such as paint thinner, lighter fluid, gasoline, lead, zinc, and hydrochloric acid, which are used in the preparation of this drug. Damaged skin can become gangrenous, leading to sloughing of tissue down to the bone, often requiring extensive amputation \[ 14 \]. Use of krokodil was first reported in Russia in , and by cases were reported in Europe and the United States Arizona, Utah, Oklahoma, and Illinois \[ 15 \]. The second drug that should be considered is levamisole, an increasingly common adulterant detected in the majority of cocaine seized in the United States and worldwide \[ 18 , 19 \]. Levamisole is a popular adulterant because it is inexpensive, similar in appearance to cocaine, and enhances cocaine's effects. Use of levamisole-adulterated cocaine, including snorting, injecting, or smoking, may lead to several complications related to an induced vasculopathy. Dermatological manifestations may include fixed drug eruptions, lichen planus, ulceration, nodules, erythema nodosum leprosum, nonspecific maculopapular rashes, and hemorrhagic bullae \[ 18 , 20 \]. The characteristic lesions are rapidly progressive cutaneous ecchymoses, raised purpura, and bullae resulting in a distinct stellate lesion with erythematous borders and a necrotic center, which have a predilection for the ears and cheeks Figures 2 and 3 \[ 18 , 20 , 21 \]. In addition to the dermatological manifestations, agranulocytosis, leukoencephalopathy, and acute kidney injury suspected to be from renal tubular necrosis can also be caused by levamisole \[ 21 \]. Vasculitis is another common skin and soft-tissue manifestation that can be related to illicit drug use. Cocaine-induced midline destructive lesions, such as nasal septal and palatal perforations, are well-recognized effects of snorting cocaine that can mimic granulomatosis with polyangiitis, characterized by ANCA positivity specifically, anti—human neutrophil elastase \[ 27 \]. Cocaine has also been reported to cause urticarial vasculitis, Churg-Strauss vasculitis, necrotizing granulomatous vasculitis, palpable purpura, Buerger disease, and scleroderma, which are either induced or unmasked by unknown mechanisms \[ 26 \]. A rare complication of marijuana use is local arteritis, most often affecting the lower limbs, and may present as Raynaud phenomenon or as claudication followed by development of ulcers or gangrene, resembling Buerger disease \[ 51 \]. The proposed mechanisms for these manifestations are related to vasoconstriction or actions of a contaminant \[ 26 \]. PWUD presenting with shortness of breath or pleuritic chest pain may have complications of drug use other than pneumonia. It is characterized by fever, dyspnea, pleuritic chest pain, and hemoptysis that can progress to hypoxemia and respiratory failure. Symptoms usually occur within 48 hours of crack cocaine use \[ 27 , 28 \]. Imaging can show diffuse bilateral alveolar infiltrates, interlobular septal thickening, peribronchial nodules, ground glass opacities, or nonspecific consolidation. Bronchoalveolar lavage is similarly nonspecific \[ 27 , 28 \]. Inhalation of cocaine can also be associated with a chronic, often subclinical, diffuse alveolar hemorrhage, for which proposed mechanisms include vasoconstriction, pulmonary infarction, and cocaine-induced thrombocytopenia \[ 27 , 28 \]. Bronchospasm is a separate and distinct entity from crack lunch which has been reported with use of freebase cocaine cocaine heated to remove impurities in both known asthmatics and nonasthmatics. There have also been several reported cases of new-onset severe acute asthma within a few months after the start of heroin use \[ 29 \]. In addition to crack lung, other complications of illicit drug use may present with respiratory symptoms. Intravenous stimulant use is associated with pulmonary foreign body granulomas, pulmonary artery muscular hypertrophy, and fibrous intimal proliferation and has been linked to idiopathic pulmonary hypertension \[ 27 , 52 , 53 \]. Pulmonary vascular granulomatosis is caused by embolization or inhalation of the drug itself, contaminants, or insoluble filler materials such as silica, cellulose, and talc into the lungs and other organs Figure 4. Pulmonary vascular granulomatosis can progress to a pneumoconiosis-like interstitial fibrosis or pulmonary hypertension, both of which can be severe or fatal \[ 27 \]. Pulmonary edema has been reported with use of stimulants eg, cocaine and amphetamines , as well as heroin \[ 27 , 28 \]. Barotrauma-related injuries, including pneumomediastinum, pneumothorax, and pneumopericardium have been reported after the use of MDMA 3,4-methylenedioxy-methamphetamine , heroin, cocaine, and marijuana \[ 28 \]. Direct puncture of the lung while performing 'pocket shots' ie, injection directly into the jugular or subclavian veins can also lead to direct lung injury \[ 27 \]. Computed tomographic scan of patient with pulmonary granulomatosis from cocaine adulterated with talc. The first concern for PWUD presenting with a sepsis-like syndrome should be bacteremia. PWUD can also present with bloodstream infections caused by less common organisms, such as Lactobacillius, Cornyebacteria, and Bacillus very rarely, Bacillus anthracis , which should be considered as well as the more common bacterial causes and not discounted as a possible contaminant \[ 58 — 62 \]. We have recently seen several cases of nontuberculous atypical mycobacterial bacteremias clustered among intravenous drug users hospitalized for drug-related bacterial infections and receiving antibiotics through peripherally inserted central catheters. These patients had fever and tachycardia, and Gram stains of their blood showed gram-positive rods that were originally mistaken for contaminant until sent to specialty laboratories for identification. If a person who has a history of drug use presents with a sepsis-like syndrome with no growth in blood cultures, there are other illicit drug complications to consider. It characteristically occurs 10 to 30 minutes after injection of heroin. Research has shown that a gram-negative bacterium, Enterobacter agglomerans , colonizes the cotton plant and produces an endotoxin, which may be responsible for the fevers \[ 63 \]. The syndrome is usually self-limited, yet the symptoms may be worrisome and lead PWUD to seek emergency care \[ 32 , 64 \]. Several of the emerging drugs, including synthetic cannabinoids, cathinone derivatives, and piperazine derivatives, can also cause hyperthermia and tachycardia and have been further linked to cases of serotonin syndrome. Urine toxicology assays used at most hospitals will not detect these drugs, so if there is a concern about illicit drug use, it is important to specifically ask the patient about these substances \[ 9 , 10 , 33 \]. One clue that a person with hyperthermia and tachycardia might be using these drugs is acute kidney injury secondary to rhabdomyolysis. In a similar manner to cocaine, MDMA, cathinone derivatives, synthetic cannabinoids, and piperazine derivatives may cause rhabdomyolysis and acute kidney injury by increasing skeletal muscle use and metabolic demand while also causing vasoconstriction, resulting in hypoperfusion and poor heat dissipation \[ 12 , 34 \]. Altered mental status is common in PWUD presenting to the emergency room and often leads to concern about possible meningitis or encephalitis. In addition to central nervous infections, healthcare providers should consider other causes of altered mental status, including stroke, movement disorders, and seizures caused by illicit drug use or withdrawal syndromes. Cocaine and methamphetamine use are well-known causes of cerebral vasospasm and stroke, but other illicit drugs, such as marijuana, synthetic cathinones, and cathinone derivatives, have also been linked with cerebrovascular complications. Ischemic and hemorrhagic strokes have also been observed with MDMA use, possibly related to similar sympathomimetic mechanisms or high fever triggering disseminated intravascular coagulation \[ 35 \]. There are also a few distinct neurological syndromes that present with specific nerve involvement and could be mistaken for strokes. Although decreasing in incidence, clostridial infection from Clostridium tetani and C. There have been several outbreaks of black tar heroin—related tetanus and botulism in California, China, Saudi Arabia, and Western Europe \[ 66 — 69 \]. Withdrawal from heroin can cause acute esotropia, or strabismus, which typically resolves after the withdrawal period is over \[ 70 \]. In persons who injected crush-resistant opiates, 2 cases have been reported of opiate-associated hearing loss, thought to be secondary to cochlear ischemia \[ 71 \]. Common causes of seizures include benzodiazepine and alcohol withdrawal. Less recognized causes of seizures include sympathomimetic, drugs such as synthetic cannabinoids, cathinone derivatives, and piperazine derivatives \[ 11 \]. Several states health departments, including those in New York, Colorado, and Georgia, have issued alerts about symptoms that can results from ingestion, including severe agitation, hallucinations, seizures and tremors \[ 74 — 76 \]. Both heroin and cocaine can be associated with leukoencephalopathy, although the imaging findings and clinical presentation may be slightly different. Leukoencephalopathy associated with heroin use is characterized by demyelination in the cerebellum or limbic system and white matter edema and is suspected to be due to oligodendrocyte mitochondrial dysfunction and apoptosis. This clinical picture is associated with a mild cerebrospinal fluid pleocytosis and cerebellar signal abnormalities at magnetic resonance imaging Figure 5 \[ 38 \]. Leukoencephalopathy from cocaine—thought to be mostly related to levamisole adulteration—has magnetic resonance imaging findings of spongiform leukoencephalopathy with white matter lesions similar to toxic-metabolic injury, primarily affecting the frontal lobe \[ 22 \]. Illicit drug use can cause a variety of abdominal symptoms. Withdrawal from opiates may present like an infectious gastroenteritis with diaphoresis, nausea, vomiting, and diarrhea. Acute viral hepatitis B, C, or D can present with nausea, vomiting, and abdominal pain, and in the early stages patients may be seronegative despite high viral loads. Both methamphetamine and cocaine are known to cause intestinal ischemia with subsequent infarct, necrosis, bleeding, or perforation as a result of splanchnic vasoconstriction and enhanced thrombosis \[ 39 , 40 \]. Chronic use of marijuana or synthetic cannabinoids is associated with cannabinoid hyperemesis syndrome, which presents with periods of nausea, vomiting, and abdominal pain, often associated with compulsive bathing or showering with hot water \[ 41 , 42 \]. It behooves all clinicians to stay up to date on complications of illicit drug use. Knowledge of emerging trends in illicit drug use can facilitate specific questions to assess both infectious and noninfectious risks and create a culturally sensitive and nonjudgmental atmosphere. In addition to addressing acute or subacute complications of drug use, encounters with PWUD represent a prime opportunity for counseling patients regarding the risks of continued drug use and making efforts to link them to treatment programs. Financial support. Potential conflicts of interest. All other authors report no potential conflicts. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. As a library, NLM provides access to scientific literature. Clin Infect Dis. Find articles by Alysse G Wurcel. Find articles by Elisabeth A Merchant. Find articles by Roger P Clark. Find articles by David R Stone. All rights reserved. For Permissions, please e-mail: journals. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Cathinones: methcathinone, mephedrone, methylenedioxy-pyrovalerone, methylone, ethylone, butylone, methedrone \[ 9 — 11 \]. Identified in as the principal psychoactive component of Khat Catha edulis leaves; first synthesized in , explored for their stimulant, antidepressant and appetite suppressant properties. Khat, bath salts, ivory wave, vanilla sky, white rush, white lightning, white dove, meow meow, M-CAT, bubbles, cloud 9, explosion, impact, energy 1, bloom, blue silk. Oral; intranasal; can be inhaled, intravenous, intramuscular, or rectal. Similar to amphetamines and catecholamines; inhibition of vesicular monoamine transporters for serotonin, dopamine, and norepinephrine; release of intracellular neurotransmitter stores; inhibition of MAO. Stimulation, euphoria, friendliness, sexual arousal, and perceptual disturbances. Anxiety, paranoia, hallucinations, psychosis, aggression, impaired working memory, bruxism, seizures, hypertension, tachycardia, coronary vasospasm, dysrhythmia, rhabdomyolysis, acute kidney injury, hyponatremia, hyperkalemia, metabolic acidosis, hyperthermia serotonin syndrome, disseminated intravascular coagulation, multiorgan failure, death. Cannabinoids \[ 9 , 11 — 13 \]. Derivatives of THC, first synthesized in the s and studied for treatment of pain, anxiety and nausea. K2, spice, happy tiger incense, smoke, aroma, Aztec fire, black mamba, blueberry posh, Bombay blue, blaze, bliss, eclipse, krypton, Mr Smiley, Yucatan fire, Zohar, sensation vanilla. Alteration in sensory perception and processing of stimuli in the hippocampus, amygdala, and prefrontal cortex via reduction of GABA release and increase in dopamine and glutamate release. Euphoria, relaxation, disinhibition, altered perception and consciousness; similar to marijuana. Anxiety, confusion, agitation, mood dysregulation, paranoia, psychosis including long term , perceptual disturbances, suicidal ideation, sedation, memory impairment, tremors, seizures, nausea, vomiting, diaphoresis, xerostomia, mydriasis, tachycardia, hypertension, chest pain, acute MI, acute kidney injury, respiratory depression, tachyphylaxis, death. Krokodil desomorphine \[ 14 , 15 \]. Introduced as an analgesic in the s, withdrawn in over concerns about addictive potential. Piperazine derivatives \[ 11 , 16 \]. Initially developed as antihelminthics, also explored for their antidepressant properties. Central serotonogic effects; increased release and reuptake inhibition of dopamine, serotonin, and norepinephrine. Salvia divinorum \[ 9 , 11 , 16 , 17 \]. Member of the mint family endemic to Mexico; historically used for its mind-altering effects. Salvia, diviner's sage, mystic sage, magic mint, Sally D, Maria pastora, Purple sticky. Trancelike state, hallucinations, altered perception of self and environment, mood improvement. Hallucinations, confusion, anxiety, dysphoria, paranoia, psychosis, unmasked schizophrenia, language impairments, drowsiness, headache, diuresis. Levamisole \[ 18 — 22 \]. Veterinary antihelminthic developed in the s and currently approved by the FDA only as adjuvant chemotherapy. Immunostimulatory and immunomodulatory properties, increases brain dopamine levels; produces amphetaminelike metabolites. Agranulocytosis, vasculopathy, dermatological lesions, renal injury, leukoencephalopathy. Clenbuterol \[ 23 — 25 \]. Agitation, tachycardia, palpitations, chest pain, myocardial injury, neuromuscular symptoms. Krokodil \[ 14 \]. Rash with scaly, green appearance, ulcerations, destruction of skin, muscle, cartilage, gangrene and skin sloughing. Levamisole \[ 18 , 20 , 21 \]. Characteristic lesions are stellate lesion with erythematous borders and a necrotic center frequent on ears and cheeks. Cocaine \[ 26 \]. Urticarial vasculitis, Churg-Strauss vasculitis, necrotizing granulomatous vasculitis, palpable purpura, Buerger disease. Crack lung \[ 27 , 28 \]. Within 48 h of cocaine smoking: fever, dyspnea, pleuritic chest pain, hemoptysis, hypoxemia, respiratory failure. Imaging shows diffuse alveolar infiltrates, interlobular septal thickening, peribronchial nodules, ground glass opacities, nonspecific consolidation BAL with eosinophila, hemosiderin-laden macrophages, IgE deposition, hyaline membrane formation peripheral eosinophila. Subclinical alveolar hemorrhage \[ 27 , 28 \]. Largely asymptomatic; possible hemoptysis or nonspecific pulmonary symptoms. Diffuse alveolar hemorrhage with hemosiderin-laden macrophages in BAL fluid. Bronchospasm \[ 27 \]. Pulmonary edema \[ 28 , 29 \]. Radiographic evidence of bilateral or unilateral pulmonary edema; BAL fluid may reveal high protein concentrations. Pulmonary granulomatosis \[ 27 , 29 \]. Cotton fever \[ 30 — 32 \]. Fever, other typical sepsis features typically occurs 10—30 min after injection; usually self-limited. Sympathomimetic effects \[ 9 — 12 , 33 , 34 \]. MDMA, piperazine derivatives, synthetic cannabinoids, cathinone derivatives. Tachycardia, hyperthermia, maybe be rhabdomyolysis with acute kidney injury. Synthetic cannabinoids, cathinone derivatives and piperazine derivatives not detected in standard urinary toxicology screens. Stroke \[ 11 , 35 \]. Cocaine, methamphetamine, MDMA, synthetic cannabinoids, cathinone derivatives, marijuana. Abrupt onset of focal neurological symptoms, possibly accompanied by change in mental status or loss of consciousness. Cranial nerve palsies \[ 36 , 37 \]. Cranial neuropathy including diplopia, opthalmoplegia, ptosis, and facial nerve palsy ; may be accompanied by cellulitis, with possible necrotizing fasciitis and gangrene. Seizures \[ 9 — 11 , 33 \]. Synthetic cannabinoids and cathinone derivatives not detected in standard urinary toxicology screens. Heroin \[ 38 \]. Altered mental status, restlessness, apathy, cerebellar speech disturbance, ataxia, hyperactive reflexes, spasticity, tremor, choreoathetoid movements, hypotonia, areflexia, respiratory failure. Levamisole-adulterated cocaine \[ 22 \]. Confusion, altered mental status, language impairment, visual changes, focal neurological deficits. Intestinal ischemia \[ 39 , 40 \]. Acute abdomen, abdominal pain, nausea, vomiting, diarrhea, melena, bloody stool, fevers, signs of shock. Cannabinoid hyperemesis syndrome \[ 41 , 42 \]. Abdominal pain, nausea and vomiting with relief of symptoms during warm bathing or showering. Marijuana but not synthetic cannabinoids at standard toxicology screening.

Buying Heroin Saly