18 in a patient who develops these symptoms, especially
if the patient has a vague medical history, labile affect,
and delusional behavior.9,41
Levamisole: Levamisole has been discovered as
a common adulterant added to cocaine. Unlike other
cutting agents, levamisole is added at the onset of
manufacturing in the countries of origin and is readily
available and inexpensive. Levamisole adds bulk and
weight to the cocaine and goes unnoticed by cocaine
users because it has a similar appearance, taste, and
melting point as pure cocaine. It also has its own
stimulant effects and enhances the euphoric effects of
cocaine.
Levamisole was used in humans as treatment of colon
Part 18
cancer, nephritic syndrome, and rheumatoid arthritis
because of its immunomodulating effects, but it was
withdrawn from the market in 2000 because of neutro-
::
penia, agranulocytosis, and vasculitis. Currently, it can
only be used in veterinary medicine as an antihelmin-
Psychosocial Skin Disease
thic medication.
Side effects of levamisole-adulterated cocaine are
widely reported. Most specific is levamisole-induced
necrosis syndrome (LINES), which should be consid-
ered in patients who present with a distinctive reti-
form purpura on the ears (Fig. 101-5) with or without
lesions elsewhere (particularly on the nose, cheeks, and
extremities); the retiform purpura may also present
Figure 101-5 Levamisole. Characteristic purpuric erup-
tion on the ear following levamisole toxicity. (Reproduced
with permission from Hennings C, Miller J. Illicit drugs:
1710 what dermatologists need to know. J Am Acad Dermatol.
2013;69:135-142.)
Kang_CH101_p1705-1716.indd 1710
with hemorrhagic bullae or ulceration. This is usually
associated with leukopenia (especially neutropenia)
and high titers of perinuclear antineutrophil anti-
bodies and anti-myeloperoxidase antibodies, which
are present in more than 70% of cases. Other testing
that suggests LINES includes presence of cytoplas-
mic antineutrophil antibodies and anti–proteinase-3
antibodies, which are present in approximately 50%
of cases. Other serologic studies may be positive for
antinuclear antibodies, antiphospholipid antibodies,
and the lupus anticoagulant. Biopsy specimens show
leukocytoclastic vasculitis, thrombotic vasculopathy,
vascular occlusion, or a combination of these. Vascular
deposits of immunoglobulin M, immunoglobulin A,
immunoglobulin G, and complement C3 on immuno-
fluorescence studies point toward a vasculitis caused
by levamisole-adulterated cocaine.
There also have been reports of pyoderma gangreno-
sum in patients using levamisole-adulterated cocaine.
The lesions are consistent with classic pyoderma gan-
grenosum, but patients have serologic profiles that are
similar to those seen in LINES.42
Unfortunately, levamisole is difficult to detect
because of its short half-life (5 to 6 hours) and requires
specific testing that is not readily available. Treat-
ment consists of removing levamisole exposure, and
mild organ involvement usually is managed with
corticosteroids.43
HEROIN (ALSO KNOWN AS “SMACK,”
“H”, “SKA”, OR “JUNK”)
Heroin is an opiate that causes euphoria, addiction,
respiratory depression, and miosis. It is synthesized
from morphine, a naturally occurring substance
extracted from the seed pod of the Asian opium poppy
plant. It is typically sold as a white or brownish pow-
der or as a black sticky substance called black tar heroin.
Heroin base (common in Europe) can only dissolve
in water when mixed with an acid; the most com-
monly used are citric acid powder and lemon juice.
Hydrochloride salt, mainly found in the United States,
requires only water to dissolve. Most of the time,
heroin is heated, drawn into a syringe or eyedropper
through cotton, and then injected. A heroin abuser may
inject up to 4 times a day. Because of decreasing prices
and the increases in purity, heroin may now be snorted
or smoked by inhaling its vapors, either with tobacco
in a rolled cigarette or by heating the drug on alumi-
num foil.
There are many cutaneous signs of heroin abuse.
Because it is often injected, the signs listed above for
IDUs are the most common cutaneous evidence of
use. Four percent of addicts develop urticaria, which
can last for days. They can develop a “high pruritus,”
which is intense itching, especially on their genitals
and on their face. “Puffy hand syndrome” (Fig. 101-6)
is the condition where edema develops in the dorsal
hands but not the fingers. This is mainly caused by
lymphatic damage resulting from quinine, which is an
adulterant that is added to heroin.12 There have been
03/12/18 2:35 pm

Figure 101-6 Puffy hand syndrome. Example of dorsal
hand edema following intravenous drug use.
a few cases of penile ulcers and necrotizing cellulitis
of the scrotum when heroin was injected into the dor-
sal vein of the penis.44 Pemphigus vegetans,45 fixed
drug eruptions, toxic epidermal necrolysis, necrolytic
migratory erythema not associated with glucagonoma,
and acanthosis nigracans11 have all been described
with heroin abuse.8 Sometimes users resort to other
drugs when heroin is not available. One of the com-
monly used alternatives to heroin is tripelennamine
with pentazocine (called Ts and blues). Injection causes
severe ulceration with hyperkeratosis that follows a
linear pattern.
“CLUB DRUGS”
Methylenedioxymethamphetamine
(MDMA, Ecstasy): The main active ingredient in
the popular club drug ecstasy is 3,4-methylenedioxy-
methamphetamine (MDMA), which is used for its abil-
ity to induce a sense of euphoria and enhance sensory
perception via effects on multiple neurochemical path-
ways.46 MDMA is typically ingested as a tablet. When
prepared in its pure powder form it is referred to as
“molly” and can be snorted or orally ingested. MDMA
is often combined with a wide variety of other drugs,
such as amphetamine derivatives, caffeine, and aspi-
rin, when manufactured in tablet form for ingestion.
Few cutaneous manifestations following use/abuse
have been reported as its deleterious adverse effects
on the kidney, liver, and neuropsychiatric systems are
more commonly encountered and studied. An acne-
iform eruption aptly labeled “ecstasy pimples” has
been described,47 as has a widespread guttate psoria-
siform eruption.
γ-Hydroxybutyrate (also known as “Liq-
uid Ecstasy,” “Liquid X,” or “Fantasy”):
γ-Hydroxybutyrate (GHB) is a popular “party drug”
based on its euphoric and aphrodisiac properties. It
is also used as a “rape drug” in the nightclub scene
based on its ability to induce a reversible coma as well
as short term memory loss. Specific cutaneous features
following its use are not well described. However,
Kang_CH101_p1705-1716.indd 1711
GHB use can cause an overdose syndrome in which
pale skin is prominent and should prompt immediate
18
medical attention if use is suspected.48
Methamphetmine (also known as
“Speed,” “Meth,” “Chalk,” “Ice,” “Crystal,”
“Crank,” or “Glass”): Methamphetamine is made
by the reduction of ephedrine or pseudoephedrine in
“meth labs.” It can be made in a single 2-L bottle using
batteries and fertilizer, which makes meth labs more
mobile and the drug more accessible. The process of
making methamphetamine is very toxic and flam-
mable. It causes euphoria, increased energy, anxiety,
aggression, hallucinations, and severe withdrawal. It
may be injected, smoked, or snorted.8 Signs of meth-
Chapter 101 :: Drug Abuse
amphetamine abuse are intense pruritus, body odor,
weight loss, premature aging, and hyperhidrosis.
“Meth mouth”, which consists of numerous dental
caries and enamel erosions starting at the gum line,
develops in users.49 It is caused by a combination of
xerostomia, bruxism (clenching and grinding of the
teeth), and poor dental hygiene. Formication may also
develop, especially on the face. Acne excoriee and
lichenoid drug eruptions have been reported from
methamphetamine use.50
Other Amphetamines and Methylpheni-
date—Uppers, Speed, Eye Openers, Pick
Me Ups: The CNS stimulants amphetamine and
methylphenidate are used for narcolepsy to improve
alertness and appear to decrease abnormalities in
brain structure and function found in attention defi-
cit hyperactivity disorder.51 Formication and obsessive
skin-picking, as well as urticaria and acne, have been
reported.
Hallucinogens—Lysergic Acid Diethyl-
amide, Mushrooms: Lysergic acid diethylamide
(LSD, acid) is found in ergot, a fungus cultivated from
rye and other grains, which is often ingested in liquid
form for its ability to alter one’s sense of time and sen-
sory perception. Psilocybin and its active metabolite
psilocin (4-hydroxy-N,N- dimethyltryptamine) are the
psychoactive compounds of various forms of halluci-
nogenic mushrooms ingested for their mind altering
properties.52 Dry mouth appears to be the main cutane-
ous effect.
Sedatives: Cutaneous reactions to sedatives are
rare. The sedative class of drugs includes cannabis,
benzodiazepines, and hydroxybutyrate. Drug reac-
tions are rarely associated with benzodiazepines,
including morbilliform hypersensitivity eruptions,
erythema multiforme to clonazepam, and acute gener-
alized exanthematous pustulosis.
CANNABIS (ALSO KNOWN AS
“MARIJUANA,” “POT,” “WEED,” OR
“MARY JANE”)
Cannabis is a mixture of dried shredded leaves and 1711
flowers of the Cannabis sativa plant. The psychoactive
03/12/18 2:35 pm
18 chemical compound is ∆9-tetrahydrocannabinol
(THC). The potency of marijuana has increased
over the years and is now 5 times stronger than
the marijuana used in the 1970s. Since its legaliza-
tion in some states of the United States, marijuana
use has increased in those states by approximately
20% according to early data. Although recreational
use tends to be for its ability to produce euphoria,
medicinal use is gaining acceptance. Treatment of
pain, glaucoma, muscle spasm, nausea, seizures,
poor appetite, and inflammation are only a few
of the disorders for which cannabinoids are being
used and investigated. There are topical formula-
tions that profess to improve the appearance of
Part 18
ulcers or gangrene.55 Duplex ultrasound can be used to
differentiate between cannabis arteritis and atheroscle-
rosis. Cannabis arteritis shows occlusion of peripheral
arteries below the knee, whereas atherosclerosis has
calcified plaques in the iliofemoral arteries. Treatment
is for the patient to stop cannabis use and to take low-
dose (81 mg) aspirin. For severe cases, iloprost (0.5 to
2 ng/kg/min), which is a prostaglandin analog, can be
given.56
CUTTING AGENTS
Drugs of abuse often contain additional ingredients
besides the active compound the user desires to con-

aging skin. sume. These ingredients can be added intentionally

There are 4 ways to consume marijuana: inhala- to increase the volume of the product for additional
tion, oral, sublingual or topical application. Inhalation profit, or, it may be unintentionally included in the
causes an effect within minutes, peaks at approxi- final product as a result of the chemical manufactur-
::

mately 1 hour, and wanes in approximately 2 hours. ing process. So-called cutting agents can be divided
Psychosocial Skin Disease

Inhalation occurs via smoking or vaporization (vap- into diluents and adulterants. Diluents, such as dirt,
ing). Marijuana can be smoked in joints (hand-rolled baking soda, talc, and mannitol, are added to expand
cigarettes), bongs (pipes), or blunts (marijuana cigars). the volume of the drug for increased distribution.57
Other drugs, such as cocaine, may be mixed with it. Adulterants, such as caffeine, hydroxyzine, diltiazem,
Vaping (see below) is also gaining popularity. Oral levamisole, and phenacetin, are added to enhance the
ingestion is becoming more common as cannabis effect of the main active ingredient or facilitate admin-
is used for medical purposes and is legal in several istration of the drug.
states. Onset of action for oral consumption is slower Several cutting agents deserve special mention
than for inhalation, with initial effects taking 30 min- because of their potential to induce cutaneous
utes or longer and peaking at approximately 2 hours; manifestations following exposure. Most notable
total duration of effects can be as long as 6 hours. The among these is levamisole in cocaine and arsenic
effects from oral consumption have been described as in cannabis. Diluents such as talc and starch are
more “intense” than those from inhalation. Dosage of reported to cause foreign-body granulomas after
marijuana taken orally can be difficult to titrate; irregu- parenteral use with various drugs (Fig. 101-7).58
lar effects and overdose are more common with this Another example of an emerging adulterant leading
form. Cannabis edibles include the classic brownies to adverse outcomes with heroin use is clenbuterol.
and cookies, as well as other formulations, including Although unremarkable for its skin manifestations,
lollipops, fudge, “cannabutter,” oils and tinctures, and several case series have described dangerous car-
baked in breads and pizza. Sublingual use includes diac events.59
product in dissolvable strips, lozenges, and sublingual
sprays. Onset of action may be earlier than in oral con-
sumption. Finally, cannabis can be delivered topically
via transdermal patches, oils, salves, lotions, and bath
salts. Transdermal patches may deliver enough active
ingredient to cause a “high” but usually only produce
local effects.
There are few cutaneous signs of cannabis use. Acne,
ranging from mild to severe, has been described. Aller-
gic reactions, including contact dermatitis, also have
been reported. Cannabis arteritis is a serious vascular
complication that can occur with chronic use. Cannabis
arteritis is rare, with approximately 50 cases reported
in the literature despite more than 5 million daily users
worldwide. It presents as peripheral ischemia and
necrosis, most often of the lower limbs. Cannabis arte-
ritis is one of the most frequent causes of peripheral
arterial disease in adults younger than age 50 years
and is a subtype of thromboangiitis obliterans.53 It may
present with Raynaud phenomenon and digital necro-
sis. Cannabis arteritis is thought to be caused by the
combined vasoconstrictive effects of THC and arsenic, Figure 101-7 Talc granulomas. Multiple granulomas on
1712 arsenic being a common contaminant in marijuana.54 the bilateral legs from intravenous use of drugs contain-
Claudication may present before the development of ing talc as a cutting agent.

Kang_CH101_p1705-1716.indd 1712 03/12/18 2:36 pm