pyoderma gangrenosum induced by levamisole- adulterated ... mds... · systemic steroids in 6 of 8...
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Pyoderma Gangrenosum Induced by Levamisole-Adulterated Cocaine: Clinical, Serological, and
Histological Findings in a Cohort of Patients
Haneol Sam Jeong, BA, BBA1; Heather Layher, DO2; Lauren Cao, MD1; Travis Vandergriff, MD1; Arturo Dominguez, MD1
1Department of Dermatology, UT Southwestern Medical Center 2Brooke Army Medical Center, San Antonio Uniformed Services Health Education
Consortium, Dermatology Residency Program, San Antonio
Presented at the 2016 Medical Dermatology Society Meeting, Washington, DC
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Levamisole Synthetic imidazothiazole derivative Early uses: Cancer, RA, IBD Mechanism: T lymphocyte proliferation and
dose-dependent neutrophil chemotaxis1
Adverse effects: Agranulocytosis (3-10%) Current use: Anti-helminthic
Levamisole in Cocaine Bulking agent (80% of supply) Why a popular additive agent?
Physical similarity Nicotinic acetylcholinergic system2
Indirect serotonin agonist3
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Clinical Presentation
Lesion Distribution4
Patients Upper Extremity
Lower Extremity
Trunk Face Ears Nose Oral Arthralgias
Total 34/55 46/55 22/55 26/55 40/55 21/55 4/55 17/55
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Laboratory Evaluation4
Histopathology: Vasculopathy:
Hyaline thrombi occluding dermal vessels in the absence of vasculitis
Vasculitis Fibrin in vessel walls Leukocytoclasia Erythrocyte extravasation
NPN Biopsy Lev CRP MPO PR3C-
ANCAP-
ANCAANA RF
C-IgM
C-IgG HNE C3 C4 Cryo
Total 31/52
T 24/50,
V 8/50,
T/V 18/50
15/24 16/24 25/41 26/44 9/48 42/48 24/47 5/27 20/29 5/23 11/11 6/32 10/33 4/40
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Only now being reported in the literature Multiple isolated case reports5-10
Incomplete serologic evaluation
Study Cohort Cohort: 8 consecutive patients, 22 separate
clinical encounters (2011 – 2015) Demographics:
Age (Mean): 43.6 years Gender: 87.5% Female
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Lesion Distribution Lesion Morphology
Up
pe
r E
xtr
em
ity
Do
rsa
l Ha
nd
an
d F
ing
ers
Lo
we
r E
xtr
em
ity
Tru
nk
/ B
ack
Fa
ce
Ea
rs
No
se
Ora
l
Art
hra
lgia
s
Ve
sico
pu
stu
lar
Bu
llo
us
Ulc
era
tive
Ve
ge
tati
ve
Cri
bif
orm
Sca
rrin
g
Re
tifo
rm P
urp
ura
6/8 4/8 8/8 3/8 3/8 3/8 1/8 1/8 1/8 3/8 7/8 8/8 1/8 5/8 3/8
75% 50% 100% 37.5% 37.5% 37.5% 12.5% 12.5% 12.5% 37.5% 87.5% 100% 12.5% 62.5% 37.5%
Extremity involvement common Upper = 75% | Lower = 100%
Facial / Aural / Nasal involvement uncommon Morphology reflects diversity / clinical evolution of PG
lesions
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Serologic Titers in Patients with Levamisole-Induced Pyoderma Gangrenosum
Patient NPN Biopsy Lev CRP MPO PR3 c-ANCA p-ANCA ANA RF C-IgM C-IgA
Total 2/8 8/8 0/8 6/8 7/8 4/8 0/8 7/8 3/8 1/8 5/8 0/8
25% 100% 0% 75% 87.5% 50% 0% 87.5% 37.5% 12.5% 62.5% 0%
C-IgG C3 C4 CryoB2GP
IgM
B2GP
IgA
B2GP
IgG
PhosSer
IgM
PhosSer
IgA
PhosSer
IgG
Lupus
AntiOther
Total 3/8 0/8 0/8 3/8 3/8 1/8 2/8 3/8 0/8 3/8 3/8
Histone AB, DsDNA Ab,
Anti-Prothrombin
IGG, Anti-Prothrombin
IGM
37.5% 0% 0% 37.5% 37.5% 12.5% 25% 37.5% 0% 37.5% 37.5%
ANA, Antinuclear antibody; anti-prothombin IgG, prothrombin IgG antibody; anti-prothrombin IgM, prothrombin IgM antibody; B2GP IgA, beta-2 glycoprotein IgA antibody; B2GP IgG, beta-2
glycoprotein IgG antibody; B2GP IgM, beta-2 glycoprotein IgM antibody; C3, decreased C3 amount; C4, decreased C4 amount; c-ANCA, cytoplasmic antineutrophil cytoplasmic antibody; C-
IgA, cardiolipin IgA antibody; C-IgG, cardiolipin IgG antibody; C-IgM, cardiolipin IgM antibody; CRP, elevated C-reactive protein; DsDNA AB, double-stranded DNA antibody; Histone AB, anti-
histone antibody; Lev, levamisole detected; MPO, antimyeloperoxidase antibody; NPN, neutropenia; NR, not reported; p-ANCA, perinuclear antineutrophil cytoplasmic antibody; PhosSer IgA,
phosphatidyl serine IgA antibody; PhosSer IgG, phosphatidyl serine IgG antibody; PhosSer IgM, phosphatidyl serine IgM antibody; PR3, antiproteinase-3 antibody; RF, rheumatoid factor.
Elevations in diverse panel of auto-antibodies At least one anti-phospholipid antibody (100%) P-ANCA (87.5%)
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Cocaine Use: 100% Reported (Confirmed – urine toxicology in every patient at least once)
Histopathology: Neutrophil-dominated diffuse dermal infiltrate (All) Vasculitis – 5 of 8 patients Vasculopathy – 3 patients (setting of dermal
infiltrate)
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Infectious Workup Impetiginization common (6 of 8 patients) Variety of pathogens (MRSA, Pseudomonas, Strep
Group A and B, Corynebacterium, Proteus, E. Coli) All Periodic acid-Schiff, Fite, and other stains
negative
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Treatment: abstinence + optimal wound care Systemic steroids in 6 of 8 patients (accelerated
recovery, esp. with hand involvement)
Future considerations: Harm-reduction strategy Patient noted “suppression with prednisone”.
Recurred when prednisone ran out Patient self-testing?
Recurrence – 100% driven by cocaine relapse
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Difficult to test for levamisole No internal testing Short half-life
Serology – elevated autoantibodies
No associated disease or precipitating factor for PG
Clinical progression Lesion induction following cocaine use (median 1 week) Improvement / resolution with abstinence Recurrence with relapse
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Common end-point – cutaneous ulceration
Clinical Progression Levamisole PG: pustule / bulla ulceration
cribiform scarring
Levamisole Vasculitis: inflammatory retiform purpura hemorrhagic bullae ulceration atrophic scarring)
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PG is a unique presentation of Levamisole-contaminated cocaine use
Pustular & bullous subtypes common
Extremity involvement common Face, ears, and nose involvement less frequent
Serology – elevated auto-antibody titers P-ANCA Anti-phospholipid antibodies
Histopathology – diffuse dermal neutrophilic infiltrate
Treatment - cocaine avoidance / gentle wound care Short courses of steroids on case-by-case basis Super-infection common Harm-reduction strategies
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