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

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

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

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

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

Lesion Distribution Lesion Morphology

Up

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ity

Do

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ing

ers

Lo

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xtr

em

ity

Tru

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/ 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

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%)

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)

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

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

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

Common end-point – cutaneous ulceration

Clinical Progression Levamisole PG: pustule / bulla ulceration

cribiform scarring

Levamisole Vasculitis: inflammatory retiform purpura hemorrhagic bullae ulceration atrophic scarring)

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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