Histological Findings in a Cohort of Patients Haneol Sam Jeong, BA, - PowerPoint PPT Presentation

Pyoderma Gangrenosum Induced by Levamisole- Adulterated Cocaine: Clinical, Serological, and Histological Findings in a Cohort of Patients Haneol Sam Jeong, BA, BBA 1 ; Heather Layher, DO 2 ; Lauren Cao, MD 1 ; Travis Vandergriff, MD 1 ; Arturo Dominguez, MD 1 1 Department of Dermatology, UT Southwestern Medical Center 2 Brooke 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 chemotaxis 1 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 system 2  Indirect serotonin agonist 3 

Clinical Presentation Lesion Distribution 4 Patients Upper Lower Trunk Face Ears Nose Oral Arthralgias Extremity Extremity Total 34/55 46/55 22/55 26/55 40/55 21/55 4/55 17/55

Laboratory Evaluation 4 C- P- C- NPN Biopsy Lev CRP MPO PR3 ANA RF C-IgG HNE C3 C4 Cryo ANCA ANCA IgM T 24/50, Total 31/52 V 8/50, 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 T/V 18/50 Histopathology: Vasculopathy:  Hyaline thrombi occluding dermal vessels in  the absence of vasculitis Vasculitis  Fibrin in vessel walls  Leukocytoclasia  Erythrocyte extravasation 

Only now being reported in the literature  Multiple isolated case reports 5-10  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 Dorsal Hand and Fingers Cribiform Scarring Retiform Purpura Upper Extremity Lower Extremity Vesicopustular Trunk / Back Arthralgias Vegetative Ulcerative Bullous Nose Face Ears Oral 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% B2GP B2GP B2GP PhosSer PhosSer PhosSer Lupus C-IgG C3 C4 Cryo Other IgM IgA IgG IgM IgA IgG Anti Histone AB, DsDNA Ab, Anti- Total 3/8 0/8 0/8 3/8 3/8 1/8 2/8 3/8 0/8 3/8 3/8 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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