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, 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 PR3 C- ANCA P- ANCA ANA 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

Upper Extremity Dorsal Hand and Fingers Lower Extremity Trunk / Back Face Ears Nose Oral Arthralgias Vesicopustular Bullous Ulcerative Vegetative Cribiform Scarring Retiform Purpura

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 Cryo B2GP IgM B2GP IgA B2GP IgG PhosSer IgM PhosSer IgA PhosSer IgG Lupus Anti Other 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

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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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• 10. Roche E, Martinez-Menchon T, Sanchez-Carazo JL, et al. Two cases of eruptive pyoderma gangrenosum

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• 11. Su WP, Davis MD, Weenig RH, Powell FC, Perry HO. Pyoderma gangrenosum: clinicopathologic

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