PYODERMA GANGRENOSUM : AN INFLAMMATORY B ASED WOUND Tracey C. Vlahovic, DPM FFPM RCPS (Glasg) Clinical Professor, Dept of Podiatric Medicine, Temple University School of Podiatric Medicine, Philadelphia, PA
PYODERMA GANGRENOSUM: AN INFLAMMATORY BASED WOUND
Feb 09, 2023
Biopsy edge of ulcer for pathology and culture.
It is a diagnosis of exclusion
Remember vascular studies– does patient have the
circulation to heal the ulcer(s)?
Get pain management involved when needed
Treat the biofilm ‐ colonizing bacteria may be driving
some of the immune response
Topical therapy alone may be sufficient for small lesions.
Systemic therapy:
Oral Steroids for initial therapy
Consider steroid sparing agents quickly.
Welcome message from author
PYODERMA GANGRENOSUM: AN INFLAMMATORY BASED WOUND
Transcript
Pyoderma Gangrenosum and other Inflammatory Based WoundsPYODERMA GANGRENOSUM: AN INFLAMMATORY BASED WOUND
Tracey C. Vlahovic, DPM FFPM RCPS (Glasg) Clinical Professor, Dept of Podiatric Medicine, Temple University School of Podiatric Medicine, Philadelphia, PA
CONFLICTS OF INTEREST: NONE
I will be discussing the off-label use of various medications
DDX of nonhealing wounds “DIIDNTHEAL”
Diabetes Infection Inflammation –not in original mnemonic Drugs – steroids, antimetabolites Nutritional Tissue necrosis – local or systemic ischemia Hypoxia Excessive tension postsurgical or dynamic location Another wound – competition between several areas Low temperature – i.e. on extremities Adapted from Stillman, RM. Wound Care:emedicine
General Surgery
1. Vascular Disease
2. Other inflammatory diseases:
Panniculitis
Pyoderma Gangrenosum (PG) Clinical features
• Leg is the most common site: 80% in some studies
• Age: 4th-5th decade most common
• Female predominance including pediatric, post-operative and peristomal subsets
PG Clinical Features
Time to appropriate diagnosis delayed
PG clinical features: Pathergy and Pain
Ulceration appearing at the sites of trauma - 1/5 to 1/2 of cases - Thought to be due to abnormal neutrophil
activation - Be cautious when injecting these wounds!!!
- Extreme pain - Pain clinic referral is essential for most patients.
Diagnosis of PG
Typical clinical pattern:
border.
• painful
Clinical findings of cribriform scarring
Presence of systemic disease associated with PG
– Especially inflammatory bowel dx
PG Associated Conditions
86 had histopathology: 46 showed alternative dx
– Vascular occlusive or venous disease
– Vasculitis – Cancer – Primary infection – Drug-induced or exogenous
tissue injury – Other inflammatory
disease
Workup of Leg Ulcers: Biopsy Early
• Biopsy : –Grayish border ifpossible
–Edge of ulcer in undermined area • do not biopsy the interior of the ulcer bed
• Send for hematoxylin and eosin(H&E)stain • Prepare to have specimen sent to a dermatopathologist
–Send tissue culture for: • Bacterial, Mycobacterial, Fungal culture
• Consider viral culture
PG workup, continued
Look for hx, signs or symptoms of IBD, CTD, pathergy
PG can occur in extracutaneous areas: Eyes, lungs, liver, spleen,
GI tract , CNS, bone and heart
LABS for All patients:
Hepatitis B and C studies, HIV
Guided by history and exam:
ANA survey, ANCA, Antiphospholipid antibodies
PT/PTT
CXR
PG Workup, Other Testing
• Consider age appropriate cancer workup. – PG may be paraneoplastic – particularly
myelodysplastic syndrome, myeloma, paraproteins, leukemia.
– especially considering patient may need immune suppression.
• STRONGLY consider vascular studies to evaluate bloodflow. – Especially in patients over50.
» This may be PG but is the vascular supply sufficient to heal the ulcer?
How to Treat PG? A Logical Approach
• 5 major treatmentconsiderations:
Treat the ulcer.
Treat the pain.
PG Therapies
– Ustekinumab – Anti-IL-1 biologics
• Local (topical) – Corticosteroids
• Topical or intralesional
Small slow growing PG: topical therapies: Locally acting antiinflammatories
Topical or intralesional steroids
PG: Treat the inflammation: Topical cyclosporine
Restasis® 0.05% (Allergan)
Reduction in pain, size
Oral cyclosporine—the difference?
First presentation 11/2012
6/2013
Antimicrobial and anti-inflammatory
Applied QD,
May be too irritating for frequent use
Can be very painful
Can rotate into every other or every third dressing change
Monitor for inflammation/pathergy
No controlled trials
May cause pathergy; consider use in non- inflammatory, stable PG wounds
Proceed with caution and frequent monitoring
Pretreat with: Corticosteroids, Dapsone, Pentoxyphylline
Consider lower setting for NPWT
May combine with STSG
JEADV 2016 Pichler et al Ghersi, M. M. et al. Arch Dermatol 2007;143:1249-1251
PG: Treat the Inflammation
• Small, slowly growing – try topical treatment
• Moderate sizeand slowly growing– try topical or less potentially toxic regimensfirst
• Rapidly enlarging – start with aggressive therapy immediately
Moderate-slow growing PG: Treat the Inflammation
• Systemic therapies plus topicals –Immune modulatory (less suppressive)
• Antiinflammatory oral antibiotics: tetracyclines, macrolides, sulfonamides
• Specific antineutrophil agents: dapsone and/or colchicine.
• No published data for PG but consider: –Pentoxyphylline
» improve circulation + weak inhibitor ofTNF
–NSAIDS
Inflamed large or rapidly growing PG: systemic plus topical Start with rapidly acting induction therapy Prednisone 0.5 – 1.0 mg/kg/day or Infliximab 510 mg/kg day
1,14, 42 then q48 wks Plan to wean as quickly as possible as the PG improves
Start a steroid sparing agent(s) as well or soon thereafter Topical steroid, calcineurin inhibitor or other topical agent Add dapsone or colchine for antineutrophil effect Dapsone helps with pneumocystis prophylaxis in patients on
steroids Tetracycline derivative (doxycycline) for antiinflammatory
and antibacterial effects Add more aggressive immune suppression May add other biologic
PG: Treat the Inflammation
• Combination therapy better thanmonotherapy?
– Seems to be relatively equal evidence for the efficacy of:
• Mycophenolate mofetil
comfortable. No specific trials for combination
therapy
Try to use combinations that have been studied in other
diseases
Only drug that has been studied in randomized, double-blind, placebo-controlled trial forPG
Brooklyn et al. Gut. 2006 Apr;55(4):505-9
-Half received drug at week 0 -If no improvement at wk 2, open label drug was offered -69% of 29 pts improved -21% remission at 6weeks
Not a true biologic for PG: apremilast
8/4/2017 12/2017, start of apremilast 7/2/2018
PG: Should I debride?
In general, discourage repetitive debridement +/ grafting
Scenarios for surgery:
Extensive infection
Once PG activity is controlled, may consider graft
High risk of recurrence in graft donor site as well as in the original site
PG: Hydrosurgical debridement and grafting
Wounds 2018 30 (3): 57-61
Treatment of PG: An Algorithm
Small and stable
Large and rapidly
aggressive systemic
Grafting Appropriate wound care
Methotrexate Azathioprine
CAUSE?
PG: Summary Biopsy edge of ulcer for pathology and culture. It is a diagnosis of exclusion Remember vascular studies– does patient have the
circulation to heal the ulcer(s)? Get pain management involved when needed Treat the biofilm colonizing bacteria may be driving
some of the immune response Topical therapy alone may be sufficient for small lesions. Systemic therapy:
Oral Steroids for initial therapy Consider steroid sparing agents quickly.
Most steroid sparing agents take 12 16 weeks to reach full effect. Give it a chance!!
Be flexible – different therapies for different patients. Wean medications slowly after healing as recurrence is
possible
References
Patel, S, Fitzmarice C, Duong C, et al. Effective Strategies for the Management of Pyoderma Gangrenosum: A comprehensive review. Acta Derma Venereol 2015;95:525531.
Bhat R. Pyoderma Gangrenosum: An update. Indian Dermatology Online Journal 3 (1) Jan – April 2012.
Tamir A, Landan M, Brenner S. Topical treatment with 1% Sodium Cromolate in Pyoderma Gangrenosum. Dermatology 1996;192:252254.
Tsele E,Yu R, Chu A. Pyoderma Gangresosum – response to topical Nitrogen Mustard. Clin Exper Dermatol 1992;17:437440.
Miller J, Yentzner B, Clark A et al. Pyoderma gangrenosum: an review and update of new therapies. J Am Acad Dermatol 2010 Apr;62(4):64654.
Sinnya s, Hamza S. Pyoderma gangrenosum of the breast treated with intravenous immunoglobulin. J Dermatol Case Rep. 2013 Jun 30;7(2):648.
Suzuki K, Sieczka E, Tranbaugh R, Hoffman D. Pyoderma gangrenosum masquerading as a sternal wound infection following cardiac surgery. Int J Surg Case Rep. 2015;6C:1635
Fedi MC, Quercetani R, Lotti T. Recalcitrant pyoderma gangrenosum responsive to cyclosporine. Int J Dermatol. 1993 Feb. 32(2):119.
Daniels NH, Callen JP. Mycophenolate mofetil is an effective treatment for peristomal pyoderma gangrenosum.Arch Dermatol. 2004 Dec. 140(12):14279
Okhovat JP, Shinkai K. Pyoderma gangrenosum. JAMA Dermatol. 2014 Sep. 150(9):1032
Reichrath J, Bens G, Bonowitz A, Wolfgang T. Treatment recommendations for pyoderma gangrenosum: An evidencebased review of the literature based on more than 350 patients. J Am Acad Dermatol 2005 Aug. 53(2):27383.
Thank you!!! [email protected]
Tracey C. Vlahovic, DPM FFPM RCPS (Glasg) Clinical Professor, Dept of Podiatric Medicine, Temple University School of Podiatric Medicine, Philadelphia, PA
CONFLICTS OF INTEREST: NONE
I will be discussing the off-label use of various medications
DDX of nonhealing wounds “DIIDNTHEAL”
Diabetes Infection Inflammation –not in original mnemonic Drugs – steroids, antimetabolites Nutritional Tissue necrosis – local or systemic ischemia Hypoxia Excessive tension postsurgical or dynamic location Another wound – competition between several areas Low temperature – i.e. on extremities Adapted from Stillman, RM. Wound Care:emedicine
General Surgery
1. Vascular Disease
2. Other inflammatory diseases:
Panniculitis
Pyoderma Gangrenosum (PG) Clinical features
• Leg is the most common site: 80% in some studies
• Age: 4th-5th decade most common
• Female predominance including pediatric, post-operative and peristomal subsets
PG Clinical Features
Time to appropriate diagnosis delayed
PG clinical features: Pathergy and Pain
Ulceration appearing at the sites of trauma - 1/5 to 1/2 of cases - Thought to be due to abnormal neutrophil
activation - Be cautious when injecting these wounds!!!
- Extreme pain - Pain clinic referral is essential for most patients.
Diagnosis of PG
Typical clinical pattern:
border.
• painful
Clinical findings of cribriform scarring
Presence of systemic disease associated with PG
– Especially inflammatory bowel dx
PG Associated Conditions
86 had histopathology: 46 showed alternative dx
– Vascular occlusive or venous disease
– Vasculitis – Cancer – Primary infection – Drug-induced or exogenous
tissue injury – Other inflammatory
disease
Workup of Leg Ulcers: Biopsy Early
• Biopsy : –Grayish border ifpossible
–Edge of ulcer in undermined area • do not biopsy the interior of the ulcer bed
• Send for hematoxylin and eosin(H&E)stain • Prepare to have specimen sent to a dermatopathologist
–Send tissue culture for: • Bacterial, Mycobacterial, Fungal culture
• Consider viral culture
PG workup, continued
Look for hx, signs or symptoms of IBD, CTD, pathergy
PG can occur in extracutaneous areas: Eyes, lungs, liver, spleen,
GI tract , CNS, bone and heart
LABS for All patients:
Hepatitis B and C studies, HIV
Guided by history and exam:
ANA survey, ANCA, Antiphospholipid antibodies
PT/PTT
CXR
PG Workup, Other Testing
• Consider age appropriate cancer workup. – PG may be paraneoplastic – particularly
myelodysplastic syndrome, myeloma, paraproteins, leukemia.
– especially considering patient may need immune suppression.
• STRONGLY consider vascular studies to evaluate bloodflow. – Especially in patients over50.
» This may be PG but is the vascular supply sufficient to heal the ulcer?
How to Treat PG? A Logical Approach
• 5 major treatmentconsiderations:
Treat the ulcer.
Treat the pain.
PG Therapies
– Ustekinumab – Anti-IL-1 biologics
• Local (topical) – Corticosteroids
• Topical or intralesional
Small slow growing PG: topical therapies: Locally acting antiinflammatories
Topical or intralesional steroids
PG: Treat the inflammation: Topical cyclosporine
Restasis® 0.05% (Allergan)
Reduction in pain, size
Oral cyclosporine—the difference?
First presentation 11/2012
6/2013
Antimicrobial and anti-inflammatory
Applied QD,
May be too irritating for frequent use
Can be very painful
Can rotate into every other or every third dressing change
Monitor for inflammation/pathergy
No controlled trials
May cause pathergy; consider use in non- inflammatory, stable PG wounds
Proceed with caution and frequent monitoring
Pretreat with: Corticosteroids, Dapsone, Pentoxyphylline
Consider lower setting for NPWT
May combine with STSG
JEADV 2016 Pichler et al Ghersi, M. M. et al. Arch Dermatol 2007;143:1249-1251
PG: Treat the Inflammation
• Small, slowly growing – try topical treatment
• Moderate sizeand slowly growing– try topical or less potentially toxic regimensfirst
• Rapidly enlarging – start with aggressive therapy immediately
Moderate-slow growing PG: Treat the Inflammation
• Systemic therapies plus topicals –Immune modulatory (less suppressive)
• Antiinflammatory oral antibiotics: tetracyclines, macrolides, sulfonamides
• Specific antineutrophil agents: dapsone and/or colchicine.
• No published data for PG but consider: –Pentoxyphylline
» improve circulation + weak inhibitor ofTNF
–NSAIDS
Inflamed large or rapidly growing PG: systemic plus topical Start with rapidly acting induction therapy Prednisone 0.5 – 1.0 mg/kg/day or Infliximab 510 mg/kg day
1,14, 42 then q48 wks Plan to wean as quickly as possible as the PG improves
Start a steroid sparing agent(s) as well or soon thereafter Topical steroid, calcineurin inhibitor or other topical agent Add dapsone or colchine for antineutrophil effect Dapsone helps with pneumocystis prophylaxis in patients on
steroids Tetracycline derivative (doxycycline) for antiinflammatory
and antibacterial effects Add more aggressive immune suppression May add other biologic
PG: Treat the Inflammation
• Combination therapy better thanmonotherapy?
– Seems to be relatively equal evidence for the efficacy of:
• Mycophenolate mofetil
comfortable. No specific trials for combination
therapy
Try to use combinations that have been studied in other
diseases
Only drug that has been studied in randomized, double-blind, placebo-controlled trial forPG
Brooklyn et al. Gut. 2006 Apr;55(4):505-9
-Half received drug at week 0 -If no improvement at wk 2, open label drug was offered -69% of 29 pts improved -21% remission at 6weeks
Not a true biologic for PG: apremilast
8/4/2017 12/2017, start of apremilast 7/2/2018
PG: Should I debride?
In general, discourage repetitive debridement +/ grafting
Scenarios for surgery:
Extensive infection
Once PG activity is controlled, may consider graft
High risk of recurrence in graft donor site as well as in the original site
PG: Hydrosurgical debridement and grafting
Wounds 2018 30 (3): 57-61
Treatment of PG: An Algorithm
Small and stable
Large and rapidly
aggressive systemic
Grafting Appropriate wound care
Methotrexate Azathioprine
CAUSE?
PG: Summary Biopsy edge of ulcer for pathology and culture. It is a diagnosis of exclusion Remember vascular studies– does patient have the
circulation to heal the ulcer(s)? Get pain management involved when needed Treat the biofilm colonizing bacteria may be driving
some of the immune response Topical therapy alone may be sufficient for small lesions. Systemic therapy:
Oral Steroids for initial therapy Consider steroid sparing agents quickly.
Most steroid sparing agents take 12 16 weeks to reach full effect. Give it a chance!!
Be flexible – different therapies for different patients. Wean medications slowly after healing as recurrence is
possible
References
Patel, S, Fitzmarice C, Duong C, et al. Effective Strategies for the Management of Pyoderma Gangrenosum: A comprehensive review. Acta Derma Venereol 2015;95:525531.
Bhat R. Pyoderma Gangrenosum: An update. Indian Dermatology Online Journal 3 (1) Jan – April 2012.
Tamir A, Landan M, Brenner S. Topical treatment with 1% Sodium Cromolate in Pyoderma Gangrenosum. Dermatology 1996;192:252254.
Tsele E,Yu R, Chu A. Pyoderma Gangresosum – response to topical Nitrogen Mustard. Clin Exper Dermatol 1992;17:437440.
Miller J, Yentzner B, Clark A et al. Pyoderma gangrenosum: an review and update of new therapies. J Am Acad Dermatol 2010 Apr;62(4):64654.
Sinnya s, Hamza S. Pyoderma gangrenosum of the breast treated with intravenous immunoglobulin. J Dermatol Case Rep. 2013 Jun 30;7(2):648.
Suzuki K, Sieczka E, Tranbaugh R, Hoffman D. Pyoderma gangrenosum masquerading as a sternal wound infection following cardiac surgery. Int J Surg Case Rep. 2015;6C:1635
Fedi MC, Quercetani R, Lotti T. Recalcitrant pyoderma gangrenosum responsive to cyclosporine. Int J Dermatol. 1993 Feb. 32(2):119.
Daniels NH, Callen JP. Mycophenolate mofetil is an effective treatment for peristomal pyoderma gangrenosum.Arch Dermatol. 2004 Dec. 140(12):14279
Okhovat JP, Shinkai K. Pyoderma gangrenosum. JAMA Dermatol. 2014 Sep. 150(9):1032
Reichrath J, Bens G, Bonowitz A, Wolfgang T. Treatment recommendations for pyoderma gangrenosum: An evidencebased review of the literature based on more than 350 patients. J Am Acad Dermatol 2005 Aug. 53(2):27383.
Thank you!!! [email protected]
Related Documents
