Abstract
Background: Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood. Objective: Use data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology. Methods: Ten PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR. Results: All PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype. Limitations: Small sample size was the main limitation. Conclusion: We put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units.
| Original language | English (US) |
|---|---|
| Article number | 1980 |
| Journal | Frontiers in Immunology |
| Volume | 8 |
| Issue number | JAN |
| DOIs | |
| State | Published - Jan 15 2018 |
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Keywords
- Autoimmune
- CD4
- Cytokine
- IL-36G
- Pathophysiology
- Pilosebaceous unit
- Pyoderma gangrenosum
- T cell
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Classic ulcerative pyoderma gangrenosum is a T cell-mediated disease targeting follicular adnexal structures : A hypothesis based on molecular and clinicopathologic studies. / Wang, Elizabeth A.; Steel, Andrea; Luxardi, Guillaume; Mitra, Anupam; Patel, Forum; Cheng, Michelle Y.; Wilken, Reason; Kao, Jason; de Ga, Kristopher; Sultani, Hawa; Merleev, Alexander A.; Marusina, Alina I.; Brassard, Alain; Fung, Maxwell A; Konia, Thomas; Shimoda, Michiko; Maverakis, Emanual Michael.
In: Frontiers in Immunology, Vol. 8, No. JAN, 1980, 15.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Classic ulcerative pyoderma gangrenosum is a T cell-mediated disease targeting follicular adnexal structures
T2 - A hypothesis based on molecular and clinicopathologic studies
AU - Wang, Elizabeth A.
AU - Steel, Andrea
AU - Luxardi, Guillaume
AU - Mitra, Anupam
AU - Patel, Forum
AU - Cheng, Michelle Y.
AU - Wilken, Reason
AU - Kao, Jason
AU - de Ga, Kristopher
AU - Sultani, Hawa
AU - Merleev, Alexander A.
AU - Marusina, Alina I.
AU - Brassard, Alain
AU - Fung, Maxwell A
AU - Konia, Thomas
AU - Shimoda, Michiko
AU - Maverakis, Emanual Michael
PY - 2018/1/15
Y1 - 2018/1/15
N2 - Background: Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood. Objective: Use data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology. Methods: Ten PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR. Results: All PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype. Limitations: Small sample size was the main limitation. Conclusion: We put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units.
AB - Background: Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood. Objective: Use data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology. Methods: Ten PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR. Results: All PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype. Limitations: Small sample size was the main limitation. Conclusion: We put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units.
KW - Autoimmune
KW - CD4
KW - Cytokine
KW - IL-36G
KW - Pathophysiology
KW - Pilosebaceous unit
KW - Pyoderma gangrenosum
KW - T cell
UR - http://www.scopus.com/inward/record.url?scp=85040831273&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040831273&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.01980
DO - 10.3389/fimmu.2017.01980
M3 - Article
AN - SCOPUS:85040831273
VL - 8
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - JAN
M1 - 1980
ER -