Wang EA, Steel A, Luxardi G, Mitra A, Patel F, Cheng MY, Wilken R, Kao J, de Ga K, Sultani H, Merleev AA, Marusina AI, Brassard A, Fung MA, Konia T, Shimoda M, Maverakis E, et al.
Frontiers in immunology. Date of publication 2018 Jan 15;volume 8():1980.
1. Front Immunol. 2018 Jan 15;8:1980. doi: 10.3389/fimmu.2017.01980. eCollection
2017.
Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting
Follicular Adnexal Structures: A Hypothesis Based on Molecular and
Clinicopathologic Studies.
Wang EA(1), Steel A(1), Luxardi G(1), Mitra A(1), Patel F(1), Cheng MY(1), Wilken
R(1), Kao J(1), de Ga K(1), Sultani H(1), Merleev AA(1), Marusina AI(1), Brassard
A(1), Fung MA(1)(2), Konia T(1)(2), Shimoda M(1), Maverakis E(1).
Author information:
(1)Department of Dermatology, University of California, Davis, Sacramento, CA,
United States.
(2)Department of Pathology, University of California, Davis, Sacramento, CA,
United States.
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.
DOI: 10.3389/fimmu.2017.01980
PMCID: PMC5775228
PMID: 29379508
