Neutrophilic Dermatoses Pyoderma Gangrenosum · PDF filePyoderma Gangrenosum Pyo- prefix for...
Transcript of Neutrophilic Dermatoses Pyoderma Gangrenosum · PDF filePyoderma Gangrenosum Pyo- prefix for...
Unusual Chronic Wounds
Neutrophilic Dermatoses
Pyoderma Gangrenosum
Pyoderma Gangrenosum
Pyo- prefix for pus Derma- another term for dermis, alternatively
skin or disease of the skin Gangrenosum- referring to gangrene, which is
not quite correct
Final Thoughts
Inflammatory Bowel Disease Ulcerative condition Presence of high bacterial load
Peptic Ulcer Disease Ulcerative condition First discovery of H.Pylori in 1982
80% of all microbes on and in the human bodyas identified by free DNA analysis have yet tobe speciated or cultured
Common Wisdom
Diagnosis by Pattern recognition Associated conditions Nonspecific histopathology
Differential Diagnosis
Other Cutaneous Ulcerating conditions SWEET syndrome Behcet Disease Chancroid Allergic Granulomatosis (Churg-Strauss
Syndrome) Ecthyma Gangrenosum Leukocytoclastic Vasulitis Insect Bite
Differential Diagnosis
Basal Cell Carcinoma Wegener's Granulomatosis Hidradenitis Suppurativa
Differential Diagnosis
Basal Cell Carcinoma Wegener's Granulomatosis Hidradenitis Suppurativa
Associated Conditions
Inflammatory bowel disease (UC, Crohn's) Arthritides (Rheumatoid, Seronegative) Hematologic Disease
Myeloid metaplasia Myelofibrosis, Myelocyticand hairy cell leukemias
Monoclonal gammopathies Autoinflammatory disease
PAPA Granulomatosis
50% no associated condition
molecules such as interleukin-8 (IL-8), interferon gamma (IFN-γ), C3a, C5a, and Leukotriene B4
Clinical Presentation
Most commonly focal Peri-stomal Lower extremity Almost anywhere
Occasionally disseminated
Clinical Presentation
Painful Papule Necrosis Ulceration Rapidly Spreading Pathergy
Pathergy
Reactivation of pathologic process with minortrauma
Characteristic of PDG wounds
Do's and Don'ts
Do search for underlying illness Do apply simple non-traumatic dressing Do consider the differential diagnosis Don't agressively debride it Don't rush to operate on it Don't be afraid to do something counter-intuitive
Pharmacologic/Biological Control
Nonspecific anti-inflammatory Intralesional, topical, high dose systemic
corticosteroid Cytokine modulating biologics
Monoclonal antibodies against TNFalpha, IL-2b
Enbrel, Remicade, Humira, Simponi, Cimzia Cyclosporine-downregulates inflammatory
cytokine production Macrolides
Tacrilimus T-cell inhbitor
Pharmacologic/biologic agentcontrol
Micophenylate Thalidomide Plasmapheresis
Focus on the Neutrophil
Single most common white cell in circulation Produced in bone marrow, circulates until
activated to migrate into tissue Short lived; 5-90 hours, once activated 1-2 days
in tissue 3 modes of action
Phagocytosis Exocytosis (Degranulation) Neutrophil Extracellular tTraps
Neutrophil Migration
Neutrophils are called into tissue byinflammatory molecules produced by residentcells in the tissue
molecules such as interleukin-8 (IL-8),interferon gamma (IFN-γ), C3a, C5a, andLeukotriene B4
Many cells are capable of sending aninflammatory signal, but resident macrophagesor dendritic cells may be the source of theneutrophil summoning signal
Neutrophil Kill Mechanism
Phagocytosis Engulf microbe once it is tagged as foreign Dump enzymes, reactive oxygen species into
phagosome Kill and digest microbe
Neutrophil Kill Mechanism
Degranulation Release microbial toxins into extracellular
matrix Kill microbes by contact with extracellular
enzymes and other neutrophil derivedmolecules
Neutrophil Kill Mechanism
Neutrophil Extracellular Traps
DNA “spider web” Immobilizes microbes for destruction by
mechanisms that do not require phagocytosis
The neutrophil in Tissue destruction
Exocytosis (degranulation) Multiple types of granule, multiple molecules Collagenase, elastase, matrix
metalloproteinase Pus- made up of neutrophils, cellular debris,
usually bacteria PDG produces sterile pus, or incidentally
colonized pus.
The Neutrophil in Tissue Destruction
Do normal neutrophils participate in PDG? Why would a cell whose lifespan is 1-2 days
contribute to a process that goes on formonths?
Do bacteria play a role? Is tissue destruction a result of neutrophil
degranulation? Why would neutrophils act so fulminantly? What can you do to turn off the evil neutrophils?
How Can We Stop the KillerNeutrophil?
Turn off the local stimulus for summoning theNeutrophil
Corticosteroid, Monoclonal antibody, Otherantimetabolites
Turn off the Neutrophil itself Corticosteroid, anti-rejection medications; block stimulus molecules, block tissue
destructive molecules
Pathogenesis of PyodermaGangrenosum
Neutrophil recruitment Liquifaction necrosis Ulceration
Could there be a microbe involved?