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?