Discuss the pathogenesis of cellulitis in patients with diabetes mellitus.

1. Pathogenesis of Cellulitis
seen in patients with diabetes mellitus
Presented by Cheng-Yi

2. –Harrison’s Manual of Medicine, 17th edition
An acute inflammatory condition of the skin,
is characterized by localized pain, erythema,
swelling and heat.

3. Causes
Infection.

4. Causes
Non Infectious.
Autoimmune Drug reaction

5. Risk Factors
Neuropathy
Peripheral vascular
disease
Poor glycemic
control

6. Neuropathy
Sensory
Autonomic Motor

7. Sensory
Autonomic
Motor
Diminish the perception of
pain and temperature
Diminish sweat secretion,
resulting in dry & cracked skin
Lead to foot deformities,
which causes pressure-
induced soft tissue damage

8. Pathogenesis
4 pathways
Protein Kinase C
Hexosamine PathwayPolyol Pathway
Advanced Glycation
End-products
Hyperglycemia

9. Protein Kinase C
Hexosamine PathwayPolyol Pathway
Advanced Glycation
End-products
Excess formation of
ROS

10. Excess formation of
ROS
Poly(ADP-ribose) Polymerase Pathway
Promote inflammatory reactions &
neuronal dysfunction

11. Edwards JL, Vincent AM, Cheng HT, Feldman EL., Diabetic neuropathy: mechanisms to management.,
Pharmacol Ther. 2008 Oct;120(1)

12. Risk Factors
Neuropathy
Peripheral vascular
disease
Poor glycemic
control

13. Pathogenesis
Impair blood flow necessary for
healing ulcers & infections

14. D.M.
Hyperglycemia Free Fatty Acid Insulin Resistance
Oxidative Stress
PKC Activation
RAGE Activation
Mark A. Creager, MD; Thomas F. Lüscher, MD, FRCP, Diabetes and Vascular Disease Pathophysiology, Clinical
Consequences, and Medical Therapy: Part I, American Heart Association, Inc.

15. Oxidative Stress
PKC Activation
RAGE Activation
↓NO
↑ET-1
↑AT II
↑AP-1
↑NF-κB
↑TF
↑PAI-1
↓NO
Vasoconstriction Inflammation Thrombosis
Mark A. Creager, MD; Thomas F. Lüscher, MD, FRCP, Diabetes and Vascular Disease Pathophysiology, Clinical
Consequences, and Medical Therapy: Part I, American Heart Association, Inc.

16. Risk Factors
Neuropathy
Peripheral vascular
disease
Poor glycemic
control

17. Pathogenesis
Hyperglycemia
Impairs neutrophil function &
reduces host defense

18. Reference
• Matthew E. Falagas, MD, MSc, and Paschalis I. Vergidis, MD,
Narrative Review: Diseases That Masquerade as Infectious
Cellulitis, Ann Intern Med. 2005;142:47-55.
• Edwards JL, Vincent AM, Cheng HT, Feldman EL., Diabetic
neuropathy: mechanisms to management., Pharmacol Ther. 2008
Oct;120(1)
• Mark A. Creager, MD; Thomas F. Lüscher, MD, FRCP, Diabetes and
Vascular Disease Pathophysiology, Clinical Consequences, and
Medical Therapy: Part I, American Heart Association, Inc.
• Clinical manifestations, diagnosis, and management of diabetic
infections of the lower extremities In: UpToDate