Pathogenesis of Cellulitisseen in patients with diabetes mellitus

Presented by Cheng-Yi

–Harrison’s Manual of Medicine, 17th edition

An acute inflammatory condition of the skin, is characterized by localized pain, erythema,

swelling and heat.

Causes

Infection.

Causes

Non Infectious.

Autoimmune Drug reaction

Risk Factors

Neuropathy

Peripheral vascular disease

Poor glycemic control

Neuropathy

Sensory

Autonomic Motor

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

Pathogenesis 4 pathways

Protein Kinase C

Hexosamine PathwayPolyol Pathway

Advanced Glycation End-products

Hyperglycemia

Protein Kinase C

Hexosamine PathwayPolyol Pathway

Advanced Glycation End-products

Excess formation of ROS

Excess formation of ROS

Poly(ADP-ribose) Polymerase Pathway

Promote inflammatory reactions & neuronal dysfunction

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

Risk Factors

Neuropathy

Peripheral vascular disease

Poor glycemic control

Pathogenesis

Impair blood flow necessary for healing ulcers & infections

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.

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.

Risk Factors

Neuropathy

Peripheral vascular disease

Poor glycemic control

Pathogenesis

Hyperglycemia

Impairs neutrophil function & reduces host defense

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