Rashes and Skin Ulcers in Diabetes Mellitus

Pathogenesis Overview

• Advanced glycation end-products (AGEs): Hyperglycemia accelerates nonenzymatic glycosylation of collagen and structural proteins, reducing acid solubility and enzymatic degradation of dermal collagen. Cutaneous AGE levels correlate with retinopathy, nephropathy, and other microvascular complications.
• Hyperinsulinemia / insulin resistance: Excess insulin acts on IGF-1 receptors on keratinocytes and fibroblasts, driving conditions like acanthosis nigricans.
• Immune dysfunction: Hyperglycemia and ketoacidosis impair chemotaxis, phagocytosis, and bactericidal activity of white blood cells, predisposing to aggressive infections.
• Neuropathy + vasculopathy: Peripheral sensory neuropathy and peripheral vascular disease (PVD) combine to produce foot ulcers and impair wound healing.

1. Conditions With a Known Metabolic Mechanism

Acanthosis Nigricans (AN)

• Appearance: Velvety, hyperpigmented, brown-black thickening of skin at flexural/intertriginous areas (axillae, neck, groin). Can also affect extensor surfaces.
• Mechanism: Hyperinsulinemia stimulates IGF-1 receptors on keratinocytes, causing proliferation.
• Associations: Strongly linked to insulin resistance (Type 2 DM), obesity, polycystic ovary syndrome. Also seen with certain malignancies (gastric carcinoma) and drugs (glucocorticoids, nicotinic acid, estrogens).
• Treatment: Difficult; weight loss and metformin (to improve insulin sensitivity) may help. Topical calcipotriol, retinoids, or keratolytics used with variable success. - Fitzpatrick's

Eruptive Xanthomas

• Appearance: Sudden crops of red-yellow papules on the buttocks, extensor surfaces, often with an erythematous base.
• Mechanism: Hypertriglyceridemia in poorly controlled diabetes causes triglyceride-laden macrophage foam cell deposits in the dermis.
• Treatment: Glycemic control and lipid-lowering therapy lead to regression. - Dermatology 5e; Rosen's

Diabetic Thick Skin / Limited Joint Mobility (LJM / Cheiroarthropathy)

• Appearance: Thickened, waxy, smooth skin on the hands and fingers with painless flexion contractures beginning at the 5th digit DIP joint and progressing radially. The classic "prayer sign" - inability to approximate the palmar surfaces fully.

Fig. 137-3 - The prayer sign in LJM. (A) Normal; (B) diabetic - note the gap between the interphalangeal joints. Fitzpatrick's Dermatology

• Prevalence: 30-50% of adults with Type 1 DM; also common in Type 2.
• Associations: Longer duration of diabetes, higher HbA1c (2.5-fold increased risk per unit HbA1c increase), and microvascular disease.
• Treatment: Tight glycemic control is the cornerstone of both prevention and management. - Fitzpatrick's

Scleredema Diabeticorum

• Diffuse, non-pitting induration of the posterior neck and upper back, distinct from scleroderma.
• Caused by dermal mucin and collagen accumulation from AGE formation.

2. Conditions of Unknown or Debated Pathogenesis

Diabetic Dermopathy ("Skin Spots")

• Most common cutaneous finding in diabetes.
• Appearance: Discrete, atrophic, brownish, slightly depressed macules/patches typically <15 mm on the shins (pretibial area).
• Mechanism: Possibly related to trauma with altered healing due to microangiopathy; not directly proportional to glycemic control.
• Clinical note: Often overlooked; presence correlates with other microvascular complications (retinopathy, nephropathy). No specific treatment needed. - Rosen's; Dermatology 5e

Necrobiosis Lipoidica (NL)

• Appearance: Begins as erythematous papules or nodules, typically on the pretibial region. Lesions expand and coalesce into a single area of atrophic, yellow-waxy skin with a red-brown border and overlying telangiectasias. The center frequently ulcerates.
• Association: ~0.3% of diabetics; however, up to 65% of NL patients have DM. Can precede the diagnosis of diabetes.
• Mechanism: Unknown - proposed theories include microangiopathy, immune complex deposition, and abnormal collagen metabolism.
• Treatment: Difficult. Options include potent topical or intralesional corticosteroids (at the active border), PUVA, cyclosporine, TNF-alpha inhibitors, and platelet-derived growth factor. Wound care for ulcerated lesions. - Andrews'; Fitzpatrick's

Granuloma Annulare (GA)

• Appearance: Erythematous annular papules/plaques, particularly the disseminated variant (hundreds of lesions over the trunk/extremities).
• Association with DM: The exact relationship is controversial - disseminated GA is more strongly linked to diabetes than the localized form.
• Mechanism: Unknown; thought to involve altered collagen/macrophage interaction.

Bullosis Diabeticorum (Diabetic Bullae)

• Appearance: Spontaneous, tense, non-inflammatory bullae filled with clear (occasionally hemorrhagic) fluid on the distal lower extremities, especially the feet and toes. No preceding trauma.

Bullosis diabeticorum showing a tense fluid-filled bulla on the great toe. Andrews' Clinical Atlas

• Mechanism: Uncertain - microangiopathy may be a contributor.
• Outcome: Usually heal spontaneously within weeks without scarring. Treatment is conservative (sterile drainage if large; avoid rupture). - Rosen's; Dermatology 5e

Acquired Perforating Dermatosis

• Appearance: Pruritic keratotic papules, primarily on the legs.
• Association: Seen in diabetics, particularly those with concurrent renal failure (dialysis patients). Also occurs in prurigo nodularis context.
• Transepidermal elimination of altered dermal collagen is the proposed mechanism. - Fitzpatrick's

3. Infections (Immunologic Dysfunction)

4. Diabetic Foot Ulcers (Skin Ulcers)

Fig. 137-5 - Bilateral neuropathic ulcers at pressure points in a 56-year-old man with 20 years of diabetes. Fitzpatrick's Dermatology

Pathogenesis

1. Peripheral sensory neuropathy - loss of protective sensation allows unrecognized pressure injury. Diminished neuropeptide signaling impairs wound healing.
2. Peripheral vascular disease - ischemia impairs tissue perfusion and healing.
3. Pressure / foot deformity - Charcot arthropathy creates high-pressure points; callus precedes ulceration. Ill-fitting footwear was the most common identifiable cause in one study of 314 patients.

Types of Ulcers

Management - Step-by-Step

Fig. 137-6 - Diagnostic and treatment algorithm for diabetic ulcers. Fitzpatrick's Dermatology

1. Off-loading - total contact casting or removable cast walker is the gold standard. No weight-bearing.
2. Sharp debridement of necrotic tissue and callus.
3. Infection control - assess for cellulitis and osteomyelitis; appropriate antibiotics.
4. Moist wound care - moisture-retentive dressings.
5. Vascular assessment - if pulses absent or ABI ≤0.8, refer for vascular surgery evaluation.
6. Glycemic optimization - tight control (HbA1c target <7%).
7. Adjunctive therapies - recombinant PDGF (becaplermin) provides modest benefit when combined with off-loading and debridement. Bilayered living skin equivalents showed 56% healing at 12 weeks vs. 38% for standard care alone.
8. If no improvement by 4 weeks: reassess for occult infection, compliance, and consider advanced wound biologics. - Fitzpatrick's; Harrison's

Complete Summary Table of Diabetic Skin Conditions