What causes skin ulcers with fat necrosis?

Causes of Skin Ulcers with Fat Necrosis

Skin ulcers with fat necrosis are most commonly caused by alpha-1 antitrypsin deficiency, pancreatic disorders, cancer, trauma, and necrotizing infections, with each having distinct pathophysiological mechanisms and clinical presentations. 1

Alpha-1 Antitrypsin Deficiency-Associated Panniculitis

• Necrotizing panniculitis is a well-recognized complication of alpha-1 antitrypsin (AAT) deficiency, characterized by inflammatory and necrotizing lesions of skin and subcutaneous tissue 1
• Most commonly seen in individuals with severe PIZZ deficiency (two-thirds of cases), but can also occur in PIMZ, SS, and MS phenotypes 1
• Typically presents as painful, hot, red, tender nodules on thighs and/or buttocks that progress to spontaneous ulcerations 1
• Ulcerations drain a clear, yellow, oily, odorless fluid that is sterile on culture 1
• Trauma precipitates the disease in approximately one-third of patients 1
• Histopathologically characterized by fat necrosis with normal-appearing fat juxtaposed to inflammatory and necrotic panniculus 1
• Fragmentation and loss of elastic tissue in areas of inflammation are frequently observed 1

Pancreatic Disorders

• Pancreatic disorders are a major cause of skin ulcers with fat necrosis due to the release of pancreatic enzymes 2, 3
• Conditions include:
  • Acute and chronic pancreatitis 3
  • Pancreatic carcinoma 3
  • Intraductal papillary mucinous neoplasm (IPMN) 2
• Pancreatic lipase and colipase escape from the pancreas and attack adipose tissue 3
• Can present as subcutaneous nodular fat necrosis with skin erythema and pain 2
• Fat necrosis can occur not only in peritoneal-retroperitoneal regions but also in peripheral tissues including subcutaneous tissue throughout the body 3, 4
• Disseminated fat necrosis can involve mesenteric, subcutaneous, and intramedullary fat 4

Cancer-Related Causes

• Rapidly growing tumors can cause cutaneous ulceration due to alterations in blood supply to the overlying skin 1
• When tumors grow faster than the skin's ability to stretch, necrosis and ulceration can occur 1
• Cancer treatments such as radiation therapy can lead to death of tumor cells and subsequent ulceration 1
• Spontaneous gangrene associated with C. septicum occurs predominantly in patients with gastrointestinal malignancy 1
• Metastatic cancer to the skin can lead to ulceration with underlying fat necrosis 1

Trauma and Pressure-Related Causes

• Pressure ulcers develop when compression of skin against bone causes ischemic injury to underlying fat and muscle 5
• This ischemic injury precedes necrosis of dermis and epidermis 5
• Trauma may precipitate fat necrosis in approximately one-third of patients with AAT deficiency-associated panniculitis 1
• Mechanical or self-induced trauma can lead to skin ulceration and fat necrosis 1
• Surgical procedures, particularly those involving the bowel or penetrating abdominal trauma, can lead to polymicrobial necrotizing infections with fat necrosis 1

Infectious Causes

• Necrotizing soft tissue infections can cause extensive fat necrosis 1
• Clostridial myonecrosis (gas gangrene) causes rapid tissue destruction and fat necrosis, most commonly due to C. perfringens 1
• Fournier gangrene, a variant of necrotizing soft-tissue infection involving the genitalia, can cause superficial gangrene with fat necrosis 1
• Necrotizing fasciitis can be monomicrobial (S. pyogenes, S. aureus, V. vulnificus, A. hydrophila) or polymicrobial (up to 15 different anaerobic and aerobic organisms) 1
• Anaerobic streptococcal myositis causes a more indolent infection with fat necrosis, usually associated with trauma or surgical procedures 1

Vascular Causes

• Venous and arterial insufficiency can lead to leg ulcers with fat necrosis 5
• Venous insufficiency results from incompetency of valves connecting superficial to deep venous systems 5
• Arterial insufficiency is caused by atherosclerosis leading to occlusive arterial disease 5
• Diabetic foot ulcers develop due to a combination of atherosclerosis and peripheral neuropathy 5

Management Considerations

• Treatment depends on the underlying cause but generally includes:
  • Thorough debridement of necrotic tissue 6, 7
  • Appropriate wound dressing selection based on wound characteristics 6, 7
  • Pressure offloading for pressure-related ulcers 6, 7
  • Assessment and treatment of infection 6, 7
• For AAT deficiency-associated panniculitis, augmentation therapy with purified human AAT or fresh frozen plasma appears rational, safe, and effective 1
• For symptomatic fat necrosis, treatment options include:
  • Conservative management for asymptomatic or small lesions 8
  • Aspiration, ultrasound-assisted liposuction, or needle aeration for oil cyst and moderately sized areas 8
  • Excision and debridement for calcified and large areas of fat necrosis 8