How should I manage and treat a 56‑year‑old woman with diabetes who presents with focal panniculitis and subcutaneous fat necrosis?

Management of Focal Panniculitis and Subcutaneous Fat Necrosis in a 56-Year-Old Diabetic Woman

In this diabetic patient with focal panniculitis and subcutaneous fat necrosis, immediately obtain a deep excisional biopsy reaching subcutaneous fat and medium-sized vessels to establish the specific etiology, then test plasma alpha-1 antitrypsin levels and pancreatic enzymes (lipase, amylase) to guide definitive treatment. 1, 2, 3

Immediate Diagnostic Steps

Biopsy Requirements

• Perform a deep excisional biopsy with adequate subcutaneous fat tissue and medium-sized vessels—superficial punch biopsies represent the most common diagnostic error and frequently miss the pathology 1, 2, 3
• Divide the specimen for histopathological evaluation to classify as septal versus lobular panniculitis and identify vasculitis, fat necrosis patterns, and the presence of "ghost cells" (anucleated adipocytes with thick shadowy walls) 1, 4

Essential Laboratory Testing

• Test plasma alpha-1 antitrypsin (AAT) levels in all cases of biopsy-proven severe panniculitis, particularly with necrotizing or ulcerative features, as this requires specific augmentation therapy 5, 1, 2, 3
• Measure serum lipase and amylase levels to evaluate for pancreatic disease, which can cause subcutaneous fat necrosis even when asymptomatic 6, 7, 4
• Check complete blood count, liver function tests, and inflammatory markers to assess for systemic involvement 2

Etiology-Specific Treatment Algorithm

If Alpha-1 Antitrypsin Deficiency is Confirmed (PIZZ, PIMZ, or other deficient phenotypes)

• Initiate augmentation therapy with purified human AAT or fresh frozen plasma as primary treatment—this restores plasma and local tissue AAT levels and represents the most effective intervention 5, 1, 2
• Add dapsone either alone in less severe cases or combined with augmentation therapy for additional therapeutic benefit 5, 1, 2
• Provide antismoking counseling, as cigarette smoking reduces functional AAT capacity through oxidation and increases risk of complications 5, 2
• Consider liver transplantation in severe cases with cirrhosis, as this has led to permanent cure by restoring plasma AAT levels 2

If Pancreatic Disease is Identified (Elevated Lipase/Amylase or Imaging Findings)

• Treat the underlying pancreatic disorder aggressively, as subcutaneous fat necrosis results from hematogenous-borne trypsin and lipase causing distant fat necrosis 6, 7, 4
• Recognize that pancreatic panniculitis can be fatal, particularly when associated with acute pancreatitis or pancreatic carcinoma with multi-organ failure 7
• Obtain abdominal CT or MRI to evaluate for pancreatic carcinoma, pseudocyst, or pancreatitis, as the pancreatic disease may be asymptomatic 6, 4
• Consider this a red flag for occult malignancy when panniculitis is widespread, persistent, shows frequent relapses, or has tendency to ulcerate 6

If Necrobiosis Lipoidica is Suspected (Common in Diabetics)

• Recognize that necrobiosis lipoidica produces septal panniculitis involving all dermis and often subcutaneous fat in diabetic patients 8
• Optimize glycemic control as primary intervention 8
• Consider anti-inflammatory and immunosuppressive agents for symptomatic lesions 8, 9

If Vasculitis-Associated Panniculitis is Found on Biopsy

• Initiate treatment with cyclophosphamide combined with high-dose glucocorticoids for polyarteritis nodosa presenting with cutaneous panniculitis 1, 2
• Use intravenous pulse glucocorticoids over high-dose oral glucocorticoids for severe disease 2

If Malignancy-Associated Panniculitis or Subcutaneous Panniculitis-Like T-Cell Lymphoma

• For subcutaneous panniculitis-like T-cell lymphoma without hemophagocytic syndrome, start systemic corticosteroids or other immunosuppressive agents (5-year survival 91%) 1, 2
• For disease with hemophagocytic syndrome, immediately initiate multi-agent chemotherapy—this represents a medical emergency with 5-year survival dropping to 46% 1, 2
• Treat both the hemophagocytic lymphohistiocytosis and the underlying neoplasm simultaneously 2
• Consider cyclosporine A for clonal cytophagic histiocytic panniculitis 2

Monitoring Strategy

• Perform serial clinical examinations focusing on new nodules, ulcerations, or systemic symptoms rather than repeated invasive procedures or imaging 1
• For patients with peripheral motor neuropathy secondary to panniculitis, use serial neurologic examinations rather than repeated electromyography 1, 2
• Follow-up abdominal vascular imaging is recommended for patients with severe panniculitis with abdominal involvement who become clinically asymptomatic 2

Critical Pitfalls to Avoid

• Never rely on superficial biopsies—inadequate biopsy depth is the most common diagnostic error 1, 2, 3
• Do not assume idiopathic disease without comprehensive workup including AAT deficiency testing and pancreatic enzyme evaluation, as specific etiologies require targeted therapy 3, 6
• Recognize that panniculitis can be lethal, especially when associated with cirrhosis or emphysema in AAT deficiency, acute pancreatitis with multi-organ failure, or hemophagocytic syndrome in lymphoma 5, 1, 7
• Do not delay treatment in suspected hemophagocytic syndrome—this is a medical emergency requiring immediate multi-agent chemotherapy 1, 2
• Always exclude malignancy-associated panniculitis, particularly when nodules are widespread, persistent, frequently relapsing, or ulcerating 6
• In diabetic patients, consider that the underlying pancreatic disease may be completely asymptomatic, yet still cause life-threatening panniculitis 6, 4