What is the diagnostic workup and management for panniculitis presenting with tender erythematous nodules on the thighs, buttocks, abdomen, or arms?

Panniculitis: Diagnostic Workup and Management

Immediate Diagnostic Priority

Obtain a deep excisional biopsy that includes adequate subcutaneous fat and reaches medium-sized dermal vessels—this is the single most critical step, as superficial biopsies represent the most common diagnostic error and frequently miss the underlying pathology. 1, 2

Essential Diagnostic Workup

Biopsy Technique

• Perform a deep excisional or "double" punch biopsy extending well into subcutaneous fat, as inadequate depth is the primary cause of missed diagnoses in panniculitis 1, 3
• Divide the specimen for histopathological classification (septal versus lobular panniculitis, presence of vasculitis) and microbiological culture 1, 4
• When polyarteritis nodosa is suspected with peripheral neuropathy, obtain a combined nerve-and-muscle biopsy of clinically involved tissue rather than nerve alone 1

Mandatory Laboratory Testing

• Test plasma alpha-1 antitrypsin (AAT) levels in ALL cases of biopsy-proven severe panniculitis, particularly those with necrotizing or ulcerative features—this is a Grade A recommendation because AAT deficiency requires specific augmentation therapy 1, 2
• Measure inflammatory markers (ESR and C-reactive protein) for diagnostic and prognostic purposes 1
• When lymphocytic infiltrate is present on histology, perform autoantibody screening including ANA, anti-dsDNA, and complement levels to evaluate for lupus panniculitis 1
• Consider HLA-B27 testing if clinical features suggest vasculitis-associated panniculitis or Behçet-like disease 1

Imaging and Neurologic Studies

• Obtain abdominal vascular imaging (CT or MR angiography) when polyarteritis nodosa is suspected to confirm diagnosis and identify arterial stenoses or aneurysms 1
• Perform electromyography and nerve-conduction studies initially if vasculitis-related panniculitis with neuropathy is suspected 1

Etiology-Specific Treatment Algorithms

Alpha-1 Antitrypsin Deficiency-Associated Panniculitis

Initiate augmentation therapy with purified human AAT or fresh frozen plasma immediately—this is the most effective treatment as it restores plasma and tissue AAT levels. 1, 5

• Add dapsone either alone in less severe cases or combined with augmentation therapy for additional benefit 1, 5
• Provide family screening and intensive antismoking counseling as essential management components 5
• Consider liver transplantation in severe cases, which has achieved permanent cure by restoring plasma AAT levels 5

Critical caveat: AAT deficiency-associated panniculitis can be lethal, especially when associated with cirrhosis or emphysema 1, 5

Erythema Nodosum (Most Common Form)

The American College of Gastroenterology and European Crohn's and Colitis Organisation recommend the following approach 6:

• First-line: Treat the underlying disease (inflammatory bowel disease flare, infection, drug reaction) as EN is closely related to disease activity 6, 5
• Second-line: Administer systemic corticosteroids for severe cases 6, 5
• Third-line: Use immunomodulation with azathioprine, infliximab, or adalimumab for resistant cases or frequent relapses 6, 5

Clinical diagnosis is usually sufficient—biopsy shows non-specific focal panniculitis and is not routinely required 6

Subcutaneous Panniculitis-Like T-Cell Lymphoma (SPTCL)

The National Comprehensive Cancer Network provides clear survival-based guidance 1, 5:

• WITHOUT hemophagocytic syndrome: Start systemic corticosteroids or other immunosuppressive agents (5-year survival: 91%) 1, 5
• WITH hemophagocytic syndrome: Immediately initiate multi-agent chemotherapy due to aggressive nature (5-year survival drops to 46%) 1, 5
• Consider cyclosporine A, which has demonstrated efficacy in clonal cytophagic histiocytic panniculitis and SPTCL with hemophagocytic features 5

Critical pitfall: Do not delay treatment in suspected hemophagocytic syndrome—this is a medical emergency requiring immediate chemotherapy 1

Vasculitis-Associated Panniculitis (Polyarteritis Nodosa)

The American College of Rheumatology recommends 1, 5:

• Initiate cyclophosphamide combined with high-dose glucocorticoids for polyarteritis nodosa presenting with cutaneous panniculitis 1, 5
• For severe disease, use intravenous pulse glucocorticoids over high-dose oral formulations 5
• In cyclophosphamide-intolerant patients, substitute other non-glucocorticoid immunosuppressive agents 5

Infectious Panniculitis (Nocardia)

The Infectious Diseases Society of America recommends 1, 5:

• First-line: Sulfamethoxazole-trimethoprim (SMX-TMP) 1, 5
• Alternatives: Sulfadiazine, amikacin, imipenem, meropenem, ceftriaxone, minocycline, moxifloxacin, linezolid, or dapsone 1, 5
• Duration: Continue treatment for 6-24 months depending on dissemination extent and immunosuppression degree 5
• Perform surgical debridement for necrotic nodules or large subcutaneous abscesses 5

Malignancy-Associated Panniculitis

Simultaneously treat both the hemophagocytic lymphohistiocytosis and the underlying neoplasm, as recommended by the European Hematology Association 5

Monitoring Strategy

• Perform serial clinical examinations focusing on new nodules, ulcerations, or systemic symptoms rather than repeated invasive procedures 1
• For peripheral motor neuropathy secondary to panniculitis, use serial neurologic examinations rather than repeated electromyography to reduce patient burden 1, 5
• In patients with prior severe panniculitis and abdominal vascular involvement who become asymptomatic, obtain repeat abdominal vascular imaging, especially if initial studies showed aneurysmal disease 1, 5

Critical Pitfalls to Avoid

• Never accept a superficial biopsy—always insist on deep excisional specimens reaching subcutaneous fat and medium-sized vessels 1, 2, 3
• Never assume idiopathic disease without comprehensive workup including AAT deficiency testing, as specific etiologies require targeted therapy 2
• Always exclude malignancy-associated panniculitis, which requires treatment of both the underlying neoplasm and any associated hemophagocytic lymphohistiocytosis 1
• Recognize that panniculitis can be lethal, particularly when associated with cirrhosis, emphysema in AAT deficiency, or hemophagocytic syndrome in lymphoma 1, 5