What investigations should be performed in a patient presenting with panniculitis?

Investigations for Panniculitis

Obtain a deep excisional biopsy reaching medium-sized vessels and adequate subcutaneous fat tissue as the single most critical investigation, since superficial biopsies frequently miss the pathology and represent the most common diagnostic error. 1, 2

Essential Biopsy Technique

• Perform a deep excisional or "double" punch biopsy that captures subcutaneous fat and medium-sized vessels of the dermis, as inadequate depth is the most frequent cause of diagnostic failure 3, 1, 4

• Divide the specimen for multiple analyses: send portions for histopathological evaluation (to classify as septal versus lobular panniculitis and identify vasculitis), microbiological culture, and T-cell clonality studies if lymphoma is suspected 1, 5, 6

• Avoid superficial punch biopsies in suspected panniculitis, as they yield nonspecific findings and delay diagnosis by months 4

Laboratory Investigations

Mandatory Initial Testing

• Measure plasma alpha-1 antitrypsin (AAT) levels in all cases of biopsy-proven severe panniculitis, particularly those with necrotizing or ulcerative features, as AAT deficiency requires specific augmentation therapy 1, 2

• Obtain inflammatory markers (ESR and CRP) at baseline for diagnostic and prognostic assessment 3

Etiology-Specific Testing Based on Clinical Presentation

• Test for autoantibodies (ANA, anti-dsDNA, complement levels) if lupus panniculitis is suspected based on lymphocytic infiltration on histology 3, 5

• Perform coagulation studies (protein C, protein S, antithrombin III, factor V Leiden, antiphospholipid antibodies) in cases of nodular thrombophlebitis to identify underlying coagulopathy 5

• Check serum lipase levels (often markedly elevated >15,000 U/L) if pancreatic panniculitis is suspected, and investigate for pancreatic disease or acinar cell carcinoma 7

• Order HLA-B27 testing if clinical features suggest vasculitis-associated panniculitis or Behçet's disease 3, 5

Imaging Studies

Vascular Imaging

• Obtain abdominal vascular imaging (CT angiography or MR angiography) in suspected polyarteritis nodosa to establish diagnosis, determine disease extent, and identify characteristic arterial stenoses and occlusions 3, 8

• Perform follow-up abdominal vascular imaging in patients with severe panniculitis and abdominal involvement who achieve clinical remission, particularly when baseline imaging demonstrates aneurysmal disease 3, 8

Additional Imaging

• Consider chest imaging to evaluate for emphysema in AAT deficiency-associated panniculitis 2

• Obtain imaging of affected areas to assess disease extent, especially in subcutaneous presentations 2

Neurologic Assessment

• Perform electromyography/nerve conduction studies initially to confirm and characterize peripheral neuropathy in suspected vasculitis-associated panniculitis 3, 8

• Use serial neurologic examinations rather than repeated electromyography for ongoing monitoring of established peripheral motor neuropathy 3, 1, 8

• Consider combined nerve and muscle biopsy (rather than nerve biopsy alone) in suspected polyarteritis nodosa with peripheral neuropathy, sampling clinically affected tissue 3

Diagnostic Algorithm by Clinical Pattern

Septal Panniculitis

• Erythema nodosum with typical presentation (tender red-violet nodules 1-5 cm on anterior lower legs) does not require biopsy; focus investigations on identifying the underlying cause (inflammatory bowel disease, infection, sarcoidosis) 2, 5, 9

• Atypical septal panniculitis requires deep biopsy to differentiate between leukocytoclastic vasculitis, superficial thrombophlebitis, cutaneous polyarteritis nodosa, and extension of dermal processes 5, 9

Lobular Panniculitis

• Classify based on inflammatory cell type: lymphocytic infiltrate suggests lupus panniculitis versus subcutaneous panniculitis-like T-cell lymphoma (requires T-cell clonality studies); histiocytic infiltrate suggests sarcoidosis or cytophagic histiocytic panniculitis; neutrophilic infiltrate requires careful clinicopathologic correlation 5, 6

Critical Pitfalls to Avoid

• Never accept a superficial biopsy result as definitive in suspected panniculitis—the most common diagnostic error is inadequate tissue depth 1, 2, 4

• Do not delay investigation when panniculitis is associated with systemic symptoms, as it can be lethal (especially with cirrhosis/emphysema in AAT deficiency or hemophagocytic syndrome in lymphoma) 1, 2

• Always submit tissue for microbiological culture to exclude infectious causes (Nocardia, atypical mycobacteria, fungi) that require specific antimicrobial therapy 2, 5

• Repeat biopsy if initial results are nonspecific and clinical suspicion remains high, as panniculitis shows different histopathologic findings at different evolutionary stages 5, 6, 4

• Screen for malignancy-associated panniculitis in older patients with high lipase levels or atypical features, as this requires treatment of both the underlying neoplasm and any associated hemophagocytic lymphohistiocytosis 1, 2, 7