How should focal panniculitis (in children and adults) and subcutaneous fat necrosis of the newborn be managed and treated?

Management and Treatment of Focal Panniculitis and Subcutaneous Fat Necrosis

Subcutaneous Fat Necrosis of the Newborn (SCFN)

SCFN is a self-limiting panniculitis that requires conservative management with close monitoring for hypercalcemia, which develops in approximately 63% of cases and represents the most serious complication requiring prolonged medical treatment. 1

Clinical Recognition and Diagnosis

• SCFN presents as hard, purple or erythematous subcutaneous nodules typically appearing on the upper back, cheeks, buttocks, and limbs within the first few weeks of life 2
• Risk factors include maternal gestational diabetes, maternal hypertensive diseases, macrosomia (>4000g), birth asphyxia, meconium aspiration, and therapeutic hypothermia 2, 1
• Deep excisional biopsy with adequate tissue is recommended for atypical cases, as superficial biopsies may miss the pathology; histology typically shows granulomatous inflammation in 98% of cases 3, 2
• Ultrasound can demonstrate increased echogenicity of subcutaneous tissue with loss of definition of adipocytes 4

Conservative Management Approach

• The nodules spontaneously resolve within 3-6 months in most cases without specific intervention 5, 4
• No active treatment is required for the skin lesions themselves, as they undergo complete regression 4
• Focus management on monitoring and treating complications rather than the panniculitis itself 5

Hypercalcemia Monitoring and Management

All infants with SCFN require serial calcium monitoring for at least 6 months, as hypercalcemia can develop late and reach life-threatening levels. 6, 1

• Check serum calcium levels at diagnosis, then weekly for the first month, then every 2-4 weeks for 6 months 2, 6
• In hypercalcemic cases (70.5% of those monitored), parathormone is suppressed in 89.3% 2
• Treatment for hypercalcemia includes:
  • Low-calcium, low-vitamin D formula or maternal diet modification if breastfeeding 6
  • Increased fluid intake to promote calcium excretion 6
  • Corticosteroids (prednisone 1-2 mg/kg/day) for refractory cases 6
  • Bisphosphonates in severe, persistent cases 6

Nephrocalcinosis Surveillance

• Hypercalcemia can lead to nephrocalcinosis, which may persist long-term and potentially cause chronic kidney disease 6, 1
• Perform renal ultrasound at diagnosis of hypercalcemia and repeat during follow-up if hypercalcemia is prolonged 6
• Three of 30 patients (10%) in one cohort developed nephrocalcinosis, emphasizing the need for careful monitoring 1

Special Considerations

• SCFN can occur in both preterm and term infants, with preterm infants also developing significant complications including hypercalcemia 5
• The pathophysiology involves crystallization of saturated fatty acids in subcutaneous tissue, triggered by hypoxia and cold stress 2

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Focal Panniculitis in Children and Adults

Erythema Nodosum (EN)

EN is treated primarily by addressing the underlying disease activity, with systemic corticosteroids reserved for severe cases and immunomodulators for resistant or relapsing disease. 7

• EN presents as raised, tender, red or violet subcutaneous nodules of 1-5 cm diameter on extensor surfaces, particularly anterior tibial areas 7
• Clinical diagnosis is typically sufficient; biopsy shows non-specific focal panniculitis if performed 7
• Treatment algorithm:
  • First-line: Treat underlying condition (e.g., inflammatory bowel disease flare) 7
  • Second-line: Systemic corticosteroids for severe cases 7
  • Third-line: Azathioprine, infliximab, or adalimumab for resistant cases or frequent relapses 7

Alpha-1 Antitrypsin Deficiency-Associated Panniculitis

Augmentation therapy with purified human alpha-1 antitrypsin or fresh frozen plasma is the most effective treatment, as it restores plasma and local tissue levels. 3

• Test for alpha-1 antitrypsin deficiency in all cases of biopsy-proven severe panniculitis, particularly factitious and necrotizing cases 3
• Treatment options:
  • First-line: Augmentation therapy with purified human AAT or fresh frozen plasma 3
  • Alternative: Dapsone alone in less severe cases or combined with augmentation therapy 3
  • Definitive: Liver transplantation has led to permanent cure in severe cases by restoring plasma AAT levels 3
• Essential adjuncts: Family screening and antismoking counseling 3

Vasculitis-Associated Panniculitis

Treat with cyclophosphamide and high-dose glucocorticoids for polyarteritis nodosa with cutaneous involvement, using intravenous pulse glucocorticoids for severe disease. 3

• For severe disease: Initiate with IV pulse methylprednisolone (500-1000 mg/day for 3 days) before transitioning to oral prednisone 0.5-1 mg/kg/day (maximum 60-80 mg/day) 3, 8
• Cyclophosphamide is the preferred non-glucocorticoid immunosuppressive agent 3
• For patients unable to tolerate cyclophosphamide, consider alternative immunosuppressive agents 3
• Follow-up abdominal vascular imaging is recommended for patients with history of severe panniculitis with abdominal involvement who become clinically asymptomatic 3

Malignancy-Associated Panniculitis

Treatment must address both the hemophagocytic lymphohistiocytosis and the underlying neoplasm simultaneously. 7, 3

• Cyclosporin A has shown efficacy in clonal cytophagic histiocytic panniculitis and subcutaneous panniculitis-like T-cell lymphoma with features of HLH 7, 3
• For subcutaneous panniculitis-like T-cell lymphoma without hemophagocytic syndrome: Systemic steroids or other immunosuppressive agents first (5-year survival 91%) 3
• For subcutaneous panniculitis-like T-cell lymphoma with hemophagocytic syndrome: Immediate multi-agent chemotherapy (5-year survival 46%) 3

Infectious Panniculitis (Nocardia)

• First-line: SMX-TMP 3
• Alternatives: Sulfadiazine, sulfasoxazole, amikacin, imipenem, meropenem, ceftriaxone, cefotaxime, minocycline, moxifloxacin, linezolid, or dapsone 3
• Duration: 6-24 months depending on extent of dissemination and degree of immunosuppression 3
• Surgical debridement for necrotic nodules or large subcutaneous abscesses 3

Common Pitfalls

• Inadequate biopsy depth is a common diagnostic pitfall; obtain deep excisional specimens that include subcutaneous fat and potentially medium-sized vessels 3
• Panniculitis can be lethal, especially when associated with complications such as cirrhosis or emphysema in AAT deficiency 3
• In SCFN, failure to monitor calcium levels for at least 6 months can miss late-onset hypercalcemia 6, 1