What is the cause and treatment for panniculitis?

Causes and Treatment of Panniculitis

Alpha-1 antitrypsin deficiency is a significant cause of panniculitis, and treatment should be directed at the underlying cause with augmentation therapy using purified human alpha-1 antitrypsin or fresh frozen plasma when this etiology is identified. 1

Causes of Panniculitis

Panniculitis is an inflammation of the subcutaneous fat that can have various etiologies. The main causes include:

1. Alpha-1 antitrypsin deficiency (AAT deficiency)

   • Presents as necrotizing panniculitis with distinctive features
   • Most commonly associated with severe PIZZ deficiency, but can occur with PIMZ, SS, and MS phenotypes 1
   • Trauma may precipitate the disease in approximately one-third of cases

2. Infectious causes

   • Streptococcal infections
   • Tuberculosis
   • Other bacterial, fungal, or parasitic infections 2

3. Inflammatory conditions

   • Sarcoidosis
   • Inflammatory bowel disease (particularly Crohn's disease and ulcerative colitis) 1
   • Behçet's disease 3

4. Malignancy-associated

   • Pancreatic disorders (acinar cell carcinoma) 4
   • Lymphoma (particularly subcutaneous panniculitis-like T-cell lymphoma) 1

5. Drug-induced panniculitis

6. Idiopathic causes

Clinical Presentation

The clinical presentation varies depending on the type of panniculitis:

• AAT deficiency-associated panniculitis:

  • Painful, hot, red, tender nodules typically on thighs and/or buttocks
  • Mean age of onset is 40 years with equal sex distribution
  • Spontaneous ulcerations with drainage of clear, yellow, oily, odorless sterile fluid
  • Can be lethal, especially when associated with other AAT deficiency complications 1

• Erythema nodosum (most common form of panniculitis):

  • Raised, tender, red or violet subcutaneous nodules of 1-5 cm
  • Usually affects extensor surfaces, particularly anterior tibial areas
  • Often associated with underlying disease activity in inflammatory conditions 1, 3

Diagnostic Approach

1. Skin biopsy:

   • Critical for differential diagnosis
   • Deep excisional specimens with large amount of tissue are required
   • Should differentiate between septal and lobular panniculitis, and presence/absence of vasculitis 5
   • Part of the biopsy should be submitted for microbiological analysis when infection is suspected

2. Laboratory testing:

   • Alpha-1 antitrypsin levels and phenotyping (recommended for all cases of severe panniculitis) 1
   • Complete blood count, inflammatory markers
   • Specific tests based on clinical suspicion (tuberculosis testing, pancreatic enzymes)

Treatment Approach

Treatment should be directed at the underlying cause:

1. For AAT deficiency-associated panniculitis:

   • Augmentation therapy with purified human AAT or fresh frozen plasma is rational, safe, and effective
   • Dapsone, either alone in less severe cases or combined with augmentation therapy
   • Family screening and antismoking counseling are essential
   • Note: Corticosteroids, antibiotics, or cytostatic drugs appear useless in this form 1

2. For erythema nodosum:

   • Treatment of the underlying disease
   • Systemic corticosteroids are usually required
   • For resistant cases: immunomodulation with azathioprine, infliximab, or adalimumab 1
   • Symptomatic care with NSAIDs, potassium iodide, and colchicine 6

3. For pyoderma gangrenosum (a severe form of neutrophilic panniculitis):

   • Immunosuppression is the mainstay of treatment
   • First-line: systemic corticosteroids
   • For refractory cases: intravenous cyclosporine, tacrolimus, or infliximab
   • Infliximab has shown significant efficacy in controlled trials 1

4. For malignancy-associated panniculitis:

   • Treatment of the underlying malignancy
   • For lymphoma-associated panniculitis: regimens containing etoposide, cyclophosphamide, or methotrexate 1
   • For pancreatic panniculitis: treatment of the underlying pancreatic disorder 4

Important Considerations and Pitfalls

1. Misdiagnosis: AAT deficiency-associated panniculitis is often misdiagnosed as Weber-Christian panniculitis, but it has distinctive features and treatment requirements 1

2. Delayed diagnosis: Skin manifestations may precede the diagnosis of underlying disorders by months, particularly in pancreatic disease 4

3. Inadequate biopsy: Insufficient depth or size of biopsy specimen can lead to misdiagnosis 5

4. Treatment resistance: Failure to identify and treat the underlying cause will result in poor response to symptomatic treatments

5. Mortality risk: Some forms of panniculitis, particularly AAT deficiency-associated and malignancy-associated types, can be lethal if not properly diagnosed and treated 1