What is the management of cutaneous Polyarteritis Nodosa (PAN)?

Management of Cutaneous Polyarteritis Nodosa

For cutaneous PAN, treat with non-glucocorticoid immunosuppressive agents (azathioprine or methotrexate) combined with glucocorticoids rather than glucocorticoids alone, as this approach minimizes steroid toxicity while effectively controlling disease activity. 1

Disease Classification and Treatment Approach

Cutaneous PAN is classified as nonsevere disease because it lacks life- or organ-threatening manifestations, presenting instead with uncomplicated cutaneous disease such as nodules, livedo reticularis, and ulcerations. 1 This classification is critical because it determines the treatment intensity required.

First-Line Treatment Strategy

Combination therapy with non-glucocorticoid immunosuppressive agents plus glucocorticoids is recommended over glucocorticoid monotherapy. 1 The rationale for this approach includes:

• Glucocorticoid-sparing effect: Adding immunosuppressive agents allows for lower cumulative steroid doses, reducing long-term toxicity 1
• Improved disease control: Although some patients achieve remission with steroids alone, a substantial number ultimately require additional therapy, making upfront combination treatment more practical 1
• Prevention of progression: Early aggressive treatment may prevent evolution to more severe manifestations 2

Specific Medication Regimens

Glucocorticoid dosing for cutaneous PAN:

• Moderate-dose oral glucocorticoids: Prednisone 0.25–0.5 mg/kg/day (adults; generally 10–40 mg/day) 1
• Taper slowly once disease control is achieved 1

Non-glucocorticoid immunosuppressive options:

• Azathioprine (preferred first-line agent) 1
• Methotrexate (alternative first-line agent) 1
• Mycophenolate mofetil has not been well studied in PAN and should be avoided 1

Alternative Approaches for Mild Cases

For patients with very mild cutaneous manifestations and strong preferences to avoid immunosuppression, a trial of short-course moderate-dose corticosteroids may be considered, with close monitoring for inadequate response. 3 However, this contradicts the guideline-based approach and should only be used in exceptional circumstances with shared decision-making. 1

NSAIDs alone (salicylates) may relieve pain and symptoms in patients with very moderate flare-ups but do not address the underlying inflammatory process and should not be considered definitive treatment. 3, 2

Duration of Treatment

Discontinue non-glucocorticoid immunosuppressive therapy after 18 months of sustained remission rather than continuing indefinitely. 1 This recommendation balances the risk of relapse against the cumulative toxicity of prolonged immunosuppression.

Special Considerations

Streptococcal Association

• Check anti-streptolysin O (ASO) titers in all patients 3
• Treat with penicillin if ASO titers are elevated, as streptococcal infection may trigger or perpetuate cutaneous PAN 3

Hepatitis B Screening

• Always exclude HBV-associated PAN before initiating immunosuppression, as HBV-related disease requires a completely different treatment approach centered on antiviral therapy rather than immunosuppression 2, 4, 5

Monitoring Strategy

• Serial clinical examinations to assess skin lesions, pain, and systemic symptoms 1
• Regular assessment for development of systemic manifestations that would reclassify the disease as severe 1
• Monitor for glucocorticoid-related adverse effects, particularly with prolonged use 1

Common Pitfalls to Avoid

Do not treat cutaneous PAN with cyclophosphamide unless it progresses to severe systemic disease with organ-threatening manifestations. 1 Cyclophosphamide is reserved for severe PAN and exposes patients to unnecessary toxicity when used for isolated cutaneous disease.

Do not use superficial skin punch biopsies for diagnosis, as they miss the medium-sized vessels in the deep dermis where the pathology occurs. 1, 6 Always obtain deep-skin biopsies reaching the dermis and subcutaneous tissue.

Do not assume all cutaneous nodular disease is benign cutaneous PAN. Perform abdominal vascular imaging to exclude systemic involvement if there are any concerning features such as weight loss, hypertension, or laboratory abnormalities. 1