What are potential systemic treatments for a 63-year-old woman with severe widespread cutaneous sarcoidosis who is allergic to hydroxychloroquine (Plaquenil) and doxycycline (Vibramycin)?

Systemic Treatment Options for Severe Widespread Cutaneous Sarcoidosis

For a 63-year-old woman with severe widespread cutaneous sarcoidosis who is allergic to hydroxychloroquine and doxycycline, methotrexate should be considered as the first-line systemic treatment option, followed by TNF-alpha inhibitors like infliximab if methotrexate is ineffective or not tolerated. 1

First-Line Treatment Options

Systemic Corticosteroids

• Oral corticosteroids remain the mainstay of treatment for severe cutaneous sarcoidosis 1
• Typically start with prednisone 0.5-1 mg/kg daily
• Can achieve improvement or remission in up to two-thirds of patients 1
• However, effects are often limited to the duration of treatment, with recurrences common upon tapering 1
• For lupus pernio specifically, only 20% of patients achieve complete or near-complete resolution with systemic corticosteroids alone 1
• Long-term use associated with substantial side effects, especially in older patients

Methotrexate

• Recommended as a steroid-sparing agent or first-line therapy when corticosteroids are contraindicated 1, 2
• Dosing: 10-30 mg weekly 2
• Monitor for hematological, gastrointestinal, pulmonary, and hepatic toxicities
• Can be used alone or in combination with low-dose corticosteroids

Second-Line Treatment Options

TNF-alpha Inhibitors

• Consider for refractory disease when first-line treatments fail 1
• Infliximab: 3-10 mg/kg IV at weeks 0,2, and 6, then as needed 2
  • Most widely studied biological agent for cutaneous sarcoidosis
  • Particularly effective for refractory cutaneous disease 1
• Adalimumab: 40 mg subcutaneously weekly or every 2 weeks 2
  • Alternative when infliximab is not tolerated or contraindicated

Other Immunosuppressive Agents

• Azathioprine: Alternative steroid-sparing agent 1, 3
• Leflunomide: Option for patients who cannot tolerate methotrexate 3
• Mycophenolate: Consider for patients with contraindications to other agents 3

Thalidomide

• Dosage: 50 to >400 mg/day 2
• Limited but promising supporting data for cutaneous sarcoidosis
• Restricted access in many countries due to teratogenicity
• Not a concern in a 63-year-old woman, but requires monitoring for neuropathy

Treatment Algorithm

1. Initial Treatment:

   • Start with oral corticosteroids (prednisone 0.5-1 mg/kg/day) if no contraindications
   • OR start with methotrexate (10-15 mg weekly, titrate up to 25 mg as needed) if corticosteroids are contraindicated

2. If inadequate response after 4-8 weeks:

   • Add methotrexate if started on corticosteroids alone
   • OR consider switching to TNF-alpha inhibitor (infliximab)

3. For refractory disease:

   • Consider infliximab (if not already tried)
   • Alternative options include other immunosuppressants (azathioprine, leflunomide, mycophenolate)
   • Consider thalidomide for highly refractory cases

4. Monitoring:

   • Assess response every 4-8 weeks initially
   • Once stable, can extend to every 3-6 months
   • Monitor for drug-specific adverse effects

Special Considerations

• Lupus pernio: More resistant to treatment and may require more aggressive therapy 1, 4
• Combination therapy: Often more effective than monotherapy for severe cases
• Steroid-sparing strategies: Important to minimize long-term corticosteroid exposure
• Rituximab: May be considered for severe, refractory systemic disease when other options fail 1

Caveats and Pitfalls

• Avoid assuming all antimalarials are contraindicated - if the patient is only allergic to hydroxychloroquine, chloroquine might still be an option (though cross-reactivity is possible)
• Be aware that methotrexate can take 4-12 weeks to show full effect
• TNF-alpha inhibitors carry increased risk of infections and should be used with caution
• Always screen for latent tuberculosis before starting TNF-alpha inhibitors
• Consider the impact of comorbidities when selecting therapy (e.g., liver disease would contraindicate methotrexate)

The most recent evidence suggests that while corticosteroids remain effective, early introduction of steroid-sparing agents is preferred to minimize long-term corticosteroid exposure and associated adverse effects 4. For this 63-year-old woman with severe widespread cutaneous sarcoidosis, methotrexate represents the most appropriate first-line option given her allergies to hydroxychloroquine and doxycycline.