What are the treatment options for a 60‑year‑old woman with severe cutaneous sarcoidosis who is allergic to hydroxychloroquine and has inadequate control on low‑dose oral prednisone and methotrexate 15 mg weekly?

Treatment Options for Severe Cutaneous Sarcoidosis with Inadequate Control

Add infliximab as a third-line biologic agent to your current regimen, as it is the preferred treatment for refractory cutaneous sarcoidosis that has failed corticosteroids and methotrexate. 1, 2

Immediate Next Steps: Optimize Current Therapy

Before escalating to biologics, ensure methotrexate is optimized:

• Increase methotrexate to 20-25 mg weekly (you are currently on 15 mg), as doses up to 25 mg weekly are commonly used in sarcoidosis and may provide better disease control. 1, 3
• Switch from oral to subcutaneous methotrexate administration if not already done, as this improves bioavailability and may enhance efficacy. 1
• Allow 3-6 months at the optimized dose to assess therapeutic response before declaring treatment failure. 1, 2

Third-Line Biologic Therapy: Infliximab

If disease remains inadequately controlled after optimizing methotrexate, proceed to infliximab:

• Infliximab is the first-choice biologic agent for cutaneous sarcoidosis refractory to corticosteroids and methotrexate, with multiple clinical trials supporting its efficacy specifically for skin manifestations. 1, 2
• Dosing regimen: 5 mg/kg IV at weeks 0,2, and 6, followed by maintenance infusions every 4-8 weeks. 4, 2
• Combining infliximab with low-dose methotrexate (continuing your current 15-20 mg weekly) may reduce the risk of developing anti-drug antibodies and improve long-term efficacy. 2
• Screen for latent tuberculosis before initiating anti-TNF therapy, as reactivation is a serious risk. 2

The European Respiratory Society specifically recommends infliximab for patients with cutaneous sarcoidosis who have failed glucocorticoids, and it has demonstrated effectiveness in reducing skin lesions. 2

Alternative Third-Line Options

If infliximab is contraindicated or not accessible:

• Adalimumab (40 mg subcutaneously weekly or every 2 weeks) is an alternative anti-TNF agent with some evidence of effectiveness in cutaneous sarcoidosis, though less robust than infliximab. 1, 5
• Rituximab has limited data but has shown some effectiveness in refractory sarcoidosis cases, though it is not the preferred biologic. 1

Adjunctive Topical Therapy

While systemic therapy is being optimized:

• Apply potent topical corticosteroids (clobetasol 0.05%) to localized lesions for symptomatic relief. 5
• Consider intralesional triamcinolone (3-10 mg/mL) for particularly disfiguring or symptomatic individual lesions. 5
• Topical tacrolimus 0.1% may help with localized skin disease, particularly for symptomatic redness or itching. 1

Important Monitoring and Prophylaxis

Given your multi-drug immunosuppression:

• Consider Pneumocystis jirovecii pneumonia prophylaxis (trimethoprim-sulfamethoxazole single-strength daily or double-strength three times weekly) if you are on ≥20 mg prednisone equivalent with methotrexate for >6 months. 1
• Ensure pneumococcal and annual influenza vaccination. 2
• Monitor for methotrexate toxicity with complete blood count and liver function tests every 8-12 weeks. 3
• Proton pump inhibitor for gastrointestinal prophylaxis while on corticosteroids. 4

Treatment Duration and Goals

• Continue infliximab for 2-3 years if you achieve a good response, then consider discontinuation after demonstrating disease stability for at least 2-3 years. 2
• Taper prednisone to ≤10 mg daily as soon as disease control is achieved with the addition of infliximab, to minimize long-term steroid toxicity including weight gain and reduced quality of life. 1

Critical Pitfalls to Avoid

• Do not continue inadequate therapy indefinitely—if there is insufficient response after 3-6 months of optimized methotrexate, escalate to biologics rather than accepting poor disease control. 1, 2
• Avoid prolonged high-dose corticosteroid monotherapy, as this causes significant toxicity without addressing the underlying disease progression. 2
• Do not use etanercept, as it has been found ineffective in most sarcoidosis patients. 1

Why Not Other Options?

Since you are allergic to hydroxychloroquine, this eliminates what would otherwise be an excellent option for cutaneous sarcoidosis (hydroxychloroquine is particularly effective for skin manifestations and would typically be combined with topical steroids as first-line therapy). 2, 6, 7 Azathioprine and leflunomide are alternative second-line agents but are generally less effective than methotrexate for cutaneous disease. 3 Thalidomide has shown promise in cutaneous sarcoidosis but has restricted access due to teratogenicity and is typically reserved for cases where other options have failed. 5, 8