Off-Label Treatments for Papulosquamous Diseases: Insights from Dr. Adam Friedman

At the 2025 ODAC Dermatology Conference, we had the privilege of hearing from Dr. Adam Friedman, a renowned expert in dermatology and the chair of the department of dermatology at the George Washington, as he shared his expert insights into the evolving landscape of off-label treatments for challenging dermatologic conditions. Dr. Friedman addressed the complexities of managing conditions such as severe seborrheic dermatitis, pityriasis rosea, lichen planus, pityriasis rubra pilaris (PRP), and discoid lupus. He provided a deep dive into both historical and novel therapeutic strategies, shedding light on emerging off-label options and their clinical efficacy in improving patient outcomes. The focus was on offering dermatologists a deeper understanding of novel and sometimes unconventional treatment options for conditions that are difficult to manage with standard therapies. His presentation not only outlined the treatment protocols but also emphasized the importance of personalized care in the management of these persistent and difficult-to-treat conditions.

Severe Seborrheic Dermatitis

Dr. Friedman provided an in-depth look at systemic therapies for severe cases of seborrheic dermatitis that don’t respond to typical topical treatments. He recommended oral antifungals such as itraconazole, fluconazole, and terbinafine, with specific dosing schedules provided¹:

• • Itraconazole: 200mg daily for 7 days, followed by a maintenance dose of 200 mg once daily for two days each month.
  • Fluconazole: 200mg weekly for 4 weeks or 300 mg weekly for 2 weeks.
  • Terbinafine: 250mg daily for 4-6 weeks.

For those with more persistent or severe cases, Dr. Friedman also discussed low-dose isotretinoin (10-20 mg every other day), which has shown greater efficacy in improving seborrheic dermatitis compared to oral itraconazole, antifungal shampoos, or salicylic acid-based soaps.² He noted that isotretinoin, even at lower doses, led to greater symptom relief, especially in cases that did not respond to standard treatments. The pooled dose used across various studies was 9.2 mg per day for 4 months, demonstrating significant improvements in the severity of symptoms.

Pityriasis Rosea

Pityriasis rosea is a self-limiting condition often treated with supportive measures, but Dr. Friedman highlighted some promising off-label treatments. Although historically we use topical corticosteroids, oral-antihistamines, and anti-itch lotions, these often can have limited efficacy. Given the involvement of HHV6/7, he discussed the use of valacyclovir (1g three times daily for 7 days) as an off-label option, suggesting that this antiviral could provide improvement, with some patients reporting significant benefits within two weeks of starting treatment.³ Additionally, L-lysine supplementation (3 grams for up to three days as a loading dose, followed by 500 mg daily for 30 days) was mentioned as another off-label treatment, although more data may be needed to confirm its effectiveness.⁴

Lichen Planus

Lichen planus is a chronic inflammatory condition that affects the skin and mucous membranes, often with recalcitrant involvement. Dr. Friedman outlined several off-label treatments that have been shown to benefit patients with disseminated and recalcitrant disease:

• • Retinoids: Acitretin (17.5-30 mg daily) until remission then 10mg every day or every other day as tolerated and isotretinoin (0.3-0.5 mg/kg/day). For older patients, acitretin is a preferred systemic treatment due to its ability to provide immediate relief from both the inflammatory symptoms and itching associated with lichen planus. This retinoid helps normalize keratinocyte proliferation, which is essential in treating LP’s hyperkeratotic lesions. For younger patients with severe or recalcitrant LP, isotretinoin (0.3–0.5 mg/kg/day) has shown to be effective. Dr. Friedman mentioned that isotretinoin can help reduce the intensity of skin lesions in these patients, though it is typically reserved for more resistant cases. Isotretinoin’s effectiveness is largely due to its ability to reduce inflammation and normalizing epidermal turnover, offering a potent therapeutic approach for younger individuals.

• • Methotrexate (MTX): Although methotrexate (15–20 mg once weekly for duration of 10 weeks) is a common treatment for LP, Dr. Friedman expressed that he is less enthusiastic about using MTX compared to other options. Methotrexate is effective, but Dr. Friedman noted that the side effects profile, particularly liver toxicity, can make it less preferable in long-term management. He prefers other systemic therapies that may offer a better balance of efficacy and safety.
  • Antimalarials: Hydroxychloroquine (200 mg twice daily, max dose 5.5 mg/kg body weight) was noted as beneficial, especially in mucosal LP. However, Dr. Friedman cautioned that this antimalarial agent could sometimes induce a psoriasiform rash, which complicates its use in LP patients. Because of this potential adverse effect, hydroxychloroquine is not always the first-line choice, although it can be beneficial for some cases.
  • Dapsone: 50-150 mg daily was discussed as an option.

For mucosal LP, Dr. Friedman discussed other historical off-label offerings including but not limited to doxycycline (100 mg twice daily for 6 months), systemic corticosteroids (e.g., prednisolone 0.3–0.5 mg/kg/day), methotrexate (7.5-20 mg/weekly), hydroxychloroquine (200-400 mg qd for 6 months), retinoids, and lastly low dose cyclosporine (1–2.5 mg/kg).

Dr. Friedman pointed out the potential involvement of IL-17, a pro-inflammatory cytokine, in the pathogenesis of LP.⁵ With this understanding, biologic treatments targeting IL-17 have emerged as promising options. He shared a patient case with LP of the fingernails and toenails, who demonstrated significant improvement following treatment with secukinumab. This case supports the growing body of evidence suggesting that biologics targeting IL-17 may offer significant clinical benefits, especially in cases where other systemic treatments have failed.

Another case report presented by Dr. Friedman highlighted the use of dupilumab (300 mg every two weeks for two months), a monoclonal antibody targeting IL-4 and IL-13, in the management of lichen planus. This treatment showed notable improvement, particularly in itch control.

Discoid Lupus (DLE)

Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus that can cause scarring and pigmentation changes, particularly when left untreated. Dr. Friedman discussed the importance of photoprotection, smoking cessation, topical and intra-lesional steroids for limited disease.

For treatment of modest/refractory disease, the following off-label options were mentioned:

• • Prednisone (~0.5 mg/kg/day) for rapid symptom reduction
  • Hydroxychloroquine (200 mg QD-BID) (based on weight)
  • Quinacrine (100 mg QD)
  • Chloroquine (125-250 mg QD) (based on weight)

In addition, for treatment of diffuse/refractory disease, the following off-label options were mentioned:

• • Prednisone (~1 mg/kg/day)
  • Mycophenolate mofetil (1000-1500 mg BID)
  • Methotrexate (15-25 mg QWK)
  • Azathioprine (2-3 mg/kg/day)
  • Thalidomide (25-100 mg qHS), lenalidomide (2.5-10 mg qHS)
  • Dapsone (25-100 mg BID)

Dr. Friedman also briefly touched upon newer biologic agents like anifrolumab, an interferon receptor antagonist, which showed promise in systemic lupus erythematosus and could potentially benefit patients with DLE.

Pityriasis Rubra Pilaris (PRP)

Pityriasis rubra pilaris (PRP) is a rare and challenging condition to treat. Dr. Friedman emphasized the potential benefits of systemic retinoids, such as acitretin, in managing PRP, noting that it can help to reduce hyperkeratosis and inflammation. Methotrexate and UV therapy (specifically PUVA and narrowband UVB) were also suggested as options for managing the condition. Biologics like risankizumab and guselkumab have shown promise in recent studies.⁶

Dr. Friedman shared findings from PRP skin studies that compared samples from patients to those with psoriasis, atopic dermatitis, and healthy controls, which identified IL-1b as a key mediator in the inflammatory process, offering new insights into potential therapeutic targets.⁷

Conclusion

Dr. Friedman’s presentation provided an extensive review of off-label treatments for various dermatologic diseases, emphasizing the need for dermatologists to remain open to emerging therapies. The session showcased several treatment options that go beyond the conventional guidelines, often offering patients with difficult-to-treat conditions a better chance at symptom relief.

References:

1. 1. Desai S, McCormick E, Friedman A. An Up-to-Date Approach to the Management of Seborrheic Dermatitis. J Drugs Dermatol. 2022;21(12):1373-1374. doi:10.36849/JDD.1022
   2. King A, Tan MG, Kirshen C, Tolkachjov SN. Isotretinoin for the management of moderate-to-severe seborrheic dermatitis: A systematic review. J Am Acad Dermatol. 2023;89(5):1063-1066. doi:10.1016/j.jaad.2023.07.010
   3. Ashforth GM, Youssef S, Bhagavathi V, Wassef C, Miller JH. What’s old is new: Valacyclovir for the treatment of pityriasis rosea, a retrospective case series. JAAD Case Rep. 2023;37:98-102. Published 2023 May 20. doi:10.1016/j.jdcr.2023.05.015
   4. Dos Santos VAB, Pedrazini MC. L-lysine as an Alternative Treatment for Pityriasis Rosea (PR) [Letter]. Clin Cosmet Investig Dermatol. 2024;17:433-434. Published 2024 Feb 13. doi:10.2147/CCID.S461722
   5. Żychowska M, Batycka-Baran A, Baran W. Increased Serum Level and High Tissue Immunoexpression of Interleukin 17 in Cutaneous Lichen Planus: A Novel Therapeutic Target for Recalcitrant Cases?. Dis Markers. 2020;2020:6521274. Published 2020 Jul 24. doi:10.1155/2020/6521274
   6. Rahman SM, Ahmed F, Haque A. Role of IL-23 inhibitors including risankizumab and guselkumab in the treatment of pityriasis rubra pilaris. Arch Dermatol Res. 2024;316(6):334. Published 2024 Jun 6. doi:10.1007/s00403-024-03137-3
   7. Schmauch E, Severin Y, Xing X, et al. Targeting IL-1 controls refractory pityriasis rubra pilaris. Sci Adv. 2024;10(27):eado2365. doi:10.1126/sciadv.ado2365

This information was presented by Dr. Adam Friedman during the 2025 ODAC Dermatology Conference. The above session highlights were written and compiled by Dr. Nidhi Shah.