Upadacitinib Shows Promise in Refractory Lichen Amyloidosis

Lichen amyloidosis (LA) is a chronic, pruritic form of primary localized cutaneous amyloidosis characterized by deposition of keratin-derived amyloid in the skin without systemic involvement.¹ Treatment is challenging, and durable successes with conventional options (eg, topical/oral corticosteroids, colchicine, phototherapy) are largely anecdotal.² 

Recent reports suggest biologic and small-molecule approaches may help: several case reports describe improvement with dupilumab (Dupixent; Sanofi and Regeneron), and at least one report notes response to upadacitinib (Rinvoq; AbbVie), a selective JAK1 inhibitor, in LA.^3-6 Given the role of IL-31 in pruritic dermatoses and the centrality of JAK-STAT signaling, both IL-4/IL-13 blockade and JAK1 inhibition are mechanistically plausible; comparative evidence hints JAK inhibition may more strongly suppress IL-31 signaling than dupilumab in related disease contexts.^7-10

This case report describes a patient with long-standing, treatment-refractory lichen amyloidosis who experienced minimal benefit from dupilumab but achieved rapid and near-complete remission with upadacitinib.¹¹

Case Presentation

A woman in her late 20s presented with a decade-long history of intractable pruritic papules and plaques affecting her lower extremities. Examination revealed coalescing brown-to-brawny papules forming cobblestoned plaques extending from the ankles to the thighs. Standard therapies—including topical and oral corticosteroids, colchicine, and antihistamines—had failed to control symptoms. She had intermittently used commercial tanning beds with only partial relief.

A skin biopsy confirmed lichen amyloidosis. Although narrowband UV-B therapy was initially considered, insurance denial delayed further treatment, and the patient was lost to follow-up for 10 years. When she re-presented in her late 30s, disease had progressed to involve approximately 40% body surface area.

She was started on dupilumab (600 mg loading, followed by 300 mg every 2 weeks), which provided modest pruritus relief but no improvement in skin texture or pigmentation after 6 months. Dupilumab was discontinued, and upadacitinib15 mg orally once daily was initiated.

Within one month, the patient reported marked reduction in both pruritus and plaque thickness. By 6 months, she achieved complete resolution of itch and near-complete clearance of cutaneous lesions. She tolerated therapy well without adverse events.

Clinical Implications

This case provides several important insights into the management of lichen amyloidosis and highlights how targeted therapies may reshape treatment options for refractory disease:

• Refractory nature of LA: Patients often cycle through multiple conventional therapies with little improvement.
• Role of IL-31: Both dupilumab and upadacitinib downregulate IL-31, a cytokine central to pruritic dermatoses. Emerging evidence suggests JAK inhibitors may exert a stronger inhibitory effect than IL-4/IL-13 blockade alone.
• Rapid and sustained improvement: In this case, upadacitinib provided symptom relief within weeks and near-complete remission within months—outcomes rarely seen with traditional options.
• Future potential: Controlled studies are needed, but accumulating reports highlight JAK inhibition as a promising therapeutic avenue for patients with treatment-resistant LA.

Conclusion

Lichen amyloidosis remains a difficult-to-treat condition with limited therapeutic success from conventional options. This case demonstrates rapid and sustained remission with upadacitinib after failure of multiple therapies, including dupilumab. By targeting the JAK-STAT pathway and downstream pruritogenic cytokines such as IL-31, upadacitinib may offer a new treatment paradigm for refractory cases.

Jennifer Lightowler, MMSc, PA-C, is a board-certified dermatology physician assistant and medical writer in Connecticut.

References

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