A 65-year-old man with treatment-refractory primary cutaneous amyloidosis experienced rapid pruritus relief and marked lesion improvement following off-label treatment with ivarmacitinib, according to a case report published in Frontiers in Medicine.
Primary cutaneous amyloidosis, also known as primary localized cutaneous amyloidosis, is a chronic pruritic dermatosis characterized by amyloid deposition in the dermis without systemic involvement. Researchers described a patient with a 15-year history of severe pruritus involving the limbs, buttocks, back, and other body areas, followed by the development of hyperpigmented papules on the limbs and buttocks.
The patient had previously received levocetirizine, loratadine, compound glycyrrhizin, topical corticosteroids, tacrolimus, acitretin, and thalidomide. Some therapies produced insufficient clinical improvement, whereas others were discontinued because of adverse effects including dry mouth, cracked lips, epistaxis, and numbness of the lips and limbs.
The patient had no significant medical history, no family history of similar skin disorders, and no history of atopic dermatitis, allergic rhinitis, asthma, or conjunctivitis. Physical examination showed rough, hyperpigmented skin with numerous dark brown hard papules on the limbs and buttocks, some with bleeding, excoriation, and crusting. Baseline pruritus was rated 10 on a 10-point visual analog scale.
Histopathologic examination of a left leg biopsy demonstrated hyperkeratosis, acanthosis, eosinophilic amorphous deposits in the papillary dermis, and perivascular inflammatory infiltrate. Congo red staining showed brick-red deposits along collagen bundles, supporting the diagnosis of primary cutaneous amyloidosis.
Because of poor tolerance and inadequate response to prior therapies, the researchers initiated ivarmacitinib, a selective Janus kinase 1 (JAK1) inhibitor, at 4 mg orally once daily.
The patient reported pruritus relief on the first night of treatment. Within 1 week, pruritus had largely resolved. At 1 month, hyperkeratotic and lichenified plaques had flattened, hyperpigmentation had faded, and the visual analog scale score had decreased to 0. By 2 months, papules and plaques had largely subsided, leaving faint postinflammatory hyperpigmentation.
No adverse events or laboratory abnormalities attributable to ivarmacitinib were reported during the 2-month treatment period and follow-up.
The researchers noted that dysregulated immune responses involving interleukin (IL)-4, IL-13, IL-31, and Janus kinase/signal transducer and activator of transcription signaling may contribute to primary cutaneous amyloidosis pathogenesis. They also noted that prior case reports described improvement in lichen amyloidosis associated with atopic dermatitis following treatment with the JAK inhibitors baricitinib and abrocitinib. In contrast, the current case involved isolated primary cutaneous amyloidosis without comorbid atopic dermatitis.
The paper additionally highlighted a mechanistic distinction between ivarmacitinib and dupilumab. Whereas dupilumab targets IL-4 and IL-13 signaling, ivarmacitinib was proposed to simultaneously inhibit IL-31, IL-4, and IL-13 pathways implicated in pruritus and T helper 2 inflammation. The drug demonstrated activity against these inflammatory and pruritic signaling pathways in atopic dermatitis studies. The researchers also cited clinical trial data in atopic dermatitis suggesting ivarmacitinib may have a lower propensity for serious infections and herpes zoster reactivation compared with pan-JAK inhibitors, although this was not evaluated in the current case report.
“This case highlights the feasibility of using ivarmacitinib to treat isolated PCA phenotypes without comorbid AD, expanding the therapeutic landscape for this condition,” wrote lead study author Xiaofan Liao, of the Department of Dermatology, Affiliated Nanshan Hospital of Shenzhen University, Shenzhen, China, and colleagues.
The researchers emphasized that the findings were limited by the single-patient design and short follow-up duration. They called for further studies to confirm efficacy, establish optimal dosing, evaluate long-term safety, and clarify the precise role of JAK1 inhibition in primary cutaneous amyloidosis.
Disclosures: The researchers reported funding from the Sanming Project of Medicine in Shenzhen and the Shenzhen Medical Research Fund. They declared no conflicts of interest
Source: Fronters in Medicine
