NEW YORK – Better understanding of disease pathology and possible therapies have opened the pathway to improved outcomes for patients with primary cutaneous amyloidosis (PCA), according to Jordan P. Talia, MD, director of complex medical dermatology at the Icahn School of Medicine at Mount Sinai Hospital, New York.
PCA is a rare depositional disorder estimated to affect fewer than 50,000 people in the United States. The exact cause of the disease is not completely understood.
"In the past, there were not a lot of good options for treating many depositional skin disorders but a new framework for thinking about and treating these diseases is emerging," Talia said at the annual Mount Sinai Winter Symposium on Advances in Medical and Surgical Dermatology, where he presented an update on cutaneous amyloidosis.
Accurately diagnosing and categorizing amyloidosis is key to better treatment, Talia said. Cutaneous amyloidosis can be broadly separated into two disease states: PCA, which is limited to the skin and is treated by dermatologists, and secondary cutaneous amyloidosis, which involves internal organs in addition to the skin and has historically been managed by rheumatologists and hematologists.
Among patients with PCA, the disease can be categorized as macular amyloidosis (MA) and lichen amyloidosis (LA), with material derived from epidermal keratinocytes, and nodular amyloidosis (NA), with material derived from immunoglobulin light chain amyloids. In patients with suspected NA, Talia suggests testing for autoimmune disorders.
Standard-of-care treatment options for treating MA and LA have been systemic therapies, including cyclosporine, cyclophosphamide, colchicine, and retinoids; topical treatments, including tacrolimus, corticosteroids, dimethyl sulfoxide, capsaicin, and retinoids; laser and light treatments, including CO2, fractionated CO2, Nd:YAG, and Erbium YAG lasers; and phototherapy (narrowband UVB and UVA with and without psoralen). However, these treatments have had limited efficacy because they are "not geared towards disease-generating genes," Talia noted.
However, mutations in the OSMR gene, encoding OSMR beta, and the IL31RA gene, encoding lIL-31RA, have been identified in some families with PCA.
In addition, immunohistochemistry analysis of skin biopsies of patients with primary cutaneous localized amyloidosis (LA and MA) revealed an increase in expression of OSMR beta and IL-31RA compared with control groups. This insight could eventually lead to potential genetic targets for LA and MA treatments, Talia said.
Findings related to these targets in conjunction with case studies describing successful use of monoclonal antibodies and Janus kinase (JAK) inhibitors to treat patients with PCA highlight the "new framework" for treating PCA, he said.
He referred to a case study of two adults with atopic dermatitis (AD) and concomitant LA treated with the monoclonal antibody dupilumab at the standard AD dose who achieved near complete clearing of their skin after treatment.
Similarly, he also described a case of a 41-year-old man with a family history of LA who exhibited diffuse flesh-colored papules on his trunk and upper and lower extremities. The patient had failed treatment (with no improvement in pain or itch) with topical steroids, narrowband UVB, and concurrent oral acitretin 25 mg daily. Subsequently the patient was treated with the oral JAK inhibitor upadacitinib at 30 mg daily and experienced, "significant improvement."
These findings, Talia said, support further research in these treatments for patients with MA and LA:
- Topical JAK inhibitors
- Dupilumab, tralokinumab, and lebrikizumab for LA in patients without concurrent AD
- IL-31RA inhibition with nemolizumab
- OSMR beta inhibition with vixarelimab
Talia had no relevant disclosures to report.
Myles Starr in a medical journalist based in New York City.
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