Upadacitinib for treatment‐resistant Lichen amyloidosis

Dear Editor, Lichen amyloidosis (LA) is a skin-limited amyloidosis which occurs following deposition of extracellular heterogenic amyloid proteins in the dermis. Along with macular and nodular amyloidosis, LA belongs to the group of primary cutaneous localized amyloidosis.1 The disease occurs sporadically and in 10% with a familial background (with mutations normally found in OMSRβ and IL31RA, genes encoding the interleukin (IL-)31 receptor subunits oncostatin-M and IL-31 receptor A).2 LA occurs following apoptotic degeneration of basal keratinocytes and liberation of cytokeratin in the dermis, where is converted into amyloid material. Phenotypically LA shows disseminated grey-brown to red lichenoid or verruciform papules with a tendency to coalesce into indurated plaques, most frequently affecting shins, ankles, dorsa of the feet, upper arms and back.3 The main symptom is the constant and disabling itch, sometimes accompanied by pain, which dramatically limits quality of life. The primary therapeutic objective therefore is the management of itch.3 Yet, treatment options are scarce.1 Beside application of topical steroids, which are considered the gold standard, topicals (vitamin D3-derivates, retinoids, capsaicin and tacrolimus), systemic drugs (retinoids, mycophenolate mofetil, ciclosporin A, amitriptyline), phototherapy modalities (narrow band UVB or PUVA) and laser treatments (carbon dioxide-, erbium-, pulsed-dye) have shown efficacy.1 Here, we report of a 41-year-old man of Caucasian ethnicity with a positive family history of LA who was referred to our centre due to unquenchable itch and pain on the back, arms and legs. Clinically, he presented coalescent, skin coloured, lichenoid papules of 2–3 mm size, which covered his whole upper back. Scattered papules were present on the upper arms and shins (Figure 1a). A skin biopsy from the upper back showed compact orthohyperkeratosis, epidermal hyperplasia and hypergranulosis, pincer-like extension of the rete ridges enclosing homogenized connective tissue with individual pigmented cells in the papillary dermis, single dyskeratotic cells and a superficial perivascular lymphohistiocytic infiltrate with amorphous eosinophilic material (Figure 2a). Based on these findings, we confirmed the diagnosis of LA. A treatment with topical steroids (mometasone and clobetasol) and narrow band UVB (UVB-311 nm) phototherapy were of no benefit. After 4 weeks, we added oral acitretin 25 mg daily. This approach did not reduce itch and pain either. Based on first clinical and experimental reports and pathophysiological considerations on LA, we decided for a compassionate care use of upadacitinib 30 mg daily. Upadacitinib is a Janus kinase 1 inhibitor (JAK1i).4-7 Dermatology Life Quality Index before treatment was 26 and itch—as assessed by the means of the Visual Analogue Scala (VAS)—was 9/10. Over the 3 months of treatment with upadacitinib, we could observe a slight improvement of skin changes with a modest flattening of skin papules. Importantly, the patient reported from an impressive reduction of itch and pain (Figure 2b). Histologically, we observed a reduction in epidermal thickness (from 560 μm at baseline, to 520 μm after 1 and 280 μm after 3 months of treatment), thinning of the stratum corneum with minimal acanthosis, normalization of the rete ridges, reduced dermal amyloid deposition and reduction of the inflammatory infiltrate (Figure 2a). Upadacitinib has been shown to profoundly ameliorate itch in patients with pruriginous conditions like atopic dermatitis8 but also in heritable disorders like epidermolysis bullosa.9 This can be explained by the effects of upadacitinib on inflammatory pathways and on the neurosensory system, and more specifically on the interruption of IL-31 signalling, which is a central mediator in T-cell-mediated itch.4 JAK1i have a direct effect on T-cells, but also on the neurosensory system by blocking IL-31 and IL-4 signalling in primary afferent sensory neurons, which carry receptors for both cytokines.4, 10 This report shows first evidence that selective JAK1 inhibition can control severe itch in patients with treatment unresponsive skin disorders like LA. Dr. Farzan Solimani is participant in the BIH Charité Clinician Scientist Program funded by the Charité – Universitätsmedizin Berlin, and the Berlin Institute of Health at Charité (BIH). The patient in this manuscript have given written informed consent to publication of their case details. The authors declare no conflict of interests.