Dear Editor,
Lichen Amyloidosis (LA) is an uncommon, primary cutaneous amyloidosis associated with chronic, idiopathic pruritus. Clinical presentation of LA includes skin colored to hyperpigmented, papules coalescing into plaques with a rippled appearance on the extensors.1 LA most commonly presents in the fifth to sixth decade of life and has no curative treatments. Overall response to current therapies is poor. Here, we discuss Janus kinase (JAK) inhibition as a targeted treatment strategy for LA following a case showing complete response to the JAK inhibitor (JAKi) upadacitinib.
A 66-year-old female presented to clinic with intense pruritus of the shins for 40 years. Physical examination showed hyperpigmented, hyperkeratotic papules coalescing into rippling linear plaques with thick overlying scale on the lower legs between the knees and ankles (body surface area 10%) (Figure 1). Punch biopsy revealed lichenification, hyperkeratosis, and squamatization of the basal cells, with amorphous globi of eosinophilic material and scattered pigment laden macrophages adjacent to the dermal-epidermal junction. (Figure 2). Congo red staining was focally positive for amyloid deposits. The findings were consistent with lichen amyloidosis (LA). Over many years, her LA and accompanying itch were unresponsive to numerous topical (corticosteroids, tacrolimus, menthol, pramoxine), oral (hydroxychloroquine, methotrexate, apremilast, acitretin, antihistamines, tricyclic antidepressants, anticonvulsants), photo- (narrowband UVB), and injectable (dupilumab, etanercept, corticosteroids) therapy. Oral corticosteroids and cyclosporine provided only mild relief, but both were associated with intolerable side effects. Following a discussion of therapeutic risks and benefits, she was started on the JAK inhibitor (JAKi) upadacitinib at 15 mg daily. Within 1 week her itch was eliminated (NRS worst itch from 10 to 0), and after one month, her legs were almost clear (IGA 1) with complete regression of the rippled plaques after three months (IGA 0) (Figure 1). She continues to remain symptom after one year of upadacitinib.
Figure 1.
Lichen amyloidosis on the legs at baseline and then one and three months following oral upadacitinib.
Figure 2.
Histopathology showing lichen amyloidosis with hematoxylin and eosin (4x, 20x) and congo red (20x) stains.
Lichen amyloidosis results from extracellular deposition of amyloid-derived intermediate filaments in the skin.2 Chronic pruritis and scratching play a central role in disease pathogenesis. Diagnosis is dependent upon history, clinical exam, and ultimately, histopathology showing amyloid deposition.
Evidence showing consistent benefit from any one specific treatment modality is limited. Reported treatment options associated with partial relief include topical or intralesional corticosteroids, topical tacrolimus, phototherapy, laser therapy, and systemic medications such as oral retinoids, cyclosporine, cyclophosphamide, and thalidomide. These agents are frequently used due their immunomodulatory effects in relieving itch and breaking the itch-scratch cycle. This case report suggests that upadacitinib might be a highly efficacious, targeted treatment modality for patients with LA. JAK signaling may indeed occupy a central role in LA itch and inflammation as has been recently characterized in type 2 inflammatory diseases (T2IDs).3 Amyloid deposition is thought to be driven by a chronic itch-scratch cycle in LA2 – reminiscent of the neuroinflammation-driven pathology observed in T2IDs like atopic neurodermatitis and prurigo nodularis. Breaking the itch-scratch cycle may be responsible for the rapid clinical response observed in our case.
Further studies are needed to understand the role of JAK signaling in the pathophysiology of LA and the role of JAKi’s in treatment of LA.
Abbreviations used:
- LA
Lichen Amyloidosis
- UVB
Ultraviolet B
- JAK
Janus kinase
- JAKi
Janus kinase inhibitor
- DVT
Deep venous thrombosis
- PE
Pulmonary embolism
- NRS
Numeric rating scale
- IGA
Investigator’s global assessment
- T2IDs
Type 2 inflammatory diseases
Footnotes
Conflicts of interest: RC has served as an advisory board member, consultant, and/or investigator for AbbVie, Arcutis, Arena, Argenx, Beiersdorf, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, EPI Health, Incyte, L’Oréal, National Eczema Association, Pfizer Inc., Regeneron, Sanofi, and UCB, and speaker for AbbVie, Dermavant, Eli Lilly and Company, EPI Health, Incyte, LEO Pharma, Pfizer Inc., Regeneron, Sanofi, and UCB.
References
- 1.Guillet C, Steinmann S, Maul JT, Kolm I. Primary Localized Cutaneous Amyloidosis: A Retrospective Study of an Uncommon Skin Disease in the Largest Tertiary Care Center in Switzerland. Dermatology. 2022;238(3):579–586. doi: 10.1159/000518948 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Schreml S, Szeimies RM, Vogt T, Landthaler M, Schroeder J, Babilas P. Cutaneous amyloidoses and systemic amyloidoses with cutaneous involvement. Eur J Dermatol. Mar-Apr 2010;20(2):152–60. doi: 10.1684/ejd.2010.0842 [DOI] [PubMed] [Google Scholar]
- 3.Oetjen LK, Mack MR, Feng J, et al. Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch. Cell. Sep 21 2017;171(1):217–228 e13. doi: 10.1016/j.cell.2017.08.006 [DOI] [PMC free article] [PubMed] [Google Scholar]