Researchers from the National Defense Medical College in Tokorozawa, Japan, discovered a novel mechanism that might contribute to hyperpigmentation in cutaneous lesions of mastocytosis, including systemic mastocytosis (SM).
The mechanism is mediated by stem cell factor (SCF), protease-activated receptor-2 (PAR-2), and phosphorylated Erk1/2 (pErk1/2).
“Interaction of mast cell accumulation in the dermis with epidermal keratinocytes through the mast cell protease/PAR-2 axis appears to participate in the hyperpigmentation of cutaneous lesions of mastocytosis in addition to melanocyte activation by SCF released from accumulating mast cells,” the researchers explained in a letter to the editor published in the Journal of the European Academy of Dermatology and Venereology.
They observed basal hyperpigmentation in skin samples from patients with mastocytosis, which was not associated with an increase in the number of melanocytes. Immunofluorescence analyses showed an abnormal accumulation of mast cells expressing mast cell tryptase in the upper dermis, as well as upregulation of PAR-2 in mastocytosis pigmented lesions. Moreover, the expression of epidermal PAR-2 was higher in skin lesions than in healthy skin.
Read more about SM etiology
Further studies showed that pErk1/2 was expressed in the epidermis of mastocytosis samples, but it was scarcely observed in healthy skin, suggesting that PAR-2 could contribute to melanosome uptake. SCF was also detected in accumulating mast cells from patients’ skin samples, and its expression was enhanced in skin lesions compared to healthy skin, suggesting that SCF from pathological mast cells may also affect melanogenesis in melanocytes within skin lesions.
The researchers used skin samples from 3 patients with different subtypes of mastocytosis, including SM, urticaria pigmentosa (ie, a variant of maculopapular cutaneous mastocytosis), and cutaneous mastocytoma, and from healthy control individuals.
Reference
Hashimoto T, Okuzawa M, Okuno S, Satoh T. Mast cell protease/protease-activated receptor-2 axis: another mechanism of pigmentation in cutaneous lesions of mastocytosis. J Eur Acad Dermatol Venereol. Published online December 21, 2022. doi:10.1111/jdv.18823
