Pseudoxanthoma elasticum-like papillary dermal elastolysis: report of four Japanese cases and an immunohistochemical study of elastin and fibrillin-1

Abstract

We report four patients with pseudoxanthoma elasticum-like papillary dermal elastolysis (PDE). Multiple small papules on the neck, clinically resembling pseudoxanthoma elasticum, and loss of the elastic fibre network in the papillary dermis were found in each case. Immunohistochemical staining for elastin and fibrillin-1 in one patient demonstrated the disappearance of elastin and fibrillin-1 in the papillary dermis. Site-matched normal skins of the elderly showed intact elastin but a lack of fibrillin-1 in the papillary dermis. The younger normal skins revealed intact elastin and fibrillin-1. The results suggest that fibrillin-1 is absent from the papillary dermis of the normal-appearing neck skin of the elderly and that the primary defect in PDE may be in elastin rather than in fibrillin-1.

Differential Inhibition of Membrane Type 3 (MT3)-Matrix Metalloproteinase (MMP) and MT1-MMP by Tissue Inhibitor of Metalloproteinase (TIMP)-2 and TIMP-3 Regulates Pro-MMP-2 Activation

“…A recent study using chimeric MT-MMPs demonstrated that the catalytic domains of MT1-and MT3-MMP, which are responsible for TIMP-2 binding, are major determinants for the lower efficiency of MT3-MMP in promoting pro-MMP-2 activation (67). Together, these observations suggest that under conditions of MT1-MMP and MT3-MMP co-expression in cells (35,68), activation of pro-MMP-2 is likely to proceed preferentially via the MT1-MMP/TIMP-2 axis.…”

“…MT3-MMP (MMP-16), which was originally cloned from human melanoma tissue and human placenta (30), is expressed in a variety of normal (30 -33) and tumor (7,(33)(34)(35) tissues. Studies with a purified active MT3-MMP lacking the transmembrane domain have shown that the truncated enzyme cleaves a variety of ECM components and is inhibited by TIMP-2 and TIMP-3 but not by TIMP-1 (29).…”

Pseudoxanthoma elasticum–like papillary dermal elastolysis: A large case series with clinicopathological correlation

“…8 Some authors explain the exclusive female predominance with the likelihood of women to seek medical care more often for cosmetic concerns. 5 The pathogenesis of PXE-like PDE is still obscure. It is mainly believed that it is related to ultraviolet radiation, intrinsic aging, or abnormal elastogenesis.…”

The Multifaceted Complexity of Genetic Diseases: A Lesson from Pseudoxanthoma Elasticum

“…However, the pathomechanistic details and the role of predisposing genetic factors are unknown. In papillary dermal elastolysis, white-yellow papules resembling PXE can be observed in aged women (60-80 years), although, in contrast to PXE, these lesions are histologically characterized by loss of elastin in the papillary dermis (Ohnishi et al, 1998). Moreover, elastic fibres similar to those of PXE have been observed in the lesional skin of patients with a variety of inflammatory skin diseases in the absence of clinical evidence of PXE (Bowen et al, 2007), in calcific elastosis, lipedema, lipodermatosclerosis, granuloma annulare, lichen sclerosus, morphea profunda, erythema nodosum, septal panniculitis, basal cell carcinoma and fibrosing dermatitis (Bowen et al, 2007;Taylor et al, 2004).…”