Pathological characteristics of pigmented pretibial patches and vascular-immune abnormalities in diabetic patients

doi:10.12122/j.issn.1673-4254.2026.01.07

Abstract

Abstract:

Objective To explore pathological and immune cell infiltration characteristics of pigmented pretibial patches in diabetic patients. Methods Forty-two diabetic patients undergoing thigh amputation at Tianjin Medical University Chu Hsien-I Memorial Hospital were enrolled. Before the operation, the pretibial skin of the patients were examined and sampled for HE and Masson staining. The thickness of the epidermis and the density of blood vessels in the dermis were compared between patients with and without pigmented pretibial patches. The expressions of VEGFA and VEGFR2 in the skin tissues were detected using Western blotting, and CD4⁺ and CD8⁺ cells and the CD4/CD8 ratio were analyzed with immunohistochemical staining. Results Compared with the patients without pigmented pretibial patches, the patients with pigmented pretibial patches showed obvious thickening of the epidermal spinous layer, irregular downward extension of the epidermal projections, hyperkeratosis, melanin deposition in the basal layer, increased capillaries in the dermis, and localized, well-defined inflammatory cell infiltration around the blood vessels. In pigmented pretibial patches group, Masson staining revealed irregular arrangement, thickening and hyaline degeneration of collagen fibers, significantly increased epidermal thickness and blood vessel density in the dermis, increased CD4⁺ cells and the CD4/CD8 ratio, and reduced CD8⁺ cells. Conclusion The pigmented pretibial patches in diabetic patients show obvious pathological changes possibly due to vascular and immune abnormalities.

Key words: pigmented pretibial patches, diabetic dermopathy, diabetic complications, vascular-immune abnormalities

Xinbang LIU, Bai CHANG. Pathological characteristics of pigmented pretibial patches and vascular-immune abnormalities in diabetic patients[J]. Journal of Southern Medical University, 2026, 46(1): 66-73.

Figures/Tables 6

Fig.1 HE and Masson staining of skin tissues from diabetic patients with and without pigmented pretibial patches (PPP). A, B: HE staining in PPP group. C, D: HE staining in non-PPP group. E, F: Masson staining in PPP group. G, H: Masson staining in non-PPP group. Original magnification: ×10 in A, C, E, G; magnification: ×40 in B,D, F, H. ▲: Melanin deposition sites; ●: Areas of capillary proliferation; ■: Regions of inflammatory cell infiltration; ★ : Locations of collagen fibers with hyaline degeneration. (A, C, E, G: Scale bar=200 μm; B, D, F, H: Scale bar=400 μm).

Tab.1 Comparison of histopathological characteristics between the two groups

Characteristics	PPP group (n=17)	non-PPP group (n=25)	P
Epidermis layer thickness (μm)	114.59±27.52	98.24±19.57	<0.05
Dermal MVD (no./mm²)	19.17±8.08	12.73±6.87	<0.01
CD4	1.72±0.79	1.04±0.66	<0.01
CD8	0.53±0.18	0.74±0.36	<0.05
CD4/CD8 ratio	2.69 (2.24, 3.71)	1.54(1.23, 1.73)	<0.01

Fig.2 Immunohistochemical staining for detecting CD34 expression in the skin tissue from PPP (A) and non-PPP (B) groups (×100). Black arrows indicate the areas with microvessel proliferation.

Fig.3 Immunohistochemical staining for CD4 and CD8 for comparison of T-cell profiles between the two groups. A,B: Immunohistochemical staining for CD4 in PPP group. C, D: Immunohistochemical staining for CD8 in PPP group. E,F: Immunohistochemical staining for CD4 in non-PPP group. G,H: Immunohistochemical staining for CD8 in non-PPP group; magnification ×40 (A, C, E, G); magnification ×100 for (B, D, F, H).

Fig.4 Comparison of epidermal thickness, dermal microvascular density and expression levels of CD4 and CD8 between PPP group and non-PPP group (n=42). *P<0.05, **P<0.01 vs non-PPP group.

Fig.5 Western blotting showing elevated protein expression levels of VEGFA and VEGFR2 in PPP group versus non-PPP group (n=6). **P<0.01 vs non-PPP group.

References 31

[1]	Demir S, Nawroth PP, Herzig S, et al. Emerging targets in type 2 diabetes and diabetic complications[J]. Adv Sci (Weinh), 2021, 8(18): e2100275. doi：10.1002/advs.202100275
[2]	邓小鸽, 李先行, 冯志海, 等. 糖尿病胫前色素斑研究进展[J]. 中国皮肤性病学杂志, 2022, 36(6): 724-8.
[3]	孙建方. 糖尿病与皮肤病[C]//2023全国中西医结合皮肤性病学术会议论文汇编. 昆明, 2023: 15-6.
[4]	Morgan AJ, Schwartz RA. Diabetic dermopathy: a subtle sign with grave implications[J]. J Am Acad Dermatol, 2008, 58(3): 447-51. doi：10.1016/j.jaad.2007.11.013
[5]	王臣廷, 安向莲, 吕翠君, 等. 2型糖尿病病人并发大血管病变的危险因素分析[J]. 中西医结合心脑血管病杂志, 2023, 21(19): 3607-9.
[6]	张帆. 2型糖尿病患者慢性并发症与皮肤病变的相关性[J]. 中国卫生工程学, 2022, 21(3): 494-5, 498.
[7]	袁丽华. 糖尿病胫前色素斑临床意义初探[J]. 交通医学, 2023, 37(1): 67-70.
[8]	Kiziltan ME, Benbir G, Akalin MA. Is diabetic dermopathy a sign for severe neuropathy in patients with diabetes mellitus? Nerve conduction studies and symptom analysis[J]. Clin Neurophysiol, 2006, 117(8): 1862-9. doi：10.1016/j.clinph.2006.05.007
[9]	刘婕妤, 郑妙艳, 常宝成, 等. 胫前黑斑与糖尿病微血管病变关系的研究[J]. 中华全科医师杂志, 2013, 12(2): 99-103.
[10]	武曦蔼, 严美花, 张浩军, 等. 糖尿病胫前色素斑与2型糖尿病患者心血管事件发病风险关系的队列研究[J]. 中国糖尿病杂志, 2018, 26(1): 32-5.
[11]	Houck GM, Morgan MB. A reappraisal of the histologic findings of pigmented pretibial patches of diabetes mellitus[J]. J Cutan Pathol, 2004, 31(2): 141-4. doi：10.1111/j.0303-6987.2004.00133.x
[12]	Brugler A, Thompson S, Turner S, et al. Skin blood flow abnormalities in diabetic dermopathy[J]. J Am Acad Dermatol, 2011, 65(3): 559-63. doi：10.1016/j.jaad.2010.06.010
[13]	敖小凤. 2型糖尿病胫前黑斑患者微血管病变及免疫功能的探讨[D]. 天津: 天津医科大学, 2008.
[14]	中华医学会糖尿病学分会, 朱大龙. 中国2型糖尿病防治指南(2020年版)[J]. 中华内分泌代谢杂志, 2021, 37(4): 311-98.
[15]	仝小林. 糖尿病中医药临床循证实践指南: 2016版[M]. 北京: 科学出版社, 2016.
[16]	武曦蔼, 徐远, 华传金, 等. 糖尿病胫前色素斑的中医证候特点研究[J]. 中华中医药杂志, 2014, 29(3): 742-4.
[17]	Chen D, Zhao ZX, Liu P, et al. Adventitial Vasa vasorum neovascularization in femoral artery of type 2 diabetic patients with macroangiopathy is associated with macrophages and lymphocytes as well as the occurrence of cardiovascular events[J]. Thromb Haemost, 2023, 123(10): 989-98. doi：10.1055/s-0043-1768162
[18]	Abdollahi A, Daneshpazhooh M, Amirchaghmaghi E, et al. Dermopathy and retinopathy in diabetes: is there an association[J]?Dermatology, 2007, 214(2): 133-6. doi：10.1159/000098572
[19]	丁佳, 范剑波, 李定中. 2型糖尿病患者肾脏病变与胫前色素沉着斑的相关性分析[J]. 现代实用医学, 2019, 31(7): 889-91, 844.
[20]	梁波, 林家煜. 糖尿病胫前黑斑患者TH17、Treg的表达及其与糖尿病足的相关性研究[J]. 糖尿病新世界, 2021, 24(19): 1-5.
[21]	Sibbald C, Reid S, Alavi A. Necrobiosis lipoidica[J]. Dermatol Clin, 2015, 33(3): 343-60. doi：10.1016/j.det.2015.03.003
[22]	Spigariolo CB, Giacalone S, Nazzaro G. Pigmented purpuric dermatoses: a complete narrative review[J]. J Clin Med, 2021, 10(11): 2283. doi：10.3390/jcm10112283
[23]	Kusari A, Ahluwalia J. Lichen planus[J]. N Engl J Med, 2018, 379(6): 567. doi：10.1056/nejmicm1802078
[24]	张继玲, 曹碧兰, 袁伟, 等. 白癜风患者皮损中CD4⁺, CD8⁺T淋巴细胞及朗格汉斯细胞的检测[J]. 中国皮肤性病学杂志, 2008, 22(11): 649-51.
[25]	马孝秋, 左韬, 马贤德, 等. 基于VEGFA/VEGFR2-PI3K/AKT信号轴探讨化瘀明目方含药血清抑制高糖及VEGF诱导人视网膜微血管内皮细胞血管新生的分子机制[J]. 中药新药与临床药理, 2025, 36(2): 197-205.
[26]	Melin H. An atrophic circumscribed skin lesion in the lower extremities of diabetics[J]. Acta Med Scand, 1964, 176: 1-75.
[27]	McCash S, Emanuel PO. Defining diabetic dermopathy[J]. J Dermatol, 2011, 38(10): 988-92. doi：10.1111/j.1346-8138.2011.01251.x
[28]	邱明才, 林珊, 高志红, 等. 有胫前黑斑的2型糖尿病患者皮肤黑斑和肾活检[J]. 天津医药, 2004, 32(5): 257-9, 322-3.
[29]	Cheng SZ, Chen ZJ, Peng F, et al. Exploration progress on inflammatory responses and immune regulatory mechanisms in diabetic retinopathy[J]. J Inflamm Res, 2025, 18: 11895-909. doi：10.2147/jir.s527784
[30]	Hu YN, Tang JY, Yu D, et al. Correlation and diagnostic significance of CD4 T cell subsets and NLRP3 inflammasome in ulcerative colitis: the role of the NLRP3/T-bet/GATA3 axis[J]. BMC Gastroenterol, 2025, 25(1): 23. doi：10.1186/s12876-025-03603-w
[31]	Olvera-Barrios A, Lilaonitkul W, Heeren TFC, et al. Impact of anti-VEGF treatment for diabetic macular oedema on progression to proliferative diabetic retinopathy: data-driven insights from a multicentre study[J]. BMJ Open Ophthalmol, 2025, 10(1): e002234. doi：10.1136/bmjophth-2025-002234