Letter to the Editor: September 2024

J Clin Aesthet Dermatol. 2024;17(9):14–15.

Why does Pigmented Purpuric Dermatosis Result in Residual Pigmentation in Contrast to Senile Purpura?

Dear Editor:

Pigmented purpuric dermatosis (PPD),¹ a rare inflammatory, purpuric skin disorder, is characterized by tiny purpuric rashes and pigmented spots (Figure 1A) that most commonly affect the lower extremities. The exact pathology of PPD and even the mechanism underlying the characteristic “pigmentation” associated with the disease remain unclear. To date, despite being referred to as a pigmentation disorder, the mechanism of pigmentation remains unknown in contrast to the presentation of senile purpura (SP) (Figure 1B),² which is characterized by bleeding lesions that do not cause residual pigmentation.

SP² (Figure 1B) is a common benign condition characterized by recurrent diffuse purpura and purple ecchymoses distributed across the extensor surfaces of the forearms after minor trauma secondary to age-induced thinning and weakening of the skin. SP² is commonly observed in older individuals and is rarely associated with residual pigmentation despite repeated exposure. 

PPD¹ is associated with typical pigmentation secondary (Figure 1A) to hemosiderin deposition, contributing to an aesthetic burden on patients. Although PPD shows several clinical subtypes,¹ no significant intergroup histological differences are observed in the inflammatory response, characterized by lymphocytic infiltration surrounding microvessels.¹ Recent studies have reported a strong association between PPD and periodontal bacteria,³ which emphasizes the inflammatory nature of this condition. A fundamental difference between SP and PPD is that bleeding in patients with SP occurs secondary to mechanical vascular injury in contrast to vascular inflammation and perhaps microvascular vasculitis in PPD.⁴ However, both erythrocytes and hemosiderin deposition result in pigmentation in PPD. As previously reported, the management of PPD pigmentation is extremely challenging.³ The author will verify whether the difference between SP and PPD is attributable to the same bleeding.

Hemosiderin and ferritin. The association between hemosiderin and ferritin has been conclusively established;^5,6 however, the mechanism underlying the role of ferritin⁷ in hemosiderin pigmentation remains unknown. Ferritin,⁷ the primary intracellular iron-storage protein in nearly all cells, including prokaryotes and eukaryotes, maintains iron in a soluble and non-toxic form. Research suggests that ferritin, a universal intracellular protein that stores and releases iron in a controlled manner, may be involved in PPD pigmentation. ⁷  

Iron-induced pigmentation. Iron-induced pigmentation has been experimentally investigated in mice;⁸ a large volume of iron injection can result in darker pigmentation. Hemosiderin granules were identified extracellularly between collagen bundles in skin specimens; however, these changes faded over the subsequent eight months.⁸ The correlation between gingival pigmentation, skin color, and serum ferritin levels⁵ has been established in dentistry; gingival pigmentation is considered a sign of iron deposition, suggesting the role of ferritin⁷ in iron-induced pigmentation.

Hemosiderin-pigmentation and lymphocytic inflammation. The finding also supports the role of inflammation and vasculitis (in contrast to mere angiopathy)⁹ as essential pathogenetic contributors to PPD.^1,4 PPD cannot be classified as vasculopathy; and its hemorrhage occurs secondary to vascular inflammation. Huang et al⁴ reported that 16 percent of analyzed cases were determined to be lymphocytic vasculitis. Therefore, it is inappropriate to consider the role of angiopathy in the development of PPD, and PPD-induced pigmentation may be attributable to competition between ferritin protein and hemosiderin iron. 

Conclusion. SP² involves trauma-induced hemorrhage; however, the pooled blood is easily absorbed and would not result in residual pigmentation. However, PPD becomes a binding protein between hemosiderin and ferritin in the presence of inflammation, which leads to iron-related pigmentation, which is not easily absorbed. Some researchers describe PPD as a vasculopathy and not vasculitis.⁹ However, accumulated evidence suggests that PPD is associated with lymphocytic inflammation of skin microvessels and lymphocytic vasculitis.⁴ The most characteristic pigmentation associated with this disease provides conclusive evidence in this context. We should not try to combine vasculitis with leukocytic cells; a completely separate entity of lymphocytic vasculitis exists.

Moreover, no report has described residual pigmentation in cases of leukocytoclastic vasculitis,¹⁰ which suggests that PPD, an inflammation caused by lymphocytes, involves some mechanism that favors hemosiderin pigmentation, in contrast to simple bleeding, such as that observed in SP,² or leukocyte inflammation, such as leukocytoclastic vasculitis.¹⁰ 

With regard,

Yasuhiro Horiuchi, MD

Keywords. Pigmented purpuric dermatosis, senile purpura, hemosiderin, pigmentation, ferritin

Affiliations. Dr. Horiuchi is with the Division of Dermatology, Tsuruse Orthopedic Clinic in Saitama, Japan. 

Funding. No funding was provided for this article.

Disclosures. The author reports no conflicts of interest relevant to the content of this article.

References

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2. Cho SI, Kim JW, Yeo G, et al. Senile purpura: Clinical features and related factors. Ann Dermatol. 2019;31(4):472–475. 
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