Human skin is repeatedly exposed to UVR that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, as melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. Skin pigmentation is of great cultural and cosmetic importance, yet the role of melanin in photoprotection is still controversial. This article outlines the major acute and chronic effects of UVR on human skin, the properties of melanin, the regulation of pigmentation and its effect on skin cancer prevention.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1751-1097.2007.00226.x

The Protective Role of Melanin Against UV Damage in Human Skin

The genetic basis underlying normal variation in the pigmentary traits of skin, hair and eye colour has been the subject of intense research directed at understanding the diversity seen both between and within human populations. A combination of approaches have been used including comparative genomics of candidate genes and the identification of regions of the human genome under positive selection, together with genome-wide and specific allele association studies. Independent selection for different pigmentation gene sets has been found between Asian, European and African populations. Several genome-wide association studies for pigmentation have now been conducted and identified single nucleotide polymorphism (SNP) markers in known, TYR, TYRP1, OCA2, SLC45A2, SLC24A5, MC1R, ASIP, KITLG and previously unknown SLC24A4, IRF4, TPCN2, candidate genes. The contribution of SNP polymorphisms present in populations from South Asia have been tested and alleles found at TYR, SLC45A2 and SLC24A5 can largely account for differences between those of darkest and lightest skin reflectance using a simple additive model. Skin and hair colour associations in Europeans are found within a range of pigmentation gene alleles, whereas blue-brown eye colour can be explained by a single SNP proposed to regulate OCA2 expression. Functional testing of variant alleles has begun to connect phenotype correlations with biological differences. Variant MC1R alleles show direct correlations between the biochemical signalling properties of the encoded receptor and the red-hair fair skin pigmentation phenotype. Direct testing of a range of clonal melanocyte cultures derived from donor skin tissue characterized for three causal SNPs within SLC45A2, SLC24A5 and OCA2 has assessed their impact on melanin content and tyrosinase enzyme activity. From a culmination of genetic and functional studies, it is apparent that a number of genes impacting melanosome biogenesis or the melanin biosynthetic pathway are candidates to explain the diversity seen in human pigmentation.

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Molecular genetics of human pigmentation diversity

Neuromelanin in human dopamine neurons: comparison with peripheral melanins and relevance to Parkinson's disease.

Phenotypic variation between human populations in skin pigmentation correlates with latitude at the continental level. A large number of hypotheses involving genetic adaptation have been proposed to explain human variation in skin colour, but only limited genetic evidence for positive selection has been presented. To shed light on the evolutionary genetic history of human variation in skin colour we inspected 118 genes associated with skin pigmentation in the Perlegen dataset, studying single nucleotide polymorphisms (SNPs), and analyzed 55 genes in detail. We identified eight genes that are associated with the melanin pathway (SLC45A2, OCA2, TYRP1, DCT, KITLG, EGFR, DRD2 and PPARD) and presented significant differences in genetic variation between Europeans, Africans and Asians. In six of these genes we detected, by means of the EHH test, variability patterns that are compatible with the hypothesis of local positive selection in Europeans (OCA2, TYRP1 and KITLG) and in Asians (OCA2, DCT, KITLG, EGFR and DRD2), whereas signals were scarce in Africans (DCT, EGFR and DRD2). Furthermore, a statistically significant correlation between genotypic variation in four pigmentation candidate genes and phenotypic variation of skin colour in 51 worldwide human populations was revealed. Overall, our data also suggest that light skin colour is the derived state and is of independent origin in Europeans and Asians, whereas dark skin color seems of unique origin, reflecting the ancestral state in humans.

Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms.

Pigmentation of human skin is closely involved in protection against environmental stresses, in particular exposure to ultraviolet (UV) radiation. It is well known that darker skin is significantly more resistant to the damaging effects of UV, such as photocarcinogenesis and photoaging, than is lighter skin. Constitutive skin pigmentation depends on the amount of melanin and its distribution in that tissue. Melanin is significantly photoprotective and epidermal cells in darker skin incur less DNA damage than do those in lighter skin. This review summarizes current understanding of the regulation of constitutive human skin pigmentation and responses to UV radiation, with emphasis on physiological factors that influence those processes. Further research is needed to characterize the role of skin pigmentation to reduce photocarcinogenesis and to develop effective strategies to minimize such risks.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-0749.2006.00358.x

Regulation of human skin pigmentation and responses to ultraviolet radiation.

Background: One determining factor of skin colour is the distribution pattern of melanosomes within keratinocytes. Melanosomes in keratinocytes of light skin as in Caucasians are distributed as membrane-bound clusters, whereas the melanosomes in keratinocytes of dark skin as in African/American individuals tend to be larger and distributed individually. It has been shown that melanin content, melanin composition and the size of melanosomes in the human epidermis vary considerably with both ethnicity and chronic sun exposure. 

Objectives: To assess quantitatively the distribution pattern of melanosomes that have been transferred to keratinocytes in the photoprotected (volar forearm) skin from normal Asian individuals and to compare these data with those from light-skinned Caucasian and dark-skinned African/American individuals. 

Methods: Electron microscopy was used. 

Results: We have demonstrated that melanosomes within keratinocytes of Asian skin are distributed as a combination of individual and clustered melanosomes with a proportion of 62.6% vs. 37.4%, respectively. This contrasts with dark and light skin keratinocytes where melanosomes are predominantly individual (88.9%) and clustered (84.5%), respectively. Analysis of mean +/- SD melanosome size also revealed a progressive variation in size with ethnicity, melanosomes in dark skin being the largest (1.44 +/- 0.67 microm(2) x 10-2) followed in turn by those in Asian skin (1.36 +/- 0.15 microm(2) x 10-2) and Caucasian skin (0.94 +/- 0.48 microm(2) x 10-2). In addition, it was shown that the melanosomes that are individually distributed tend to have a larger size than the clustered melanosomes. 

Conclusions: The present data indicate that there may be a size gradient of melanosomes encompassing the global complexion coloration and that the melanosome distribution in keratinocytes of Asian skin is intermediate between that in light Caucasian and dark African/American skin.

The patterns of melanosome distribution in keratinocytes of human skin as one determining factor of skin colour.

Summary
A 25-year-old man presented with several prominent subcutaneous masses in the occipital region of the scalp. He had a long history of tinea capitis and tinea corporis infection. Histopathology of the occipital lesions showed mycelial aggregates in the deep dermis and subcutis. Cultures of the excised material and superficial scales grew a fungus identified as Microsporum ferrugineum. We propose the term ‘dermatophyte pseudomycetoma’ to describe this distinctive mycosis.

Dermatophyte pseudomycetoma: a case report.

BACKGROUND: Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with autoantibodies that recognize hemidesmosomal proteins. In addition to autoantibodies, the cell-mediated immune reaction is considered to play an important part in blister formation. Objectives To investigate some T-cell activation markers and inflammatory cytokines in the blister fluid and sera of patients with BP. METHODS: We measured soluble CD4 (sCD4) and soluble CD8 (sCD8), which have been, respectively, associated with CD4 and CD8 T-cell activation. Enzyme-linked immunosorbent assays were also used to quantify the production of the leucocyte chemoattractant interleukin (IL) -8 and of the cytokines IL-1alpha, IL-1beta, IL-6, IL-10 and tumour necrosis factor-alpha in the blister fluid and sera of 11 patients with BP.

RESULTS: The mean +/- SD level of sCD4 in patients' blisters (42.4 +/- 25.0 units mL-1) was significantly elevated (P < 0.005) compared with that in their sera (11.2 +/- 8.9) and that in the suction blisters of 10 healthy people (11.4 +/- 5.4; P < 0.005). Mean +/- SD IL-8 concentrations in BP blisters (4683.6 +/- 3878.1 pg mL-1) were much higher than those in their sera (17.1 +/- 18.9; P < 0.001), and were very significantly elevated (P < 0.005) in comparison with those in suction blisters of healthy persons (512 +/- 292). sCD4 levels in BP blisters were inversely related to IL-10 levels (P = 0. 03, r2 = 0.85), IL-8 levels were positively related to sCD8 levels (P = 0.01, r2 = 0.54), and IL-1beta levels were positively related to sCD8 concentrations (P < 0.005, r2 = 0.65).

CONCLUSIONS: The correlations suggest that there is a delicately orchestrated network of cytokines and cell-mediated immunity operating in BP blisters.

High levels of interleukin-8, soluble CD4 and soluble CD8 in bullous pemphigoid blister fluid. The relationship between local cytokine production and lesional T-cell activities.

1 Anhalt GJ, Kim SC, Stanley JR et al. Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med 1990; 323: 1729±35. 2 Anhalt GJ. Paraneoplastic pemphigus. Adv Dermatol 1993; 12: 77±96. 3 Hashimoto T, Amagai M, Watanabe K et al. Characterization of paraneoplastic pemphigus autoantigens by immunoblot analysis. J Invest Dermatol 1995; 104: 829±34. 4 Kim SC, Kwon YD, Lee IJ et al. cDNA cloning of the 210 kDa paraneoplastic pemphigus antigen reveals that envoplakin is a component of the antigen complex. J Invest Dermatol 1997; 109: 365±9. 5 Mahoney MG, Aho S, Uitto J et al. The members of the plakin family of proteins recognized by paraneoplastic pemphigus antibodies include periplakin. J Invest Dermatol 1998; 111: 308±13. 6 Hashimoto T, Amagai M, Ning W et al. Novel non-radioisotope immunoprecipitation studies indicate involvement of pemphigus vulgaris antigen in paraneoplastic pemphigus. J Dermatol Sci 1998; 17: 132±9. 7 Amagai M, Nishikawa T, Anhalt GJ et al. Antibodies against desmoglein 3 (pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus and cause acantholysis in vivo in neonatal mice. J Clin Invest 1998; 102: 775±82. 8 Joly P, Thomine E, Verdier S et al. Overlapping speci®cities in paraneoplastic pemphigus and pemphigus vulgaris. J Invest Dermatol 1994; 103: 65±72. 9 Ishii K, Amagai M, Hall RP et al. Characterization of autoantibodies in pemphigus using antigen-speci®c enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins. J Immunol 1997; 159: 2010±17. 10 Amagai M, Tsunoda K, Zillikens D et al. Clinical phenotype of pemphigus is de®ned by the anti-desmoglein autoantibody pro®le. J Am Acad Dermatol 1999; 40: 167±70.

T‐cell epitope mapping performed after patch testing in a patient with contact allergy to several azo dyes

Fish bile poisoning may damage human liver and kidney, causing degeneration and necrosis. Can also damage brain cells and heart muscle, resulting in nervous system and cardiovascular system lesions. This paper reports a case of a patient who developed multiple organ dysfunction syndrome (MODS) after oral administration of fish bile with Xiexin folk prescription for eye disease. In January 2020, he went to the poisoning and occupational diseases department of the emergency department of Qilu hospital. After receiving hemoperfusion, continuous renal replacement therapy (CRRT) and symptomatic support treatment, the patient was improved and discharged. CRRT combined with HP is one of the rapid and effective methods for the treatment of acute fish bile poisoning.

C.-C. Sun

Papers

The patterns of melanosome distribution in keratinocytes of human skin as one determining factor of skin colour.

Dermatophyte pseudomycetoma: a case report.

High levels of interleukin-8, soluble CD4 and soluble CD8 in bullous pemphigoid blister fluid. The relationship between local cytokine production and lesional T-cell activities.

T‐cell epitope mapping performed after patch testing in a patient with contact allergy to several azo dyes

[A case of acute fish gallbladder poisoning with multiple organ dysfunction].