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Background: Currently, there is no standard treatment for relapsed/refractory NK/T-cell lymphoma (NKTCL). Liposomal mitoxantrone (Lipo-MIT) showed good anti-tumor effect in patients with NKTCL, breaking the limitation of natural resistance of NKTCL to anthracyclines. To further improve the efficacy, we tried a combination therapy based on Lipo-MIT in patients with relapsed/refractory NKTCL. Methods: 12 patients with relapsed/refractory NKTCL were enrolled in this retrospective study, all of whom had previously received pegaspargase-based treatments. The salvage treatment was a combination regimen based on Lipo-MIT. The efficacy was evaluated after every two cycles. Results: 11 patients had stage IV NKTCL, and all but one patients had an NRI score of ≥3. The median previous lines of treatment was two (range, 1-4), and five patients were refractory to their last line of treatment. The best response rates were as follows: complete response (CR) in five (41.7%) patients, partial response in five (41.7%) patients, stable disease in one (8.3%) patient, and progressive disease in one (8.3%) patient. At a median follow-up of four months (range, 2-14), seven patients died, with a median PFS of five months and a median OS of seven months. The six-month PFS and OS rate was 44.4% and 52.1%, respectively. All patients had suffered from side effects, among which myelosuppression was most reported. Nine patients had grade three or more myelosuppression, and the median recovery time from myelosuppression was 14 days (2-35 days). Five patients had obvious skin hyperpigmentation, and the CR rate was significantly higher compared with those without skin hyperpigmentation (80% vs. 14.3%, p=0.023). Other side effects included liver insufficiency (N=4), coagulation dysfunction (N=4), acute pancreatitis (N=2), and immunotherapy-related adverse effects (irAEs, N=2). Conclusion: Combination therapy based on Lipo-MIT has a high remission rate for relapsed/refractory NKTCL, but the duration of remission needs to be further extended. Lipo-MIT has obvious myelosuppression toxicity, and active supportive therapy should be given when combined with other cytotoxic drugs.

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Serpentine supravenous hyperpigmentation (SSH) describes increased skin pigmentation that develops in the area immediately overlying the vessels through which chemotherapeutic drugs are administered. While SSH can be cosmetically distressing and there are no definitive management options, the literature is severely limited and the variations in clinical presentation, risk factors, and histopathology of SSH across patients are not well understood. We aimed to systematically summarize characteristics from current available data, and thus improve SSH awareness and management. A literature search was conducted in PubMed using specific eligibility criteria through the end of December 2022. Included articles focused on patients who experienced SSH after chemotherapy infusion. Study quality was assessed using a modified Oxford Centre for Evidence-Based Medicine quality rating scheme. Of the 41 articles identified by literature search, 24 met eligibility criteria. Two additional articles were identified through the reference sections of retrieved articles, for 26 articles total. All articles were case reports, representing 28 patients total. Locations of SSH were mostly in the forearm near the site of injection (85%), and the most common associated symptom was erythema. Histopathologic analysis was available for half of cases, the majority of which were inflammatory in nature. The most common inflammatory pattern observed was a vacuolar/lichenoid interface dermatitis. Duration of SSH ranged from days to > 1 year after the chemotherapy was stopped. Six (21%) patients were managed with topical steroids and oral vasodilators, six (21%) patients switched to central venous infusion rather than peripheral infusion, five (18%) patients received only supportive care, three (11%) patients received venous washing with chemotherapy, three (11%) patients stopped chemotherapy, and one (4%) patient reduced the chemotherapy dosage. Ten (36%) patients attained complete resolution, seven (25%) had SSH that was near resolution/fading, and three (11%) had persistent hyperpigmentation. Although SSH often spontaneously resolves once the chemotherapeutic agent is stopped, it can persist in some patients and cause significant distress. As the literature is severely limited and there are no definitive treatments, additional research using more standardized definitions and methods of assessments is necessary to improve characterization of SSH and evaluate potential interventions.

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There is growing evidence that oxidative stress plays a role in melasma and disrupts primary cilia formation. Additionally, primary cilia have been suggested to have an inhibitory role in melanogenesis. This study examined the potential link between oxidative stress, skin hyperpigmentation, and primary cilia. We compared the expression levels of the nuclear factor E2-related factor 2 (NRF2), intraflagellar transport 88 (IFT88), and glioma-associated oncogene homologs (GLIs) in skin samples from patients with melasma, both in affected and unaffected areas. We also explored the roles of NRF2, IFT88, and GLIs in ciliogenesis and pigmentation using cultured adult human keratinocytes, with or without melanocytes. Our findings revealed decreased levels of NRF2, heme oxygenase-1, IFT88, and GLIs in lesional skin from melasma patients. The knockdown of NRF2 resulted in reduced expressions of IFT88 and GLI1, along with fewer ciliated cells. Furthermore, NRF2, IFT88, or GLI1 knockdown led to increased expressions in protease-activated receptor-2 (PAR2), K10, involucrin, tyrosinase, and/or melanin. These effects were reversed by the smoothened agonist 1.1. Calcium also upregulated these proteins, but not NRF2. The upregulation of involucrin and PAR2 after NRF2 knockdown was mitigated with a calcium chelator. In summary, our study suggests that oxidative stress in NRF2-downregulated melasma keratinocytes impedes ciliogenesis and related molecular processes. This inhibition stimulates keratinocyte differentiation, resulting in melanin synthesis and melanosome transfer, ultimately leading to skin hyperpigmentation.

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Polymyxin B was widely used to treat drug-resistant gram-negative bacteria and showed a better antibacterial effect. However, it is associated with some side effects. It should be remembered that polymyxin B may cause hyperpigmentation, albeit rare. This is a case report of a 68-year-old male patient who developed hyperpigmentation following treatment of a chest infection with polymyxin B. He was a known patient with chronic kidney diasease and chronic obstructive pulmonary disease followed up in the intensive care unit due to acute exacerbation of COPD. Later, polymyxin B treatment was started due to the development of pneumonia caused by the multidrug-resistant Acinetobacter baumannii. On the second day of polymyxin B treatment, hyperpigmentation developed in the face and neck region. The fact that the patient had chronic kidney disease possibly facilitated the development of skin hyperpigmentation due to the cumulative effect of polymyxin B. Hyperpigmentation which a rare side effect of polymyxin B may occur in those with underlying kidney disease.

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BACKGROUND: Noninvasive skin rejuvenation treatment is growing in recognition to aesthetic medicine. AIM: The objective of the study was to assess the efficacy and the safety of the 675-nm laser source treatment of photodamaged hands. MATERIALS AND METHODS: The study included 21 patients (6 males and 15 females) with a mean age of 63 (± 9) years. Patients were treated with -two to three sessions of the 675-nm laser with a 1-month interval between sessions. Photos of each patient were collected at baseline, and 3 months after the last laser session. The 5-point Global Aesthetic Improvement Scale (GAIS) was recorded with their final assessment session (3 months). RESULTS: The total GAIS scores showed satisfactory results: 15 patients (71%) experienced 4 score (excellent improvement) changes and 6 patients (29%) experienced 3 score (good improvement) changes. Clinical images showed good efficacy and visible aesthetic results for the management of photodamaged skin. No serious adverse effects were recorded. CONCLUSION: This study demonstrates the safety and efficacy of for the aesthetic improvement of skin pigmentation and texture for photodamaged hands.

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Background: Understanding the connection between skin lesions and the pathology of internal organs and body systems that may have caused them is a prerequisite for successful cosmetic therapy. Aim: The aim of this study was to analyze the influence of a patient's somatic pathology on the manifestation of skin abnormalities. Materials and methods: The study was conducted according to a "case-control" design and was accompanied by a retrospective study of outpatient records of patients with the disease (group 1) and patients without it (control group). It is aimed at revealing the connection between a patient's skin manifestations and somatic pathology, as well as the effectiveness of therapeutic measures for the correction of such a condition. Results: Patients with acne and rosacea have a statistically signi-ficantly higher incidence of gastrointestinal diseases (in particular, gastritis caused by Helicobacter), diabetes mellitus, vitamin and micronutrient deficiencies, which significantly affects the effectiveness of their treatment and quality of life. In such chronic dermatoses, disruption of intestinal microbiocenosis can be considered as a co-morbid condition. Hyperpigmentation of patients' skin was caused by hormonal dysfunction (hyperestrogenism) and was accompanied by vitamin D deficiency. Conclusions: In cosmetology practice, therapy of dermatoses should be individualized and based on the analysis of the course of the disease, considering the diagnosed dysfunctions of certain organs or systems that cause skin pathological changes, as well as the preva-lence and severity of dermatosis, presence of comorbid background and mental disorders. A holistic approach in the therapy of dermatoses involving a dermatologist, a psychologist, a cosmetologist, and specialized clinicians will ensure their effective treatment.

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Nelson syndrome is a rare disorder, characterized by clinical features arising from an adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma after bilateral adrenalectomy. Common symptoms of Nelson syndrome include weight gain, vision problems, and skin hyperpigmentation, among many others. In this case report, a 58-year-old Asian female who displayed clinical features akin to Nelson syndrome despite not undergoing bilateral adrenalectomy is investigated. The patient has a past history of an ACTH-secreting pituitary macroadenoma, for which a transsphenoidal resection was performed along with radiation therapy. A year following this, she displayed severe facial and neck hyperpigmentation. According to the laboratory results obtained, the patient displayed initial high ACTH levels and low-normal AM cortisol levels, which are signs of partial adrenal insufficiency. A brain MRI was performed, which confirmed stable residual tumor tissue in the cavernous sinus. The results pointed to the adrenal glands as the cause of the hyperpigmentation, and the patient was diagnosed with primary adrenal insufficiency. To bring her ACTH levels and low-normal AM cortisol into the proper range, she was given low-dose hydrocortisone and monitored for five years. Over this time period, her hyperpigmentation improved significantly and eventually resolved entirely, and her ACTH levels were lowered, indicating that hydrocortisone was the appropriate treatment for normalizing ACTH levels. In this case, it was determined that unresponsive adrenal glands lead to high ACTH levels, which resulted in an atypical case of Nelson syndrome and the physical symptom of hyperpigmentation.

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AIM: The aim of the study was to quantitatively assess the effectiveness of microneedle mesotherapy in reducing skin discoloration. The results were analyzed using the gray-level co-occurrence matrix (GLCM) method. MATERIAL AND METHODS: The skin of the forearm (7 × 7 cm) of 12 women aged 29 to 68 was examined. Microneedle mesotherapy was performed using a dermapen with a preparation containing 12% ascorbic acid. Each of the volunteers underwent a series of four microneedle mesotherapy treatments. The effectiveness of the treatment was quantified using the methods of image analysis and processing. A series of clinical images were taken in cross-polarized light before and after a series of cosmetic procedures. Then, the treated areas were analyzed by determining the parameters of the gray-level co-occurrence matrix (GLCM) algorithm: contrast and homogeneity. RESULTS: During image pre-processing, the volunteers' clinical images were separated into red (R), green (G) and blue (B) channels. The photos taken after the procedure show an increase in skin brightness compared to the photos taken before the procedure. The average increase in skin brightness after the treatment was 10.6%, the average decrease in GLCM contrast was 10.7%, and the average homogeneity increased by 14.5%. Based on the analysis, the greatest differences in the GLCM contrast were observed during tests performed in the B channel of the RGB scale. With a decrease in GLCM contrast, an increase in postoperative homogeneity of 0.1 was noted, which is 14.5%.

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BACKGROUND: Due to relapsing nature of melasma with significant impact on quality of life, an objective measurement score is warranted, especially to follow-up the patients with melasma and their therapy response in a quantitative and precise manner. AIMS: To prove concordance of skin hyperpigmentation index (SHI) with well-established scores in melasma and demonstrate its superiority regarding inter-rater reliability. Development of SHI mapping for its integration in common scores. METHODS: Calculation of SHI and common melasma scores by five dermatologists. Inter-rater reliability was assessed by intraclass correlation coefficient (ICC) and concordance by Kendall correlation coefficient. RESULTS: Strong concordance of SHI with melasma area and severity index (MASI)-Darkness (0.48; 95% CI: 0.32, 0.63), melasma severity index (MSI)-Pigmentation (0.45; 95% CI: 0.26, 0.61), and melasma severity scale (MSS) (0.6; 95% CI: 0.42, 0.74). Using step function for mapping SHI into pigmentation scores showed an improvement of inter-rater reliability with a difference in (ICC of 0.22 for MASI-Darkness and 0.19 for MSI-Pigmentation), leading to an excellent agreement. CONCLUSION: Skin hyperpigmentation index could be an important additional cost-and time-conserving assessment method, to follow-up the patients with melasma undergoing brightening therapies in clinical studies, as well as in routine clinical practice. It is in strong concordance with well-established scores but superior regarding inter-rater reliability.

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Aim: The aim of this study was to demonstrate the effects of using a preparation containing kojic acid on skin hyperpigmentation using hyperspectral imaging, which enables a quantitative assessment of the effect of the preparation used on the reduction of skin discoloration. Materials and methods: Preliminary studies were carried out on 12 patients with post-acne skin. A hyperspectral camera with a spectral range of 400-1000 nm was used to image skin hyperpigmentation before and after the application of 3% kojic acid. Hyperspectral profiles were analyzed, and image analysis and processing methods were applied. Results: Studies performed using a hyperspectral camera have shown that kojic acid reduces skin discoloration by increasing skin brightness in 75% of patients tested, reducing skin contrast in approximately 83% and increasing skin homogeneity in approximately 67% of patients.

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BACKGROUND: H syndrome is a rare genodermatosis deriving from a mutation in the SLC29A3 gene and affecting numerous systems, particularly the skin. The syndrome exhibits different clinical characteristics involving several systems, most beginning with the letter "H." The most common clinical findings are cutaneous hyperpigmentation, flexion contracture in the fingers, hearing loss, short stature, insulin-dependent diabetes mellitus, heart anomalies, hepatosplenomegaly, and hypogonadism. Fewer than 150 cases have been reported so far and vast majority of them consisted with patients with Arab ethnicity. CASE PRESENTATION: We describe a patient presenting with short stature, developing diabetes mellitus at follow-ups, with homozygous deletion determined in exon 3 of the SLC29A3 gene, and diagnosed with H syndrome, reported due to the presence and rarity of renal involvement (hematuria and proteinuria). CONCLUSION: In conclusion, despite its rarity, endocrinologists, rheumatologists/nephrologists, and dermatologists need to be aware of H syndrome as a pleiotropic syndrome. H syndrome should be considered in the differential diagnosis of patients with cutaneous hyperpigmentation (particularly in the bilateral thigh and calf region) together with proteinuria/hematuria. In addition, periodic urine analysis should be performed in patients with H syndrome.

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X-linked adrenoleukodystrophy (X-ALD) is an inherited disease caused by a mutation in the adenosine 5'-triphosphate binding cassette subfamily D member 1 (ABCD1) gene encoding a peroxisomal transmembrane protein, which has various clinical manifestations and a rapid progression from initial symptoms to fatal inflammatory demyelination. Therefore, identification of early clinical symptoms and further early diagnosis as well as treatment can effectively prevent disease development. In this study, we reported the laboratory and radiographic features in a rare case of X-ALD with 3-year skin hyperpigmentation as the only manifestation. And the ABCD1 gene was sequenced for the patient and his parents by a high-throughput sequencing method. The results of laboratory examination showed adrenocortical hypofunction and increased serum concentrations of very long-chain fatty acids. Brain MRI showed no obvious abnormal signal shadow. A hemizygous mutation of c.521A>C was detected in the ABCD1 gene of the patient, and his mother has the same site heterozygous mutation. Therefore, this patient was diagnosed as "X-linked adrenoleukodystrophy". During the follow-up, adrenocortical hypothyroidism did not improve, and brain MRI showed few high-FLAIR signals in the white matter of the right radial corona and left parietal lobe, suggesting possible brain injury. X-ALD patients with only skin manifestations but no neurological abnormalities are easily neglected, but early diagnosis and early intervention are important ways to delay the progression of this disease. Therefore, genetic testing for early X-ALD is recommended in all male children patients with skin pigmentation as the sole clinical presentation and subsequent diagnosis of adrenal hypofunction.

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BACKGROUND: Toxicity is a major concern related to the clinical use of polymyxin B, and available safety data for renal transplant patients are limited. AIMS: We investigated the safety of polymyxin B and toxicity risk factors in renal transplant patients. METHODS: A prospective study was performed on a group of renal transplant patients who received intravenous polymyxin B between January 2018 and August 2021. Polymyxin B treatment was monitored to evaluate toxicity and risk factors. RESULTS: A total of 235 courses of polymyxin B were administered to 213 patients. Of these, 121 (51.5%) developed skin hyperpigmentation (SH), 149 (63.4%) developed neurotoxicity and 10 (5.5%) developed acute kidney injury of which 80% was reversible. Risk factors for developing SH included a high total dose by weight (odds ration [OR] 1.31, 95% confidence interval [CI] 1.08-1.60, P = .008) and the presence of neurotoxicity (OR 2.86, 95% CI 1.56-5.26, P = .001). Neurotoxicity manifested during the first 2 days of treatment. Neurotoxicity occurred most commonly in women (OR 3.84, 95% CI 1.82-8.10, P < .0001), and the presence of SH (OR 1.98, 95% CI 1.13-3.46, P = .016) was also an independent risk factor. CONCLUSIONS: Neurotoxicity and SH are the two major adverse effects of polymyxin B in renal transplant patients, which may limit its clinical use.

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Our exposure to blue light from artificial sources such as indoor lights (mainly light-emitting diodes [LEDs]) and electronic devices (e.g., smartphones, computer monitors, and television screens), has increased in recent years, particularly during the recent coronavirus disease 2019 lockdown. This radiation has been associated to skin damage across its potential in generating reactive oxygen species in both the epidermis and the dermis, skin water imbalances and of potential activating melanin production. These circumstances make it important to determine whether current blue light exposure levels under artificial illumination and electronic devices exposure can cause the previously indicated disorders as compared to solar UV and visible radiation in a typical summer day. Blue light accounted for 25% of the sun's rays, approximately 30% of radiation emitted by electronic devices, and approximately from 6% to 40% of that emitted by indoor lights. The reference equations showed that the sun was the main source of effective irradiance for immediate and persistent pigmentation as well as for potential oxidative stress in our skin. Effective blue light exposure to artificial devices is significantly lower than the solar contribution. However, its contribution must be considered as accumulative dose effect, and especially in people with hypersensitivity promoting skin hyperpigmentation.

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Abnormal skin pigmentation commonly occurs during the wound healing process due to the overproduction of melanin. Chicken egg white (CEW) has long been used to improve skin health. Previous published works had found CEW proteins house bioactive peptides that inhibit tyrosinase, the key enzyme of melanogenesis. The current study aimed to evaluate the anti-pigmentation potential and mechanism of the CEW-derived peptide (GYSLGNWVCAAK) and hydrolysates (CEWHmono and CEWHdi), using a cell-based model. All of these peptide and hydrolysates inhibited intracellular tyrosinase activity and melanin level up to 45.39 ± 1.31 and 70.01 ± 1.00%, respectively. GYSLGNWVCAAK and CEWHdi reduced intracellular cAMP levels by 13.38 ± 3.65 and 14.55 ± 2.82%, respectively; however, CEWHmono did not affect cAMP level. Moreover, the hydrolysates downregulated the mRNA expression of melanogenesis-related genes, such as Mitf, Tyr, Trp-1 and Trp-2, but GYSLGNWVCAAK only suppressed Tyr gene expression. Downregulation of the genes may lower the catalytic activities and/or affect the structural stability of TYR, TRP-1 and TRP-2; thus, impeding melanogenesis to cause an anti-pigmentation effect in the cell. Outcomes from the current study could serve as the starting point to understand the underlying complex, multifaceted melanogenesis regulatory mechanism at the cellular level.

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Melasma is a hypermelanotic skin disorder characterized by dark brown macules of symmetrical sizes and shapes that develop over time. Apart from the multiple etiological factors for melasma, such as hormonal imbalances, thyroid dysfunction, drugs, and contraceptive pills, a new and significant cause has been discovered: the effect of oxidative stress. Oxidative stress is the result of disequilibrium between reactive oxygen species and antioxidants in the cells. It is a key element that can cause skin hypopigmentation or hyperpigmentation. The physiological significance of reactive oxygen species and its function in skin health are addressed in this study. The development process and pathophysiology of reactive oxygen species with melasma disorder are also highlighted and the advantages of integrating antioxidants in clinical and experimental environments are discussed.

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BACKGROUND: The skin hyperpigmentation index (SHI), a new objective method for measuring skin hyperpigmentation, needs validation. OBJECTIVE: To gain evidence of the reliability and validity of the SHI. METHODS: Fifteen raters were divided into 3 groups (5 dermatologists, 5 nondermatologist physicians, and 5 nonphysician clinicians). Each rated 5 pigmented mole lesions with mild-to-severe hyperpigmentation to determine intra- and interrater reliability. All raters photographed the lesions and rated them using the subjective Physician Global Assessment (PGA) score. The same photographs were then assessed based on automatic computer measurement software using the online SHI tool (https://shi.skinimageanalysis.com). RESULTS: The SHI reliability was excellent for all intra- and interrater assessments, while most PGA assessments showed good intra- and interrater agreement. Between-group reliability was excellent for SHI, while moderate-to-good for PGA evaluations. Concordance between the SHI and PGA assessments was strong across all groups of assessors. CONCLUSION: There is evidence that the SHI is a reliable instrument for measuring skin hyperpigmentation, and can be used by nonexperienced clinicians.

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La enfermedad de Addison es una patología endocrinológica ocasionada por la disminución en la secreción de hormonas esteroideas por parte de la corteza adrenal; debida a múltiples etiologías (más comúnmente la tuberculosis en países en vías de desarrollo); con una evolución lenta, insidiosa y progresiva. Pudiendo llegar a una insuficiencia adrenal aguda, misma que puede llegar a ser de extrema gravedad; y en caso de no ser diagnosticada y tratada adecuadamente puede llevar a la muerte. El tratamiento primordial lo constituye la terapia hormonal sustitutiva con fármacos corticoesteroideos.

Addison's disease is an endocrinological pathology caused by the decrease in the secretion of steroid hormones by the adrenal cortex, due to multiple etiologies (most commonly tuberculosis in developing countries); with a slow, insidious and progressive evolution. Being able to reach an acute adrenal insufficiency, which can become extremely serious, and if it is not diagnosed and treated properly, it can lead to death. The primary treatment is hormone replacement therapy with corticosteroid drugs

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