Cysteamine Isobionic-Amide Complex Versus Kligman's Formula for the Treatment of Melasma: Equal Efficacy and Rapid Onset of Action.

BACKGROUND: Modified Kligman's formula (mKF) is the gold standard treatment for melasma; however, its prolonged use is not recommended due to side effects. Cysteamine is a potent, safe, and effective depigmenting agent. Here, we conducted a double-blind, randomized, and placebo-controlled clinical trial to assess the efficacy of cysteamine isobionic-amide -- a complex with enhanced depigmenting efficacy -- and compared it to mKF for the treatment of melasma. METHODS: This study involved a total of 80 patients divided into 3 groups: cysteamine-isobionic amide, placebo, or mKF. The modified Melasma Area Severity Index (mMASI) score and spectrophotometric evaluation were conducted at baseline, week 4, week 8, and week 16. Dermatological assessment, patients’ feedback, and satisfaction including quality-of-life scores were also collected. RESULTS: At week 4, cysteamine isobionic-amide and mKF groups showed an equivalent onset of action in terms of mMASI and skin pigmentation contrast reduction. The 2 groups significantly reduced melasma severity and improved the overall skin condition with a comparable efficacy at week 16. Quality of life of melasma patients was significantly improved in the cysteamine isobionic-amide group at week 8 and further at week 16 (P<0.001) compared to the mKF group. Patients’ feedback and satisfaction were higher with the cysteamine isobionic-amide product compared to mKF. CONCLUSION: Cysteamine isobionic-amide provided a rapid onset of action and was as effective as the mKF for the treatment of melasma. The data suggest that cysteamine isobionic-amide could potentially be an acceptable alternative to mKF for the long-term treatment of melasma. J Drugs Dermatol. 2024;23(2):9-16.  doi:10.36849/JDD.7428.

Feasibility of High-Cellular-Resolution Full-Field, Artificial-Intelligence-Assisted, Real-Time Optical Coherence Tomography in the Evaluation of Vitiligo: A Prospective Longitudinal Follow-Up Study.

Vitiligo, a psychologically distressing pigmentary disorder characterized by white depigmented patches due to melanocyte loss, necessitates non-invasive tools for early detection and treatment response monitoring. High-cellular-resolution full-field optical coherence tomography (CRFF-OCT) is emerging in pigmentary disorder assessment, but its applicability in vitiligo repigmentation after tissue grafting remains unexplored. To investigate the feasibility of CRFF-OCT for evaluating vitiligo lesions following tissue grafting, our investigation involved ten vitiligo patients who underwent suction blister epidermal grafting and laser ablation at a tertiary center between 2021 and 2022. Over a six-month period, clinical features, dermoscopy, and photography data were recorded. Utilizing CRFF-OCT along with artificial intelligence (AI) applications, repigmentation features were captured and analyzed. The CRFF-OCT analysis revealed a distinct dark band in vitiligo lesion skin, indicating melanin loss. Grafted areas exhibited melanocytes with dendrites around the epidermal-dermal junction and hair follicles. CRFF-OCT demonstrated its efficacy in the early detection of melanocyte recovery and accurate melanin quantification. This study introduces CRFF-OCT as a real-time, non-invasive, and in vivo evaluation tool for assessing vitiligo repigmentation, offering valuable insights into pigmentary disorders and treatment responses.

Diabetic Patients With Rosacea Increase the Risks of Diabetic Macular Edema, Dry Eye Disease, Glaucoma, and Cataract.

PURPOSE: Inflammation plays a role in diabetic eye diseases, but the association between rosacea and eye diseases in patients with diabetes remains unknown. DESIGN: This retrospective cohort study used claims data from the National Health Insurance Research Database in Taiwan to investigate the association between rosacea and eye diseases in patients with diabetes. MATERIALS AND METHODS: Taiwanese patients diagnosed as having diabetes mellitus between January 1, 1997, and December 31, 2013, and using any hypoglycemic agents were included and divided into rosacea and nonrosacea groups. After applying 1:20 sex and age matching and exclusion criteria, 1:4 propensity score matching (PSM) was conducted to balance the covariate distribution between the groups. The risk of time-to-event outcome between rosacea and nonrosacea groups in the PSM cohort was compared using the Fine and Gray subdistribution hazard model. RESULTS: A total of 4096 patients with rosacea and 16,384 patients without rosacea were included in the analysis. During a mean follow-up period of 5 years, diabetic patients with rosacea had significantly higher risks of diabetic macular edema [subdistribution hazard ratio (SHR): 1.31, 95% confidence interval (CI): 1.05-1.63], glaucoma with medical treatment (SHR: 1.11, 95% CI: 1.01-1.21), dry eye disease (SHR: 1.55, 95% CI: 1.38-1.75), and cataract surgery (SHR: 1.13, 95% CI: 1.02-1.25) compared with diabetic patients without rosacea. A cumulative incidence analysis performed up to 14 years after the index date revealed that the risks of developing ocular diseases consistently increased over time. No significant differences in diabetic retinopathy, age-related macular degeneration, retinal vascular occlusion, ischemic optic neuropathy, optic neuritis, uveitis, or retinal detachment were identified according to rosacea diagnosis. However, we observed significant associations between rosacea and psoriasis, irritable bowel syndrome, anxiety, and major depressive disorder among patients with diabetes. CONCLUSIONS: Rosacea is associated with diabetic macular edema, glaucoma, dry eye disease, and cataract development in diabetic patients, as well as increased risks of psoriasis, irritable bowel syndrome, anxiety, and depression in diabetic patients.

Optimizing surgical outcome of auricular keloid with a novel multimodal approach.

Various treatments are available for auricular keloids, but none has an absolute advantage. A practical and safe therapy to optimize the surgical outcome for auricular keloids is needed. We adopted a multimodal treatment of surgical enucleation, core fillet flap reconstruction, intraoperative corticosteroid injection, and immediate postoperative radiotherapy. There were no routine intralesional corticosteroid injections during follow-up. Keloid recurrences, complications, and risk factors for recurrences were analyzed. The outcome was compared with other published literatures. 45 auricular keloids were included in this study. 85.7% were female with an average age of 27.1 ± 7.5 years, and averaged size was 1.8 × 1.2 ± 0.9 × 0.6 cm. 71.1% were located at ear helix with 28.9% at the ear lobe. Nine keloids were classified as Chang-Park classification type I, 30 for type II, two for type III, and four for IV. The average radiation dosage was 1578.6 cGy. The recurrence rate was 6.7% at an average 24.1-month follow-up. There were no complications of surgery, radiotherapy, and intralesional corticosteroid injection. Our recurrence rate was lower than those in mono-adjuvant therapies of intraoperative corticosteroid injection or radiotherapy. This one-session multimodal approach optimizes treating auricular keloids with a low recurrence rate and minimal post-radiation and long-term corticosteroid injection-related complications.

Dermatoscopy of Common Lesions in Pediatric Dermatology.

The use of dermatoscopy to assist in the diagnosis of a variety of proliferative, pigmentary, inflammatory, infectious, congenital, and genetic cutaneous and skin appendage disorders is constantly increasing, as it is effective, affordable, noninvasive, and quick to perform.

Using weighted regression model for estimating cohort effect in age-period contingency table data.

BACKGROUND: Recently, the multiphase method was proposed to estimate cohort effects after removing the effects of age and period in age-period contingency table data. Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is strongly associated with cirrhosis, due to both alcohol and viral etiologies. In epidemiology, age-period-cohort (APC) model can be used to describe (or predict) the secular trend in HCC mortality. RESULTS: The confidence interval (CI) of the weighted estimates was found to be relatively narrow (compared to unweighted estimates). Moreover, for males, the mortality trend reverses itself during 2006-2010 was found from an increasing trend into a slightly deceasing trend. For females, the increasing trend reverses (earlier than males) itself during 2001-2005. CONCLUSIONS: The weighted estimation of the regression model is recommended for the multiphase method in estimating the cohort effects in age-period contingency table data. IMPACT: The regression model can be modified through the weighted average estimate of the effects with narrower CI of each cohort. METHODS: After isolating the residuals during the median polish phase, the final phase is to estimate the magnitude of the cohort effects using the regression model of these residuals on the cohort category with the weight equal to the occupied proportion according to the number of death of HCC in each cohort.

Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies.

With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5-91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate ideas for early recognition of SCAR and to discontinue offending drugs for better management.

Phytochemicals in Skin Cancer Prevention and Treatment: An Updated Review.

Skin is the largest human organ, our protection against various environmental assaults and noxious agents. Accumulation of these stress events may lead to the formation of skin cancers, including both melanoma and non-melanoma skin cancers. Although modern targeted therapies have ameliorated the management of cutaneous malignancies, a safer, more affordable, and more effective strategy for chemoprevention and treatment is clearly needed for the improvement of skin cancer care. Phytochemicals are biologically active compounds derived from plants and herbal products. These agents appear to be beneficial in the battle against cancer as they exert anti-carcinogenic effects and are widely available, highly tolerated, and cost-effective. Evidence has indicated that the anti-carcinogenic properties of phytochemicals are due to their anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenic effects. In this review, we discuss the preventive potential, therapeutic effects, bioavailability, and structure-activity relationship of these selected phytochemicals for the management of skin cancers. The knowledge compiled here will provide clues for future investigations on novel oncostatic phytochemicals and additional anti-skin cancer mechanisms.

Anticancer Drugs Induced Severe Adverse Cutaneous Drug Reactions: An Updated Review on the Risks Associated with Anticancer Targeted Therapy or Immunotherapies.

Cutaneous adverse drug reactions are commonly seen in patients with anticancer drug treatment. Anticancer drugs, including chemotherapy, target therapy, and recent immunotherapy causing skin reactions ranging from mild skin rash to life-threatening severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) with increase morbidity and mortality while they are receiving cancer treatments, have been proposed to be a result of direct skin toxicity or drug hypersensitivity reactions (these are proposed mechanism, not definite). Differentiating SCARs from other more commonly seen reactions with a better outcome help prevent discontinuation of therapy and inappropriate use of systemic immunosuppressants for presumable allergic reactions, of which will affect the clinical outcome. In this article, we have reviewed published articles from 1950 to August 2017 for SJS/TEN associated with anticancer drugs, including chemotherapy, targeted therapy, and immunotherapy. We aimed to provide an overview of SJS/TEN associated with anticancer drugs to increase clinician recognition and accelerate future studies on the pathomechanism and managements.

Segmented regression analysis of emergency departments patient visits from Septicemia in Taiwan.

BACKGROUND: The protocol for early goal-directed therapy (EGDT) is effective for improving both the costs and outcomes of septicemia treatment, including a significant reduction in case fatality. However, this complicated protocol may have a downside. Furthermore, the Joint Taiwan Critical Care Medicine Committee has launched a nationwide educational program after the publication of the Surviving Sepsis Campaign (SSC) to improve the overall survival rate from septicemia in the emergency care system of Taiwan. OBJECTIVES: To assess the impact of the EGDT protocol and SSC education programs on island-wide septicemia-related emergency department (ED) visits. METHODS: Segmented regression techniques were utilized to assess the differences in annual rates and changes in septicemia-related ED visits between 1998 and 2012. We considered annual incidence of two medical comorbidities as potential confounders: metastatic malignant neoplasms and malignant neoplasms of the lymphatic and hematopoietic tissues. RESULTS: The EGDT protocol was associated with decreased septicemia-related ED visits in 2002 (level change; p < 0.001), while the SSC education program led to a slight increase in septicemia-related ED visits in 2007 (slope change; p < 0.001). For the EGDT protocol, the number of patient visits decreased by 32.9% after the protocol was implemented in 2002 compared with the expected number without the intervention. For the SSC education program, the number of patient visits increased by 20.2% (compared with the predicted number) in 2007 after the education program was implemented. CONCLUSIONS: The EGDT protocol and SSC education program were associated with significant immediate changes and lagged intervention effects on island-wide septicemia-related ED visits.

Metabolic parameters in psoriatic patients treated with interleukin-12/23 blockade (ustekinumab).

The associations between psoriasis, metabolic syndrome and cardiovascular events are increasingly recognized. Studies have shown decreased cardiovascular events with the treatment of methotrexate and anti-tumor necrosis factor, however, effects of interleukin (IL)-12/23 blockade remain debatable. Our study investigated the effect of IL-12/23 blockade on the metabolic parameters in patients with psoriasis. We performed a retrospective cohort study to assess 93 consecutive patients with moderate to severe plaque type psoriasis who received IL-12/23 blockade (ustekinumab) for 24 weeks between January 2012 and May 2016. Metabolic parameters and disease activity (Psoriasis Area and Severity Index [PASI] score) at baseline and 24 weeks of treatment were collected. At week 24, the disease activity improved significantly (P < 0.0001), with a significant reduction of erythrocyte sedimentation rate. Conversely, body mass index was significantly elevated in PASI-75 responders at week 24 of treatment and was independent of disease severity. Fasting sugar and triglyceride levels were also elevated at week 24 in both PASI-75 responders and PASI-75 non-responders. Cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) remained unchanged. These metabolic parameters were not correlated with the improvement in disease severity after ustekinumab treatment. Nonetheless, the atherogenic index, LDL/HDL ratio and cholesterol/HDL ratio remained unchanged. Male sex and cigarette smoking are predictors of elevated plasma triglyceride levels. Our results suggest that despite tremendous improvement in disease activity after ustekinumab treatment, obesity, fasting sugar and hypertriglyceridemia still present in these patients. Regular screening of lipid profile, obesity control and smoking cessation are advised during the treatment of ustekinumab especially in male psoriatic patients with predisposing cardiovascular risks.

Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians.

OBJECTIVE: To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai). METHODS: We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)-induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database. RESULTS: We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6 drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10-10; odds ratio 27.90; 95% confidence interval [CI] 7.84-99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077-0.584). CONCLUSIONS: Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.

Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions.

Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using allopurinol.