Erythema dyschromicum perstans-like eruptions induced by epidermal growth factor receptor inhibitors in patients with lung cancer.

INTRODUCTION: Cutaneous adverse reactions to epidermal growth factor receptor inhibitors (EGFRi) are some of the most common side effects that patients experience. However, cutaneous adverse reactions that cause dyspigmentation in patients have been rarely reported. Erythema dyschromicum perstans (EDP) is a rare pigmentary condition that causes ashy-grey hyperpigmented macules and patches, with a few cases reported from EGFRi in the literature. The disfiguration caused by this condition may negatively impact patients' quality of life. Our study aimed to describe the clinical characteristics of EDP induced by EGFRi to better recognize and manage the condition. METHODS: We conducted a multicenter retrospective review at three academic institutions to identify patients with EDP induced by EGFRi from 2017 to 2023 and included sixteen patients in our study. RESULTS: The median age of patients was 66 years old, with 63% female and 37% male (Table 1). The majority of our patients were Asian (88%). All patients had non-small cell lung cancer and most patients received osimertinib. Median time to EDP was 6 months. The most common areas of distribution were the head/neck region, lower extremities, and upper extremities. Various topical ointments were trialed; however, approximately less than half had improvement in their disease and most patients had persistent EDP with no resolution. All patients desired treatment except one with EDP on the tongue, and there was no cancer treatment discontinuation or interruption due to EDP. Table 1 Patient demographics and clinical characteristics of 16 patients with EDP induced by EGFRi Case no Demographics: age, race, and sex Fitzpatrick skin type Cancer type EGFR therapy Concomitant photosensitive drug(s) Time to EDP (months) Clinical features Distribution Symptoms Treatments and clinical course EDP status from most recent follow up 1 47 y/o Asian male III Stage IV NSCLC Erlotinib None Unknown Brown-blue-gray hyperpigmented patches Bilateral shins Left thigh Xerosis Pruritus Triamcinolone 0.1% ointment for 4 months, improvement of blue discoloration Tacrolimus 0.1% BID for 9 months, improvement but no resolution Ongoing 2 62 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown hyperpigmented patches Bilateral arms Back Forehead Neck Right shin None Tacrolimus 0.1% ointment for 1 year with minor improvement Ongoing 3 69 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown macules and patches Chest Face Forehead Bilateral legs None Tacrolimus 0.1% ointment for 10 months, no improvement Ongoing 4 79 y/o White male II Stage IV NSCLC Osimertinib None 15 Mottled grey-blue hyperpigmented patches and plaques with mild scaling Bilateral arms Back Forehead Neck None Photoprotection, no improvement Ongoing 5 69 y/o Asian female III Stage IV NSCLC Osimertinib Ibuprofen 4 Blue-grey hyperpigmented macules and patches Abdomen Bilateral arms None Tacrolimus 0.1% ointment for 7 months, no improvement Ongoing 6 65 y/o Asian male III Stage IV NSCLC Osimertinib None 20 Hyperpigmented blue gray macules and patches Helix Bilateral shins None Photoprotection, no improvement Ongoing 7 66 y/o Asian female IV Stage IV NSCLC Erlotinib TMP-SMX 6 Ashy grey-brown thin plaques Back Forehead None 2.5% hydrocortisone ointment for 8 months, resolved Resolved 8 82 y/o Asian male III Stage III NSCLC Erlotinib Simvastatin 20 Ash-grey hyperpigmented patches Dorsal feet Forehead Scalp None Photoprotection Ongoing 9 57 y/o Asian female III Stage II NSCLC Erlotinib None 1 Bue-grey discoloration Tongue None No intervention Ongoing 10 51 y/o Asian female III Stage IV NSCLC Osimertinib None 9 Blue-grey hyperpigmented macules and patches Bilateral arms Axillae Groin Neck Trunk None 2.5% hydrocortisone ointment, triamcinolone 0.1% ointment, photoprotection with mild improvement Ongoing 11 67 y/o Asian male III Stage IV NSCLC Osimertinib None 7 Gray-blue macules and patches with mild background erythema and scaling Bilateral arms Ears Face Bilateral shins None Triamcinolone 0.1% ointment, protection for 6 months with mild improvement Ongoing 12 75 y/o Asian female IV Stage III NSCLC Osimertinib TMP-SMX 3 Gray-blue hyperpigmented patches Bilateral arms Abdomen Back Face Bilateral shins Pruritus Triamcinolone 0.1% and betamethasone 0.01% with relief of pruritus, lesions unchanged Triluma cream 6 months, mild improvement Ongoing 13 42 y/o Asian male IV Stage IV NSCLC Afatinib TMP-SMX 24 Grey-brown hyperpigmented patches Back Face None Hydroquinone 4% cream for 2 years with mild improvement Ongoing 14 74 y/o White female III Stage II NSCLC Osimertinib Atorvastatin 4 Grey-brown hyperpigmented patches Bilateral legs Trunk None Photoprotection Ongoing 15 64 y/o Asian female IV Stage IV NSCLC Osimertinib None 3 Gray-brown hyperpigmentation Abdomen Bilateral arms Back Bilateral legs Pruritus Triamcinolone 0.1% cream; No change, minimal concern to patient Ongoing 16 52 y/o Asian female IV Stage IV NSCLC Osimertinib None 42 Gray hyperpigmented patches with digitate shape Abdomen Bilateral flanks None Triamcinolone 0.1% cream Ongoing NSCLC, non-small cell lung cancer, TMP-SMX, Trimethoprim/Sulfamethoxazole CONCLUSIONS: We highlight the largest case series describing EDP from EGFR inhibitors, which mostly affected Asian patients with lung malignancy and on EGFR tyrosine kinase inhibitors. Clinicians should be able to recognize this condition in their patients and assess how it is affecting their quality of life, and refer to dermatology to help with management.

Serpentine supravenous hyperpigmentation induced by chemotherapy: a systematic review.

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.

Rare Variant of Leprosy Reaction (Lucio Phenomenon): A Case Series.

ABSTRACT: Lucio phenomenon (LP) is a variant of type two leprosy, characterized by necrotizing erythema, frequently found in neglected leprosy patient who experience delayed diagnosis or inappropriate treatment. Indonesia is in the third place for highest leprosy cases worldwide. Nonetheless, LP is less common, regardless being an endemic country. In this serial case, we describe the three cases of LP in lepromatous leprosy patients in Denpasar, Bali. All three cases came to our hospital with chronic wounds complained up to a year, accompanied by swollen leg, blisters, tingling sensation, and other symptoms. They had received no suitable treatment, proving LP as a neglected case in primary health care. After a period of treatment, however, patient lesions improved clinically with no physical disability. With this case series, a better understanding toward LP initial complains together with its natural history and further examination could be achieved; thus, improving the early diagnosis and management of LP.

Hyperdiluted Botulinum Toxin and Intense Pulsed Light Treatment: A Case Series to Illustrate a Novel Protocol for Hypertrophic Scar Reduction.

Hypertrophic scars can have significant and far-reaching effects on patients that range from itching to creating difficulty with mobility, all of which can negatively impact the individual's quality of life. A recent study showed that many patients with recent scars report pain, burning, pruritus, erythema, in combination with psychological difficulties that impact bodily movement, choice of clothing, and participation in leisure activities. Botulinum toxin Type A (BoNTA) and intense pulsed light (IPL) have shown promise in treating such scars. We propose a novel treatment protocol involving a 4-week intervention with hyperdiluted BoNTA injections and supplemental treatment with IPL for erythema, and a 6-month scar scale assessment and photographic documentation that occurs before and 6 months after treatment. We report four cases where using hyperdiluted BoNTA, either alone or in conjunction with IPL, substantially reduced scar size, improved overall scar appearance, and diminished erythema in areas on the face and the breasts. Although this report suggests that a schedule of alternating treatments with BoNTA and IPL may be beneficial in reducing scar size and enhancing appearance, further research is necessary to better understand the most effective dosages, the relationship between BoNTA and IPL, and the optimal management of scarring.

A comparative perspective on brucellar, pyogenic, and tuberculous spondylodiscitis.

OBJECTIVE: Non-specific features of spondylodiscitis lead to a delay and challenge in the diagnosis/differential diagnosis/treatment processes, and thus, serious complications may arise. This study aims to compare brucellar, pyogenic, and tuberculous types of spondylodiscitis, considering their demographic, clinical, and laboratory differences. This may provide more rapid management and good outcomes. PATIENTS AND METHODS: A total of 131 patients with infectious spondylodiscitis were included in the study. The patients were divided into brucellar (n=63), pyogenic (n=53), and tuberculous (n=15) types of spondylodiscitis and compared for demographic, clinical, laboratory, and imaging features. RESULTS: Tuberculous spondylodiscitis had higher scores for weight loss, painless palpation, thoracic spine involvement, and psoas abscess formation than other spondylodiscitis. Also, tuberculous spondylodiscitis had higher rates of neurologic deficit and lower rates of lumbar involvement than brucellar spondylodiscitis. Pyogenic spondylodiscitis is more likely to occur in patients who have a history of spine surgery compared to other forms of spondylodiscitis. Also, pyogenic spondylodiscitis had higher rates of fever, erythema, paraspinal abscess, white blood cell (WBC), and erythrocyte sedimentation rate (ESR) than brucellar spondylodiscitis. On the other hand, brucellar spondylodiscitis had higher rates of rural living and sweating than pyogenic spondylodiscitis. CONCLUSIONS: Weight loss, painless palpation, involved thoracic spine, psoas abscess, and neurologic deficit are symptoms favoring tuberculous spondylodiscitis. History of spine surgery, high fever, skin erythema, and paraspinal abscess are findings in favor of pyogenic spondylodiscitis. Rural living, sweating, and involved lumbar spine are symptoms that indicate brucellar spondylodiscitis. These symptoms can be used to distinguish the types of spondylodiscitis.

Differences of bioelectrical impedance in the development and healing phase of pressure ulcers and erythema in mouse model.

Pressure ulcers (PUs) are economically burdensome medical conditions. Early changes in pressure ulcers are associated with erythema. In this study, bioelectrical impedance was used to measure the differences between PUs and blanchable erythema. We divided 21 ICR mice into three groups: control, 1000 mmHg-1h, and 1000 mmHg-6h. Healthy skin, blanchable erythema, and PUs were induced on the dorsal skin. The results indicated an immediate increase in impedance, resistance, and reactance values in the pressure group after release, followed by a subsequent decrease until two days after release. Compared with the control group, impedance and reactance significantly increased by 30.9% (p < 0.05) and 30.1% (p < 0.01), respectively, in the 6 h-loading group immediately after release. One and two days after release, the 1 h-loading and 6 h-loading groups exhibited significantly different degrees of decline. One day after release, impedance and resistance decreased by 30.2% (p < 0.05) and 19.8% (p < 0.05), respectively, in the 1 h-loading group; while impedance, resistance, and reactance decreased by 39.2% (p < 0.01), 26.8% (p < 0.01), and 45.7% (p < 0.05), respectively, in the 6 h-loading group. Two days after release, in the 1 h-loading group, impedance and resistance decreased by 28.3% (p < 0.05) and 21.7% (p < 0.05), respectively; while in the 6 h-loading group, impedance, resistance, and reactance decreased by 49.8% (p < 0.001), 34.2% (p < 0.001), and 59.8% (p < 0.01), respectively. One and two days after release the pressure group reductions were significantly greater than those in the control group. Additionally, we monitored changes during wound healing. Distinguishing early PUs from blanchable erythema by noninvasive bioelectrical impedance technology may have applications value in early assessment of PUs.

XdemvyTM (Lotilaner Ophthalmic Solution) 0.25% Topical Solution for the Treatment of Demodex Blepharitis.

XdemvyTM (lotilaner ophthalmic solution) 0.25% topical solution was recently approved for the treatment of Demodex blepharitis in adults aged ≥18 years. As an antiparasitic agent, lotilaner selectively inhibits gamma-aminobutyric acid chloride channels specific to the parasite and induces spastic paralysis, leading to death of Demodex blepharitis mites. In two randomized, double-masked, vehicle-controlled, multi-center, phase-3 clinical trials (Saturn-1 and Satuirn-2), lotilaner 0.25% topical solution was investigated for the treatment of Demodex blepharitis. Patients were assigned to receive either lotilaner 0.25% topical solution or vehicle (solution that did not contain lotilaner as an active ingredient) twice daily for 6 weeks. On day 43, lotilaner group demonstrated primary efficacy in achieving collarette cure ([collarette grade 0], Saturn-1: study group 44% [92/209], vehicle 7.4% [15/204]; Saturn-2: study group 56% [108/193], vehicle 12.5% [25/200]). Secondary efficacy was achieved by eradication of mite ([0 mite/lash], Saturn-1: study group 67.9% [142/209], vehicle 17.6% [36/304]; Saturn-2: study group 51.8% [99/193], vehicle 14.6% [29/200]), composite cure ([grade 0 collarette as well as grade 0 erythema], Saturn-1: study group 13.9% [29/209], vehicle 1.0% [2/204]; Saturn-2: study group 19.2% [37/193], vehicle 4% [8/200]), and erythema cure ([grade 0 erythema], study group 19.1% [40/209], vehicle 6.9% [14/204]; Saturn-2: study group 31.1% [60/193], vehicle 9.0% [18/199]). The adverse events were mild, with the most common being pain at instillation site. The recommended regimen for lotilaner 0.25% solution is one drop in each eye twice daily for 6 weeks.

Assessing the Effect of Enzymatic Debridement on the Scar Quality in Partial-Thickness Burns to Deep Dermal Burns of the Hand: A Long-Term Evaluation.

Background and Objectives: Burn surgery on the hands is a difficult procedure due to the complex anatomy and fragility of the area. Enzymatic debridement has been shown to effectively remove burn eschar while minimizing damage to the surrounding tissue and has therefore become a standard procedure in many burn centers worldwide over the past decade. However, surprisingly, our recent literature review showed limited valid data on the long-term scarring after the enzymatic debridement of the hands. Therefore, we decided to present our study on this topic to fill this gap. Materials and Methods: This study analyzed partial-thickness to deep dermal burns on the hands that had undergone enzymatic debridement at least 12 months prior. Objective measures, like flexibility, trans-epidermal water loss, erythema, pigmentation, and microcirculation, were recorded and compared intraindividually to the uninjured skin in the same area of the other hand to assess the regenerative potential of the skin after EDNX. The subjective scar quality was evaluated using the patient and observer scar assessment scale (POSAS), the Vancouver Scar Scale (VSS), and the "Disabilities of the Arm, Shoulder, and Hand" (DASH) questionnaire and compared interindividually to a control group of 15 patients who had received traditional surgical debridement for hand burns of the same depth. Results: Between January 2014 and December 2015, 31 hand burns in 28 male and 3 female patients were treated with enzymatic debridement. After 12 months, the treated wounds showed no significant differences compared to the untreated skin in terms of flexibility, trans-epidermal water loss, pigmentation, and skin surface. However, the treated wounds still exhibited significantly increased blood circulation and erythema compared to the untreated areas. In comparison to the control group who received traditional surgical debridement, scarring was rated as significantly superior. Conclusions: In summary, it can be concluded that the objective skin quality following enzymatic debridement is comparable to that of healthy skin after 12 months and subjectively fares better than that after tangential excision. This confirms the superiority of enzymatic debridement in the treatment of deep dermal burns of the hand and solidifies its position as the gold standard.

Narrow-band UVB radiation triggers diverse changes in the gene expression and induces the accumulation of M1 macrophages in human skin.

BACKGROUND: The underlying molecular mechanisms that determine the biological effects of UVB radiation exposure on human skin are still only partially comprehended. OBJECTIVES: Our goal is to examine the human skin transcriptome and related molecular mechanisms following a single exposure to UVB in the morning versus evening. METHODS: We exposed 20 volunteer females to four-fold standard erythema doses (SED4) of narrow-band UVB (309-313 nm) in the morning or evening and studied skin transcriptome 24 h after the exposure. We performed enrichment analyses of gene pathways, predicted changes in skin cell composition using cellular deconvolution, and correlated cell proportions with gene expression. RESULTS: In the skin transcriptome, UVB exposure yielded 1384 differentially expressed genes (DEGs) in the morning and 1295 DEGs in the evening, of which the most statistically significant DEGs enhanced proteasome and spliceosome pathways. Unexposed control samples showed difference by 321 DEGs in the morning vs evening, which was related to differences in genes associated with the circadian rhythm. After the UVB exposure, the fraction of proinflammatory M1 macrophages was significantly increased at both timepoints, and this increase was positively correlated with pathways on Myc targets and mTORC1 signaling. In the evening, the skin clinical erythema was more severe and had stronger positive correlation with the number of M1 macrophages than in the morning after UVB exposure. The fractions of myeloid and plasmacytoid dendritic cells and CD8 T cells were significantly decreased in the morning but not in the evening. CONCLUSIONS: NB-UVB-exposure causes changes in skin transcriptome, inhibiting cell division, and promoting proteasome activity and repair responses, both in the morning and in the evening. Inflammatory M1 macrophages may drive the UV-induced skin responses by exacerbating inflammation and erythema. These findings highlight how the same UVB exposure influences skin responses differently in morning versus evening and presents a possible explanation to the differences in gene expression in the skin after UVB irradiation at these two timepoints.

Combined microfocused ultrasound and delicate pulsed light for facial rejuvenation: A prospective, randomized, and split-face study.

OBJECTIVES: Public's interest in noninvasive skin rejuvenation treatments continues to grow. The advantage of combination therapy lies in that it can target different aspects of skin rejuvenation. This study aimed to assess the efficacy and safety of microfocused ultrasound (MFU) combined with delicate pulsed light (DPL) for facial rejuvenation. METHODS: Twenty-one patients with facial relaxation were enrolled. All patients received whole-face MFU treatment, and one side of the face was randomly assigned to receive DPL. MFU treatment was performed at Months 0 and 3, while DPL treatment was performed at Months 1, 2, 4, and 5. The length and angle of the nasolabial fold and perioral wrinkles, melanin index (MI), erythema index (EI), transepidermal water loss (TEWL), and follow-up time were recorded at Months 0, 3, and 6. Side effects were recorded during treatment and each follow-up visit. RESULTS: Twenty patients successfully completed the study. At the sixth month, the average length of perioral wrinkles and nasolabial folds on the combined side decreased by 11.5% (pwithin < 0.001) and 6.5% (pwithin = 0.011), while 8.3% (pwithin = 0.012) and 3.8% (pwithin = 0.02) on the MFU side. Compared with MFU treatment alone, the combined treatment also showed significant improvements in nasolabial fold angle (from 28.8 ± 3.4° to 32.7 ± 5.0°) and perioral wrinkle angle (from 39.3 ± 5.0° to 43.7 ± 5.1°). In addition, the combined side had greater benefits than the MFU side in improving MI, EI, TEWL, and skin elasticity (pbetween < 0.05). Except for one patient who withdrew due to increased skin sensitivity after MFU treatment, other subjects did not experience permanent or serious side effects. CONCLUSIONS: The combination of MFU and DPL for facial rejuvenation treatment is safe and effective. The combined treatment has better efficacy in skin firmness, and improving skin tone.