Dermatological Adverse Effects Research Articles

Effects of the epidermal growth factor receptor inhibitor, gefitinib, on lipid and hyaluronic acid synthesis in cultured HaCaT keratinocytes.

Epidermal growth factor receptor inhibitors (EGFRIs) are widely used for treating various cancers, including lung, colon, head and neck cancers. However, EGFRIs have unique dermatological side effects, including acneiform eruption, dry skin, paronychia and pruritus. In this study, we investigated the molecular changes induced by an EGFRI, gefitinib, in the expression of lipogenic enzymes and hyaluronic acid (HA) regulatory proteins in HaCaT keratinocytes, and whether EGF restored these changes. HaCaT cells were treated with gefitinib, with or without EGF, and treated with tumor necrosis factor α (TNFα) for inducing an inflammatory response. The mRNA and protein expression was analyzed by real-time RT-PCR, enzyme-linked immunosorbent assay (ELISA) and western blotting. Gefitinib enhanced the TNFα-induced expression of C-C motif chemokine ligand 2 (CCL2), CCL5 and C-X-C motif chemokine ligand 10 (CXCL10), and the expression of TNFα in HaCaT cells, while EGF restored these changes. At a similar concentration range, gefitinib reduced the mRNA and/or protein expression of various lipogenic enzymes for fatty acid, cholesterol and ceramide synthesis, except acidic sphingomyelinase. Gefitinib suppressed the mRNA and protein expression of HA synthase 2 (HAS2), HAS3, cluster of differentiation 44 (CD44), hyaluronidase 1 (HYAL1) and HYAL2, except the mRNA expression of HYAL1. EGF restored the changes induced by gefitinib, except for the mRNA expression of fatty acid synthase (FASN) and elongation of very long-chain fatty acid protein (ELOVL) 6. In conclusion, EGFRIs suppress lipogenesis and HA metabolism, which may contribute to adverse dermatological effects, including barrier function impairment in cancer patients treated with EGFRIs.

A meta-analysis comparing hepatic arterial infusion chemotherapy and sorafenib for advanced hepatocellular carcinoma.

BackgroundThe majority of patients with hepatocellular carcinoma (HCC) are diagnosed in an advanced stage. Although sorafenib is recommended as the standard treatment for advanced HCC, its efficacy is limited. In some studies, hepatic arterial infusion chemotherapy has demonstrated a significant therapeutic benefit for advanced HCC compared with sorafenib. We systematically evaluated and compared the efficacy and safety of hepatic arterial infusion chemotherapy and sorafenib for advanced HCC.MethodsA systematic search of PubMed, Embase, Web of Science and the Cochrane Library up to December 31, 2020 was conducted. Study outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse effects. The hazard ratio and odds ratio with 95% confidence intervals (CI) were used to measure the pooled effect.ResultsEighteen retrospective or prospective cohort studies and one prospective controlled study were included, with 1,339 patients treated with hepatic arterial infusion chemotherapy (HAIC) and 1,060 patients treated with sorafenib. We found that hepatic arterial infusion chemotherapy was superior to sorafenib in terms of OS [hazard ratio (HR): 0.66, 95% CI: 0.46–0.95, P=0.027], PFS (HR: 0.55, 95% CI: 0.44–0.69, P<0.001), ORR [assessed using Response Evaluation Criteria in Solid Tumors (RECIST): OR: 9.02, 95% CI: 6.01–13.53, P<0.001; assessed using modified RECIST: odds ratio (OR): 3.71, 95% CI: 1.92–7.16, P<0.001], and DCR (assessed using RECIST: OR: 2.31, 95% CI: 1.40–3.83, P=0.001; assessed by modified RECIST: OR: 2.28, 95% CI: 1.22–4.28, P=0.01). Dermatological adverse effects and hypertension were significantly higher in the sorafenib group for all grades of adverse effects. However, regarding severe adverse effects, hepatic arterial infusion chemotherapy was associated with more frequent leukocytopenia and thrombocytopenia.ConclusionsHepatic arterial infusion chemotherapy demonstrated favorable efficacy and safety for advanced HCC compared with sorafenib and should be recommended for suitable patients with advanced HCC.

Localized alopecia and suppression of hypothalamic-pituitary-adrenal (HPA) axis in dogs following treatment with difluprednate 0.05% ophthalmic emulsion (Durezol\xae)

BackgroundDespite the common use of topical ophthalmic corticosteroids in dogs, detailed reports on systemic and dermatologic adverse effects are limited.ResultsNine purpose-bred research Beagles were treated with difluprednate 0.05% ophthalmic emulsion in one or both eyes 2–3 times daily. Some difluprednate treated dogs developed mild to severe alopecia of the periocular region, face, and distal pinna (5/9). The median duration of treatment prior to onset of dermatologic signs for difluprednate treated dogs was 550 days (453–1160 days). Diagnostic testing included complete blood count (CBC) and serum biochemistry, adrenocorticotropic hormone (ACTH) stimulation testing combined with endogenous ACTH measurement, and skin biopsy. The CBC and chemistry were within normal limits for all dogs. There were varying degrees of suppression of the hypothalamic-pituitary-adrenocortical (HPA) axis with difluprednate treatment. Dogs with the most profound alopecic changes had less pronounced HPA axis suppression compared to dogs with no integumentary changes. Skin biopsies demonstrated follicular atrophy and follicular keratosis. When topical difluprednate was reduced to unilateral therapy, the hair regrew on the untreated side of the face. In addition to the affected research dogs, a 7-year old female spayed Chihuahua that was being treated as a clinical patient with long-term difluprednate 0.05% ophthalmic emulsion developed generalized hypotrichosis on the head and body and a potbellied appearance. ACTH stimulation testing revealed suppression of the HPA axis with a mild increase in serum alkaline phosphatase (ALP) activity and a urine specific gravity of 1.016. The combination of clinical signs and laboratory abnormalities was supportive of iatrogenic hyperadrenocorticism.ConclusionsIn dogs long-term use of difluprednate ophthalmic emulsion results in HPA axis suppression and in some cases iatrogenic hyperadrenocorticism. A novel pattern of localized alopecia is suspected to be related to dermal absorption and local action due to superior potency and penetration compared to other commonly utilized ophthalmic corticosteroids.

Safety considerations of systemic Janus kinase inhibitors in atopic dermatitis applications.

Janus kinase (JAK) inhibitors are emerging treatments for atopic dermatitis (AD). Due to this novel role as a therapeutic option for patients with AD, we aimed to review current evidence on the pathophysiology and the safety and adverse effects (AEs) of oral JAK inhibitors for the treatment of AD utilizing the key terms atopic dermatitis, JAK inhibitors, and adverse effect or event. Our study indicated that oral JAK inhibitors have a moderate safety profile for use in AD in several reviews and phase II or III clinical trials. Headaches, nausea, and nasopharyngitis are the most commonly reported systemic AEs. Furthermore, acne, herpes simplex, herpes zoster, and eczema herpeticum are the most commonly recorded dermatological AEs. Current evidence indicates JAK inhibitors may also have less association with some of the serious AEs, although there is potential for increased risk of asthma, acute pancreatitis, neutropenia, and thrombocytopenia. Whereas data remain limited for the long-term safety of JAK inhibitor use in patients with AD, many ongoing clinical trials have promising preliminary results.

27701 Clinical recommendations to address dermatologic healthcare disparities in HIV-positive lesbian, gay, bisexual, and transgender (LGBT) patients

In the United States, 1.2 million people are living with HIV, with gay and bisexual men and transgender women disproportionately affected by the virus. While efforts are underway to improve the quality of care in lesbian, gay, bisexual, and transgender (LGBT) HIV-positive patients and address healthcare disparities in this population, innate institutional and societal stigmas often halt the progression of clinical reform. As physicians who are responsible for the management of the cutaneous manifestations of HIV and the adverse dermatologic effects of anti-retroviral therapy, dermatologists are in a unique position to treat HIV-positive LGBT patients. In an effort to improve the dermatologic care for HIV-positive LGBT patients, our review highlights a dermatologist’s role in HIV-positive LGBT care, addresses HIV and LGBT-related stigma in healthcare, and discusses three clinical interventions that can be implemented to decrease HIV-associated stigma, promote cultural competence, and improve the therapeutic alliance between HIV+ LGBT patients and dermatologists.

28226 Aromatase inhibitor-induced dermatologic adverse effects: A systematic review

Background: Aromatase inhibitors (AIs) are the mainstay of adjuvant endocrine therapy in the management of estrogen receptor–positive breast cancer in postmenopausal women. Dermatology-related adverse events (AEs) (including the skin, hair, nails, and mucosal surfaces) associated with AIs are rare but have been reported in the literature. However, to date, no systematic reviews have been performed to analyze the characteristics of patients and types of dermatology-related AEs developed as a result of AI use.

Abstract 1853: A novel anti-CTLA-4 checkpoint inhibitor prodrug to address on-target off-tumor toxicity for cancer immunotherapy

Abstract As the first approved immune checkpoint inhibitor targeting CTLA-4, ipilimumab has achieved great clinical success in cancer immunotherapy, particularly in combination with anti-PD-1 therapy. However, ipilimumab can also induce severe and sometimes fatal immune-mediated adverse reactions due to autoimmune responses in normal tissues, which may involve any organ system and cause enterocolitis, hepatitis, dermatologic adverse effects, endocrinopathies, pneumonitis, and nephritis with renal dysfunction, restricting its clinical applications. Thus, development of next generation anti-CTLA-4 antibodies with enhanced antitumor efficacy and improved safety profile is urgently needed. ADG126 is a novel anti-CTLA-4 fully human IgG1 antibody prodrug generated with Adagene SAFEbody technology, which is designed to be activated preferentially in the tumor microenvironment, limiting on-target off-tumor toxicities in normal tissues. This is realized by attaching an optimized peptide through library screening to the N-terminus of the light chain consisting of a masking moiety followed by a cleavage moiety. The masking moiety functions to block ADG126 binding to CTLA-4, however, after cleavage by proteases known to be highly expressed and active in tumor tissues but not in normal tissues, the masking moiety is released, and the antibody is then activated and able to bind and inhibit CTLA-4 function in situ, which has the potential to minimize the side effects and widen the therapeutic window compared to traditional antibodies. Nonclinical pharmacological studies demonstrate that unmasked or activated ADG126 (but not masked or inactive ADG126) binds to a unique and conserved epitope of CTLA-4 with multiple species cross-reactivity and effectively blocks the CTLA-4/B7 ligands interactions. Activated ADG126 potentiates T cell activation inducing elevated IL-2 cytokine production in the presence of a primary stimulatory signal, depletes immunosuppressive Treg activity through enhanced ADCC, and reduces immunosuppressive Treg activity specifically in the tumor microenvironment to mediate anti-tumor responses. ADG126 demonstrates efficacious anti-tumor activity in multiple syngeneic murine tumor models as single agent, as well as in combination with other immune modulatory agents. Nonclinical toxicology studies demonstrate that ADG126 is well-tolerated in cynomolgus monkeys. These results suggest that the design to have activation of ADG126 prodrug preferentially in tumors may allow treatments to deliver higher efficacious dose levels specific to the local tumor microenvironment concomitant with a superior systemic safety profile compared with other traditional anti-CTLA-4 antibodies. Thus, ADG126 may hold great promises to achieve much better efficacy and safety profile for immunotherapy against a broad spectrum of human cancers. Citation Format: Guizhong Liu, Xiaohong She, Yan Li, Felix Du, Peter Luo. A novel anti-CTLA-4 checkpoint inhibitor prodrug to address on-target off-tumor toxicity for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1853.

Management of cutaneous side effects of inflammatory bowel disease therapy: A dermatologic viewpoint.

Medications used in the treatment of inflammatory bowel disease cause a wide range of dermatologic side effects, and minimal guidance exists on how to manage them. The intention of this review article is to summarize common dermatologic adverse reactions related to inflammatory bowel disease therapy and to provide evidence-based guidance on management. We conducted a scoping review using PubMed and Google Scholar to identify studies reporting clinical information on dermatologic side effects of medications used in the treatment of inflammatory bowel disease. The most commonly reported dermatological adverse effects from inflammatory bowel disease therapy were cutaneous malignancy and cutaneous infections. Thiopurines, methotrexate, tumor necrosis factor (TNF) inhibitors, interleukin (IL)-12/23 inhibitors, and integrin inhibitors can be continued if nonmelanoma skin cancer arises during therapy and the malignancy should be surgically excised. TNF inhibitors and IL-12/23 inhibitors can be continued in the setting of stage I surgically resectable melanoma but should be discontinued in advanced melanoma. For complicated cutaneous bacterial infections, methotrexate and TNF inhibitors should be halted, and IV antibiotics should be administered. Complicated herpes zoster infection warrants discontinuation of TNF inhibitors, whereas IL-12/23 and JAK inhibitors can be continued. Inflammatory bowel disease therapies are associated with several dermatological adverse effects, and management options vary by agent. Certain agents may require discontinuation in the setting of nonmelanoma skin cancer, melanoma, and cutaneous infections. Many other dermatological adverse effects from inflammatory bowel disease therapy require specialized management or referral to dermatology.

STEVENS-JOHNSON SYNDROME DUE TO ADVERSE DRUG REACTIONS: A CASE SERIES

Stevens-Johnson syndrome (SJS) is a rare, serious disorder affecting skin and mucous membranes. It is one of the few serious dermatological adverse effects of drugs encountered in clinical practice which is characterized by blisters and rash on skin, mucous membranes, swelling over face and lips, and hyperpigmentation. After that, the outer layer of affected skin becomes dead, sheds, and starts to heal after several days of inflicting injury. Here, we present a case series of ofloxacin and chloroquine induced SJS after the consent given by patients. First case is a 62 years old male received Ofloxacin and second patient is a 40 years old male received chloroquine. Both patients experienced a severe skin reaction which was diagnosed as SJS. The above-mentioned medications will be implicated in cases of SJS. We should prescribe these medications with extreme caution.

Perspective approaches on melanogenesis inhibition

Melanogenesis is a melanin-forming process responsible for protecting the skin against ultraviolet radiation damage. An excess production of melanin, however, may result in hyperpigmentation (darkening of the skin) to adverse dermatological effects (freckles, solar lentigines, and melasma) and skin cancer. These hyperpigmentary skin disorders may also have a major effect on a person's appearance and could even result in emotional and mental distress, as well as a diminished quality of life. A large number of melanogenesis inhibitors have been discovered, but most of them appeared to have undesirable side effects. Therefore, in order to better understand the mechanisms of hyperpigmentary skin disorders and to establish effective and safe melanogenesis inhibitors, more fundamental research is needed. Apart from tyrosinase blockers, there are also alternative approaches that involve the manipulation of melanogenesis regulatory pathway such as α-melanocyte-stimulating hormone blockers, melanosome transferase inhibitors, and cytokines. This review abridges data on the different melanogenesis inhibitors and depigmentation agents from both natural and synthetic agents from the last few years.

A systematic review on treatment-related mucocutaneous reactions in COVID-19 patients.

Most of drugs could have certain mucocutaneous reactions and COVID‐19 drugs are not an exception that we focused. We systematically reviewed databases until August 15, 2020 and among initial 851 articles, 30 articles entered this study (20 case reports, 4 cohorts, and 6 controlled clinical trials). The types of reactions included AGEP, morbiliform drug eruptions, vasculitis, DRESS syndrome, urticarial vasculitis, and so on. The treatments have been used before side effects occur, included: antimalarial, anti‐viral, antibiotics, tocilizumab, enoxaparin and and so on. In pandemic, we found 0.004% to 4.15% of definite drug‐induced mucocutaneous reactions. The interval between drug usage and the eruption varied about few hours to 1 month; tightly dependent to the type of drug and hydroxychloroqine seems to be the drug with highest mean interval. Antivirals, antimalarials, azithromycin, and tocilizumab are most responsive drugs for adverse drug reactions, but antivirals especially in combination with antimalarial drugs are in the first step. Types of skin reactions are usually morbilliform/exanthematous maculopapular rashes or urticarial eruptions, which mostly may manage by steroids during few days. In the setting of HCQ, specific reactions like AGEP should be considered. Lopinavir/ritonavir is the most prevalent used drug among antivirals with the highest skin adverse reaction; ribarivin and remdisivir also could induce cutaneous drug reactions but favipiravir has no or less adverse effects. Logically the rate of dermatologic adverse effects among anivirals may relate to their frequency of usage. Rarely, potentially life‐threatening reactions may occur. Better management strategies could achieve by knowing more about drug‐induced mucocutaneous presentations of COVID‐19.

Low Dose Daily Corticosteroid Tapering Regimen Allows Highly Effective and Practical Desensitization for Multiple Myeloma Patients with Skin Rash after Immunomodulatory Drugs

Introduction: Immunomodulatory drugs (IMiDs) are being frequently used as an integral part of induction regimen as well as maintenance after Bone Marrow Stem cell Transplant (BMSCT) therapy as backbone of therapy for patients with plasma cell neoplasm (PCN) including Multiple Myeloma (MM). Therapy is often complicated by dermatologic adverse effects which may herald a favorable prognosis suggesting a more robust immune stimulation by this class of drugs. The incidence of IMiD-associated rash is up to 27% in some reports and can range from mild to moderate to severe and life threatening skin toxicity including Steven-Johnsons syndrome and toxic epidermal necrolysis. IMiD-associated skin eruptions are thought to result from differential T cell immune modulation. The optimal management strategy for IMiD induced rash is unknown. The European Myeloma Network recommends topical corticosteroids and antihistamines for localized skin reactions. For severe reactions, a desensitization protocol with prolonged 6-week steroid taper is recommended based on a case series of five patients that developed delayed cutaneous adverse effects to IMiD [Lee MJ et al]. Dexamethasone used concomitantly with IMiD as part of the treatment regimen does not decrease the occurrence of skin rash as shown by Sviggum et al. The likely explanation is that concurrent dexamethasone is not effectively able to exert immunosuppressive activity to mitigate the occurrence of cutaneous reactions. Hence, a prolonged, daily steroid protocol is required for effective desensitization. Therefore, we designed a standardized 3-week steroid rash prophylaxis protocol with a low dose daily corticosteroid tapering regimen that allows desensitization and reinstitution of the same IMiD. We assessed the impact of this desensitization regimen on clinical outcomes, by comparing patients with versus without dermatologic manifestations. Methods: Dermatologic adverse effects associated with IMiDs in our study were managed by a single oncologist using a standardized approach. A total of 87 patients were evaluated, 24 patients in the rash group vs 63 controls. A cohort of age- and gender-matched without rash (n = 63) was randomly selected from the institutional database. The effects of rash on overall and progression free survival (OS and PFS) were further estimated using Cox regression controlling for the effects of age and gender. Results: Median time to development of rash after IMiD initiation was 28 days (range 2-232 days). The incidence of rash was 27.6% (95% CI: 19.3%-37.8%). All patients were managed by temporary treatment interruption and upon clearance of rash, re-institution of the same IMiD concomitantly with a standardized 3-week steroid rash prophylaxis protocol (prednisone at 10 mg daily for 10 days, followed by 5 mg daily for 10 days, followed by 5 mg on alternate days for 10 days). As a result, all patients were able to restart the same IMiD with none re-experiencing any dermatologic adverse effect afterward. Comparing to controls without rash, there was no significant difference in PFS (p=0.769) or OS (p=0.24) in the multivariable regression model. Conclusions: Proposed 3-week corticosteroid regimen showed 100% success rate in re-instituting IMiDs without recurrence of skin rashes in our cohort. The results of our study indicate that the 30-day prednisone course is practical, well tolerated, effectively desensitizes and allows re-institution of IMiD enabling patients to enjoy comparable outcomes to those without skin rash. Whether development of rash correlates with improved outcomes is unknown. Here, outcomes were similar in both cohorts. Disclosures Caimi: Celgene Corp: Other: Incyte Corporation - Ownership - Pharmacyclics, Inc. - Ownership - Celgene Corp. - Other, Speakers Bureau; ADC Therapeutics: Research Funding; Genentech: Research Funding. de Lima:BMS: Other: Personal Fees, advisory board; Celgene: Research Funding; Pfizer: Other: Personal fees, advisory board, Research Funding; Incyte: Other: Personal Fees, advisory board; Kadmon: Other: Personal Fees, Advisory board. Malek:Bluespark: Research Funding; Takeda: Other: Advisory board , Speakers Bureau; Medpacto: Research Funding; Cumberland: Research Funding; Amgen: Honoraria; Clegene: Other: Advisory board , Speakers Bureau; Sanofi: Other: Advisory board; Janssen: Other: Advisory board, Speakers Bureau.

Protein Binding of Lapatinib and Its N- and O-Dealkylated Metabolites Interrogated by Fluorescence, Ultrafast Spectroscopy and Molecular Dynamics Simulations.

Lapatinib (LAP) is an anticancer drug generally used to treat breast and lung cancer. It exhibits hypersensitivity reactions in addition to dermatological adverse effects and photosensitivity. Moreover, LAP binds to serum proteins and is readily biotransformed in humans, giving rise to several metabolites, such as N- and O-dealkylated products (N-LAP and O-LAP, respectively). In this context, the aim of the present work is to obtain key information on drug@protein complexation, the first step involved in a number of hypersensitivity reactions, by a combination of fluorescence, femtosecond transient absorption spectroscopy and molecular dynamics (MD) simulations. Following this approach, the behavior of LAP and its metabolites has been investigated in the presence of serum proteins, such as albumins and α1-acid glycoproteins (SAs and AGs, respectively) from human and bovine origin. Fluorescence results pointed to a higher affinity of LAP and its metabolites to human proteins; the highest one was found for LAP@HSA. This is associated to the coplanar orientation adopted by the furan and quinazoline rings of LAP, which favors emission from long-lived (up to the ns time-scale) locally-excited (LE) states, disfavoring population of intramolecular charge transfer (ICT) states. Moreover, the highly constrained environment provided by subdomain IB of HSA resulted in a frozen conformation of the ligand, contributing to fluorescence enhancement. Computational studies were clearly in line with the experimental observations, providing valuable insight into the nature of the binding sites and the conformational arrangement of the ligands inside the protein cavities. Besides, a good correlation was found between the calculated binding energies for each ligand@protein complex and the relative affinities observed in competition experiments.

Ingestible Sensors and Medication Adherence: Focus on Use in Serious Mental Illness.

Background: Poor medication adherence is a major public health concern. Patients living with a serious mental illness (SMI) commonly present with non-adherence to their medication regimen, which can lead to relapse and hospitalizations. The high rates of antipsychotic non-adherence continue to persist despite several interventions and medication advances. This review evaluates the possible role of the ingestible sensor technology for medication adherence in different conditions, with a focus on use in the SMI schizophrenia. Methods: Literature searches were conducted in July 2019 in the PubMed database. Results: In small studies of ingestible sensor use, the average adherence ranged from 73.9% to 88.6% for SMI and ≥ 80% for cardiac and transplant (99.4%) patients. In SMI studies, patients were clinically stable, and the majority had a clinical global impression severity of “mild disease”. Patients generally experienced relatively minor dermatological adverse effects related to wearable sensor use. Conclusions: A medication with an ingestible sensor may help provide real-time objective medication-taking adherence information for clinicians. However, further studies are needed to understand the impact of use on adherence and improvement on treatment outcomes with the ingestible sensor technology.

A highly effective and practical desensitization regimen: Results in comparable clinical outcomes for multiple myeloma patients with skin rash after immunomodulatory drugs.

12104 Background: Immunomodulatory drugs (IMiDs) are backbone of myeloma therapy for patients with Multiple Myeloma (MM). The incidence of IMiD-associated rash is up to 27% in some reports impeding maximal benefit of this agent. The optimal management of IMiDs-associated skin is unclear. The concurrent weekly Dexamethasone (Dex) does not diminish the incidence of skin eruptions with IMiDs (Sviggum, et al. 2006), therefore we designed a low dose daily and tapering corticosteroid regimen to tame this immune response upon restarting IMiDs and allow desensitization and reinstitution of the same IMiD. Furthermore, we assessed the impact of this desensitization regimen on clinical outcome. Methods: A total of 160 patients were evaluated. The incidence of rash was found to be 13% (n = 21). A cohort of age- and gender-matched without rash (n = 39) was randomly selected. The effects of rash on overall and progression free survival (OS and PFS) were further estimated using Cox regression controlling the effects of age and gender. Results: Median time to development of rash after IMiD initiation was 28 days (range, 2-232). Rashes were graded as low (I-II) in 89% (n = 17) and high (III-IV) in 19% of pts. All pts were managed by temporary treatment interruption and upon clearance of rash, re-institution of the same IMiD concomitantly with a standardized 3-week steroid rash prophylaxis protocol (prednisone at 10 mg daily for 10 days, followed by 5 mg daily for 10 days, followed by 5 mg on alternate days for 10 days). As a result, all patients were able to restart the same IMiD with none re-experiencing any dermatologic adverse effect afterward. Comparing to no-rash controls, there was no significant difference in PFS (0.13) or OS (p = 0.12) in multivariate regression model. Conclusions: Proposed 3-week corticosteroid regimen showed 100% success rate in reinstituting IMiDs in our cohort. It may provide a highly effective and practical short term immunosuppression required to enable patients to restart IMiDs and enjoy comparable outcome to pts without skin rash.

Dermatologic adverse effects of breast cancer chemotherapy: a longitudinal prospective observational study with a review of literature.

Breast cancer patients may experience an increased chance of survival with adjuvant chemotherapy. However dermatologic adverse effects can cause major discomfort due to physical or cosmetic problems. This study aims to describe dermatologic complications in breast cancer patients during chemotherapy. This longitudinal prospective observational study included data on women with non-metastatic breast cancer whom were treated with AC-T protocol (anthracycline, cyclophosphamide, and taxane) adjuvant chemotherapy and consecutively enrolled during two years. The study was performed in an educational and tertiary referral center. The patients' information including age, body mass index (BMI), past medical history, and different dermatologic complications were collected for all participants. Of 190 enrolled women, all patients experienced alopecia, which occurred in 131 patients (68.9%) after the first cycle. Skin, mucosal, and nail involvement were respectively seen in 46 (24.2%), 51 (26.8%), and 86 (45.2%) cases. Cutaneous complications were observed mainly between thethird and sixth chemotherapy cycles. Palmoplantar erythema and palmoplantar dysesthesia were the most common cutaneous complications. Dermatologic adverse effects were significantly more frequent in the patients with an underlying disease. These findings suggest that dermatologic adverse effects of adjuvant chemotherapy are common and could be induced by all components of AC-T regimen. These complications should be skillfully managed to increase patients' comfort.

COVID-19 Pandemic & Skin Care Guidelines for Health Care Professionals.

The Novel corona virus is bringing multiple challenges for health care professionals. Skin is the biggest organ and the first line of defense against different infections and external factors. Being the front line warriors, health care professionals are susceptible to various skin conditions due to prolonged use of personal protective equipment. These adverse skin conditions are redness, irritation, itching, contact dermatitis, and aggravation of underlying skin conditions like seborrheic dermatitis and acne vulgaris. In the current global situation, the potential incidence of such adverse dermatological effects does not in any manner cause the HCPs to deviate from the strict specific precautionary hygiene rules. These skin problems are manageable with the few precautionary measures. This article explores the different skin conditions that result from personal hygiene measures and usage of protective gear and will suggest some practical advice about how to manage and protect from these different adverse skin conditions.

Cutaneous toxicities of new targeted cancer therapies: must know for diagnosis, management, and patient-proxy empowerment

The world of oncology treatment is rapidly changing, and with the investigation into and utilization of molecular signaling pathways for cancer treatment, many new targeted small-molecule oral agents have been introduced as therapies, with more new drugs appearing every year. These agents, while generally considered less toxic overall than traditional chemotherapy, are not without adverse effects. The authors undertook an extensive literature search to determine the incidence, severity, and management strategies for small-molecule oral targeted agents approved by the FDA between 2013 and 2018. Dermatologic adverse effects are among the most frequently seen with many of these targeted therapies, and may include rashes, palmar-plantar dysesthesia, alopecia, secondary skin malignancies, and hair and nail changes. Rarely, more severe cutaneous toxicities are seen, such as Stevens-Johnson Syndrome and toxic epidermal necrolysis. In many cases, there is no specific management strategy suggested in the literature for these toxicities, but frequent monitoring of the skin, prophylactic management of palmar-plantar dysesthesia, use of corticosteroids and/or antihistamines, and intervention with dose interruption are suggested depending on circumstance and severity. Patient education and timely intervention is warranted in order to ensure that patient treatment is optimized.

Frequent Hand Washing for COVID-19 Prevention Can Cause Hand Dermatitis: Management Tips.

Coronavirus disease 2019 (COVID-19) continues to spread globally, outpacing the capacity and resources of health systems worldwide. A therapeutic vaccine is not yet on the rise, and preventive measures are the current approach to restraint the transmission of cases. As the virus is highly contagious via respiratory route (droplets from infected persons, widely spread by coughing or sneezing) and via contact with contaminated surfaces, community transmission and spread can be decreased through the practice of regular and diligent hand hygiene. Frequent hand washing implies a prolonged exposure to water and other chemical or physical agents and may induce several pathophysiologic changes, such as epidermal barrier disruption, impairment of keratinocytes, the subsequent release of proinflammatory cytokines, activation of the skin immune system, and delayed-type hypersensitivity reactions. Adverse dermatologic effects, such as excessive skin dryness or even contact dermatitis (particularly the irritant subtype and, to a lesser extent, the allergic subtype), can occur, especially in individuals with a history of atopic dermatitis. These skin conditions are perfectly manageable, and applying a moisturizer immediately after washing hands or after using a portable hand sanitizer is the cornerstone in preventing the development of eczematous changes in the hands. In the current global context, the potential occurrence of these dermatological adverse events should in no way cause people to deviate from strict hand hygiene rules.

Protective effects of doxepin cream on radiation dermatitis in breast cancer: A single arm double-blind randomized clinical trial.

Breast cancer is the most frequently occurring cancer in women. Lumpectomy followed by radiotherapy is suggested to be as effective as a total mastectomy. Radiation-induced dermatitis often occurs as a result of breast radiotherapy. Recent studies suggest that doxepin has promising anti-inflammatory properties. This study was undertaken to evaluate the effects of doxepin therapy on radiation dermatitis. A double-blind randomized clinical trial was launched from 2016 to 2017, with a total of 48 patients who had undergone breast-conserving surgery and received postoperative radiation therapy. Radiotherapy was applied 5 days per week for 5 weeks. Adverse dermatological effects were evaluated by a physician at the beginning of the fifth week of radiotherapy and the patients were then randomly assigned (1:1 ratio) to receive either doxepin (5%) or placebo cream for 7 days. There were no significant differences in the dermatitis grade between doxepin and placebo groups at baseline (P > .5). The occurrence of acute dermatitis (grade 2 or higher) was significantly lower with the use of doxepin than with placebo (P ≤ .0001, Zα = 1.96 at 95% confidence interval). Doxepin cream prevents dermatitis grade 2 or higher during post-operative breast irradiation. Doxepin cream is easy to use, affordable and prevents pain and irritation.