Symmetrical drug-related intertriginous and flexural exanthema/baboon syndrome induced by traditional Chinese medicine.

BACKGROUND: Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) refers to an uncommon cutaneous adverse reaction that symmetrically involves the buttock and intertriginous areas after systemic exposure to the offending drug and is previously known as baboon syndrome. SDRIFE related with traditional Chinese medicine (TCM) has not been reported. OBJECTIVE: We presented a case of SDRIFE /baboon syndrome induced by TCM, Xi-Huang capsule. METHODS: A 57-years-old man presented with macular erythematous rash mainly on his intergluteal, inguinal, axillary, popliteal regions for a duration of 5 days. The lesions appeared a day after an oral Chinese patent medicine Xi-Huang capsule for arthralgia. Drug eruption was diagnosed. The rash disappeared completely within a week with immediate discontinuation of Xi-Huang capsule and a short term of systemic therapy with glucocorticosteroids. Patch testing was performed on the patient 1 month after complete resolution. He was patch tested with Xi-Huang capsule (5% and 10% in petroleum) using Finn Chambers on Scanpor tape and T.R.U.E. test system. Five heathy volunteers were also patch tested with the same Xi-Huang capsule. RESULTS: Patch testing to 20 common contact allergens including nickel and fragrance were negative. TCM patch test was positive. No positive results were found in five volunteers. Months later, the patient relapsed after an oral herbal Chinese medicine challenge for arthralgia. To avoid the rash recurrence, he stopped taking any Chinese herbal medicine and had complete resolution of disease. CONCLUSION: The Chinese patent drugs for external and oral have unique advantages and have been widely used in many diseases. It is important that dermatologists monitor for clinically significant manifestations of TCM, such as baboon syndrome. Patch testing could help make a definitive diagnosis.

The extent to which the last decade has yielded additional treatment options for EGFR-associated rash besides classic treatment with antibiotics and corticosteroids - A systematic review.

PURPOSE: To investigate the effectiveness of different interventions for the prevention and treatment of EGFRI treatment-induced rash (EGFRIr) that appeared in the last decade, excluding antibiotics and steroids products alone. METHOD: A systematic review was performed in 2019 and was updated in 2020. The search strategy was limited to studies published within the last 10 years on the Medline database accessed via Pubmed and the Cochrane database. The search was performed using keywords combined with AND, OR. RESULTS: The search yielded thirteen studies. The studies were divided into two categories, based on the intervention method used: four studies used creams containing vitamin K1 or vitamin K3 (henceforth classified as "Category A″) and nine studies ("Category B″) focused on different intervention methods such as laser treatment, Polydatin (PD) cream treatment, treatment with sunscreen, Adapalene gel treatment, topical aloe vera treatment, topical hydration treatment, the impact of a pre-emptive skin treatment and, finally, epidermal growth factor (EGF) ointment treatment. From "Category A″, the results vary as two studies found no benefit from cream use, while two studies indicated a possible improvement on skin reactions from cream use. In "Category B″, a benefit due to laser treatment was indicated, Polydatin-containing moisturizer showed a reduction in the incidence of rash grade ≥ II in patients treated with afatinib, while treatment with sunscreen demonstrated no benefit for the prevention of EGFRIr. Additionally, Adapalene gel use is not recommended as prophylaxis for EGFRIr, topical aloe vera may be used in the management for EGFRIr due to cetuximab, topical hydration resolved the EFGRIr, the pre-emptive skin treatment routine was well tolerated and the epidermal growth factor ointment improved all the symptoms due to EGFRI. CONCLUSIONS: The results from the studies vary, although this study focuses on reviewing treatment interventions that can be utilized, apart from antibiotics and steroids, in order to alleviate the problems of the patients suffering from EGFRIr. More specifically, the authors of this review cannot draw a conclusion from "Category A″, as the efficacy of vitamin K for the management of EGFRIr is controversial. From "Category B″, some of the suggested treatments show encouraging results, while others may prove ineffective and rather harmful for the patients.

ARTICLE: Colloidal Oatmeal Part II: Atopic Dermatitis in Special Populations and Clinical Efficacy and Tolerance Beyond Eczema.

Colloidal oatmeal has a diverse array of applications, clinical benefits, and uses beyond atopic dermatitis. First and foremost, it has been shown to be of benefit in the treatment of atopic dermatitis in skin of color. It has also been shown to be of benefit in the treatment of hand dermatitis, xerosis, psoriasis, skin manifestations of diabetes, and in the treatment of cutaneous adverse effects associated with oncologic therapies. In Part II of this 2-part series, we examine the efficacy, safety, and expansive clinical applications of colloidal oatmeal. J Drugs Dermatol. 2020;19:10(Suppl):s8-11.

Baccharis dracunculifolia (Asteraceae) essential oil displays anti-inflammatory activity in models of skin inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis dracunculifolia (Asteraceae) is a commonly used plant in traditional medicine known as "alecrim-do-campo". Popularly it has been used as an immunostimulant, antibiotic, anti-inflammatory among other applications. So far, only a few studies have investigated the B. dracunculifolia anti-inflammatory effect and none has investigated the effectiveness of essential oil on skin diseases. AIM OF THE STUDY: The study aimed at evaluating the topical anti-inflammatory activity of B. dracunculifolia essential oil (BdEO) in mice models of acute and chronic skin inflammation. MATERIALS AND METHODS: BdEO was obtained from leaves and it was analyzed with Gas Chromatograph. Topical anti-inflammatory activity of BdEO (0.1, 0.3 and 1.0 mg/ear) was evaluated in Arachidonic Acid or TPA-induced acute and chronic skin inflammation in mice. Parameters such edema, cell migration and keratinocytes proliferation were evaluated. In addition, safety and a possible mechanism of action for BdEO essential oil were also investigated. RESULTS: Our results indicate that mainly terpenoids compounds compose BdEO. In addition, topical treatment with BdEO inhibited inflammatory parameters in both acute and chronic models of skin inflammation. This protective effect was associated with reduced edema formation, smaller cellular influx into the inflamed tissue and reduction of keratinocytes hyperproliferation. Although BdEO appears to exert its anti-inflammatory effect through a corticosteroid pathway, no local or systemic side effects were observed. CONCLUSION: Taken together, the present results showed that the essential oil obtained by hydrodistillation from B. dracunculifolia leaf samples exhibit remarkable topical anti-inflammatory properties. Therefore, our study demonstrated evidence for BdEO topical anti-inflammatory efficacy and safety, suggesting that it could be considered for developing of a new phytotherapeutic formulation as treatment for skin diseases.

Chrysoeriol ameliorates TPA-induced acute skin inflammation in mice and inhibits NF-κB and STAT3 pathways.

BACKGROUND: Chrysoeriol is a flavone found in diverse dietary and medicinal herbs such as Lonicerae Japonicae Flos (the dried flower bud or newly bloomed flower of Lonicera japonica Thunb.). These herbs are commonly used for treating inflammatory diseases. Herbal extracts containing chrysoeriol have been shown to have anti-inflammatory effects and inhibit nuclear factor-kappa B (NF-κB) signaling. Some of these extracts can inhibit signal transducers and activators of transcription 3 (STAT3) signaling in cancer cells. PURPOSE: This study aimed to determine whether chrysoeriol has anti-inflammatory effects and whether NF-κB and STAT3 pathways are involved in the effects. STUDY DESIGN AND METHODS: A TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model and LPS-stimulated RAW264.7 cells were used to evaluate the effects of chrysoeriol. Griess reagent was used to measure the production of nitric oxide (NO). Western blot and enzyme-linked immunosorbent assays were employed to detect protein levels. RT-qPCR analyses were used to detect mRNA levels. Haematoxylin and eosin (H&E) staining was employed to examine the pathological conditions in animal tissues. RESULTS: In the mouse model, chrysoeriol ameliorated acute skin inflammation, evidenced by reduced ear thickness, ear weight and number of inflammatory cells in inflamed ear tissues. The compound lowered protein levels of phospho-p65 (Ser536), phospho-STAT3 (Tyr705), inducible nitric oxide synthases (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), IL-1ß and tumor necrosis factor α (TNF-α) in mouse swollen ears. In LPS-stimulated RAW264.7 cells, chrysoeriol also lowered levels of these proteins. In addition, chrysoeriol decreased the production of NO and prostaglandin E2; inhibited the phosphorylation of inhibitor of κB (Ser32), p65 (Ser536) and Janus kinase 2 (Tyr1007/1008); decreased nuclear localization of p50, p65 and STAT3; and down-regulated mRNA levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α that are transcriptionally regulated by NF-κB and STAT3 in the cell model. CONCLUSION: We for the first time demonstrated that chrysoeriol ameliorates TPA-induced ear edema in mice, and that inhibition of JAK2/STAT3 and IκB/p65 NF-κB pathways are involved in the anti-inflammatory effects of chrysoeriol. This study provides chemical and pharmacological justifications for the use of chrysoeriol-containing herbs in treating inflammatory diseases, and provides pharmacological groundwork for developing chrysoeriol as a novel anti-inflammatory agent.

Ruxolitinib Cream Has Dual Efficacy on Pruritus and Inflammation in Experimental Dermatitis.

The goal of this study was to elucidate the anti-pruritic and anti-inflammatory efficacy of ruxolitinib cream in experimentally-induced dermatitis. Atopic dermatitis (AD), the most common chronic relapsing inflammatory skin disease, significantly impairs patients' quality of life, with pruritus being a common complaint. The sensation of itch results from the interplay between epidermal barrier dysfunction, upregulated immune signaling and the activation of the central nervous system. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a central role in pro-inflammatory cytokine signaling in AD. Ruxolitinib cream is a potent and selective JAK1/2 inhibitor currently undergoing clinical evaluation in adults with mild-to-moderate AD (NCT03745638, NCT03920852 and NCT03745651). The efficacy of ruxolitinib cream was tested in murine models of acute and chronic dermatitis and was also characterized in an ex vivo human skin dermatitis model. Ruxolitinib cream was highly effective at ameliorating disease symptoms in multiple murine dermatitis models through downregulation of T helper (Th)2-driven inflammation, resulting in reduced skin thickening and decreased itch. Pathway analysis of mouse ear tissue and human skin explants underscored the role for ruxolitinib in ameliorating inflammation and reducing itch via modulation of the JAK-STAT pathway. Together, the data offer a strong rationale for the use of ruxolitinib cream as a potent therapeutic agent for the clinical management of atopic dermatitis.

Fixed drug eruption due To 2,3-dimercapto-1-propanesulfonic acid (DMPS) treatment for mercury poisoning: a rare adverse effect.

BACKGROUND: Fixed drug eruptions (FDE) are characterized by recurrent, usually solitary erythematous or dark red macular, plaque or bullous lesions, all at the same site. Among the first choices for antidotal treatment in mercury exposure, 2,3-dimercapto-1-propanesulfonic acid (DMPS) is generally a drug with a low incidence of side effects. FDE due to DMPS was not detected in our literature research and so we aimed to present this rare case. CASE REPORT: Forty-eight-year-old male patient, gunpowder and explosives factory worker, was admitted to our hospital because of mercury exposure and we started DMPS treatment. On the second day of chelation treatment, swelling and felting on lips and complaints of wound formation in genital areas started. Annular, purple color plaque on penis with no angioedema was observed. Case was regarded as FDE. Systemic and topical steroid therapy was started after termination of chelation therapy and lesions regressed with steroids. DISCUSSION: Drug eruptions are substantially common dermatological problems and can be seen in about 2.2% of inpatients. The most common unexpected effects of DMPS are allergic skin reactions. The clinical state regress rapidly after the cessation of chelation therapy.

Baicalin Ameliorates Imiquimod-Induced Psoriasis-Like Inflammation in Mice.

Baicalin is the main flavonoid from the roots of an important medicinal plant, Scutellaria baicalensis, which shows a variety biological activities. Psoriasis is a chronic immune-mediated inflammatory disease that affects the skin. The unmet need of psoriasis is that many patients do not respond adequately to available clinical treatment. In this study, we found that baicalin showed inhibited dermal inflammation in a murine model of psoriasis via topical application of imiquimod. After a 5-day topical imiquimod application, baicalin or the control vehicle cream was to applied to the lesions of BALB/c mice for a further 4 days. The erythema, scaling, and thickness of the epidermal layer significantly improved in the baicalin-treated mice. The levels of interleukin-17A, interleukin-22, interleukin-23, and tumor necrosis factor in the skin significantly decreased after baicalin treatment. Baicalin also inhibited imiquimod-induced interleukin-17A production in skin draining lymph node cells. The infiltration of γδ T cells into the skin lesions induced by imiquimod was also suppressed after baicalin treatment. These results suggest that baicalin inhibited skin inflammation through the inhibition of the interleukin-17/interleukin-23 axis in a murine model of psoriasis.

Methotrexate-induced epidermal necrosis: A case series of 24 patients.

BACKGROUND: Methotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVES: To investigate the clinicopathology, risk factors, and prognostic factors of MEN. METHODS: We enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX). RESULTS: Patients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN. LIMITATIONS: The study was limited by the small sample size. CONCLUSION: MEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation.

Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

Effects of Colloidal Oatmeal Lotion on Symptoms of Dermatologic Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors.

OBJECTIVE: The common adverse effects associated with targeted therapy for cancer, such as epidermal growth factor receptor inhibitors (EGFRIs), are dermatologic toxicities that cause the patient physical discomfort and affect treatment. Colloidal oatmeal lotion (COL) has been proven to help prevent dermatitis and xerosis. Evidence of its effect on EGFRI-induced dermatologic toxicities, however, is limited. The purpose of this study was to explore the effect of COL on EGFRI-induced dermatologic toxicities. DESIGN AND SETTING: This study used a 1-group pretest-posttest design with a convenience sample of 30 patients with cancer who developed EGFRI-induced dermatologic toxicities from a medical center in southern Taiwan. All participants applied topical COL 3 to 5 times a day for 4 consecutive weeks and received a pretest and 4 posttests. OUTCOME MEASURES: A generalized estimating equation was used to assess the impact of demographics, disease characteristics, and weeks of COL use on dermatologic toxicity severity, body surface area affected, and level of pruritus. MAIN RESULTS: Significant differences were found between the pretest and all posttests after using COL with regard to the severity, body surface area affected, and level of pruritus in participants who developed EGFRI-induced dermatologic toxicities (P < .05). There were no significant differences in demographics or disease characteristics on EGFRI-induced dermatologic toxicities. CONCLUSIONS: Based on the study results, COL could improve the symptoms of dermatologic toxicities in those receiving EGFRIs with no adverse effects. Therefore, the authors suggest the use of COL in clinical settings.

A case report: delayed high fever and maculopapules during Sorafenib treatment of ectopic hepatocellular carcinoma.

BACKGROUND: Sorafenib is the standard first-line therapy for hepatocellular carcinoma (HCC) and probably ectopic hepatocellular carcinoma (EHCC) as well. No report involves a side effect of delayed high fever of sorafenib. This manuscript describes a case of EHCC in the thoracic and abdominal cavities, who showed a delayed high fever and maculopapules during sorafenib treatment. CASE PRESENTATION: The patient is a 63-year-old Chinese male with advanced EHCC, taking sorafenib 400 mg twice daily. On the tenth day, red maculopapules appeared all over the body. On the same day, the patient began to suffer from continuous high fever. Due to these effects, the patient was asked to cease sorafenib treatment, and the high fever and maculopapules were alleviated quickly. However, the symptoms were present again upon re-challenge of sorafenib. Prednisone was then administered to control the symptoms, with the dosage gradually reduced from 30 to 5 mg/day in 1.5 months. No recurrence of fever or maculopapules has been found. Tumor response reached partial response (PR) and progression free survival (PFS) reached 392 days + by the date of Apr. 14th, 2016. CONCLUSION: EHCC could be treated like orthotopic HCC by oral administration of sorafenib, which shows good tumor response and survival benefit. Delayed high fever and maculopapules are potential, rare and severe side effects of sorafenib, and could be effectively controlled by glucocorticoid.

Pustular drug eruption due to Panax notoginseng saponins.

Panax notoginseng saponins (PNS) are a patented product in the People's Republic of China, and have extensive effects on the cardiovascular system. Here we report on four elderly patients (one male and three female) with drug eruption induced by PNS injection. All developed a sudden skin rash with pruritus from head to foot, and subsequently accepted hospitalization. In each case, PNS had been used for less than 1 week before appearance of the rash. No specific short-term medications or changes in diet or exposure to environmental factors immediately prior to appearance of the rash were identified. These four patients had some interesting features in common, ie, pustules, fever, and elevated circulating neutrophil counts, which required high-dose, long-term glucocorticoid therapy. To our knowledge, this is the first report of pustular drug eruption induced by PNS and provides a useful reference and warning for clinicians.

Fumaric acid esters in psoriasis and multiple sclerosis.

Fumaric acid esters (FAEs) are effective in patients with moderate to severe psoriasis. Recent studies also report the efficacy of one FAE component, dimethylfumarate, in relapsing forms of multiple sclerosis (MS). We describe the case of a patient with MS who developed severe plaque psoriasis during interferon-ß-1a treatment for MS. The psoriasis was unresponsive to usual topical treatments and phototherapy. The patient was started on FAE 720 mg daily, with complete remission of the psoriatic lesions and neurological stabilization at follow-up at 24 months. Our case suggests that FAEs could represent a therapeutic option for patients with MS who develop plaque psoriasis following exposure to immune-modulating agents.

Efficacy and tolerability of topical 0.2% Myrtacine® and 4% vitamin PP for prevention and treatment of retinoid dermatitis in patients with mild to moderate acne.

AIM: The aim of the present study was to evaluate the efficacy and tolerability of an emulsion of 0.2% Myrtacine® and 4% vitamin PP, compared with a simple emollient cream, in the treatment of retinoid dermatitis in patients with mild-to-moderate acne. METHODS: This was a prospective, multicenter, open-label, non-randomised, parallel-group study. Patients (age 12-49 years; skin phototype I-IV) with mild-to-moderate acne, who were treated with a topical retinoid for at least one month and had developed skin irritation were assigned to one of the two following treatments: 0.2% Myrtacine® and 4% vitamin PP (N.=116) or a simple emollient cream (N.=48). Both treatments were administered twice daily, 1-1.5 hours after the application of the topical retinoid. Study endpoints were improvement in signs and symptoms of retinoid dermatitis, global efficacy, reduction in acne severity, overall clinical outcome, patient satisfaction and tolerability. RESULTS: At day 28, compared with the simple emollient cream, 0.2% Myrtacine® and 4% vitamin PP significantly decreased signs (erythema, dryness/scaling, oedema, and roughness) and symptoms (itching, stinging, burning sensation and discomfort) of retinoid dermatitis (P<0.01). In addition, compared with the simple emollient cream, 0.2% Myrtacine® and 4% vitamin PP decreased acne severity in a significantly greater proportion of patients (P=0.023) and was associated with a better clinical outcome (mild, intermediate, clinically relevant or global improvement; P<0.001). 0.2% Myrtacine® and 4% vitamin PP was also associated with greater patient satisfaction and was better tolerated than the simple emollient cream. CONCLUSION: 0.2% Myrtacine® and 4% vitamin PP was effective and well tolerated in the treatment of retinoid dermatitis in patients with mild-to-moderate acne and significantly improved acne severity and overall clinical outcome.

[Research of xuebijing injection combined with glucocorticoid in treating dermatitis medicamentosa like of trichloroethylene with systemic inflammatory response syndrome].

OBJECTIVE: To study the better efficacy of clinic treatment for dermatitis medicamentosa like of trichloroethylene (DMLT) and observe the clinic efficacy of Xuebejing injection for DMLT patients with systemic inflammatory response syndrome (SIRS). METHODS: 16 DMLT patients with SIRS were randomly divided into control group (conventional therapy) and xuebijing group (conventional therapy plus xuebijing). We evaluated all the patients with APACHE II before treatment and checked the TNF-alpha in blood at the different time (before treatment and the 7th day of treatment). The total usages, first dosage of medrol and the time of therapy for each group were counted. RESULTS: All patients were cured, there was no significant difference according to APACHE II and TNF-alpha before treatment in two groups . The level of TNF-alpha of all the patients were decreased markedly, but more significantly in xuebijing group (P < 0.01). Moreover, the treatment group patients were given relatively less total usages, first dosage of medrol and time of therapy (P < 0.01). CONCLUSION: Xuebejing injection combined glucocorticoids can cure DMLT patients with SIRS effectively, and reduce the total usages, first dosage of medrol and time of therapy.