Papulopustular Eruption Research Articles

Erosive pustular dermatosis of the scalp induced by gefitinib: case and review of the literature

Gefitinib is a selective tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) used for the treatment of malignant neoplasms. The most frequent skin complication during gefitinib therapy is an acneiform papulopustular eruption, usually distributed in the seborrheic areas but occasionally widespread. We report a patient with erosive pustular dermatosis of the scalp, a neutrophil-mediated skin disease presenting with sterile pustules evolving into erosions and crusts on the scalp, during treatment with the EGFR inhibitor gefitinib for lung cancer. A literature review of the drug-induced cases of this rare entity is provided.

Treatment of pediatric periorificial dermatitis with topical calcineurin inhibitor and topical/oral metronidazole.

Pediatric periorificial dermatitis is a papulopustular eruption found around the facial orifices in children. Although the treatment of the disease has been largely anecdotal and experience-based, studies have shown that topical calcineurin inhibitors, as well as other topical and oral antibiotics, such as metronidazole, can be effective treatment options. However, most of the studies with a sizable number of patients have been based on the Caucasian population. Herein, we evaluated the clinical efficacy of topical calcineurin inhibitors and topical/oral metronidazole in 24 Korean patients with pediatric periorificial dermatitis. The majority of the patients showed a complete response to treatment.

Cutaneous adverse events and quality of life in outpatients receiving anticancer agents: results from an observational, cross-sectional study.

BackgroundDespite growing interest in cutaneous adverse events (CAEs) and their management in patients with cancer, they are often underreported and there are no extensive data on their impact on quality of life (QoL). Healthcare professionals should consider this issue in order to minimize its negative impact on QoL and improve patient outcomes. This study evaluates the impact of CAEs on QoL in outpatients receiving anticancer drugs and aims to determine the differences in QoL between conventional chemotherapy versus targeted therapies.MethodsA total of 114 cancer patients with CAEs were included in this observational, cross-sectional study. Patient-reported outcomes instruments (Functional Assessment of Cancer Therapy – General, Dermatology Life Quality Index, and Skindex-16) were used.ResultsMean scores in QoL indices were 65.3±13.4, 8.4±5, and 30.8±16.9 in Functional Assessment of Cancer Therapy – General, Dermatology Life Quality Index, and Skindex-16, respectively. The CAEs that had the greatest impact on dermatologic-related QoL were hand–foot skin reaction, rash, palmo-plantar erythrodysesthesia, and papulopustular eruption. No significant differences in QoL indices according to the type of treatment (conventional chemotherapy versus targeted therapy) were observed.ConclusionsCAEs, and particularly hand–foot toxicities, rashes, and papulopustular eruptions, can have an impact on QoL in outpatients receiving anticancer drugs as evaluated with three different patient-reported outcomes instruments. No differences in QoL related to CAEs were observed between conventional chemotherapy and targeted therapy.

BRAF Inhibitors for the Treatment of Papulopustular Eruptions from MAPK Pathway Inhibitors.

Inhibitors of the mitogen-activated protein kinase (MAPK) pathway are commonly used in clinical oncology. However, with the exception of BRAF inhibitors (BRAFi), MAPK pathway inhibitors such as epidermal growth factor receptor inhibitors (EGFRi) or MEK inhibitors (MEKi) are associated with dose-limiting papulopustular eruptions. Interestingly, patients treated with a combination of systemic BRAFi and MEKi experience less skin toxicities than patients on monotherapy BRAFi or MEKi. The reduction in cutaneous adverse events with combination therapy is thought to be due to a paradoxical activation of the MAPK pathway by BRAFi in keratinocytes carrying wildtype BRAF. Although treatment options for EGFRi- or MEKi-induced papulopustular eruptions exist, many patients still experience dose reduction, interruption, or discontinuation of EGFRi or MEKi. With the goal of activating MAPK signaling in the skin via BRAFi while minimizing systemic risks, we propose topical BRAFi therapy for the treatment and prevention of papulopustular eruptions due to MAPK pathway inhibitors. If effective, patients will be able to tolerate higher doses of MAPK pathway inhibitors, stay on treatment longer, and achieve better therapeutic outcomes overall.

Management of skin adverse reactions in oncology.

Chemo and targeted anticancer therapies present significant skin adverse reactions, which impair the patients' quality of life. Cutaneous toxicities lead to poor treatment adherence, drug cessation, and psychosocial distress. This review aims to summarize the current knowledge concerning the prevention and management of skin toxicity arising from these therapies. A systematic literature search on online databases was conducted. The categorization of the main preventive and treatment measures was performed according to the level of evidence. Management of skin adverse reactions of oncology treatments is very heterogeneous, which can be explained by the lack of sound evidence-based treatments. The most studied adverse effects are papulopustular eruption, xerosis, and hand-foot syndrome. Prevention of xerosis stands out as the strategy most supported by level II studies. With respect to treatment, the use of antibiotics in papulopustular eruption resulting from anti-epidermal growth factor receptor agents is the most evidence-based approach. In general, the number of studies published in the literature classified with a level II of evidence (52%) is similar to the ones classified as level IV (33%), making clear the need of more randomized controlled trials regarding the effectiveness of preventive and treatment measures of skin adverse reactions of chemo and targeted anticancer therapies.

Reduced induction of human β‐defensins is involved in the pathological mechanism of cutaneous adverse effects caused by epidermal growth factor receptor monoclonal antibodies

Epidermal growth factor receptor inhibitors (EGFRIs) frequently cause cutaneous adverse effects such as papulopustular eruptions. However, the mechanism of the reactions remains unclear. To assess the pathological mechanism of cutaneous adverse reactions caused by EGFRIs, we investigated whether EGFRIs have an influence on the innate immune response of the skin. Levels of human β-defensins (hBDs), which serve as the first line of defence against infection by pathogenic microorganisms, in the stratum corneum samples of patients treated with EGFR. monoclonal antibodies were measured before and after starting therapy. There were no obvious trends in hBD production in patients without eruptions, whereas a significant decrease in hBD1 and hBD3 production and a nonsignficant decrease in hBD2 production were observed in patients who developed papulopustular eruptions. Our results suggest that a reduction in hBD contributes to the increased incidence of papulopustular eruptions.

Effects of tyrosine kinase inhibitor therapy on skin toxicity and skin-related quality of life in patients with lung cancer: An observational study.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is the primary treatment option for patients with non-small cell lung cancer (NSCLC). However, one of the major adverse effects associated with this therapy is skin toxicity, which impacts the patient's quality of life. This study aimed to describe the severities and locations of skin toxicity, and to analyze their association with the quality of life in patients with advanced NSCLC who received EGFR-TKI therapy as first-line treatment.This cross-sectional and correlation study was conducted at a tertiary medical center in northern Taiwan between July 2015 and March 2016. Skin toxicity was assessed and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). The Skindex-16 scale was used to measure the skin disease-related quality of life.A total of 146 NSCLC patients who received EGFR-TKI therapy within the first 3 months of diagnosis were included in this study; 93.2% of these patients experienced skin toxicities. Approximately 70% of the patients developed xerosis and pruritus, while 50% had papulopustular eruptions and paronychia. The mean skin symptom impact score was 5.38 (standard deviation = 2.65). The skin-related quality of life varied widely among the participants but remained acceptable (mean score = 13.96, standard deviation = 16.55). Skin symptoms correlated significantly with poor quality of life (r = 0.50, P < .001). Younger patients and those treated with afatinib were the most affected, reporting the poorest quality of life. Patients who required EGFR-TKI dose reduction had experienced more severe skin symptoms than had patients who did not require it (7.35 vs 5.01, P < .001).Skin toxicity related to EGFR-TKI treatment impacts the quality of life in patients with NSCLC. During the treatment period, skin assessment and tailored management should be incorporated into the daily care plan.

Critical synthesis of available data in Malassezia folliculitis and a systematic review of treatments.

Folliculitis is an inflammatory process involving the hair follicle, frequently attributed to infectious causes. Malassezia, an established symbiotic yeast that can evolve to a skin pathogen with opportunistic attributes, is a common source of folliculitis, especially when intrinsic (e.g. immunosuppression) or extrinsic (high ambient temperature and humidity, clothing) impact on the hair follicle and the overlying skin microenvironment. Our aim was to critically review the pathophysiology and clinical characteristics of Malassezia folliculitis, to describe laboratory methods that facilitate diagnosis and to systematically review treatment options. Malassezia folliculitis manifests as a pruritic, follicular papulopustular eruption distributed on the upper trunk. It commonly affects young to middle-aged adults and immunosuppressed individuals. Inclusion into the differential diagnosis of folliculitis is regularly oversighted, and the prerequisite-targeted diagnostic procedures are not always performed. Sampling by tape stripping or comedo extractor and microscopic examination of the sample usually identifies the monopolar budding yeast cells of Malassezia without the presence of hyphae. However, confirmation of the diagnosis with anatomical association with the hair follicle is performed by biopsy. For systematic review of therapies, PubMed was searched using the search string "(malassezia" [MeSH Terms] OR "malassezia" [All Fields] OR pityrosporum [All Fields]) AND "folliculitis" [MeSH Terms] and EMBASE was searched using the search string: 'malassezia folliculitis.mp OR pityrosporum folliculitis.mp'. In total, 28 full-length studies were assessed for eligibility and 21 were selected for inclusion in therapy evaluation. Conclusively Malassezia folliculitis should be considered in the assessment of truncal, follicular skin lesions. Patient's history, comorbidities and clinical presentation are usually indicative, but microscopically and histological examination is needed to confirm the diagnosis. Adequate samples obtained with comedo extractor and serial sections in the histological material are critical for proper diagnosis. Therapy should include systemic or topical measures for the control of the inflammation, as well as the prevention of recurrences.

Ulcerative nodules on the entire body

Ulcerative nodules on the entire body

Mycobacterium mageritense tattoo infection: a known complication with a novel species

Non-pigmented rapidly growing mycobacteria are nontuberculous mycobacteria (NTM) capable of producing disease. We report a case of tattoo-associated NTM infection with a novel species: Mycobacterium mageritense. A 48-year-old man presented with a two-week history of a papulopustular eruption on the shaded areas of a tattoo that had been placed five weeks prior while in the Philippines. Histopathology from punch biopsies revealed suppurative granulomatous dermatitis with acid fast bacilli present. Subsequent matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometer identified the bacteria as Mycobacterium margeritense. After consultation with infectious disease specialists and culture susceptibilities, the patient was treated with three months of dual antibiotic therapy with minocycline and moxifloxacin. The patient experienced a slow but complete resolution of clinical skin findings after the course of treatment. Since discovery in 1997, M. mageritense infection has been demonstrated in a wide spectrum of disease, predominantly skin and soft tissue infections. The species has not been previously implicated in tattoo-associated NTM infections. M. mageritense should be considered as a specific type of mycobacteria in the differential diagnosis for tattoo-associated NTM infections owing to differences in antibiotic susceptibilities compared to other NTM species.

Cutaneous eruptions from ibrutinib resembling epidermal growth factor receptor inhibitor–induced dermatologic adverse events

Ibrutinib isan oral inhibitor of Bruton tyrosine kinase that is approved by the United States Food and Drug Administration for several lymphoproliferative disorders and chronic graft-versus-host disease. To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor (EGFR) inhibitor-induced dermatologic adverse events. Single-center retrospective cohort of patients referred to the Skin Toxicities Program for treatment of cutaneous eruptions while taking ibrutinib. Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae, or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. Most patients were able to continue ibrutinib therapy with focused treatment of their cutaneous toxicities. This study represents cases at a single tertiary care center and is limited to patients referred for toxicity. With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with thoseassociated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

Proteomic and Phosphoproteomic Analysis Reveals that Neurokinin-1 Receptor (NK1R) Blockade with Aprepitant in Human Keratinocytes Activates a Distinct Subdomain of EGFR Signaling: Implications for the Anti-Pruritic Activity of NK1R Antagonists.

Background: Epidermal growth factor receptor (EGFR) inhibitors can cause serious cutaneous toxicities, including pruritus and papulopustular acneiform skin eruptions. Increasingly, the neurokinin-1 receptor (NK1R) antagonist aprepitant is being utilized as an anti-pruritic agent in the treatment of EGFR-inhibitor induced pruritus. Aprepitant is believed to reduce itching by blocking NK1R on the surface of dermal mast cells. However, the effects of aprepitant on human keratinocytes remains unexplored. Methods: Herein, we examine the effects of aprepitant on EGFR stimulation in HaCaT cells using a phosphoproteomic approach including reverse phase protein arrays and Ingenuity Pathway Analysis. Changes in EGFR phosphorylation were visualized using Western blotting and the effect of EGF and aprepitant on the growth of HaCaT cells was determined using the WST-1 Cell Proliferation Assay System. Results: We found that aprepitant increased the phosphorylation of EGFR, as well as 10 of the 23 intracellular proteins phosphorylated by EGF. Analysis of phosphoproteomic data using Ingenuity Pathway Analysis software revealed that 5 of the top 10 pathways activated by EGF and aprepitant are shared. Conclusions: We propose that aprepitant produces its antipruritic effects by partially activating EGFR. Activation of EGFR by aprepitant was also seen in primary human keratinocytes. In addition to itch reduction through partial activation of shared EGFR pathways, aprepitant exerts a dose-dependent cytotoxicity to epithelial cells, which may contribute to its antitumor effects.

A new superficial needle-scraping method for assessing Demodex density in papulopustular rosacea.

Standardized skin surface biopsy (SSSB) is often performed to determine the density of Demodex mites in facial papulopustular eruptions. We aimed to test the applicability of a new, "superficial needle-scraping" (SNS) method for assessing Demodex density in papulopustular rosacea (PPR). Using SNS method, we measured the Demodex density in patients with PPR, also enrolling the patients with acne vulgaris as controls. SNS was performed by gently scraping off 5 small pustules with the convex surface of the tip of an 18# needle for examination. For comparison, SSSB was also performed in patients with PPR. Demodex density was expressed as "mites per 5 pustules" for SNS and as "mites per cm2 " for SSSB. A total of 40 patients with PPR and 35 patients with acne vulgaris were recruited. There were no statistically significant differences in age or sex between the PPR and acne groups. The Demodex density was 5.6±4.2 in the PPR group versus 0.3±1.0 in the acne group (P<.001). The cutoff of "≥3 Demodex mites per 5 pustules" gave a sensitivity of 78% and a specificity of 97%, and the area under the receiver operating characteristic curve was 0.89. Moreover, SNS and SSSB gave mutually concordant results (positive or negative) in half of the patients. Our study suggests that SNS is a simple and convenient method for assessing Demodex density of pustules in PPR and can be a useful alternative or addition to SSSB for evaluation of Demodex-associated facial papulopustular eruptions.

Sífilis Maligna Precoce em Paciente Imunodeprimido

A sífilis maligna precoce, também chamada sífilis nódulo-ulcerativa, foi descrita inicialmente por Bazin em 1859, relacionada a graus variáveis de imunodeficiência, em especial, a síndrome da imunodeficiência adquirida (SIDA) humana causada pelo vírus da imunodeficiência humana (VIH). É uma variante agressiva e generalizada da sífilis secundária com pródromos de febre, cefaleia, mialgia e artralgia, seguida de erupções papulopustulosas e necróticas. Devido à sua raridade e apresentação clínica pleomórfica, esse quadro é geralmente subdiagnosticado, o que pode levar, por vezes, ao desfecho fatal. Relatamos um caso de sífilis maligna em um paciente do sexo masculino, 40 anos, imunodeprimido por infecção pelo VIH, com manifestação cutânea atípica exuberante e sintomas constitucionais, o que se tem tornado raro devido à introdução de terapêutica antirretroviral altamente eficaz.

Association of Antibiotic Resistance With Antibiotic Use for Epidermal Growth Factor Receptor Inhibitor–Related Papulopustular Eruption

This medical record review investigates whether use of topical clindamycin and/or oral tetracyclines during management of epidermal growth factor receptor (EGFR) inhibitor–related papulopustular eruption is associated with antibiotic-resistant bacterial infection.

Cutaneous Manifestation of Behçet Disease

Behçet disease is an inflammatory disease of unknown etiology that affects various organs, such as the skin, eye, central nervous system, and blood vessels. Mucocutaneous manifestations are characterized by oral ulcers, genital ulcers, erythema nodosum, papulopustular eruptions, and thrombophlebitis. The diagnosis is based on the diagnostic criteria defined by the Japanese Ministry of Health, Labour and Welfare. Mucocutaneous manifestations often appear as the first symptoms and are important for an early diagnosis of neuro-Behçet disease.

Pulsed-dye laser as an adjuvant treatment for papulopustular eruptions from epidermal growth factor receptor inhibitors, a randomized blinded split-faced controlled trial.

To investigate the efficacy of pulsed-dye laser (PDL) as an adjunctive treatment for facial papulopustular eruptions from EGFR inhibitors (EGFRi). Fourteen patients with facial acneiform eruptions were recruited. Half side of the face was randomized to receive PDL treatment while the other side served as a control. The treatments were delivered every 2 weeks for 4 sessions. The patients were seen at baseline, weeks 2, 4, 6, 8, and 10. Erythema index (EI) measured by colorimeter, the papulopustular lesion count and physician global assessment (PGA) were obtained. Patients were allowed to use their standard treatments for their eruptions. Both arms had a significant decrease in EI from baseline at each subsequent visit. In the laser treated side, the mean (95%CI) EI decreased from 23.5 (22.24-24.76) at baseline to 16.3 (15.01-17.59) at week 10, while those of the sham were 23.49 (22.23-24.75) to 20.51 (19.22-21.8), respectively. The mean change was significantly lower in the PDL arm from week 4 onwards. The lesion counts in both groups also decreased significantly, but the mean difference between the arms was not different. PGA scores followed the same pattern as EI. Adjunctive treatment with PDL was a safe and effective treatment. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Clinical Profile of Cutaneous Adverse Effects of Epidermal Growth Factor Receptor Inhibitors: A Prospective Observational Study of 76 Cases.

Background:Epidermal growth factor receptor (EGFR) inhibitors are an extensively utilized class of chemotherapeutic agents which form an integral component of treatment in solid organ malignancies such as non-small-cell lung carcinoma, pancreatic carcinoma, colorectal carcinoma, and head and neck carcinoma. It has two subclasses: epidermal growth factor inhibitors (erlotinib) and monoclonal antibody (cetuximab). A wide array of cutaneous adverse effects has been attributed to this class of drugs, such as papulopustular eruptions, paronychia, xerosis, and changes in hair and nails.Materials and Methods:A total of 76 cases of various malignancies on EGFR inhibitors who developed cutaneous side effects while on therapy and reported or referred to us by oncologists from January 2017 to January 2018 were included in the study. All the patients who were on other associated medications or radiotherapy were excluded.Result:In all, 45 (59.2%) were males and 31 (40.7%) were females. Non-small-cell lung carcinoma was the most common carcinoma in 32 (42.1%) patients, and cetuximab was the most common drug in 29 (38.1%) cases. Papulopustular eruptions were seen in 61 (80.2%) patients, xerosis in 31 (40.7%), mucositis in 6 (7.8%), hair growth problems in 4 (5.6%), and paronychia and pyogenic granuloma in 2 (2.6%) patients each.Conclusion:Although most of the skin toxicities associated with EGFR inhibitors can be managed conservatively, a critical analysis of the cases that are significantly affected due to these side effects is required in cohesion with the treating oncologist to improve the therapeutic compliance of the drug.

The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma.

B-rapidly accelerated fibrosarcoma (BRAF) inhibitor encorafenib alone and in combination with MEK inhibitor binimetinib improves survival in BRAF-mutated melanoma patients. So far, the range of cutaneous adverse events has been characterized only for established BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (trametinib, cobimetinib). The aim of this study was to investigate cutaneous adverse events emerging in melanoma patients treated with encorafenib and binimetinib. Patients treated with BRAF and MEK inhibitors in clinical trials at the University Hospital of Zurich were identified. Frequency and features of cutaneous adverse events as well as their management were assessed based on the prospectively collected clinical and histopathological data. The events emerging during encorafenib and/or binimetinib therapy were compared to other BRAF and MEK inhibitors at the institution and in the literature. The most frequent cutaneous adverse events observed in patients treated with encorafenib alone (n=24) were palmoplantar hyperkeratosis (54%), palmoplantar erythrodysesthesia (58%) and alopecia (46%). Drug-induced papulopustular eruptions prevailed in patients with binimetinib monotherapy (n=25). The most frequent cutaneous adverse events in patients treated with encorafenib/binimetinib (n=49) were palmoplantar hyperkeratosis (10%). Compared to data published for established BRAFi, encorafenib monotherapy showed less hyperproliferative cutaneous adverse events. In contrast, palmoplantar hyperkeratosis and palmoplantar erythrodysesthesia seem to occur more often. The combination of encorafenib and binimetinib is well tolerated and induces few cutaneous adverse events.

Challenges and Advances in Rosacea Management

Rosacea is a common chronic inflammatory disorder characterized by symptoms of facial flushing and spectrums of clinical signs, including erythema, dry skin, and an inflammatory papulopustular eruption with periods of exacerbation. The current classification system developed by the National Rosacea Society Expert Committee consists of erythematotelangiectatic, papulopustular, phymatous, and ocular subtypes. Individual subtypes are likely a result of different pathogenic factors and respond best to different therapeutic regimens. Before initiation of therapy, the triggering factors should be identified and avoided. Daily applied sunscreen is a must. The main treatment modalities for rosacea include topical, systemic, laser, and light therapies. Traditional therapies include topical metronidazole or azelaic acid also oral therapy as tetracyclines or isotretinoin. Emerging therapies perhaps are more promising as topical ivermectin 1% cream which is proved to be safe and effective for the treatment of inflammatory lesions from papulopustular rosacea, Brimonidine tartrate and oxymetazoline are novel therapies to treat the erythema associated with rosacea. Other treatments as pimecrolimus 1% cream, clindamycin phosphate 1.2% + tretinoin 0.025% gel, pulsed dye laser and intense pulsed light can also be used. With the advent of novel therapeutic options for the treatment of rosacea such as subantimicrobial anti-inflammatory dose doxycycline, ivermectin and Brimonidine tartrate, there is renewed interest in the study of this disease which was once regarded as a debilitating disorder and now has become a well-known and manageable entity in the setting of these emerging therapeutic options. Herein, we describe the treatments currently available as well as the emerging and combination therapies.