Acneiform Research Articles

Acneiform Eruptions in Dermatology – A Differential Diagnosis

Acneiform Eruptions in Dermatology – A Differential Diagnosis

Epidermal growth factor receptor inhibitors selectively inhibit the expression of human β-defensins induced by Staphylococci

Epidermal growth factor receptor inhibitors (EGFRIs) have developed as one of the potential treatment options for various kinds of cancers. Although a variety of dermatological adverse reactions such as follicular acneiform eruptions is commonly encountered, the mechanism of the reactions remains unclear. We investigated the effects of EGFRIs on the expression of antimicrobial peptides against Staphylococci to study the pathomechanism of cutaneous adverse reactions caused by EGFRIs. We investigated the expressions of human β-defensins 1, 2, and 3 (hBD1, 2, and 3) from Staphylococci-stimulated normal human epidermal keratinocytes (NHEKs) cultured with or without the effects of two EGFRIs, gefitinib and erlotinib. We stimulated NHEKs with the culture supernatants of Staphylococcus aureus (S. aureus) and S. epidermidis and the live Staphylococci. We measured hBDs in the culture supernatants of NHEKs by ELISA. EGFRIs did not suppress the expressions of hBD1 and 3 induced by the supernatants of S. aureus or live S. aureus. In contrast, EGFRIs suppressed the expressions of hBD2 and 3 induced by the supernatants of S. epidermidis and hBD2 induced by live S. aureus. EGFRIs may cause cutaneous adverse effects through selectively perturbing innate immune responses induced by commensal and pathogenic bacteria.

Prospective Case Series of Cutaneous Adverse Effects Associated With Dabrafenib and Trametinib.

Dabrafenib, a novel selective small-molecule inhibitor of BRAF, has been shown to increase overall survival in patients with unresectable metastatic melanoma harboring the BRAF V600E mutation. The development of resistance has led to combination therapy with selective MEK inhibitor trametinib. Compared with vemurafenib, dabrafenib is a more recent BRAF inhibitor approved by the Food and Drug Administration in May 2013 for metastatic melanoma; fewer data are available in the current literature regarding cutaneous toxicity. We sought to present additional cutaneous side effects of dabrafenib and trametinib and follow their evolution and management. We carried out a prospective study of 14 patients treated with dabrafenib alone or with trametinib. Patients were followed every 4 weeks, and we collected detailed cutaneous symptoms, photos, and biopsy specimens. All patients presented with at least 1 adverse skin reaction. The mean duration of treatment was 24 weeks. The most common adverse effect was papillomas (7/14), followed by palmoplantar hyperkeratosis (5/14), alopecia (5/14), and seborrheic dermatitis-like eruption (2/14). Three patients who received trametinib developed an acneiform eruption (3/5). One patient developed a keratoacanthoma-like squamous cell carcinoma. Side effects presented as early as 2 weeks after starting therapy, with a mean time of onset of 9 weeks. Selective BRAF inhibitor dabrafenib and MEK inhibitor trametinib are associated with multiple skin adverse effects. Given their recent approval and the potential for malignant lesions to develop on treatment, awareness of potential adverse effects and their management is necessary.

Case of severe acneiform eruptions associated with the BRAF inhibitor vemurafenib

Case of severe acneiform eruptions associated with the <scp>BRAF</scp> inhibitor vemurafenib

Recommendations for the Prophylactic Management of Skin Reactions Induced by Epidermal Growth Factor Receptor Inhibitors in Patients With Solid Tumors.

Epidermal growth factor receptor (EGFR) inhibitors extend patient survival across a variety of tumor types. The most common EGFR inhibitor-attributable adverse events are skin reactions. Prophylactic-rather than reactive-management of skin reactions for all patients receiving EGFR inhibitors should be recommended because appropriate prophylaxis could effectively reduce the severity of skin reactions; thus, the derivation of highly effective prophylactic strategies has the potential to directly benefit patients. Accordingly, a review of the available data leads to practical and evidence-based recommendations and algorithms regarding the optimal prophylactic management of EGFR inhibitor-attributable skin reactions.

A Phase II Study of XELOX and Cetuximab as First-Line Therapy in Patients With KRAS Wild Type Metastatic Colorectal Cancer (FLEET2 Study)

BackgroundDespite the comparable clinical benefit of XELOX (capecitabine with oxaliplatin) and FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), the value of XELOX treatment in combination with cetuximab for metastatic colorectal cancer (mCRC) remains largely unknown. Patients and MethodsIn this clinical trial we evaluated the efficacy and safety of weekly/biweekly cetuximab administration combined with biweekly XELOX in patients with previously untreated v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type mCRC. The primary end point was response rate (RR) with confirmation, and the secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), dose intensity, and the safety of the protocol treatment. ResultsForty patients who fulfilled the inclusion criteria participated in this study. The median treatment cycle number was 8 and the median dose intensities were 218 mg/m2/wk for cetuximab, 34 mg/m2/wk for oxaliplatin, and 821 mg/m2/d for capecitabine. One patient showed complete response and partial response was observed in 19 patients, giving an overall RR of 50% (95% confidence interval [CI], 33.8%-66.2%). Stable disease was obtained in 13 patients, resulting in a DCR of 82.5% (95% CI, 67.2%-92.7%). The PFS was 6.5 months (95% CI, 3.5-9.6 months), and the OS was 24.3 months (95% CI, 14.9-33.7 months). The safety profile revealed the common Grade 3/4 adverse events to be acneiform eruption (12.5%), peripheral neuropathy (7.5%), and elevated alanine transaminase levels (7.5%). Grade 3/4 thrombocytopenia and neutropenia occurred only in 5.0% and 2.5% of the patients, respectively. Grade 1 hand-foot syndrome (HFS) was not uncommon (20%), whereas Grade 2/3 HFS occurred in only 3 patients (7.5%). No deaths were reported within 30 days of the last dose. ConclusionCetuximab with XELOX showed a confirmed overall RR of 50%, which was within the previously reported range of RR. The safety profile showed an acceptable rate and severity of adverse events. In light of the several advantages of XELOX, including convenience and the reported cost-saving aspects, further study of this combination therapy is warranted.

Pharmacovigilance of cutaneous drug reactions: A prospective observational study

Objective: To determine the frequency, severity and morphological pattern of ACDRs and their correlation with various risk factors.Methodology: A prospective, observational study was conducted in Muzaffarnagar Medical College & hospital, Muzaffarnagar Uttar Pradesh from Feb 2013 to Jan 2014 for one year. All patients of either sex and all age groups with suspected ACDRs attending/referred to Dermatology department were included.Results: Total of 90 cases were reported over a period of one year. ACDRs were observed with 0.5% incidence of patients attending OPD. ACDRs were commonly seen in adult age group (mean age 36.93 yrs) and have 3 or more drugs prescribed with equal gender distribution. As per Naranjo Algorithm, maximum number of ACDRs were of Possible type (74%), while 23 cases were of Probable category with female and male preponderance respectively. 71 of ACDRs were Moderate in severity (79%) followed by 11% of mild and 10% of severe category. Most common clinical pattern was Urticaria with 32 cases followed by 24 cases of Maculopapular Eruptions, 9 cases of Acneiform eruptions and 8 of fixed drug reactions and SJ Syndrome. Commonest Drug groups causing ACDRs were Antibiotics (38%) and Antiepileptics (30%).This was followed by NSAIDs induced ACDRs (9%). Phenytoin was the most common drug causing 12 ACDRs followed by 6 with Cabamazipine and Ceftrixone each and 5 cases with ATT.Conclusion: Incidence was low as compare to global incidence; better steps must be needed to strengthen the activity of pharmacovigilance in this state of the country.

Icotinib as initial treatment in lung adenocarcinoma patients with brain metastases.

BackgroundTo evaluate the antitumor activity and toxicity of icotinib as initial treatment in lung adenocarcinoma patients with brain metastases.MethodsTwenty‐one patients with histologically or pathologically documented brain metastatic lung cancer were administered icotinib as initial treatment from 2011 to 2015 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Chemotherapy response was assessed by Response Evaluation Criteria in Solid Tumors and toxicity was evaluated according to National Cancer Institute‐Common Toxicity Criteria. Icotinib was administered three times per day at a dose of 125mg.ResultsThe median overall and progression‐free survival rates were 15.2 (1.2–31.5 months, 95% confidence interval [CI] 6.6–23.7 months) and 8.9 months (0.6–30.5 months, 95% CI 3.4–14.3 months), respectively. The overall response and disease control rates were 61.9% and 90.5%, respectively. Icotinib was well tolerated, and no grade 3/4 adverse events were observed. The most common grade 1/2 adverse events included acneiform eruptions (38.1%), diarrhea (19.0%), and stomatitis (9.5%).ConclusionIcotinib is effective and well tolerated as initial treatment in lung adenocarcinoma patients with brain metastases.

When Acne is Not Acne.

Acne vulgaris (AV) is considered a straightforward diagnosis made clinically without specific diagnostic testing. However, certain disorders may simulate AV, such as multiple small epidermal cysts or deep milia, multiple osteoma cutis, multiple small adnexal neoplasms, and follicular and/or infections characterized by multiple small papules and/or pustules such as gram-positive folliculitis, gram-negative folliculitis, Malassezia folliculitis, keratosis pilaris, and flat warts. This can lead to an erroneous diagnosis and improper management. Acneiform eruptions, often associated with ingestion of certain drugs and chemicals, can confound the clinician regarding AV diagnosis. We present herein an interesting case that was originally misdiagnosed as AV.

Association between efficacy and skin rash following treatment with the lapatinib in metastatic breast cancer

Abstract Epidermal growth factor receptor (EGFR) is overexpressed in several solid human tumor types, such as colorectal, breast and lung cancers. There are strong evidences that EGFR inhibitors have an increased risk of dermatological side effects arise during the treatment of these agents. Lapatinib is an EGFR inhibitor approved for the treatment of patients with recurrent HER2-positive advanced or metastatic breast cancer. Herein, we report a 35 year old female patient, who had lung metastasis associated with breast cancer, with the presence of acneiform eruption in her face and metastatic lesions which did not progress for 17 months while she was having the lapatinib treatment for her metastatic lesions. As it is occur in all other EGFR inhibitors, the development of acneiform eruption during the lapatinib treatment might be an indicator of better and longer drug response.

Comparison of Skin Toxic Effects Associated With Gefitinib, Erlotinib, or Afatinib Treatment for Non–Small Cell Lung Cancer

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used to treat non–small cell lung cancer. Four major skin toxic effects with different incidences have been reported from clinical studies, including acneiform eruption (60%-94%), pruritus (16%-60%), xerosis (4%-38%), and paronychia (6%-12%). 1,2 However, a direct comparison of the incidences and severities of the 4 types of skin toxic effects for 3 different EGFR-TKIs in the same patient cohort has been lacking to date. Methods | This retrospective study was approved by the research ethics committee of National Taiwan University Hospital. We recruited patients within a named patient program for compassionate use before registration who had ever received afatinib treatment for non–small cell lung cancer between November 1, 2007, and April 30, 2013. Most of the pa

Acneiform eruption developing with duloxetine: a case

Duloxetine, serotonin and norepinephrine reuptake inhibitor is a strong antidepressant. It is widely used for generalized anxiety disorder, neuropathic pain and fibromyalgia syndrome as well as major depressive disorder. Its most important side effects are nausea, dryness of the mouth, constipation, sleep disorder, dizziness and fatigue. In this paper, we report a female patient who developed acneiform eruption due to duloxetine use, a different side effect than usual side effects.

A study of cutaneous adverse drug eruptions in dermatologic practice

Cutaneous adverse drug reactions (CADR) are a major problem in drug therapy and is one of the leading causes of morbidity and mortality in health care. Objectives: 1) To study the diverse clinical spectrum of CADR. 2) To assess the causality and identify the offending drug. Materials and Methods: Present study was an 18 months prospective, hospital based study conducted, recording a total of 100 patients with various cutaneous ADR. The diagnosis of cutaneous drug reactions was made mainly based on detail history and correlation between the intake of probable offending drug and the onset of rash. Results: The most common type of CADR patterns recorded among the 100 cases in the present study were Maculopapular rash (30%), Fixed drug eruption & bullous variant (19%), Acute urticaria (18%), Acneiform eruptions (6%), Erythema multiforme & Stevens – Johnson syndrome (SJS) in (5%), Exfoliative dermatitis & Photosenstivity in (4%), Angioedema, Vasculitis & Hyperpigmentation in (2%), Toxic epidermal necrolysis (TEN), Drug hypersensitivity syndrome & Pruritus in (1%) each. The drugs most often implicated were Antimicrobials(40%), NSAIDs (30%), and Anticonvulsants (11%). Antimicrobials were implicated in (43.3%) of Maculopapular rash followed by NSAIDs (33.3%). Antimicrobials (52.6%) and NSAIDs (42.1%) in FDE. Urticarial reaction was caused mainly by NSAIDs (44.3%). Life threatening severe cutaneous adverse drug reactions (SCARs) such as SJS, TEN & Drug hypersensitivity syndrome (DHS) were seen 7% of total cases. Conclusion: Although it was a monocentric study, this study revealed a high frequency of cutaneous drug reactions with different clinical presentations, induced by frequently used antibiotics, analgesics and anticonvulsants as and when used giving an interesting data with respect to onset, severity and clinical presentation. Keywords: Cutaneous adverse drug reactions, Antimicrobials, Severe Cutaneous Adverse Reactions

Acneiform Eruption Secondary to the First Perfusion of Panitumumab

Acneiform Eruption Secondary to the First Perfusion of Panitumumab

Evaluation of efficacy and safety of a focal fractional laser for the treatment of atrophic acne scars

Objective To evaluate the efficacy and safety of focal fractional laser treatment (FFLT) for atrophic acne scars. Methods A randomized, self-controlled study was performed. A total of 20 patients with atrophic facial acne scars were enrolled into this study. Treatments were randomly administered in a split-face manner. Half of each subject's face received FFLT (FFLT side) , and the other half underwent full-face fractional CO2 laser resurfacing (control side) , for one session. All the patients were followed up for 3 months after the treatment. Evaluation was based on the ECCA grading scale (echelle d'evaluation clinique des cicatrices d'acne) and patient satisfaction score. A VISIA skin detector was used to take photographs and evaluate skin texture. Moreover, physical parameters of the skin, including erythema index, melanin index and transepidermal water loss (TEWL) , were measured. Adverse effects were recorded and evaluated. Statistical analysis was carried out by paired t test, Wilcoxon paired rank test, Fisher's exact test and repeated-measure analysis of variance. Results The ECCA score decreased from 51.24 ± 17.61 at the baseline to 34.46 ± 14.99 at 3 months after the treatment at the FFLT side (t= 7.886, P 0.05). Compared with those before the treatment, skin texture scores decreased in both sides (both P 0.05) from 2 weeks to 3 months after the treatment (all P> 0.05). Conclusion FFLT can improve therapeutic outcomes in atrophic acne scars with reduced adverse reactions. Key words: Cicatrix; Acneiform eruptions; Lasers, gas; Treatment outcome; Drug toxicity

Post‐herpetic acneiform eruption: report of two cases with dermoscopic observations

Post‐herpetic acneiform eruption: report of two cases with dermoscopic observations

Efficacy, tolerability and impact on quality of life of clindamycin phosphate and benzoyl peroxide for the treatment of cetuximab-associated acneiform eruption in patients with metastatic colorectal cancer

Background: Epidermal growth factor receptor inhibitors are recent antineoplastic treatments used for the treatment of some non-cutaneous tumours, which aberrantly express EGFR. Because of their specificity, these drugs have low systemic toxicity, but frequent undesired cutaneous effects, the most common of which is an acneiform eruption, occurring after 1–3 weeks of treatment. Management of this rash is not well standardized. Objective: We evaluated efficacy, tolerability and impact on quality of life of a clindamycin phosphate 1.2%–benzoyl peroxide 5% gel in 12 male adults who developed acneiform eruption during treatment with cetuximab for metastatic colorectal cancer. Methods: Patients applied the clindamycin phosphate-benzoyl peroxide gel once daily, at evening, for 8 weeks. The Skin-Score was used to evaluate reduction of erythema, papules, pustules and pruritus, the Dermatology Life Quality Index questionnaire to evaluate the improvements of health-related quality of life. Results: Significant clinical improvements occurred after 2 weeks of treatment and were even more evident after 8 weeks (mean Skin-Score 20.54 ± 7.83, p = 1.37 × 10−6 vs. second week visit, p = 1.26 × 10−7 vs. before treatment). Accordingly, DLQI values decreased from 13.64 ± 2.01 before treatment to 6.45 ± 1.37 after 8 weeks (p = 1.12 × 10−5). Conclusion: A clindamycin phosphate-benzoyl peroxide gel may be an effective and safe option in the treatment of cetuximab-associated acneiform eruptions.

Management of Dermatologic Complications of Lung Cancer Therapies.

In recent years, oncogene-directed targeted agents and immunotherapies have expanded the treatment armamentarium for advanced lung cancer and, in particular, non-small cell lung cancer (NSCLC). Along with extended survival, these agents are accompanied by a host of cutaneous complications that affect the skin, hair, and nails. These skin complications range from the well-characterized papulopustular (acneiform) eruption of the epidermal growth factor receptor (EGFR) inhibitors to the emerging characterization of lichenoid skin eruptions seen during treatment with antibodies targeting the programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand (PD-L1). When promptly recognized and accurately diagnosed, most cutaneous adverse events can be managed with supportive treatments, avoiding the need to interrupt antitumor therapy. Furthermore, preemptive management of skin problems can lead to significantly decreased severity of many cutaneous complications of these therapies. We encourage close collaboration between dermatologists and oncologists to better characterize cutaneous toxicity, select appropriate management, and avoid unnecessary dose reduction or discontinuation while simultaneously improving patient quality of life.

Morphology-Based Diagnosis of Acneiform Eruptions.

Acne is the most common skin disease. Distinguishing between true acne vulgaris and the various acneiform eruptions is important yet sometimes challenging. Given the common nature of acne and acneiform eruptions, the pediatrician must be aware of these lesion patterns and possess the skills to effectively evaluate the pediatric presentation of these eruptions. This article discusses several of the most common acneiform eruptions, including neonatal acne and cephalic pustulosis, periorificial dermatitis (perioral dermatitis), facial angiofibromas, iatrogenic acneiform drug eruptions, and childhood rosacea.

Dermatology: A Morphologic Approach to Differential Diagnosis

Skin eruptions tend to be particularly alarming to parents. The visible evidence of a change to a body part provokes anxiety in patients and parents alike, even if the afflicted is not feeling pain or discomfort. Pediatricians are at the front line of assessing these sudden rashes. When an eruption is widespread or unfamiliar, the physician too will feel anxious, and worry about the possibility of failing to consider a diagnosis he or she may not have previously encountered. Textbooks of dermatology are brimming with obscure and esoteric diagnoses, providing an intimidating breadth of knowledge even for those of us immersed in the study of the skin. Physicians operate in fear of missing a critical diagnosis. We worry that we may have failed to consider the entity that will “crack the case.” Thus, familiarizing ourselves with a comprehensive array of possibilities is crucial, but this becomes increasingly difficult for the primary care physician faced with a myriad of complaints involving every organ system of the body. For many practitioners, this challenge is met by having a systematic approach to differential diagnosis. Within dermatology, that systematic approach can often be met by assessing the morphologic characteristics of a skin eruption and building one’s differential from that foundation. In this issue of Pediatric Annals, four distinct morphologic patterns of skin eruptions are presented. An illustrative case is used to introduce each morphology, followed by an in-depth discussion of each diagnosis and a differential enumerating several key disorders that share the particular morphologic characteristic. Drs. Sarah L. McFarland and Ingrid C. Polcari introduce the reader to acneiform eruptions in children, and expand on the topics of acne in infants, perioral dermatitis, facial angiofibromas, childhood rosacea, and acneiform drug eruptions. Dr. Lacey L. Kruse provides an approach to linear eruptions of childhood, including acquired inflammatory eruptions such as lichen striatus, congenital linear lesions such as epidermal nevus, inflammatory linear verrucous epidermal nevus and nevus sebaceous, and exogenous triggers causing linear eruptions such as contact dermatitis and phytophotodermatitis. Dr. Patricia S. Todd and colleagues discuss annular eruptions. They explore the features that distinguish granuloma annulare, tinea corporis, annular urticaria, neonatal lupus erythematosus, erythema multiforme, and erythema chronicum migrans. Finally, Dr. Duri Yun and I review blistering conditions including those related to inflammatory triggers, infection, autoimmunity, and drugs. It is my hope that these articles will provide an organized and accessible approach to formulating a logical and reasonable differential diagnosis when faced with what might at first seem to be a bizarre or alarming rash in a child.