An Analysis of Risk Factors for the Development of Acneiform Eruptions in Patients on Monoclonal Antibody Epidermal Growth Factor Receptor Inhibitors.

Acneiform eruptions occur frequently and early in patients on epidermal growth factor receptor inhibitors (EGFRi). Identification of baseline patient risk factors would prompt earlier referral to dermatology to optimize prevention and management. The primary objective of this retrospective study is to determine the association between clinical and demographic characteristics and the development of acneiform eruptions. A retrospective chart review was conducted on patients diagnosed with colon and head and neck cancers who started EGFRi between January 2017 and December 2021. Patients were followed until death or September 2022. Baseline demographic and clinical parameters were documented and patients were followed from the time of diagnosis to most recent visit for the development and management of an acneiform eruption. Regression analyses were performed to determine the association between baseline characteristics and the development of acneiform eruptions. A total of 66 patients were treated with cetuximab or panitumumab between 2017-2021 were included in the analysis. Forty-seven of the sixty-six patients developed an acneiform eruption while on EGFRi therapy (71.2%). Combination cancer therapy with another chemotherapeutic agent was associated with a lower risk of acneiform eruption (OR 0.03, P = .027). No other baseline features were statistically associated with a lower risk of acneiform eruption. Acneiform eruptions are a common cutaneous adverse event of EGFRi therapy. Ongoing research is required to elucidate risk factors for the development of acneiform eruptions, to improve the quality of life of oncology patients.

Immunosuppressant-induced cutaneous drug reactions in solid organ transplant recipients.

Solid organ transplant recipients (SOTRs) are susceptible to various cutaneous side effects as a consequence of long-term immunosuppressive therapy. Skin cancers and infections are well-studied complications that can cause death and/or allograft rejection. Other cutaneous drug reactions, such as inflammatory manifestations, have a high prevalence but are rarely studied. We analyzed these manifestations' prevalence and their association with immunosuppressants in transplant recipients from a Brazilian tertiary center. Among 532 SOTRs followed at our dermatology clinic, 60 (11.3%) developed some cutaneous adverse reactions to the immunosuppressants, with a median age at transplantation of 50.5 years and a median life span posttransplantation of seven years. Acneiform eruption was the most common drug reaction found (21 patients, 30.4%), followed by diffuse non-scarring alopecia (16 patients, 23.1%), lymphedema (10 patients, 14.5%), gingival hyperplasia (7 patients, 10.1%), hypertrichosis (6 patients, 8.7%) and sebaceous hyperplasia (9 patients, 13.1%). Adequate immunosuppression is an essential prerequisite for successful organ transplantation. In the immediate post-transplant period, significant immunosuppression is needed, but after that, the complications of excessive immunosuppression outweigh the risk of organ rejection. SORTs may present with a broad spectrum of inflammatory and cosmetic findings due to immunosuppressants that can impair life quality.

Phase I dose-escalation trial of Sym004, an anti-EGFR antibody mixture, in Japanese patients with advanced solid tumors.

Sym004 is a 1:1 mixture of two antibodies targeting non-overlapping epitopes of the epidermal growth factor receptor that antagonizes ligand binding and induces receptor downregulation. In preclinical models, it has superior antitumor activity to cetuximab and panitumumab. Japanese adults aged ≥20 years with an Eastern Cooperative Oncology Group status of 0/1 and life expectancy ≥3 months were eligible. Patients in Part A (dose escalation) had refractory or recurrent late-stage solid tumors and received Sym004 6 mg/kg/wk (n = 3), 9 mg/kg loading/6 mg/kg/wk (n = 6), 12 mg/kg/wk (n = 6), or 18 mg/kg biweekly (n = 6). Patients in expansion Part B (n = 30) had esophageal squamous cell carcinoma and received Sym004 at the dose recommended from Part A. Fifty-one patients received Sym004. No dose-limiting toxicities were observed in Part A. A dose of 12 mg/kg/wk was selected for Part B. All patients in Part B experienced treatment-related adverse events, most commonly dermatitis acneiform (76.7%). Eighteen grade ≥3 treatment-related adverse events and five serious adverse events occurred (cardiac arrest, lung infection, interstitial lung disease, toxic skin eruption, blood creatinine increase). Two patients had treatment-related adverse events resulting in death (cardiac arrest and blood creatinine increase). Five patients in Part B had a best overall response of partial response, 12 stable diseases and 12 disease progression (1 not evaluable). The objective response rate was 16.7% (95% CI: 5.6%-34.7%). Sym004 therapy was well tolerated with no dose-limiting toxicities at any dose studied. Evidence of antitumor activity was seen in patients with esophageal squamous cell carcinoma. ClinicalTrials.gov Identifier: NCT01955473.

Overview of current systemic management of EGFR-mutant NSCLC.

Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy is the standard of care for lung cancer patients with sensitising EGFR mutations (exon 19 deletion or L858R mutation). Several phase III studies have demonstrated the superiority of gefitinib, erlotinib (first generation of TKIs) or afatinib (second generation) to chemotherapy in progression-free survival and response rates. Drug-related toxicities, such as diarrhoea, acneiform skin rash, mucositis, and paronychia, are frequently encountered in patients who receive EGFR TKIs. Other rare side-effects, such as hepatic impairment and interstitial lung disease, should be identified early and managed carefully. Patients with uncommon EGFR mutations, such as G719X, S768I, and L861Q, may require special selection of EGFR TKIs. The combination of erlotinib plus bevacizumab has been accepted in certain parts of the world as an alternative front-line treatment. This review article summarizes the studies leading to the establishment of EGFR TKIs in EGFR-mutant lung cancer patients. The side-effect profiles of the current EGFR TKIs in these large trials are listed, and the management of uncommon EGFR mutations is discussed. Finally, the potential role of combination front-line treatment is discussed.

Acneiform eruptions caused by vitamin B12: A report of five cases and review of the literature.

We describe five cases of acneiform eruption caused by vitamin B12 in five females aged 37, 32, 62, 29, and 21 years, respectively. The eruption appeared from 1 week to 5 months after the beginning of the therapy with i.m. or oral vitamin B12. Clinical picture was characterized by papules and pustules located on the face. In three patients, similar lesions were also present on the neck, shoulders, chest, and upper portion of the back. Comedones and cysts were absent. In two patients, serum vitamin B12 levels were very high. Histopathologic examination in one patient revealed an eosinophilic folliculitis. Spontaneous and complete remission was observed in all patients 3-6 weeks after vitamin B12 discontinuation.

Incidence of skin toxicity in squamous cell carcinoma of the head and neck treated with radiotherapy and cetuximab: A systematic review.

PURPOSE: Radiotherapy plus cetuximab is an effective combination therapy for locally advanced head and neck squamous cell carcinoma. The aim of our study was to determine the frequency of skin toxicity in patients receiving the combined treatment. RESULTS: Forty-eight studies were included in our analysis, for a total of 2152 patients. The mean rates of G3/G4 radiation dermatitis and acneiform rash were 32.5% (SD: 20.4; 95% CI: 28.5-36.5) and 13.4% (SD: 11.5; 95% CI: 11.2-15.6), respectively. The majority of studies referred to CTCAE scales for reporting both side effects (85.7% and 92.1%, respectively). Data on the management of skin toxicity were available in only 35.4% of the reviewed literature. CONCLUSIONS: severe radiation dermatitis is a frequent side effect induced by the combination of radiotherapy and cetuximab in head and neck cancer. The lack of predictive biomarkers of toxicity hampers the possibilty to design preventive measures on a personalized basis.

A Phase Ib Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Cobimetinib and Duligotuzumab in Patients with Previously Treated Locally Advanced or Metastatic Cancers with Mutant KRAS.

LESSONS LEARNED: Cobimetinib and duligotuzumab were well tolerated as single agents and in combination with other agents.The cobimetinib and duligotuzumab combination was associated with increased toxicity, most notably gastrointestinal, and limited efficacy in the patient population tested. BACKGROUND: KRAS-mutant tumors possess abnormal mitogen-activated protein kinases (MAPK) pathway signaling, leading to dysregulated cell proliferation. Cobimetinib blocks MAPK signaling. The dual-action antibody duligotuzumab (MEHD7945A) inhibits ligand binding to both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3). Blockade of EGFR/HER3 and inhibition of mitogen-activated protein kinase (MEK) in KRAS-mutant tumors may provide additive benefit. METHODS: Patients with KRAS-mutant solid tumors were eligible for this phase Ib dose-escalation study with a planned expansion phase. Duligotuzumab was given intravenously (IV) at 1,100 mg every 2 weeks (q2w), while cobimetinib was given orally in a standard 3 + 3 design to identify the recommended phase II dose (RP2D). The primary objective was to evaluate the safety and tolerability of this combination. RESULTS: Twenty-three patients were enrolled. Dose-limiting toxicities (DLTs) included grade 4 hypokalemia and grade 3 mucosal inflammation, asthenia, and dermatitis acneiform. Seventy percent of patients experienced grade 3 or worse adverse events (AEs). Five (22%) and 12 (52%) patients missed at least 1 dose of duligotuzumab and cobimetinib, respectively, and 9 (39%) patients required a cobimetinib dose reduction. Three (13%) patients discontinued due to an AE. Best response was limited to 9 patients with stable disease and 13 patients with progressive disease. CONCLUSION: Given the limited tolerability and efficacy of this combination, the study did not proceed to expansion stage and closed for enrollment.

Frecuencia, severidad y ubicación de erupciones acneiformes en hombres y mujeres tras una cirugía ortognática: estudio descriptivo longitudinal / Frequency, severity and location of acneiform eruptions in men and women after orthognathic surgery: longitudinal descriptive study

Describir la frecuencia de erupciones acneiformes y/o exacerbaciones de un acné previo tras una cirugía ortognática. La muestra consta de 57 pacientes (n=57) de ambos sexos, sometidos a una cirugía ortognática, los cuales fueron evaluados en: el preoperatorio (0-7 días previos); en distintas etapas de la cirugía; postoperatorio inmediato (7 ­ 15 días post cirugía) y postoperatorio mediato (30 ­ 40 días postquirúrgicos). En todos los controles clínicos mencionados se determinó la presencia/ausencia, ubicación, severidad y diagnóstico de las erupciones acneiformes. El 52,6 % de los pacientes sometidos a cirugía ortognática presentaron erupciones acneiformes, siendo mayores en las mujeres en comparación con los hombres. La severidad de las erupciones acneiformes es mayor en el postoperatorio inmediato en comparación al preoperatorio y postoperatorio mediato. La ubicación más frecuente del acné corresponde a la región frontal, tanto en el preoperatorio (22,8 %) como en el postoperatorio inmediato (31,6 %). En el postoperatorio mediato la zona más frecuente es la geniana (39 %). La frecuencia de acné post cirugía ortognática es elevada, siendo mayor en mujeres que en hombres. La severidad de este acné es mayor en el postoperatorio inmediato. La región frontal corresponde a la zona más frecuente de aparición de las erupciones acneiformes en el postoperatorio inmediato y la zona geniana en el postoperatorio mediato. El diagnóstico de estas erupciones acneiformes corresponde a un acné esteroidal, por lo que se puede sugerir un posible plan de tratamiento, con el fin de mejorar el postoperatorio de las pacientes y evitar, en lo posible, futuras manifestaciones en nuevas pacientes sometidas a este tipo de cirugía.

Describe the frequency of acneiform eruptions and / or exacerbations of a previous acne after orthognathic surgery. The sample consisted of 57 patients (n = 57) of both genders, undergoing orthognathic surgery, who were evaluated with a follow-up of 2 postoperative months, at different stages of surgery; Preoperative (0-7 days), immediate postoperative (7-15 days) and mediate postoperative (30-40 days). The presence / absence, location, severity and diagnosis of acneiform eruptions were determined in all clinical controls. The frequency of acneiform eruptions corresponds to 52.6 % of patients undergoing orthognathic surgery, being higher in women compared to men in relation to the presence of acneiform eruptions and / or exacerbations of a previous acne after the intervention. The severity of acneiform eruptions is greater in the immediate postoperative period compared to the preoperative and mediate postoperative period. The most frequent location to be found in the facial region is in the frontal area, both in the preoperative (22.8 %) and in the immediate postoperative period (31.6 %). In the postoperative period, the most frequent is the genial area (39 %). The appearance of acneiform eruptions corresponds to steroidal acne. The frequency of acne post orthognathic surgery is high, being higher in women than in men. The severity of this acne is greater in the immediate postoperative period. The frontal region corresponds to the most frequent area of onset of acneiform eruptions in the immediate postoperative period and the genial area in the postoperative period. The diagnosis of these acneiform eruptions corresponds to a steroidal acne, so it is possible to suggest a possible treatment plan, in order to improve the postoperative of the patients and to avoid, as far as possible, future manifestations in new patients undergoing this type of surgery.

[Relationship between the Incidence of Hypomagnesemia and Acneiform Rash and the Therapeutic Effect of Anti-EGFR Monoclonal Antibody in Patients with Metastatic Colorectal Cancer].

PURPOSE: Although anti-EGFR monoclonal antibodies, including cetuximab and panitumumab, are highly effective in KRAS wild-type advanced colorectal cancer, these drugs frequently cause several adverse events. These events include hypomagnesemia and acneiform rash, which may lead to the dose reduction or discontinuation of therapy. In the present study, we retrospectively investigated the incidence of hypomagnesemia and acneiform rash in patients with metastatic colorectal cancer (mCRC). We examined the relationship between the incidence of such adverse events and the therapeutic effect. METHODS: Thirty-four mCRC patients receiving anti -EGFR monoclonal antibody as a first-line therapy during April 2012 to March 2015 were the subjects of the present study. The symptoms of hypomagnesemia and acneiform rash were graded in accordance with the Common Terminology Criteria for Adverse Events, v4.0. RESULTS: The incidence rates of hypomagnesemia (all grades) and the acneiform rash (≥grade 2) were 29%and 50%, respectively. Eight patients (24%) exhibited both of these adverse events. The tumor response rate was notable, as it was significantly higher in patients who experienced both of these adverse events compared to those who did not(88% vs 38% for complete response plus partial response, p=0.039). However, the tumor response rate tended to be higher, although not significantly, in patients with either of these adverse events compared to those without it. CONCLUSION: Concurrent onset of hypomagnesemia and acneiform rash may become a reliable factor capable of predicting the therapeutic effect of anti-EGFR monoclonal antibody.

Cetuximab-induced cutaneous toxicity.

BACKGROUND: Epidermal growth factor receptor inhibitors are recently utilized by oncologists in advanced cases of certain malignancies. However, these agents are associated with numerous cutaneous adverse reactions. OBJECTIVE: To systematically review the cutaneous toxicity of cetuximab-treated patients. METHODS: An analysis of a series of 24 patients (20 men and 4 women) treated with cetuximab (12 patients with head and neck cancer and 12 patients with colorectal cancer) was performed with respect to relevant clinical characteristics. RESULTS: A total of 22 patients (91.7%) developed pustular or maculopapular follicular eruption, often referred to as acneiform rash. One patient (4.2%) developed paronychia in the course of cetuximab therapy. All patients with head and neck cancer had a combination treatment with radiotherapy and experienced radiation dermatitis accompanied by skin xerosis. Anaphylactic reaction was observed in three patients (12.5%). CONCLUSIONS: The most frequent cutaneous side effect reported in this series was acneiform eruption. The authors observed that all women with acneiform rash had only limited facial involvement, whereas all but one man experienced more widespread lesions of the face, the back and the chest. We found no association between the extent and severity of cutaneous eruptions (grade 1 vs. grade 2) and patients' response to therapy.

Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review.

Isotretinoin (13-cis retinoic acid) is an effective treatment for severe cystic or recalcitrant acne vulgaris; however, concerns have been raised regarding its potential association with depression and suicidal behavior. We sought to explore the proposed relationship between isotretinoin use and the risk of depression and attempted and completed suicide in patients with acne vulgaris by performing a systematic literature search for studies reporting primary data on depression and suicidal behavior in patients treated with isotretinoin for acne vulgaris. Nine studies met the qualifying criteria for our analysis. Rates of depression among isotretinoin users ranged from 1% to 11% across studies, with similar rates in oral antibiotic control groups. Overall, studies comparing depression before and after treatment did not show a statistically significant increase in depression diagnoses or depressive symptoms. Some, in fact, demonstrated a trend toward fewer or less severe depressive symptoms after isotretinoin therapy. This decrease was particularly evident in patients with pretreatment scores in the moderate or clinical depression range. No correlation between isotretinoin use and suicidal behavior was reported, although only one retrospective study presented data on this topic. Although the current literature does not support a causative association between isotretinoin use and depression, there are important limitations to many of the studies. The available data on suicidal behavior during isotretinoin treatment are insufficient to establish a meaningful causative association.

Incidence of acneform reactions after laser hair removal.

There have been several studies published on the side effects of laser hair removal, but none specifically looked at acneform reactions. The aim of this study is to obtain an accurate assessment of the incidence of acneform reactions after laser hair removal in relation to skin type, laser type, site of treatment, polycystic ovarian syndrome history (PCOS), age, and sex of the patient. This is a multi-centre prospective study of patients presenting for laser hair removal. Data were gathered using a questionnaire completed by the staff who performed the treatment. The incidence of acneform reactions was 6%. The following variables showed a statistically significant effect on the percentage of patients with reactions: age, with younger patients more likely to develop lesions; those treated with the Nd:YAG laser type were more likely to develop lesions than those treated with the alexandrite; and the Fitzpatrick skin type V showed the highest incidence of acneform lesions, followed by skin types II and IV. History of PCOS, number of prior treatments, use of aloe vera cooling gel, and the sex of the patient had no apparent effect on the incidence of acneform lesions. Acneform reactions are relatively common after laser hair removal; however, in the majority of cases, the severity of the reaction was mild and lasted for a short duration.

Skin diseases in south-east Nigeria: a current perspective.

BACKGROUND AND OBJECTIVE: The incidence of skin diseases in south-east Nigeria during the present decade was analyzed and compared with results from other parts of Nigeria, particularly those in the same zone, obtained more than 30 years ago. This study was carried out to update the recent clinical picture of skin diseases in our environment in view of the rapid development, urbanization and advances in the region. PATIENTS AND METHODS: Consecutive new patients seen at the dermatology clinic of the University of Nigeria, Teaching Hospital, Enugu, Nigeria, from February 1999 to March 2001 were included in this prospective study. Only cases seen and examined by the author were included in this study to ensure uniformity of diagnosis. RESULTS: A total of 2871 patients were observed within the study period. Adults accounted for 69.7% and were aged between 18 and 73 years, while the male:female ratio was 1.3:1. Allergic skin diseases (24.9%) were the commonest skin disorders identified, as opposed to infestations which accounted for an extremely high result of 33.7% (for the same region between 1968 and 1971). In second place was infections/infestations (19.1%). A reversal of picture was thus observed. Within the allergic disorders; eczemas/dermatitis were found to be the most prevalent followed by follicular (13.7%) and pigmentary disorders (11.1%). Sexually transmitted diseases and HIV/AIDs have increased significantly and accounted for 5.4%. Blistering diseases (1.1%) and malignancies (0.5%) occurred less frequently, similar to results found in recent decades for the same region. CONCLUSION: The current picture of skin diseases in south-east Nigeria has changed significantly from mere infections to allergic skin, follicular and pigmentary disorders. Cutaneous lesions secondary to STDs and HIV/AIDs have also increased. Skin lesions related to malnutrition, kwashiorkor and starvation were not observed nor were cutaneous tuberculosis, yaws or pediculosis, while blistering disorders and malignancies remained almost the same. The current picture is similar to that in other developing and Afro-Caribbean countries. Primary-care physicians and health-care providers in Nigeria/Africa need to be aware of the globally changing pattern of skin diseases in the region to enable the allocation of necessary resources (financial, material and human) to manage these skin diseases.

Association between blood concentration of polychlorinated biphenyls and manifestations of symptoms and signs in chronic "Yusho" patients from 1986 to 1997.

To examine the association between blood PCB level and manifestations of symptoms and signs by Yusho patients, a cross-sectional study was conducted using the results of nationwide health examination for Yusho. The subjects were the officially identified Yusho patients who admitted the health examination from 1986 to 1997. The number of examinees with known blood PCB level was 334 in 1986, and decreased to 214 in 1997. The numbers of male and female patients were similar. The geometric mean (95% confidence interval) of blood PCBs concentration was 4.05 ppb (3.75 to 4.37) in 1986 and 2.85 ppb (2.63 to 3.08) in 1997. Multiple logistic regression analysis was carried out for the data of each year with log-transformed blood PCB level as an explanatory variable and a manifestation of a sign or symptom as a response variable. Sex and age adjusted odds ratio and significance level (P) were computed. Positive association of blood PCB level with manifestations of comedones on the trunk and acneiform eruptions on the genital and gluteal regions was statistically significant for five, eight and six times, respectively. No other symptoms or signs showed such strong associations. Associations between manifestations of these signs and blood PCB level, however, did not seem to diminish in the twelve years of observation. It is suggested that the positive association of these signs with blood PCB level will still be maintained.