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Clinical Drug Investigation Sep 2019The use of targeted therapies, when added to conventional chemotherapy, has significantly improved clinical outcomes and survival of cancer patients. While targeted... (Review)
Review
The use of targeted therapies, when added to conventional chemotherapy, has significantly improved clinical outcomes and survival of cancer patients. While targeted therapies do not have the systemic adverse reactions of chemotherapy, they are associated with toxicities that can be severe and impair patient quality of life and adherence to anti-cancer treatment. Panitumumab and cetuximab, two monoclonal antibodies against epidermal growth factor receptor (EGFR), are recommended for the treatment of metastatic colorectal cancer (mCRC). The majority of patients with mCRC who are treated with anti-EGFR therapy develop skin toxicities, including papulopustular rash (the most common), xerosis, painful cracks and fissures on the palms and soles of the feet, paronychia, pruritus, and abnormal hair and eyelash growth; they are also more prone to skin infections. Given the involvement of EGFR in normal epidermis physiology, development and function, skin toxicities caused by anti-EGFR therapy are not unexpected. In recent years, recommendations have been formulated for the prevention and treatment of anti-EGFR therapy-related skin toxicities. Indeed, proper and timely management of these toxicities is important for ensuring uninterrupted anti-cancer treatment and optimal outcomes. Here, we review the current knowledge of anti-EGFR therapy-related skin toxicities and the latest recommendations for their management. We also present a treatment approach for papulopustular rash based on the combination of fusidic acid plus betamethasone in a lipid-enriched topical formulation. The effectiveness of this approach is documented by the presentation of five cases successfully treated in clinical practice for anti-EGFR therapy-related rash.
Topics: Antineoplastic Agents, Immunological; Cetuximab; Colorectal Neoplasms; ErbB Receptors; Exanthema; Humans; Neoplasm Metastasis; Panitumumab; Patient Compliance; Practice Guidelines as Topic; Quality of Life
PubMed: 31264159
DOI: 10.1007/s40261-019-00811-7 -
Cutaneous and Ocular Toxicology Sep 2019Papulopustular rash is the most common cutaneous adverse effect during targeted tumour therapy particularly with epidermal growth factor receptor inhibitors (EGFRIs)....
Papulopustular rash is the most common cutaneous adverse effect during targeted tumour therapy particularly with epidermal growth factor receptor inhibitors (EGFRIs). To evaluate the adverse skin reactions, mainly papulopustular rash, caused by targeted tumour therapy. We retrospectively analysed the data of patients who were diagnosed papulopustular rash due to targeted chemotherapeutic agents between January 2016 and August 2018. Demographic characteristics of the patients, the type of malignancy, chemotherapeutic agents causing papulopustular rash, clinical features and grade of the rash, treatment modalities used for the rash, other associated cutaneous adverse reactions, and the need for dose-modification or discontinuation of the chemotherapy were recorded. A total of 39 patients (26 males, 13 females) with a median age of 60 (range 32-86) years were included in the study. EGFRIs such as erlotinib, lapatinib, cetuximab, and panitumumab were the main drugs causing papulopustular rash in 2 (5.1%), 3 (7.6%), 18 (46.1%), and 13 (33.3%) patients, respectively. Imatinib, bevacizumab in combination with oxaliplatin, and everolimus in combination with exemestane and goserelin were responsible in three patients. The most commonly affected area was the face (87.1%) followed by the trunk (56.4%), scalp (25.6%), and extremities (23%). The rash was recorded as grade 1, 2, and 3 in 18, 13, and 6 of the patients, respectively. Grade 3 rash was lead to dose interruptions in 5 (12.8%) patients with subsequent reintroduction at a lower dose in 4 (10.2%) of them and discontinuation of the therapy in 1 (2.5%) patient. Pruritus, xerosis, paronychia, increased growth of the eyelashes, mucositis, hand-foot syndrome (HSF), and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) are other skin toxicities associated with the targeted tumour therapy. With the increasing use of targeted therapies, dermatologists are now confronted with extensive spectrum of skin toxicities. Therefore, it is critical for dermatologists to be aware of these toxicities so as to develop the best approach without discontinuation of cancer therapy.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cetuximab; ErbB Receptors; Erlotinib Hydrochloride; Exanthema; Female; Humans; Lapatinib; Male; Middle Aged; Molecular Targeted Therapy; Panitumumab; Pruritus; Retrospective Studies
PubMed: 31010330
DOI: 10.1080/15569527.2019.1594874 -
Open Access Macedonian Journal of... Mar 2019Tyrosine kinase inhibitors (TKIs) have been introduced for the treatment of lung cancer, improving progression-free survival, objective response rate, and quality of...
BACKGROUND
Tyrosine kinase inhibitors (TKIs) have been introduced for the treatment of lung cancer, improving progression-free survival, objective response rate, and quality of life. However, TKIs can lead to cutaneous toxicities, including papulopustular rash, xerosis, paronychia with/without pyogenic granulomas, scalp disorders, facial hair and/or eyelash growth.
AIM
In this study, we describe retrospectively all cases of mucocutaneous side effects in patients with lung cancer under TKIs referring to our outpatient for the skin care of oncological patients.
METHODS
We included patients referring from January 2016 to January 2018 affected by lung cancer and under TKIs. We collected data about the clinical exam, clinical photography, dermoscopy, histology and direct microscopic examination for each patient and we performed retrospectively descriptive analyses to assess whether a specific TKIs is linked significantly to particular cutaneous toxicity.
RESULTS
The majority of skin toxicities were due to afatinib, and the most common skin reaction was rash. We selected 60 patients with skin reactions, treated by TKIs for lung cancer. The majority of skin toxicities were due to afatinib (47/102 adverse reactions) and erlotinib (39/102). The most common skin reaction was rash (63% of patients), followed by xerosis (30%) and granulomas (30%). There was no significant relationship between a specific type of cutaneous reaction and specific EGFRi except for granulomas, developed more frequently in patients under afatinib (p < 0.05).
CONCLUSION
Most of our patients (63%) developed a cutaneous rash under TKIs. Most commonly afatinib was the drug involved, although it wasn't the most used EGFRi. Moreover, we noticed a significant correlation between afatinib therapy and appearance of granulomas.
PubMed: 30976343
DOI: 10.3889/oamjms.2019.170 -
Georgian Medical News Feb 2019The purpose of the study was to study the frequency of detection and population density of the mite in rosacea patients depending on the clinical form, the location of...
The purpose of the study was to study the frequency of detection and population density of the mite in rosacea patients depending on the clinical form, the location of the morphological elements on the face and some parameters of the functional state of the skin. We observed 55 patients (38 women and 17 men) aged from 30 to 65 years old with disease duration from 6 months to 10 years. According to clinical forms, 35 had PPR and 20 - ETR (erythematous - telangiectatic rosacea). By location of the rash elements, the following types are distinguished: central, medial, asymmetric, lateral, and total. The mite was identified by a microscopic method. The functions of the skin barrier of the face skin: moisture, oiliness, dryness were determined using a bio-impedance analyzer (BIA). As shown by the results of the study of the above parameters in the observed patients, a high density of the mite population (> 5 per cm2) was noted in cases of total, medial and central type of their location. This indicator was in direct correlation with parameters such as skin fat content and moisture. 75% of patients in this group were diagnosed with PPR. In the group of patients with medium and low population density of mites (<5 per cm2), the lateral, asymmetric and central type of their location were dominated in 65% of patients with ETNR. This group of patients showed low levels of skin fat and moisture, relatively high rates of dryness. Thus, the population density of the mites is dependent on the intensity of the anatomical location of the sebaceous glands of the face skin. An analysis of the results obtained in the study of the role of mite in the pathogenesis of rosacea led us to the conclusion: in rosacea patients, a correlation was found between the increase in the population density of mites, the type of element arrangement and the severity of dermatosis, which proves the role of the mite as one of the most frequent but not obligatory pathogenetic factors in the development of this dermatosis, especially its papulopustular form.
Topics: Adult; Aged; Animals; Face; Female; Humans; Male; Microscopy; Middle Aged; Mite Infestations; Mites; Rosacea; Skin
PubMed: 30958297
DOI: No ID Found -
Acta Dermato-venereologica Jun 2019
Topics: Administration, Oral; Administration, Topical; Child, Preschool; Dermatitis, Perioral; Diagnosis, Differential; Erythromycin; Exanthema; Facial Dermatoses; Female; Humans; Metronidazole; Treatment Outcome
PubMed: 30834453
DOI: 10.2340/00015555-3159 -
Frontiers in Pediatrics 2018Here we describe two term male infants diagnosed with X-linked CGD who present, in addition to frequent infection, with a unique papulopustular skin rash. CGD is caused...
Here we describe two term male infants diagnosed with X-linked CGD who present, in addition to frequent infection, with a unique papulopustular skin rash. CGD is caused by a number of genetic defects that impair phagocyte function. This disease results in recurrent infections and granuloma formation. Rarely do patients develop cutaneous symptoms, unless associated with autoimmune disorders such as systemic erythematous lupus (1). Each male infant mentioned here was diagnosed with CGD based on abnormal DHR testing and confirmatory genetic testing. The presenting papulopustular dermatitis was initially characterized as non-classic appearing eczema and subsequently found to be refractory to usual eczema treatment and antibiotics. After obtaining written informed consent from both families, we have documented photographs of the development of a characteristic rash in two newly diagnosed infants with CGD. One infant underwent cutaneous biopsy with histologic evaluation and negative cultures. The dermatitis for both infants was refractory to topical and systemic therapies, and resolved after bone marrow transplantation. Our objective was to characterize cutaneous findings in X-linked CGD and emphasize the importance of considering further immune workup in patients who present with unusual cutaneous findings that do not fit with common infant rashes in conjunction with concerning features for primary immunodeficiency.
PubMed: 30766861
DOI: 10.3389/fped.2018.00429 -
PloS One 2018Topical application of Vitamin K1 has been demonstrated to effectively treat papulopustular skin rash, a serious and frequently encountered side effect of Epidermal...
Topical application of Vitamin K1 has been demonstrated to effectively treat papulopustular skin rash, a serious and frequently encountered side effect of Epidermal Growth Factor Inhibitors (EGFRIs). Systemic absorption of vitamin K1 from skin and the resultant consequence of antagonizing EGFRIs anticancer effects jeopardizes the clinical acceptability of this rather effective treatment. The purpose of the present study was to rationally formulate and evaluate the release rate and transdermal absorption of a wide range of Vitamin K1 dermal preparations with a variety of physiochemical properties. A library of 33 formulations with were compounded and tested for Vitamin K1 permeation using hydrophobic membranes and porcine skin mounted in a Fran diffusion cells. Our results demonstrate the lowest diffusion for water-in-oil emulsions, which also demonstrated a negligible transdermal absorption. The statistical analysis showed a significant correlation between in vitro and ex vivo results. While viscosity did not have a significant impact on the diffusion or absorption of vitamin K1, an increase in the lipid content was correlated with an increase in transmembrane diffusion (not with transdermal absorption). Overall, formulation design significantly impacts the release rate and transdermal absorption of vitamin K1, and confirms the possibility of minimal systemic distribution of this vitamin for this specific purpose.
Topics: Administration, Topical; Animals; Antineoplastic Agents; Dermatologic Agents; Diffusion; Emulsions; Gels; In Vitro Techniques; Lipids; Membranes, Artificial; Ointments; Skin; Skin Absorption; Skin Cream; Skin Diseases; Surface-Active Agents; Sus scrofa; Viscosity; Vitamin K 1; Water
PubMed: 30289881
DOI: 10.1371/journal.pone.0204531 -
BMJ Case Reports Aug 2018Cetuximab and osimertinib are epidermal growth factor receptors (EGFRs) inhibitors used in the treatment of several malignancies. These agents have been associated with...
Cetuximab and osimertinib are epidermal growth factor receptors (EGFRs) inhibitors used in the treatment of several malignancies. These agents have been associated with several skin lesions, the most common being papulopustular acneiform rash involving the face, neck, chest and back. Herein, we describe a unique toxic effect of these agents involving the fingertips and lateral aspects of fingers in a small patient series. The lesions presented approximately 4 weeks into treatment were cut-like and caused local discomfort/pain. Application of a colloidal solution allowed for partial resolution of these lesions in one patient, while discontinuation of the drug led to the disappearance of the lesions in another. Thus, we call for awareness of this unique skin toxicity with the use of EGFR inhibitors in patients with cancer.
Topics: Administration, Topical; Aged; Antineoplastic Agents; Cetuximab; Colloids; Colonic Neoplasms; Dermatologic Agents; Drug Eruptions; ErbB Receptors; Female; Fingers; Humans; Lung Neoplasms; Male; Middle Aged; Treatment Outcome
PubMed: 30068575
DOI: 10.1136/bcr-2017-224144 -
Dermatologic Therapy Jul 2018Acneiform rash is a commonly reported side effect to certain types of medications, including antipsychotic agents. Its clinical presentation consists mainly of...
Acneiform rash is a commonly reported side effect to certain types of medications, including antipsychotic agents. Its clinical presentation consists mainly of papulopustular lesions. Other types of lesions, such as nodular or cystic, can also be observed. Body distribution of the lesions follows a similar pattern to acne vulgaris. Depending on the severity of the case, drug-induced acne may be treated in different ways. In mild cases, the use of topical antibiotics and retinoids in combination is usually effective. With more severe forms, it may be necessary to add oral antibiotics, such as tetracyclines, but a good response is not always achieved. Identification of the drug responsible for the side-effect is mandatory in refractory eruptions. Herein, we present the case of an Aripiprazole-induced acneiform rash successfully treated with oral Isotretinoin. The treatment was effective and well tolerated and there was no need to discontinue the psychopharmacological medication. This is the first study to report this modality of treatment.
Topics: Acneiform Eruptions; Administration, Oral; Adult; Antipsychotic Agents; Aripiprazole; Dermatologic Agents; Drug Eruptions; Humans; Isotretinoin; Male; Remission Induction; Schizophrenia, Paranoid; Skin; Treatment Outcome
PubMed: 30019366
DOI: 10.1111/dth.12637 -
Acta Dermatovenerologica Croatica : ADC Apr 2018Clindamycin is a lincomycin-derived antibiotic useful for the treatment of anaerobic and Gram-positive aerobic bacterial infections. Cutaneous adverse reactions are... (Review)
Review
Clindamycin is a lincomycin-derived antibiotic useful for the treatment of anaerobic and Gram-positive aerobic bacterial infections. Cutaneous adverse reactions are usually maculopapular exanthemas, although hypersensitivity syndrome, acute generalized exanthematous pustulosis, and Stevens-Johnson syndrome have also been reported (1). We report the case of a patient with a maculopapular rash triggered by clindamycin who developed cutaneous lesions on striae distensae (SD). A 47-year-old woman was referred to our clinic for pruritic cutaneous lesions which had started 6 days earlier. Her past clinical history included hypertension, hypothyroidism, hyperuricemia, cholecystectomy, caesarean section, and endometriosis-related abdominal surgery, and she was taking levothyroxine, allopurinol, imidapril, and omeprazole. The skin rash first developed on her neck and back on the 3rd day of clindamycin oral treatment (300 mg every 6 hours), which was prescribed as antibiotic prophylaxis for a tooth implant. General malaise (but not fever) was also reported. Physical examination revealed an erythematous maculopapular eruption symmetrically distributed on the neck, abdomen, and back (Figure 1, A), with isolated lesions involving the proximal upper and lower limbs (Figure 1, B). There was a striking vertical distribution of skin lesions along the SD on the lateral sides of the abdomen (Figure 1, C). No mucosal involvement was found, and laboratory studies showed no abnormalities. Clindamycin withdrawal was followed by prescription of a course of oral deflazacort, starting at 30 mg daily and tapering down during a 9-day period. On the 5th day of treatment, the rash had almost cleared with minimal desquamation (Figure 1, D). Eight weeks after clearance of the skin rash, informed consent was obtained in order to perform an allergological evaluation of clindamycin, including prick and intradermal (ID) tests on the forearm and patch tests on the upper back (2). For patch testing, powder of the commercial capsules (Dalacin®) was diluted in petrolatum (pet.) and water (aq.), resulting in a final 1% clindamycin dilution. Parenteral clindamycin preparations were used in therapeutic concentrations for prick tests (150 mg/mL) and dilutions in saline of 1/100 and 1/10 for the ID test. Other authors have reported that these concentrations do not seem to irritate the skin (3-6). Prick and ID tests were assessed after 20 min and 24 hours, respectively. Patch tests were removed after the 2nd day, and late reactions were evaluated on day 2 and day 4. Prick and ID test results after 20 min were negative. Late results of ID tests with clindamycin (1.5 and 15 mg/mL) were positive: erythematous infiltrated papules about 7×7 mm and 18×15 mm were observed at 24 hours and lasted until the 8th day. Patch tests with clindamycin 1% in pet. and 1% in aq. were also positive (+ on day 2 and day 4). Positive late skin tests suggested delayed-type non-IgE-mediated allergic clindamycin hypersensitivity. Oral challenge tests are considered to be the gold standard to establish or exclude drug hypersensitivity. Due to the positive result of late skin test to clindamycin, oral challenge was not performed in our patient (3,5). The Koebner isomorphic phenomenon has been described in cutaneous reactions induced by drugs, such as antibiotics and chemotherapy. Chronic pressure on the skin is probably involved in the onset of skin lesions in hand-foot eruptions induced by tyrosine kinase inhibitors (sorafenib and sutinib). Solar exposure and cutaneous trauma also seem to play a role in the location of papulopustular eruptions caused by endothelial growth factor receptor inhibitors (erlotinib) (7). More frequent involvement in traumatized skin and surgical scars has been reported in the context of linear IgA bullous dermatosis and leukocytoclastic vasculitis triggered by vancomycin and cefuroxime (8). SD are produced by non-penetrating physical trauma, similar to friction or pressure. Different dermatoses can develop along SD skin lesions (like plaque psoriasis, pustular psoriasis, lichen planus, vitiligo, discoid lupus erythematosus, lupus vasculitis, urticarial vasculitis, or chronic graft-versus-host disease) (9). Bevacizumab, etretinate, and corticosteroid-induced ulcers, hyperpigmentation caused by bleomycin, and urticariform lesions triggered by diclofenac are examples of different type of drug-induced abnormalities involving SD (10). In summary, we identified clindamycin as the cause of the cutaneous reactions that occurred in our patient on the basis of the results of the skin tests and clinical history. Our findings confirmed a delayed-type hypersensitivity reaction, possibly involving a T-cell-mediated immunologic mechanism. Intradermal and patch tests were found to be useful in order to confirm the diagnosis (4,5). We did not find reports in the literature of drug-induced cutaneous eruptions along the SD as a manifestation of a Koebner phenomenon. Clinical underreporting of this phenomenon could explain the scarce literature on this cutaneous adverse reaction.
Topics: Administration, Oral; Biopsy, Needle; Clindamycin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Eruptions; Female; Follow-Up Studies; Humans; Immunohistochemistry; Middle Aged; Patch Tests; Risk Assessment; Severity of Illness Index; Striae Distensae; Withholding Treatment
PubMed: 29782303
DOI: No ID Found