Mucocutaneous Adverse Effects Research Articles

An observational prospective study of mucocutaneous adverse effects of chemotherapeutic drugs and radiotherapy

Background There is an enormous advancement in chemotherapeutic drugs and radiotherapy. With the advancement, the adverse effects in patients receiving chemotherapeutic drugs and radiotherapy have also increased. Hence identifying and treating adverse effects of chemotherapeutic drugs and radiotherapy is of utmost importance for patients. This study will help us to find out the various mucocutaneous adverse effects associated with various new chemotherapeutic drugs and radiation. Our objective is to find out the frequency of mucocutaneous manifestation in patients receiving chemotherapy and radiotherapy and also to know and assess the various patterns and severity of mucocutaneous involvement in chemotherapy and radiotherapy. Methods This will be an observational prospective study that will be conducted in a tertiary care cancer hospital [Siddharth Gupta Memorial Cancer Hospital] and patients coming to OPD of AVBRH in the Department of Dermatology from 15th December 2023 to 15 September 2024, who will be presenting with the mucocutaneous adverse effects. Detailed History and Cutaneous examination will be performed and graded according to Common Terminology Criteria for Adverse Events v5. The various mucocutaneous adverse effects will be compiled and grading will be done. This study will help us to find out the various mucocutaneous adverse effects associated with various new chemotherapeutic drugs and radiation. Results We will study the various mucocutaneous manifestations in patients with solid organ malignancy or hematological malignancy receiving chemotherapy and radiotherapy.

Comparative Study Between Tacrolimus 0.1% Ointment Versus Topical White Soft Petrolatum Jelly in the Treatment of Oral Retinoid-Induced Cheilitis

Retinoids are used topically as well as orally, and the most commonly used oral retinoids are isotretinoin and acitretin. Mucocutaneous adverse effects are frequently seen with the use of systemic retinoids, the most common being cheilitis, which is dose-dependent and seen in almost all patients using it. To study the comparative effect of topical tacrolimus 0.1% ointment versus topical white soft petrolatum jelly in the treatment of cheilitis due to retinoids. A total of 26 patients with cheilitis post-treatment with isotretinoin were enrolled in this cross-sectional study conducted over a period of 6 months. They were randomized into two groups of 13 patients each to receive topical tacrolimus 0.1% ointment and soft petrolatum jelly twice daily, respectively. Patients were followed up weekly with clinical photographs. Resolution of cheilitis was assessed on the basis of photograph and ICGS score. About 84.6% of patients of group A and 53.8% of patients of group B showed resolution of symptoms within 1 week of treatment. A significant difference was seen in duration for complete cheilitis resolution and relapse rate in the two groups. Our study concludes that oral retinoid-induced cheilitis shows faster and more significant resolution with twice-daily topical tacrolimus 0.1% ointment application compared to twice-daily topical petrolatum jelly.

A systematic review of isotretinoin dosing in acne vulgaris

AbstractHow does low‐dose oral isotretinoin compare with recommended and high‐dose oral isotretinoin in terms of efficacy, adverse effect profile, duration of remission, economic profile and rate and severity of relapse? A systematic literature search of EMBASE, MEDLINE, PubMed and The Cochrane Library from 1983 to July 2022 was conducted to identify randomised control trials (RCTs), cohort studies and cross‐sectional studies investigating the treatment of acne vulgaris with oral isotretinoin. This systematic review of the literature sought to explore and compare the use of different isotretinoin dosing regimens. Primary outcomes were efficacy, relapse, and safety profiles of oral isotretinoin of varying doses. Secondary outcomes included adverse events and economic considerations. The quality of studies, including risk of bias was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). A total of 32 studies were included. Severe acne responds better to conventional or high fixed daily doses of isotretinoin. In cases of mild to moderate acne, where oral isotretinoin was prescribed, clearance rates were comparable with low, conventional or high dosage regimens. Despite this, relapse was more frequent in those treated with a lower dose. The severity of mucocutaneous adverse effects worsens as the dose of isotretinoin is increased. Comparison between studies was challenging due to differing methods of assessment, outcome measures and duration of follow‐up. This review highlights the need for an adequately powered RCT comparing low, conventional and high doses of oral isotretinoin to establish optimal dosing for treatment and prevention of relapse in acne vulgaris.

Mucocutaneous adverse effects of remdesivir and favipiravir in patients with Covid-19 infection: A systematic review

Introduction: Remdesivir and favipiravir are two antiviral medicines used in the treatment of Covid-19 infection widely. The studies pertaining to the mucocutaneous adverse events of these two drugs are scarce. Hence, we performed a systematic review to bridge the above gap. Materials and Methods: The study is performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. All original articles, case series, and case reports pertaining to mucocutaneous adverse drug reactions caused by remdesivir and favipiravir, while any of these drugs were administered in Covid-19-infected patients, were included in the present study. Results: Six articles were identified pertaining to the mucocutaneous adverse reactions of remdesivir, of which two were original articles and four were case reports. Four case reports pertaining to the mucocutaneous adverse events of favipiravir are included in this study. The details regarding the same are elaborated in the main manuscript. Conclusion: In the present systematic analysis, the mucocutaneous adverse events of the two widely used antiviral medications in Covid-19 were described. This articles throws light on the aspects which are hardly reported or discussed in the literature.

Evaluation of biophysical skin parameters and hair changes in patients with acne vulgaris treated with isotretinoin, and the effect of biotin use on these parameters.

Impairment of biotin metabolism with the use of isotretinoin and the mucocutaneous side effects observed in patients using isotretinoin suggests that they are a result of decreased enzyme activity. We aimed to determine the pattern of skin and hair changes in patients with acne receiving isotretinoin and how these changes were affected by biotin added to the treatment. Sixty patients were divided into two groups. Each group contained 30 patients. Groups A and B received 0.5mg/kg/day isotretinoin, and 10mg/day biotin supplement was added to Group B. Both groups were evaluated using a digital dermoscope for hair changes and with a DermaLab® Combo device for transepidermal water loss (TEWL), skin retraction, skin hydration, and skin sebum levels at the beginning and end of the fourth month. In group B, the anagen hair ratio increased (P=0.034) and the telogen hair ratio decreased significantly (P=0.003). Skin sebum and the skin retraction values decreased in both groups. Skin hydration decreased significantly in group A (P=0.001), but there was no significant decrease in group B (P=0.43). Biotin (10mg/day) given in addition to isotretinoin treatment decreased telogen and increased anagen hair rates and helped to maintain skin hydration. The use of 10mg/day biotin can prevent the mucocutaneous adverse effects of isotretinoin treatment.

Drug survival and safety profile of acitretin monotherapy in patients with psoriasis: A multicenter retrospective study.

Acitretin is a nonimmunosuppresive systemic agent used in the treatment of psoriasis. Despite its frequent use, research on drug survival and adverse effects is limited. This study aims to evaluate drug survival, factors associated with survival, and adverse effects. Database of the six tertiary referral center for psoriasis patients treated with acitretin between November 2014 and April 2020 were retrospectively analyzed. Demographics of patients, adverse effects, and also drug survival were analyzed. Of 412 patients, 61.2% were male, and 38.8% were female. Common clinical adverse effects were cheilitis (71.4%), dry skin (62.5%), and palmoplantar skin peeling (37.2%). High triglyceride and high total cholesterol levels were observed in 50.0% and 49.5% of patients, respectively. Median survival time (95% confidence interval [CI]) was 18 (13.6-22.4) months. Statistically significant risk factors affecting drug discontinuation were having psoriatic arthritis, age under 65, and receiving previous systemic treatment. Drug survival rates were 56.6%, 25.9%, and 19.8% at 1, 5, and 8 years, respectively. Although mucocutaneous adverse effects of the acitretin were quite frequent, severe, life-treatining ones were infrequent. This old, relatively inexpensive and safe treatment remains a good alternative for the treatment of psoriasis.

Mucocutaneous adverse effects of the genital and perianal skin from isotretinoin therapy

Mucocutaneous adverse effects of the genital and perianal skin from isotretinoin therapy

Adalimumab-induced photosensitivity and oral erosions in rheumatoid arthritis

Tumour necrosis factor-alpha (TNF-α) inhibitors have been successfully used in the treatment of various immune-mediated inflammatory diseases. However, these agents are frequently associated with mucocutaneous adverse effects.1 Anti-TNF-α-induced lupus erythematosus...

Cutaneous Adverse Drug Reactions to Targeted Chemotherapeutic Drugs: A Clinico-Epidemiological Study.

Background:Targeted chemotherapeutic drugs have led to a remarkable improvement in the survival of cancer patients but also have resulted in the increased incidence of uncommon but specific muco-cutaneous adverse effects.Aims:This study aimed to highlight the spectrum of such cutaneous adverse drug reactions and to derive a causal association.Materials and Methods:A hospital-based, descriptive study was carried out in the dermatology outpatient department between August 2016 and July 2018, on patients referred from the state cancer institute, who developed muco-cutaneous lesions after the initiation of targeted chemotherapeutic drugs.Results:A total of 80 patients, 59 (74%) males and 21 (26%) females of mean age 45.83 ± 16.37 years (range 4–70 years) developed one or more uncommon albeit specific muco-cutaneous adverse effects. Among them, papulopustular and acneiform eruptions were found in 21 patients (26.25%), and PRIDE complex was seen in 3 patients. Sixteen patients (20.00%) developed palmar-plantar erythrodysesthesia, 8 patients (10%) developed lichenoid drug eruption, and 5 patients (6.25%) developed flagellate dermatitis. Twenty-two (27.5%) patients showed nail changes, the most common, being melanonychia.Conclusion:There has been a paradigm shift in the management of both hematopoietic and solid cancers with the advent of targeted chemotherapeutic drugs leading to an increase in uncommon and specific drug reactions. Early recognition of these decreases morbidity, improves quality of life, and allows continuation of the life saving chemotherapy.

Long-term mucocutaneous adverse effects of imatinib in Indian chronic myeloid leukemia patients.

Short-term mucocutaneous adverse effects are well documented with imatinib. However, studies on long-term adverse effects and in the ethnic population are lacking. To study the long-term mucocutaneous adverse effects of imatinib and factors predicting these adverse effects. In this cross-sectional study, consenting adult chronic myeloid leukemia patients on imatinib for more than 250 days were recruited. The details of imatinib treatment were retrieved from hematology clinic records. Four hundred and thirty-eight patients who were on imatinib for a mean duration of 1820 days were recruited. A mean number of 1.42 ± 0.98 cutaneous adverse effects were seen per patient. Melasma-like pigmentation, periorbital edema, oral lichenoid reaction, cutaneous hypopigmentation, and vesicobullous eruptions were seen in 236 (53.9%), 81 (18.5%), 70 (16%), 42 (9.6%), and 12 (2.7%) patients, respectively. Drug-induced cutaneous eruptions (9.1%) and cutaneous hypopigmentation (9.6%) were seen less frequently. Cutaneous hyperpigmentation was more likely seen in younger patients (P = 0.001) and females (P < 0.001). On multivariate analysis, female gender was a significant risk factor for developing cutaneous hyperpigmentation and periorbital edema. Cutaneous hyperpigmentation and periorbital edema are common long-term adverse effects of imatinib in Indian patients. Female gender is a significant risk factor for the development of both these adverse effects.

Clinical and Histologic Features of Lichenoid Mucocutaneous Eruptions Due to Anti-Programmed Cell Death 1 and Anti-Programmed Cell Death Ligand 1 Immunotherapy.

Antagonist antibodies to programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have shown remarkable activity in multiple tumor types. Recent US Food and Drug Administration approval of such agents for advanced melanoma, non-small cell lung cancer, and renal cell carcinoma has hastened the need to better characterize their unique toxicity profiles. To provide a clinical and pathologic description of the lichenoid mucocutaneous adverse effects seen in patients receiving anti-PD-1/PD-L1 treatment. Patients with advanced cancer who were referred to dermatology at Yale-New Haven Hospital, a tertiary care hospital, after developing cutaneous adverse effects while receiving an anti-PD-1 or PD-L1 antibody therapy either as monotherapy or in combination with another agent were identified. Medical records from 2010 to 2015 and available skin biopsy specimens were retrospectively reviewed. Patient demographic characteristics, concurrent medications, therapeutic regimen, type of disease, previous oncologic therapies, clinical morphology of cutaneous lesions, treatment of rash, peripheral blood eosinophil count, tumor response, and skin histologic characteristics if biopsies were available. Patients were 13 men and 7 women, with a mean (range) age of 64 (46-86) years. The majority of cases (16 [80%]) had a clinical morphology consisting of erythematous papules with scale in a variety of distributions. Biopsies were available from 17 patients; 16 (94%) showed features of lichenoid interface dermatitis. Eighteen patients were treated with topical corticosteroids, and only 1 patient required discontinuation of anti-PD-1/PD-L1 therapy. Only 4 of 20 patients (20%) developed peripheral eosinophilia. Sixteen patients (80%) were concurrently taking medications that have been previously reported to cause lichenoid drug eruptions. Papular and nodular eruptions with scale, as well as mucosal erosions, with lichenoid features on histologic analysis were a distinct finding seen with anti-PD-1/PD-L1 therapies and were generally manageable with topical steroids. Concurrent medications may play a role in the development of this cutaneous adverse effect.

Effectiveness and Safety of Acitretin in Children with Plaque Psoriasis: A Multicenter Retrospective Analysis.

Acitretin is licensed for and is most commonly used to treat psoriasis. Little information exists about its efficacy and safety in childhood and adolescent psoriasis. Retrospective analysis of a group of children and adolescents (<17 years of age) with moderate to severe plaque psoriasis treated with acitretin between 2010 and 2014 at Italian dermatology clinics. Patients were identified through databases or registries. The study population consisted of 18 patients with a median age of 9.5 years at the start of therapy. The median maintenance dosage per day was 0.41 mg/kg. Eight patients (44.4%) achieved complete clearance or good improvement of their psoriasis, defined as improvement from baseline of 75% or more on the Psoriasis Area and Severity Index at week 16. Three had three or more courses of treatment with short disease-free intervals. In three patients, acitretin treatment was ongoing at the time of data collection. The mean total duration of treatment in responders was 22.7 months. One patient discontinued treatment because of arthralgia. The remaining nine patients (50%) discontinued treatment because it was ineffective. Mucocutaneous adverse effects occurred in all patients, but did not affect therapy maintenance. In this retrospective case series, acitretin was a moderately effective, well-tolerated treatment in children with moderate to severe plaque psoriasis. Given the small number of patients, statements about long-term safety are not possible.

Mucocutaneous manifestations in patients on chemotherapy with pediatric hematological malignancies

Introduction: A wide variety of chemotherapeutic agents are currently in use for the treatment of hematological malignancies in children. A spectrum of mucocutaneous adverse effects has been attributed to these agents, however, the data largely consists of case reports and case series. Material and Methods: Proforma of all pediatric patients up to 18 years of age, with confirmed hematological malignancies (lymphoma and leukemia), undergoing chemotherapy, and attending the pediatric hemato-oncology clinic of a tertiary care hospital over a period of 2 years were analyzed. A detailed history, mucocutaneous examination and investigations were recorded as per the proforma. The results are presented as mean ± standard deviation. The prevalence of various side effects of chemotherapy is presented as percentages. Results: The age of the patients ranged from 1.2 to 14 years (mean age: 6.6 ± 3.2 years). The duration of the disease ranged from 2 to 122 weeks. Mean duration of chemotherapy was 23.9 ± 24.7 weeks. The analysis consisted of 38 (76%) males and 12 (24%) females (M: F: 3.2:1). Seventy-four percent of the patients had B-cell acute lymphoblastic leukemia (ALL), 6 patients had T-cell ALL, 3 patients had Philadelphia chromosome (+) T-cell ALL, 3 patients had non-Hodgkins lymphoma (NHL) and one patient had hemophagocytic lymphohistiocytosis (HLH). Methotrexate (72%) was the most common agent used followed by vincristine (68%), 6-mercaptopurine (58%), daunomycin (48%), and asparaginase (30%). Hyper-pigmentation was the most common cutaneous side effect noticed in 6 patients. Three patients developed abscess. Two patients each developed tinea corporis, petechie, and thrombophlebitis. One patient each had scabies, pityriasis versicolor, miliaria rubra, allergic contact dermatitis, lip lick cheilitis, ear discharge, and conjunctivitis. One patient developed acute methotrexate toxicity. A total of 24 patients developed mucosal lesions, with aphthous ulcer (20%) being the most common, followed by oral candidiasis (12%) and herpes labialis (12%). Seventeen (34%) patients had diffuse anagen effluvium. Most common change affecting the nails among the study patients was Beau's lines for both fingernails (26%) and toenails (36%). Other less common changes included melanonychia, leuconychia, Mees lines, Muehrcke's nails, half and half nails, etc. Conclusion: The mucocutaneous manifestations associated with chemotherapy cause significant morbidity and possibly mortality in children. A proper knowledge of these manifestations can help in early identification and withdrawal of the offending agents and preventing the morbidity with appropriate and timely management.

Hidroksiüre'nin Neden Olduğu Longitidunal Melanonişi

Hydroxyurea is a chemotherapeutic agent which is used in the management of myeloproliferative disorders. Mucocutaneous adverse effects and nail hyperpigmentation can be observed in long-term treatment. Cases of hydroxyurea-induced melanonychia develop predominantly in female patients and the most common pattern is longitudinal bands. Here we present a case of 65-year-old woman patient that has longitudinal melanonychia on the nails of the hands, observed at the eighteenth month of the treatment of hydroxyurea. By means of this case, it is aimed to be aware of the cutaneous side effects of hydroxyurea which is commonly used in myeloproliferative disorders

Compound mucocutaneous adverse effects of oral capecitabine in a patient.

Compound mucocutaneous adverse effects of oral capecitabine in a patient.

Capecitabine-induced hand-foot syndrome

Capecitabine is an oral fluoropyrimidine carbamate and a prodrug of 5- fluorouracil, used in treatment of colorectal and breast carcinoma, which fail to respond to standard chemotherapies. A variety of muco-cutaneous adverse effects has been recognized. The pathogenesis of such manifestations still remains an enigma though various theories have been proposed. We report a case of localized cutaneous hyperpigmentation of the palms and soles secondary to capecitabine in a woman that underwent sigmoidectomy and was in her second cycle of chemotherapy. Since these drugs causing HFS has become commoner in its use in the recent years, due to its relative ease in administration and the relative unawareness of this syndrome among dermatologists makes it a prudent topic to be reported.

Mucocutaneous complications of smoking cessation therapies

Despite widespread knowledge of the morbidity and mortality associated with smoking, this addictive practice continues to be quite prevalent throughout the United States, as about one-fifth of the population smokes cigarettes. Because of the financial burden, and the significant psychosocial and health implications of smoking, many individuals are now attempting to quit, and often using some type of pharmacotherapy for assistance. Given that dermatologists will likely encounter patients using smoking cessation aids, it is important to be aware of their potential mucocutaneous adverse effects. We present a brief review of the dermatologic complications associated with smoking cessation therapies. Hopefully, this article will alsoremind dermatologists to encourage smoking cessation at every visit.

Hydroxyurea‐induced dermatomyositis: true amyopathic dermatomyositis or dermatomyositis‐like eruption?

Hydroxyurea-induced dermatomyositis is a rare adverse reaction of long-term hydroxyurea therapy. It has been reported under different names; however, the exact classification and nomenclature of this eruption have been the subject of much debate, and a more precise term is still awaiting. Herein, we review the different aspects of this reaction and suggest a new term that might help to minimize the confusion about its nomenclature. We describe a 68-year-old woman who had been on long-term hydroxyurea therapy for the treatment of chronic myeloid leukemia for nine years. She presented with typical dermatomyositis-like lesions and many of the other mucocutaneous adverse effects of hydroxyurea. Skin examination revealed typical Gottron's papules on the dorsa of the hands, atrophy, xerosis, acquired ichthyosis, photosensitivity, cutaneous, oral and nail hyperpigmentation, acral erythema, palmoplantar keratoderma, actinic keratoses, and leg ulcers. There was no clinical or laboratory evidence of proximal muscle weakness. Cessation of hydroxyurea was associated with remarkable improvement of the skin lesions. Hydroxyurea-induced dermatomyositis is a rare drug-induced dermatomyositis characterized by skin lesions identical to classic dermatomyositis without clinical or laboratory evidence of myositis. We propose that the term hydroxyurea-induced amyopathic dermatomyositis that adequately describes the findings reported in this subset of patients would be more precise and specific.

Stevens-Johnson syndrome complicating adalimumab therapy in rheumatoid arthritis disease

The efficacy of adalimumab, a fully human anti-tumor necrosis factor-α recombinant antibody, has dramatically improved the quality of life of patients with rheumatoid and psoriatic arthritis and Crohn's disease. Because it is fully human, one should not expect immune reactions to this molecule. Adverse reactions to adalimumab are limited mainly to injection site reactions and are very common. We, however, report a case of Stevens-Johnson syndrome that required hospitalization and cessation of adalimumab in a patient with rheumatoid arthritis (RA). In this case report, a 53-year-old woman with RA developed severe mucositis, peripheral rash and desquamation and fever concomitant with the fifth dose of 40 mg adalimumab. Infective etiologies were excluded. The patient responded rapidly to IV hydrocortisone and was able to be commenced on infliximab without recurrence of the Stevens-Johnson syndrome. Severe skin reactions induced by TNF-α antagonists can be very serious, and prescribers need to be aware of the potential for the mucocutaneous adverse effects from the use of these agents, particularly due to the significant morbidity and mortality that are associated with SJS.

Oral lesions associated with hydroxyurea treatment

Hydroxyurea (HU) is an antimetabolic agent commonly used in myeloproliferative disorders and hematological diseases as well as in severe psoriasis. Despite of usually be well tolerated, sometimes it can induce immunosuppression and mucocutaneous adverse effects associated with discomfort or pain. Nevertheless, oral mucosal adverse reactions are extremely uncommon and present as ulcers, tongue depapilation and dyschromia. Complete remission of adverse effects is usually observed after withdrawal of the medication. The aim of this paper is to report two patients with oral lesions related to HU treatment. T0 he patients were adequately managed by changing hydroxyurea with imatinib mesilate. Oral lesions are rare complications of long-term hydroxyurea treatment and may be an indication of stopping therapy and substitution with imatinib mesilate.