Mucocutaneous Adverse Reactions Research Articles

Development and Validation of a Novel Score to Predict Mortality in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: CRISTEN.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, severe mucocutaneous adverse reactions. Severity prediction at early onset is urgently required for treatment. However, previous prediction scores have been based on data of blood tests. This study aimed to present a novel score that predicts mortality in patients with SJS/TEN in the early stages based on only clinical information. We retrospectively evaluated 382 patients with SJS/TEN in a development study. A clinical risk score for TEN (CRISTEN) was created according to the association of potential risk factors with death. We calculated the sum of these risk factors using CRISTEN, and this was validated in a multinational survey of 416 patients and was compared with previous scoring systems. The significant risk factors for death in SJS/TEN comprised 10 items, including patients' age of ≥65 years, ≥10% body surface area involvement, the use of antibiotics as culprit drugs, the use of systemic corticosteroid therapy before the onset, and mucosal damage affecting the ocular, buccal, and genital mucosa. Renal impairment, diabetes, cardiovascular disease, malignant neoplasm, and bacterial infection were included as underlying diseases. The CRISTEN model showed good discrimination (area under the curve [AUC]= 0.884) and calibration. In the validation study, the AUC was 0.827, which was statistically comparable to those of previous systems. A scoring system based on only clinical information was developed to predict mortality in SJS/TEN and was validated in an independent multinational study. CRISTEN may predict individual survival probabilities and direct the management and therapy of patients with SJS/TEN.

NOT THE USUAL CULPRIT DRUG! AN EXTREMELY RARE CASE OF TOXIC EPIDERMAL NECROLYSIS SECONDARY TO ITRACONAZOLE.

Toxic epidermal necrolysis (TEN) is a severe mucocutaneous adverse reaction, potentially life threatening, which occurs mainly due to drugs and involves more than 30% of the body surface area. Here, we report an extremely rare case of TEN secondary to itraconazole developing in a young female who was prescribed itraconazole for tinea cruris with corporis. Cutaneous side effects of itraconazole are rare and usually mild. It can manifest as maculopapular rash, xed drug eruption, urticaria and angioedema. But development of TEN secondary to itraconazole is extremely uncommon and rarely implicated as a culprit drug for TEN. In countries with high prevalence of tinea cruris and corporis, dermatologists and clinicians should be aware about the possibilities of adverse reactions that can occur due to itraconazole.

Use of Cyclosporine for the Treatment of Stevens- Johnson syndrome and Toxic Epidermal Necrolysis Induced by Carbamazepine- A Case Report

Stevens Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare, potentially life threatening, severe mucocutaneous adverse reactions characterised by extensive epidermal detachment, erosion of mucosa and severe constitutional symptoms. However, the use of Carbamazapine may be associated with a plethora of adverse effects, the most serious being SJS/TEN, wherein the patient typically presents with fever, skin eruption and mucosal involvement. It occurs between 1/1,000 and 1/10,000 new exposures to the drug. Here, the authors report a case of severe life threatening SJS/TEN induced by Carbamazepine in a three-year-old boy who presented with high grade fever, skin rash and all mucosal involvement. This condition is best approached with immediate discontinuation of offending drug and prompt administration of oral cyclosporine. The case is being reported to emphasise the need for timely diagnosis and prompt treatment with Cyclosporin for successful outcome as it can cause irreversible organ damage or death if untreated early

Mucocutaneous Adverse Effects of Remdesivir and Favipiravir in Patients with Covid-19 Infection

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.

A comparative review on mucocutaneous reactions caused by Covid-19 infection versus Covid-19 vaccination.

The prevalence and severity of mucocutaneous manifestations in Covid‐19 infection are generally higher than those reported in Covid vaccines. Therefore, comparing the mucocutaneous reactions of the Covid‐19 infection and vaccination is necessary to enhance our knowledge about such reactions and guide us to evaluate the risk of infection or vaccination. A thorough literature search was conducted on PubMed, Google Scholar, and EBSCO (LISTA), and 2069 articles were downloaded. After screening, 11 studies remained for the final review. The literature review revealed that the prevalence and severity of postvaccine mucocutaneous adverse reactions have been less common compared to Covid‐19 infection. Postvaccine adverse reactions primarily occurred after the first dose administration and such reactions were manageable with antihistamines and corticosteroids administration. This comparative analysis highlights the frequency and potential severity of mucocutaneous reactions due to Covid‐19 infection and Covid‐19 vaccination. It also affirmed that potentially critical (serious) mucocutaneous reactions are more likely to occur in Covid‐19 infection compared to Covid vaccination. Moreover, postvaccine reactions predominantly happened after the first dose and were reported to be non‐life‐threatening, self‐manageable and with a lower incidence of potentially critical events. It was also concluded that the incidence of mucocutaneous reactions decreased in the following doses. Hence, given the low rate of such reactions following Covid‐19 vaccination, vaccines have a lower risk of mucocutaneous reactions occurrence than Covid‐19 infection. Further, due to the limited number of studies, we recommend that large‐scale trials evaluate such reactions comparing various types of Covid‐19 vaccines in healthy individuals and those with autoimmune skin disorders.

A Rare Case of Life-Threatening Extensive Mucocutaneous Adverse Reaction Induced by Docetaxel in a Breast Cancer Patient: Toxic Epidermal Necrolysis, a Case Report with Review of Literature

AbstractFever and extensive necrosis with 30% or more epidermal involvement along with mucous membrane is known as toxic epidermal necrolysis (TEN). It is a life-threatening mucocutaneous disease and is usually drug induced. We report a rare case of docetaxel-induced TEN. A patient with metastatic breast carcinoma received single agent docetaxel and developed severe skin and mucous membrane reaction involving more than 30% of the skin, and managed conservatively in intensive care unit but she succumbed to her illness. Although common toxicities reported with docetaxel include alopecia, nail damage, myelosuppression, and erythema multiforme major, TEN after docetaxel is very rare and can be a life-threatening complication as in our case.

Mucocutaneous Adverse Reactions to COVID-19 Vaccines: Do Excipients Play a Role?

Abstract is missing (Short communication)

Prevention and treatment of mucocutaneous adverse reactions associated with epidermal growth factor receptor inhibitors

The epidermal growth factor receptor (EGFR) signaling is aberrantly overexpressed in many solid malignancies, making it an important target for anti-cancer biologic agents. Among them, epidermal growth factor receptor inhibitors (EGFRIs), which have been widely used in clinical practice, include anti-EGFR monoclonal antibodies and tyrosine kinase inhibitors. A proportion of patients treated with EGFRIs develop specific, dose-dependent skin toxicity such as papulopustular rash, paronychia, xerosis and itch. These side effects can cause physical and psychosocial discomfort that may result in dose reduction, discontinuance, or replacement of the current EGFRIs treatment. Correct diagnosis and treatment of these skin and mucosal adverse effects associated with EGFRIs is of great significance for the tertiary prevention of malignant tumors. A review on EGFRI-related mucocutaneous adverse reactions is presented here, focusing on the pathogenesis, the various clinical manifestations, the strategies for prevention and treatment of these conditions.

Mucocutaneous Side Effects of Antineoplastic Drugs Used in Cancer Therapy in Erbil

Background and objectives: Mucocutaneous side effects of antineoplastic drugs can produce both local and systemic mucocutaneous adverse reactions that sometimes misinterpreted with other cancer related dermatological mani- festations such as infection, paraneoplastic diseases, and nutritional deficiency. The aim of the study was to identify the most common mucocutaneous side effects associated with antineoplastic drugs to be looked for and managed properly. Methods:A study was conducted on patients receiving anti-cancer therapy. Data were collected from 109 patients, of which 87 were females and 22 were males, with biopsy proven malignancies. Forty one patients were on single chemotherapy and 68 were on combined chemotherapy. Seventy seven patients were on conventional chemo- therapy, 29 on hormonal therapy and 13 on immune target therapy. Detailed history was obtained from the patients. Afterwards each patient subjected to full dermatological examination involving skin, mucosa, hair and nail. Results: Hair changes were the most common adverse effect noticed in (31.71%) of the patients with anagen effluvium being the most common (68 cases), followed by skin changes in (28.29%). Nail changes were observed in (20.49%) of the cases and the most common changes were melanonychia that was noticed in 22.The mucosal changes accounted for (19.51%) of the cases and 36 patients complained of apthus ulcer. Conclusions:This study showed that adverse effects of antineoplastic drugs can cause a great degree of morbidity to cancer patients on chemotherapy although most of the complications subsided with cessation of the therapy without causing permanent damage.

Mucocutaneous Adverse Reactions of Cancer Chemotherapy and Chemoradiation.

Background:With the introduction of newer anti-cancer agents, the adverse effects have become more rampant which call for concern in the treatment of patients with cancer. Hence, the assessment and management of dermatological adverse effects of anti-cancer therapy have become a significant part of the care of patients with cancer and require proper and close collaboration between the dermatologists and the oncologists.Aims:To assess the frequency and pattern of mucocutaneous adverse reactions to cancer chemotherapy and chemoradiation and grade them according to their severity and to identify hematological and biochemical changes related to cancer chemotherapy-induced mucocutaneous adverse reactions.Materials and Methods:This was a descriptive study done among 226 patients in an Indian tertiary care hospital, who presented with mucocutaneous adverse reactions to either chemotherapy alone or combination of chemotherapy and radiation to dermatology, medical oncology and radiotherapy outpatient departments. Detailed history and examination were undertaken. Visual analog score (VAS) was employed to quantify pain and pruritus. Correlation of various biochemical and hematological parameters with chemotherapy-induced adverse reactions was attempted and grading of adverse reactions was done based on the severity scale of Common Terminology Criteria for Adverse Events (CTCAE).Results:The common cutaneous adverse reactions observed in our study were nail changes (194 patients; 85.84%), followed by skin changes (191; 84.51%), hair changes (159, 70.35%), mucosal changes (34, 15.04%), and other miscellaneous manifestations. Grade 1 manifestations comprised of 49.91% of total manifestations followed by Grade 2 (45.45%) and Grade 3 (5.64%). In addition to bleomycin, other chemotherapeutic agents also had been shown to produce flagellate dermatitis in our study.Conclusion:Nail changes, skin changes, hair changes and mucosal changes occurred frequently as a significant side effect of chemotherapy, which a physician should be aware of, while selecting a chemotherapeutic drug.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: An Analysis of Triggers and Implications for Improving Prevention

BackgroundStevens-Johnson syndrome and toxic epidermal necrolysis are severe mucocutaneous adverse drug reactions characterized by extensive epidermal detachment. The mortality rates have been reported to vary between 1% and 5% for Stevens-Johnson syndrome and 25% and 35% for patients with toxic epidermal necrolysis. Studies have shown that early recognition and prompt withdrawal of the causative agent leads to increased patient survival. MethodsA retrospective chart review was conducted on 64 patients admitted to Vancouver General Hospital with a diagnosis of Stevens-Johnson syndrome or toxic epidermal necrolysis from 2001 to 2011. The aim of this study was to identify the medications most often implicated in triggering Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as to delineate the timeline of identification and removal of these triggers. ResultsA trigger was identified in 75% of cases. Allopurinol was the single most common offending agent (20% of cases). Anticonvulsants and antibiotics were common triggers. The offending agent was often removed at time of hospital admission/diagnosis but not at onset of symptoms. A history of prior culprit drug exposure with previous mucocutaneous adverse reaction was noted in 19% of cases with identified triggers. Asians and Native North Americans had a higher mortality than whites, and Asians more frequently had allopurinol as a trigger. ConclusionsThe onset and high mortality rate of Stevens-Johnson syndrome/toxic epidermal necrolysis may be related to unawareness of the early signs and symptoms of Stevens-Johnson syndrome and toxic epidermal necrolysis, the common drug triggers that cause it, and what investigations (human leukocyte antigen typing in Asians) can be done to prevent it.

Zoledronic acid-associated symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): report of baboon syndrome in a woman with recurrent metastatic breast cancer after receiving zoledronic acid

Baboon syndrome is a distinctive skin reaction in which the patient typically develops erythematous buttocks that appear similar to those of a baboon. The non-contact allergenic variant of baboon syndrome is also referred to as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). Zoledronic acid is a bisphosphonate that is used in patients with metastatic cancer to prevent bone complications. Zoledronic acid-associated baboon syndrome is described in a woman with recurrent metastatic breast cancer. PubMed was used to search the following terms, separately and in combination: baboon syndrome, breast cancer, symmetrical drug-related intertriginous and flexural exanthema, and zoledronic acid. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated. Zoledronic acid has infrequently been associated with mucocutaneous adverse reactions. However, baboon syndrome has not previously been observed in patients receiving zoledronic acid. The reported woman developed baboon syndrome after her initial exposure to zoledronic acid. Non-contact allergenic drug-induced baboon syndrome has most commonly been associated with antibiotics such as beta-lactams and penicillins. Zoledronic acid-associated baboon syndrome has not previously been observed in cancer patients. Baboon syndrome (SDRIFE variant) was observed in a woman with recurrent metastatic breast cancer after her first exposure to zoledronic acid. In summary, SDRIFE can occur in oncology patients receiving zoledronic acid and zoledronic acid should be added to the list of medications associated with the potential to cause non-contact allergenic drug-induced baboon syndrome.

Identification of risk factors for carbamazepine-induced serious mucocutaneous adverse reactions: A case-control study using data from spontaneous adverse drug reaction reports.

Objectives:To identify risk factors other than genetic for severe carbamazepine-induced mucocutaneous reactions, that is, SJS, TEN, and exfoliative dermatitis (ED).Materials and Methods:We did a case-control study using data from the Swedish national database of spontaneously reported adverse drug reactions (ADRs). We selected all patients who had been reported from January 1, 1965 to March 31, 2010 as having experienced SJS (n = 78), TEN (n = 6), or ED (n = 8), and assessed as at least possibly related to carbamazepine. We also included diagnoses possibly representative of early signs of these serious conditions, that is, erythema multiforme (EM, n = 34) and scaly rash (n = 13). We compared data on demographics, drug treatment, and clinical features for these patients (cases, n = 139) with those from patients who had experienced any other type of ADR from carbamazepine during the same time period (controls, n = 887).Results:After adjustment for multiple comparisons, alcohol abuse was statistically significantly more common among cases than controls (34.5% vs 8.7%, odds ratio 5.5 [95% confidence interval 3.6-8.4], P = 3.14 × 10-14 ). The same was seen for SJS and EM individually.Conclusion:Alcohol abuse is a possible risk factor for serious carbamazepine-induced mucocutaneous reactions.

Erythema Annulare Centrifugum due to Pegylated Interferon-α-2a plus Ribavirin Combination Therapy in a Patient with Chronic Hepatitis C Virus Infection

Pegylated interferon-α combined with ribavirin is the current standard treatment for chronic hepatitis C virus infection. During interferon and ribavirin therapy, both local and generalized mucocutaneous adverse reactions have been reported. Erythema annulare centrifugum induced by this therapy regimen has not been reported previously. A 29-year-old woman was referred to our clinic for a 1-week history of slightly pruritic annular erythematous eruptions on the lower extremities and hands. The eruptions had first occurred on the hands 3 to 4 days after pegylated interferon-α-2a plus ribavirin combination therapy for hepatitis C virus infection. Histopathologic examination supported the diagnosis of erythema annulare centrifugum. The lesions completely regressed within 2 weeks after the cessation of treatment but recurred on similar localizations within 24 hours with the same therapy. It was thought that erythema annulare centrifugum was induced by pegylated interferon-α-2a plus ribavirin combination therapy. Erythema annulare centrifugum is considered an inflammatory skin disease with unknown etiology. It is thought to represent a hypersensitivity reaction to some triggering factors, including infections, immunologic disorders, malign neoplasms, foods, pregnancy, and drugs. We report the first case of erythema annulare centrifigum induced by pegylated interferon-α-2a plus ribavirin combination therapy.

Tranexamic Acid–Induced Toxic Epidermal Necrolysis

To report a case of toxic epidermal necrolysis (TEN) induced by orally administered tranexamic acid in a patient with liver cirrhosis and acute rectal bleeding. A 67-year-old male with a history of liver cirrhosis due to alcohol consumption with ascitic decompensation, esophageal varices, and multifactorial renal insufficiency presented with rectal bleeding. The patient was prescribed oral tranexamic acid (1000 mg every 8 hours), with partial resolution of symptoms. Ten days after treatment with tranexamic acid began, a purplish macular rash appeared over the patient's trunk. The dose of tranexamic acid was reduced to 1000 mg every 12 hours, adjusting for renal function. In the following days the lesions extended and became confluent with blisters and epidermal necrosis. Multiple mucosal surfaces were also affected. He denied allergies to any medications and had no history of tranexamic acid exposure. Treatment with tranexamic acid was suspended and fluid replacement therapy, oral prednisone therapy (0.4 mg/kg per day), and N-acetylcysteine 2 g every 6 hours was started, with the empiric diagnosis of TEN. Results of a skin biopsy were compatible with TEN. Resolution of the skin lesions was favorable, but after 2 weeks the patient died secondary to acute renal failure, respiratory infection, and multiorgan failure. TEN is a rare, severe mucocutaneous adverse reaction. Although infrequent, TEN has a significant impact on public health because of its high mortality. Its pathogenesis is unclear, but it seems to be a form of delayed hypersensitivity. To our knowledge, a well-documented case of TEN following tranexamic acid use has not been reported (MEDLINE search to June 2012). There have been recent reports of skin hypersensitivity reactions through different mechanisms (immunologic and nonimmunologic). The Naranjo probability scale indicates a probable relationship between the development of TEN and tranexamic acid use in our patient. This appears to be the first report of a case of TEN that occurred in a patient being treated with oral tranexamic acid. Clinicians should be made aware of this potential severe cutaneous adverse reaction that may be caused by tranexamic acid administration.

A Longitudinal Cohort Study of Mucocutaneous Drug Eruptions During Interferon and Ribavirin Treatment of Hepatitis C

To describe dermatologic side effects encountered during treatment of patients with chronic hepatitis C, and analyze factors predisposing to such reactions. Treatment of hepatitis C virus (HCV) infection with interferon (IFN) and ribavirin is associated with a number of mucocutaneous adverse reactions that have not been adequately studied. A retrospective cohort study design was used to longitudinally describe mucocutaneous drug eruptions during IFN and ribavirin therapy in HCV-infected patients. Factors predictive of mucocutaneous eruptions were analyzed by the use of Kaplan-Meier curves and Cox proportional hazard model. A total of 286 HCV-infected consecutive patients were treated with one of the IFNα formulations plus ribavirin. The mean age was 51.1 years (SD 5.6). There were 6 female patients. There were 5 patients who were also infected with human immunodeficiency virus (HIV). Fifty-six percent of the patients were white, 37% were African American, and 14% were Hispanic. Twenty-one percent of all study patients developed mucocutaneous drug eruptions. The most common drug eruptions were eczematous drug eruptions (48%), seborrheic dermatitis (11%), and xerosis (8%). Dermatologic eruptions were a contributing factor in the decision to discontinue antiviral treatment in 10% of cases. Use of Pegylated IFN formulations (hazard ratio=1.86; 95% confidence interval, 1.04-3.34) and presence of HIV coinfection (hazard ratio=4.46; 95% confidence interval, 1.61-12.92) were associated with increased rate of skin reactions. Mucocutaneous reactions during IFN and ribavirin treatment of hepatitis C are common and are associated with HIV infection and use of Pegylated IFN.

Skin Manifestations Associated with Chemotherapy in Children with Hematologic Malignancies

Chemotherapy used in the treatment of malignancies produces multiple mucocutaneous adverse reactions that may be clinically challenging. These mucocutaneous reactions are common and sometimes not diagnosed. The objective of this study was to determine the clinical patterns of the mucocutaneous manifestations during and after chemotherapy in children with a hematologic malignancy and to determine whether nutritional status influences the clinical presentation. We recruited patients aged 6 months to 16 years diagnosed with leukemia and lymphoma from a pediatric hematology outpatient clinic between November 2008 and May 2010. The patients were divided into two groups: Group 1, recently diagnosed patients, included in the study before receiving chemotherapy, and Group 2, patients in surveillance who had not had chemotherapy for at least 3 months. A dermatologic examination was performed, and biopsy and mycological and bacteriological tests were conducted if necessary, with 6 months of follow-up. We evaluated 89 patients and included 65 in the study: 40 boys and 25 girls with an average age of 8.3 years. All patients had skin lesions at some time during their baseline assessment or follow-up. The manifestations found were anagen effluvium, xerosis, and acral hyperpigmentation. To our knowledge, this is the first comparative study of skin manifestations associated with chemotherapy in a Mexican pediatric population. The mucocutaneous manifestations associated with chemotherapy are important causes of morbidity. All of the children in our study had skin lesions on assessment. We did not find an association between skin manifestations and nutritional status.

Avaliação dos efeitos adversos clínicos e alterações laboratoriais em pacientes com acne vulgar tratados com isotretinoína oral

Oral isotretinoin therapy has completely changed the treatment of acne. The clinical adverse effects of isotretinoin are classified into two groups: mucocutaneous and systemic toxic. Laboratory alterations such as dyslipidemia and increase of hepatic enzymes are reported. To evaluate the tolerability of oral isotretinoin with special attention to lipid metabolism, hepatic function, and clinical adverse reactions. 150 patients clinically diagnosed with acne being treated with oral isotretinoin were included in the study. Clinical and laboratory evaluations were conducted before the start of therapy, one month after, and every three months thereafter until the completion of treatment. Of the 150 patients evaluated, 48% were female and 52%, male. They were aged from 15 to 32 years. The most prevalent mucocutaneous adverse reaction associated with isotretinoin therapy was cheilitis, reported by 94% of the patients. Systemic clinical effects were much less common. Cholesterol, triglyceride, and transaminase levels were assessed and significant changes were not observed during treatment. Patients showed adverse effects compatible to those described in the literature, which are mostly controlled with symptomatic medication. Isotretinoin is a safe drug and adverse and laboratory effects are well tolerated.

Mucocutaneous adverse effects of hydroxyurea: a prospective study of 30 psoriasis patients.

Hydroxyurea is an anti-tumour agent most commonly used to treat chronic myeloproliferative disorders in doses up to 4 g per day. Dermatological adverse effects reported so far have been observed predominantly in these patients. As we are treating selected psoriasis patients with low dose hydroxyurea we attempted to define the spectrum and chronology of dermatological adverse effects in this group of patients prospectively. Of the 29 evaluable patients, 19 (65.5%) developed a mucocutaneous adverse reaction after a mean duration of 6.4 weeks of treatment. Pigmentation of nails, skin or mucosa was the most common observation and was seen in 17 (58.6%) patients. Other less common findings were xerosis, diffuse alopecia, oedema of the legs, oral ulcers and actinic psoriasis. Adverse effects subsided in 11 (57.9%) patients during a mean follow up of 18 weeks. Three hitherto unreported side-effects - scleral pigmentation, acquired ichthyosis and pigmentation of lunula of the nails - were noted. This first study of dermatological adverse effects of hydroxyurea therapy on Asian psoriatic patients reveals several new findings. Pigmentation of skin, nails and mucosa appears to be very common and occurs early. Serious dermatological side-effects probably do not occur with low dose (up to 1.5 g per day) hydroxyurea in patients with psoriasis.