Methotrexate related cutaneous adverse drug reactions: a systematic literature review

Objectives Recently, there is an increased number of reports being published on Methotrexate (MTX) related cutaneous manifestations. We aimed to identify and critically appraise descriptive studies describing the MTX related skin manifestations, treatment approach, and their outcomes. Methodology An extensive literature search was performed in the PubMed, Embase, and Scopus databases from inception to April 2021 without any restrictions along with the bibliographic search of included studies, grey literature search, and a snowball search was performed in Google and Google Scholar to identify the relevant literature. Descriptive studies reporting MTX related cutaneous manifestations were considered for the review. The study selection, data extraction, and quality assessment were conducted by two independent reviewers and any disagreements were settled by consensus with the third reviewer. Results 31 out of 8,365 descriptive studies including 38 patients (22 females and 16 males) aged between 12 and 78 years prescribed for the management of rheumatoid arthritis, ankylosing spondylitis, and psoriasis were included in this review. Toxic epidermal necrolysis (TEN), papular eruption, vasculitis, erosions of psoriasis, ulcerated psoriatic plaques, local reactions, keratinocyte dystrophy, erythema multiforme, drug rash with eosinophilia and systemic symptoms, Steven Johnson syndrome and photosensitive dermatitis were the majority of MTX induced cutaneous reactions. Immediate withdrawal of MTX, providing appropriate care with anti-inflammatory, topical steroids, and supplementation with folic acid were reported to be effective for the management of the MTX related cutaneous manifestations. Conclusions Clinicians and healthcare professionals should be aware of possible acute cutaneous drug reactions induced by MTX to avoid further consequences and fatal conditions. Immediate withdrawal of MTX and supportive care were reported as an efficacious therapeutic management of acute cutaneous drug reactions. PROSPERO Registration number CRD42020220038.

A study and evaluation of cutaneous adverse drug reaction in the patients attending dermatology department of tertiary care teaching hospital in Eastern Uttar Pradesh

Background: Cutaneous adverse drug reactions (CADRs) are most frequently reported type of ADRs and can be caused by variety of drugs. The clinical patterns of adverse cutaneous drug reactions and the drug responsible for them is changing every year due to the emergence of newer molecules and changing trends in the use of drugs.Methods: This was a prospective, cross-sectional and observational study done for a period of 6 months to evaluate the clinical pattern of CADRs and their causative drugs in the tertiary health care.Results: Over all 55 patients were detected with cutaneous adverse drug reaction. The majority of CADRs were in the age group of 18-35 years (63.46%). Fixed drug eruptions (FDE) being the most common adverse cutaneous drug reaction (34.68%) followed by maculopapular rash (23%), NSAIDs being the most common, followed by antimicrobial agents.Conclusions: Knowledge of these drug eruptions, the causative drugs are essential for the clinicians and implementing the ADRs reporting and monitoring system, one can promote drug safety and better patients care, among health care professionals.

Drug toxicoderma: possible causes, clinical manifestations and approaches to management at the outpatient’s stage

Adverse cutaneous drug reactions are skin manifestations resulting from systemic drug administration. Toxicoderma under medication treatment is the most common adverse cutaneous reaction with difficulty to diagnose, especially at early stages. The development and active introduction of new drugs into practice, uncontrolled self-medication of patients, polypharmacy, and repeated contact with one and the same preparation, contribute to the growth of toxicoderma. Doctors should treat patients with toxicoderma carefully, as it can be developed at any time and have different clinical manifestations. The pathogenesis of toxicoderma is not fully understood, which limits the possibility of the diagnosis, treatment and prevention. The benefit/risk ratio evaluation of prescribing medications is the basis of pharmacological safety and doctors, especially of primary health care (general practitioners), should always put it into practice.

Nevirapine-induced Stevens-Johnson syndrome in children living with HIV in South Africa

Background: Although adverse drug reactions resulting from the use of nevirapine (NVP) are well described in adults (estimated frequency of 6% – 10%), it has previously been considered less common in children (0.3% – 1.4%). Stock-outs of antiretroviral agents occur frequently in South Africa and result in interruptions in therapy and drug substitutions.Objectives: To report on a case series of paediatric patients who suffered cutaneous drug reactions to NVP at rates not previously described in children.Method: We describe a retrospective observational case series of six children living with HIV who developed Stevens-Johnson Syndrome (SJS) following exposure to NVP because of a prolonged stock-out of efavirenz 200 mg tablets in South Africa.Results: Of the 392 paediatric patients receiving antiretroviral therapy at the institution, 172 were affected by the efavirenz stock-out. Of these, 85 children were changed to NVP of which six developed NVP-induced SJS (7.1% incidence rate). The median time between initiating NVP and developing symptoms was 27 days (range 12–35 days). All patients responded well to NVP cessation and symptomatic treatment. One patient was referred for specialist care. Two patients were successfully rechallenged with efavirenz after developing SJS and three continued lopinavir/ritonavir.Conclusions: This is the second largest case series of NVP-induced SJS in children to date and raises the possibility that the incidence of SJS in children may be higher than previously described. Further research is required to explore the risk factors associated with NVP-induced SJS in children. This case series highlights the negative impact of drug stock-outs on patient health outcomes.

Cutaneous Drug Reactions in Children Attending a Tertiary Care Hospital

Background: Cutaneous drug reaction (CDR) is a growing health hazard in the world. Adverse drug reactions are common complications in drug therapy. About 3-8% of all hospital admissions are the results of adverse drug reactions, among them 2-3% are children and these can cause significant disability to patients. Early identification and management of adverse cutaneous drug reaction has both short term and long term prognostic significance. Objective: To know the cutaneous reaction to drugs in children in a tertiary care hospital. Study design: Hospital based descriptive, observational study. Subjects: 50 children with cutaneous drug reactions were studied in the department of Dermatology and Pediatric respectively in Rajshahi Medical College Hospital, Rajshahi. Methods: Data were collected by detailed history taking, physical examination and laboratory investigations in a prefixed data collection sheet and with the help of GOLD guideline after taken informed consent of the patient. Results: This study showed a significant male predominance. Male: female ratio was 1.08:1 .In this study prevalence was highest among 1-5 years age group. Cotrimoxazole, NSAIDs, anticonvulsant and quinolone were most offending medications. Maculopapular eruption, Stevens Johnson Syndrome, fixed drug eruption and urticaria were most common morphological types. Majority of CDRs were noted with oral route of administration. It was observed that almost all the CDRs that were reported involved mainly the skin. Majority of adverse cutaneous drug reactions reported were moderate in severity. Conclusion: Frequency distribution of the offending drugs and the adverse reactions revealed that adverse cutaneous drug reactions occurred mostly by cotrimoxazole, NSAIDs and quinolones. Maculopapular rash and Stevens Johnson Syndrome were the most common morphological types. A better understanding of the mechanisms underlying CRDs is important in drug development and in patient care. TAJ 2020; 33(2): 56-62

Clinical Profile of Adverse Cutaenous Drug Reactions in Patients with Human Immunodeficiency Virus

Background: Adverse cutaneous drug reactions (ACDRs) are common problems in patients during the treatment of various diseases. The clinical feature varies from mild manifestation such as morbilliform, urticaria, and contact dermatitis, to severe manifestation such as Stevens - Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). Patients infected with the human immunodeficiency virus (HIV) have an increased risk of developing ACDRs due to immune system disruption. This study aimed to describe the clinical features of ACDRs in HIV patients and the drugs that cause ACDRs. Method: This study was a retrospective study using secondary data from medical records of HIV patients with ACDRs who visited Teratai Clinic of Dr. Hasan Sadikin General Hospital Bandung from 2014 to 2018. Total sampling was applied and results were presented in percentage. Results: There were 94 HIV patients with ACDRs out of 557 HIV patients. Adverse cutaneous drug reactions are commonly found in males aged 20-39 years old. The clinical features found were morbilliform (85.6%), SJS (8.9%), urticaria (4.4%), and erythroderma (1.1%). The most common drugs causing ACDRs were Cotrimoxazole (30%), Efavirenz (28.9%), and Nevirapine (16.7%). Conclusion: The prevalence of ACDRs in HIV patients in this study is 16.9%. The most common clinical features are morbilli form and SJS with Cotrimoxazole, Efavirenz, and Nevirapine causing most of the ACDRs.