Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs), which include Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also known as drug-induced hypersensitivity syndrome), acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption, are life-threatening conditions. The pathogenesis of SCARs involves T cell receptors recognizing drug antigens presented by human leukocyte antigens, triggering the activation of distinct T cell subsets. These cells interact with keratinocytes and various immune cells, orchestrating cutaneous lesions and systemic manifestations. Genetic predisposition, impaired drug metabolism, viral reactivation or infections, and heterologous immunity influence SCAR development and clinical presentation. Specific genetic associations with distinct SCAR phenotypes have been identified, leading to the implementation of genetic screening before prescription in various countries to prevent SCARs. Whilst systemic corticosteroids and conventional immunomodulators have been the primary therapeutic agents, evolving strategies, including biologics and small molecules targeting tumour necrosis factor, different cytokines, or Janus kinase signalling pathways, signify a shift towards a precision management paradigm that considers individual clinical presentations.

Triggers, clinical manifestations and assessment of paediatric fixed drug eruptions: A systematic review of the literature.

Fixed drug eruption (FDE) is a cutaneous drug reaction characterised by recurrent skin lesions occurring at the same site after each exposure to a causative agent. There is currently limited evidence in the paediatric population. The objective of this systematic review is to investigate the clinical features, causative agents and management of paediatric FDE. A systematic search of the English and French literature on paediatric FDE was conducted using the Medline and Embase databases. After full-text article review, 92 articles were included, representing a total of 233 patients. Antibiotics were the most frequent triggering agents, mainly sulfonamides (65.0% of antibiotics). Systemic symptoms were rare, and most patients only received supportive therapy. One hundred and six patients (106) performed a test to confirm the causative agent. Of these, 72.6% had oral provocation tests (OPTs) and 28.3% had patch tests. The patient's age, presence of bullous lesions and mucosal lesions were similar between tested and untested patients. It did not seem to influence the decision to perform OPTs. Paediatric FDE is a non-severe skin drug reaction. Antibiotics were the most reported triggering agents. Drug testing, including oral provocation test, was safely performed in the paediatric population.

Osimertinib-induced Keratitis and Secondary Toxic Epidermal Necrotic Drug Eruption- A Case Report and Literature Review.

BACKGROUND: Osimertinib is a third-generation Tyrosine Kinase inhibitor, mainly used in non-small cell lung cancer with EGFR mutation. Its efficacy and safety have been confirmed by clinical practice. Toxic epidermolysis necrotizing disease (TEN) is a severe drug eruption that is rare in clinics and has a high mortality rate. Toxic epidermal necrotic drug rash caused by Osimeritinib is even rarer. OBJECTIVE: To investigate the rare side effects of Osimertinib through a case of toxic Epidermal necrosis. CASE PRESENTATION: A 63-year-old female patient was diagnosed with lung adenocarcinoma with brain metastases, and genetic testing revealed an EGFR21 exon mutation. The disease progressed 24 days after the administration of gefitinib, then the patient switched to Osimertinib (80 mg QD) and, resulting in keratitis and secondary systemic toxic epidermolysis necrotizing disease (TEN). Finally, the patient died. CONCLUSION: Although the clinical use of osimertinib is becoming widespread, the side effects may not be fully understood. Clinicians should pay more attention to the occurrence of the side reaction and deal with it in time.

Reflectance confocal microscopy as a complementary diagnostic tool for greyish-brown dermatoses in children.

Mastocytosis, lichen planus pigmentosus (LPP), fixed drug eruption (FDE) and café-au-lait macules (CALM) have a similar appearance, often lead to misdiagnosis and missed diagnoses. At the outpatient clinic at Tianjin Children's Hospital in 21 patients with mastocytosis, 18 with LPP, 11 with FDE and 12 with CALM we evaluated the characteristics and distinguishing features of their dermatoses using reflectance confocal microscopy (RCM). In mastocytosis, the dermal papillary rings generally had a significantly increased bright refractive index and the superficial dermis was filled with moderate refractive flocculent material. In LPP, the dermal papillary rings were absent and numerous different-sized cellular structures were densely distributed in the superficial dermis. In FDE, the dermal papillary rings were intact with a significantly increased bright refractive index. In CALM, normal dermal papillary rings were detected with a uniformly slightly increased refractive index and no obvious abnormality in the superficial dermis. RCM allows for real-time visualization of the major key diagnostic and distinguishing features of four greyish-brown dermatoses in children.

In Situ Patch Test and Repeated Open Application Test for Fixed Drug Eruption: A Multicenter Study.

BACKGROUND: Few studies have evaluated allergy workup in fixed drug eruption (FDE) in a large population. OBJECTIVE: To evaluate the sensitivity of a standardized allergy workup for diagnosing the cause of FDE, with a focus on in situ repeated open application tests (ROATs). METHODS: In a retrospective multicenter study, we analyzed the practice of conducting a complete allergy workup for the etiological diagnosis of FDE. It consisted of 3 steps: in situ patch tests (PTs) for all cases except pure mucosal involvement, followed by in situ ROAT if in situ PT results were negative, and finally a drug challenge (DC). The in situ ROAT involved daily application of the suspected drug on a previously affected FDE site for 7 days. RESULTS: Of 98 suspected FDE cases, 61 patients (median age 61 y; male-to-female ratio 1.8) with a complete allergy workup were included. In 4 cases, even the DC yielded negative results. Among the remaining 57 patients with a positive workup, implicated drugs included paracetamol (12 cases), ß-lactams (11 cases), imidazoles (9 cases, including 5 with metronidazole), nonsteroidal anti-inflammatory drugs (8 cases), iodinated contrast media (4 cases), cotrimoxazole (3 cases), and various other drugs in 10 patients. The diagnosis was confirmed by in situ PT in 17 of 54 cases (31.5%), in situ ROAT in 14 of 40 cases (35%) (with 4 cases showing remote reactivation of FDE sites), and DC in 26 cases. CONCLUSIONS: The sequential allergy workup involving successively in situ PT, in situ ROAT, and DC is a reliable and safe method for diagnosing the cause of FDE. In situ tests exhibited a sensitivity of over 50%.

Drug eruptions and the vulva.

Drug reactions affecting the vulva are understudied and underreported, with some having the potential to cause serious morbidity through long-term sequelae. We conducted a literature review to investigate the current evidence about vulval drug eruptions. We aimed to establish the extent of drug reactions affecting the vulva, identify the common culprit drugs, and review current evidence and guidelines regarding their management. The vulval involvement seen in Steven-Johnson syndrome, toxic epidermal necrolysis and fixed drug eruption forms the focus of this review, but we also summarize the current evidence regarding less common reactions.