Fixed drug eruption secondary to etoricoxib.

Fixed drug eruptions (FDE) are adverse cutaneous drug reactions and a form of delayed type 4 hypersensitivity reaction characterised by recurrent lesions at the same site each time a specific drug is taken. They most commonly result in cutaneous lesions presenting as an erythematous round or oval macule or plaque. FDEs have rarely been reported to affect oral mucous membranes and tend to have a bullous or aphthous-like appearance with erythema. Almost half of patients report an increase in the severity of symptoms with prolonged exposure to the offending medication. The most commonly attributed classes of drug are antibiotics (tetracyclines and sulphonamides) alongside non-steroidal anti-inflammatory drugs. Cutaneous adverse reactions to etoricoxib, a highly selective COX-2 inhibitor, have been reported. Here we describe an adverse reaction restricted to the oral mucosa.

A Clinico-Epidemiological Study of Cutaneous Adverse Drug Reactions in a Tertiary Care Centre of Eastern India.

Background: Adverse drug reactions (ADRs) are major problems in the drug therapy. Cutaneous adverse drug reactions (CADRs) are the most common ADRs. The pattern of CADRs differs among various drugs. Aims: To record various morphological patterns of CADRs and their causal relationships among patients attending in a tertiary care centre. Materials and Methods: An observational, cross-sectional, clinical study was conducted for a duration of one and a half years in a tertiary care centre in eastern India. Patients presenting with suspected CADRs were included if drug identity could be ascertained. Clinical profiling and drug history were recorded, and causality assessment was carried out as per the Naranjo scale. Result: The commonest CADR in our study was fixed drug eruption (FDE) 48.61%, followed by SJS-TEN spectrum 16.66%, maculopapular rash 11.11% and so on. Severe cutaneous adverse drug reactions (SCARs) such as SJS, TEN, SJS-TEN Overlap, AGEP and DRESS accounted for 18 cases (25%). The most common culprit drugs were antimicrobials (54.16%), followed by nonsteroidal anti-inflammatory drugs (15.27%) and anticonvulsants (12.5%). Most of the CADRs were in probable category. Conclusion: The pattern of CADRs and the drugs causing them in our study population are similar to some previous studies but somewhat different from most of the previous Indian studies. The incidence of SCARs was significantly higher than in previous other studies in India and abroad.

Analysis of Cutaneous Adverse Drug Reactions (ADR) Reported at an ADR Monitoring Center of a Tertiary Care Teaching Institute in Central India.

Background Cutaneous adverse drug reactions (ADRs) are among the most frequent ADRs. Knowledge of the pattern of cutaneous ADRs (CADRs) and causal drugs helps prevent and reduce the incidence of CADR, which in turn reduces the incidence of hospitalization and expenses for the patient. Objectives To analyze CADR according to demographic profile, morphological pattern, causative drugs, severity, and outcome in patients suffering from CADRs. Materials and methods Retrospective data analysis was conducted in the Adverse Drug Reaction Monitoring Centre (AMC) of the tertiary care teaching institute between February 2020 and September 2023 under the Pharmacovigilance Program of India (PvPI). All ADRs reported were analyzed based on the following parameters: total number of ADRs reported, number of CADRs, information related to demographic parameters, the clinical presentation of CADRs, and suspected medication. Causality assessment was done using the World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) scale. Severity was assessed using a modified Hartwig and Seigel scale. Results A total of 125 CADRs were analyzed. Considering the gender-wise distribution, 65 females and 60 males suffered from CADR. The most common drug category responsible for CADRs was antimicrobials (63.2%), followed by topical agents (12.8%). Maculopapular rash (33.6%) was the most common presenting symptom, followed by itching (27.2%). Few patients suffered from serious CADRs such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).  Conclusion A wide clinical spectrum of CADRs ranging from maculopapular rash to fixed-drug eruption to serious SJS was observed in our study. The most common causative agents for CADRs were antimicrobials, followed by topical agents and NSAIDs. For early diagnosis and management of CADRs, it is critical to have data on the potential cutaneous adverse effects of commonly used drugs, to educate the patients regarding common early symptoms of drug reactions (e.g., erythematous rash, edema, urticaria, mucosal erosions, itching, burning of skin, etc.), and to monitor the patient, especially during the start of therapy. To ease the burden of CADRs, a therapeutic plan of anticipating, avoiding, recognizing, and responding to ADRs should be implemented.

Erythema Multiforme-Like Fixed Drug Eruption During Azathioprine and Hydroxychloroquine Treatment for Systemic Lupus Erythematosus Mimicking Rowell Syndrome: A Rare and Challenging Clinical Scenario.

Background. Fixed drug eruption and Rowell syndrome stand as intriguing entities with overlapping clinical and pathological features. Case Presentation. A 32-year-old female patient presented with a tender and pruritic rash on the left upper chest for 3 days. Clinical examination revealed a flaring rash on the chest, under her left eye, tongue, and lips. The patient had a significant past medical history of systemic lupus erythematous with positive (ANA, Sm, dsDNA, ribosomalP, RNP) antibodies, hypocomplementemia, inflammatory arthritis, discoid lupus, leukopenia, thrombocytopenia, and immune thrombocytopenic purpura, and avascular necrosis affecting both hips and her right knee. At the time of presentation, the patient was on azathioprine 150 mg daily and hydroxychloroquine 200 mg twice daily. Skin biopsy of the left upper chest revealed interface dermatitis with necrotic keratinocytes at the dermal-epidermal junction. Superficial and, in some areas, deep perivascular and peri adnexal lymphocytic infiltrates were observed, accompanied by eosinophils. CD123 staining highlighted 16% of the inflammatory cells. Direct Immunofluorescence for IgG, IgA, IgM, C3, and fibrinogen revealed positive linear basement membrane staining for IgG and fibrinogen, with no significant staining for the remaining immunoreactants. Considering the patient's history of medicine usage, and negative SS-A and SS-B antibody, a fixed drug eruption was favored. Discussion. This article discusses the clinical presentations, pathophysiological mechanisms, and diagnostic criteria for fixed drug eruption and Rowell syndrome. Conclusion. Awareness of the distinct clinical and histopathologic features of fixed drug eruption and Rowell syndrome, particularly when sharing cutaneous manifestations, underscores the importance of a comprehensive diagnostic approach and laboratory testing.

A Clinico-Epidemiological Study of Fixed Drug Eruption with a Special Focus on the Causative Agent and the Clinical Patterns.

Background: Fixed drug reaction (FDE) is characterized by the development of well-circumscribed, round, erythematous macules and plaques on cutaneous or mucosal surface following ingestion of the offending drug. Aim and Objectives: To study the etiological agents responsible for FDE and to study the clinical patterns of FDE due to different drugs. Materials and Methods: It was a hospital-based observational cross-sectional clinical study. The study period was 24 months. Fifty patients were included. The study was done after a literature search, hypothesis generation, protocol write-up, ethical submission, ethical clearance, patient enrollment, data collection, data analysis, and research. The patients were selected on the basis of the Naranjo scoring system. The patients with a history of combination drug intake were not included in the study. Results: A total of 0.11% patients presented with FDE in the study period. Out of them, 52% of the patients belonged to 20-39 years age group, having sex ratio of 1.6:1. About 64% of the patients presented with multiple lesions, whereas 36% had a single lesion. A total of 46% patients presented with first episode and 54% had recurrent episodes. The mean time intervals of first and subsequent episodes were 6.5 days and 4.3 hours, respectively. Also, 16% patients had a history of herpes infection. Extremities were more affected followed by trunk and mucosa. Fluoroquinolones were the most common etiological agent found in 56% patients having cutaneous (48%) and mucosal lesions (14%). The most common drug was norfloxacin (36%) followed by both paracetamol (12%) and metronidazole (12%). Fluoroquinolones were the most common drugs implicated in bullous lesions and generalized bullous FDE. Limitations: The study population was small and the study was for a limited period of time. Conclusion: The patient should be aware of the offending drug and opt for any alternative agent after visiting the physician.

Nimesulide-Induced Fixed Drug Eruption Followed by Etoricoxib-Induced Fixed Drug Eruption: An Unusual Case Report and Review of the Literature.

Fixed drug eruption (FDE) is a well-recognized, non-immediate, drug hypersensitivity reaction, often attributed to the use of various medications, most commonly non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Cross-reactivity between related NSAIDs in FDE has been reported, but among chemically unrelated NSAIDs, is rare. Herein, we present a rare well-documented case where a patient initially displayed tolerance to etoricoxib after experiencing a nimesulide-induced FDE. Subsequently, the patient developed an etoricoxib-induced FDE, accompanied by the development of bullous lesions. This case report and the literature review on comparable FDE occurrences shed light on the intricate nature of FDEs, suggesting the possibility of cross-reactivity between chemically related and unrelated NSAIDs or the emergence of new drug-specific T cells without cross-reactivity after multiple exposures to a drug in a susceptible patient. Our case underscores the importance of increased awareness and vigilance among both physicians and patients in the realm of personalized medicine. Further research is needed to unravel the intricate mechanisms behind these drug eruptions, improve diagnostic approaches, and enhance patient care.

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.

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%.

Recurrent Fluconazole-Induced Fixed Drug Eruption of the Digit with Nail Matrix Involvement: A Case Report and Review of the Literature.

Introduction: Fixed drug eruptions (FDEs) are cutaneous hypersensitivity reactions due to an offending drug and are rarely associated with nail involvement. Moreover, FDEs associated with fluconazole use are sparsely reported in literature. Case Presentation: We report a case of a recurrent FDE with involvement of one finger and corresponding Beau's lines due to fluconazole use. The diagnosis of FDE secondary to fluconazole use was confirmed histopathologically, with improvement after the application of twice daily 0.05% clobetasol propionate ointment. Conclusion: FDEs are hypersensitivity reactions that occur after exposure to an offending drug. FDEs uncommonly affect the nail matrix and are often not caused by fluconazole. It is important for dermatologists to assess for changes in the nail plate when evaluating a patient with FDE and evaluate all medications a patient is taking.

Chlorthalidone-Induced Fixed-Drug Eruption: Unmasking an Uncommon Reaction to a Common Diuretic.

Fixed-drug eruptions (FDEs) are dermatological reactions characterized by specific skin lesions triggered by certain medications. Our case reports commonly used medications that can cause drug-induced skin reactions. Chlorthalidone, a widely used diuretic, had not been prominently linked to FDEs. Here, we present the case of a 45-year-old African-American male who developed classic FDE skin lesions following the initiation of chlorthalidone therapy. This case underscores the imperative for further investigation and heightened awareness among healthcare professionals regarding chlorthalidone-associated FDEs. Findings suggest that such reactions might be more prevalent than previously acknowledged, underscoring the significance of prompt diagnosis and effective management of drug-induced skin responses. Notably, the patient's lesions showed complete resolution upon discontinuing the diuretic, reinforcing the causal relationship. This case is an essential reminder of the importance of vigilance in monitoring patients for adverse drug reactions, even in unlikely medications, such as chlorthalidone.​​​​​​.

Fixed Drug Eruptions With Flavoured Liquid Formulations of Over-the-Counter Analgesics: A Case Report.

Type 4 hypersensitivity reactions convey a number of conditions that include fixed drug eruptions (FDEs). They share similar pathophysiologic backgrounds and sometimes presentation but can have very variable prognostications. Drugs are amongst the possible causes with acetaminophen and other NSAIDs being reported very frequently. We present a case of a patient reacting to flavoured oral ibuprofen and acetaminophen formulations, exhibiting FDEs with bullae formation. We describe our successful challenge to non-flavoured acetaminophen and ibuprofen. We briefly discuss FDEs in regard to their incidence, pathophysiology, and management.

Case report: Generalized bullous fixed drug eruption mimicking epidermal necrolysis.

Generalized bullous fixed drug eruption (GBFDE) is the most severe form of fixed drug eruption and can be misdiagnosed as epidermal necrolysis (EN). We report the case of a 42-year-old male patient presenting with more than 50% skin detachment without defined areas of exanthema or erythema and a history of one prior event of EN caused by acetaminophen (paracetamol), allopurinol, or amoxicillin 1.5 years ago. The initial diagnosis was GBFDE or EN. The histology of a skin biopsy was unable to distinguish between the two diseases. The course of the disease, the later clinical presentation, and the medical and medication history, however, were in favor of a diagnosis of GBFDE with two potentially culprit drugs: metamizole and ibuprofen. Moxifloxacin, enoxaparin sodium, hydromorphone, and insulin human were administered concomitantly, which makes them suspicious as well. Unfortunately, the patient received an additional dose of metamizole, one of the possible causative drugs, and he developed another bullous reaction within 1 month. This led to the diagnosis of GBFDE due to metamizole. This report highlights the challenges of distinguishing two rare diseases and elucidates the importance of distinct clinical presentation and detailed medication history.

Neutrophilic fixed drug eruption, a histopathologic variant or an expected finding?-A report of two cases and review of the literature.

Fixed drug eruption (FDE) is an adverse drug reaction characterized by recurrent circumscribed lesions at the same location upon re-exposure to the culprit medication, resulting in distinct postinflammatory hyperpigmentation. Histopathologically, FDE demonstrates a predominantly lymphocytic interface or lichenoid infiltrate with basal cell vacuolar changes and keratinocyte dyskeratosis/apoptosis. The term "neutrophilic fixed drug eruption" has been used to describe cases in which the inflammatory infiltrate is predominantly neutrophilic. The infiltrate can extend deeper in the dermis, potentially mimicking a neutrophilic dermatosis such as Sweet syndrome. We present two cases and review the literature to discuss the possibility that a neutrophilic inflammatory infiltrate may be an expected finding in FDE, rather than a histopathologic variant.