IL-36γ is highly expressed in psoriatic skin lesions and promotes neutrophil infiltration through the induction of neutrophil chemotactic chemokines. While IL-36γ has been established to play an important role in the pathogenesis of psoriasis, its localization in the psoriatic epidermis has not been fully elucidated, and the difference in its expression patterns among other inflammatory skin diseases remains unclear. We investigated IL-36γ localization using immunohistochemistry in skin specimens from patients with psoriasis vulgaris (n = 36), generalized pustular psoriasis (n = 11), pyoderma gangrenosum (n = 6), palmoplantar pustulosis (n = 6), tumor necrosis factor inhibitor-induced paradoxical reaction (n = 3), pustular drug eruption (n = 5), atopic dermatitis (n = 11), tinea infection (n = 3), and mycosis fungoides (n = 9), as well as uninvolved skin adjacent to benign tumors (n = 4). Staining scores were assessed based on intensity and distribution, and nuclear positivity was compared among diseases. IL-36γ was strongly expressed in the upper epidermis of psoriasis vulgaris and generalized pustular psoriasis, with staining scores significantly higher than those in atopic dermatitis and adjacent normal skin. Expression in pyoderma gangrenosum, palmoplantar pustulosis, paradoxical reaction, and pustular drug eruption was comparable to psoriasis vulgaris. Nuclear staining of IL-36γ was frequent in psoriasis vulgaris (33/36, 92%) and generalized pustular psoriasis (11/11, 100%), but absent in pyoderma gangrenosum. The difference in nuclear positivity between psoriasis and pyoderma gangrenosum was statistically significant. These findings confirm that IL-36γ is highly expressed in psoriatic lesions but is not specific to psoriasis, as it is also upregulated in other inflammatory skin diseases. Nuclear staining was observed in psoriasis but not in pyoderma gangrenosum, suggesting a potential disease-specific localization pattern. The biological significance and mechanism of nuclear localization remain unclear, as the IL-36γ molecule lacks a nuclear localization signal. Our findings highlight that the localization of IL-36γ differs among inflammatory skin diseases, suggesting that it may reflect pathogenic differences and warrant further investigation.

Severe cutaneous adverse reactions are a spectrum of life-threatening immune mediated adverse drug reactions characterized by extensive skin involvement with the potential for organ injury. It is composed of four main entities: drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. With prominent hypereosinophilia (>1500 eosinophils/µL), hypereosinophilic syndrome also warrants consideration, albeit rarely triggered by medications. In addition, there may also be concern for infectious etiologies, particularly in patients with notable travel history or immunosuppression. Herein, we present the case of a 65-year-old man with multiple myeloma who was started on several medications simultaneously for the induction of chemotherapy and who developed a full-body pruritic and maculopapular rash and peripheral eosinophilia 2-to-4 weeks after initiation of these medications. He had a recalcitrant course, which required multiple rounds of systemic steroids and other treatments. After a detailed history, physical examination, and additional investigation coupled with high clinical suspicion, a diagnosis, and treatment plan was made.

Abstract Acute generalized exanthematous pustulosis (AGEP) is a pustular drug eruption characterized by superficial pustules, commonly caused by β-lactam antibiotics. Management of AGEP involves discontinuation of the offending medication and supportive therapy with topical corticosteroids and analgesia, given the self-limiting nature of this condition. In contrast, Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is characterized by the sudden onset of painful, inflamed skin lesions associated with fever. SS typically requires investigations for associated conditions and systemic corticosteroids, resulting in rapid improvement within days. We present a case of AGEP-like SS, initially diagnosed clinically as AGEP in the setting of intravenous antibiotic use, where the patient deteriorated, despite antibiotics being stopped. Skin biopsy revealed papillary dermal oedema with neutrophilic infiltrate, and scattered histiocytoid cells and eosinophils, resulting in a revised diagnosis of AGEP-like SS. The patient was started on oral corticosteroids and achieved complete resolution of disease within 2 days. This case highlights AGEP-like SS as an important differential diagnosis in patients presenting with AGEP-like eruptions, as the management of AGEP and SS is different.

Pustular mycosis fungoides (pMF) is a rare variant of MF characterized by the clinical and histopathological formation of pustules. We report a 71-year-old Japanese woman with established MF who developed a generalized pustular eruption temporally triggered by systemic interferon (IFN)-γ administration. Clinically, the patient presented with generalized erythema with coalescing pustules mimicking generalized pustular psoriasis or acute generalized exanthematous pustulosis. Histological examination revealed the simultaneous presence of spongiform pustules of Kogoj and large transformed CD30+ atypical lymphoid cells. The pustules resolved rapidly upon the discontinuation of IFN-γ and the administration of systemic antibiotics. Cytokine analysis at the onset of pustulosis revealed marked elevations in serum IL-8, IL-18, IL-23, and IL-6 compared with healthy controls; these levels normalized during remission. This case suggests that systemic IFN-γ can act as a trigger for pMF. Furthermore, the distinct cytokine profile highlights that the IL-23/IL-17/IL-8 axis may be a crucial mediator in the pathogenesis of pMF.

Azithromycin, a macrolide antibiotic, an azalide derivative of erythromycin, is a Schedule H drug that can be procured from pharmacies in India only with a prescription. Despite the strict regulations, it is commonly available as an over-the-counter (OTC) medication in most pharmacies in India. A 33-year-old male had complaints of fever and sore throat, for which he self-administered tablet Azithromycin 500 mg once daily for three days. Two days after the last dose, he noticed the development of an itchy, erythematous rash. He was diagnosed with acute generalised exanthematous pustulosis (AGEP). Azithromycin was discontinued immediately, and he was treated in the ICU with corticosteroids and antihistamines. Acute Generalised Exanthematous Pustulosis (AGEP) is a rare and self-limiting Severe Cutaneous Adverse Reaction (SCAR) induced by medications. It presents with the rapid appearance of numerous non follicular, sterile pustules on a widespread erythematous base, often accompanied by fever and neutrophilic leukocytosis.This case highlights the potential for azithromycin, a commonly used and generally well-tolerated antibiotic, to induce rare but significant cutaneous reactions such as AGEP. Clinicians should remain vigilant when prescribing antibiotics, especially in patients who present with new-onset rashes during or after therapy.

We report the case of a 52-year-old male patient with pulmonary tuberculosis who, 72 hours after initiating antituberculosis therapy, developed a severe drug-induced toxicoderma. The clinical presentation was characterized by intense pruritus, erythematous rash, eczema, and diffuse skin desquamation with a positive Nikolsky sign. Given the suspicion of a severe adverse reaction, the antituberculosis regimen was immediately discontinued, and management with fluid support and topical corticosteroids was initiated. Skin biopsy revealed a perivascular lymphoplasmacytic infiltrate, lymphocytic exocytosis, and neutrophilic aggregates, findings consistent with a reactive inflammatory process induced by drugs. The discussion focuses on the immunological complexity of the case, which exhibited overlapping clinical and histological features between type IVc (cytotoxic) and type IVd (neutrophilic) hypersensitivity reactions, suggesting a combined form within the spectrum of toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). In addition to cutaneous involvement, the patient developed a mixed pattern of liver injury that resolved following drug withdrawal. After complete remission of the lesions was achieved, a stepwise and monitored reintroduction of the regimen was carried out, which was well tolerated. This case underscores that early diagnosis and prompt discontinuation of the causative agent are the most critical prognostic factors in preventing fatal outcomes in drug-induced toxicodermas associated with first-line antituberculosis medications.

Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction, attributed to drugs in the majority (>90%) of cases, although it may also be associated with acute viral infections and mercury exposure. It is a rare condition, with an estimated incidence of 1–5 cases per million population per year. This study is a retrospective analysis of seven cases of drug-induced AGEP. Data were obtained from VigiFlow, a pharmacovigilance database used for adverse drug reaction reporting and analysis. Individual Case Safety Reports (ICSRs) of AGEP reported between July 2021 and February 2024 were analysed for patient characteristics, clinical presentation, outcomes, and suspected drugs. Causality and severity were assessed using the WHO-UMC causality scale and the Modified Hartwig and Siegel severity scale, respectively. Statistical analysis was performed using Jamovi version 2.3.28. Among the seven cases, there was a predominance of females (male:female ratio 1:6), with a mean age of 34.7 years. Antimicrobials were implicated in 85.7% of cases, while non-steroidal anti-inflammatory drugs (NSAIDs) accounted for 14.3%. Itching and fever were present in all cases, and leucocytosis was observed in 85.7% of patients. The mean latency period was 2.29 days. Based on severity assessment, 42.9% of cases were moderate and 57.1% were severe. According to the WHO-UMC causality scale, 57.1% of cases were classified as probable and 42.9% as possible. The mean resolution time was 8.71 days. AGEP is a rare but clinically significant adverse drug reaction; therefore, prompt recognition and reporting are essential. Strengthening pharmacovigilance systems is crucial for improving patient safety. Keywords: Acute generalised exanthematous pustulosis, Cutaneous adverse drug reaction, Pharmacovigilance

Acute generalized exanthematous pustulosis (AGEP) is a rapid-onset pustular dermatosis characterized by widespread sterile pustules on erythematous skin, commonly triggered by medications. Etoricoxib, a selective COX-2 inhibitor widely used for inflammatory and pain conditions, is a rare but recognized cause of drug-induced AGEP. A female patient in her forties had prescribed oral etoricoxib 90 mg two times a day for the management of dental pain. After that patient started to develop multiple bilateral symmetrical pustules with erythematous base present over both bilateral upper limb and lower limb. Patient was treated with Inj. Hydrocortisone intravenous stat, Tab. Prednisolone 40 mg orally once a day, Tab. Azithromycin 500 mg once a day, Tab. Levocetirizine 5 mg orally twice a day and Tab. Pantoprazole 40 mg twice a day for 5 days. For pustules over skin patient was treated with fremycetin cream and betamethasone cream. Patient was recovered in seven days. The adverse drug reaction was assessed as certain by the WHO causality scale and probable by the Naranjo scale. Severity was categorized as moderate (Level 3) using the Modified Hartwig and Siegle scale, while preventability assessment indicated that the reaction was definitely preventable. Keywords: Acute generalized Exanthematous Pustulosis, Etoricoxib

We describe a rare case of acute generalised exanthematous pustulosis (AGEP) occurring during pembrolizumab therapy in a patient with metastatic lung adenocarcinoma and longstanding chronic plaque psoriasis. Clinical and histopathological findings confirmed AGEP rather than generalised pustular psoriasis, and cessation of pembrolizumab and treatment with acitretin led to complete resolution. This case highlights the importance of early recognition and multidisciplinary management of immunotherapy-related cutaneous toxicity.

Letter: Propranolol-Induced Acute Generalized Exanthematous Pustulosis Confirmed by Patch Testing: A Case Report.

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction in children. In this systematic review of 47 cases, a male predominance was observed, and medications remained the most common trigger for AGEP, with a higher contribution from infectious etiologies compared with frequencies reported in adult studies. Management primarily involved cessation of the inciting drug, topical corticosteroids, and supportive care. These findings provide practical guidance for early recognition and evaluation of pediatric AGEP.

Acute generalized exanthematous pustulosis (AGEP) is a rare but serious adverse skin reaction usually caused by drugs. We reported a 4-year-old boy diagnosed with Kawasaki disease (KD) accompanied by AGEP who presented with typical symptoms of KD, including fever, scarlet-like rash, swollen extremities, cervical lymph node swelling, conjunctival congestion, strawberry tongue, and cracked red lips on admission. On Day 5 of illness, a pustular eruption occurred and the patient was subsequently diagnosed with AGEP. After a double dose of intravenous immunoglobulin (IVIG) and treatment with methylprednisolone and aspirin, the patient recovered and had no cardiovascular complications. KD and AGEP can coexist, and pustular rash is not always a cutaneous manifestation of Kawasaki disease.

Allopurinol, the most used urate-lowering drug for the treatment of gout, is associated with rare but life-threatening severe cutaneous adverse reactions (SCARs) such as Stevens–Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, but not Acute Generalised Exanthematous Pustulosis (AGEP). They are characterised by severe skin and systemic involvement and are associated with substantial morbidity and a high risk of mortality. This narrative review summarises evidence on the clinical presentation, epidemiology, risk factors, and preventive strategies for allopurinol-induced SCARs. Key risk factors include the presence of the HLA-B*58:01 allele, renal impairment, older age, female sex, heart disease, higher starting doses of allopurinol, and certain ethnicities, e.g., South Asian, Han Chinese, and African populations likely due to the higher prevalence of the HLA-B*58:01 allele. Risk mitigation strategies include genetic testing for HLA-B*58:01 in high-risk ethnic groups and avoiding allopurinol in those that are positive for the HLA-B*58:01 allele, starting allopurinol at a low-dose (e.g., 50–100 mg/day) and up-titrating it gradually at 4-week intervals, and avoiding high-dose allopurinol in those with risk factors (e.g., chronic kidney disease stage ≥3). In addition, risk stratification using prediction tools may enable a safer use of allopurinol.

Acute generalized exanthematous pustulosis (AGEP) and acute localized exanthematous pustulosis (ALEP) are rare T-cell-mediated hypersensitivity reactions most commonly triggered by medications but increasingly recognized after exposure to iodinated contrast media (ICM). With the growing use of contrast-enhanced imaging, clinicians are more frequently faced with diagnostic and management challenges in patients with suspected ICM-induced reactions and with decisions regarding future contrast exposure. This systematic review aimed to synthesize published cases of ICM-associated AGEP and ALEP, with a particular focus on clinical recognition, diagnostic evaluation in routine practice, acute management, and implications for future imaging. The review was registered in PROSPERO (CRD420251140990). Searches of PubMed/MEDLINE, Web of Science, and the Serbian Citation Index (SCIndeks) were conducted without language or date restrictions through September 9, 2025, supplemented by backward and forward citation searching. Thirty-one publications reporting 53 patients were included. Patient age ranged from 4 to 93 years (median 56 years), and most were female (64.1%). AGEP accounted for 96.2% of cases, while ALEP was rare (3.8%). AGEP was associated with iomeprol, iodixanol, iohexol, iopromide, ioversol, iopamidol, and iobitridol. ALEP was linked to iomeprol and ioversol. Onset was typically rapid, with a median of 1 day after ICM exposure. Recurrent reactions occurred in 18.9% of patients, often with shorter latency upon re-exposure. Reported management most frequently involved topical corticosteroids, systemic corticosteroids, and antihistamines. Nearly all patients (98.1%) recovered. Clinicians should recognize ICM as potential triggers of AGEP and ALEP and pursue appropriate diagnostic evaluation and allergological assessment to guide safe future imaging.

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous drug reaction characterized by sterile pustules on erythematous skin. Azathioprine (AZA)-induced AGEP is rare, with few cases documented. We report a 50-year-old female with autoimmune hepatitis who developed a widespread pustular rash five days following the beginning of AZA therapy. Histopathology confirmed subcorneal pustules accompanied by eosinophilic infiltrates, indicative of AGEP. The discontinuation of AZA and systemic corticosteroids resulted in swift remission. This instance highlights the significance of prompt identification and discontinuation of medication to prevent adverse consequences.

Acute generalized exanthematous pustulosis (AGEP) is a drug-induced severe cutaneous adverse reaction (SCAR) characterized by an acute extensive erythematous pustular eruption. Integrated analyses including Asian cohorts remain scarce. A total of 503 AGEP cases were analyzed by combining two distinct, routinely-collected data cohorts: (1) a literature-derived cohort (PubMed, Embase, Web of Science, and CNKI) and (2) a hospital-based clinical cohort from a tertiary-care center in China. The hospital cohort data were collected retrospectively from January 2015 to July 2025. Demographic, etiologic, clinical, laboratory and therapeutic characteristics were summarized. Drugs were stratified by median latency (3 days) into short- versus long-latency groups to explore class-specific patterns. Drugs triggered 94.6% of cases, mainly β-lactam antibiotics (20.7%), non-β-lactam antibiotics (16.3%), and hydroxychloroquine (10.4%). With a 3-day median latency threshold, antibiotic-related reactions showed short latency, whereas antimalarials, analgesics, and antifungals exhibited longer latency. Hospitalization occurred in 75.1%, and systemic involvement in 20.2% (mostly hepatic or renal). Mucosal lesions were infrequent (oral 8.7%, genital 1.8%). Among those tested, patch tests were positive in 71.6%. Systemic corticosteroids were the mainstay (63.8%) of treatment, with cyclosporine (3.7%) and intravenous immunoglobulin (2.5%) used as adjuncts. A few refractory cases received biologics, including IL-17 inhibitors (eg secukinumab, brodalumab) and IL-36 receptor blockade (spesolimab), achieving partial or complete response. Eight deaths (1.6%) were documented, mainly among older, comorbid, polymedicated patients. AGEP displays distinct drug class-specific latency signatures and occasional systemic morbidity. We propose a conceptual AGEP causality triage framework integrating latency and allergologic evidence to enhance culprit identification in polypharmacy settings. Given the mechanistic involvement of the IL-36-Th17/IL-17 axis, biologic agents targeting IL-17 or IL-36 pathways show promise in severe or corticosteroid-refractory AGEP, warranting confirmation in larger prospective studies.

Background/Objectives: Acute generalized exanthematous pustulosis (AGEP) is a severe drug-induced cutaneous reaction characterized by the abrupt onset of sterile pustules, fever, neutrophilia, and a T cell-mediated type IVd hypersensitivity response. This narrative review synthesizes current evidence on pharmacological triggers, immunopathogenic mechanisms, diagnostic criteria, and differential diagnosis to provide a clinically oriented framework. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, ScienceDirect, and SpringerLink for studies published between 2000 and 2025, complemented by selected clinical reference sources. Studies addressing clinical features, immunological pathways, pharmacovigilance signals, and diagnostic tools for AGEP were included. Synthesis of Evidence: β-lactam antibiotics remain the most frequent triggers, while increasing associations have been reported with hydroxychloroquine, targeted therapies, immune checkpoint inhibitors, psychotropic agents, and vaccines. Immunopathogenesis is driven by IL-36 activation, CXCL8/IL-8–mediated neutrophil recruitment, and IL36RN mutations, explaining overlap with pustular psoriasis. Diagnostic accuracy improves through integration of drug latency, clinical morphology, histopathology, biomarkers, and standardized tools such as the EuroSCAR score. Conclusions: AGEP is a complex pustular reaction induced by diverse drugs and amplified by IL-36-mediated inflammation. Accurate diagnosis requires a multidimensional approach supported by structured algorithms and robust pharmacovigilance to identify evolving drug-associated patterns.

We read with interest the article by Pathak et al. (Clin Exp Dermatol 2026; 51:144–6), which analysed nearly 55 years of acute generalized exanthematous pustulosis data from the US Food and Drug Administration Adverse Event Reporting System database. We add some new perspectives.

Background The clinical characteristics of hydroxychloroquine (HCQ)‐induced acute generalized exanthematous pustulosis (AGEP) remain inadequately defined. This research sought to define the incidence and clinical course of AGEP following HCQ administration. Methods We performed a retrospective analysis of clinical cases of HCQ‐induced AGEP by systematically reviewing both Chinese and English medical databases up to October 31, 2025. Results A total of 76 patients were included in the analysis, with a median age of 45 years (range: 9, 79), of which 65 (85.5%) were female. The median duration from the initiation of HCQ to the onset of symptoms was 5 days (range: 2, 122). In addition to the presence of nonfollicular, pinhead‐sized pustules on erythematous and edematous skin, patients frequently exhibited fever (73.9%) and pruritus (59.4%). Laboratory evaluations typically revealed elevated peripheral blood neutrophil counts, erythrocyte sedimentation rate, and C‐reactive protein levels in individuals with AGEP. Symptoms resolved in all patients with a median duration of 18.5 days (range: 5, 119) following the cessation of HCQ and appropriate management. Conclusion While HCQ is widely used in dermatology and rheumatology, AGEP remains a rare adverse event. Skin symptoms in patients taking HCQ should prompt consideration of this diagnosis. Prolonged latency of HCQ‐induced AGEP is predominantly observed in female patients with rheumatic conditions. Timely recognition and management of AGEP are critical to guide appropriate drug management and ensure patient safety.

A 14-year-old girl, under medical oncology follow-up due to a hypothalamic-chiasmatic pilomyxoid astrocytoma, was referred for evaluation of skin lesions appearing 4 days after starting trametinib. She was not taking any other medications. Physical examination showed numerous monomorphic pustules on the chest, back, and proximal arms (Figure 1). She had no general malaise, fever, or other systemic symptoms. Dermoscopy revealed pustules with perifollicular erythema, tortuous vessels and hypopigmentation of the hair shafts interspersed with pigmented hairs (Figure 2). A punch biopsy was taken from one of the follicles (Figure 3). Histopathology revealed a dermal inflammatory infiltrate with histiocytes and neutrophils surrounding the periphery of a ruptured follicle. In the stratum corneum, neutrophils, inflammatory debris, keratin remnants and clusters of spherical oval spores were identified (Figure 3, H&E, 100×). Malassezia globosa was isolated in Dixon agar. In addition to the truncal lesions, the patient also demonstrated erythema, papulopustules and yellow scales on the forehead, nose, and cheeks, involving the nasolabial folds (Figure 4). These findings were consistent with seborrheic dermatitis and folliculitis, both manifestations of Malassezia infection. Trametinib administration was discontinued and treatment was initiated with oral itraconazole 50 mg every 12 h for 2 weeks and topical miconazole 2% and hydrocortisone 1% creams, with a good response. The patient is currently stable with itraconazole 50 mg weekly and washes with ciclopirox olamine. Bacterial swabs were not performed because the clinical and histopathological findings were consistent with Malassezia folliculitis. Malassezia folliculitis is an underdiagnosed disease, often mistaken for acne [1]. In addition, patients may have seborrheic dermatitis or pityriasis versicolor at the same time. The dermoscopy of Malassezia folliculitis has been described recently [2, 3]. Findings include folliculocentric pustules, perilesional erythema, dotted/linear/tortuous vessels, grayish-brown scales [3], hypopigmentation of the hair follicle, hypopigmentation of the proximal hair shaft, coiled hairs and hair breakage. These features differ from those seen in the main differential diagnosis, acne vulgaris, which typically presents with polymorphic lesions including comedones, papules, and nodules, as well as a lack of perifollicular pigmentary or vascular changes. Other important diagnoses to consider include acute generalized exanthematous pustulosis (AGEP), which is characterized by non-follicular pustules accompanied by systemic symptoms and leukocytosis. Notably, there are no cases of AGEP associated with trametinib described in the literature, although cases have been reported with vemurafenib, a BRAF inhibitor [4]. Bacterial folliculitis does not present with perifollicular hypopigmentation, and eosinophilic pustular folliculitis, often presents with urticarial plaques and intense pruritus. Malassezia folliculitis and pityriasis versicolor share some dermoscopy features, such as folliculocentricity and follicular hypopigmentation [5]. However, the lack of pustules combined with a diffuse scaling pattern is more consistent with the second diagnosis. Wood's lamp examination can reveal green fluorescence in the affected follicles, due to metabolites produced by Malassezia spp. [6]. Similar dermatologic toxicities have been reported with other MEK inhibitors including cobimetinib and binimetinib. However, acneiform dermatitis and papulopustular rashes have been specifically related to trametinib. The most frequent histopathologic finding in trametinib-associated reactions is suppurative folliculitis, usually caused by S. aureus [7]. Recently, acneiform eruptions that resolved successfully with fluconazole have been described in a series of five patients receiving trametinib [8]. Fluconazole doses of 100–200 mg/day were administered for 2 weeks, with a maintenance regimen of one, three, or seven times per week depending on the severity. Therefore, most dermatologic toxicities, including Malassezia folliculitis, can be managed without the discontinuation of the causative drug. However, severe reactions such as AGEP-like eruptions or diffuse bacterial folliculitis, may require temporary interruption. Dermatologists should be aware of the cutaneous reactions associated with trametinib to avoid unnecessary interruption of treatment. We emphasize the use of dermoscopy in this underdiagnosed disease, as well as the effectiveness of empirical treatment with oral antifungals in follicular eruptions associated with trametinib. The authors declare no conflicts of interest.