A Study of Cutaneous Adverse Drug Reactions at a Tertiary Care Center in Andhra Pradesh, India.

INTRODUCTION: Practically all physicians encounter a diverse range of suspected cutaneous adverse drug reactions (CADRs) in their daily clinical practice. The skin and mucosa are the most often encountered areas for the early presentation of numerous adverse drug reactions. Cutaneous adverse drug reactions are classified as benign or severe. The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCARs). OBJECTIVE: To determine the varied clinical and morphological presentations of CADRs and to identify the culprit drug and common drugs causing CADRs. MATERIALS AND METHODS: Patients with clinical features suspected of CADRs presenting to the outpatient department (OPD) of dermatology, venereology, and leprosy (DVL) between December 2021 to November 2022 at Great Eastern Medical School and Hospital (GEMS), Srikakulam, Andhra Pradesh, India, were considered for the study. This was a cross-sectional, observational study. The patient's clinical history was taken in detail. This included chief complaints (symptoms, site of onset, duration, drug history, latency time between drug administration and the appearance of cutaneous lesions), family history, associated diseases, the morphology of lesions, and mucosal examination. Upon drug discontinuation, improvement in cutaneous lesions and systemic features were noted. A complete general examination, systemic examination, dermatological tests, and mucosal examination were performed. RESULTS: A total of 102 patients were involved in the study, of whom 55 were males and 47 were females. The male-to-female ratio was 1.17:1, with a slight male majority. The most common age group was 31 to 40 years for both males and females. Itching was the predominant complaint in 56 patients (54.9%). The mean latency period was shortest in urticaria (2.13+/- 0.99 hours) and longest in lichenoid drug eruption (4.33+/- 3.93 months). Most patients developed symptoms after a week of taking the drug (53.92%). A history of similar complaints was present in 38.23% of patients. Analgesics and antipyretics (39.2%) were the most common culprit drugs followed by antimicrobials (29.4%). Among analgesics and antipyretics, aceclofenac (24.5%) was the commonest culprit drug. Benign CADRs were observed in 89 patients (87.25%), and severe cutaneous adverse reactions (SCARs) were observed in 13 patients (12.74%). The common CADRs presented were drug-induced exanthem (27.4%). Imatinib-induced psoriasis vulgaris and lithium-induced scalp psoriasis were observed in one patient each. Severe cutaneous adverse reactions were observed in 13 patients (12.74%). Anticonvulsants, nonsteroidal anti-inflammatory drugs (NSAIDs), and antimicrobials were the culprit drugs for SCARs. Eosinophilia was present in three patients, deranged liver enzymes was present in nine patients, a deranged renal profile was present in seven patients, and death occurred in one patient with toxic epidermal necrolysis (TEN) of SCARs. CONCLUSION: Before prescribing any drug to a patient, a detailed drug history and family history of drug reactions need to be obtained. Patients should be advised to avoid over-the-counter usage of medications and self-administration of drugs. If adverse drug reactions occur, it is advised to avoid readministration of the culprit drug. Drug cards must be prepared and given to the patient, mentioning the culprit drug as well as the cross-reacting drugs.

Corneal epithelial permeability to fluorescein in humans by a multi-drop method.

PURPOSE: The permeability of the corneal epithelium to fluorescein Pdc is an indicator of the health of the ocular surface. It can be measured in a clinical setting by determining the accumulation of fluorescein in the stroma following administration of the dye on the ocular surface. Here we demonstrate a new multi-drop method for the measurement of Pdc by a spot fluorometer. METHODS: Twenty-nine healthy participants were recruited for this study. First, a probe-drop of fluorescein (0.35%, 2 µL) was instilled on the conjunctiva. The clearance of the dye from the tears was immediately measured using the fluorometer. Following this, two loading drops (2%; 6 µL each) were administered 10 min apart. Fifteen minutes later, the ocular surface was washed and fluorescence from the stroma Fs was measured. Permeability was calculated using Pdc = (Q x Fs)/ (2 x AUC), where Q is the stromal thickness and AUC is the area under the fluorescence vs. time curve for the loading drops. RESULTS: After the probe drop, the tear fluorescence followed an exponential decay (elimination rate constant; kd = 0.41 ± 0.28 per min; 49 eyes of 29 subjects), but the increase in Fs was negligible. However, after the loading drops, the measured Fs was ~ 20-fold higher than the autofluorescence and could be recorded at a high signal to noise ratio (SNR > 40). The intra-subject variability of kd was insignificant. Since fluorescein undergoes concentration quenching at > 0.5%, the value of AUC for the loading drops was estimated by scaling the AUC of the probe drop. The calculated Pdc was 0.54 ± 0.54 nm/sec (n = 49). A Monte Carlo simulation of the model for the multi-drop protocol confirmed the robustness of the estimated Pdc. CONCLUSIONS: The new multi-drop method can be used in place of the single-drop approach. It can overcome a lack of sensitivity in fluorometers of high axial resolution. The Pdc estimated by the multi-drop method is ~ 11-fold higher than previously reported but closer to the value reported for other drugs with equivalent octanol/water partition coefficient.

Ocular Spot Fluorometer Equipped With a Lock-In Amplifier for Measurement of Aqueous Flare.

PURPOSE: To evaluate a custom-made ocular fluorometer for detection of intensity of light scatter (ILS) from the anterior chamber (A/C) as an objective measure of aqueous flare. METHODS: The fluorometer, equipped with a lock-in amplifier, was employed in the scatter mode to detect ILS from A/C. Measurements were performed with two illumination slit widths of 0.5 and 0.25 mm. The axial resolution at these slit widths were 80 and 200 µm, respectively. Healthy and pseudophakic eyes, with grade 0 Standardization of Uveitis Nomenclature (SUN) score, were employed as control subjects. ILS was also recorded in a cohort of patients who had undergone phacoemulsification and showed grades 1+ or 2+ on postoperative days 1 and 4. RESULTS: The inter- and intraobserver variabilities in the measurement of ILS were not significant. In cataract patients, ILS was significantly higher on postoperative day 1 relative to healthy eyes. By day 4, ILS decreased significantly and was only marginally different from ILS in quiet pseudophakic eyes or healthy eyes. Eyes with higher SUN scores showed proportionately increased ILS. The receiver-operator characteristic analysis indicated no advantage in using the smaller slit width in discriminating ILS at different SUN scores although it provided higher axial resolution. CONCLUSIONS: The lock-in-based spot fluorometer is reliable for measurement of ILS with high precision and accuracy.The measured ILS correlates linearly with SUN scores and can be used to provide a higher granularity for recording aqueous flare. TRANSLATIONAL RELEVANCE: The instrument can be used in the clinical management of uveitis and drug development toward uveitis.