Drug-induced Pruritus Research Articles

Drug-induced Pruritus to Escitalopram

ABSTRACT Drug-induced pruritus is a dermatological adverse event that is usually underreported. The negative impacts of the unpleasant itching sensation largely affect the quality of life and adherence to the treatment. Here, we report a case of drug-induced pruritus to escitalopram – the most widely used medication in the treatment of depression and anti-anxiety in India; hence, it is pertinent to be familiar with such rare adverse drug reactions which may assist in early detection and better quality of care to the patient.

Comprehensive Study of Drug-Induced Pruritus Based on Adverse Drug Reaction Report Database.

Drug-induced pruritus triggers a desire to scratch, thereby diminishing one's quality of life. Certain instances of this phenomenon follow complex mechanisms of action that diverge from histamine-mediated pathways, known contributors to pruritus. However, investigations into the relationship between drugs and pruritus are limited. In this study, data mining techniques were employed to comprehensively analyze the characteristics of drugs linked to pruritus, using the FDA's Adverse Event Reporting System (FAERS) data. Reports linked to pruritus demonstrated noteworthy differences in gender, age, and weight when compared with non-pruritus cases. Among the leading candidates for drugs prompting pruritus were ophthalmic drugs, systemic antibacterials, contrast media, dermatological antifungals, and dermatological preparations. A principal component analysis showed that the second principal component served as an indicator for distinguishing between onsets at mucous membranes or the skin's surface. Additionally, the third principal component functioned as an indicator for categorizing administration methods as either invasive or noninvasive. Furthermore, a hierarchical cluster analysis conducted on these obtained principal components revealed the potential for classifying drugs based on the site of pruritus onset and the method of drug administration. These findings contribute to the development of targeted prevention and treatment strategies for avoiding pruritus in clinical practice.

2020 guidelines for the diagnosis and treatment of cutaneous pruritus.

The mechanisms underlying itch are not fully understood. Physicians usually encounter difficulty controlling itch in generalized pruritus. Since only a small percentage of patients with generalized pruritus respond to antihistamines (H1 receptor antagonists), a variety of itch mediators and mechanisms other than histaminergic signals are considered to be involved in itch for these non-responsive patients. In 2012, we created guidelines for generalized pruritus. Those guidelines have been updated and revised to make some of the definitions, diagnostic terms, and classifications more applicable to daily clinical practice. Cutaneous pruritus as designated in these guidelines is a disease characterized by itch without an observable rash. Generalized pruritus (without skin inflammation) is defined as the presence of itch over a wide area, and not localized to a specific part of the body. This entity includes idiopathic pruritus, pruritus in the elderly, symptomatic pruritus, pregnancy-associated pruritus, drug-induced pruritus, and psychogenic pruritus. Localized pruritus (without skin inflammation) represents fixed itch localized to a specific part of the body, and includes anogenital pruritus, scalp pruritus, notalgia paresthetica, and brachioradial pruritus. These guidelines outline the current concepts and specify the diagnostic methods/treatments for cutaneous pruritus.

A group of cationic amphiphilic drugs activates MRGPRX2 and induces scratching behavior in mice

Mas gene-related G protein-coupled receptors (MRGPRs) are a G protein-coupled receptor family responsive to various exogenous and endogenous agonists, playing a fundamental role in pain and itch sensation. The primate-specific family member MRGPRX2 and its murine orthologue MRGPRB2 are expressed by mast cells mediating IgE-independent signaling and pseudoallergic drug reactions. Our aim was to increase knowledge about the function and regulation of MRGPRX2/MRGPRB2, which is of major importance in prevention of drug hypersensitivity reactions and drug-induced pruritus. To identify novel MRGPR (ant)agonists, we screened a library of pharmacologically active compounds by utilizing a high-throughput calcium mobilization assay. The identified hit compounds were analyzed for their pseudoallergic and pruritogenic effects in mice and human. We found a class of commonly used drugs activating MRGPRX2 that, to a large extent, consists of antidepressants, antiallergic drugs, and antipsychotics. Three-dimensional pharmacophore modeling revealed structural similarities of the identified agonists, classifying them as cationic amphiphilic drugs. Mast cell activation was investigated by using the 3 representatively selected antidepressants clomipramine, paroxetine, and desipramine. Indeed, we were able to show a concentration-dependent activation and MRGPRX2-dependent degranulation of the human mast cell line LAD2 (Laboratory of Allergic Diseases-2). Furthermore, clomipramine, paroxetine, and desipramine were able to induce degranulation of human skin and murine peritoneal mast cells. These substances elicited dose-dependent scratching behavior following intradermal injection into C57BL/6 mice but less so in MRGPRB2-mutant mice, as well as wheal-and-flare reactions following intradermal injections in humans. Our results contribute to the characterization of structure-activity relationships and functionality of MRGPRX2 ligands and facilitate prediction of adverse reactions such as drug-induced pruritus to prevent severe drug hypersensitivity reactions.

Pruritus Associated with Commonly Prescribed Medications in a Tertiary Care Center

Background: Sparse data are available on rates of drug-induced pruritus, a well-recognized adverse reaction. We sought to assess relative rates of pruritus associated with commonly prescribed medications. Methods: Using the electronic medical record system EPIC, retrospective data were collected on patients seen at Johns Hopkins who received a medication of interest in a five-year period (2013–2018). Sequential criteria were used to identify the subpopulation who presented with a chief complaint of “pruritus” or diagnosis of “itching” within three months of receiving drugs. Results: We identified 9802 patients with pruritus after drug initiation and 1,085,404 patients without. A higher proportion of those with pruritus were female (70%) than those without (58%), p < 0.001. Patients in both groups were most commonly 50 to 79 years old. A higher proportion of patients with pruritus were black (40%) compared to those without (23%), p < 0.001. In this study, the highest rates of pruritus were observed with heparin (1.11%), trimethoprim-sulfamethoxazole (1.06%), and calcium channel blockers (0.92%). Psychiatric/neurologic drugs used to treat pruritus were associated with low rates of itch. Conclusions: Certain cardiovascular and antimicrobial agents are associated with increased frequencies of pruritus. This knowledge may guide providers in clinical selection of commonly used agents to minimize adverse effects associated with reduced compliance.

203 Drug-induced pruritus in a tertiary care health system

203 Drug-induced pruritus in a tertiary care health system

Effectiveness of Intrathecal Morphine for Analgesia following Elective Caesarean Section

Aims: This study evaluates the effectiveness of usage of 0.2 mg intrathecal morphine as post-operative analgesia and its effect on activity of mother after elective cesarean section. Methods: This hospital based prospective, randomized, double-blinded and placebo controlled study was carried out at Nagarik Community Teaching Hospital, Bhaktapur between 2012 January to 2014 November after the approval was taken from the hospital authority and the written informed consent from the participating patients. Fifty women of ASA I or II physical status undergoing cesarean section under sub-arachnoid block was randomized into two groups – P group (placebo group, n = 25) and M group (Treatment group, n = 25). P Group received hyperbaric bupivacaine 2.3ml, 0.5% bupivacaine (11.5 mg) and M Group received morphine 0.2 ml (0.2 mg) plus bupivacaine 2.3ml, 0.5% (11.5 mg) intrathecally. All subjects received 8 mg ondansetron intravenously 30 minutes before surgery to prevent possible drug-induced pruritus and post-operative nausea and vomiting. 1000 mg rectal acetaminophen suppository was given at the end of the surgery. Pain, nausea and pruritus during the first 24 hours using visual analog scale were recorded by a trained nurse or attending doctor who was not involved in the study. Results: Duration of complete analgesia and the time to request for additional analgesics was longer in M Group than in P Group. Similarly, the active movement is earlier in M Group than in P Group. There were no significant differences in adverse effects between the groups. Conclusions: Addition of morphine 0.2 mg to heavy bupivacaine intrathecally reduced post-operative pain and analgesic requirements without any significant difference in adverse effects.

NK-1 Antagonists and Itch.

Substance P (SP) is an important mediator of pro-inflammatory mechanisms in the skin. It targets multiple cells such as keratinocytes, mast cells, and fibroblasts which are involved in the cutaneous generation of pruritus. This suggests that SP is an interesting target for therapy. In fact, in recent case reports and case series, SP antagonists demonstrated a significant antipruritic effect in acute and chronic pruritus such as drug-induced pruritus, paraneoplastic pruritus, prurigo nodularis, cutaneous T-cell lymphoma, and brachioradial pruritus.

Drug-induced pruritus

Pruritus, especially chronic pruritus, has long been underestimated and leads to high psychological strain in the affected patients. Even today, in spite of receiving increased attention, the underlying etiology cannot always be identified. We review potential underlying pathologic mechanisms of drug-induced pruritus, focusing among others on current dermato-oncological medications in terms of their pruritogenic risks. Acute pruritus must be distinguished from chronic pruritus which lasts for a minimum of 6 weeks. There are various therapeutic approaches for drug-induced pruritus. As a first step, the drug causing the pruritus has to be identified; then the intake of that drug has to be ceased or modified. This may not always be possible, as in the case of chemotherapy agents. With regard to the demographic development of the population with increasing life expectancy and the resulting increasing polypharmacy, drugs will have to be taken into account as a possible cause for pruritus more often in the future. It would be desirable to routinely assess pruritus as a possible adverse effect in regulatory drug studies.

Drug-induced Pruritus: A Review

Pruritus is an unpleasant sensation that leads to scratching. In addition to several diseases, the administration of drugs may induce pruritus. It is estimated that pruritus accounts for approximately 5% of all skin adverse reactions after drug intake. However, to date there has been no systematic review of the natural course and possible underlying mechanisms of drug-induced pruritus. For example, no clear distinction has been made between acute or chronic (lasting more than 6 weeks) forms of pruritus. This review presents a systematic categorization of the different forms of drug-induced pruritus, with special emphasis on a therapeutic approach to this side-effect.

Clinical Classification of Itch: a Position Paper of the International Forum for the Study of Itch

Chronic itch is a common and distressing symptom that arises from a variety of skin conditions and systemic diseases. Despite this, there is no clinically based classification of pruritic diseases to assist in the diagnosis and cost-effective medical care of patients with pruritus. The proposed classification focuses on clinical signs and distinguishes between diseases with and without primary or secondary skin lesions. Three groups of conditions are proposed: pruritus on diseased (inflamed) skin (group I), pruritus on non-diseased (non-inflamed) skin (group II), and pruritus presenting with severe chronic secondary scratch lesions, such as prurigo nodularis (group III). The next part classifies the underlying diseases according to different categories: dermatological diseases, systemic diseases including diseases of pregnancy and drug-induced pruritus, neurological and psychiatric diseases. In some patients more than one cause may account for pruritus (category "mixed") while in others no underlying disease can be identified (category "others"). This is the first version of a clinical classification worked out by the members of the International Forum for the Study of Itch. It is intended to serve as a diagnostic route for better evaluation of patients with chronic pruritus and aims to improve patients' care.

Paroxetine in the treatment of severe non-dermatological pruritus: a randomized, controlled trial

Severe pruritus may be an idiopathic phenomenon or associated with advanced systemic disease. It is one of the most distressing and difficult to treat symptoms. Uncontrolled studies have suggested that, in patients experiencing severe pruritus, paroxetine appeared to have a rapid anti-pruritic effect. This study was a prospective double-blind, randomized within patient comparison of paroxetine and placebo. The intensity of pruritus was measured subjectively with a numerical analogue scale. The primary endpoint of the trial was the mean pruritus score, measured for seven days after randomization and after cross-over. The secondary endpoint was individual global response to the treatment. Response was defined as at least 50% reduction of intensity of pruritus in the last three days of the treatment period vs. baseline. Adverse effects and patient satisfaction and preferences were also recorded. Twenty-six patients were included in the study; 17 of them had solid tumors, 4 had hematological malignancies and 5 had various nonmalignant or idiopathic conditions. Eight patients had drug-induced pruritus (none opioid-induced), 7 patients had paraneoplastic pruritus and 3 had cholestatic pruritus. After a run-in period, patients were randomly assigned to treatment with 20 mg paroxetine or placebo. The crossover took place after 7 days. Two patients discontinued treatment because of adverse effects of paroxetine. Twenty-four patients treated with paroxetine had lower pruritus intensity scores over the 7 treatment periods (mean±SE = 5.2 ± 0.32) as compared to placebo (mean±SE = 6.0±0.32). Mean difference between placebo and paroxetine was 0.78 (95% CI = 0.37–1.19). Nine of twenty-four patients (37.5%) fulfilled criteria of response. The onset of anti-pruritic action was observed usually after 2–3 days, irrespective of the order of treatment. The outcome of this study indicates that paroxetine is effective in the treatment of severe pruritus of non-dermatological origin.

Antimalarial drug-induced aquagenic-type pruritus in patients with lupus.

Antimalarial drug-induced aquagenic-type pruritus in patients with lupus.