Persistent Pruritus Research Articles

The Analysis Study of Effect of Acupuncture on the Treatment of Atopic Itch: A Comprehensive Systematic Review

Background: Atopic dermatitis is a common inflammatory skin disorder characterized by recurrent eczematous lesions and severe itching. Given its chronic nature and association with persistent pruritus, exploring therapies like acupuncture may offer valuable relief and enhance patient outcomes. This systematic review aims to explore the efficacy and mechanisms of acupuncture as a treatment for atopic pruritus based on the literature of the last decade. Methods: The study followed PRISMA 2020 guidelines, reviewing English-language publications from 2014 to 2024. Editorials, duplicate reviews from the same journal, and papers lacking a DOI were excluded. The literature search was conducted using PubMed, SagePub, SpringerLink, and Google Scholar. Result: A total of 630 articles were initially identified through online databases (PubMed, SagePub, SpringerLink, and Google Scholar). After three rounds of screening, eight relevant studies were selected for full-text analysis. Conclusion: Acupuncture shows potential as a noninvasive and effective treatment for reducing pruritus and associated symptoms in patients with atopic dermatitis and other pruritic conditions. The observed benefits, such as decreased itch intensity, improved quality of life, and reduced medication use, underline its value as an adjunct therapy.

Prevalence and Association of Pruritus and Its Current Treatment During the First Year of Dialysis: A DOMESTICO Study.

Pruritus is common in dialysis patients and associated with impaired health-related quality of life (HRQoL) and sleep disturbances. Its pathophysiology remains unclear resulting in limited treatment options and lack of treatment guidelines. The exact trajectory of pruritus after dialysis initiation nor the state of current medical treatment has been studied. Incident dialysis patients (n=1438), included in the Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO), were studied. Outcome parameters were prevalence of pruritus, severity of pruritus and the use of antipruritic medication, repeatedly measured during the first year of dialysis. Associations between treatment, pruritus and quality of life were longitudinally studied using linear mixed models. The prevalence of pruritus ranged from 50.5% to 56.6% during the first year of dialysis. Throughout the year approximately 35% experienced persistent pruritus and 40% fluctuating pruritus. During follow-up 21.5% to 26.5% received medical treatment for pruritus. Emollients were associated with more severe pruritus (adjusted β = 0.31, 95% CI 0.15; 0.48), the remaining treatments did not show any association. Pruritus was significantly associated with lower physical and mental HRQoL (adjusted β = -2.04, 95% CI -2.78; -1.30 and β = -1.73, 95% CI -2.51; -0.94, respectively), irrespective of treatment. During the first year of dialysis, pruritus is highly prevalent, predominantly fluctuating, and associated with impaired HRQoL. The minority of patients received medical treatment; in our study current treatment was not associated with an improvement of pruritus. These results highlight the need for more awareness among clinicians and for the development of effective treatment options.

Anicteric Cholestasis Syndrome with Pruritus Revealing Systemic Sarcoidosis

Introduction: Sarcoidosis is a systemic granulomatosis of unknown aetiology characterised by the formation of non-caseating granulomas in organs. Hepatic involvement can be difficult to diagnose. Material and method: We report the case of a 30-year-old female patient with a long history of intractable pruritus revealing systemic sarcoidosis. Case report: A 30-year-old female patient presented with a persistent pruritus without jaundice or fever. Examination revealed tender hepatomegaly and scratch lesions. Laboratory tests revealed elevated liver enzymes with cholestasis, and serum protein electrophoresis showed an inflammatory profile. The different viral hepatitis tests were non-contributory. Alpha fetoprotein was normal. Abdominal ultrasound and CT scans revealed a heteronodular hepatomegaly. The first liver biopsy was consistent with autoimmune hepatitis lesions. The disease improved with general corticosteroid therapy and azathioprine. Two years later, with the persistence of the pruritus, blood calcium levels and angiotensin-converting enzyme tests were found to be elevated. A new liver biopsy showed epitheliogigantocellular granulomas without caseous necrosis. A thoracic CT scan revealed mediastinal adenopathy. This suggested systemic sarcoidosis. The patient progressed well clinically and radiologically on general corticosteroids with adjuvant therapy and azathioprine. Conclusion: Sarcoidosis is a systemic disease that can affect most tissues and organs. Hepatic involvement is frequent and more often difficult to diagnose.

Maralixibat in progressive familial intrahepatic cholestasis (MARCH-PFIC): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders, the most prevalent being BSEP deficiency, resulting in disrupted bile formation, cholestasis, and pruritus. Building on a previous phase 2 study, we aimed to evaluate the efficacy and safety of maralixibat-an ileal bile acid transporter inhibitor-in participants with all types of PFIC. MARCH-PFIC was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study conducted in 29 community and hospital centres across 16 countries in Europe, the Americas, and Asia. We recruited participants aged 1-17 years with PFIC with persistent pruritus (>6 months; average of ≥1·5 on morning Itch-Reported Outcome [Observer; ItchRO(Obs)] during the last 4 weeks of screening) and biochemical abnormalities or pathological evidence of progressive liver disease, or both. We defined three analysis cohorts. The BSEP (or primary) cohort included only those with biallelic, non-truncated BSEP deficiency without low or fluctuating serum bile acids or previous biliary surgery. The all-PFIC cohort combined the BSEP cohort with participants with biallelic FIC1, MDR3, TJP2, or MYO5B deficiencies without previous surgery but regardless of bile acids. The full cohort had no exclusions. Participants were randomly assigned (1:1) to receive oral maralixibat (starting dose 142·5 μg/kg, then escalated to 570 μg/kg) or placebo twice daily for 26 weeks. The primary endpoint was the mean change in average morning ItchRO(Obs) severity score between baseline and weeks 15-26 in the BSEP cohort. The key secondary efficacy endpoint was the mean change in total serum bile acids between baseline and the average of weeks 18, 22, and 26 in the BSEP cohort. Efficacy analyses were done in the intention-to-treat population (all those randomly assigned) and safety analyses were done in all participants who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov, NCT03905330, and EudraCT, 2019-001211-22. Between July 9, 2019, and March 4, 2022, 125 patients were screened, of whom 93 were randomly assigned to maralixibat (n=47; 14 in the BSEP cohort and 33 in the all-PFIC cohort) or placebo (n=46; 17 in the BSEP cohort and 31 in the all-PFIC cohort), received at least one dose of study drug, and were included in the intention-to-treat and safety populations. The median age was 3·0 years (IQR 2·0-7·0) and 51 (55%) of 93 participants were female and 42 (45%) were male. In the BSEP cohort, least-squares mean change from baseline in morning ItchRO(Obs) was -1·7 (95% CI -2·3 to -1·2) with maralixibat versus -0·6 (-1·1 to -0·1) with placebo, with a significant between-group difference of -1·1 (95% CI -1·8 to -0·3; p=0·0063). Least-squares mean change from baseline in total serum bile acids was -176 μmol/L (95% CI -257 to -94) for maralixibat versus 11 μmol/L (-58 to 80) for placebo, also representing a significant difference of -187 μmol/L (95% CI -293 to -80; p=0·0013). The most common adverse event was diarrhoea (27 [57%] of 47 patients on maralixibat vs nine [20%] of 46 patients on placebo; all mild or moderate and mostly transient). There were five (11%) participants with serious treatment-emergent adverse events in the maralixibat group versus three (7%) in the placebo group. No treatment-related deaths occurred. Maralixibat improved pruritus and predictors of native liver survival in PFIC (eg, serum bile acids). Maralixibat represents a non-surgical, pharmacological option to interrupt the enterohepatic circulation and improve the standard of care in patients with PFIC. Mirum Pharmaceuticals.

A Novel Recombinant Human Filaggrin Segment (rhFLA-10) Alleviated a Skin Lesion of Atopic Dermatitis.

Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is marked by impaired skin barrier function and persistent pruritus. It significantly deteriorates patients' quality of life, making it one of the most burdensome non-lethal skin disorders. Filaggrin plays a crucial role in the pathophysiology of barrier disruption in AD, interacting with inflammatory mediators. It is an integral part of the extracellular matrix architecture, serving to protect the skin barrier and attenuate the inflammatory cascade. In this study, we engineered a novel recombinant human filaggrin (rhFLA-10) expression vector, which was subsequently synthesized and purified. In vitro and ex vivo efficacy experiments were conducted for AD. rhFLA-10, at low concentrations (5 to 20 μg/mL), was non-toxic to HACaT cells, significantly inhibited the degranulation of P815 mast cells, and was readily absorbed by cells, thereby exerting a soothing therapeutic effect. Furthermore, rhFLA-10 demonstrated anti-inflammatory properties (p < 0.05). In vivo, efficacy experiments further substantiated that rhFLA-10 could effectively ameliorate AD in mice and facilitate the repair of damaged skin (p < 0.001). These findings underscore the considerable potential of rhFLA-10 in the treatment of AD.

Doped-MXene assists in deciphering metabolic signature of psoriasis and unraveling dysregulated leukotriene metabolism

Psoriasis, characterized by erythematous plaques, desquamation, persistent pruritus, and discomfort, significantly compromises the quality of life for afflicted individuals. The intricate interplay of immunological, genetic, and environmental factors has left the molecular intricacies of psoriasis only partially elucidated, underscoring the imperative to unravel these intricate mechanisms. In contradistinction to conventional techniques such as nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS), the burgeoning laser desorption/ionization (LDI) metabolic paradigm holds substantial promise in elucidating the molecular mechanism of psoriasis. Nonetheless, achieving heightened sensitivity and high-throughput metabolite detection within intricate clinical biosamples mandates stringent requisites, encompassing favourable ionization efficiency and high surface area. Henceforth, we proffered a dual-strategy entailing the utilization of transition metal carbides (MXene) with unique morphology and the integration of multi-walled carbon nanotubes (MWCNTs) to ameliorate these challenges for psoriasis. We have corroborated the morphological architecture, elemental composition, and efficacy of LDI when applied to MWCNTs-doped MXene. Egregiously, through the employment of both animal models and clinical specimens, we attained diagnostic efficiencies of 0.959 and 0.924 via receiver operating characteristic (ROC) curve analysis, respectively, for discrimination psoriasis from control individuals. Doped MXene evinced exceptional signal amplification and imperviousness to salt and protein interference. Furthermore, enrichment pathway analysis unveiled a significant escalation in leukotriene E4 and arachidonic acid levels within the psoriasis cohort. Harnessing LDI metabolic fingerprints, concomitant with MWCNTs-doped MXene, expedited the recognition of the distinct metabolic characteristics inherent to psoriasis, thereby laying bare the dysregulation in leukotriene metabolism. This epochal breakthrough holds immense potential to usher in new vistas for exploring the underlying mechanisms governing the onset and progression of psoriasis-related disorders, thereby significantly contributing to the refinement of psoriasis health management strategies.

Orexin neurons play contrasting roles in itch and pain neural processing via projecting to the periaqueductal gray

Pain and itch are recognized as antagonistically regulated sensations; pain suppresses itch, whilst pain inhibition enhances itch. The neural mechanisms at the central nervous system (CNS) underlying these pain-itch interactions still need to be explored. Here, we revealed the contrasting role of orexin-producing neurons (ORX neurons) in the lateral hypothalamus (LH), which suppresses pain while enhancing itch neural processing, by applying optogenetics to the acute pruritus and pain model. We also revealed that the circuit of ORX neurons from LH to periaqueductal gray regions served in the contrasting modulation of itch and pain processing using optogenetic terminal inhibition techniques. Additionally, by using an atopic dermatitis model, we confirmed the involvement of ORX neurons in regulating chronic itch processing, which could lead to a novel therapeutic target for persistent pruritus in clinical settings. Our findings provide new insight into the mechanism of antagonistic regulation between pain and itch in the CNS.

Persistent pruritus associated with worse quality of life in patients with chronic hepatitis.

Prevalence and severity of pruritusamong US patients with chronic hepatitis B and C (HBV, HCV) are not well-documented. Chronic Hepatitis Cohort Study (CHeCS) patients were surveyed to examine pruritus prevalence and impact on quality of life (QoL). Patients who reported experiencing pruritus ≥3 on a Numeric Rating Scale (NRS) within the past 30 days were invited to participate in a 6-month study using the SF-36 questionnaire. General regression (univariate followed by multivariable modelling) was used to analyse pruritus intensity and eight QoL dimensions. Among 1654 patients (HBV = 358, HCV = 1296, HBV/HCV = 6), pruritus prevalence was significantly higher among patients with HCV than those with HBV (44% vs. 35%; p < .05). One hundred and twenty-three patients (21 HBV and 102 HCV) participated in the QoL study (72% ≥60 years; 50% men; 25% Black; 37% with cirrhosis; 66% had BMI > 25). Mean NRS was 4.9-5.3. QoL responses for social functioning and emotional well-being were higher (70-72 points) than responses for energy/fatigue (50-51). Antiviral treatment rates were higher in HCV (92%, SVR 99%) than HBV (71% ever, 43% ongoing). Multivariable analyses showed no significant effect of hepatitis type or antiviral treatments on itch. Antihistamines were associated with severe itch. Higher NRS was associated with significantly reduced QoL. Each unit increase in NRS was associated with a 2-3 unit decline in emotional well-being, general health, physical function, energy/fatigue, social functioning and emotional health. Pruritus negatively affects many viral hepatitis patients, regardless of antiviral treatment status. Improved treatment options are needed to address its impact on QoL.

Treatment of Patient with Cutaneous Lupus Erythematosus with Roflumilast Cream 0.3%

Introduction: Cutaneous lupus erythematosus (CLE) is the cutaneous form of a common autoimmune disease, lupus erythematosus, driven by a dysfunction within the adaptive and innate immune system. CLE is subcategorized further into acute, subacute and chronic disease. Here we report a case of a patient with systemic and refractory cutaneous disease with improvement in manifestations demonstrating efficacy following treatment with roflumilast cream 0.3% in a complex chronic CLE patient with uncontrolled disease, intense pruritus and scarring. Case Report: A 48-year-old Asian female with history of smoking, chronic refractory SLE since 2008 with a new onset of pruritic rash. Previous therapies including thalidomide, hydroxychloroquine, methotrexate, mycophenolate mofetil, numerous research trials, oral and intramuscular steroids that failed to control her systemic LE. A Rheumatology colleague referred the patient for new onset cutaneous manifestations. Initial presentation revealed lesions involving 2% of the occipital scalp. Pathology confirmed the diagnosis of discoid lupus. Intralesional triamcinolone , plus topical betamethasone dipropionate 0.05% twice daily (BID) and timolol 0.5% OP solution for wound healing were initiated. Fifteen months later the patient had disease progression of her CLE on to her scalp, face, legs and arms, with the chief complaint of persistent pruritus despite oral prednisone, hydroxychloroquine and thalidomide. The patient’s rheumatologist requested alternative treatment for cutaneous disease without use of long term topical high potency steroids. A second series of intralesional triamcinolone injections plus betamethasone dipropionate 0.05% BID for 3-4 weeks and titrate down to 2-3 applications per week, and addition of roflumilast cream 0.3% was initiated once daily to her face, scalp, and lower legs. On the third office visit, four weeks later, the patient reported pruritus and cutaneous manifestations in lower legs controlled and scalp and face have marked improvement. After 8 weeks on this regimen, the patient return reported that scalp and face continued to improve and disease on the legs continue to be controlled despite not using topical treatment for four weeks. Roflumilast cream 0.3% once daily was continued as monotherapy. Two months later, the patient reported that her skin was fully controlled was starting to repigment with monotherapy. Conclusions: This case report of a 48-year-old female with refractory treatment resistant chronic SLE and CLE treated with roflumilast cream 0.3%, a phosphodiesterase-4 (PDE-4) inhibitor, resulted in disease control, the symptom improvement of improved pruritus as well as repigmentation of the skin. The results observed in this patient suggest this topical intervention, if implemented at the beginning of treatment for cutaneous onset of disease, may have the potential to halt the progression of cutaneous involvement. This case report serves to highlight a promising intervention that may lead to better cutaneous control without long term side effects of topical steroid use.

Extramammary Paget&amp;rsquo;s disease: Persistent pruritus vulvae is an alarming symptom in primary care

No abstract available

Diagnosis and management of intrahepatic cholestasis in pregnancy

Intrahepatic cholestasis of pregnancy is caused by a dysfunction of the hepatocytes, typical of pregnancy. High concentrations of sex hormones and genetic predisposition appear to be important factors for their development. The incidence depends on the ethnic composition of the population and the diagnostic criteria used. It is characterized by increasing and persistent pruritus, increased concentrations of bile acids, usually in the late second or third trimester of pregnancy. It leads to the occurrence of uteroplacental hypoxia that increases the risk of meconium amniotic fluid, preterm delivery, preeclampsia, postpartum hemorrhage, neonatal respiratory distress syndrome, and perinatal death. Therapeutic management is aimed at reducing clinical symptoms, normalizing maternal biochemical changes, and preventing fetal complications. The main pharmacological treatment consists of the administration of ursodeoxycholic acid. The objective of this research is to evaluate the diagnosis and management of intrahepatic cholestasis of pregnancy

Mechanisms and treatments of neuropathic itch in a mouse model of lymphoma.

Our understanding of neuropathic itch is limited due to a lack of relevant animal models. Patients with cutaneous T cell lymphoma (CTCL) experience severe itching. Here, we characterize a mouse model of chronic itch with remarkable lymphoma growth, immune cell accumulation, and persistent pruritus. Intradermal CTCL inoculation produced time-dependent changes in nerve innervations in lymphoma-bearing skin. In the early phase (20 days), CTCL caused hyperinnervations in the epidermis. However, chronic itch was associated with loss of epidermal nerve fibers in the late phases (40 and 60 days). CTCL was also characterized by marked nerve innervations in mouse lymphoma. Blockade of C-fibers reduced pruritus at early and late phases, whereas blockade of A-fibers only suppressed late-phase itch. Intrathecal (i.t.) gabapentin injection reduced late-phase, but not early-phase, pruritus. IL-31 was upregulated in mouse lymphoma, whereas its receptor Il31ra was persistently upregulated in Trpv1-expressing sensory neurons in mice with CTCL. Intratumoral anti-IL-31 treatment effectively suppressed CTCL-induced scratching and alloknesis (mechanical itch). Finally, i.t. administration of a TLR4 antagonist attenuated pruritus in early and late phases and in both sexes. Collectively, we have established a mouse model of neuropathic and cancer itch with relevance to human disease. Our findings also suggest distinct mechanisms underlying acute, chronic, and neuropathic itch.

Prurigo Nodularis: Literature Review

Multiple, hard, flesh-to-pink papules, plaques, and nodules, often seen on the extensor surfaces of the limbs, are characteristic of prurigo nodularis, a persistent skin condition. The itchy lesions may strike people of any age. It often occurs in tandem with another condition that causes constant itching, such atopic dermatitis or another dermatosis. The clinical symptoms are the primary indicators. However, there may be numerous instances when lichen simplex chronic us and hypertrophic lichen planus are indistinguishable from a clinical standpoint. Therefore, it is crucial to confirm the diagnosis by dermoscopy and histology. Many other therapy strategies are being used, including those using powerful antipruritics, immunomodulators, and neuromodulators. After a diagnosis has been made, treatment might take a long time, thus patient education and counseling are crucial to ensuring they stick with the plan. A subset of chronic prurigo, prurigo nodularis (PN) manifests as hyperkeratotic, very itchy papules and nodules that are often seen in a symmetrical pattern. PN develops with persistent pruritus in the setting of a wide variety of dermatological, systemic, neurological, or mental disorders. Although the specific pathophysiology of PN is not well understood, chronic scratching may be a primary cause. Topical steroids, capsaicin, calcineurin inhibitors, ultraviolet (UV) treatment, systemic injection of gabapentinoids, -opioid receptor antagonists, antidepressants, and immunosuppressants are the current gold standard in treating PN. Clinical trials are being conducted on cutting-edge therapeutic modalities such blockers of neurokinin-1, opioid, and interleukin-31 receptors.

Diagnosis and Management of Intrahepatic Cholestasis of Pregnancy- A Retrospective Clinical Audit

Introduction: Pregnant women presenting with pruritus, serum bile acid (SBA) ≥10 µmol/L and/or alanine transaminase (ALT) &gt;30 U/l is diagnostic of intrahepatic cholestasis of pregnancy (ICP). A retrospective audit was performed to look at the diagnosis, management and outcomes of ICP patients in University Malaya Medical Center (UMMC). Methods: SBA requests from Obstetrics and Gynaecology Department from 1st January 2016 to 31st December 2020 were extracted from Laboratory Information System (LIS). The medical records (preexisting medical conditions, maternal and perinatal outcomes) of ICP were obtained. Mild and severe ICP were defined based on SBA 10-40µmol/L and SBA &gt;40 µmol/L, respectively. Results: SBA was requested for 202 pregnant women. The prevalence of ICP in our cohort was 0.18% (47 out of 26,697 deliveries). The average gestation at diagnosis was 35 weeks. Both SBA and liver enzymes were elevated in 25 (53.2%) whereas only SBA was elevated in 20 (42.6%) women. In two women, the diagnosis was made based on clinical symptoms and elevated liver enzyme alone. All with ICP had a livebirth and 31.9% were preterm. Severe ICP was noted in eight (17%) and all had cesarean section, whereas, in mild ICP, only 17 (44%) had a caesarean section. In those with normal SBA (n=149) at initial presentation, a repeat SBA was performed only in 12 (8.1%). Postpartum follow-up of ICP patients was observed in only 10 (21.2%). Conclusion: Despite being an uncommon diagnosis in our population, early diagnosis and timely delivery is important to reduce the major perinatal adverse outcomes. In women with persistent pruritus but without the biochemical evidence of ICP at the time of presentation should have repeat SBA and LFT done.

SEVERE PRURITUS AS A PRESENTING SYMPTOM OF HODGKIN'S LYMPHOMA

<h3>Introduction</h3> Pruritus has a broad differential diagnosis. Rarely, this symptom may be the sole manifestation of an underlying malignancy. A patient with 5 years of severe upper body pruritus with no other systemic symptoms was subsequently diagnosed with Hodgkin's lymphoma. <h3>Case Description</h3> A 43-year-old male presented to the allergy-immunology clinic for evaluation of severe pruritus of 3 years' duration; he reported nocturnal worsening awakening him from sleep. The pruritus was refractory to antihistamines but was partially responsive to ice packs. There were no associated constitutional or respiratory symptoms, or lymphadenopathy. CBC with differential and CMP were normal. Omalizumab therapy was administered for 3 months; however, the severe pruritus persisted. Neuropathy work-up by neurology was negative. Dermatology evaluation yielded a diagnosis of folliculitis. Work-up for auto-immune disease by rheumatology was negative. After a total of 5 years of pruritus without identifiable cause, he presented for evaluation of a new-onset supraclavicular mass. Chest CT revealed a large anterior mediastinal mass and a massive conglomerate of lymph nodes. Subsequent biopsy revealed classic Hodgkin's lymphoma. <h3>Discussion</h3> This case underscores that persistent pruritus may be the presenting symptom of malignancy. Pruritus associated with malignancy is classically refractory to antihistamines and may not be accompanied by classic systemic symptoms. While rare, it is important to keep this atypical presentation of malignancy in the differential.

TREATMENT OF DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS) WITH MEPOLIZUMAB

<h3>Introduction</h3> The standard treatment for DRESS involves stopping the culprit drug and often a prolonged course of systemic corticosteroids. Long-term systemic corticosteroids can have major adverse effects. We present a case of DRESS successfully managed with mepolizumab, an interleukin-5-antagonist, to decrease systemic corticosteroids. <h3>Case Description</h3> A 53-year-old male with a history of poorly controlled type 2 diabetes complicated by foot osteomyelitis was treated with vancomycin, ertapenem, and gabapentin. In three weeks, his absolute eosinophil count (AEC) increased to 1100/µL from a baseline of 300/µL. One week later he developed a diffuse morbilliform eruption, facial swelling, AEC of 2200/µL, and acute renal injury. He was diagnosed with DRESS. Vancomycin, ertapenem, and gabapentin were stopped, and he was treated with intravenous methylprednisolone. Vancomycin was presumed to be the likely culprit. By day 7 of hospitalization, his rash and creatinine improved and AEC decreased to 300/µL. He was discharged on oral prednisone 60mg and an adjusted insulin regimen due to elevated blood glucose. Two days post-discharge, his AEC increased to 3700/µL and he had persistent pruritus but improving rash. He was given mepolizumab 100mg and an oral corticosteroid taper. Within a week, AEC was zero. He was given a second dose of mepolizumab 100mg six weeks after the first dose as AEC increased to 900/µL. Three months post-discharge after a 7-week taper of steroids, he has not had recurrence of DRESS, AEC is ≤ 500/µL, and HbA1C remains within goal. <h3>Discussion</h3> Mepolizumab shows promise as a novel and safe steroid-sparing treatment for DRESS.

DELAYED ANAPHYLAXIS TO SHRIMP EXPOSURE: IS THIS A THING, AND WHO IS AT RISK?

<h3>Introduction</h3> Anaphylaxis is a systemic hypersensitivity reaction which is rapid in onset. Delayed anaphylaxis from food ingestion, (ie > 2hrs) is rare. <h3>Case Description</h3> A 17 year old female, previously tolerant to shrimp, experienced a documented delayed anaphylaxis 6 hours following ingestion of shrimp. Shrimp ingestion occurred at 21:30 without incident. The patient felt otherwise well and retired to sleep. At 03:40 the patient awoke to systemic pruritus and full body urticaria with an episode of brief loss of consciousness. She was taken to ER. There the patient experienced nausea, angioedema, and dyspnea. The patient received 0.5 mg IM epinephrine at 06:17 and monitored. At 07:55, 10 mg cetirizine was given to treat persistent pruritus. Discharge was at 10:30 on cetirizine without evidence of a biphasic anaphylaxis. A previous milder reaction to shrimp occurred a few weeks earlier. Skin prick testing (SPT) confirmed allergy House Dust Mite (HDM) (17mm) to D. Farinae and D. Pteronyssinus. Shrimp allergen extract was negative; however, prick-to-prick testing to shrimp was positive to raw shrimp 7mm and cooked shrimp 5mm with 3mm to histamine control. <h3>Discussion</h3> HDM and shrimp share the major muscle muscle allergen tropomyosin. In this case, presentation of shrimp tropomyosin leading to anaphylaxis was delayed, suspected from the digestive process of the meal, in a child previously tolerant to shrimp. This case highlights the need to extend the window of anaphylaxis investigation to 6 hours in patients cross-sensitized to tropomyosin from HDM DF-DP and shrimp ingestion.

S3229 A Case of Cholestatic Drug-Induced Liver Injury After Ashwagandha Root Supplementation

Introduction: Ashwagandha root is an ancient Indian Ayurvedic herbal medicine sometimes referred to as “Indian Winter cherry” or “Indian Ginseng,” that is growing in popularity for its purported benefits of weight loss, muscle building and stamina benefits, and cognition promoting effects. In vitro studies suggest possible benefits of ashwagandha to include muscle growth, exercise stamina, weight loss, hepatocellular carcinoma targeting, and others, but no large scale studies have been done to test for safety or adverse effects. Rare case reports of drug induced liver injury (DILI) related to ashwagandha have been documented. Case Description/Methods: 19-year-old male presented to our hospital with severe pruritus and new onset jaundice after starting Ashwagandha. Two weeks after starting he developed progressive pruritus without any noted rash. Five days after the onset of pruritis he noted jaundice with nausea and dark urine, no abdominal pain. Initial labs showed a total bilirubin 7.6, AP 149, ALT 144 and AST 74. He had imaging including MRI and CT scan which were unremarkable. He was discharged with prn hydroxyzine for itching and told his DILI would resolve with time. A month since discontinuing the ashwagandha supplements his pruritus and jaundice worsened and he arrived to our hospital for evaluation. He was treated with cholestyramine, ursodiol and antihistamines. His bilirubin ultimately nadired at 30. Was also started on low dose naltrexone, and discharged. Returned for short hospital stay with severe pruritis. His t. bili remained similar compared to prior at 29, with normal INR. He was started on low dose rifampin given persistent pruritus, with mild improvement, and ultimately discharged with close follow-up. Discussion: Ashwagandha root is a rare cause of cholestatic liver injury. The Drug Induced Liver Injury Network (DILIN) were able to identify five incidences of drug induced liver injury related to ashwagandha. The clinical course of our patient closely matches the six total cases described in the literature so far. Latency period of 2 weeks to the development of jaundice. He then had a prolonged course of cholestatic liver injury after discontinuing supplements that lasted several months. Ashwagandha-containing herbal medications can result in severe cholestatic liver injury, without the development of chronic DILI or progression to acute liver failure. This case report further re-enforces the importance of careful monitoring and awareness of our patients’ supplemental health products. Table 1. - Bilirubin and symptoms trend Days since Symptom onset 6 days 36 days 42 days 44 days 46 days 49 days 52 days 56 days 67 days Total Bilirubin Level 7.6 25 30 29 31.3 21.2 18 16.6 - Symptoms Jaundice/pruritis Worsening jaundice/pruritis/pale stools Persistent pruritis AMS vs. panic attack, persistent pruritis Mild improvement pruritis - Pruritis improving - Pruritis resolved, visible jaundice improving

The use of metformin in the treatment of Intrahepatic cholestasis of pregnancy

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disease. It is characterized by persistent pruritus, usually occurring after 30 weeks of pregnancy, and by elevated levels of bile acids and transaminases, which decrease over the course of 2-3 weeks postpartum. [1,2]The occurrence of ICP in the mother may be associated with significant complications in the fetus, such as: preterm labor, intrauterine asphyxia, or sudden fetal death. Currently, the treatment of choice is ursodeoxycholic acid (UDCA).[2,6] Recently, it was observed that the administration of metformin in cases not responding to standard therapy improved lipid disorders in pregnant women.&#x0D; &#x0D; The aim of the study: The aim of the study is to present the possibility of using metformin in the treatment of ICP in pregnant women not responding to standard treatment and to present a clinical case..&#x0D; Material and methods: The work is a review of the literature on the management of ICP and the use of metformin in the treatment of lipid metabolism disorders, as well as a brief case report of a patient with intrahepatic cholestasis of pregnancy.&#x0D; Description of the state of knowledge: Metformin is an oral antidiabetic drug belonging to the group of biguanides. However, the latest observations show that metformin also has a beneficial effect on the liver function and on the lipid metabolism in pregnant women. In these patients, the levels of bile acids and liver enzymes decreased after the use of metformin.&#x0D; Summary: The mechanism of action of metformin explaining its beneficial effect on the lipid metabolism in pregnant women with intrahepatic cholestasis is not fully understood.

New and Upcoming Topical Treatments for Atopic Dermatitis: A Review of the Literature.

Atopic dermatitis (AD) is a chronic inflammatory dermatosis with periods of exacerbation and remissions. AD is characterized by intense, persistent pruritus and heterogeneity in clinical symptomatology and severity. Therapeutic goals include the amelioration of cutaneous eruptions, diminishing relapses and eventually the disease burden. To date, topical corticosteroids (TCS) and calcineurin inhibitors (TCI) have yet been deemed the mainstay of topical treatments in AD management. Nevertheless, despite their indisputable efficiency, TCS and TCI are not indicated for continuous long-term use given their safety profile. While research in AD has concentrated predominantly on systemic therapies, more than 30 novel topical compounds are under development. The existing data appear encouraging, with some regimens that are already FDA-approved (ruxolitinib was the most recent in September 2021) and several pharmaceutical pipeline products for mild-to-moderate AD that are in an advanced stage of development, such as tapinarof, difamilast and roflumilast. Larger, long-term studies are still required to evaluate the efficacy and safety of these novel compounds in the long run and weigh their advantages over present treatments. In this review, we aim to provide an overview of the latest knowledge about AD topical treatments, echoing upcoming research trends.