Type Hypersensitivity Reaction Research Articles

Drug hypersensitivity in drug-resistant tuberculosis

ObjectiveTo evaluate drug resıstant tuberculosis patients who developed drug hypersensitivity to antituberculosis drug. MethodsThis was a retrospective study. The primary aim of the study is to determine the demographic and clinical characteristics of patients who develop drug hypersensitivity in drug resistant tuberculosis patients. The secondary aim of the study is to examine the treatment results. Demographic features, tuberculosis diagnostic indicator, clinical signs of developing hypersensitivity reaction, reaction time, and treatment were evaluated. ResultsA total of 25 patients were included in the study. The prevalence of hypersensitivity in drug resistance patients was 11.9%. Twelve (48%) of the cases were women. Mean age (mean ± SD) was 37.24 ± 14.44 years; early type hypersensitivity reaction in 13 (52%). Three patients were isoniazid resistant; 19 patients were multidrug-resistant (MDR); 2 patients were pre-extensive drug resistant (Pre-XDR), 1 patient was extensive drug resistance (XDR) tuberculosis. The most common skin findings were maculopapular eruption and urticaria. But also we had seen ısole angıodema, urtıcarıa and angıoedema, erythema multıforme, lıchenoıd drug eruptıon and drug rash with eosinophilia and systemic symptoms. In patients who developed a hypersensitivity reaction, the responsible agent was identified in 14 cases in total. Among the drugs, pyrazinamide, ethambutol, moxifloxacin, amikacin, para amino salicylic, prothionamide, and cycloserine are the responsible agents. When evaluated in terms of treatment results, 15 (60%) patients successfully completed the treatment. ConclusionOur study is the first study in the literature that evaluated the drug hypersensitivity in drug resıstance tuberculosis patients. Drug hypersensitivity that develops with tuberculosis treatment may lead to discontinuation or change in treatment. İt can cause treatment failure, drug resistance, relapse, and even death. In resistant tuberculosis, the already existing resistance pattern may become more difficult to treat. Success can be achieved with the right management in these patients who have few treatment options, more drug side effects, and high treatment failure rates. The established regimen should be curative and prevent recurrence.

Immunomodulatory Activity of the Aqueous Extract of the pith of Citrus limon L. (Rutaceae) Using Cyclophosphamide Induced Myelosuppression

The genus Citrus species have been widely used in the relief of arthritic pain in traditional medicine. Citrus limon pith was one of the constituents of herbal decoctions taking daily for prevention against Coronavirus disease during covid -19 era. This study investigated the immunomodulatory activity of the aqueous extract of the pith of C. limon using cyclophosphamide-induced myelosuppression and delayed type hypersensitivity reaction in Wistar rats. Thirty-six rats were divided into six groups of six animals each. Three groups served as the control while the remaining three groups were given 150, 300, 600 mg/kg of extract respectively via oral route for 13 days. Groups II to VI were administered cyclophosphamide 30 mg/kg i.p on day 11, 12, and 13. On the 14th day, blood samples were collected for haematological parameters analysis. Delayed type hypersensitivity reaction was carried out using 24 animals divided into four groups of six animals each. Phytochemical screening revealed the presence of triterpenoids, flavonoids, and carbohydrates. LD50 was found to be greater than 3000 mg/kg. C. limon extract on cyclophosphamide-induced myelosuppression showed a statistically significant (P<0.05) increase in the white blood cells (WBC), platelets and lymphocytes counts at all extract doses. In the delayed type of hypersensitivity reaction, percentage increase in inflammation was 24.3%, 31.5% and 43% at extract doses of 150, 300 and 600 mg/kg. The findings of this study have shown that the aqueous extract of the pith of C. limon possessed immunostimulatory activity.

Worldwide Prevalence of Antibiotic-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Antibiotics are an important risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most severe types of drug hypersensitivity reaction with a mortality rate up to 50%. To our knowledge, no global systematic review has described antibiotic-associated SJS/TEN. To evaluate the prevalence of antibiotics associated with SJS/TEN worldwide. The MEDLINE and Embase databases were searched for experimental and observational studies that described SJS/TEN risks since database inception to February 22, 2022. Included studies adequately described SJS/TEN origins and specified the antibiotics associated with SJS/TEN. Two reviewers (E.Y.L. and C.K.) independently selected the studies, extracted the data, and assessed the risk of bias. A meta-analysis using a random-effects model was performed in the studies that described patient-level associations. Subgroup analyses were performed to explore the heterogeneity. The risk of bias was assessed using the Joanna Briggs Institute checklist, and the certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Prevalence of antibiotic-associated SJS/TEN was presented as pooled proportions with 95% CIs. Among the 64 studies included in the systematic review, there were 38 studies that described patient-level associations; the meta-analysis included these 38 studies with 2917 patients to determine the prevalence of single antibiotics associated with SJS/TEN. The pooled proportion of antibiotics associated with SJS/TEN was 28% (95% CI, 24%-33%), with moderate certainty of evidence. Among antibiotic-associated SJS/TEN, the sulfonamide class was associated with 32% (95% CI, 22%-44%) of cases, followed by penicillins (22%; 95% CI, 17%-28%), cephalosporins (11%; 95% CI, 6%-17%), fluoroquinolones (4%; 95% CI, 1%-7%), and macrolides (2%; 95% CI, 1%-5%). There was a statistically significant heterogeneity in the meta-analysis, which could be partially explained in the subgroup analysis by continents. The overall risk of bias was low using the Joanna Briggs Institute checklist for case series. In this systematic review and meta-analysis of all case series, antibiotics were associated with more than one-quarter of SJS/TEN cases described worldwide, and sulfonamide antibiotics remained the most important association. These findings highlight the importance of antibiotic stewardship, clinician education and awareness, and weighing the risk-benefit assessment of antibiotic choice and duration.

Immunostimulatory and Antimicrobial Claims of Super-7 Herbal Mixture (SHM) and Odogwu Cleanser Herbal Mixture (OCHM) Commercially Available in Enugu State, Nigeria

The continuous increase in resistance associated with conventional drugs is gradually shifting focus to herbal remedies as an alternative globally. This study was designed to investigate the immunostimulatory and antimicrobial claims of Super-7 herbal mixture (SHM) and Odogwu cleanser herbal mixture (OCHM) commercially available in Enugu State, Nigeria. Immunomodulatory properties of the products on the Delayed Type Hypersensitivity reaction (DTHr), the Primary and Secondary humoral response and the <i>in vivo</i> leucocyte mobilization were evaluated using a total of one hundred and forty-six (146) Swiss albino rats. The spectrum of antimicrobial activity was evaluated by agar well diffusion method using eight (8) selected microorganisms. The LD₅₀ of both products was greater than 100% ml/kg body weight. OCHM elicited significant (p<0.05) dose dependent increase in total leucocyte and neutrophil counts compared to Levamisole (2.5mg/kg) and the untreated group. A 100% ml/kg SHM (78.07%) also exhibited significantly (p<0.05) higher oedema inhibitory potentials compared to the standard drug (levamisole = 65.78%). Samples of SHM demonstrated dose dependent antibacterial activities against <i>B. subtilis </i>and <i>S. typhi</i>, while only exhibiting antifungal activity against<i> C. albicans </i>(IZD = 9.0±0.0 mm). OCHM was observed to inhibit <i>E. coli, S. typhi, S. aureus, B. subtilis, S. typhi </i>and the fungus<i> C. albicans</i>. An average bioload of 2.8 x 10⁴±1.0 CFU/ml which was higher than the average count (2.8 x 10⁴±1.0 CFU/ml) obtained for OCHM. Conclusively, this study showed that samples of SHM and OCHM exhibited significant immunostimulatory and antimicrobial properties, but also recorded the presence of microbial contaminants.

Fixed drug eruptions- A Case Report

Fixed drug eruption (FDE) is typically establishes as round or oval, sharply delineated erythematous or edematous plaques. Essentially it is a drug-induced cutaneous reaction that happens at the similar site with each exposure to a specific medication. A extensive spectrum of drugs can occasionally give rise to numerous contrary orofacial manifestations, predominantly dry mouth, taste disturbances, oral mucosal ulceration, and/or gingival swelling. However, the etiology of the FDE is still unknown, it is a delayed type of hypersensitivity reaction that occurs as lesions. By limiting the use of the term allergic to those reactions that are immunologically arbitrated or can reasonably be reputed to be, approximations are that drug allergy may account for 6–10% of these adverse reactions.

An asymmetric morbilliform eruption in an adult male

An asymmetric morbilliform eruption in an adult male

Hypersensitivity to Biological Treatments in Juvenile Idiopathic Arthritis: How Should It Be Managed?

Juvenile idiopathic arthritis (JIA) is one of the most frequent diseases in the practice of pediatric rheumatology. JIA treatments have been modified and improved with the use of biological drugs along with technological innovations. However, different types of hypersensitivity reactions to biological drugs have also been reported. Anaphylaxis and infusion reactions occurring during the intravenous infusion require a critical approach in the acute period. On the other hand, the detection of drug-related late-type reactions and the development of antibodies to the agent highlight the need for an understanding of the drug-induced etiology to prevent the patient from continuing the treatment with the culprit drug. The chronic disease process, concomitant immune dysregulation, and multiple drug use may result in these hypersensitivity reactions. In this review, the hypersensitivity reactions to the biological treatments used in patients with juvenile idiopathic arthritis and the management of these conditions are discussed.

Evaluation of Anti-Inflammatory and Immunomodulatory Activities of Ayapoonaga Chenduram, Seenthil Choornam and their Combination in Wistar Rats

Ayapoonaga chendooram (APNC) and Seenthilchoornam (SC) are two polyherbal Siddha formulations that traditionally have been used as a folklore medicine to treat rheumatism, orchitis, bronchitis, asthma, tuberculosis (TB), and cough. In the present study, an attempt has been made to demonstrate the antiinflammatory and immunomodulatory activities of individual APNC and SC and also in their combination (APNC+SC). The acute anti-inflammatory effect of APNC, SC and their combination was evaluated in carrageenan-induced hind paw edema in wistar rats. Diclofenac sodium was used as reference drug for comparison. The immunomodulatory activity was evaluated in rats by studying the hemagglutination antibody (HA) titer, delayed type hypersensitivity (DTH) reactions and the Ig E levels. The cyclophosphamide is used as an immunosuppressant.Diclofenac Sodium (50mg/kg) significantly inhibited the carrageenan-induced hind paw edema, indicating its strong anti-inflammatory activity. APNC (65 mg/kg b.w.p.o) at 2nd hour and APNC+SC (13+200 mg/kg b.w.) at 3rd hour had shown moderate inhibition of paw edema, indicating their mild-moderate anti-inflammatory activity but statistically, no significant difference was observed (p&gt;0.05). Oral administration of APNC, SC, and APNC + SC for 21 days increases the left paw volume at 1st hour and 2nd hour resulting in hypersensitivity reaction in rats. The agglutination (dilution factor 1:200) was visually observed in APNC 130mg/kg b.w. (moderate agglutination) and in APNC + SC (high agglutination) results in humoral immunity. Mild increased levels of Ig E were observed in APNC (30 mg/kg b.w.), SC (200 mg/kg b.w.) and in APNC + SC (65+1000 mg/kg b.w.). Under the conditions of the present study, single oral administration of APNC, SC and their combination has shown mild anti-inflammatory activity against carrageenan induced paw edema in experimental rats. The immunity has been stimulated by APNC (13mg/kg b.w.) and SC (2000mg/kg b.w.).

DESENSITIZATION TO EXTENSIVELY HYDROLYZED FORMULA IN INFANT WITH COW'S MILK PROTEIN ALLERGY

<h3>Introduction</h3> Cow's Milk Protein Allergy (CMPA) is typically managed by avoidance. Limited evidence of oral desensitization for delayed-type hypersensitivity (DTH) reactions exist in the drug literature. We present a case of desensitization with hydrolyzed formula in an infant with CMPA. <h3>Case Description</h3> Allergy was consulted by NICU for a 5-month-old male infant with formula intolerance. Infant was born at term with gastroschisis and short bowel syndrome, with need for small bowel resection and gastrostomy tube placement. Maternal breast milk was insufficient to meet the infant's needs. Transition to formula was complicated by the development of bloody stools with cow's milk and hydrolyzed cow's milk formula consistent with CMPA. Introduction of elemental formulas was limited by the development of delayed onset vomiting and diarrhea felt to be consistent with Food Protein Induced Enterocolitis Syndrome (FPIES) to cornstarch. Donor breast milk was not available for outpatient use. Oral desensitization to Alimentum RTF, a cornstarch free hydrolyzed formula was successful, and the patient was discharged on this formula. <h3>Discussion</h3> Both FPIES and CMPA are predominantly delayed type hypersensitivity reactions. While desensitization approaches initially developed for management of IgE mediated drug allergy, similar approaches have been successful in management of both IgE mediated food allergy and delayed type hypersensitivity reactions to drugs. We report a potential option for oral desensitization in a patient with CMPA for whom typical therapy was contraindicated.

FACIAL CONTACT DERMATITIS CAUSED BY PENCIL ERASERS

<h3>Introduction</h3> Allergic contact dermatitis is a delayed type hypersensitivity reaction that can occur in previously sensitized individuals. While contact dermatitis prevalence in kids may be as high as 20-25%, the exact prevalence is unknown. Patch testing should be performed in patients concern for allergic contact dermatitis to determine the cause and prevent future reactions. <h3>Case Description</h3> A 16-year-old female with a history of eczema presents with a 2-year history of an intermittent itchy and flaky rash over her forehead and face. She initially was treated for seborrheic dermatitis without improvement. She denies changes in cosmetics or soaps. So far, fluocinolone oil and Vaseline seem to help the most, but nothing has prevented the rash from coming back. She was referred to allergy and T.R.U.E. test panel including 36 allergens was placed. At 96 hours, patch test showed 1+ reaction to mercapto mix. Upon discovering this sensitivity, patient recalls that when her rash started, she and her friends were using pencil erasers as earring backs. The erasers had irritated her ears, so she removed them, and the rash on her forehead coincidentally improved prior to patch testing. <h3>Discussion</h3> This case highlights the importance of patch testing even without a known exposure as an allergen must be identified and avoided to prevent recurrence of allergic contact dermatitis. Mercapto mix compounds are found in natural rubber, butyl rubber, nitrile, or neoprene products including gloves, athletic shoes, rubber-bands, erasers, and headphones. Allergy to mercapto mix is rare with most studies reporting <1% prevalence.

Delayed type hypersensitivity reactions to various allergens may differently model inflammatory skin diseases.

Treatment of inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, is undergoing transformative changes, highlighting the need to develop experimental models of skin inflammation in humans to predict treatment responses. We topically or intradermally administered four common sensitizers (dust mite (DM), diphencyprone (DPCP), nickel (Ni), and purified protein derivative (PPD)) to the backs of 40 healthy patients and the skin hypersensitivity response was biopsied and evaluated using immunohistochemistry, RNA-seq, and RT-PCR. All agents induced strong increases in cellular infiltrates (T-cells and dendritic cells) as compared to untreated skin (p < .05), with variable T helper polarization. Overall, DPCP induced the strongest immune responses across all pathways, including innate immunity (IL-1α, IL-8), Th1 (IFNγ, CXCL10), Th2 (IL-5, CCL11), and Th17 (CAMP/LL37) products, as well as the highest regulatory tone (FOXP3, IL-34, IL-37) (FDR <0.01). Nickel induced Th17 (IL-17A), Th1 (CXCL10) and Th2 (IL-4R) immune responses to a lesser extent than DPCP (p < .05). PPD induced predominantly Th1 (IFNγ, CXCL10, STAT1) and Th17 inflammation (IL-17A) (p < .05). DM induced modulation ofTh2 (IL-13, CCL17, CCL18), Th22 (IL-22), and Th17/Th22 (S100A7/9/12) pathways (p < .05). Barrier defects that characterize both AD and psoriasis were best modeled by DPCP and Ni, followed by PPD, including downregulation of terminal differentiation (FLG, FLG2, LOR, LCEs), tight junction (CLDN1/CLDN8), and lipid metabolism (FA2H, FABP7)-related markers. Our data imply that DPCP induced the strongest immune response across all pathways, and barrier defects characteristic of AD and psoriasis.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - III - Cow's milk allergens and mechanisms triggering immune activation

BackgroundThe immunopathogenesis of cow's milk protein allergy (CMPA) is based on different mechanisms related to immune recognition of protein epitopes, which are affected by industrial processing. PurposeThe purpose of this WAO DRACMA paper is to: (i) give a comprehensive overview of milk protein allergens, (ii) to review their immunogenicity and allergenicity in the context of industrial processing, and (iii) to review the milk-related immune mechanisms triggering IgE-mediated immediate type hypersensitivity reactions, mixed reactions and non-IgE mediated hypersensitivities. ResultsThe main cow’s milk allergens – α-lactalbumin, β-lactoglobulin, serum albumin, caseins, bovine serum albumins, and others – may determine allergic reactions through a range of mechanisms. All marketed milk and milk products have undergone industrial processing that involves heating, filtration, and defatting. Milk processing results in structural changes of immunomodulatory proteins, leads to a loss of lipophilic compounds in the matrix, and hence to a higher allergenicity of industrially processed milk products. Thereby, the tolerogenic capacity of raw farm milk, associated with the whey proteins α-lactalbumin and β-lactoglobulin and their lipophilic ligands, is lost. ConclusionThe spectrum of immunopathogenic mechanisms underlying cow's milk allergy (CMA) is wide. Unprocessed, fresh cow's milk, like human breast milk, contains various tolerogenic factors that are impaired by industrial processing. Further studies focusing on the immunological consequences of milk processing are warranted to understand on a molecular basis to what extent processing procedures make single milk compounds into allergens.

Surgical antibiotic prophylaxis: current issues of beta-lactams use

The most common prescriptions for antibiotics in surgery are in the area of surgical antibiotic prophylaxis. According to clinical guidelines, beta-lactams, in particular, first and second generation cephalosporins, and in some cases aminopenicillins, should be used as drugs of choice. These drugs are leaders with regards to assessing the contribution of drugs of various pharmacological groups to the formation of drug allergies. However, real clinical practice reveals fewer cases of true allergy to beta-lactams compared to self-reported data by patients. Both underestimation and overestimation of the risks of hypersensitivity reactions with cephalosporins and penicillins is critical to the ultimate outcome of patient management. This review includes the main characteristics of drugs used for antibiotic prophylaxis in surgery and highlights topical issues of beta-lactam allergy and management of patients with various types of hypersensitivity reactions.

Sis-25, a meroditerpenoid derivative with a cyclobutane scaffold, inhibits activated T cell proliferation by targeting GSK3β in vitro and in vivo

A series of novel scopariusicide derivatives were designed and synthesized starting from the main diterpenoid from the aerial parts of Isodon scoparius. Sis-25 was the most effective compound among them. The potential mechanism(s) of its immunosuppressive activity in vitro, as well as its effects on delayed type hypersensitivity (DTH) reaction and imiquimod-induced dermatitis in vivo were investigated in this study. Sis-25 inhibited anti-CD3/anti-CD28 mAbs, PHA or alloantigen-induced T cell proliferation without obvious cytotoxicity. Sis-25 was a highly selective inhibitor of GSK3-β and inhibited the mTOR/p70S6K pathway but not the PI3K/Akt, p38 MAPK/ERK 1/2 and JAK3/STAT5 pathways. Furthermore, Sis-25 significantly inhibited IFN-γ, IL-6 and IL-17 expression but not IL-10 expression in activated T cells. Finally, Sis-25 treatment mitigated the DNFB-induced DTH reaction and ameliorated imiquimod-induced dermatitis. In summary, Sis-25 exerted significant immunosuppressive activity by targeting GSK3β in vitro and in vivo. Sis-25 may guide the design of new drugs for more effective and safer treatments of autoimmune diseases and provide new insight into developing utilizations of Isodon scoparius.

Pharmacological Role of Capparis decidua (Forssk.) Edgew in Preventing Cyclophosphamide-induced Myelosuppression and Modulating Innate and Adaptive Immune Response.

BackgroundCapparis decidua (Forssk.) Edgew is reported to be practiced in the traditional system of medicine for the management of various immunological pathologies.PurposeThe current study was designed to evaluate the modulatory effects of C decidua on different immune responses.Research DesignC decidua was extracted in 70% methanol and the crude extract (Cd.Cr) was analyzed by FTIR and GCMS. In vivo models were employed to assess the actions of Cd.Cr on cyclophosphamide-induced myelosuppression, innate and adaptive immune responses.ResultsGCMS and FTIR analysis indicated the presence of flavonoids, phenols, terpenoids and lipids. Cd.Cr evoked a significant and dose-dependent increase in percent neutrophil adhesion (15.97 ± .81, 27.47 ± .79 and 38.35 ± 1.08) and the phagocytic index (3.1 ± .04, 3.96 ± .06 and 5.28 ± .13) at the doses of 30, 100 and 300 mg/kg. Cd.Cr also potentiated haemagglutinating antibody titre, immunoglobulins and cytokines (interferon-γ and interleukin-2) production for 4 weeks, after exposure to sheep erythrocytes, and delayed type hypersensitivity reaction significantly (P < .05). The restoration of hematological profile and antioxidant enzyme activities, by Cd.Cr, indicated the prevention of cyclophosphamide-induced myelosuppression and oxidative stress.ConclusionsThe findings of this study suggest that C decidua holds immunomodulatory activity by thus possesses therapeutic potential for the management of immunological diseases.

Cutaneous Adverse Drug Reactions (CADRs)-Statistical Analysis of the Causal Relationship between the Drug, Comorbidities, Cofactors, and the Cutaneous Reaction-A Single-Centered Study.

Cutaneous adverse drug reactions (CADRs) are among the most common types of drug hypersensitivity reactions. The purpose of this study was to evaluate the clinical spectrum of CADRs and to determine the causal relationship between drugs, comorbidities, cofactors or concomitant symptoms, and cutaneous reactions. A retrospective hospital-based study was carried out over a period of 10 years at the Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology at the University of Warmia and Mazury in Olsztyn to record various CADRs, comorbidities, cofactors, and the suspected drug in hospitalized patients. The data were subjected to statistical analysis. CADRs were diagnosed in a total of 140 patients, 32.14% of whom were men and 67.86% of whom were women. The mean age was 66.33 years. The most commonly suspected drugs were Allopurinol 12.86%, Amoxicillin with clavulanic acid 10%, Amoxicillin 9.29%, Paracetamol 6.43%, Metronidazole 5%, and Carbamazepine 5%. Attention should be paid to the possibility of using a substitute for a suspected drug if CADRs arise, or discontinuing a drug that is unjustifiably overused. The results of the present study should also prompt research into a potential treatment that could be implemented concurrently with a drug that has a high predisposition to cause CADRs.

A novel oral paclitaxel and HM10381 (oraxel)-treated metastatic breast cancer: A phase I study (KX-ORAX-CN-007).

1104 Background: This phase I study assessed the pharmacokinetics, safety, antitumor activity of oral paclitaxel and HM10381 (Oraxel) in patients with metastatic breast cancer. Methods: Oraxol (oral paclitaxel 205 mg/m2 plus HM30181A 15 mg) daily for 3 consecutive days weekly for up to 16 weeks was administered to patients. The primary objective endpoint was pharmacokinetic analysis. The secondary endpoint were objective response rate (ORR) and safety. For pharmacokinetic analysis, timed blood samples were collected. Results: Twenty-four female patients were enrolled from Apr 2019 to Aug 2019. The median age was 53 years (range: 35 to 70 years). The mean lines and median line of treatment were 2.5 and 2, respectively. Previous breast cancer treatments included chemotherapy in 23 (96%) patients, hormonal therapy in 20 (83%) patients. Prior taxanes therapy was reported in 20 (83%) patients. There were 15 patients in efficacy dataset. The best ORR (Investigator) was PR in 40%, SD in 53%, and PD in 7%. The best overall response rate (ICRRC) was PR in 36%, SD in 57%, and PD in 7% of patients. There were no hypersensitivity-type reactions. Adverse events of interest neutropenia, neurotoxicity, and diarrhea were reported as 20 (83%)，7 (29%) and 11 (46%), retrospectively. A total of 15 (63%) patients experienced Grade ≥3 TEAEs, including neutrophil count decreased in 11 (46%) patients, WBC count decreased in 8 (33%) patients. Treatment related SAE was reported in 1 (4.17%) patient experienced febrile neutropenia, pneumonia, and septic shock. The PK data indicated that the efficacy response is not associated with oral paclitaxel exposure parameters AUC or Cmax. Conclusions: The study showed that Oraxol as novel oral chemotherapy agent shows promising antitumor activity in patients with metastatic breast cancer, manageable toxicity, and no hypersensitivity-type reactions. Clinical trial information: NCT04993040.

Role of Vitamin D &amp; Immunoglobulins E in patients of Seasonal Allergic Conjunctivitis

Introduction: Allergic conjunctivitis is in fact a bunch of diseases affecting the visual surface and is usually related with type1 hypersensitivity reactions. Two acute disorders, seasonal allergic conjunctivitis and perennial allergic conjunctivitis, exist, as do 3 chronic illnesses, vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis. Seasonal allergic conjunctivitis is related with seasonal hypersensitivities that ordinarily happen amid the spring and summer months, and in some cases amid the fall. Exposure to dust, grass and other airborne allergens causes seasonal allergic conjunctivitis. Low levels of vitamin D somewhat related to allergic disorders. This study show a relationship between Serum vitamin D and Immunoglobulin’s E in patients of seasonal allergic conjunctivitis Objective: To evaluate serum vitamin D and serum total immunoglobulin E levels in patients with seasonal allergic conjunctivitis (SAC). Material and Methods Study design: quantitative cross sectional Duration: Six months i.e. 1st September 2021 to 28th February 2022 Data Collection procedure: A cross sectional study was conducted on 100 patients. The study was conducted in Holy Family Hospital Rawalpindi. Ethical approval was taken from ethical committee. An educated consent was taken from the participants. 60 patients in this study presented with seasonal allergic conjunctivitis and 40 healthy normal persons were included. Serum vitamin D and serum total IgE levels were calculated. Results: The average age of the participant in this study was in between 30-50 years of age. In SAC group 40 were males and 20 females. Group two healthy normal consist of 25 males and 15 females. There is a significant decrease of vitamin D level in patients who were diagnosed seasonal allergic conjunctivitis and IgE levels were high when compared to normal healthy group Conclusion: In conclusion, we demonstrated lower plasma vitamin D levels in patients with SAC compared with the control bunch. To conclude a certain association between vitamin D status and allergic conjunctivitis, both multicenter larger case arrangement and further studies examining the impacts of vitamin D supplementation ought to be performed in the long run. Keywords: Vitamin D, seasonal allergic conjunctivitis, IgE, Allergy

P040 A Tale of Three Rashes

Abstract Background/Aims Skin rashes are commonly an external marker of internal disease and are often useful in the diagnosis of a variety of systemic diseases managed by rheumatologists. I present a case of a lady who developed three discrete episodes of different skin rashes over the course of two months that represented three different underlying pathologies but were nevertheless intrinsically linked. Methods In September 2019, a 42-year-old lady returned from holiday in Thailand with mosquito bites on her arms and legs. She presented to another hospital with fevers, myalgias and severe arthralgias. Her CRP was raised at 128mg/l and she was given intravenous cefuroxime for 3 days followed by oral co-amoxiclav for presumed infected mosquito bites. Shortly after starting the intravenous cefuroxime, she developed a second rash on her torso, arms and legs. She was seen a week after discharge from hospital with ongoing severe arthralgias although her CRP had settled and was prescribed celecoxib 200mg twice daily. In October 2019, she developed pedal oedema and a non-blanching, purpuric rash across her shins bilaterally and presented to out-patient clinic. Results In clinic, she complained of widespread large and small joint polyarthralgias but there was no synovitis on examination. An anti-streptolysin O titer (ASOT) was negative but IgM and IgG antibodies to Chikungunya were positive. Her CRP was raised at 22 mg/l and a urinalysis was negative for blood and protein. A diagnosis of Chikungunya fever transmitted by mosquito bites was made followed by a maculopapular drug eruption secondary to cefuroxime and subsequent Henoch Schonlein Purpura (HSP) secondary to recent infection. Her symptoms were treated with a reducing course of prednisolone 40mg once a day and her rashes and arthralgias settled over the course of 2 months. Her urinalysis remained negative for blood and protein throughout. Conclusion Chikungunya virus is an arthropod-borne virus that is transmitted by mosquito bites. It can cause fevers, severe polyarthralgias (70-100% of cases) and polyarthritis (44-63% of cases). Chronic arthritis has been reported in 25% to 75% of cases. Chikungunya fever is endemic in parts of Western Africa but is also common in many regions of Asia. Maculopapular drug eruptions are the most common type of drug hypersensitivity reaction and are characterized by a generalised eruption of erythematous macules and/or papules after initiating drug therapy. Maculopapular drug eruptions are common side effects of cephalosporins. HSP is a small vessel leucocytoclastic vasculitis characterized by palpable purpura. The purpuric rash is typically symmetrical and located primarily in pressure dependent areas such as the lower extremities. Many cases of HSP are preceded by an upper respiratory tract infection such as Streptococcus but many other infectious agents have been implicated as possible triggers. Disclosure M.A. Lee: None.

Ginger Rhizome Rot Caused by the Enterobacter cloacae in Tangshan, China.

Ginger (Zingiber officinale ROSC.) is an important economic crop in China, especially the rhizome tissue has a high medicinal value. In July 2019, the symptom of ginger rhizome rot appeared in Tangshan city of Hebei Province, with incidence rates of 15%. The diseased part of ginger rhizome became soft and presented light brown maceration. Serious internal all erosion, only have epidermis, gray-white juice overflowed the epidermis, and with foul smell. The surface of ginger rhizome was disinfected with 1% NaOCl, and colonies were isolated and purified on nutrient agar (NA) solid medium by streak plate method. Eight isolates were obtained from 15 diseased tissue samples. Further morphological, physiological and biochemical identification of the pure cultured bacteria were carried out. Two isolates of bacteria were picked for further analysis. The bacteria were gram-negative bacilli, which were milky white and round protuberances on NA solid medium. Physiological and biochemical test results showed that isolates were facultatively anaerobic, gelatin liquefaction; negative for indole, methyl red, hydrogen sulfide production and the Voges-Prauskauer test (V-P); positive for D-glucose, sucrose, sorbitol, inositol, mannitol and citrate utilization. A typical hypersensitive reaction was induced on 12-week-old tobacco (Nicotiana benthamiana) leaves, which were inoculated by injecting suspensions of the isolated strain (108 CFU/mL) at 25℃ after 24-h. These characteristics were consistent with Enterobacter spp. To further assess the identity of the species, the genomic DNA was extracted from one bacterium（SDXJ1）. The partial 16S rRNA gene and specific rpoB and gyrB genes were amplified and sequenced with primers 27F/1492R, CM7/CM31b and UP1f/UP2r (Brady et al. 2013, Mollet et al. 1997, Lane 1991). The obtained 16S and rpoB sequences (GenBank accession MK937637, MZ911902 and MZ911901) of the isolate showed 99.33%, 99.21% and 99.57% identity to the corresponding sequences of Enterobacter cloacae in GenBank (CP055458, AP022228 and AP022519). Maximum likelihood analysis was performed, and the phylogenetic tree clustered with E. cloacae (MEGAX, Bootstrap n=1000). The pathogenicity of the isolates was tested on ginger plants and rhizomes tissue. The bacterial suspensions (108 CFU/mL) of two isolates were injected into the basal stem and rhizomes center of 6 healthy ginger seedlings respectively, and control groups were treated with sterile water. The inoculated plants were kept in a moist chamber (28°C, 16-h light and 8-h dark period) and ginger rhizomes were placed in the incubator (30°C, 16-h light and 8-h dark period). Seven days after inoculation, the ginger tubers showed symptoms of decay, and 20 to 25 days later, the ginger plant leaves browned and died. The pathogenicity test was repeated 4 times and all controls were healthy. The pathogens of symptomatic plants and ginger rhizomes were studied. They were identified as E. cloacae by physiological, biochemical and molecular biological methods, fulfilling Koch's hypothesis. This is the first report of the ginger rhizome rot caused by the Enterobacter cloacae in Tangshan, China. The research results are of great significance for the prevention and control of the disease. Our laboratory has reported that Citrobacter freundii can cause Ginger Rot. (Zhao et al. 2021) Whether the two strains infect alone or compound in the field still needs to be further explored.