Severe Hypersensitivity Research Articles

Novel Protocol for Rapid Desensitization of Melphalan in a 5-Year-Old Boy Undergoing Conditioning for Hematopoietic Stem Cell Transplantation: A Case Report

Hematopoietic stem cell transplantation is a potentially life-saving therapy under certain conditions. Hypersensitivity reaction to chemotherapeutic drugs may interfere with this treatment. Griscelli syndrome type 2 is a rare autosomal recessive disease characterized by hypopigmentation of skin and hair, causing silver gray hair; this disease may develop a fatal condition called hemophagocytic lymphohistiocytosi. The main curative treatment for hemophagocytic lymphohistiocytosi is hematopoietic stem cell transplantation. Melphalan is an important drug in hematopoietic stem cell transplantation preparation regimen. This drug is only stable for 60 minutes following reconstitution with normal saline. There is a recommended 12- to 20-step desensitization protocol for moderate to severe hypersensitivity reaction to chemotherapeutic drugs. However, due to the short term stability of melphalan, this protocol cannot be employed in desensitization. In this case report, we presented a novel protocol for rapid desensitization of melphalan in a 5-year-old boy with immediate, moderate to severe hypersensitivity reaction, during hematopoietic stem cell transplantation. To obtain 50 mg total melphalan , we prepared solutions of drug in two bags; one with 12.5mg in 35 cc normal saline, and other with 25 mg in 35 cc normal saline. Each solution was infused during 60 minutes by incremental infusion rate, and the total of 50 mg melphalan was successfully infused.

A Survey on Knowledge Gaps in Assessment and Management of Severe Drug Hypersensitivity Reactions: Multicenter Cross-Sectional Study of Australian Health Care Providers.

Severe drug hypersensitivity reactions (DHRs) are often encountered by health care professionals (HCPs). We evaluated knowledge of doctors and pharmacists in the assessment and management of severe DHRs using a structured questionnaire. A cross-sectional study was conducted in 4 metropolitan hospital networks in Melbourne, Australia. A 13-question, scenario-based multiple-choice questionnaire to assess specific knowledge domains in drug hypersensitivity syndrome recognition, causality attribution, cross-reactivity patterns, appropriate diagnostic tests, and therapy was administered to HCPs of various vocation and specialty groups. Data were analyzed according to profession, self-reported experience, and preparedness in managing severe DHRs. Two hundred thirty-eight participants (45.0% senior doctors, 24.4% junior doctors, and 30.7% pharmacists) across a range of subspecialties achieved an overall median score of 7 (IQR, 5-8)-overall 55.6% correct responses to all questions-with senior doctors outperforming junior doctors and pharmacists (P<.001). The best performance by all participants was in DHR syndrome recognition (60.9%), and the poorest was in diagnostics/therapy (52.0%). HCP group and experience level were significantly associated with better performance in the knowledge domains of cross-reactivity and diagnostics/therapy (P = .003 and <.001, respectively), but not in the domains of syndrome recognition and causality attribution (P >.05). Levels of self-reported preparedness in DHR management were not associated with performance rates in any of the knowledge domains. This study demonstrated significant knowledge gaps in the recognition and management of severe drug hypersensitivity reactions. Targeted multidisciplinary education of staff caring for these patients is needed to improve knowledge gaps.

Differential response to biologics in a patient with severe asthma and ABPA: a role for dupilumab?

BackgroundAllergic bronchopulmonary aspergillosis (ABPA) is a severe hypersensitivity reaction to aspergillus species colonizing the airways of patients with asthma or cystic fibrosis. Biologics including anti-IgE and anti-IL5 antibodies have strongly changed the treatment of severe asthmatics and have partly been reported to be effective in the treatment of ABPA. Recently, dupilumab, an anti-IL4-Rα antibody which inhibits signaling by the Th2-cytokines IL4 and IL13, has been approved for the treatment of severe asthma.Case presentationHere, we report the case of a 49-year-old woman with severe asthma and ABPA, who was uncontrolled despite maximum inhalative therapy, anti-IL5-Rα antibody and continuous oral steroid therapy. Moreover, trials of itraconazole as well as omalizumab showed insufficient efficacy. Lung function revealed peripheral obstruction. FeNO and IgE were increased, eosinophils were suppressed under treatment while marked increases had been documented previously. Switching to dupilumab led to a complete resolution of pulmonary symptoms, resolution of exacerbations and complete withdrawal of oral steroids. A drastic improvement in lung function was noted, with an increase in FEV1 of almost 1 l. FeNO was normalized and IgE strongly reduced.ConclusionOur case highlights that a patient may exhibit differential treatment responses to the currently available asthma biologics and suggests switching treatment if outcome is insufficient. A potential role for dupilumab in the treatment of ABPA warrants future studies.

Distribution and polarization of microglia and macrophages at injured sites and the lumbar enlargement after spinal cord injury

Spinal cord injury (SCI) causes loss of locomotor function and chronic neuropathic pain (NeP). Hematogenous macrophages and activated microglia are key monocytic lineage cell types in the response to SCI, and each has M1- and M2-phenotypes. To understand the roles of these cells in neuronal regeneration and chronic NeP after SCI, differences in distribution and phenotypes of activated microglia and infiltrated macrophages after SCI were examined at the injured site and the lumbar enlargement, as a remote region. Chimeric mice were used for differentiating activated microglia from hematogenous macrophages. The prevalences of activated microglia and infiltrating macrophages increased at day 14 after SCI, at the time of most severe pain hypersensitivity, with mainly M1-type hematogenous macrophages at the injured site and M2-type activated microglia at the lumbar enlargement. Peak expression of TNF-α, an M1-induced cytokine, occurred on day 4 post-SCI at the injured site, but not until day 14 at the lumbar enlargement. Expression of IL-4, a M2-induced cytokine, peaked at 4 days after SCI at both sites. These results suggest different roles of activated microglia and hematogenous macrophages, including both phenotypes of each cell, in neuronal regeneration and chronic NeP after SCI at the injured site and lumbar enlargement. The prevalence of the M1 over the M2 phenotype at the injured site until the subacute phase after SCI may be partially responsible for the lack of functional recovery and chronic NeP after SCI. Activation of M2-type microglia at the lumbar enlargement in response to inflammatory cytokines from the injured site might be important in chronic below-level pain. These findings are useful for establishment of a therapeutic target for prevention of motor deterioration and NeP in the time-dependent response to SCI.

SO084SILDENAFIL DRUG IN HEMODIALYSIS PATIENTS WITH PULMONARY HYPERTENSION

Abstract Background and Aims Pulmonary hypertension (PH) is not an uncommon progressive condition in prevalent hemodialysis (HD) patients, associated with high morbidity and mortality. Sildenafil drug has limited studies about the efficacy of the drug and optimal dose among prevalent HD patients with PH. Aim of the study to assess the effects of sildenafil drug on estimated Pulmonary Artery pressure value (ePAP) mmHg via transthoracic Doppler Echocardiography and 6-minute walk test ( 6MWT) among hemodialysis patients with pulmonary hypertension. Method Randomized, double-blind, placebo-controlled clinical trial, from December 2018 to May 2019, involving 60 eligible patients on regular adequate HD with PH, estimated Pulmonary Artery Pressure (ePAP) ≥35 mmHg via Doppler echocardiography. HD patients with mean age 52.6±10.8 year divided randomly into 3 groups: Group 1 (20 patients) received 25 mg sildenafil, group 2 (20 patients) received 50 mg sildenafil and group 3 (20 patients) who received placebo as daily dose treatment for 3 months duration. Every patient in the study was subjected to full history taking and clinical examination. Exclusion Criteria: Current treatment of pulmonary hypertension, patient with evident history of cardiac diseases or chronic pulmonary diseases or systemic autoimmune diseases, portal hypertension, HIV, patients with uncontrolled hypertension or severe anaemia or hypersensitivity to sildenafil, treatment with any drugs that may interact with sildenafil all were excluded from the study. Transthoracic echocardiography was done at the begging of the study and after three months in mid-week non-dialysis day for assessment of the change in ePAP, pulmonary artery pressure calculated using the modified Bernoulli equation, and assessment of right ventricular functions . Exercise capacity assessment by 6MWT to assess the clinical response to the drug, was done for every patient at the start of the study and after 3 months of treatment. Clinically meaningful change estimate for the 6MWT considered as increase more than 30 meters. Results Significant increase in mean of 6 MWT in both group 1,2 received 25 mg,50 mg sildenafil respectively after 3 m duration of treatment versus non-significant change in placebo group as basal 6 MWT was (171 ±45, 214 ±58, 175 ±39) meters in group 1,2 and placebo group respectively (p&amp;gt;0.05). Means 6 MWT post-treatment were (205 ±57, 258 ±59, 182 ±49) meters (P&amp;lt;0.001) in group 1, 2&amp;3 respectively, as post Hoc test results, showed significant increase in 6MWT2 in group 2 in comparison to group 1 and placebo group (P&amp;lt;0.01), as shown in figure (1).There was a significant decrease in e PAP in each group of studied groups after treatment (P&amp;lt;0.01). As mean basal ePAP1 measures were (48 ±9, 43.5 ±16, 48.5 ±12) mmHg in group 1,2,3 respectively (P&amp;gt;0.05).There were no significant differences between the studied groups regarding means of ePAP2 post-treatment were ( 42 ±9, 39 ±15, 44.5±8) mmHg in group 1,2,3 respectively (P&amp;gt;0.05). However, the degree of severity of PH was more improved after treatment duration with sildenafil as in group 1 there were 5 patients downgraded from moderate to mild and 2 patients downgraded from severe to moderate after treatment. In group 2 there were 4 patients downgraded from moderate to mild PH and 2 patients downgraded from severe to moderate PH. In 3rd group (placebo group) only one patient downgraded from moderate to mild PH. There were 4 patients dropouts from the study two of them from group 2 (receiving 50mg) due to sildenafil related side effects appeared through the study. Conclusion This a clinical trial confirmed the efficiency of both 50mg and 25mg sildenafil daily dose in reducing e PAP and improving functional exercise capacity in chronic haemodialysis patients with pulmonary hypertension disease.

Optimization of a rat lumbar IVD degeneration model for low back pain.

IntroductionIntervertebral disc (IVD) degeneration is often associated with low back pain and radiating leg pain. The purpose of this study is to develop a reproducible and standardized preclinical model of painful lumbar IVD degeneration by evaluation of structural and behavioral changes in response to IVD injury with increasing needle sizes. This model can be used to develop new therapies for IVD degeneration.MethodsForty‐five female Sprague Dawley rats underwent anterior lumbar disc needle puncture at levels L4‐5 and L5‐6 under fluoroscopic guidance. Animals were randomly assigned to four different experimental groups: needle sizes of 18 Gauge (G), 21G, 23G, and sham control. To monitor the progression of IVD degeneration and pain, the following methods were employed: μMRI, qRT‐PCR, histology, and biobehavioral analysis.ResultsT1‐ and T2‐weighted μMRI analysis showed a correlation between the degree of IVD degeneration and needle diameter, with the most severe degeneration in the 18G group. mRNA expression of markers for IVD degeneration markers were dysregulated in the 18G and 21G groups, while pro‐nociceptive markers were increased in the 18G group only. Hematoxylin and Eosin (H&E) and Alcian Blue/Picrosirius Red staining confirmed the most pronounced IVD degeneration in the 18G group. Randall‐Selitto and von Frey tests showed increased hindpaw sensitivity in the 18G group.ConclusionOur findings demonstrate that anterior disc injury with an 18G needle creates severe IVD degeneration and mechanical hypersensitivity, while the 21G needle results in moderate degeneration with no increased pain sensitivity. Therefore, needle sizes should be selected depending on the desired phenotype for the pre‐clinical model.

Clinical data for intravenous iron - debunking the hype around hypersensitivity.

BACKGROUNDReluctance to use intravenous (IV) iron for the treatment of iron deficiency continues due to a perceived high risk of severe hypersensitivity reactions (HSRs). Additionally, it has been hypothesized that ‘dextran‐derived’ IV iron products (e.g., ferumoxytol [FER] and ferric derisomaltose/iron isomaltoside 1000 [FDI]) have a higher risk of severe HSRs than ‘non‐dextran‐derived’ products (e.g., ferric carboxymaltose [FCM] and iron sucrose [IS]). In the present analysis, HSR data from head‐to‐head randomized controlled trials (RCTs) with IV iron products were evaluated to determine if differences in safety signals are present among these IV iron formulations.STUDY DESIGN AND METHODSReported serious or moderate‐to‐severe HSR incidence data from five RCTs (FIRM; FERWON‐NEPHRO/‐IDA; PHOSPHARE‐IDA04/‐IDA05) were used to calculate risk differences with 95% confidence intervals (CIs) for FER, FCM, FDI, and IS. The rates and risk differences for these HSRs were compared.RESULTSThe analysis included data for 5247 patients: FER (n = 997), FCM (n = 1117), FDI (n = 2133) and IS (n = 1000). Overall rates of serious or moderate to severe HSRs were low (0.2%‐1.7%). The risk differences (95% CIs) showed small differences between the IV iron formulations: FER versus FCM, −0.1 (−0.8 to 0.6); FDI versus IS, 0.1 (−0.3 to 0.5); FDI versus FCM, −0.9 (−3.7 to 1.9).CONCLUSIONRCT evidence confirms a low risk of serious or moderate to severe HSRs with newer IV iron formulations and no significant differences among existing commercially available products. Thus, RCT data show that the supposed classification of dextran‐derived versus non‐dextran‐derived IV iron products has no clinical relevance.

Alternative anti-CD20 antibody versus desensitization for lymphoma patients with drug hypersensitivity reactions requiring discontinuation of rituximab, obinutuzumab, or ofatumumab.

8062 Background: Immunotherapy with anti CD20 is often associated with mild easily manageable infusion reactions. In rare cases, patients experience severe drug hypersensitivity reactions (DHR) serum sickness or anaphylaxis. These in turn may lead to discontinuation of the drug. In our experience, switching to a different anti-CD20 agent is a feasible alternative to discontinuation or desensitization protocols. Methods: From our pharmacology database we identified all the patients that received rituximab and/or obinutuzumab, and/or ofatumumab, and/or all the patients who received a flat dose of less than 50 mL of the same drugs and were followed at our institution. From the medical record, we identified all the cases where the anti-CD20 antibody was changed due to allergy, serum sickness or other types of DHR, and all those who received minimal doses of anti-CD20 in the context of a desensitization protocol. DHRs were evaluated either by an allergist, or by retrospective review following the World Allergy Organization guidelines. Our primary comparison, was to assess the proportion of pts able to completed planned infusion of abs using either approach (Fisher’s exact Test). Results: Among 343 patients receiving at least two different anti-CD20 antibodies or a flat dose of &lt; 50 mL, we identified 44 patients experiencing severe DHRs needing intervention. At the time of the reaction, 16 (36%) received the anti-CD20 as single agent, 24 (54%) in combination with chemotherapy, 4 (9%) in combination with ibrutinib or lenalidomide. In 9 (20%) patients the reaction was defined as anaphylactoid (8 rituximab; 1 obinutuzumab) and in 8 (18%) patients, all receiving rituximab, as serum sickness. Episodes of DHR were addressed with either desensitization (n = 29) or change of anti-CD20 agent (n = 25), 9 patients received both of these approaches, one patient switched anti-CD20 antibodies twice. Overall, 21 desensitizations were successful (72.4%), 8 failed; 23 changes of anti-CD20 were successful (92%) and 2 failed (p = 0.09). Conclusions: In patients with DHR use of an alternative anti-CD20 antibody is safe and is an alternative or complementary approach to anti-CD20 desensitization.

Use of an angioplasty wire in transseptal puncture: A new application of an old technique

ObjectiveWe wondered if a modification of the conventional transseptal puncture technique performed with an angioplasty wire could be useful in patients with contrast hypersensitivity or allergy-like reactions. MethodsThis study comprised our initial experience in 22 patients with atrial fibrillation who were scheduled for an electrophysiology study (EPS) and pulmonary vein ablation and who had a contraindication for iodinated contrast administration. ResultsOf the 22 patients, 16 were men and ages ranged from 27 to 74 years (mean 56 years). Overall successful transseptal access was achieved in all 22. A control echocardiogram was performed in all patients. There were no complications in any case and no significant differences were found from the conventional transseptal puncture technique regarding procedure or fluoroscopy time. ConclusionsA modification of the conventional transseptal puncture technique performed with fluoroscopy and EPS catheters for anatomical reference and an angioplasty wire is an option in cases with severe contrast hypersensitivity.

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients

BackgroundCongenital fibrinogen deficiency is an ultra‐rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder. MethodsHemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA®, Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four‐point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined. ResultsTwenty‐five afibrinogenemia patients were treated with HFC: 24 for on‐demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92‐0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95‐0.999). Mean ± standard deviation (SD) increase in MCF was 5.8 ± 2.5 mm one hour after the first HFC infusion (mean ± SD dose, 61.88 ± 11.73 mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80 mg/kg [34.09‐225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82‐1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies. ConclusionsHuman fibrinogen concentrate was efficacious for on‐demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia.

Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: the FERWON-NEPHRO randomized, open-label, comparative trial

BackgroundThe optimal intravenous (IV) iron would allow safe correction of iron deficiency at a single infusion over a short time. The FERWON-NEPHRO trial evaluated the safety and efficacy of iron isomaltoside 1000/ferric derisomaltose (IIM) in patients with non-dialysis-dependent chronic kidney disease and iron deficiency anaemia.MethodsIn this randomized, open-label and multi-centre trial conducted in the USA, patients were randomized 2:1 to a single dose of 1000 mg IIM or iron sucrose (IS) administered as 200 mg IV injections up to five times within a 2-week period. The co-primary endpoints were serious or severe hypersensitivity reactions and change in haemoglobin (Hb) from baseline to Week 8. Secondary endpoints included incidence of composite cardiovascular adverse events (AEs).ResultsA total of 1538 patients were enrolled (mean estimated glomerular filtration rate 35.5 mL/min/1.73 m2). The co-primary safety objective was met based on no significant difference in the incidence of serious or severe hypersensitivity reactions in the IIM and IS groups [0.3% versus 0%; risk difference: 0.29% (95% confidence interval: –0.19; 0.77; P > 0.05)]. Incidence of composite cardiovascular AEs was significantly lower in the IIM versus IS group (4.1% versus 6.9%; P = 0.025). Compared with IS, IIM led to a more pronounced increase in Hb during the first 4 weeks (P ≤ 0.021), and change in Hb to Week 8 showed non-inferiority, confirming that the co-primary efficacy objective was met.ConclusionsCompared with multiple doses of IS, a single dose of IIM induced a non-inferior 8-week haematological response, comparably low rates of hypersensitivity reactions, and a significantly lower incidence of composite cardiovascular AEs.

Undressing drug reactions, one cell at a time

Single-cell transcriptomic analysis allowed successful treatment of a patient with refractory severe drug-induced hypersensitivity syndrome.

Therapeutic Effects of Mesenchymal Stem Cells on a Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Model.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are the most severe cutaneous drug hypersensitivity reactions, which are unpredictable adverse drug reactions. SJS/TEN is associated with significant mortality and morbidity; however, effective treatment is difficult. Mesenchymal stem cells (MSCs) are well-known for their anti-inflammatory and tissue regeneration properties. The purpose of the present study was to verify whether MSCs could be applied for the treatment of SJS/TEN. We developed an SJS/TEN mouse model using peripheral blood mononuclear cells from a lamotrigine-induced SJS patient. MSCs were injected into the model to verify the treatment effect. In SJS model mice treated with MSCs, ocular damage rarely occurred, and apoptosis rate was significantly lower. We demonstrated a therapeutic effect of MSCs on SJS/TEN, with these cells presenting a potential novel therapy for the management of this disorder.

Clinical value of in vitro tests for the management of severe drug hypersensitivity reactions.

Drug hypersensitivity reactions (DHRs) occasionally present with severe cutaneous adverse reactions (SCARs) which result in a high risk of morbidity and mortality. Although SCARs are rare, the occurrence could lead to a significant increase in healthcare and economic burden, especially when more than one possible culprit drug is implicated. Therefore, the accurate identification of the culprit drug(s) is important for correct labeling and subsequent patient education and avoidance. To date, clinical evaluation using causality assessment has limitations because the assessment may be inaccurate due to the overlapping timelines when multiple drugs are initiated/continued. Moreover, drug provocation tests (DPTs) which is the gold standard in diagnosis, are contraindicated, and in vivo skin tests may also be associated with risks of triggering SCAR. The European Network for Drug Allergy recommended that in vitro tests, if available, should be performed before any in vivo tests. Basophil activation tests and lymphocyte transformation tests, could serve as reliable in vitro tests for both immediate and delayed-type DHR. Many academic medical centers with affiliated laboratory services offer these tests in the diagnostic evaluation of SCARs in clinical practice. This not only complements identification of the culprit drug(s), but may also be used to test for potentially non cross-reactive alternatives, hence avoiding DPTs. In this review, we summarize the roles of in vitro tests in identifying the culprit drug(s) in SCARs, issues with utilization and interpretation of test results, and our experience in clinical practice.

Tolerability to paracetamol and preferential COX-2 inhibitors in patients with cross-reactive nonsteroidal anti-inflammatory drugs hypersensitivity.

BackgroundAcetylsalicylic acid/aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used drugs that may cause hypersensitivity reactions in a substantial proportion of patients. Physicians ought to be aware of these situations.ObjectiveWe aimed to present the clinical characteristics and rates of tolerability to cyclooxygenase (COX)-2 inhibitor analgesics in patients who had admitted due to multiple cross-reactive type of NSAID hypersensitivity.MethodsThe files of the patients who had admitted with multiple NSAIDs-induced symptoms were investigated retrospectively. Age, sex, underlying diseases, clinical manifestation, skin test results, and drug provocation test results were analyzed.ResultsIn 105 patients with multiple cross-reactive type of NSAID hypersensitivity, we found the rate of cross-reactivity to any of the relatively safe alternatives including paracetamol, meloxicam, and nimesulide to be 16.1%. The rate of cross-reactivity to these relatively safe drugs was significantly higher in patients with a history of anaphylaxis induced by NSAID intake (p = 0.006).ConclusionThe diagnosis of COX-1-mediated multiple NSAID hypersensitivity can be often established with a detailed history. Although rare, severe hypersensitivity reactions may be observed in these patients. Undesired situations for both patients and physicians may be avoided by testing relatively safe paracetamol and COX-2 inhibitors in experienced centers.

Oral manifestations of herbal medicine induced Steven Johnson syndrome in 3 Nigerian paediatric patients: case report

Steven-Johnson syndrome (SJS) is a rare medical emergency that is characterized by widespread skin and mucosal lesions. Oral mucosal involvement is seen in 90% of SJS and it is often widespread and confluent. In the majority of the cases, the symptoms are associated with an adverse drug reaction, usually to non-steroidal anti-inflammatory drugs, sulfonamides, anti-epileptics, or antibiotics. Recently, SJS associated with herbal medicine has been reported. This paper aims to report 3 cases of SJS with marked oral manifestations, following the use of local herbal medicine, diagnosed in a children´s hospital in Nigeria within a year. Three children aged 1.5, 9 and 10 years presented in our emergency unit with features of SJS, history of the use of local herbal medicine to cure an ailment was elicited in all cases before admission into our hospital. All the cases presented with cutaneous exfoliating exanthema and bullous eruptions with oral mucosa appearing as painful crusted erythematous lesions. One of the 3 cases, a male patient, presented clinically with septicaemia complicated with anaemia as well as nasal involvement. Discontinuation of herbal medicine in all cases resulted in a relief of symptoms. A multidisciplinary approach of management was instituted with resultant total recovery of patients. This case report addresses the fact that severe hypersensitivity reactions can occur with the use of herbal medicine. Emphasis should be on active vigilance in the use of herbal medicine.

Oxaliplatin induced laryngospasm: a case series

Oxaliplatin is a third-generation platinum derivative used as a first-line agent in the treatment of colorectal carcinoma, biliary tract cancer and gastric cancers and can be used as a neoadjuvant/adjuvant in these cancers. The dose limiting toxicity is peripheral neuropathy, others include hypersensitivity reactions, haematological toxicity and pulmonary fibrosis. Hypersensitivity reactions can extend from milder reactions like urticaria, rash to severe symptoms like hypotension and laryngospasm. The laryngospasm due to oxaliplatin is reported to be reversible with corticosteroids, antihistamines and oxygen. This case series suggest that oxaliplatin has a propensity to cause severe hypersensitivity reaction presenting as laryngospasm not with a single dose but with subsequent doses of oxaliplatin. Prompt symptomatic treatment with corticosteroids leads to reversal of symptoms and improvement in the condition of the patient.

An Update on the Management of Severe Cutaneous Drug Hypersensitivity Reactions.

Severe cutaneous drug hypersensitivity reactions involve of different mechanisms , some of which are life-threatening, such as Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, generalized bullous fixed drug eruptions, serum sickness and serum sickness-like reaction and drug-induced vasculitis. These reactions may have substantial morbidity and mortality. In the past years, successive studies have provided new evidence regarding the pathogenesis of some of these severe reactions and revealed that underlying mechanisms are highly variable. Since these reactions have unique presentations and distinct pathomechanisms, the treatment methods and response rates might be different among various entities. Although supportive and local therapies are sufficient in some of these reactions, targeted immunosuppressive treatments and even mechanistic therapies such as plasmapheresis may be required in severe ones. However, there is still insufficient evidence to support the best treatment options for these patients since number of patients and large-scale studies are limited. In this review, conventional and new treatment options for severe cutaneous drug hypersensitivity reactions are presented in detail in order to provide the contemporary approaches to lessen the morbidity and mortality relevant to these severe iatrogenic diseases.

Clinical Phenotypes of Severe Cutaneous Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions are clinically heterogenous ranging from mild to severe. Most drug hypersensitivity reactions are accompanied by cutaneous manifestations. Fever, mucous membrane involvement, large blisters, facial oedema, pustulosis and visceral involvement are clinical features that lead to suspicion of severe adverse drug reactions. Severe cutaneous adverse drug reactions (SCARs) include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis. Serum sickness like reactions, drug induced vasculitis and generalized bullous fixed drug eruptions are less severe clinical entities. SCARs are uncommon but associated with significant morbidity and mortality. Physician should be aware of specific red flags and danger signs to immediately identify these reactions. Immediate drug withdrawal is mandatory. Early diagnosis and appropriate treatment significantly affect the prognosis of the disease. The purpose of our review is to discuss clinical phenotypes of severe cutaneous drug hypersensitivity reactions.

Drug-Induced liver Injury Associated with Severe Cutaneous Hypersensitivity Reactions: A Complex Entity in Need of a Multidisciplinary Approach.

Idiosyncratic drug-induced liver injury (DILI) occasionally occurs in the setting of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). This strengthens the proposed immunologic mechanism associated with this adverse reaction. DRESS exhibits the most common association with DILI. SCARs have a wide spectrum of heterogeneous clinical presentations and severity, and genetic predisposition has been identified. In the context of SCARs, DILI present a different clinical picture, ranging from mild injury to acute liver failure. Elucidating the role of DILI in the clinical presentation and outcome of SCARs represents a challenge due to limited information from published studies and the lack of consensus on definitions. The cholestatic and mixed pattern of liver damage typically predominates in the case of DILI associated with SCARs, which is different from DILI without SCARs where hepatocellular is the most common injury pattern. Only a few drugs have been associated with both DILI and SCARs. Is this article, the criteria used for DILI recognition among SCARS have been revised and discussed, along with the drugs most commonly involved in these syndromes as well as the outcome, prognostic factors and the need for a multidisciplinary approach to improve the management of DILI in the context of SCARs.