Treatment Of Idiopathic Thrombocytopenic Purpura Research Articles

Perinatal outcomes in pregnant women with ITP: a single tertiary center experience.

In this study, we aimed to compare the maternal and neonatal outcomes in pregnant women diagnosed with idiopathic thrombocytopenic purpura (ITP) in our clinic between different platelet groups. This study was designed retrospectively. A total of 62 pregnant women with ITP were included in the study. Demographic and clinical data for all cases were evaluated. Perinatal outcomes were evaluated according to platelet counts. The median age of the patients participating in the study was 27, and their ages ranged from 21 to 44. ITP was diagnosed before pregnancy in 32.3 % (n=20) of the patients and during pregnancy in 67.7 % (n=42). The average platelet counts of the patients during the first trimester and birth were 104.8/μL (15-168) and 84/μL (16-235), respectively. The average platelet count of newborns is 242/μL. The most common (74.2 %) ITP treatment method is the combination of steroids and IVIG. The platelet count of 80.6 % of newborns is above 151/μL. There was no statistical difference between the results of both mothers and fetuses when the groups were categorized according to maternal platelet levels. In this study, no difference was observed in maternal and neonatal morbidity and mortality rates, despite the different platelet counts of patients with ITP. The cooperation of the hematology, gynecology, obstetrics, and neonatology departments is responsible for this.

Ways to Improve the Results of Treatment of Idiopathic Thrombocytopenic Purpura in Adults

Ways to Improve the Results of Treatment of Idiopathic Thrombocytopenic Purpura in Adults

Modified osteochondral autograft transplantation for steroid-induced osteonecrosis of femoral head in idiopathic thrombocytopenic purpura: a case report and literature

Osteochondral autograft transplantation (OAT) has been commonly applied in the knee and ankle while the technique has not yet been a popularity in the femoral head. In this article, we present a 28-year-old female patient, who has a history of 1-year-use of glucocorticoid in the treatment of idiopathic thrombocytopenic purpura, with steroid-induced osteonecrosis of the femoral head (SONFH). She underwent surgical hip dislocation, osteochondroplasty, OAT, and internal fixation. Her Harris Hip Score improved from 64 to 82 in 36 months to follow-up. The case is valuable considering that a single, instead of several, 1.5 cm autograft was harvested from the non-bearing part of the same femoral head. This modification dispensed with the need of surgery for harvesting autograft from knee or ankle and reduced the structural vulnerability brought by the multihole donor part of the femoral head.

Fostamatinib: a novel treatment for idiopathic thrombocytopenic purpura

Fostamatinib: a novel treatment for idiopathic thrombocytopenic purpura

Glucocorticosteroid-induced complications in patients with idiopathic thrombocytopenic purpura

Glucocorticosteroids (GCS) are the first-line treatment for idiopathic thrombocytopenic purpura (ITP). Despite their high efficacy in patients with newly diagnosed ITP, an adequate level of platelets remains after GCS withdrawal in only less than 20 % of patients. Additionally, GCS use is associated with an increased risk of different adverse reactions, including serious and life-threatening ones. Thrombopoietin receptor agonists represent a relatively new class of drugs for treating ITP as a second-line therapy. This paper reviews the risks of GCS pharmacotherapy, as well as the evidence supporting the use of thrombopoietin receptor agonists as both first-line and second-line treatment for patients with ITP.

Idiopathic Thrombocytopenic Purpura: Current Limitations and Management.

Idiopathic thrombocytopenic purpura (ITP), also known as immune thrombocytopenia, is a blood disorder characterized by a reduction in the number of platelets. A reduction in the number of platelets beyond the normal levels leads to several consequences. A severe reduction in blood platelet levels leads to a rash of purple spots on the skin, joints, etc.due to leakage in the small blood vessels, easy bruising, bleeding gums, intestinal bleeding, and hemorrhage. Suppose a case of ITPresolves in fewer than six months. In that case, it is an acute case of ITP. Still, if a case settles in more than six months, it is a case of ITP. The cause of a reduced platelet count can be increased peripheral destruction or impaired production; this is termed an autoimmune condition in which the body's immune system attacks platelets thinking it to be a foreign antigen. ITP in children occurs commonly following a previous viral attack. Even though evaluating patients' reports is useful for understanding and guiding the treatment, these estimates might not be regularly evaluated in clinical settings. First-line drugs in the treatment of ITP are corticosteroids, and long-term use of these drugs has several side effects, such as excessive increase in weight, mental health disturbances, and sleep disturbances; additional therapies to treat hemorrhage are usually momentary. As a result, it is essential to recognize the flaws in current procedures and adopt innovative measures for the management and minimization of difficulties.

A phase 1 study of the SYK inhibitor fostamatinib and weekly paclitaxel for recurrent platinum-resistant ovarian cancer.

5574 Background: Response to chemotherapy in patients (pts) with recurrent platinum-resistant ovarian cancer (PROC) is generally < 15%. Spleen tyrosine kinase (SYK) is overexpressed in PROC and is a key mediator of paclitaxel resistance in ovarian cancer cells. Fostamatinib (Fos), an orally available inhibitor of SYK, is currently FDA approved for the treatment of idiopathic thrombocytopenic purpura. The active form of Fos (R406) was shown to synergistically enhance taxane-mediated cytotoxicity in preclinical ovarian cancer models. This phase 1 study aimed to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of Fos when combined with standard weekly paclitaxel (wPac) for pts with PROC. Methods: Pts with PROC, defined as progression ≤6 months of last platinum, were eligible. A modified toxicity probability interval (mTPI) dose escalation design was used to determine the MTD/RP2D and response was assessed using RECISTv1.1 criteria. All pts received paclitaxel (wPac) 80mg/m2 intravenously on Days 1, 8, and 15, of a 28-day cycle. Fos was administered orally twice a day (BID) on a continuous schedule. Three dose levels (DL) were planned: DL1 - 100mg, DL2 - 150mg, and DL3 - 200mg. MTD was determined based on cycle 1 dose-limiting toxicities (DLTs) and responses were assessed every 2 cycles. A dose expansion cohort to further assess adverse events (AEs) and tolerability was performed. Results: 27 eligible pts, median age 62 years (range 35-79 years) with high-grade serous (n = 18), clear cell (n = 4), carcinosarcoma (n = 3), or other (n = 2) histology were treated at 3 centers. Twelve pts were treated in the dose escalation cohort (DL1 = 6, DL2 = 3, DL3 = 3). Common AEs at least possibly attributed to Fos, wPac, or both included diarrhea (70%), fatigue (52%), anemia (44%), neutropenia (33%), nausea (33%), hypertension (30%), and dysgeusia (30%). Treatment-emergent grade 3-4 AEs were neutropenia (37%), anemia (26%), and thromboembolic event (22%). During DL1, updated toxicity management guidelines not consistent with the original protocol were released and 2 of the 3 pts treated prior to the amendment were not considered evaluable for DLT. Thus 3 more pts were enrolled to DL1 after the amendment. Of the 10 pts evaluable for DLT in dose escalation, no DLTs were reported on any of the 3 DLs (DL1 = 4, DL2 = 3, DL3 = 3). DL3 was selected for dose expansion. One of 15 pts in the dose expansion cohort had a DLT (neutropenia) and one patient had a grade 5 infection. Of 18 pts treated at DL3, 7 (39%) had partial or complete response (95% CI: 17.3, 64.3%). Overall, 27 patients received a median of 3 cycles (range 0-10). Analysis of pharmacokinetic and correlative molecular studies of target expression are ongoing. Conclusions: The RP2D of Fos will be 200 mg orally BID when combined with wPac. AE profile of the combination was as expected and the combination demonstrated promising efficacy in pts with recurrent PROC. Clinical trial information: NCT03246074 .

Prognosis and risk factors of chronicity in childhood idiopathic thrombocytopenic purpura: a single-center experience

Objective: In previous studies, chronicity risk factors for idiopathic thrombocytopenic purpura (ITP) are unclear. This study aimed to evaluate the outcome of children with ITP and determine the chronicity risk factors.
 
 Methods: This study retrospectively examined the demographics, laboratories, outcome, and chronicity risk factors among sixty children with ITP and obtained the data from the computer system. We analyzed demographics, treatment, and laboratory risk factors for chronic ITP by IBM SPSS and used binary logistic regression analysis.
 
 Results: Of 60 children with ITP, 32 (53.3%) had acute, 25 (41.7%) had chronic, and 3 (5%) had persistent ITP. Demographics, laboratories (age

Combination of immunotherapy and Kampo medicines for a patient with autoimmune autonomic ganglionopathy

Combination of immunotherapy and Kampo medicines for a patient with autoimmune autonomic ganglionopathy

A Review of Clinical Studies for Chinese Medicine Treatment of Idiopathic Thrombocytopenic Purpura Using the CNKI Database

Objectives: The aim of this study was to analyze the latest clinical studies on Korean medicine treatment of idiopathic thrombocytopenic purpura (ITP) in the Chinese National Knowledge Infrastructure (CNKI) database.Methods: We searched the last 6 years of clinical studies discussing Oriental medicine-based treatments for ITP in the CNKI database. A meta-analysis of 13 RCTs was performed by synthesizing the outcomes, including the measured platelet count and total effective rate. The quality of the studies was assessed using Cochrane’s risk of bias (RoB) tool. RevMan 5.4.1 software was used for data analysis.Results: Of the 15 selected studies, 1 was a non-randomized controlled trial (nRCT), 2 were case series, and 12 were randomized controlled trials (RCTs). Treatments in all studies included oral herbal medicine. The most frequently used herbal decoction was the Liangxue Jiedu prescription (凉血解毒方), and the most commonly used herb was Agrimonia pilosa (仙鶴草), Astragali Radix (黃芪), Fossilia Glycyrrhizae Radix et Rhizoma (甘草), and Rehmannia glutinosa Liboschitz ex Steudel (地黃). The meta-analysis showed significantly better improvement in platelet counts and total effective rate for ITP in the treatment group than in the control group.Conclusion: Treatment with herbal medicine was effective in treating ITP. However, the significance of this conclusion is somewhat limited due to the low quality of the available studies. Multifaceted and scientifically designed clinical studies are required to develop treatments for ITP based on Korean medicine. The results of this study could be used as basic data for further ITP studies.

Endothelial nitric oxide synthase Glu298Asp gene polymorphism in the cases of idiopathic thrombocytopenic purpura.

BackgroundNitric oxide (NO) can induce apoptosis in megakaryocytes. Stimulatory function of NO on platelet production may be important in the pathophysiology of idiopathic thrombocytopenic purpura (ITP). NO is produced by three isoforms of NO synthase (NOS). The endothelial nitric oxide synthase (eNOS) isoform has been detected in platelets. Polymorphism of the eNOS gene, which supplies NO synthesis, changes the functions of this enzyme. In this study, the role of eNOS Glu298Asp gene polymorphism in etiopathogenesis, its course, and treatment of ITP was investigated.MethodsSixty-six patients [51 newly diagnosed ITP (ND-ITP), 15 chronic ITP (CH-ITP), and 60 healthy controls (HC)] were enrolled in this study.ResultsIn all patients, the frequency of the GT genotype was 48.5%. The frequency of the GG genotype was determined to be 40.9% and the TT genotype was 10.6%. The most common allele in all patients was the G allele. eNOS Glu298Asp gene polymorphism might be a risk factor in the etiopathogenesis of ITP. Patients with the GG genotype were thought to have a high intention for CH-ITP. Patients with the GG genotype responded effectively to medical treatment using IVIG therapy. The presence of the G allele was observed to have a positive effect on the medical treatment of patients with CH-ITP, whereas the T allele exhibited a negative effect.ConclusionIn the present study, a significant correlation was found between ITP and eNOS Glu298Asp gene polymorphism. This correlation suggested that eNOS Glu298Asp gene polymorphism might be a risk factor in the ethiopathogenesis of ITP.

The Effectiveness of The Treatment of Idiopathic Thrombocytopenic Purpura with Modern Drugs

Abstract: This article discusses the effectiveness of treatment of idiopathic thrombocytopenic purpura with modern drugs and its new methods. Primary immune thrombocytopenia, commonly referred to as idiopathic thrombocytopenic purpura (ITP), is an acquired autoimmune disease characterized by isolated thrombocytopenia. Keywords: treatment, idiopathic thrombocytopenic purpura, modern drugs, new methods, clinical fetures, disease

NMR-Based Metabolomics Identify Metabolic Change in Spleen of Idiopathic Thrombocytopenic Purpura Patients.

Idiopathic thrombocytopenic purpura (ITP) is a common hematological disease and the abnormal platelet destruction in the spleen is a critical pathological mechanism for ITP. However, the metabolomic change in the spleen caused by ITP is still unclear. In the present study, the metabolomic information of 18 ITP and 20 normal spleen samples were detected by using 1H high-resolution magic angle spinning NMR spectroscopy (1H MAS NMR). Compared with normal spleen, the concentrations of acetate, alanine, glutamine, glycerol, isoleucine, lysine, valine, phenylalanine, leucine, and methanol in ITP spleen tissue were elevated and 3-hydroxybutyric acid, ascorbate, asparagine, ethanol, glycogen, low-density lipoprotein, malonate, myo-inositol, glycerophosphocholine, pyroglutamate, and taurine were decreased. Amino acids metabolic pathways, such as branched-chain amino acids pathway, were identified as the main involved pathways based on enrichment analysis. The decrease in taurine level in the spleen was the most obvious metabolic signature involving ITP with high sensitivity and specificity to distinguish the spleen of ITP from the normal (CI: 0.825–0.982). Notably, the level of taurine in the spleen was negatively correlated with the efficacy of splenectomy (r = 0.622, p = 0.006). Collectively, the data from our study revealed previously unknown ITP-related metabolomic changes in the spleen and found a potential diagnostic and efficacy-predictive biomarker for ITP treatment.

Therapy of Adults Affected By Idiopathic Thrombocytopenic Purpura with 3 Cycles Pulses of High-Dose Dexamethasone (HD-DXM): A Prospective Randomized Clinical Trial

Introduction : Idiopathic thrombocytopenic purpura(ITP) is an autoimmune disorder characterized by platelet destruction leading to decreased platelet count and an increased risk of bleeding. The first line treatment of ITP is still corticosteroid therapy. Prednisone (PDN) is the standard corticosteroid therapy in ITP practical guideline. Recent studies suggested pulsed high-dose dexamethasone (HD-DXM) given at a dose 40 mg/day to a 4-day course treatment as an alternative corticosteroid to reduce the duration and the adverse effect of corticosteroid therapy. In this randomized controlled clinical trial our aim was to compare the efficacy and the relapse free survival time of 3 therapy cycles of HD-DXM versus conventional treatment with PDN for untreated adult patients with ITP.Method : This was a monocenter, randomized, controlled , clinical trial approved by ethics committee on medical research in Isfahan University of Medical Sciences(IUMS) and also registered in clinical trial.gov(NCT02914054). The eligible patients for this study were aged 18 or older of both genders with newly diagnosed primary ITP according to the international working group (IWG) guideline .Eligible patients were randomly assigned to either enroll conventional Prednisone therapy or pulses of high dose Dexamethasone (HD-DXM) treatment. In HD-DXM arm, DXM was administered intravenously at 40 mg in 500cc normal saline (0.9% saline) during 1 hour for consecutive 4 days and then stopped. This cycle was repeated in 14 days interval to receive 3 cycles of treatment. Patients in PDN arm received PDN orally at 1.0 mg/kg body weight daily for 4 consecutive weeks. After achieving responses the medication tapered gradually to less than 15mg daily or terminated over 4-6 weeks aimed at maintaining platelet count over 30 ×109/L. Cell blood count was performed every week in the first month of treatment and then each month to 1 one year or until loss of response. Baseline parameters such as platelet count were compared between two arms by Fisher exact test. A logistic regression model was used to evaluate the correlation between response and baseline parameters. All patients entered to study provided written informed consent in accordance with the Declaration of Helsinki.Results : 36 cases were given high dose Dexamethasone another 36 cases were given prednisone as control group. The following results were obtained: (1) at the end of the 3rd cycle, the overall response rate was higher in the HD-DXM group than in the prednisone group; (2) the relapse rate of the HD-DXM group was lower than the control group after 12 months discontinuation;(3) Adverse effect of corticosteroid therapy was less than the control group (p value<0.05).Conclusion : Treatment with 3 cycles of HD-DXM pulses is an effective method for untreated ITP patients with less adverse effect of corticosteroid in comparison with conventional prednisone therapy. DisclosuresNo relevant conflicts of interest to declare.

Pharmacokinetics of Eltrombopag in Healthy Chinese Subjects and Effect of Sex and Genetic Polymorphism on its Pharmacokinetic and Pharmacodynamic Variability.

Eltrombopag is the first oral, small-molecule, non-peptide thrombopoietin receptor agonist for the treatment of idiopathic thrombocytopenic purpura. This study investigated the pharmacokinetics of eltrombopag in healthy Chinese subjects and evaluated the effect of sex and genetic polymorphisms on its variability. Forty-eight healthy subjects were administered a single dose of eltrombopag (25mg). Plasma concentrations of eltrombopag were determined using a validated liquid chromatography-tandem mass spectrometry method, and platelet counts were determined by blood tests. CYP1A2 rs762551, CYP2C8*3 rs10509681, CYP2C8*3 rs11572080, UGT1A1 rs887829, UGT1A3 rs3806596, and BCRP rs2231142 polymorphisms were genotyped by Sanger sequencing. A back-propagation artificial neural network (BP-ANN) model was constructed to predict pharmacokinetics based on physiological factors and genetic polymorphism data. Compared with male subjects, female subjects who received a single 25-mg dose of eltrombopag exhibited a significantly increased mean maximum plasma concentration (Cmax) and significantly decreased apparent clearance. Additionally, CYP1A2 rs762551 C>A single nucleotide polymorphism influenced distribution and elimination. C-allele carriers exhibited 30% higher systemic exposure and 20% lower apparent clearance compared with homozygous A-allele carriers. Mean percentage increases in platelet counts from baseline to Day 5 were 9.38% and 17.06% in male and female subjects, respectively. The BP-ANN model had a high goodness-of-fit index and good coherence between predicted and measured concentrations (R=0.98979). Sex and CYP1A2 rs762551 C>A were associated with the pharmacokinetic variability of eltrombopag in healthy Chinese subjects. Females exhibited a better platelet-elevating effect compared with males administered the same dosage. The developed BP-ANN model based on physiological factors and genetic polymorphism data could be promising for applications in pharmacokinetic studies. https://www.Chinadrugtrials.org.cn CTR20190898.

Treatment of ITP

Helicobacter eradication therapy is the first-line therapy for patients with Helicobacter positive idiopathic thrombocytopenic purpura (ITP) in Japan. Indications for treatement in patients with Helicobacter negative, or post-Helicobacter eradicated ITP are platelet counts less than 20×106/l or severe bleeding. The first-line treatment for these patients is corticosteroids. Thrombopoietin receptor agonists (TPO-RAs), rituximab, and splenectomy are second-line treatments for patients with corticosteroid refractory ITP. The choice of a second-line treatment should be determined in consideration of the advantages and disadvantages of each treatment. TPO-RAs are effective in over 80% of patients; however, long-term administration is usually needed. Rituximab treatment ends in four weeks, but its durable response rate is relatively low. The durable response rate of splenectomy is relatively high; however, it causes long-term complications. Effective treatments for patients with ITP who are refractory to second-line treatments have not been established. Some novel drugs are under clinical trials, and a treatment strategy for these patients is expected to be established.

Rituximab Induced Interstitial Lung Disease Diagnosis, Treatment Outcome, and Risk’s Factor, a Place for Transbronchial Pulmonary Cryobiopsy

Rituximab (RTX) is a mouse/human chimeric anti-CD20 IgG1 monoclonal antibody, approved in late 1998 by the FDA. Effectively used as a single agent or combined with a chemotherapy regimen to treat lymphoma, RTX is a significant step forward in the arsenal treatment of idiopathic thrombocytopenic purpura, systemic lupus erythematous, rheumatoid arthritis, and autoimmune hemolytic anemia. Side effects of RTX are commonly seen during the first infusion in up to 50% of patients and include fever, chills, and rigors. These side effects are generally transient and related to the tumor burden, probably due to a greater degree of complement activation and proinflammatory cytokine release. Severe lung toxicity like cryptogenic organizing pneumonia, pneumonitis, and interstitial lung diseases are infrequent, with most of the knowledge coming from case reports.

A simple HPLC assay for determining eltrombopag concentration in human serum.

Eltrombopag, a thrombopoietin receptor agonist, is used for the treatment of idiopathic thrombocytopenic purpura (ITP) and aplastic anemia. We developed a HPLC assay for the determination of serum eltrombopag concentration in ITP patients. An aliquot of a serum sample spiked with diclofenac as the internal standard (IS) was treated with acetonitrile to precipitate the proteins. Eltrombopag and the IS were separated on an octadecylsilyl silica-gel column using a mobile phase consisting of 10 mM 1-pentanesulfonic acid sodium salt, acetonitrile, and acetic acid. The detection wavelength was set at 265 nm. The calibration curve was linear at the concentration range of 0.15-12.5 μg/mL for eltrombopag (r = 0.9987). The recoveries of eltrombopag from the serum samples were greater than 95.9% with coefficients of variation (CVs) being less than 2.8%. The CVs for the intra-day and inter-day assays were 1.9-11.8% and 1.0-11.8%, respectively. This assay method could be used for therapeutic drug monitoring of eltrombopag in ITP patients.

Thrombopoietin Receptor Agonists: Clinical Use and Evaluation of Treatment Efficacy

Idiopathic thrombocytopenic purpura (ITP), or primary immune thrombocytopenia, is an orphan disease associated with thrombocytopenia. One of the most recent and promising approaches to ITP treatment is the use of thrombopoietin receptor agonists (TPO-RAs). The scope of TPO-RA use is expanding rapidly, which stimulates the development of both innovator and generic (or biosimilar) medicines. The aim of the paper was to assess TPO-RA role in ITP treatment, methodological approaches to TPO-RA development, and feasibility of using the platelet count as a pharmacodynamic marker in bioequivalence studies of peptide TPO-RAs in healthy volunteers. Clinical development of new medicines for the treatment of thrombocytopenia includes comparative, parallel-group trials lasting about a year. The standard approach to bioequivalence studies, which is based on the results of comparative pharmacokinetic studies, can be used in marketing authorisation applications for generic non-peptide TPO agonists, while peptide TPO agonists have to comply with specific requirements for biosimilar products. The orphan status of ITP does not affect the development strategy and study design, but it limits the number of patients that could be included into the study. In the absence of valid surrogate biomarkers of efficacy, demonstration of comparable clinical efficacy of the biosimilar and reference drug is usually required in a randomised, parallel, preferably double-blind comparative study. On the other hand, clinical comparability of the biosimilar and reference drug can also be demonstrated in comparative pharmacodynamic studies, if the selected biomarker is a well-established and valid surrogate marker which correlates with patient clinical outcome. Platelet count is a key parameter in both diagnosis of diseases associated with low platelet levels and assessment of treatment efficacy. Therefore, it can be used as a pharmacodynamic marker in bioequivalence studies of biosimilar peptide TPO-RAs. It was concluded that such studies could be performed in healthy volunteers, and not in patients, whose participation in clinical trials is limited due to the orphan status of ITP.

Epidermolysis bullosa acquisita as an adverse effect from rituximab therapy

Rationale:Rituximab is a monoclonal antibody directed against B cells and is a first-line agent for the treatment of B cell lymphoma and a second-line agent for the treatment of idiopathic thrombocytopenic purpura (ITP). It has also been used for the treatment of several other autoimmune diseases. Epidermolysis bullosa acquisita (EBA) has never been reported as an adverse effect resulted from rituximab therapy.Patient concerns:A 54-year-old female presented with relapse of the ITP for around eight months. She was treated with rituximab. Intramuscular chlorpheniramine and intravenous methylprednisolone and cimetidine were used as premedication before rituximab infusion. The infusion was initially started at 50 mg/h for 1 h followed by 100 mg/h till the end of infusion. The day after rituximab infusion, the patient noticed pruritic blisters on both arms and chest skin. The next day, the lesions increased in severity and extent.Diagnosis:The skin biopsy established the diagnosis of EBA. H&E staining revealed subepidermal blisters infiltrated by inflammatory cells, including eosinophils and lymphocytes. Direct immunofluorescence (DIF) showed linear deposition of IgG and C3 at the dermoepidermal junction. Indirect immunofluorescence with the patient's serum on salt-split skin revealed exclusive dermal binding of circulating IgG antibasement membrane antibodies at a titer of 1:160.Interventions:She was treated with intravenous methylprednisolone and was continued on oral prednisolone.Outcomes:The lesions regressed. Six weeks later, she had a recurrence of similar lesions but in milder form. This episode subsided in 4 to 5 days with topical steroid application.Lessons:Physicians should consider this diagnosis when a patient develops bullous skin eruptions while undergoing Rituximab therapy.