Azathioprine Dose Research Articles

Feasibility of Reduced Clinical Monitoring in Patients with Inflammatory Bowel Disease Treated with Thiopurine Therapy

BackgroundOutpatient visits and laboratory assessments are routinely scheduled every 3 to 4 months in thiopurine-treated patients with inflammatory bowel disease (IBD) to timely detect thiopurine-related adverse events (AEs). AEs that require therapy adjustment beyond 12 months of treatment are rare.Aim and MethodsThis single-center prospective cohort study evaluated the safety of a reduced 6-monthly monitoring strategy in steroid-free patients with quiescent IBD on stable dose of azathioprine, mercaptopurine, or thioguanine monotherapy. The primary outcome was thiopurine-related AEs requiring therapy adjustments during a follow-up period of 24 months. Secondary outcomes included all AEs including laboratory toxicity, disease flares until 12 months, and the net monetary benefit from this strategy concerning IBD-related health care use.ResultsWe enrolled 85 patients with IBD (median age 42 years, 61% Crohn’s disease, 62% female), with a median disease duration of 12.5 years and median thiopurine treatment duration of 6.7 years. During follow-up, 3 patients (4%) ceased thiopurines due to AEs: recurrent infections, non-melanoma skin cancer, and gastrointestinal complaints (nausea, vomiting). At 12 months, 25 laboratory toxicities were observed (including 13% myelotoxicity, 17% hepatotoxicity); none required therapy adjustments and all were transient. A reduced monitoring strategy had a net benefit of €136 per patient.ConclusionThree patients (4%) ceased thiopurine therapy due to thiopurine-related AEs, while no laboratory toxicity required therapy adjustments. Monitoring frequency of every 6 months seems feasible in patients with stable IBD on long-term (median duration > 6 years) maintenance thiopurine therapy and may contribute to reduced patient-burden and health care costs.

Gender differences in SLE: report from a cohort of 417 Caucasian patients

BackgroundSLE is an autoimmune disease that predominantly affects women. As most epidemiological and interventional studies are on populations with a clear female prevalence, the influence of gender in disease course,...

Impact of Duodenal Pathology on Oral Drug Bioavailability and Disease Outcomes in Pediatric Crohn’s Disease

Crohn's disease with upper gastrointestinal tract involvement occurs more often in children than adults and has the potential to interfere with oral drug absorption. We aimed to compare disease outcomes in children receiving oral azathioprine for the treatment of Crohn's disease with (DP) and without (NDP) duodenal pathology at diagnosis. Duodenal villous length, body mass index (BMI), and laboratory studies were compared in DP vs. NDP during the first year post-diagnosis, using parametric/nonparametric tests and regression analysis (SAS v9.4); the data are reported as the median (interquartile range) or the mean ± standard deviation. Thiopurine metabolite concentration (pmol/8 × 108 erythrocytes) 230-400 was considered therapeutic for 6-thioguanine nucleotides (6-TGN), and >5700 was considered hepatotoxic for 6-methylmercaptopurine (6-MMPN). Twenty-six of the fifty-eight children enrolled (29 DP, 29 NDP) started azathioprine for standard medical care, including nine DP and ten NDP who had normal thiopurine methyltransferase activity. Duodenal villous length was significantly shorter in DP vs. NDP (342 ± 153 vs. 460 ± 85 μm; p < 0.001) at diagnosis; age, sex, hemoglobin, and BMI were comparable between groups. A trend toward lower 6-TGN was observed in the DP vs. NDP subset receiving azathioprine (164 (117, 271) vs. 272 (187, 331); p = 0.15). Compared to NDP, DP received significantly higher azathioprine doses (2.5 (2.3, 2.6) vs. 2.2 (2.0, 2.2) mg/kg/day; p = 0.01) and had an increased relative risk of sub-therapeutic 6-TGN. At 9 months post-diagnosis, children with DP had significantly lower hemoglobin (12.5 (11.7, 12.6) vs. 13.1 (12.7, 13.3) g/dL; p = 0.01) and BMI z-scores (-0.29 (-0.93, -0.11) vs. 0.88 (0.53, 0.99); p = 0.02) than children with NDP. For children with Crohn's disease, duodenal pathology, marked by villous blunting, increased the risk of sub-therapeutic 6-TGN levels, despite higher azathioprine dosing during the first year post-diagnosis. Lower hemoglobin and BMI z-scores at 9 months post-diagnosis suggest the impaired absorption/bioavailability of nutrients, as well as oral drugs, in children with duodenal disease.

Optimización del tratamiento de la colitis ulcerosa leve a moderada: Consenso Delphi CU-Forum

Background and objectiveUlcerative colitis (UC) clinical guidelines include the best available evidence, although not all clinical situations are answered, so their management can be controversial. The aim of this study is to identify the situations of mild to moderate UC susceptible to controversy and to evaluate the degree of agreement or disagreement with specific proposals. MethodsInflammatory bowel disease (IBD) expert discussion meetings were used to identify criteria, attitudes and opinions regarding the management of UC. A Delphi questionnaire was then developed with 60 items regarding antibiotics, salicylates and probiotics; local, systemic and topical corticosteroids; and immunosuppressants. ResultsConsensus was reached in 44 statements (73.3%); 32 in agreement (53.3%) and 12 in disagreement (20.0%). Some of them were: it is not necessary the systematic use of antibiotics despite the severity of the outbreak, being reserved when there is suspicion of infection or systemic toxicity; when faced with a mild-moderate outbreak of UC and in patients who do not respond to aminosalicylates, it is appropriate to use a dose of beclomethasone of 10mg/day for one month and 5mg/day for another month; it is advised that the dose of azathioprine be administered in a single dose. ConclusionsIBD experts agree on most of the proposals identified for managing mild to moderate UC and there is a need for scientific evidence in some specific situations where expert opinion may be helpful.

Hepatitis E Virus Infection in Patients with Chronic Inflammatory Bowel Disease Treated with Immunosuppressive Therapy.

Medical treatment of inflammatory bowel disease (IBD) has evolved significantly, and treatment with immunomodulators is recommended. These medications may alter the patient's immune response and increase the risk of opportunistic infections. Our aim was to evaluate the prevalence and the incidence of acute or chronic HEV infection in IBD patients under immunomodulatory treatment. We conducted a retrospective, multicenter, observational study between 2017 and 2018. IBD outpatients hospitalized for the infusion of immunomodulators were included in 16 French centers. During their daily hospitalization, blood samples were drawn for HEV serology (IgM and IgG) and HEV RNA detection. A total of 488 patients were included, of which 327 (67%) patients had Crohn's disease and 161 (33%) ulcerative colitis. HEV IgM was detected in 3 patients, but HEV RNA was undetectable in all patients. The HEV IgG seroprevalence rate was 14.2%. IgG-positive patients were older at sampling (p = 0.01) and IBD diagnosis (p = 0.03), had higher seafood consumption (p = 0.01) and higher doses of azathioprine (p = 0.03). Ileal and upper digestive tract involvement was more frequent in IgG-positive patients (p = 0.009), and ileocolic involvement was more frequent in IgG-negative patients (p = 0.01). Under multivariate analysis, age > 50 years [OR: 2.21 (1.26, to 3.85), p = 0.004] was associated with previous HEV infection. Systematic screening for HEV infection is not needed among IBD patients on immunomodulatory medications. However, in the event of abnormal liver test findings, HEV should be part of the classic diagnostic assessment.

Comparison of Short-Term Post-Thymectomy Outcomes by Time-Weighted Dosages of Drug Requirements between Thymoma and Non-Thymoma Myasthenia Gravis Patients.

(1) Background: Early thymectomy is suggested in all clinically indicated myasthenia gravis (MG) patients. However, short-term clinical response after thymectomy in MG patients has been limitedly described in the literature. This study aimed to compare the 5-year post-thymectomy outcomes between thymoma (Th) and non-thymoma (non-Th) MG patients. (2) Methods: MG patients aged ≥18 years who underwent transsternal thymectomy and had tissue histopathology reports in Songklanagarind Hospital between 2002 and 2020 were enrolled in a retrospective review. The differences in the baseline demographics and clinical characteristics between ThMG and non-Th MG patients were studied. We compared the time-weighted averages (TWAs) of daily required dosages of pyridostigmine, prednisolone or azathioprine to efficiently maintain daily living activities and earnings between the MG patient groups during 5 consecutive years following thymectomy. Post-thymectomy clinical status, exacerbations or crises were followed. Descriptive statistics were used for analysis with statistical significance set at p < 0.05. (3) Results: ThMG patients had significantly older ages of onset and shorter times from the MG diagnosis to thymectomy. Male gender was the only significant factor associated with ThMG. TWAs of the daily MG treatment drug dosages required showed no differences between the groups. Additionally, the rates of exacerbations and crises were not different, but decremental trends were shown in both groups after the thymectomies. (4) Conclusions: The daily dosage requirements of MG treatment drugs were not different. There was a trend of decreasing adverse event rates despite no statistically significant differences during the first 5 years after thymectomy in ThMG and non-ThMG patients.

Treatment of autoimmune hepatitis: Budesonide does not solve our problems.

Treatment of autoimmune hepatitis: Budesonide does not solve our problems.

P729 Evaluation of hepatobiliary pathologies using transient elastography in patients with inflammatory bowel disease: What about the effect of drugs?

Abstract Background In this study, we evaluated hepatobiliary involvement in inflammatory bowel disease (IBD) with FibroScan® (transient elastography) and examined drug effects on liver fibrosis and steatosis. We particularly focused on the effect of azathioprine (AZT) on spleen stiffness (SS). Methods A total of 352 subjects were included in this study, including 298 IBD patients and 54 healthy controls. LSM (liver stiffness measurement), SS, and CAP™ (controlled attenuation parameter) scores were measured by FibroScan®. In addition to disease and patient characteristics; laboratory tests, and effect of the drugs were evaluated and compared within the groups. Results The patient and control groups were similar in terms of age and gender. The characteristics of the groups are shown in Table 1. Mean LSM (5.2±3.1kPa vs 4.5±1,1kPa), mean SS (22.69±13,10kPa vs 17.96±7,44kPa), CAP™ score (hepatosteatosis) (233±56dB/m vs 224±47dB/m) were significantly higher in the patients with IBD than in the control group (p&amp;lt;0.05). Liver fibrosis and steatosis grades are shown in Figure 1. A positive correlation was found between CAP™ score and male gender, hypertension, diabetes, BMI, smoking, penetrating disease, GGT, triglyceride, LSM, and SS (p&amp;lt;0.05). LSM (5.7±3,1kPa vs 5.0±3,1kPa) was significantly higher in patients with extraintestinal involvement (p&amp;lt;0.05). In patients with significant liver fibrosis (F2-3-4), the frequency of anti-TNF treatment was lower (44,4% vs 69,5%; p=0,008) (Figure 2). In patients who use alcohol regularly compared to nondrinkers (25.54±14,83kPa vs 21.05±11,24kPa) SS was significantly higher (p&amp;lt;0.05). Additionally, in patients using AZT≥100 mg/day compared to those using AZT&amp;lt;100 mg/day (23.48±14,61kPa vs 19.99±11,84kPa; p&amp;lt;0,05) SS was significantly higher (Figure 3). AZT dose was positively correlated with SS (Spearman analysis; r=0.182 and p=0.013); however, no correlation was found with the duration or cumulative dose of AZT. The mean level of platelets was significantly higher in patients with IBD than in controls (300±104x10³/µL vs 251±52x10³/µL, p=0,001); however, there was no correlation between SS and trombosit level (p&amp;gt;0,05). 83% of patients were in clinical remission (Mayo score≤2/CDAI&amp;lt;150). No positive correlation was found between disease activity and SS in IBD patients. AZT-associated non-cirrhotic portal hypertension was detected in only one patient. Conclusion In this study, fatty liver, liver fibrosis, and SS were found to be significantly higher in IBD patients than in healthy controls. Although there is no relationship with the duration of AZT therapy, AZT dose was positively correlated with SS. We recommend that spleen stiffness should be evaluated in patients who use high doses of AZT (≥100 mg/day).

P791 Up to one third of rapid thiopurine-S-methyltransferase metabolizers manifest clinical and/or laboratory azathioprine side effects: A single centre experience

Abstract Background According to ECCO-ESPGHAN consensus guidelines, azathioprine (AZA) can be used for maintenance of remission in paediatric Inflammatory Bowel Disease (IBD). AZA side effects are well documented. Haematological toxicity affects 2-14% of patients and pancreatitis affects up to 7% of them, requiring modification of AZA dosage or its cessation. Thiopurine-S-methyltransferase (TPMT) activity should be tested prior to AZA commencement. Slow metabolizers should not be started on AZA and intermediate ones should get a dose reduction. This study evaluates the incidence of AZA side effects in TPMT rapid metabolizers. Methods Retrospective evaluation of prospectively collected data in children tested for TPMT and who received AZA between 3/13 and 10/22. Focusing on the incidence of both clinical and laboratory side effects in rapid metabolizers. Results Ninety children had TPMT tested. Only 1 intermediate a 1 slow metabolizer were identified. All rapid metabolizers were diagnosed with IBD, 62 (70,5%) with Crohn’s (CD), 16 (18,2%) with Ulcerative Colitis (UC), 7 with Very Early Onset IBD (VEO-IBD) and 1 with IBD undifferentiated. Forty-seven were male (53,4%) and 41 female. The median age at diagnosis was 13.5±3,9 years. Of the 88 rapid metabolizers, 82 (93%) received AZA. The remaining 6 had different treatment strategies. Clinical and/or laboratory side effects were documented in 27 cases (32,9%). Haematological toxicity was most frequent affecting 19 participants (23.1%). In 13 cases (68,4%) leukopenia resolved spontaneously, in 4 cases (21%) dose reduction was required, and in 3 cases (15,8%) AZA had to be stopped. Pancreatitis was identified in 6 patients (7,3%). Half of the cases were discovered by laboratory findings and the remainder had a clinical correlate. In 2 cases, laboratory pancreatitis normalized on follow-up examination, in the remaining ones AZA had to be withdrawn. Clinical intolerance was found twice, once requiring split dosage, and once dose reduction. Haematological toxicity manifested on average within 10,9 months since treatment start (0.5-43 months), pancreatitis within 0,54 months with one case manifesting after 79 months of treatment. In this single case, autoimmune pancreatitis is debated. Clinical intolerance appeared within days from AZA commencement. Boys had AZA side effects slightly more frequently (15/27, 55%). CD patients had AZA side effects the most (16/27, 59%). However, CD was the most common diagnosis in the cohort. Conclusion Being a rapid TPMT metabolizer should reduce the risk of AZA side effects. However, these data demonstrate a 32,9% occurrence of them, emphasising the importance of clinical and laboratory follow-up in patients on AZA.

Frequency and Correlates of Mild Cognitive Impairment in Myasthenia Gravis

Antibodies against acetylcholine receptors (AChRs) can also target nicotinic AChRs that are present throughout the central nervous system, thus leading to cognitive dysfunctions in patients with myasthenia gravis (MG). However, the presence of cognitive impairment in MG is controversial, and the factors that may influence this risk are almost completely unknown. In this study, the frequency of mild cognitive impairment (MCI) in MG, as well as the clinical, immunological, and behavioral correlates of MCI in MG were evaluated. A total of 52 patients with MG underwent a comprehensive assessment including motor and functional scales, serological testing, and neuropsychological and behavioral evaluation. The frequency of MCI was 53.8%, and the most impaired cognitive domains were, in order, visuoconstructive/visuospatial skills, memory, and attention. After multivariate analysis, only pyridostigmine use was inversely associated with the presence of MCI, while a trend toward a positive association between MCI and disease severity and arms/legs hyposthenia was found. Correlation analyses showed that daily doses of prednisone and azathioprine significantly correlated with depressive symptomatology, while disease severity significantly correlated with depressive symptomatology and sleep disturbance. The presence of MCI is rather frequent in MG and is characterized by multidomain amnestic impairment. Such preliminary data need further confirmation on larger case series.

Real-World Evidence of Effectiveness and Safety of Vedolizumab for Inflammatory Bowel Disease in Taiwan: A Prospective Nationwide Registry (VIOLET) Study.

This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.

Efficacy and Safety Comparison of Basic Fibroblast Growth Factor-Related Decapeptide 0.1% Solution (bFGFrP) Plus Oral PUVA Combination Therapy with Oral PUVA Monotherapy in the Treatment of Vitiligo.

Phototherapy in its different forms, is mainstay of vitiligo management. Combining treatment modalities like topical calcipotriol (for quicker, more intense repigmentation), Low dose azathioprine with PUVA have proven to be beneficial in management of vitiligo due to different mechanisms of repigmentation and their synergistic effects. Topical bFGF-related decapeptide (bFGFrP) application followed by sun exposure/ UVA phototherapy yields effective repigmentation. bFGFrP has shown to aid the targeted phototherapy in smaller lesions and its combinations with other treatment modalities have been very promising. However, there is paucity of studies on combination treatments; especially oral PUVA along with bFGFrP. This study was aimed at evaluating safety and efficacy of combination of bFGFrP with Oral PUVA in vitiligo (larger body surface area 20% or more). Phase IV, randomized, multicentre study (N = 120) in adult patients with stable vitiligo of 6 months treatment period with monthly follow up visits. Psoralen (Tab. Melanocyl) dosage 0.6 mg/kg orally 2 h before exposure to UVA phototherapy. Oral PUVA therapy, initially, at an irradiation dose 4 J/cm2 (PUVA group), followed by increments 0.5 J/cm2 every four sittings if tolerated for twice weekly. Primary end point was improvement in extent of repigmentation (EOR) in target lesion (at least 2 cm × 2 cm in greatest dimension, without leukotrichia), while secondary endpoints were improvement in patient global assessment (PGA) and safety at end of 6 months of treatment period in bFGFrP + oral PUVA combination group and Oral PUVA monotherapy group. End of 6 months, significantly greater EOR >50%) was achieved in 61.8% (34 patients, n = 55) from combination group while 30.2% (16 patients, n = 53) from the oral PUVA monotherapy group (n = 53). Regarding Grade of repigmentation (GOR), complete repigmentation was observed 5.5% (3 patients, n = 55) in combination group whereas no patient showed complete repigmentation in monotherapy group (p ≤ 0.05), PGA showed significant overall improvement in combination group (p ≤ 0.05); 6 patients (10.9%) from combination group Vs one (1.9%) showed complete improvement. During treatment period, there were no reported adverse events. Addition of bFGFrP to oral PUVA therapy resulted in intense and faster induction of repigmentation than oral PUVA monotherapy with favorable safety profile.

106 A CASE OF COMPLETE ATRIOVENTRICULAR BLOCK AND ALTERNATING BUNDLE BRANCH BLOCK DUE TO FULMINANT MYOCARDITIS

Abstract A 41-year-old man, without previous cardiological history, presented at the emergency department with hypotension and multi-organ failure. Laboratory testing showed elevated white cell blood count (16780/mcL; normal value 4000-11000/mcL; 90% neutrophils), high-sensibility troponin I (23247 ng/L; normal value &amp;lt;18 ng/L) and NT-pro-BNP (21914 pg/mL; normal value &amp;lt;300 pg/mL). At electrocardiogram (EKG) there was sinus rhythm with complete atrioventricular block and alternating right and left bundle branch block. Echocardiography revealed a moderate left ventricular (LV) dilatation, mild LV hypertrophy, severe biventricular dysfunction (LV Ejection Fraction - EF - 30%) with dense spontaneous echo contrast and moderate pulmonary hypertension (systolic pulmonary artery pressure 51 mmHg). After positioning a temporary pacemaker, the patient was transferred to our Cardiac Intensive Care Unit. After initial hemodynamic stabilization with endovenous inotropes, diuretics, and mechanical circulatory support (intra-aortic balloon pump), coronary angiography was performed showing normal coronary arteries. Since fulminant myocarditis was suspected and magnetic resonance was not feasible due to the patient's instability, an endomyocardial biopsy (EMB) was performed with the evidence of myocardial edema, initial myocardial fibrosis, and the concomitant presence of lymphocytic and eosinophilic endo-myocarditis (despite normal eosinophilic blood count) without evidence of active viral replication. After careful exclusion of latent or active infections, high doses of corticosteroids and azathioprine were initiated, with rapid laboratoristic and clinical response. EKG showed AV block regression and QRS width's normalization, so the pacemaker was removed. LVEF rapidly improved and was completely normalized at discharge after two weeks. In the early follow-up, a cardiac magnetic resonance (CMR) was performed with evidence of persistency of mildly dilated LV, normalization of LV wall thickness and biventricular function, a diffuse increase of T1 relaxation time, increased T2 signal of the anterior and septal walls, and intramural anteroseptal late gadolinium enhancement (LGE). Fulminant myocarditis is a rare presentation of acute myocarditis, with low incidence but high mortality. The inflammation of the myocardium itself leads to acute heart failure, cardiogenic shock, and cardiac arrhythmias, including sinus arrest, AV block, ventricular tachycardia, and ventricular fibrillation during the acute phase. In our case, AV block could be an expression of anteroseptal involvement, documented at CMR. This localization has already been associated with worse clinical presentation and could be a marker of poor prognosis. Diagnosis and treatment of fulminant myocarditis require EMB, to obtain information about the etiology and active viral replication in the heart tissue. In our case, the florid inflammatory state and the absence of viral replication allowed prompt treatment with immunosuppressors, with a quick and full recovery of biventricular function in only two weeks.

Prevalence and risk factors of herpes zoster infection in patients with rheumatic diseases not receiving biologic or targeted therapies.

The objective was to study the prevalence and risk factors of herpes zoster (HZ) infection in patients with rheumatic diseases. Consecutive patients with rheumatic diseases not receiving biologic/targeted DMARDs who attended our rheumatology clinics between March and August 2019 were retrospectively reviewed. Episodes of HZ infection since their first clinic attendance were identified. Laboratory results (total white cell count, neutrophil-to-lymphocyte ratio (NLR), serum albumin, globulin, and creatinine) and use of immunosuppressive medications were compared between those with (preceding infection) and without (preceding last visit) HZ infection. Cox regression analysis was performed to identify factors associated with the first HZ infection in all patients. 1,479 patients were studied (88.3% women, age 45.0 ± 15.8years). Systemic lupus erythematosus (SLE) (38.7%) and rheumatoid arthritis (28.3%) were the commonest rheumatic diseases. After a follow-up of 14,715 patient-years (9.9 ± 7.0years), 219 (14.8%) patients developed 258 episodes of HZ infection, giving an overall prevalence of 1.75/100-patient years. The prevalence rates of HZ were highest in SLE and inflammatory myopathies (2.54 and 2.58 per 100 patient-years, respectively). Patients who experienced HZ reactivation were younger, more likely to have SLE, and had significantly lower serum albumin/globulin levels but higher NLR. Significantly more patients with HZ reactivation were using prednisolone and other immunosuppressive drugs in the visits preceding HZ infection. The cumulative risk of having HZ reactivation at 24 and 48months was 4.9% and 7.6%, respectively. Cox regression analysis revealed that a diagnosis of SLE, increasing age, higher NLR, use of cyclophosphamide, and increasing doses of prednisolone, azathioprine, hydroxychloroquine and leflunomide were independently associated with HZ infection. Reactivation of HZ is fairly common in patients with rheumatic diseases. Underlying SLE, age, neutrophil/lymphocyte ratio, and immunosuppressive therapies are independent risk factors. Key Points • Herpes zoster (HZ) infection is fairly common in patients with rheumatic diseases undergoing conventional DMARD or immunosuppressive therapies. • Underlying SLE, increasing age, higher neutrophil/lymphocyte ratio and increasing dosages of immunosuppressive drugs are independent risk factors. • Patients with rheumatic diseases, particularly SLE, should be encouraged to receive HZ vaccination.

DETERIORATION OF RESPIRATORY STATUS IN A CVID PATIENT WITH GLILD AND COVID-19

<h3>Introduction</h3> Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) is a serious inflammatory complication of Common Variable Immunodeficiency (CVID), typically requiring immunomodulation in an already immunodeficient patient. <h3>Case Description</h3> A 34-year-old male with CVID, heterozygous for pathogenic variant c.310T>C (p.Cys104Arg) in TNFRSF13B, on immunoglobulin replacement therapy, and biopsy-confirmed GLILD that was in remission in Fall 2020 presented for follow up. GLILD was treated with rituximab weekly from March-April 2019 and azathioprine 150 mg daily. His azathioprine dose was decreased in June 2019 to 100 mg daily secondary to recurrent infections while on therapy. Despite the decreased azathioprine dose, he felt well and follow up CT Chest in September 2019 showed near-complete resolution of lung nodules. Treatment was discontinued after two of the anticipated 3-4 cycles. His second rituximab course was completed from September-November 2019, and azathioprine was decreased to 50 mg maintenance dose and stopped in November 2020. He contracted COVID-19 in Winter 2021 requiring hospitalization and treatment with remdesivir and dexamethasone. He recovered from COVID-19 and his respiratory symptoms returned to baseline. In June 2021, however, he developed progressive dyspnea, lymphadenopathy, and CT Chest performed in September showed multiple pulmonary nodules concerning for recurrence of GLILD. A second round of rituximab and mycophenolate mofetil has been started due to concern for relapse vs. inadequate treatment of GLILD. <h3>Discussion</h3> Our case highlights the diagnostic dilemma of determining the cause of this patient's ongoing respiratory disease. The possibilities include GLILD relapse due to incomplete treatment or ineffective treatment, or sequelae of COVID-19 infection.

S2738 Isolated Celiac Artery Vasculitis Presenting as Ileus in a Patient With Ulcerative Colitis

Introduction: Small case series have reported an association between IBD and large vessel vasculitides, ANCA-associated vasculitis, and cutaneous vasculitis. Gastrointestinal (GI) involvement of vasculitis can be a severe complication, resulting in mesenteric ischemia, ileus, or GI bleeding, and often requires aggressive medical or surgical interventions. We report a case of celiac artery vasculitis presenting as abdominal pain and ileus in a patient with ulcerative colitis (UC). Case Description/Methods: A 69 year old male with an 11 year history of UC in remission on infliximab and azathioprine (AZA) presented to the emergency room with abdominal pain and constipation for five days. He had decreased AZA from 200 mg to 100 mg one month prior. Initial CT abdomen and pelvis showed stranding surrounding the celiac artery, fluid-filled small bowel loops, and segmental areas of distal colon collapse with proximal colon distention. He developed progressive small bowel and colonic distention with cecum diameter of 10 cm. A colonoscopy was performed for decompression. He had no evidence of active UC. EGD demonstrated dusky appearing gastroesophageal junction and inflammation with cratered ulcers in the gastric cardia and body. Biopsies confirmed ischemic necrosis. CTA demonstrated perivascular inflammation of a patent celiac artery without evidence for dissection, suggestive of acute vasculitis. ESR and CRP were 50 mm/hr and 7.8 mg/dL respectively. Myeloperoxidase, serine-proteinase 3, rheumatoid factor, ANA, were negative. He was started on methylprednisolone IV with oral prednisone taper at discharge, and AZA was increased to 200 mg daily. A CT one month later showed minimal residual inflammation. ESR and CRP had normalized. (Figure) Discussion: We present the first case of isolated celiac artery vasculitis in a patient with IBD. A diagnosis of IBD often precedes vasculitis, and patients are typically on immunosuppressive therapy at the time of onset. Anti-TNF agents have been implicated as a potential inciting cause. Although it is unclear whether long-term anti-TNF therapy precipitated vasculitis in our patient, the dose reduction in AZA prior to presentation may have unmasked vasculitis. This was supported by his rapid clinical and radiographic improvement with combination of steroids and increased AZA dose despite continuation of infliximab. This case highlights the importance of maintaining a high degree of suspicion for vasculitis in patients with IBD on immunosuppressive therapy presenting with ischemia or ileus.Figure 1.: A 69 year old male underwent EGD for evaluation of abdominal pain and NG tube placement; he was found to have inflammation with a dusky appearing mucosa at the gastroesophageal junction (GEJ) (A). Non-bleeding gastric ulcers with overlying pigment (Forrest Class IIc) were identified (B). H&E stain image shows the GEJ biopsy with extensive ischemic necrosis and hemorrhage (C). Initial CTA abdomen/pelvis shows fat stranding surrounding the celiac artery (D).

Association of mycophenolate and azathioprine use with cognitive function in systemic lupus.

Cognitive dysfunction (CD) is a common manifestation of SLE that can have detrimental consequences for those affected. To date, no treatments have been approved for SLE-CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given thatthese medications have demonstrated neuroprotective qualities in prior studies. Consecutive adult SLE patients presenting to a single healthcare center were considered for participation. The ACR neuropsychological battery for SLE was administered to consenting patients at 0, 6 and 12 months. Scores were compared with age- and sex-matched controls. Primary outcome was CD, defined as a z-score ≤-1.5 in two or more cognitive domains. Mixed-effects logistic regression models were constructed to estimate the odds of CD with respect to AZA and MMF use. A total of 300 participants representing 676 patient visits completed the study; 114 (38%) met criteria for CD at baseline. The cumulative AZA dose (g/kg) was associated with reduced odds of CD [odds ratio (OR) 0.76 (95% CI 0.58, 0.98), P = 0.04]. Years of AZA treatment was also associated with reduced odds of CD [OR 0.72 (95% CI 0.54, 0.97), P = 0.03]. MMF use was not associated with CD. AZA use was associated with significantly lower odds of SLE-CD, while MMF use was not. Additional studies are warranted to further investigate the relationship of AZA and SLE-CD.

Outcome of thymectomy in myasthenia gravis patients at Neurological Institute of Thailand

Background &amp; Objective: Myasthenia gravis is the most common neuromuscular junction disorders and is caused by autoantibodies against acetylcholine receptors at the postsynaptic muscle endplate. Although thymectomy is current standard treatment but the benefit in long-term outcomes and in non- thymomatous generalized MG patients with negative AChR antibody are still unclear. The objective is to determine the treatment outcomes of thymectomy in non-thymomatous generalized MG patients with or without AChR antibody and identify features related to remission. Methods: Retrospective chart review of the patients diagnosed with non-thymomatous generalized MG from January 1st, 2014 to December 31th, 2018. Patients were classified into two groups: patients with thymectomy (thymectomy group) and patients with no thymectomy (medication group). Results: Seventy-six patients were included. All baseline clinical features, investigations and treatment response were compared. At 6 and 12 months follow up, most patients in both groups had a good response to treatment. At 24 months follow up, ratio of patients in thymectomy group with complete stable remission is higher than in medication group (25% vs. 7.5%) and all patients in this group had positive acetylcholine receptor antibody. The patients in thymectomy group required lower dosage of prednisone, azathioprine and cholinesterase inhibitors than in medication group. Conclusion: Thymectomy was associated with a high probability of achieving remission, reduced cholinesterase inhibitors and immunosuppressive drugs when compared to medication group. Therefore, thymectomy should be strongly considered for non-thymomatous generalized MG patient with positive AChR antibody; and may be considered in non-thymomatous generalized MG patients with negative AChR antibody.

Prevalence of hepatotoxicity and myelosuppression with alternate day use of azathioprine and glucocorticoids for treatment of dermatological conditions in dogs.

The use of azathioprine (AZA) in dogs is limited by the potential for hepatotoxicity and myelosuppression. To determine the prevalence of AZA-associated hepatotoxicity in dogs with dermatological conditions receiving alternate-day AZA. The hypothesis was that dogs receiving AZA every other day (EOD) would have a lower prevalence of hepatotoxicity compared to published data for dogs receiving daily AZA. A secondary aim was to determine the prevalence of AZA-associated myelosuppression over the same time period and population. Forty-one client-owned dogs with dermatological conditions treated with AZA EOD and glucocorticoids with clinical and haematological follow-up available for a minimum of two months of AZA therapy. Retrospective analysis of data from April 1994 to July 2020. Hepatotoxicity was defined as elevation of alanine aminotransferase (ALT) at least twofold above the reference range. Azathioprine-associated hepatotoxicity was observed in two of 41 dogs (4.9%), with onset at 18 and 40 days, respectively. One dog receiving AZA at 1.9mg/kg EOD had a fourfold increase in ALT. The other dog (AZA dose 2.3mg/kg EOD) had a 30-fold increase in ALT. Azathioprine was not associated with thrombocytopenia, anaemia or neutropenia in any dogs. Lymphopenia developed in one dog (2.4%) with onset at 105 days. Alternate-day AZA administration with tapering glucocorticoids was well-tolerated in dogs with dermatological conditions.

Monotherapy with thiopurines in stricturing Crohn's disease: A real-life experience from low- and middle-income countries.

Stricturing Crohn's disease (CD) is difficult to manage medically with limited treatment options, anti-tumor necrosis factor (TNF) therapy being the first-line therapy. Although thiopurines are also recommended first-line treatment option for maintenance of remission in steroid-dependent CD, evidence on their use in stricturing CD is lacking. We evaluated the efficacy of azathioprine (AZA) in patients with stricturing CD. In thisretrospective cohort study (January 2005 to July 2020), patients with stricturing CD who were managed with AZA as a primary therapy for at least 6months, and had a follow-up of at least 6 months after AZA initiation were included. Disease characteristics, complications, long-term response, and adverse events were noted. One hundred andfifteen patients were included (mean age 33.8±14 years, 67.8% males, median disease duration 98 months [IQR: 60-158], median follow-up duration 60 months [IQR: 50-96]). 46.1% (n=53) patients had significant anemia at presentation, and 73% (n=84) had isolated small bowel involvement. Median dose of AZA was 100 mg (equivalent to 1.5 mg/kg). Median therapy and follow-up duration (after AZA initiation) was 17 (IQR: 9-42) and 33 months (IQR 18-60), respectively. The cumulative probability of maintainingresponse without treatment failure at 1, 2, and 5 years was 73.1%, 40.7%, and 18.5%, respectively. Among patients with AZA failure, 15.6% received methotrexate, 13% received anti-TNFs, and 9.5% underwent surgery. Significant anemia (&lt;10 g/dL) at presentation and steroid dependence predicted AZA failure. 31.3% patients experienced adverse events, commonest being leukopenia (n=29, 25.2%). Azathioprine demonstrated good short-term and modest long-term response rates in patients with stricturing CD.