Oral Azathioprine Research Articles

THU0311 CERTOLIZUMAB THERAPY IN REFRACTORY UVEITIS DUE TO IMMUNE-MEDIATED INFLAMMATORY DISEASES (IMID). MULTICENTER STUDY OF 39 PATIENTS

Background:Infliximab and adalimumab therapy has significantly improved the prognosis of patients with non-infectious refractory uveitis. However, there is not enough evidence for the use of other anti-TNF drugs such as Certolizumab Pegol (CZP).Objectives:To evaluate the efficacy and safety of CZP in uveitis secondary to Immune-Mediated Inflammatory Diseases (IMID).Methods:Multicenter study of 39 patients with uveitis due to IMID refractory to glucocorticoids and conventional immunosuppressants. Efficacy of CZP was evaluated with the following ocular parameters: best corrected visual acuity (BCVA), anterior chamber cells, macular thickness and presence of retinal vasculitis. Efficacy of CZP was compared between baseline, 1st week, 1st and 6th month, and 1st and 2nd year. Statistical analysis was performed with the STATISTICA software (Statsoft Inc. Tulsa, Oklahoma, USA).Results:39 patients/56 affected eyes (18 men/21 women) with a mean age of 40.5±11.9 years were studied. IMIDs included were: spondyloarthritis (n=17), psoriatic arthritis (6), Crohn (3), JIA (2), Behçet (2), reactive arthritis (2), rheumatoid arthritis (1), relapsing polychondritis (1), pars planitis (1), Birdshot (1) and idiopathic uveitis (3). Uveitis pattern was as follows: anterior (n=30), posterior (4), panuveitis (3) and intermediate (2).Previous CZP, patients received: oral prednisone (n=18) methylprednisolone bolus (1), methotrexate (22), azathioprine (10), cyclosporine (4), leflunomide (2), mycophenolate mofetil (2) and cyclophosphamide (1). 77% of patients had received previous biological therapy, with a mean of 1.6±1.2 biological drugs per patient. Gestational desire was the reason for prescribing CZP in 8 patients. CZP was administered in monotherapy in 16 patients and in the remaining 23 patients combined with conventional immunosuppressants.After a median follow-up of 24 [6-36] months, most of the ocular variables analysed showed a rapid and significantly sustained improvement (Table). CZP was discontinued in 11 patients for the following reasons: remission (n=1), insufficient response of ocular symptoms (n=1) and limited response of extraocular manifestations (n=9). No serious adverse effects were reported.Conclusion:CZP seems to be effective and safe in patients with refractory uveitis due to IMID.TableBaseline1stweek1stMonth6thMonth1styear2ndyearBCVA (mean±SD)0.77±0.290.77±0.30*0.82±0.29*0.85±0.26*0.86±0.27*0.88±0.23*Tyndall (median [IQR])0 [0-2]0 [0-2]0 [0-1]*0 [0-0]*0 [0-0]*0 [0-0]*OCT (mean±SD)355±61.5-284.1±40.4*-224.8±121.1*-Retinal Vasculitis (eyes affected, %)2 (3.6)0 (0)0 (0)0 (0)0 (0)0 (0)*p<0.05Disclosure of Interests:José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Janssen and Celgene, Speakers bureau: Pfizer and Lilly, Vanesa Calvo-Río Grant/research support from: MSD and Roche, Speakers bureau: AbbVie, Lilly, Celgene, Grünenthal, UCB Pharma, Lara Sanchez-Bilbao Grant/research support from: Pfizer, Iñigo González-Mazón: None declared, Ignacio Torre-Salaberri: None declared, Álvaro García Martos: None declared, Amalia Sanchez-Andrade: None declared, Ángel García-Aparicio: None declared, JR De Dios-Jiménez Aberásturi: None declared, ANA URRUTICOECHEA-ARANA: None declared, Olga Maíz: None declared, Raul Veroz Gonzalez: None declared, Andrea García-Valle: None declared, Sergio Rodríguez Montero: None declared, Roberto Miguélez: None declared, Vega Jovani: None declared, Marisa Hernández-Garfella: None declared, Arantxa Conesa: None declared, Olga Martínez González: None declared, Paula Rubio Muñoz: None declared, Belén Atienza-Mateo: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

LB004A RANDOMIZED, CONTROLLED TRIAL OF RITUXIMAB VERSUS AZATHIOPRINE AFTER INDUCTION OF REMISSION WITH RITUXIMAB FOR PATIENTS WITH ANCA-ASSOCIATED VASCULITIS AND RELAPSING DISEASE

Abstract Background and Aims Rituximab is an effective therapy for induction of remission in ANCA-associated vasculitis (AAV). However, the effect of rituximab is not sustained, and subsequent relapse rates are high, especially in patients with a history of relapse. The RITAZAREM trial (ClinicalTrials.gov identifier: NCT01697267) is an international, multi-center, open-labelled, randomized, controlled trial of patients with AAV with relapsing disease comparing the efficacy, after induction of remission with rituximab, of two relapse-prevention strategies: repeat dosing of rituximab or daily oral azathioprine. Method Patients with AAV were recruited at the time of relapse and received induction therapy with rituximab and glucocorticoids. If remission was achieved by month 4, patients were randomized in a 1:1 ratio to receive either rituximab (1000 mg every 4 months for 5 doses) or azathioprine (2 mg/kg/day) as maintenance therapy. Patients were followed for a minimum of 36 months, with the primary outcome being time to disease relapse. The formal hypothesis testing plan initially considers the hazard ratio for relapse across all time periods. If, and only if this global test is significant at a 5% level then the hazard ratios during the treatment period and the follow-up periods are considered separately. Results 190 patients were enrolled and 170 randomized at 4 months (85 to rituximab; 85 to azathioprine). The data are complete on all patients up to at least month 24. Median age was 59 years (range 19-89), with a prior disease duration of 5.3 years (0.4-38.5). 123/170 (72%) patients had a history of testing positive for anti-proteinase 3 ANCA; 47/170 (28%) for myeloperoxidase ANCA; 104/170 (61%) were enrolled having suffered a major relapse, and 48/170 (28%) received a pre-specified higher dose glucocorticoid induction regimen. Rituximab was superior to azathioprine in preventing disease relapse with a preliminary overall hazard ratio (HR) estimate of 0.36 (95% CI 0.23-0.57, p <0.001) and a during-treatment HR estimate of 0.30 (95% CI 0.15-0.60, p<0.001) (Figure 1). After adjustment, none of the randomization stratification covariates (ANCA type, glucocorticoid induction regimen, or relapse severity) had a significant differential effect on the primary outcome. By 24 months after entry, 20 months after randomization, 11/85 (13%) patients in the rituximab group had experienced a relapse compared to 32/85 (38%) patients in the azathioprine group. In the rituximab group 2/11 (18%) relapses were classified as major, compared to 12/32 (38%) in the azathioprine group. 19/85 (22%) patients in the rituximab group and 31/85 (36%) patients in the azathioprine group experienced at least one severe adverse event (SAE). 25/85 (29%) and 42/85 (49%) patients in the rituximab group developed hypogammaglobulinaemia (IgG <5g/l) and non-severe infections respectively, compared to 21/85 (25%) and 41/85 (48%) in the azathioprine group. Conclusion In the RITAZAREM trial, following induction of remission with rituximab, rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse. There were no new major safety signals for use of these medications in this population.

OP0026 A RANDOMIZED, CONTROLLED TRIAL OF RITUXIMAB VERSUS AZATHIOPRINE AFTER INDUCTION OF REMISSION WITH RITUXIMAB FOR PATIENTS WITH ANCA-ASSOCIATED VASCULITIS AND RELAPSING DISEASE

Background:Rituximab (RTX) is an effective therapy for induction of remission in ANCA-associated vasculitis (AAV). However, the effect of RTX is not sustained, and subsequent relapse rates are high, especially in patients with a history of relapse.Objectives:The RITAZAREM trial is an international, multi-center, open-labelled, randomized, controlled trial of patients with AAV with relapsing disease comparing the efficacy, after induction of remission with RTX, of two relapse-prevention strategies: repeat dosing of RTX or daily oral azathioprine (AZA).Methods:Patients with AAV were recruited at the time of relapse and received induction therapy with RTX and glucocorticoids. If remission was achieved by month 4, patients were randomized in a 1:1 ratio to receive either RTX (1000 mg every 4 months for 5 doses) or AZA (2 mg/kg/day) as maintenance therapy. Patients were followed for a minimum of 36 months, with the primary outcome being time to disease relapse.Results:190 patients were enrolled and 170 randomized at 4 months (85 to RTX; 85 to AZA). The data are complete on all patients up to at least month 24. Median age was 59 years (range 19-89), with a prior disease duration of 5.3 years (0.4-38.5). 123/170 (72%) patients had a history of testing positive for anti-proteinase 3 ANCA; 47/170 (28%) for myeloperoxidase ANCA; 104/170 (61%) were enrolled having suffered a major relapse, and 48/170 (28%) received a pre-specified higher dose glucocorticoid induction regimen (Table 1).Table 1.Baseline characteristics of patients enrolled in RITAZAREM trialRituximab (N=85)Azathioprine (N=85)Total (N=170)Age, years: median (range)57 (18-89)61 (27-83)59 (18-89)Female, number (%)42 (49.4%)44 (51.8%)86 (50.6%)Disease duration, years: median (range)5.8 (0.4-38.5)4.9 (0.4-25.8)5.3 (0.4-38.5)Prior cyclophosphamide therapyNumber of patients (%)67/85 (78.8%)66/85 (77.6%)133/170 (78.2%)Cumulative dose, grams (g): median (range)7.1 g (0.2-301)12 g (1.0-146)10 g (0.2-301)Prior rituximab therapyNumber (%) patient33/85 (38.8%)27/85 (31.8%)60/170 (35.3%)Cumulative dose, grams (g): median (range)3.2 g (2.0-16.0)5.4 g (1.5-14.0)3.9 g (1.5-16.0)Glucocorticoid induction regimen1mg/kg/day starting dose24/85 (28.2%)24/85 (28.2%)48/170 (28.2%)0.5mg/kg/day starting dose61/85 (71.8%)61/85 (71.8%)122/170 (71.8%)ANCA typeAnti-proteinase 361/85 (71.8%)62/85 (72.9%)123/170 (72.4%)Anti-myeloperoxidase24/85 (28.2%)23/85 (27.1%)47/170 (27.6%)Relapse type upon entry into trialSevere52/85 (61.2%)52/85 (61.2%)104/170 (61.2%)Non-severe33/85 (38.8%)33/85 (38.8%)66/170 (38.8%)RTX was superior to AZA in preventing disease relapse with a preliminary overall hazard ratio (HR) estimate of 0.36 (95% CI 0.23-0.57, p <0.001) and a during-treatment HR estimate of 0.30 (95% CI 0.15-0.60, p<0.001) (Figure 1). After adjustment, none of the randomization stratification covariates (ANCA type, glucocorticoid induction regimen, or relapse severity) had a significant differential effect on the primary outcome. By 24 months after entry, 20 months after randomization, 11/85 (13%) patients in the RTX group had experienced a relapse compared to 32/85 (38%) patients in the AZA group. 19/85 (22%) patients in the RTX group and 31/85 (36%) patients in the AZA group experienced at least one severe adverse event (SAE). 25/85 (29%) and 42/85 (49%) patients in the RTX group developed hypogammaglobulinaemia (IgG <5g/l) and non-severe infections respectively, compared to 21/85 (25%) and 41/85 (48%) in the AZA group.Figure 1.Relapse-free survival in RITAZAREM trial: rituximab versus azathioprineConclusion:In the RITAZAREM trial, following induction of remission with RTX, RTX was superior to AZA for preventing disease relapse in patients with AAV with a prior history of relapse. There were no new major safety signals for use of these medications in this population.Disclosure of Interests:Rona Smith Grant/research support from: Roche, David Jayne Grant/research support from: ChemoCentryx, GSK, Roche/Genentech, Sanofi-Genzyme, Consultant of: Astra-Zeneca, ChemoCentryx, GSK, InflaRx, Takeda, Insmed, Chugai, Boehringer-Ingelheim, Peter A. Merkel Grant/research support from: AstraZeneca, Bristol-Myers Squibb, Boeringher-Ingelheim, Celgene, ChemoCentryx, Genentech/Roche. Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Kypha, TerumoBCT., Consultant of: AbbVie, AstraZeneca, Biogen, Bristol-Myers Squibb, Boeringher-Ingelheim, Celgene, ChemoCentryx, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Insmed, Jannsen, Sparrow, Kiniksa.

THU0410 COMPANION IMMUNOSUPPRESSION WITH AZATHIOPRINE INCREASES THE FREQUENCY OF PERSISTENT RESPONSIVENESS TO PEGLOTICASE IN PATIENTS WITH CHRONIC REFRACTORY GOUT

Background:Pegloticase is a mammalian recombinant uricase coupled to monomethoxy polyethylene glycol that is approved in the US for treatment of patients with chronic refractory gout and causes profound reductions in serum urate. However, treatment with pegloticase is limited by the induction of anti-drug antibodies and loss of responsiveness in nearly half of treated patients.Objectives:The goal of this study was to determine whether co-therapy with azathioprine (AZA) would increase the frequency of chronic refractory gout patients who had persistent urate lowering from pegloticase therapy.Methods:This open label multicenter study enrolled subjects with chronic gout who failed to lower serum urate to <6 mg/dL despite medically indicated doses of urate lowering therapy (NCT02598596). Patients were screened for adequate levels of the AZA metabolizing enzyme thiopurine methyl transferase and then started on daily oral AZA 1.25 mg/kg for 1 week and then 2.5 mg/kg for the remainder of the trial. Blood levels of AZA metabolites 6-thioguanine and 6-methylmercaptopurine were measured biweekly. After receiving 2 weeks of AZA, patients were started on pegloticase (8 mg IV) and were treated biweekly for 24 weeks. The primary endpoint was the persistent lowering of serum urate to <6 mg/dL at the last three consecutive study visits. Patients who had an increase in serum urate to >6 mg/dL while on therapy did not receive additional pegloticase. All patients received infusion prophylaxis with hydrocortisone as well as gout flare prophylaxis.Results:To date, 12 patients have been enrolled. All patients were male, 75% white and 25% African American. Mean age was 62.4 ± 14.7 years, the mean BMI was 31.1 ± 4.5 and the mean duration of gout was 13.8 ± 9.2 years. At baseline, all patients had visible tophi; 58.3% suffered from gout flares; 81.8% had hypertension; 45.5% had dyslipidemia and 9.0% had coronary artery disease. Of the 12 patients, 6 have completed the full course of treatment with persistent urate lowering and 2 remain on treatment also with persistent urate lowering (figure). 2 patients lost the urate lowering effect, both after 2 doses of pegloticase, and did not receive additional therapy. 1 patient experienced an infusion reaction during the first dose (1 infusion reaction in 90 infusions [1.1%] in the entire trial to date) and 1 subject had subjective symptoms of AZA intolerance with no laboratory abnormalities; these subjects discontinued the study and were not evaluable for the endpoint. No adverse events related to AZA were reported and gout flares were noted in 6 subjects (mean 1.5 flares/patient with flares).Conclusion:AZA can be used safely in subjects with chronic refractory gout and appears to increase the frequency of subjects experiencing long term lowering of serum urate.

A localized non-healing ulcer: an unusual clinical presentation of pemphigus vulgaris

<p>Pemphigus vulgaris is an autoimmune blistering disorder commonly involving oral mucosa and skin<strong> </strong>with characteristic acantholysis that results in formation of fluid filled blisters and painful erosions. Herein we report a case distinguished by its unusual clinical presentation.<strong> </strong>A twenty-five year old man, presented to our outpatient department of dermatology, complaining of ulcer on forehead in the last one year. Examination revealed single ulcer covered with crust on right side of forehead. Clinically lupus vulgaris, pyoderma gangrenosum, recurrent herpes simplex, leishmaniasis and pemphigus vulgaris were kept as differential diagnosis. Tzanck smear revealed multiple acantholytic cells and mild neutrophilic inflammatory infiltrate. Histological examination of biopsy sample showed suprabasal clefting, acantholytic cells and mild perivascular dermal lymphocytic infiltrate. Features were suggestive of pemphigus vulgaris. Significant improvement occurred after three months of treatment with oral prednisolone, azathioprine and topical steroid. Although oral and skin involve­ment is common, in the form of flaccid blisters and erosions, but non healing ulcer is unusual. This may represent a period of limited activity during this chronic disease. There is paucity of data in literature regarding this. So, this<strong> </strong>case report highlights a, perhaps unique, clinical presentation of this autoimmune disease.<strong></strong></p>

IgG4 Related Peri-aortitis: A Case Diagnosed in Combined Military Hospital, Dhaka

IgG4 related disease is a multi-organ immune-mediated condition which links many disorders previously regarded as isolated, a single-organ disease without any known underlying systemic condition. It may mimic anymalignant, infectious and inflammatory disorders. It was recognized as a unified entity only 10 years ago. Histopathology is the key to diagnosis. The three central pathology features of IgG4 related disease are lymphoplasmacytic infiltration, stroriform fibrosis, and obliterative arteritis. It is important to promptly diagnose IgG4 related disease because this disease commonly manifests as swelling of the affected organs, which must be differentiated from true neoplasms. Periaortitis or periarteritis is one of the clinical features of IgG4 related diseases. IgG4 related arterial lesions occur mainly in the aorta and its main branches and radiologically characterized by homogeneous arterial wall thickening corresponding to pathological features of IgG4 related sclerosing inflammation in the adventitia. There are 5 types of IgG4 related peri-aortitis, out of which Type 2 is most common. IgG4 related peri-aortitis generally respond to glucocorticoids in its inflammatory stage, but recurrent or refractory cases are common. Greater awareness of this disease is needed to ensure earlier diagnoses to prevent severe organ damage. A 38-year-old male was diagnosed as Type 2 IgG4 related periaortitis 2 years ago in CMH, Dhaka. He was treated with oral steroid and Azathioprine with a rewarding outcome.
 Journal of Armed Forces Medical College Bangladesh Vol.14 (2) 2018: 217-219

Diagnóstico y manejo de la enfermedad pulmonar intersticial de la esclerosis sistémica en condiciones sanitarias desafiantes

A 51-year-old woman presented with swelling in both hands and a 3-months history of triphasic Raynaud phenomenon. She denied cough and dyspnea. The physical examination was notable for swollen hands, facial telangiectasia and salt and pepper lesions. She had no skin fibrosis. The determination of antinuclear antibodies and antitopoisomerase were positive. A spirometry demonstrated a forced vital capacity of 86% of the predicted. High resolution chest computed tomography revealed bilateral, basal and subpleural ground glass opacities. These findings were consistent with the diagnosis of Scleroderma-Related Interstitial Lung Disease. Moreover, due to the absence of skin fibrosis, a diagnosis of systemic sclerosis sine scleroderma was made. Infusions of endovenous cyclophosphamide were indicated at 4-week intervals, followed by oral azathioprine. This case showed that using PFT as the single screening method for SSc-ILD may cause clinicians to miss a significant number of patients and that the absence of pulmonary symptoms does not exclude lung disease in patients with normal FVC.

Metastatic Crohn Disease: A Clinicohistological Appraisal From a Tertiary Care Center in India.

Granulomatous dermatitis due to noncontiguous involvement of Crohn disease (CD) of the gut has been described as metastatic CD (MCD). MCD is the rarest form of cutaneous manifestations of CD. This study aims to analyze the clinicohistological features of MCD in a tertiary care center of India. A retrospective review of patients diagnosed clinically and histologically with MCD over past 5 years was performed. Data on cutaneous features, histological findings, and response to treatment were collected. Twelve patients (3 men and 9 women) with a mean age of 29 years were identified. All women had vulval involvement in the form of edema (80%), ulceration (60%), and fistula (20%). Among the 3 men, 2 had perineal and scrotal swelling and ulcer, whereas the third patient presented with leg ulcer. Intestinal CD was already diagnosed in 50% patients (5/10) at cutaneous presentation, whereas it was diagnosed subsequently in 30% (3/10) cases. Histological examination revealed nonnecrotizing granulomatous inflammation in the dermis in 11 patients (92%). Additional histological features included eosinophilic infiltrate (58%), panniculitis (33%), and vasculitis (33%). The patients were treated with various combinations of oral prednisolone, metronidazole, minocycline, azathioprine, and subcutaneous adalimumab with partial relief. MCD shows a wide spectrum of clinical presentation, with anogenital involvement being the most common. Histology reveals nonnecrotizing granulomas in the dermis in majority of the cases. The diagnosis is extremely challenging in patients without gastrointestinal involvement at presentation, and thus, a high index of suspicion is imperative.

Intratympanic infliximab is a safe and effective rescue therapy for refractory immune-mediated hearing loss.

To determine the efficacy and safety of the intratympanic infiltration of infliximab at the hearing threshold of patients in follow-up for refractory immune-mediated hearing loss. 17 patients were collected with relapses, despite maintenance treatment with oral azathioprine associated or not with oral prednisone at low doses (between 5 and 7.5ml/day) or refractory relapses to previous intratympanic corticoid treatment being 19 affected ears infiltrated. We measured the hearing threshold by Pure-Tone Average (PTA) 500-3000Hz, 125-8000Hz and 250-8000Hz in pre-infiltration (baseline) and follow-up 3weeks post-infiltration with auditory threshold at frequencies 125-8000Hz. The average age was 50.68years (±15.23years). After the administration of intratympanic infliximab, an improvement of the hearing threshold was showed in the Pure-Tone Average (PTA) calculated at 500-3000Hz (p = 0.004), 125-8000Hz (p = 0.001) and 250-8000Hz (p = 0.006). An immediate improvement in low frequencies also was observed: 125, 250 and 500Hz (p = 0.009, p = 0.002 and p < 0.001 respectively) also at 1000Hz (p = 0.004) and a persistence of the effect at 3months in the low frequencies: 125Hz (p = 0.020), 250Hz (p = 0.006) and 500Hz (p = 0.002). Infliximab intratympanic infiltration improves the hearing threshold in patients with immune-mediated hearing loss. The effect of improving the hearing threshold is higher in low frequencies and persists within 3months of the infiltration. The administration of intratympanic infliximab is an effective and safe technique.

Clinical profile and therapeutic response to rituximab in an adult Filipino patient with myelin oligodendrocyte glycoprotein (MOG) autoimmunity: A case report

Myelin Oligodendrocyte Glycoprotein (MOG) autoimmunity has recently emerged as an entity distinct from its clinical brother, Neuromyelitis optica (NMO) and its associated spectrum disorders (NMOSD). While these present in the same vein of transverse myelitis and optic neuritis, they differ in pathogenesis and biomarker positivity, with implications on treatment. This is the first known reported case of MOG positivity in the Philippines. A 25-year old Filipino female developed blurring of vision on the right with spontaneous resolution after three days. Three years later, she presented with numbness of the left arm and trunk, with T1 sensory level. Non-contrast cranial MRI showed T2-FLAIR hyperintense lesion on the left corona radiata. Spine MRI showed T2 hyperintensity from C3 to C4. Ophthalmologic evaluation confirmed bilateral optic neuritis. Pulse steroid therapy provided resolution of symptoms, with resolution of MRI lesions on repeat study after eight months. Symptoms recurred one month after, with triparesis after two months, in spite of oral steroids and Azathioprine. Patient was referred to our institution, and repeat MRI showed enhancing intramedullary lesions from C2 to C5 level. She was seronegative for aquaporin-4 assay. Spinal fluid studies revealed normal protein and IgG, with negative oligoclonal bands. Serum antibodies to MOG were detected. Therapy with Rituximab was given on the fourth and fifth months after disease recurrence, and has been relapse free with EDSS score of 1. NMOSD patients will benefit from MOG antibody testing where available, as this will have implications on treatment and prognosis.

Childhood IgA Vasculitis (Henoch Schonlein Purpura)-Advances and Knowledge Gaps.

Immunoglobulin A vasculitis (IgAV; formerly Henoch Schonlein Purpura) is the most common form of childhood vasculitis. It can occur in any age and peaks around 4–6 years old. It demonstrates seasonal variation implicating a role for environmental triggers and geographical variation. The diagnosis is made clinically and 95% of patients will present with a rash, together with any from a triad of other systems—gastrointestinal, musculoskeletal, and renal. Most cases of IgAV in children have an excellent outcome. Treatment may be required during the acute phase for gastrointestinal involvement and renal involvement, termed IgAV nephritis (previously HSP nephritis), is the most serious long-term manifestation accounting for ~1–2% of all childhood end stage kidney disease (ESKD). It therefore requires a period of renal monitoring conducted for 6–12 months. Patients presenting with nephrotic and/or nephritic syndrome or whom develop significant persistent proteinuria should undergo a renal biopsy to evaluate the extent of renal inflammation and there are now international consensus guidelines that outline the indications for when to do this. At present there is no evidence to support the use of medications at the outset in all patients to prevent subsequent renal inflammation. Consensus management guidelines suggest using oral corticosteroids for milder disease, oral, or intravenous corticosteroids plus azathioprine or mycophenolate mofetil or intravenous cyclophosphamide for moderate disease and intravenous corticosteroids with cyclophosphamide for severe disease. Angiotensin system inhibitors act as adjunctive treatment for persisting proteinuria and frequently relapsing disease may necessitate the use of immunosuppressant agents. Renal outcomes in this disease have remained static over time and progress may be hindered due to many reasons, including the lack of reliable disease biomarkers and an absence of core outcome measures allowing for accurate comparison between studies. This review article summarizes the current evidence supporting the management of this condition highlighting recent findings and areas of unmet need. In order to improve the long term outcomes in this condition international research collaboration is urgently required.

Sweet’s syndrome: A Therapeutic challenge

Sweet’s syndrome: A Therapeutic challenge - IJCED- Print ISSN No: - 2581-4710 Online ISSN No:- 2581-4729 Article DOI No:- 10.18231/j.ijced.2019.037, IP Indian Journal of Clinical and Experimental Dermatology-IP Indian J Clin Exp Dermatol

Anti-neutrophil cytoplasmic antibody (ANCA)-associated scleritis: A diagnostic challenge and outcome

Aim of the workThis report aims to present the clinical challenge in managing a case of anterior scleritis associated with anti-neutrophil cytoplasmic antibody (ANCA), which was masquerading as recurrent conjunctivitis and the lines of management and disease course. Case reportA 68-year-old Malaysian male presented with bilateral blurring of vision associated with pain and redness for one-week duration. He had prior episodes of eye redness and discomfort, which was temporarily relieved with a course of corticosteroid eye drops, on presumptive diagnosis of conjunctivitis. Visual acuity was 6/18 bilaterally. Anterior segment examination showed diffuse conjunctival and episcleral injection which was tender on palpation. There was no posterior segment involvement in both eyes. Patient was tested positive for ANCA and proteinase 3 (PR3). Urinalysis showed proteinuria and hematuria. Chest X-ray was clear with no evidence of pulmonary infiltrations, nodules, cavitation or pleural effusion. Electrocardiogram showed left ventricular hypertrophy with right bundle branch block. The patient also had sensorineural hearing loss. A diagnosis of ANCA-associated scleritis was made and patient was treated with a combination of oral glucocorticoids and azathioprine. The patient had two episodes of anterior scleritis and developed bilateral peripheral ulcerative keratitis (PUK) which resulted in permanent visual impairment with no further progress. Ongoing rheumatology service work-up for systemic vasculitis could not classify the case. ConclusionANCA-associated vasculitis can have atypical ocular presentation and can be clinically misdiagnosed as conjunctivitis. Long term visual and systemic complications can be prevented with early detection and prompt immunosuppressive treatment.

Refractory Ocular Behçet’s Disease; Outcome of Low Dose Infliximab

A 40-year-old woman had been suffering of many symptoms of Behcet’s disease (BD) since her childhood without being diagnosed. She had recurrent mouth ulcers and from the age of 21 vulva ulcers followed by loss of vision due to central retinitis and later also ankle arthritis. At the age of 31, uveitis due to BD was diagnosed. The fact that BD is often not recognized in Bangladesh explains the marked delay in her diagnosis. The initial central retinitis responded well to oral glucocorticoids, azathioprine and cyclosporine, but in the course of time she became refractory to these agents. Considering her financial constraints, low dose Infliximab (3mg/kg) was used resulting in a remarkable but temporal improvement, she came in remission by using 5mg/kg regimen with increased interval time. We summarize the treatment options for ocular involvement in BD patients Conclusions: In countries like Bangladesh diagnosis of Behcet’s disease can be delayed. Early cooperation of dermatologists and eye surgeons with rheumatologists is necessary. Most cases of resistant ocular BD can nowadays be successfully treated with anti TNF-agents. Promising results are published with other biologics for refractory and multi-resistant cases.

Rituximab as induction therapy in refractory myasthenia gravis: 18month follow-up study.

Myasthenia gravis is an immune-mediated disorder characterized by easy fatigability and diurnal variation in skeletal muscle weakness. Aim of therapy is to prevent crisis and maintain remission. However, despite standard therapy, some remain refractory to treatment. To look for efficacy of rituximab in treating refractory myasthenia gravis (MG) in the form of MGFA-PIS score, number of crisis, and dose reduction in immunotherapies. A retrospective study was performed in patients with myasthenia gravis (MG) referred to the All India Institute of Medical Sciences (AIIMS) from January 2012 to December 2017 with follow-up of at least 6 months. Eight refractory MG patients (six AchR positive and two Musk-positive) were identified on oral corticosteroids and azathioprine. After four cycles of rituximab, all patients showed a dose reduction of whom seven were completely tapered off prednisone and there was a 53.8% dose reduction in azathioprine. All patients were continued on AZA after RTX infusion unless contraindicated. Seven achieved minimal manifestation (MM)-2 status as per the MGFA-PIS scale. None of the patients had infusion associated reactions or cytopenia post-RTX infusion. In this small retrospective study, we used RTX as induction therapy and results suggest that repeated RTX infusions may not be necessary as it adds to cost of therapy, especially in LMIC like India.

A randomized comparative study of the effect of betamethasone oral mini-pulse therapy versus oral azathioprine in progressive nonsegmental vitiligo

To the Editor: In progressive vitiligo the available therapeutic modalities are limited. Systemic corticosteroid in the form of oral mini-pulse (OMP) therapy has been successfully used in several studies.1-3 There is always a need for another immunosuppressant, and with its effect on both T and B lymphocytes, azathioprine can be a potential alternative.4

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 1: treatment and prevention.

This review is part of a series of annual updates summarizing the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2016 with a focus on treatment and prevention of AE. There is reasonable evidence of benefit for topical corticosteroids, calcineurin inhibitors, a glycyrrhetinic acid-containing preparation (Atopiclair® ), oral ciclosporin, oral azathioprine, narrowband ultraviolet B radiation and education programmes. Overall, there is evidence that topical corticosteroids and calcineurin inhibitors have similar efficacy and that both can prevent AE flares when used twice weekly as maintenance therapy. However, topical calcineurin inhibitors are costlier and have more adverse reactions, thus topical corticosteroids should remain the standard of care for patients with AE. There is no evidence that multiple applications are better than once-daily application of topical corticosteroid. There is inconsistent evidence to support omalizumab and specific allergen immunotherapy use in AE. There is some evidence that vitamin D supplementation and synbiotics reduce AE severity, although the margin of improvement may not be clinically meaningful. There is little evidence to support the use of wet wraps or of complementary/alternative medicine (including Chinese herbal medicine). There is some evidence to suggest that a diet high in fish in infancy may be preventative for AE, but other dietary interventions for the prevention of AE show little promise. This review provides a succinct guide for clinicians and patients wishing to remain up to date with the latest evidence for the treatment and prevention of AE.

Alopecia Areata in 12 years old female treated with Oral Azathioprine: A case report and review

Alopecia Areata (AA) is an autoimmune condition that attacks the hair follicles. AA typically presents as smooth, sharply demarcated, round patches of hair loss without atrophy. We reported a case of Alopecia Areata (AA) in 12 years old female treated with oral azathioprine.

Comparative study of safety and efficacy of oral betamethasone pulse therapy and azathioprine in vitiligo

Background: Vitiligo is a common skin disorder causing depigmented macules that can impair a patient's quality of life. There are number of treatment modalities are available but at the present, there are no studies compairing betamethasone pulse therapy versus azathioprine daily therapy in treatment of vitiligo. Objectives: To compare the safety and efficacy of Azathioprine daily and Betamethasone pulse therapy in the treatment of in vitiligo. Materials and Methods: We included two vitiligo patient groups. namely group A and group B Patients of group A were given oral Azathioprine to be given 50mg twice daily and those of second group B, Betamethasone were given as a single oral dose of 5 mg on two consecutive days per week. Therapy in both groups was given for a total of 6months with follow up at 1, 3 and 6th month. Clinical photographs were taken at each visit. Side-effects if any were noted. Results were calculated with help of VASI score (vitiligo area severity index). Results: At the baseline: The patients to group A (SD 3.81± 2.3) and of group B (SD 3.76± 2.28) were having depigmented patches (P = 0.90). At the first follow up: Although there was significant improvement with perifollicular repigmentation started in both groups but the patients are of group B (SD 3.38±2.06) were showing slower response as compared to oral group A (SD 3.70± 2.28). At the second follow up: Remarkable improvement is seen in both groups compared (P = 0.17). At the third follow up: Significant improvement is seen in both groups compared (P = 0.09). Conclusions: Azathioprine and betamethasone pulse therapy are equally effective in treatment of vitiligo.

Alopecia areata treated with oral azathioprine: A case series

Alopecia areata is commonly encountered non scarring alopecia with clinical presentations ranging from localised bald patches to extensive involvement. Clinical course is variable ranging from self limiting disease to chronic relapsing and recalcitrant disease. Topical and oral corticosteroids; nonetheless being front line agents for the treatment of alopecia areata;are not advocated for long term administration due to potentially undesirable systemic side effects. Hence the need of steroid sparing immunosuppresive agents like Azathioprine is warranted which have desired therapeutic action without much systemic adverse effects. We report a case series of 4 patients of alopecia areata treated with systemic azathioprine monotherapy.