Additional Immunosuppressive Agents Research Articles

Continuous Intermittent Intravenous Immunoglobulin in Heart Transplant Recipients with Elevated Donor-Specific Antibody Levels

<h3>Purpose</h3> Donor-specific antibodies (DSA) develop following heart transplantation (HT), and are associated with antibody-mediated rejection (AMR). However, treatment of persistently elevated DSA levels remains unclear. We aimed to evaluate the use of intermittent intravenous immunoglobulin (IVIg) for the treatment of elevated DSA. <h3>Methods</h3> We identified all adult HT recipients receiving monthly IVIg infusions between September 2019 and October 2020. Patient information including serial DSA levels, as well as hemodynamic and echocardiographic characteristics, were collected from the electronic health record. <h3>Results</h3> The cohort included 17 patients with a mean age of 57 +/- 15 years, 65% were male, & median time from HT was 48 months. 7 patients had prior biopsy-proven AMR, 7 had high mean fluorescence intensity (MFI) DSA alone, and 3 had allograft dysfunction without proven etiology. The average left ventricular ejection fraction (LVEF) prior to IVIg was 50% +/- 14%. Prior to intermittent IVIg 12 patients (71%) received an additional immunosuppressive agent (thymoglobulin, bortezomib, rituximab, belatacept), while 11 of them (65%) also received plasmapheresis. The mean duration of IVIg following pAMR was 7.6 +/- 7 months. DSA MFI decreased by 27% in patients with confirmed diagnosis of AMR and by 10% in those with elevated DSA alone after initiating intermittent IVIg (figure). Both LVEF and cardiac index improved in all three groups following initiation of IVIg infusions. Pulmonary capillary wedge pressure (PCWP) decreased in the elevated DSA and allograft dysfunction groups while it increased in the AMR group. Seven patients were admitted for suspected rejection after starting treatment. <h3>Conclusion</h3> DSA MFI declined and LVEF improved following initiation of intermittent IVIg infusions. Further study is needed to determine whether IVIg can prevent <i>de novo</i> or recurrent AMR.

Preexisting and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs

Autoimmune cytopenias (AICs) affect 5% to 9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs—ibrutinib, idelalisib, and venetoclax—have a prominent role in the treatment of CLL, but their impact on CLL-associated AICs is largely unknown. In this study, we evaluated the characteristics and outcome of preexisting AICs and described the incidence, quality, and management of treatment-emergent AICs during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab, and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody). A history of preexisting AICs was reported in 104 (13%) of 815 patients. Interestingly, 80% of patients whose AICs had not resolved when treatment with a targeted drug was started experienced an improvement or a resolution during therapy. Treatment-emergent AICs occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib therapy, and in 7% during venetoclax therapy, with an estimated incidence rate of 5, 6, and 69 episodes per 1000 patients per year of exposure in the 3 treatment groups, respectively. The vast majority of patients who developed treatment-emergent AICs had unfavorable biological features such as an unmutated IGHV and a del(17p) and/or TP53 mutation. Notably, despite AICs, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib, or venetoclax seems to have a beneficial impact on CLL-associated AICs, inducing an improvement or even a resolution of preexisting AICs in most cases and eliciting treatment-emergent AICs in a negligible portion of patients.

Shrinking lung syndrome treated with rituximab in pediatric systemic lupus erythematosus: a case report and review of the literature

BackgroundShrinking lung syndrome (SLS), a rare complication of systemic lupus erythematosus (SLE) characterized by dyspnea, low lung volumes, and a restrictive pattern on pulmonary function tests (PFTs), has only been reported in a few children. Given the rarity of SLS there is a paucity of literature regarding its optimal treatment. Outcomes are variable, with case reports documenting some improvement in most patients treated with corticosteroids, with or without additional immunosuppressive agents. However, most reported patients did not recover normal lung function. We report full recovery of a child with SLE and SLS following treatment with rituximab and review the current literature.Case presentationAn 11-year-old boy presented with a malar rash, myositis, arthritis, oral ulcers, leukopenia, anemia, positive lupus autoantibodies and Class II nephritis. He was diagnosed with SLE and treated with corticosteroids, hydroxychloroquine, azathioprine, and subsequently mycophenolate with symptom resolution. At age 14, his SLE flared coincident with a viral chest infection. He presented with a malar rash, polyarthritis, increased proteinuria and pleuritis which all improved with corticosteroids and ongoing treatment with mycophenolate. Six weeks later he presented with severe dyspnea, markedly decreased lung volumes, but otherwise normal chest X-ray (CXR) and high-resolution chest computed tomography (HRCT). He was found to have severely restricted PFTs (FEV1 27%, FVC 29%; TLC 43%). After additional investigations including echocardiography, pulmonary CT angiography, and diaphragmatic fluoroscopy, he was diagnosed with SLS and treated with rituximab and methylprednisolone. At 1 month his symptoms had improved, but he still had dyspnea with exertion and severely restricted PFTs. At 6 months his FVC and TLC had improved to 51 and 57% respectively, and were 83 and 94% respectively at 4 years. He had returned to all baseline activities, including competitive hockey.ConclusionsAlthough extremely rare, it is important to recognize SLS as a possible cause of dyspnea and chest pain in a child with SLE. Optimal treatment strategies are unknown. This is the second reported case of a child treated with rituximab for SLS who recovered normal lung function. International lupus registries should carefully document the occurrence, treatment and outcome of patients with SLS to help determine the optimal treatment for this rare complication.

Post-transplant cyclophosphamide as graft-versus-host disease prophylaxis in HLA matched sibling donor stem cell transplantation for patients with acute leukemia.

e19523 Background: Graft-versus-host disease (GVHD) is a life-threatening complication of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT). Calcineurin inhibitor (CNI) and methotrexate (MTX) have been used as the standard GVHD prophylaxis in HLA-matched HSCT. Promising clinical trial data using high dose post-transplant Cyclophosphamide (PT-Cy) with or without additional immunosuppressive agents (IS) have shown that it’s an effective, well tolerated alternative. However, experiences are limited with controversial results. Methods: We analyzed 62 patients with Acute Leukemia (39 males, 23 females) with age ranges from 18 to 60 years underwent allogeneic HSCT from matched sibling donors (MSD) using reduced intensity chemotherapy at Maadi Armed Forces Medical Hospital after informed consent. They were randomized into 2 groups according to GVHD prophylaxis regimen. The 1st group (40 patients) received MTX in the following doses; day+2 (15mg), day +4 (10 mg), day +6 (10 mg) with Cyclosporine (5mg/kg) from day -3 till day +90 and Mycophenolate (MMF) (2 -3gm/day) from day +1 till day +30. The 2nd group(22 patients) received PT-Cy (45 mg/kg/day) on days +3 and +4 with Cyclosporine (5mg/kg) from day +5 till day +30 &amp; MMF:(2-3gm /day) from day +5 till +30. Results: At median 1 year Post Allo, PT-Cy was associated with statistically significant lowering of chronic GVHD (cGVHD) incidence compared to MTX group (22.7%, 56.4%) respectively (P = 0.011). Incidence of acute GVHD (aGVHD) at day +100 was (40%, 22.7%) in group 1, 2 respectively (P = 0.169). 92% of patients in group 1 and 86.4 % of patients in group 2 were engrafted with full donor chimerism on day +30 (P = 0.659). The cumulative incidence of relapse at 4 years after transplantation was 17.9 % for group 1 and 36.4 % for group 2 (P &gt; 0.05). Relapse related mortality were 16.2% among MTX group while 27.3% in PT-Cy group (P = 0.10). Transplant related mortality (TRM) in MTX group were; Severe aGVHD (8%), cGVHD (10%), Hepatic Toxicity (8%), Nephrotoxicity (2.7%) &amp; ARDS (5.4%). In PT-Cy group TRM were; septicemia (18%), severe aGVHD (4.5%) &amp; ARDS (4.5%). Cumulative 4 years Disease Free Survival (DFS) &amp; Overall survival (OS) in PT-Cy group were (51.8 %, 46.4%) respectively while (69.3%, 39%) in MTX group which is statistically non-significant (P &gt; 0.05). Conclusions: For GVHD prophylaxis in MSD, PT-Cy is a safe alternative that reduces the risk of cGVHD in comparison with MTx based regimen without affecting Relapse rate, DFS or OS.

Pediatric Sympathetic Ophthalmia: 20 Years of Data From a Tertiary Eye Center in India.

To examine the clinical profile of sympathetic ophthalmia among the pediatric age group. Retrospective review of patients 18 years and younger with sympathetic ophthalmia seen in a tertiary eye care center between 1997 and 2017. Of 20 patients included in the study, 70% were male. The most common inciting event for sympathetic ophthalmia was trauma (85%), followed by vitreoretinal surgery (15%). All patients were treated with systemic steroids. Seventeen patients received additional corticosteroid-sparing immunosuppressive agents, and 4 patients (20%) required more than one immunosuppressive agent. Azathioprine was the most commonly used corticosteroid-sparing immunosuppressive agent. The most common complications were cataract (50%) and ocular hypertension (30%). The mean presenting best corrected visual acuity in the sympathizing eye was 1.15 ± 0.99 logarithm of the minimum angle of resolution (logMAR), which improved to 0.54 ± 1.00 logMAR following treatment. Visual outcome was good (6/12 or better) in 70% of the sympathizing eyes, and 3 of the exciting eyes in the current study had good visual outcomes after the treatment. Prompt and effective management with corticosteroid-sparing immunosuppressive therapy in children with sympathetic ophthalmia allows favorable control of the disease and retention of good visual acuity. [J Pediatr Ophthalmol Strabismus. 2020;57(3):154-158.].

91-Year-Old Man With Upper Extremity Ecchymoses

91-Year-Old Man With Upper Extremity Ecchymoses

Abstract ES1-2: Detecting and Managing Immunotherapy-related Toxicities Wisely

Abstract With the increasing use of immunotherapy, multidisciplinary breast cancer teams have to get used to recognising and managing immune-related side effects. Although immune checkpoint inhibitors are generally well tolerated, they can cause a wide range of side effects which often differ from those commonly seen with other types of cancer treatment. These immune-mediated side effects include inflammatory or autoimmune reactions which can resemble autoimmune diseases. Side effect patterns can be highly variable in terms of timing, severity and organ manifestation. They appear at any time, sometimes even months after the last treatment, and can affect any part of the body. The risk of developing immune-related side effects generally increases with longer treatment-duration. Most commonly affected body systems are skin, endocrine organs, the gastrointestinal tract, liver and lungs, but even very rare manifestations such as neurological disorders or myocarditis need to be considered as they can be serious. Before considering patients for immunotherapy, they should be carefully assessed with regards the risk of developing immune-related side effects. Patients with a history of autoimmune disorders are generally at risk of worsening of their autoimmune disease with immunotherapy. Early recognition and intervention are critical for the effective management which often includes the use of corticosteroids and occasionally additional immunosuppressive agents. Interdisciplinary working within oncology groups as well as with associated specialties is critical for optimal patients management. With effective management most immune-related side effects resolve and patients can continue their treatment. Citation Format: P Schmid. Detecting and Managing Immunotherapy-related Toxicities Wisely [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES1-2.

Anti-PD1 antibodies in patients aged ≥ 75 years with metastatic melanoma: A retrospective multicentre study

BackgroundAdvanced age is associated with comorbidities and immune system impairment, which may influence the efficacy and tolerability of immune checkpoint inhibitors. There is evidence that anti-PD1 antibodies in advanced melanoma are equally effective in patients >65 years. However, data on patients >75 years are lacking as co-morbidities and logistics often exclude them from clinical trials. MethodsWe retrospectively reviewed the clinical records of older patients with advanced melanoma undergoing any-line treatment with an anti-PD1 (nivolumab/pembrolizumab) to investigate its clinical effectiveness and toxicity in a real-life setting. Clinical response was assessed using RECIST criteria and toxicity was evaluated according to CTCAE 4.0. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and the Cox model was used to assess potential prognostic factors. Results174 patients were considered; 59.2% males, median age 79 years (range 75–93). The majority had a performance status of 0 and normal lactate dehydrogenase (LDH) levels (55.2% and 52.4%, respectively). 69.1% had multiple co-morbidities. 56.9% received nivolumab. 36.7% of cases showed an objective response and the disease control rate was 56.3%. Median OS was 17.2 months [95% CI: 8.87-not reached] and a better prognosis was observed for patients with normal LDH (p < .001) and lower performance status (p < .001). Treatment was well tolerated, only 11 patients experiencing severe (grade 3/4) toxicity. There were no treatment-related deaths. Adverse events were managed with corticosteroids and additional immunosuppressive agents were unnecessary. ConclusionsAnti-PD1 antibodies appear effective and well tolerated in older patients with advanced melanoma.

Respuesta a gamaglobulina endovenosa en arteritis de Takayasu de difícil manejo

La arteritis de Takayasu (AT ) es una vasculitis de grandes vasos que afecta a la aorta y a sus ramas principales. Los esteroides son la piedra angular del tratamiento; sin embargo, más de la mitad de los pacientes recaen, requiriendo inmunosupresores adicionales. Estudios abiertos han sugerido que metotrexate, ciclofosfamida, azatioprina, micofenolato mofetil y terapia anti-TNF pueden ser útiles en estos casos. Se reporta un caso de una paciente con AT con múltiples recaídas pese a metotrexate, esteroides, rituximab, ciclofosfamida, infliximab, revascularización percutánea y quirúrgica. Se decidió el uso de gammaglobulina endovenosa (IVIg), con control total y sostenido de manifestaciones vasculíticas, suspensión de esteroides y disminución de los reactantes de fase aguda

Minimal change disease and focal segmental glomerulosclerosis

Minimal change disease (MCD) or minimal change glomerulonephritis and focal segmental glomerulosclerosis (FSGS) are the two major causes of nephrotic syndrome in children and young adults. Both disease entities resemble each other and can sometimes only be discriminated on the basis of their clinical courses. MCD and FSGS display two classical examples that share acommon pathophysiology in which the glomerular podocyte and the cytoskeleton of its foot processes play important roles. Therefore, the term "podocytopathy" was introduced for both diseases. In this article, we compare their differences and similarities, and summarized new data on pathophysiology and treatment. In adults, only arenal biopsy including electron microscopy allows for the discrimination of MCD and FSGS and other differential diagnoses. The identification of aprimary or secondary form of the disease is based on the clinical course. Data from studies on the treatment are sparse; hence, treatment is still based on high-dose steroids followed by additional immunosuppressive agents. In secondary forms, treatment of the underlying disease is elementary.

Steroid-free remission in lupus: myth or reality; an observational study from a tertiary referral centre.

Whether maintaining steroid-free remission is feasible in Indian patients with systemic lupus erythematosus (SLE). In 148 patients with SLE including 78 lupus nephritis (LN) previously put into remission, steroid therapy was gradually tapered off. Patients received glucocorticoids for median 1855days (interquartile range (IQR) 901-2834) before discontinuing. Median duration of follow-up was 539days (IQR 266.25-840.75). Flare occurred in 31 patients (20.9%; 95% confidence interval (CI) 15.17-28.19, renal flare in 12.16% (18/148, 95% CI 7.83-18.41)). Most of the flares occurred in the first year of follow-up (41.9%, 13/31). Overall 93.5% (29/31) of flares occurred in those who received ≤ 8years of glucocorticoids, compared to 6.5% (2/31) of flares in others (p = 0.009). Median flare-free survival was 611days (95% CI 518-704). Multivariate Cox regression identified the following predictors of flare-free survival: duration of disease (hazard ratio (HR) 0.89, 95% CI 0.84-0.94, p < 0.001), duration of glucocorticoid before discontinuing (HR 1.000086, 95% CI 1.000047-1.00012, p < 0.001) and second immunosuppressive (HR 1.89, 95% CI 1.251-2.87, p = 0.003). Additional risk factors of a renal flare-free survival among patients with LN were initial dose of glucocorticoids (HR 0.97, 95% CI 0.94-0.99, p = 0.005) and presence of haemolytic anaemia (HR 2.43, 95% CI 1.067-5.54, p = 0.035). About 20% patients undergo exacerbation of disease activity after glucocorticoid withdrawal. Treatment for ≥ 8years before discontinuing and an additional immunosuppressive agent improve the chance of flare-free survival.

Adult minimal-change disease: observational data from a UK centre on patient characteristics, therapies, and outcomes

BackgroundMinimal change disease (MCD) is a common cause of the nephrotic syndrome in adults with limited evidence on its treatment and prognosis. We examined the presenting characteristics, treatments, and outcomes of adult patients with MCD in our centre.MethodsThis was an observational cohort study using retrospectively-collected data. All patients who had a renal biopsy reported as MCD between 1996 and 2012 were included, and data were collected at baseline and during follow-up. Statistical analysis included Cox-regression analysis to examine which factors were associated with risk of relapse.ResultsSeventy-eight patients were included, and had a median age of 36 years, and were 60% male and 73% white. Median follow-up time was 72 months. 37% were in AKI at presentation, which was significantly associated with a lower serum albumin and older age. Although 10% were steroid-resistant, 98% achieved remission at a median time of 5 weeks. 61% relapsed, at a median time of 11 months, and patients had a median number of 2 relapses during follow-up. A higher eGFR was associated with an increased risk of relapse (hazard ratio 1.18 [1.03–1.36] per 10 mL/min increase in eGFR), and females were significantly more likely than males to have an early relapse. Nearly half of the cohort required an additional immunosuppressive agent on top of glucocorticoids, the most commonly used being calcineurin inhibitors. Five patients subsequently developed FSGS: these patients had a lower baseline creatinine, a higher serum albumin, a longer time to remission, and were more likely to be steroid-resistant. Follow-up renal function was generally preserved, but follow-up creatinine was higher in those who had presented with AKI, and in those who had been commenced on a RAS inhibitor after biopsy. Infection requiring admission, diabetes mellitus and venous thromboembolism developed in 14%, 12%, and 12% of patients respectively.ConclusionsNearly all adults with MCD achieve remission, but relapses and disease- and therapy-related complications are common. In our cohort, eGFR and gender were associated with risk of relapse, and these previously undescribed associations could be explored further in future work.

Identical Twin Small-bowel Transplantation Without Maintenance Immunosuppression: A 5-year Follow-up and Literature Review.

BackgroundThe availability of an identical twin donor that allows avoidance of complications related to graft rejection and immunosuppression represents an ideal treatment option for irreversible intestinal failure.Methods and ResultsWe described a 45-year-old woman who lost most of her small bowel due to acute superior mesenteric thrombosis received a living-related small bowel transplant from her identical-twin sister. Monozygosity was established by buccal smear DNA amplification using short tandem repeat. A pretransplant panel-reactive antibody was 47.5% with several HLA antibodies in higher titers. The patient received a brief course of steroids without any additional immunosuppressive agents after transplantation. Her postoperative course was uneventful without an episode of rejection or infection. The preformed HLA antibodies steadily declined over time after transplantation. At a 5-year follow-up, the patient achieved full enteral autonomy from parenteral nutrition with a regular lifestyle.ConclusionsIdentical-twin intestinal transplantation appears to provide the best outcomes by avoiding complications related to rejection and immunosuppression. We provide evidence that it may confer greater long-term immunological advantages even in a high-immunologic risk recipient.

Management of adverse events related to checkpoint inhibition therapy.

SummaryIO treatments (immuno-oncology treatments) have become reality and are now daily practice or, in some cases, a daily challenge. New recommendations are being made with the prime purpose of increasing alertness and awareness as well as emphasizing standard operating strategies to deal with immune-related adverse events (ir-AEs) in patients treated with immune checkpoint inhibitors (ICI). This brief review refers to systemic reviews, guidelines and meta-analyses, randomized controlled trials and case series published from 2000 to the present. Existing recommendations for optimal management of toxicities vary according to organ systems affected and grading. Grade 1 toxicities (exception to the rule: neurologic, hematologic, cardiac manifestation) require close monitoring. Grade 2 toxicities prompt immediate treatment interruption combined with corticosteroid administration (prednisone or methylprednisolone 0.5–1 mg/kg/day) until the symptoms revert to grade 1 or less. ir-AEs up to grade 3 or 4 justify suspension of treatment together with increased dosage of prednisone or methylprednisolone (1–2 mg/kg/day) combined with close monitoring to continuously adapt the current immunosuppressive strategy. In some cases, a different additional immunosuppressive agent has to be evaluated. Only when all symptoms have disappeared and immunosuppressive treatment produces a response can all immunosuppressive agents be tapered. Endocrinopathies are the exception to the rule and are mostly controllable by hormone replacement, at least in low-grade manifestation. This short review focuses on the main aspects that help manage immune-related side-effects and elucidates all the additional aspects surrounding and contributing to successful treatment and management of cancer patients.

Infection-associated vasculitides.

Vasculitides are disorders characterized by inflammation of the vessel walls, often caused by autoimmunity, but sometimes as a result of microbial invasion. Almost all types of microbes including bacteria, viruses, protozoa and fungi have been incriminated in the pathogenesis of vasculitis. Accurate etiological diagnosis is important since immunosuppressive treatment may lead to further deterioration if infection is the cause of vasculitis. Clinical features sometimes provide clues to the etiology. Further evaluation requires a focused and cost-effective plan of laboratory investigation. The investigations aim at establishing the diagnosis of vasculitis and identify the causative organism. An accurate diagnosis of vasculitis optimally requires histological examination and imaging. For infection-associated vasculitis, the identification of the organism requires studies of stained specimens, cultures, and/or detection of antigens and antibodies. Ideally, the treatment involves administration of an appropriate antimicrobial. In non-self-limiting types of vasculitides, glucocorticoids are needed when the symptoms are progressive, with vital organs involvement, and sometimes, when there is no antimicrobial agent of proven efficacy against the incriminated agent. Additional immunosuppressive agents or interventions must be considered when the disease is severe and/or post-infective immune mechanisms are involved in the pathogenesis, e.g., severe HBV- or HCV-associated vasculitides. Available preventative vaccinations are also crucial. The incidence of HBV-associated vasculitides dramatically decreased following HBV vaccination campaigns, and other infection-associated vasculitides may as well in the future.

Systemic lupus erythematosus and ocular involvement: an overview.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of undefined etiology and with remarkably heterogeneous clinical features. Virtually any organ system can be affected, including the eye. SLE-related eye involvement can be diagnosed in approximately one-third of the patients and is usually indicative of disease activity. An early diagnosis and the adoption of suitable therapeutic measures are necessary to prevent sight-threatening consequences, especially in patients with juvenile SLE. Periocular lesions, such as eyelid involvement and orbital inflammation, are relatively rare and, in case of orbital masses, may require a biopsy control. Keratoconjunctivitis sicca or secondary Sjögren's syndrome is the most frequent ophthalmic manifestation of SLE. According to its variable severity, lubricating tear drops may be sufficient in mild cases, whereas cyclosporine-A ophthalmic solution, glucocorticoids (GCs), methotrexate, and/or other immunosuppressive drugs may be required in the more severe cases. Partial occlusion of the lacrimal punctum by thermal cautery is rarely applied. Although uncommon, episcleritis and scleritis can sometimes be detected as an initial finding of SLE and reveal themselves as moderate to intense ocular pain, redness, blurred vision, and lacrimation. Unilateral or more often bilateral retinopathy is responsible for visual loss of variable severity and is ascribed to vasculitis of the retinal capillaries and arterioles. In addition to the combined treatment suitable for all patients with active SLE, intravitreal bevacizumab should be considered in cases of severe vaso-occlusive retinopathy and laser photocoagulation in cases of neovascularization. Purtscher-like retinopathy is likely ascribable to the formation of microemboli that results in retinal vascular occlusion and microvascular infarcts. Choroidal disease is characterized by monolateral or bilateral blurred vision. Because of the choroidal effusion, retinal detachment and secondary angle-closure glaucoma may occur. Ischemic optic neuropathy is characterized by acute-onset and progressive binocular visual impairment as a consequence of occlusion of the small vessels of the optic nerves due to immune complex vasculitis. Intravenous GC boluses followed by oral GCs and/or, in case of recurrence, intravenous cyclophosphamide and/or rituximab are commonly employed. Neovascularization can be treated by intravitreal bevacizumab and progression of retinal ischemic areas by retinal laser photocoagulation. Ocular adverse events (AE) have been described following the long-term administration of one or more of the drugs presently used for the treatment of SLE patients. Posterior subcapsular cataracts and secondary open-angle glaucoma are common AE of the prolonged GC administration. The long-term administration of hydroxychloroquine (HCQ) sulfate is well known to be associated with AE, such as vortex keratopathy and in particular the often irreversible and sight-threatening maculopathy. Length of administration>5years,>1000g total HCQ consumption,>6.5mg/kg daily dosing, coexistence of renal disease, and preexisting maculopathy are all considered risk factors for HCQ-induced retinopathy. Ocular AE of additional immunosuppressive and biological agents are still poorly known, given the worldwide more limited experience with their long-term use. A thorough ophthalmological control is strongly recommended at closer intervals for all SLE patients, in step with the total length of exposure to the drugs and the cumulative dose administered.

Everolimus for pediatric patients with acute graft-versus-host disease after hematopoietic stem cell transplantation

Acute graft-versus-host disease (aGVHD) is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Due to the poor prognosis for patients not responding to first-line steroids treatment, improvements in aGVHD therapy are needed. Everolimus is a promising candidate that combines immunosuppressive properties with anti-neoplastic effects. Here, we retrospectively reviewed the efficacy of everolimus with steroids as primary treatment in 13 patients with grade II to grade IV aGVHD after HSCT. Among them, 12 (92.3%) had complete response to everolimus with steroids without additional immunosuppressive agents. The median duration of therapy was 76 days (range 20–110). Asymptomatic hypertriglyceridemia was the most common therapy complication (69.2%), but treatment interruption was not needed. Thrombotic microangiopathy was rare (7.7%), but can be quickly solved by stopping everolimus and cyclosporine treatment. Other toxicities were manageable. Two patients developed chronic GVHD (15.4%), limited in one and extensive in the other. The overall survival was 76.9% with a median follow-up of 3.4 years after HSCT (range 0.7–5.7). Accordingly, everolimus with steroids were feasible for patients with aGVHD after HSCT as primary treatment. Further large-scale studies are required.

Clinical Spectrum of Medium-Sized Vessel Vasculitis.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of medium-sized visceral vessels. However, cutaneous arteritis (CA) and gastrointestinal (GI) vasculitis are forms of single-organ vasculitis having indistinguishable histopathologic findings from PAN. The aim of this study was to evaluate and compare the clinical characteristics, treatment, and outcomes of patients with systemic PAN, CA, and GI vasculitis. Retrospective cohorts were assembled, consisting of patients with PAN, CA, and GI vasculitis between 1980 and 2014. The demographics, clinical characteristics, treatment, and outcomes of patients were abstracted from medical records. We included 48 patients with PAN, 41 patients with CA, and 19 patients with GI vasculitis. The disease of 1 patient evolved from CA to systemic PAN during the disease course. At diagnosis, 94% of patients with PAN, 93% of patients with CA, and 67% of patients with GI vasculitis were treated with glucocorticoids. Additional immunosuppressive agents were used in 67% of PAN, 37% of GI vasculitis, and 32% of CA cases. The 5-year cumulative relapse rate was 45.2% in CA, and only 9.6% in PAN during a followup of approximately 6 years. No deaths were observed in the CA group. The survival rate at 10 years was 66% in the PAN group and 61% in the GI vasculitis group. Systemic PAN, CA, and GI vasculitis take different clinical courses and therefore may be different diseases, rather than existing on a spectrum of the same disease. Progression of CA to systemic PAN is very rare. Relapse risk is low during followup in PAN. Patients with CA have a higher relapse rate than those with systemic PAN, possibly due to less use of immunosuppressive therapy in CA.

Characterization of isolated retinal vasculitis. Analysis of a cohort from a single center and literature review.

Isolated retinal vasculitis (IRV) is an inflammatory condition of unknown etiology confined to the retinal vessels. In contrast to secondary retinal vasculitis (RV), IRV has not been well characterized. To describe and characterize isolated forms of RV. We performed a retrospective review (2006-2016) of IRV patients from a multidisciplinary Uveitis Unit. RV diagnosis was based on funduscopic and fluorescein angiography findings. To distinguish between secondary RV and IRV, evaluations included clinical assessment, several inflammatory, autoimmune and microbiological laboratory markers, and a chest radiography. Ophthalmological features at disease onset, therapeutic interventions, ocular relapses, visual outcomes and laboratory findings were recorded. Our cases were subsequently compared with those from a literature review. Among 192 patients with RV, 11 (5.7%) were diagnosed with IRV. Seven patients with initially presumed IRV were reclassified as secondary after further evaluation. IRV generally affected adult women. Bilateral ocular involvement and retinal phlebitis were common findings. 72% of patients presented with visual loss, which was severe in 27%. Treatments used included systemic glucocorticoids (82%), additional immunosuppressive agents (27%), intravitreal therapy (37%), panretinal photocoagulation (37%) and pars plana vitrectomy (26%). The annual relapse rate was 0.46. Although final visual acuity was considered good in 86%, 45% experienced worsening and only 27% improved. IRV is a rare sight-threatening condition. Despite intensive local and systemic immunosuppressive treatment, visual improvement is observed in only 27% of cases. When IRV is suspected, a differential diagnosis excluding a systemic disease is always warranted. A multidisciplinary approach and a guided clinical, laboratory and imaging evaluation have proven to be useful to distinguish retinal single-organ vasculitis from secondary forms of RV.

ANCA-negative Churg-Strauss Syndrome

A rare and a disease of unknown etiology, Churg-Strauss syndrome (CSS) is a granulomatous necrotizing small vessel vasculitis characterized by the presence of asthma, sinusitis, and hypereosinophilia, which is initially described by Churg and Strauss in 1951. Because of its clinical and pathological features that overlap with those of the other anti-neutrophil antibody (ANCA)-associated systemic vasculitides (AASVs) and now the disease is classified as AASVs. The ANCA status may dictate the clinical phenotype. ANCA-positive patients are significantly more likely to have disease manifesta­tions associated with small-vessel vasculitis, including oecrotising glomemlonephritis, mononeuritis and purpura, whereas ANCA-negative cases predominantly likely to have cardiac and lung involvement. The objective of this case report is to point out the possibility of vasculitic rash in ANCA-negative CSS in a 35-year-old man and the disease rarely occurs in Bangladeshi population. We analyze the history, clinical examinations and relevant investigations related to the patient to establish the diagnosis in our department. The clinical scenario and biopsy help us to attain the diagnosis. But due to unavailability of patients' cohort we have limitations of comparison of ANCA status in Bangladeshi populations. Though ANCA-positive and ANCA-negative CSS differ phenotypically, primary therapy for both the conditions is systemic glucocorticoids. Additional immunosuppressive agents like cyclophosphamide, mycophenolate mofetil, azathioprine, rituxin1ab are occasionally added in patients with more advanced or refractory disease.