Hyperlipidemia: Prevalence, Monitoring, Management, Interactions with Immunosuppressive Agents, and Follow-Up

Abstract Background Ulcerative proctitis (UP) accounts for a significant proportion of cases of ulcerative colitis (UC) and implies limited involvement of the rectum. Some patients presenting initially with UP may progress to more extensive colitis (inflammation found distally to the rectum-sigmoid junction). Although several predictive factors for this progression have been described, none has been established as definitive. We aimed at determining risk factors predictive of proximal disease extension in UP. Methods Retrospective analysis of data from 97 patients (67% female) with UP (Montreal Classification: E1) with at least 12 months of follow-up at the IBD tertiary centre from January 2001 up to December 2018. Proximal extension was evaluated endoscopically during follow-up and was defined as E1 progressing to E2/E3. Factors examined comprised age, gender, race, presence of extra-intestinal manifestations, Mayo endoscopic score, disease relapse, use of corticosteroids, immunosuppressive and biological agents and colectomy. We used univariate analysis (Chi-square test) to assess the association of individual factors to proximal disease extension. Results A total of 29 (29.9%) patients experienced proximal disease extension during a mean follow-up of 137.36 ± 86.63 months. The following factors were significantly associated with proximal disease extension: higher initial Mayo score (p = 0.035) and higher initial disease severity (p = 0.0024). Use of corticosteroids initially (86.2% vs. 41.2%, p <0.0001), increased disease relapse rate (86.2% vs. 20.6%, p < 0.0001)and the need for immunosuppressive agents (57.1% vs. 13.6%, p <0.0001) or biological agents (42.9% vs. 10.3%, p <0.0001) were all significantly higher among UP patients with disease proximal extension, when compared with non-extensors. Colectomy was also associated with proximal disease extension (p = 0.0002). No significant association was found between UP proximal extension and gender, race, age at diagnosis and extraintestinal manifestations. Conclusion UP is a dynamic disease that may progress over time. UP patients with increased clinical and endoscopic severity at the diagnosis are likely to evolve with proximal extension and should be more carefully followed up. Reference

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Clinical, Endocrine and Imaging Characteristics of Patients with Primary Hypophysitis

Hormone and Metabolic Research ◽

10.1055/s-0044-101036 ◽

2018 ◽

Vol 50 (04) ◽

pp. 296-302 ◽

Cited By ~ 12

Author(s):

Anna Angelousi ◽

Carolina Cohen ◽

Soledad Sosa ◽

Karina Danilowicz ◽

Lina Papanastasiou ◽

...

Keyword(s):

Natural History ◽

Immunosuppressive Agents ◽

Hormonal Treatment ◽

Response To Treatment ◽

High Dose ◽

Partial Recovery ◽

Gonadal Dysfunction ◽

Imaging Characteristics ◽

Primary Hypophysitis

AbstractPrimary hypophysitis (PH) is a rare disease with a poorly-defined natural history. Our aim was to characterise patients with PH at presentation and during prolonged follow-up. Observational retrospective study of 22 patients was conducted from 3 centres. In 14 patients, PH was confirmed histologically and in the remaining 8 clinically, after excluding secondary causes of hypophysitis. All patients had hormonal and imaging investigations before any treatment. Median follow up was 48 months (25–75%: 3–60). There was a female predominance with a female/male ratio: 3.4:1. Eight out of 22 patients had another autoimmune disease. Headaches and gonadal dysfunction were the most common symptoms. Five patients presented with panhypopituitarism; 17 patients had anterior pituitary deficiency, and 7 had diabetes insipidus. At presentation, 9 patients were treated surgically, 5 received replacement hormonal treatment, and 8 high-dose glucocorticoids from whom 5 in association with other immunosuppressive agents. Six patients showed complete recovery of pituitary hormonal deficiencies while 6 showed a partial recovery during a 5-year follow-up period. No difference was found between patients treated with surgery and those treated medically. The overall relapse rate was 18%. PH can be manifested with a broad spectrum of clinical and hormonal disturbances. Long-term follow-up is required to define the natural history of the disease and response to treatment, since pituitary hormonal recovery or relapse may appear many years after initial diagnosis. We suggest that surgery and immunosuppressive therapy be reserved for exceptional cases.

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Anti-PLA2R Antibodies as a Prognostic Factor in PLA2R-Related Membranous Nephropathy

American Journal of Nephrology ◽

10.1159/000437236 ◽

2015 ◽

Vol 42 (1) ◽

pp. 70-77 ◽

Cited By ~ 26

Author(s):

Sjoerd A.M.E.G. Timmermans ◽

Myrurgia A. Abdul Hamid ◽

Jan Willem Cohen Tervaert ◽

Jan G.M.C. Damoiseaux ◽

Pieter van Paassen ◽

...

Keyword(s):

Membranous Nephropathy ◽

Immunosuppressive Agents ◽

Immunosuppressive Treatment ◽

Survival Rates ◽

Spontaneous Remission ◽

Correct Selection ◽

Persistent Proteinuria ◽

Phospholipase A2 Receptor ◽

Elisa Testing

Background: The natural course of idiopathic membranous nephropathy (MN) varies, as it is known through favorable outcomes in most patients. However, one third of patients with idiopathic MN will slowly progress to end-stage renal disease (ESRD). To prevent disease progression, patients at high risk to develop ESRD are treated with immunosuppressive agents. Therefore, a correct selection of patients who need immunosuppressive treatment is important. Methods: Here, we evaluated the prognostic value of anti-phospholipase A2 receptor 1 antibody (anti-PLA2R) levels regarding clinical outcome in a well-defined cohort of 73 PLA2R-related MN patients with long-term follow-up. At baseline, patients were subdivided into patients with either low or high antibody levels based on ELISA testing. Results: Spontaneous remission rates were highest among patients with low anti-PLA2R levels (79%; hazard ratio 2.72 (95% CI 1.22-6.08), p = 0.02) after a median follow-up of 2.9 (95% CI 0.8-5.0, p < 0.001) years, whereas high anti-PLA2R levels were associated with persistent proteinuria (p = 0.04) and/or the need for immunosuppressive therapy (p < 0.001). Renal survival rates were 97% at 5 years, 93% at 10 years, and 89% at 15 years; however, this was not different between the anti-PLA2R groups. ESRD occurred significantly faster in patients with severe proteinuria as compared to patients with either mild (p = 0.02) or moderate proteinuria (p = 0.05). Conclusions: Low anti-PLA2R levels may predict spontaneous remissions in patients with PLA2R-related MN. Therefore, we suggest that quantification of anti-PLA2R is of value to monitor these patients.

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Use of Mesenchymal Stem Cells To Treat Pediatric Patients with Severe (Grade III–IV) Acute Graft Versus Host Disease Refractory to Steroid and Other Agents on a Compassionate Use Basis.

Blood ◽

10.1182/blood.v110.11.2971.2971 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2971-2971 ◽

Cited By ~ 2

Author(s):

Vinod K. Prasad ◽

Kenneth G. Lucas ◽

Gary I. Kleiner ◽

July-An M. Talano ◽

David Jacobsohn ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Induction Therapy ◽

Graft Versus Host Disease ◽

Immunosuppressive Agents ◽

Compassionate Use ◽

Graft Versus Host ◽

Grade Iii ◽

Acute Graft

Abstract Background: Severe acute Graft versus Host Disease (aGvHD) refractory to steroids and other immunosuppressive agents carries a high mortality and very poor prognosis. Preliminary studies have shown that mesenchymal stem cells (MSC; Prochymal™ Osiris Therapeutics Inc.) can have immunosuppressive and tissue regenerative properties. We hypothesized that MSC might have efficacy in the treatment of GvHD. Methods: Between July 2005 and June 2007, 12 children (10 boys, 9 Caucasian) at 5 centers with aGvHD who failed steroid and additional immunosuppressive agents (median exposure 3 others) were treated with MSC provided by Osiris for compassionate use after FDA and local IRB approval. MSCs were administered per manufacturer’s instructions, without HLA or other matching, to eligible patients in a median of 30 days (range 16–181) from diagnosis of aGvHD. The cell dose for “induction therapy” was 8×106 cells/kg/dose in first 2 patients and 2×106 cells/kg/dose in all subsequent patients. Cells were given by IV infusion over 1 hour 2×/week for 4 weeks and initial response was assessed at the end of this induction therapy. “Maintenance therapy” 1×/week was continued in patients showing response. Results: The median patient age was 6 yrs (range 0.4–15) and all but one had received unrelated donor transplant (8 UCB, 3 adult MUD). GvHD Grade III and IV was present in 7 and 5 patients respectively. All patients had advanced (stage 3 or 4) gut disease, and 6 also had liver and/or skin involvement. Acute GvHD was diagnosed a median of 81 days (range 22–98) post-transplant and MSC were started at a median of 119 days (range 38–279) post-transplant. Three patients had renal failure requiring dialysis which had developed prior to MSC therapy. Patients received a median of 8 doses (range 3–21) of MSC. A total of 124 doses of MSCs were administered. No infusional or other identifiable toxicity was seen in any patient. One osteopetrosis patient developed ectopic lesions in the scalp and foot, however biopsy showed that no MSC DNA was present. With a median follow-up of 102 days (range 36–756) all 12 patients responded to therapy, with 6 patients having a complete response (CR), and the remainder having a partial response (PR) as defined by an improvement of at least one stage in one system without any worsening in another. Two of the PR patients are still being treated. Two patients responded, stopped therapy and later relapsed, requiring further MSC therapy to which they partially responded. Of 12, 6 patients died a median of 68 days (range 36–185) from the start of therapy. Three each died of multi-system organ failure and infection. Three of these were on dialysis pre-therapy. Conclusion: With short term follow-up in young children, MSC appears to be safe and likely have beneficial activity in severe treatment refractory aGvHD. Additional studies are underway to evaluate the efficacy of this agent in this clinical setting.

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Mesenchymal Stem Cells for Treatment of Refractory Chronic Graft-Versus-Host Disease.

Blood ◽

10.1182/blood.v110.11.4968.4968 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4968-4968

Author(s):

Weng Jianyu ◽

Xin Du ◽

Xiang Peng ◽

Zhang Xiumin ◽

Suijin Wu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Graft Versus Host Disease ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Immunosuppressive Agents ◽

Steroid Resistant ◽

Host Disease ◽

Graft Versus Host

Abstract Refractory extensive chronic graft-versus-host disease (GVHD) after allogeneic stem-cell transplantation (SCT) is associated with high mortality [Margolis J., SeminOncol 2000].However, conventional therapies including steroids are often unsuccessful in those patients with multiorgan involvement and are associated with significant therapy-related complications and poorly life quality. Mesenchymal stem cells (MSCs) have immunomodulatory effects [Tse WT et al., Transplantation 2003; Spees JI et al.,Proc Natl Acad Sci USA 2003]. Recently MSCs have been given intravenously to treat seven steroid resistant acute GVHD patients and one patient with chronic GVHD. MSCs effects in chronic GVHD is rarely known, although this successfully experience suggests that MSCs have been well tolerated and had a powerful immunosuppressive effects on acute GVHD. [Katarina Le Blanc et al., Lancet 2004; Olle Ringden., Transplantation 2006 ]. Here, we present our experience of using MSCs for treatment of Thirteen patients with refractory chronic GVHD. Between May 2005 and March 2007, thirteen patients (8 male, 5female) with hematological malignancies with a median age of 26(range:15 to 40) years who had received peripheral stem cells from sibling donors. All patients developed steroid resistant or extensive chronic GVHD, with progressive involvement of the skin(13), liver(10), oral mucosa(12),ocular glands(12), and thrombocytopenia (1) when the immunosuppressive agents were taped after five to twenty-four months. The MSC dose was median 1.0 ×106 cells/kg body weight of the recipient. In all, thirteen patients had at least received one dose, seven patients received more than two doses. MSC donors were in seven cases HLA-identical siblings, six unrelated mismatched donors. No side-effects were seen after MSCs infusions. All patients have responded after follow-up of the median time 15 months. One patient with moderate cGVHD had a complete responses, and discontinued all of the immunosuppressive agents without relapse more than 18.4 months after MSC infusion. Three moderate and two patients with severe chronic GVHD improved to mild degree, and six severe turned to moderate degree. Complete resolution was seen in gut(2/3), liver(5/10), skin(5/13), oral(6/12) and eye(2/12). One patient responded in skin, liver, oral mucose and eye, but developed in lung (bronchiolitis obliterans, BO) score of 2 which are considered severe chronic GVHD. Mean follow-up periods was 27m (rang: 14 to48m), Leukemia free survival(LFS)rate were 85%(11/13), and the overall survival (OS)rate were 92.3%(12/13). Our experience suggests that MSC infusion is a safe and effective adjunct therapy for refractory extensive chronic GVHD with resistance to conventional therapy. But more prospective, controlled studies with MSCs for treatment of GVHD should be performanced to evaluate this new treatment exactly.

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Lymphoproliferative disease of granular T lymphocytes presenting as aplastic anemia

Blood ◽

10.1182/blood.v96.10.3644.h8003644_3644_3646 ◽

2000 ◽

Vol 96 (10) ◽

pp. 3644-3646 ◽

Cited By ~ 2

Author(s):

Ronald S. Go ◽

Ayalew Tefferi ◽

Chin-Yang Li ◽

John A. Lust ◽

Robert L. Phyliky

Keyword(s):

T Lymphocytes ◽

Aplastic Anemia ◽

Cytotoxic T Lymphocytes ◽

T Lymphocyte ◽

Clinical Characteristics ◽

Immunosuppressive Agents ◽

Lymphoproliferative Disease ◽

Granular Lymphocytes ◽

Chronic Neutropenia

Lymphoproliferative disease of granular T lymphocyte (T-LDGL), also known as T-cell large granular lymphocyte leukemia, is a clonal disorder of cytotoxic T lymphocytes that is clinically manifested as chronic neutropenia and anemia. Association with autoimmune disorders is common. In 9 patients, T-LDGL is reported as presenting as aplastic anemia. The clinical characteristics were similar to acquired aplastic anemia. Morphologic evidence of increased granular lymphocytes in the peripheral blood and an excess of CD3+/CD8+/CD57+ cells in the bone marrow were found in most cases. Cyclophosphamide was ineffective, but noncytotoxic immunosuppressive agents generally produced a good response. After a median follow-up of 49 months, 5 patients had died from the disease or related complications. Median survival was 40 months. Aplastic anemia can be a presenting manifestation of T-LDGL, and T-LDGL should be considered in the differential diagnosis of acquired aplastic anemia.

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Lung nodules and IgG4 related disease: a single-center based experience

10.21203/rs.3.rs-46476/v1 ◽

2020 ◽

Author(s):

Yan Xie ◽

Anji Xiong ◽

Tony Marion ◽

Yi Liu

Keyword(s):

Lung Diseases ◽

Immunosuppressive Agents ◽

Ground Glass Opacity ◽

Lung Nodules ◽

Bronchial Wall ◽

West China Hospital ◽

West China ◽

Related Disease ◽

Igg4 Related Disease

Abstract Background and objective: This study was undertaken in an attempt to characterize the frequency and clinical features of lung nodules in IgG4 related disease (IgG4-RD) patients as an insight for help with the diagnosis of lung nodules.Methods: A retrospective study was carried out in West China Hospital, Sichuan University from January 2012 to December 2018, 89 patients with definite IgG4-RD were enrolled.Results: Fifty of 89 patients with definite IgG4-RD had radiologically confirmed lung nodules, 6 of whom were diagnosed with definite IgG4 related lung disease. Lung nodules detected in more than 40 patients were small and solid, always with regular margins. Multiple (41/50) and bilateral (34/50) distributions was also a major characteristic of these lung nodules. Lobulation and speculation were simultaneously detected in 3 patients, including 2 patients combined with pleural indentation. Calcification of nodules was detected in only one patient. Thirty-seven patients also had additional radiological abnormalities of lungs, including ground-glass opacity (21/50), thickening of pleura (9/50), thickening of interlobular septa (4/50), thickening of bronchial wall (3/50), pleural effusion (4/50), mass (3/50), interstitial changes (5/50), and mediastinal or hilar lymphadenopathy (32/50). Most patients (44/50) were treated with glucocorticoids alone or combined with immunosuppressive agents. Sixteen patients received a re-examination by chest computed tomography (CT) scan after treatment, 10 of whom showed a decrease in the size and/or the number of nodules.Conclusions: The incidence of lung nodules in IgG4-RD patients can be high. For an IgG4-RD patient with lung nodules, the possibility that the lung nodules related to IgG4-RLD is high. It is hard to differentiate IgG4 related lung nodules from other lung diseases, in particular, lung cancer. Radiological characteristics and positive responses to glucocorticoids and immunosuppressive agents can help with the differential diagnosis. For these patients, regular follow-up is also important.

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Outcomes of treatment of juvenile idiopathic arthritis related uveitis with TNF-alpha inhibitors

Pediatrician (St Petersburg) ◽

10.17816/ped5460-64 ◽

2014 ◽

Vol 5 (4) ◽

pp. 60-64

Author(s):

Ekaterina Vladimirovna Gaidar ◽

Mikhail Mikhaylovich Kostik ◽

Ludmila Stepanovna Snegireva ◽

Margarita Fedorovna Dubko ◽

Vera Vasilyevna Masalova ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Immunosuppressive Therapy ◽

Immunosuppressive Agents ◽

Tnf Alpha ◽

Early Administration ◽

Systemic Corticosteroids ◽

Alpha Receptors ◽

Membrane Bound

The aim of the study was to evaluate the efficacy of two anti-TNF-alpha biological agents: Adalimumab (humanized monoclonal anti-TNF-alpha antibody) and Infliximab (chimeric monoclonal antibody that binds both circulating and membrane-bound TNF-alpha receptors) in treatment of Juvenile Idiopathic Arthritis related uveitis. 37 children (73 % girls) with uveitis associated with aggressive forms of JIA who failed Methotrexate and topical treatment; Methotrexate and other immunosuppressive agents and systemic corticosteroids were included in the study. The age of patients at the beginning of biological therapies ranged 5-17 years. In ADA group the remission was observed in 61 % of cases, in 18 % we saw the reduction of flare-ups and in 14 % of children we registered exacerbation of the disease which was caused in most cases by discontinuation of non-biological drug. In INF group we observed remission in 78 % of the cases, no improvement in 22 %. The speed of remission in JIA associated uveitis treated with ADA and INF depended on the severity of uveitis, the time between the beginning of the disease and administration of immunosuppressive therapy. Early administration of anti-TNF-alpha agents, when there is no results from standard immunosuppressive therapy, allowed us to achieve remission in a shorter period of time and also allowed as to decrease the severity of complications of uveitis, as well as reduce the side effects of immunosuppressive therapy, especially of corticosteroids. This study needs to be continued to enroll more patients and to increase the follow-up time to evaluate the long-term efficacy and safety of anti-TNF-alpha agents in JIA associated uveitis.

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Methimazole-Induced Leukocytoclastic Vasculitis: A Case Report

Case Reports in Dermatology ◽

10.1159/000503990 ◽

2019 ◽

Vol 11 (3) ◽

pp. 303-309 ◽

Cited By ~ 2

Author(s):

Weeratian Tawanwongsri ◽

Pamela Chayavichitsilp

Keyword(s):

Leukocytoclastic Vasculitis ◽

Immunosuppressive Agents ◽

Thyroid Function Test ◽

Skin Lesions ◽

Definitive Treatment ◽

Antithyroid Drugs ◽

Drug Induced ◽

First Case ◽

Radioiodine Ablation

Major identifiable causes of leukocytoclastic vasculitis include certain infections and medications. Amongst antithyroid drugs, methimazole (MMI) is rarely implicated as a culprit drug. We report the first case, in Thailand, of MMI-induced leukocytoclastic vasculitis in a 41-year-old Thai female who had received MMI for relapsed Graves’ disease. MMI was discontinued and cholestyramine at a dose of 4 g four times daily was given instead. Her rashes on both legs resolved dramatically at 1-week follow-up. However, thyroid function test revealed unimproved thyrotoxicosis. She subsequently underwent radioiodine ablation as a definitive treatment. There were neither recurrent skin lesions nor other systemic involvements during the 3-month follow-up period. Notably, the most crucial step in the management of drug-induced leukocytoclastic vasculitis is the discontinuation of the offending drug in order to avoid further progression of the disease. The administration of immunosuppressive agents may not be necessary in patients with mild severity and non-vital organ involvement.

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Lymphoproliferative disease of granular T lymphocytes presenting as aplastic anemia

Blood ◽

10.1182/blood.v96.10.3644 ◽

2000 ◽

Vol 96 (10) ◽

pp. 3644-3646 ◽

Cited By ~ 30

Author(s):

Ronald S. Go ◽

Ayalew Tefferi ◽

Chin-Yang Li ◽

John A. Lust ◽

Robert L. Phyliky

Keyword(s):

T Lymphocytes ◽

Aplastic Anemia ◽

Cytotoxic T Lymphocytes ◽

T Lymphocyte ◽

Clinical Characteristics ◽

Immunosuppressive Agents ◽

Lymphoproliferative Disease ◽

Granular Lymphocytes ◽

Chronic Neutropenia

Abstract Lymphoproliferative disease of granular T lymphocyte (T-LDGL), also known as T-cell large granular lymphocyte leukemia, is a clonal disorder of cytotoxic T lymphocytes that is clinically manifested as chronic neutropenia and anemia. Association with autoimmune disorders is common. In 9 patients, T-LDGL is reported as presenting as aplastic anemia. The clinical characteristics were similar to acquired aplastic anemia. Morphologic evidence of increased granular lymphocytes in the peripheral blood and an excess of CD3+/CD8+/CD57+ cells in the bone marrow were found in most cases. Cyclophosphamide was ineffective, but noncytotoxic immunosuppressive agents generally produced a good response. After a median follow-up of 49 months, 5 patients had died from the disease or related complications. Median survival was 40 months. Aplastic anemia can be a presenting manifestation of T-LDGL, and T-LDGL should be considered in the differential diagnosis of acquired aplastic anemia.

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