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1.
Begelomab for severe refractory dermatomyositis: A case report.
De Lorenzo, R, Sciorati, C, Monno, A, Cavalli, S, Bonomi, F, Tronci, S, Previtali, S, Rovere-Querini, P
Medicine. 2021;(9):e24372
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Abstract
RATIONALE Severe refractory idiopathic inflammatory myopathy (IIM) represents a challenge for the clinician. The lack of efficacy of available tools reflects our incomplete insight into the molecular events sustaining the inflammatory tissue damage in these patients. We present the first case of refractory IIM treated with anti-dipeptidyl peptidase-4 (DPP-4)/cluster of differentiation 26 (CD26) monoclonal antibody. PATIENT CONCERNS A 55-year old man presented with proximal muscle weakness, diffuse erythematous skin lesions which rapidly evolved into ulcerations, dysphagia and dysphonia. DIAGNOSIS Increased serum creatine kinase levels and histological findings at muscle and skin biopsies were compatible with the diagnosis of dermatomyositis (DM). Several lines of treatment failed to control the disease including steroids, mycophenolate mofetil, tacrolimus, intravenous immunoglobulins and rituximab. Despite therapy, the patient also had recurrent intestinal vasculitis causing bowel perforation. Concurrently, DPP-4/CD26 expression in the patient's skin and skeletal muscle was observed. INTERVENTIONS The patient was treated with begelomab, a murine immunoglobulin G2b monoclonal antibody against DPP-4/CD26. OUTCOMES Dysphagia, skin lesions and intestinal vasculitis resolved and the patient experienced a significant improvement of his quality of life. CONCLUSION Blockade of DPP-4/CD26, which is expressed on T cells and mediates T cell activation and function, is safe and might be effective in patients with refractory DM.
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Successful treatment of refractory juvenile generalized pustular psoriasis with secukinumab monotherapy: A case report and review of published work.
Ho, PH, Tsai, TF
The Journal of dermatology. 2018;(11):1353-1356
Abstract
Juvenile generalized pustular psoriasis (GPP) is rare and often resistant to conventional systemic therapy such as methotrexate, retinoic acid and cyclosporin A. GPP can be induced by deficiency of interleukin (IL)-36 receptor antagonist (DITRA). No standardized guidelines are available for juvenile GPP or DITRA, and a uniformly safe and effective biologic agent has not been identified. However, multiple biologics approved for use in plaque-type psoriasis have also been used in GPP. Herein, we report a case of a 6-year-old Taiwanese boy with GPP and homozygous mutation at c.115+6T>C within the IL-36 receptor antagonist (IL36RN) gene, who was treated successfully with secukinumab after failure of prior methotrexate, acitretin, cyclosporin A, etanercept and adalimumab. Similar to two previously reported non-adult cases of GPP successfully treated with secukinumab, our case also demonstrated a history of repeated treatment failures with several conventional oral systemic agents and biologics. Different from these two cases, however, ours is the first of juvenile GPP successfully treated with secukinumab monotherapy, without using other systemic agent concurrently during the use of secukinumab.
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3.
SIADH in Systemic JIA Resolving After Treatment With an IL-6 Inhibitor.
Hodax, JK, Bialo, SR, Yalcindag, A
Pediatrics. 2018;(1)
Abstract
Interleukin-6 (IL-6) is implicated in the pathogenesis of both systemic juvenile idiopathic arthritis (SJIA) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but the 2 have not been previously described as occurring together. We report a case of a 6-year-old girl with symptoms of arthralgia, daily fevers, evanescent rash, lymphadenopathy, and laboratory evaluation showing elevated inflammatory markers, consistent with SJIA. At presentation, the patient had hyponatremia with a sodium level of 128 mEq/L. She had low serum osmolality with elevated urine osmolality, consistent with SIADH. Hyponatremia improved temporarily during times of fluid restriction as expected in SIADH, but did not resolve until SJIA was treated successfully with tocilizumab, an IL-6 receptor antibody that inhibits IL-6 activity. The positive response to treatment with tocilizumab supports the role of IL-6 in the pathogenesis of both SJIA and SIADH. Patients with SJIA should be monitored for SIADH to avoid complications of untreated hyponatremia.
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4.
Primary hypothyroidism and isolated ACTH deficiency induced by nivolumab therapy: Case report and review.
Zeng, MF, Chen, LL, Ye, HY, Gong, W, Zhou, LN, Li, YM, Zhao, XL
Medicine. 2017;(44):e8426
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Abstract
RATIONALE Nivolumab is a monoclonal IgG antibody blocking programmed death receptor-1 (PD1), leading to restoration of the natural T-cell-mediated immune response against the cancer cells. However, it also causes plenty of autoimmune-related adverse events, which often involves endocrine system. PATIENT CONCERNS A 54-year-old male with renal clear cell carcinoma was treated with nivolumab intravenously. Routine monitoring showed elevated thyroid-stimulating hormone and low free thyroxine after the 6th administration of nivolumab. After the 12th administration, he developed general fatigue, recurrent hypoglycemia, and relative hypotension. Laboratory tests showed low sodium, low morning cortisol without correspondence increase of corticotrophin (ACTH). Other pituitary hormones were normal. MRI showed no space-occupying lesions, but heterogeneous enhancement of the pituitary gland. DIAGNOSES Primary hypothyroidism and isolated ACTH deficiency. The etiologies were assumed to be nivolumab induced autoimmune lymphocytic thyroiditis and hypophysitis, respectively. INTERVENTIONS Hormone replacements with levothyroxine and acetate cortisone were given orally. Nivolumab was adjusted to lower dose and longer interval. OUTCOMES The patient felt good after adequate replacement. Nivolumab was returned to routine dose and interval six months later. And the metastasis was not obviously progressed during this time. LESSONS The present report provides the first detailed presentation of combined hypothyroidism and isolated ACTH deficiency induced by nivolumab. Adrenal deficiency often develops insidiously. We suggest routine monitoring of fasting blood-glucose, blood pressure and serum sodium as well as thyroid function during nivolumab and other cancer immunotherapies. When unexpected fatigue, hypoglycemia, hypotension or hyponatremia appeared, adrenal deficiency should be taken into consideration.
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Coexisting myasthenia gravis, myositis, and polyneuropathy induced by ipilimumab and nivolumab in a patient with non-small-cell lung cancer: A case report and literature review.
Chen, JH, Lee, KY, Hu, CJ, Chung, CC
Medicine. 2017;(50):e9262
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Abstract
RATIONALE Immune checkpoint inhibitors have led to the development of new approaches for cancer treatment with positive outcomes. However, checkpoint blockade is associated with a unique spectrum of immune-related adverse events (irAEs), which may cause irreversible neurological deficits and even death. PATIENT CONCERNS We presented a case of a 57-year-old man with non-small-cell lung cancer.who developed ptosis, dyspnea, and muscle weakness as initial symptoms with progression after the treatment with ipilimumab and nivolumab. DIAGNOSES Myasthenia gravis was confirmed by serum acetylcholine receptor antibody and single fiber electromyography. Myositis was identified by high level of serum creatine phosphokinase and electromyography. Polyneuropathy was identified by nerve conduction study. INTERVENTIONS The patient underwent treatment with steroid and pyridostigmine. Respiratory rehabilitation was also performed. OUTCOMES Dyspnea and muscle weakness improved gradually. Ipilimumab and nivolumab were permanently discontinued. LESSONS This case has increased the clinical awareness by indicating that the checkpoint inhibitors-related neurological irAEs could be complicated and simultaneously involve multiple neurological systems. Early recognition and complete evaluation are critical in clinical practice.
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[Myopathy in patients with Waldenströms macroglobulinemia. A case study and an overview of autoimmune expressions of type IgM monoclonal immunoglobulins].
Adam, Z, Kissová, J, Pour, L, Krejčí, M, Ševčíková, E, Koukalová, R, Čermáková, Z, Černá, M, Král, Z, Mayer, J
Vnitrni lekarstvi. 2015;(9):821-8
Abstract
Waldenströms macroglobulinemia which was manifested by muscle pain and anemia. The female patient had suffered from back pain for about 3 years before she came to our clinic. In the last year pain in the muscles of the upper and lower extremities developed in addition to back pain. This led to the suspicion of polymyositis. However this was not confirmed by a special examination. The patient was diagnosed with clearly established infiltration of lympho-plasmacytic lymphoma and 10.8 g/l of type IgM monoclonal immunoglobulin in the bone marrow. Serum myoglobin levels and serum CK activity were repeatedly significantly increased. Therefore the treatment with anti-CD20 monoclonal antibody (Mabthera) 375 mg/m2 i. v. was started, administered once a month, with cyclophosphamide 500 mg/m2 i. v. on days 1 and 15 of a 28-day cycle, and dexamethasone 20 mg from 1st through to 4th days and 15th through to 18th days of the treatment cycle. There were 8 cycles planned. Already after a 5th cycle, the disappearance of monoclonal immunoglobulin (negative immunofixation), normalisation of myoglobin and CK values and significant relief from muscle pain were achieved. The hemoglobin concentrations before treatment were significantly reduced, while they were normalised after treatment. After 5 cycles, the complete remission of Waldenströms disease was reached according to biochemical parameters, and normalisation of the serum myoglobin and creatine kinase levels was achieved.
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Buccal localization of Crohn's disease with long-term infliximab therapy: a case report.
Ciacci, C, Bucci, C, Zingone, F, Iovino, P, Amato, M
Journal of medical case reports. 2014;:397
Abstract
INTRODUCTION Cheilitis granulomatosa causes persistent idiopathic lip swelling and ulceration and it can sometimes be recognized as a unique or early manifestation of Crohn's disease. Spontaneous remission is rare and with the lack of controlled trials, different therapeutic approaches have been used. Some cases have been treated with an exclusion diet in the attempt to rule out diet allergens, while the most popular treatments include antibiotics such as tetracycline and clofazimine tranilast, benzocaine topical or intralesional steroids, and cheiloplasty, with different outcomes. CASE PRESENTATION We describe the case of a 23-year-old Caucasian man, primarily diagnosed with cheilitis granulomatosa for a severe lower lip swelling, and then with Crohn's disease of the terminal ileum and anus. Treatment of Crohn's disease with an anti-tumor necrosis factor alpha agent (infliximab) successfully induced remission of both the gastrointestinal disease and the oral lesion. CONCLUSIONS Our recommendation is that physicians should be able to recognize cheilitis granulomatosa as a possible marker of a more complex systemic disease and proceed first with an accurate physical examination, and further suggest investigations of the bowel. In cases of Crohn's disease, a therapy with biological agents can be successful.
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[A case of infliximab-related liver damage -case report and literature review].
Arai, O, Omoto, K, Notohara, K, Shibata, N, Kuboki, M, Ikeda, H
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology. 2013;(1):104-11
Abstract
A 50-year-old woman was admitted to our hospital with complaints of loss of vision, diarrhea and arthralgia. She was given a diagnosis of Behçet disease and given infliximab (IFX) to halt the progression of acute vision loss. Liver damage was detected after the fourth IFX dose. We assumed that this was a drug-induced condition caused by salazosulfapyridine (SASP). However, the liver damage worsened, and the condition did not improve even after discontinuing SASP. Thus, therapy to enhance hepatic function was initiated. Histological analysis of liver biopsy specimens showed centrilobular spotty necrosis and periportal hepatitis. We diagnosed autoimmune hepatitis rather than drug-induced liver damage. Because of liver function deterioration, we initiated steroid treatment and rapid improvement was observed. Therefore, liver function should be carefully monitored during IFX administration for patients with genetic predispositions to autoimmune hepatitis, such as human leukocyte antigen-DR4.
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Effect of infliximab induction therapy on secondary systemic amyloidosis associated with Crohn's disease: case report and review of the literature.
Pukitis, A, Zake, T, Groma, V, Ostrovskis, E, Skuja, S, Pokrotnieks, J
Journal of gastrointestinal and liver diseases : JGLD. 2013;(3):333-6
Abstract
Secondary systemic (AA) amyloidosis is reported as a serious complication that occurs in long-standing Crohn's disease (CD), with an incidence of 0.3-10.9%. Various therapeutic approaches using medicines and elemental diet have been recommended, but still there are no established standards of treatment for secondary systemic amyloidosis in CD. Only a few studies have shown the role of TNFα ihibitors in the treatment of AA amyloidosis over a long term period. We report the case of a 24-year-old male with CD complicated by AA amyloidosis with renal and gastrointestinal tract involvement treated with infliximab as induction therapy. Intestinal AA amyloidosis progression occurred at the same time with the development of CD as an early complication, whereas duration of CD prior to the diagnosis of renal AA amyloidosis was 6 years. Infliximab therapy (3 infusions) caused a significant decrease of serum amyloid A protein (by 97.9%), C-reactive protein (by 70%), improvement of disease activity index, and CD caused clinical symptoms. At the same time gradual progression of the renal damage (reduction of renal function) was not affected by the treatment. Direct efficacy of infliximab infusions on serum amyloid protein level may support the hypothesis of TNFα induced reduction on the progression of AA amyloidosis described in previous study reports. Targeted histological analysis of tissue biopsy is crucial to clarify the presence of AA amyloidosis in CD induced multiorgan damage cases.
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Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes.
Dillard, T, Yedinak, CG, Alumkal, J, Fleseriu, M
Pituitary. 2010;(1):29-38
Abstract
Anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) therapies represent a novel approach to cancer treatment via disruption of immune tolerance to antigens located on tumor cells. Disruption of immune tolerance, however, may occur at a cost. A host of immune related adverse events (IRAEs) are associated with anti-CTLA-4 therapy. Autoimmune hypophysitis has been reported in up to 17% of patients with melanoma and renal cell carcinoma treated with this therapy. Familiarity with the spectrum of IRAEs connected to these therapies is paramount for endocrinologists, oncologists and those involved in the care of these subjects. We review here key aspects of diagnosis and treatment of anti-CTLA-4 antibody therapy resultant IRAEs. We describe the first two cases of hypopituitarism in prostate cancer subjects undergoing experimental therapy with ipilimumab. The clinical evidence strongly suggests that the prostate cancer subjects developed autoimmune hypophysitis as a consequence of anti-CTLA-4 treatment. High dose glucocorticoid treatment resulted in markedly improved symptoms, and resolution of focal symptoms and diabetes insipidus. One subject recovered pituitary-thyroid axis function after 9 months; however, both continue to require GC replacement. These cases highlight the importance of early screening and treatment for hypopituitarism in all subjects undergoing treatment with anti-CTLA-4 therapy to prevent a potentially fatal outcome from secondary adrenal insufficiency, a readily treatable disease. We recommend mandatory long term follow-up to monitor the development of other hormonal deficits.