scholarly journals Hemophagocytic Lymphohistiocytosis after Initiation of Combined Immunotherapy for Metastatic Melanoma

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Gambichler T ◽  
◽  
Rached NA ◽  
Nowack N ◽  
Behle B ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Checkpoint Inhibitors ◽  
Delayed Diagnosis ◽  
High Dose ◽  
Laboratory Findings ◽  
Case Presentation ◽  
Inappropriate Treatment ◽  
Autoimmune Conditions ◽  
Prompt Diagnosis

Hemophagocytic Lymphohistiocytosis (HLH), which is a severe, potentially fatal condition characterized by T lymphocyte overactivation, is predominantly caused by infections, hematological malignancies, and autoimmune conditions. HLH due to therapy with Immune Checkpoint Inhibitors (ICI) has rarely been reported. We describe a 60-year-old male with metastatic melanoma who developed HLH after the initiation of nivolumab plus ipilimumab treatment. Prompt diagnosis and high-dose mono-prednisolone therapy resulted in rapid resolution of his subjective symptoms and laboratory findings. Apart from this case presentation we provide a brief overview on clinical characteristics of previously observed ICI-induced HLH cases. Given the increasing use of ICI in a variety of cancers, the frequency of HLH will very likely raise. HLH morbidity and mortality are often the result of delayed diagnosis and inappropriate treatment. Hence, HLH must be considered in ICI-treated cancer patients who present with symptoms such as fever, cytopenias and hyperferritinemia.

scholarly journals Acute colonic pseudo-obstruction following nivolumab and ipilimumab combination therapy for metastatic melanoma

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Mami Ishibashi ◽  
Yoshihiro Ishida ◽  
Atsushi Otsuka ◽  
Shuji Yamamoto ◽  
Kenji Kabashima
Keyword(s):  
Combination Therapy ◽  
Adverse Events ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
High Dose ◽  
Prompt Treatment ◽  
Prompt Diagnosis

Immune-related adverse events (irAEs) are commonly observed in patients treated with immune checkpoint inhibitors (ICI), and prompt diagnosis and treatment of irAEs is of utmost importance. Gastrointestinal (GI) events are among the most frequent irAEs and the hallmark symptom is diarrhea. Intestinal hypomotility as irAEs is exceedingly rare, and needs wider recognition given that the presentation is insidious.Here, we report a case of 79-year-old woman with metastatic melanoma under nivolumab and ipilimumab combination therapy. She developed ileus symptom, and was diagnosed with acute colonic pseudo-obstruction. The symptom relieved soon after administering high-dose prednisolone five days after the onset. ICI therapy was discontinued.Intestinal hypomotility as GI irAEs is exceedingly rare and there have been five reported cases to our knowledge. In reviewing past cases, we speculate that the prompt initiation of corticosteroids resulted in a favorable outcome. Our case illustrates that early recognition of these rare irAEs is essential in order to ensure prompt treatment.

scholarly journals Hemophagocytic lymphohistiocytosis: a rare and life-threatening diagnosis

2021 ◽  
Vol 9 (12) ◽  
pp. 3705
Author(s):  
Anu Yarky ◽  
Vipan Kumar ◽  
Nidhi Chauhan ◽  
Neha Verma
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Clinical Presentation ◽  
Laboratory Findings ◽  
Delay In Diagnosis ◽  
Life Threatening ◽  
Sporadic Cases ◽  
Prompt Diagnosis ◽  
Excessive Activation ◽  
Variable Clinical Presentation ◽  
Secondary Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome of excessive activation of immune system. It frequently affects infants from birth to 18 months of age, but is also observed in children and adults of all ages. HLH can occur as a familial or sporadic disorder, and it is triggered by a variety of events, Infection being the most common trigger both in familial and in sporadic cases. Prompt treatment is very critical in cases of HLH, but the greatest barrier is often delay in diagnosis due to the rarity of this syndrome, variable clinical presentation, and lack of specificity of the clinical and laboratory findings. The key clinical features of HLH are high persistent fever, hepatosplenomegaly, blood cytopenia, elevated aminotransferase and ferritin levels, and coagulopathy. A diagnosis of HLH is mostly under-recognized, and is associated with high mortality, especially in adults; thus, prompt diagnosis and treatment are essential. We here present a rare case of HLH in an adult which was non-familial and infection being the trigger causing secondary hemophagocytic lymphohistiocytosis.

Lamotrigine-associated hemophagocytic lymphohistiocytosis

2021 ◽  
Vol 14 (1) ◽  
pp. e238183
Author(s):  
Nawar Suleman ◽  
Metin Ozdemirli ◽  
David Weisman
Keyword(s):  
Immune System ◽  
Immune Activation ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Clinical Presentation ◽  
Paediatric Population ◽  
Laboratory Findings ◽  
Life Threatening ◽  
Rheumatological Disease ◽  
Prompt Diagnosis ◽  
Variable Clinical Presentation

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder of excessive immune activation. It is mostly seen in the paediatric population and is rarely observed in adults. HLH can be inherited or acquired and is commonly triggered by activation of the immune system by an underlying viral infection or in immune system deficiency such as malignancy or underlying rheumatological disease. HLH is a difficult entity to diagnose due to the rarity of this disorder, variable clinical presentation and non-specific clinical and laboratory findings. HLH carries a high mortality if left untreated, and therefore prompt diagnosis and initiation of immunosuppressive, immunomodulatory and cytostatic medications are critical to improve survival in affected patients. Here, we present a case of lamotrigine-associated HLH. To our knowledge, only eight other cases of lamotrigine-associated HLH have been reported in adult patients.

scholarly journals Severe Myositis, Myocarditis, and Myasthenia Gravis with Elevated Anti-Striated Muscle Antibody following Single Dose of Ipilimumab-Nivolumab Therapy in a Patient with Metastatic Melanoma

2019 ◽  
Vol 2019 ◽  
pp. 1-3 ◽  
Author(s):  
Mahdieh Fazel ◽  
Patrick M. Jedlowski
Keyword(s):  
Myasthenia Gravis ◽  
Metastatic Melanoma ◽  
Intravenous Immunoglobulin ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Supportive Therapy ◽  
Prolonged Treatment ◽  
High Dose ◽  
Myasthenic Crisis ◽  
Respiratory Compromise

Immune checkpoint inhibitors targeting programmed cell death protein 1 and cytotoxic T-lymphocyte associated protein 4 have improved survival in patients with metastatic melanoma, especially in combination (i.e., ipilimumab-nivolumab). Postmarketing surveillance has identified rare but at times life-threatening adverse effects associated with these agents in combination and as monotherapy, which include myocarditis, myositis, myasthenia gravis (MG), and hepatotoxicity. Further evaluation of immune checkpoint therapy-induced MG identified the rapid clinical progression, prolonged treatment/supportive therapy course, and higher frequency of myasthenic crisis in these patients versus those with idiopathic MG. More rapid incorporation of aggressive treatment options (i.e., intravenous immunoglobulin, plasmapheresis) may be necessary in these cases. Anti-striational antibodies are often detected in individuals with myasthenia gravis and concurrent myositis and myocarditis. A high-index of suspicion is necessary to assist with rapid treatment initiation as these patients can rapidly deteriorate into respiratory compromise. A case of a 78-year-old woman with metastatic melanoma status after combination therapy with ipilimumab-nivolumab that developed transaminitis, myositis, myocarditis, and myasthenia gravis (with positive anti-striational antibodies) five days after the first cycle, is presented. Despite high dose intravenous methylprednisolone and intravenous immunoglobulin treatment, she ultimately entered hospice care eight days after hospital admission, 36 days after her first cycle.

scholarly journals A case of dual-mechanism immune-related anaemia in a patient with metastatic melanoma treated with nivolumab and ipilimumab

2020 ◽  
Vol 8 (1) ◽  
pp. e000380 ◽  
Author(s):  
Daniel J Olson ◽  
Padma Rajagopal ◽  
Melissa Y Tjota ◽  
Girish Venkataraman ◽  
Jason J Luke ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Rare Case ◽  
Checkpoint Inhibitors ◽  
Underlying Mechanism ◽  
Pure Red Cell Aplasia ◽  
Severe Anaemia ◽  
Red Cell ◽  
Case Presentation ◽  
Mechanism Of Toxicity ◽  
Dual Mechanism

BackgroundThe combination of the immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab is a mainstay of treatment for selected patients with metastatic melanoma. This combination also results in more frequent immune-related adverse events (irAEs) than either ICI alone. These irAEs can be severe and their pathogenesis is poorly understood.Case presentationWe report a case of a woman with metastatic melanoma, treated with combined ipilimumab and nivolumab, who developed severe anaemia. While initial workup revealed autoimmune haemolytic anaemia, the anaemia persisted despite corticosteroids and paradoxical reticulocytopenia was observed. Bone marrow biopsy demonstrated a CD8+T cell-mediated destruction of the red cell precursors implying concurrent pure red cell aplasia. Both processes resolved after the addition of cyclosporine A.ConclusionsThis report describes a rare case of two concurrent mechanisms of haematological irAE in a patient treated with combined ICI therapy. Successful treatment resulted only after the second underlying mechanism of toxicity was uncovered. Prompt recognition of these unusual presentations of rare irAEs is now key to effective irAE management.

scholarly journals Hodgkin’s Lymphoma Revealed by Hemophagocytic Lymphohistiocytosis in a Child

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Sarra Benmiloud ◽  
Mohamed Hbibi ◽  
Sana Chaouki ◽  
Sana Abourazzak ◽  
Moustapha Hida
Keyword(s):  
Infectious Disease ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Hodgkin’S Lymphoma ◽  
Delayed Diagnosis ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Histopathologic Examination ◽  
Initial Manifestation ◽  
Common Causes ◽  
Life Threatening

Hemophagocytic lymphohistiocytosis (HLH) is a severe life-threatening disorder, responsible for extensive phagocytosis of hematopoietic cells and causing a multisystem organ failure. If lymphomas are common causes of HLH, the association with Hodgkin’s lymphoma is rarely described in children. We report a case of a 9-year-old boy presenting with HLH as an initial manifestation of Hodgkin’s lymphoma. He has been suffering from persistent high fever, asthenia, weight loss, and hepatosplenomegaly with no lymphadenopathy. The diagnosis of HLH secondary to infectious disease was initially worn. The patient received high-dose intravenous immunoglobulin with broad-spectrum antibiotics. However, his state got worse with the onset of dry cough and pleural effusion. Histopathologic examination of pleural fluid showed the presence of Reed-Sternberg cells. The outcome was favorable after treatment by corticosteroid and chemotherapy. Hodgkin’s lymphoma revealed by HLH is a source of delayed diagnosis and should be borne in mind in children.

scholarly journals Combination immune checkpoint inhibitor therapy nivolumab and ipilimumab associated with multiple endocrinopathies

2018 ◽  
Vol 2018 ◽  
Author(s):  
Florence Gunawan ◽  
Elizabeth George ◽  
Adam Roberts
Keyword(s):  
Diabetes Insipidus ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Acid Decarboxylase ◽  
Total Testosterone ◽  
High Dose ◽  
List Type ◽  
Antibody Testing ◽  
Symptom Resolution

Summary Immune checkpoint inhibitors are the mainstay of treatment for advanced melanoma, and their use is being increasingly implicated in the development of autoimmune endocrinopathies. We present a case of a 52-year-old man with metastatic melanoma on combination nivolumab and ipilumimab therapy who developed concurrent hypophysitis, type 1 diabetes mellitus (T1DM) and diabetes insipidus. He presented prior to third cycle of combination treatment with a headache, myalgias and fatigue. Biochemistry and MRI pituitary confirmed anterior pituitary dysfunction with a TSH: 0.02 mU/L (0.5–5.5 mU/L), fT4: 5.2 pmol/L (11–22 pmol/L), fT3: 4.0 pmol/L (3.2–6.4 pmol/L), cortisol (12:00 h): <9 nmol/L (74–286 nmol/L), FSH: 0.7 IU/L (1.5–9.7 IU/L), LH: <0.1 IU/L (1.8–9.2 IU/L), PRL: 1 mIU/L (90–400 mIU/L), SHBG: 34 nmol/L (19–764 nmol/L) and total testosterone: <0.4 nmol/L (9.9–27.8 nmol/L). High-dose dexamethasone (8 mg) was administered followed by hydrocortisone, thyroxine and topical testosterone replacement. Two weeks post administration of the third cycle, he became unwell with lethargy, weight loss and nocturia. Central diabetes insipidus was diagnosed on the basis of symptoms and sodium of 149 mmol/L (135–145 mmol/L). Desmopressin nasal spray was instituted with symptom resolution and normalization of serum sodium. Three weeks later, he presented again polyuric and polydipsic. His capillary glucose was 20.8 mmol/L (ketones of 2.4 mmol), low C-peptide 0.05 nmol/L (0.4–1.5 nmol/L) and HbA1c of 7.7%. T1DM was suspected, and he was commenced on an insulin infusion with rapid symptom resolution. Insulin antibodies glutamic acid decarboxylase (GAD), insulin antibody-2 (IA-2) and zinc transporter-8 (ZnT8) were negative. A follow-up MRI pituitary revealed findings consistent with recovering autoimmune hypophysitis. Immunotherapy was discontinued based on the extent of these autoimmune endocrinopathies. Learning points: The most effective regime for treatment of metastatic melanoma is combination immunotherapy with nivolumab and ipilumimab, and this therapy is associated with a high incidence of autoimmune endocrinopathies. Given the high prevalence of immune-related adverse events, the threshold for functional testing should be low. Traditional antibody testing may not be reliable to identify early-onset endocrinopathy. Routine screening pathways have yet to be adequately validated through clinical trials.

Myocarditis and diaphragmatic rhabdomyolysis with respiratory failure in a patient with metastatic melanoma treated with Nivolumab

2021 ◽  
pp. 107815522110674
Author(s):  
Cinzia Baldessari ◽  
Giuseppe Pugliese ◽  
Marta Venturelli ◽  
Stefano Greco ◽  
Leonardo Ferrara ◽  
...  
Keyword(s):  
Adverse Event ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Vital Signs ◽  
High Dose ◽  
Diaphragmatic Dysfunction ◽  
Acute Rhabdomyolysis ◽  
Clinical Benefits ◽  
History Of ◽  
Diaphragmatic Weakness

Introduction Immunotherapy dramatically changed history of melanoma patients with a clinical benefit never seen before. Nevertheless, severe and unexpected adverse effects can occur, fortunately rarely. Case presentation We reported the case of a 75-year-old male patient affected by metastatic melanoma who developed myocarditis and acute rhabdomyolysis with secondary diaphragmatic dysfunction and consequent pulmonary restrictive syndrome after Nivolumab monotherapy. Blood tests and ultrasonography of the diaphragm revealing left hypokinesis suggested a Nivolumab-related rhabdomyolysis, as an immune-mediated adverse event. The rhabdomylolysis involved the diaphragm with consequent diaphragmatic weakness and respiratory distress. Mangement & outcome The patient had a slow but slight and progressive improvement of symptoms and vital signs post-treatment with high-dose corticosteroids. Discussion With this case report, we want to highlight the importance of rapid recognition and treatment of rare and unexpected, but potential serious immune-related adverse events. These events might happen despite the remarkable clinical benefits of immune checkpoint inhibitors. We do not know which patients will benefit from these therapies and why, when and in which cases adverse event will occur: we must not lower our attention.

Influence of age and cancer history on prevalence of autoimmunity in patients with metastatic melanoma: A large retrospective study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22016-e22016
Author(s):  
Aaron N. Holmes ◽  
Xiaoyang Wang ◽  
Helen Swede ◽  
Upendra P. Hegde
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Survival Rates ◽  
Primary Melanoma ◽  
Study Groups ◽  
Cancer Type ◽  
Cancer History ◽  
Autoimmune Conditions ◽  
Cutaneous Cancer

e22016 Background: While immune checkpoint inhibitors (ICIs) have improved the survival rates of metastatic melanoma in recent years, immune-related adverse events (irAEs) remain a major toxicity. Studies have established that pre-existing autoimmunity increases the risk of severe irAEs following ICI therapy (1). Melanoma is common cancer in older patients, and older age is believed to be a risk factor of autoimmunity. However, there is controversy concerning the influence of age increasing the risk of irAEs between clinical trials, which exclude patients with confirmed or suspected autoimmunity, and less-selective but lower-power case reports (2). In order to understand potential irAE risk following ICI treatment, we measured the prevalence of pre-existing autoimmune disease by age and cancer type. Methods: We studied 293,938 patients aged 18-106 years old who were treated at the University of Connecticut Health Center between 2000 and 2018 using GE Centricity’s IDX database. Patients were organized into four study groups based on International Classifications of Diseases codes (ICD-9 and ICD-10), specifically primary melanoma and three comparisons groups: non-cutaneous neoplasms alone, melanoma with non-cutaneous neoplasms, and patients without cancer history. A list of 340 ICD codes corresponding to 105 autoimmune conditions were queried. Results: Non-cutaneous cancer, in the absence or presence of melanoma, was associated with a higher prevalence of autoimmunity (27.0%, 29.4%, respectively) compared to the rates in patients with melanoma alone and those without cancer history (11.1%, 8.7%, respectively, p < 0.05). In patients with both melanoma and non-cutaneous cancers, those with metastases had an 11.7% increase in autoimmune prevalence compared to patients without metastases (p < 0.0001), the largest metastasis-associated increase observed across all cancer groups. Lastly, a logistic regression demonstrated that age is weakly correlated with autoimmunity (r = 0.01, p < 0.0001). Conclusions: The findings suggest that a history of metastasis, non-cutaneous cancer, and advanced age are associated with a higher prevalence of pre-existing autoimmunity in melanoma patients. As ICIs are indicated for metastatic melanoma, our findings warrant future studies and careful risk assessment of autoimmunity in senior patients.

scholarly journals Case report of acquired hemophagocytic lymphohistiocytosis associated with progression of monoclonal gammopathy of unknown significance (MGUS)

2018 ◽  
Vol 5 (1) ◽  
pp. 19
Author(s):  
Li Liu ◽  
Lydia C Contis ◽  
Octavia Melvina Palmer
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Organ Damage ◽  
Patient Treatment ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Unknown Significance ◽  
Novel Association ◽  
Prompt Diagnosis

Background: Acquired hemophagocytic lymphohistiocytosis (HLH) is an aggressive hyperinflammatory syndrome. Without prompt diagnosis and proper treatment, it can be life-threatening. HLH is commonly present in the setting of other autoimmune disorders, infection, organ transplantation, and malignancy.  However, to our knowledge, HLH associated with monoclonal gammopathy of undetermined significance (MGUS) has not been reported.Case presentation: A 67-year-old woman with an extensive history of MGUS and renal transplant presented with progressive fatigue, weight loss, intermittent fevers, splenomegaly, and pancytopenia. Serum protein electrophoresis with immunofixation identified a new monoclonal protein IgG lambda and a rapidly increasing pre-existing free kappa light chain. A bone marrow biopsy revealed focal clusters of kappa restricted plasma cells which comprised less than 10\% of marrow cellularity. Skeletal survey was negative for osteolytic lesions. She was also free of any end-organ damage.  Histological examination showed a prominent increase in histiocytes and macrophages, many of which show erythrophagocytosis and lymphophagocytosis. Together with her clinical presentation along with a hyperferritinemia, a diagnosis of HLH was confirmed utilizing the criteria of the Histiocyte Society. The patient underwent a splenectomy. Prompt treatment with etoposide and high dose dexamethasone eventually stabilized the patient and resulted in a full recovery, which coincided with the disappearance of the serum monoclonal IgG lambda.Conclusions: This report reveals a novel association of HLH with the progression of MGUS. Familiarity with this syndrome and its association with other conditions is indicated to ensure prompt diagnosis and appropriate patient treatment.

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