Autoimmune paraneoplastic syndromes associated to lung cancer: A systematic review of the literature: Part 5: Neurological auto-antibodies, discussion, flow chart, conclusions

Sculier, Claudine; Bentea, Georgiana Pintea; Ruelle, Lucien; Grigoriu, Bogdan; Coureau, Michelle; Gorham, Julie; Sideris, Spyridon; Holbrechts, Stéphane; Lafitte, Jean-Jacques; Meert, Anne-Pascale; Durieux, Valérie; Berghmans, Thierry; Sculier, Jean-Paul

doi:10.1016/j.lungcan.2017.07.026

Cited by 10 publications

(9 citation statements)

References 165 publications

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“…The most frequent manifestations found were rheumatoid arthritis (5.9%), psoriasis (2.8%), polymyalgia rheumatica (1.8%), Addison disease (1%), systemic lupus erythematosus (SLE-−0.9%), ulcerative colitis (0.8%), giant cell arteritis (0.8%), sicca syndrome (0.6%), regional enteritis (0.5%), and Meniere disease (0.5%). However, these autoimmune manifestations can be very broad as it has been recently reviewed for lung cancer in a series of articles curated by Jean Paul Scuiler (1,(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Toxicity of Immune -Checkpoint Inhibitors in Patients With Preexisting Autoimmune Disorders

et al. 2020

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Immunotherapy is an important armamentarium for cancer treatment nowadays. Apart from their significant effectiveness in controlling disease they also generate potential severe immune related adverse effects. Preexistence of immune related conditions may eventually predispose to the development of more severe complication and extreme caution have been taken in treating these patients. We performed a literature review searching for case reports and case series in order to offer evidence-based data for clinical management of these patients. Preexisting serological-only immune abnormalities or presence of a predisposing genetic background does not seem to confer significant risk but existing data is scarce. Most patients with preexistent autoimmune diseases can probably treated with checkpoint inhibitors as they seem to have at least the same response rate as the general cancer population. Under treatment, a significant part of them (at least 30%) can experience a flare of their baseline disease which can sometime be severe. Life-threatening cases seems rare and disease flare can be generally managed with steroids. The volume of available data is more important for rheumatologic diseases than for inflammatory bowel diseases were more caution should be observed. However, it has to be kept in mind that new immune related adverse effects (IrAE) are seen with a similar frequency as the flare of the baseline disease. Both flare-up's and newly developed IrAE are generally manageable with a careful clinical follow-up and prompt therapy.

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Section: Introductionmentioning

confidence: 99%

Efficacy and Toxicity of Immune -Checkpoint Inhibitors in Patients With Preexisting Autoimmune Disorders

et al. 2020

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“…While our patient tested negative for anti-Hu antibodies, the development of anti-Hu antibodies is one well described mechanism of paraneoplastic neuropathy associated with both small cell lung cancer [32] and Merkel cell carcinoma [33]. Whether anti-Hu antibodies are directly toxic to neurons is unclear [34], but their presence is associated with sera that damages neurons directly in vitro [35]. A case of idiopathic myenteric ganglionitis associated with the presence of anti-Hu antibodies in a patient without a known cancer diagnosis improved coincidently with a decrease in anti-Hu antibody titer following treatment with steroids [36].…”

Section: Discussionmentioning

confidence: 99%

Fatal enteric plexus neuropathy after one dose of ipilimumab plus nivolumab: a case report

Appelbaum¹,

Wells²,

Hiatt³

et al. 2018

j. immunotherapy cancer

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BackgroundImmune checkpoint inhibitors (ICIs) are the treatment of choice for several cancers and can be associated with remarkable clinical benefit, but can also cause serious immune-related adverse events (irAEs). Management of rare and severe irAEs is challenged by an incomplete knowledge of their natural history and pathogenetic mechanisms. We report a case of fatal acute-onset gastro-intestinal (GI) hypomotility from myenteric plexus neuropathy following a single dose of ipilimumab plus nivolumab given for treatment of Merkel cell carcinoma (MCC).Case presentationA 66-year-old man with recurrent metastatic MCC involving several organs (liver, bones and disseminated retroperitoneal lymphadenopathy) developed profound pharyngeal dysphagia and ileus that started 7 days after receiving a single administration of combination immune checkpoint blockade consisting of nivolumab (3 mg/kg) and low-dose ipilimumab (1 mg/kg). A swallowing study showed oropharyngeal dysfunction and aspiration. Imaging studies were consistent with diffuse intestinal paresis. An extensive work-up did not reveal obvious causes of these symptoms, and enteric plexopathy was suspected. Empiric immune suppressive therapy was initiated urgently. Despite an escalating immunosuppressive regimen that included high dose steroids, tacrolimus and therapeutic plasma exchange, no improvement in GI motility was seen and the patient suffered repeated episodes of aspiration. Seven weeks after the onset of GI hypomotility, the patient succumbed to sepsis from intestinal perforations. At autopsy, histologic specimens obtained from the entire GI tract (pharynx to rectum) showed near complete loss of ganglion cells within the myenteric and submucosal plexuses. An associated inflammatory infiltrate was not seen, suggesting a ‘burned out’ phase of illness. C4d complement deposition was found at the ganglionic sites, suggesting antibody-mediated pathogenesis. Remarkably, at sites of previously suspected Merkel cell metastases, no residual viable Merkel cell carcinoma was identified.ConclusionsGI-tract paresis due to myenteric neuritis is a rarely reported toxicity of ICIs. Because the window of reversibility is likely to be very brief, quick and decisive interventions are warranted. Subtle functional and anatomic perturbations of the myenteric nervous system from the use of ICIs may be more prevalent than realized and should be suspected and addressed in both clinical and investigational settings.

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“…With regard to autonomic symptoms, anti-Hu antibodies usually cause chronic gastrointestinal pseudo-obstruction or acute pandysautonomia as part of encephalomyelitis or subacute sensory neuropathy [ 6 , 7 , 10 , 11 ], whereas anti-gAchR antibodies are mainly associated with subacute pandysautonomia [ 1 , 4 , 6 ]. Anti-SOX-1 antibodies are also detected in Lambert-Eaton syndrome with SCLC [ 12 , 13 ]. SOX1 reactivity is predominantly associated with anti-Hu antibodies and SCLC [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated treatment for autonomic paraneoplastic syndrome improves performance status in a patient with small lung cell carcinoma: a case report

et al. 2018

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BackgroundParaneoplastic neurological syndromes (PNS) are rare disorders associated with cancer and are believed to be immune mediated. Patients with autonomic PNS suffer from variable combinations of parasympathetic and sympathetic failure. Autonomic PNS are usually associated with other PNS, such as encephalomyelitis and sensory neuropathy; however, autonomic symptoms may rarely manifest as PNS symptoms. Autonomic symptoms, therefore, may be overlooked in patients with cancer.Case presentationWe described a 65-year-old Japanese man who was diagnosed with autonomic PNS due to small-cell lung carcinoma (SCLC) with Eastern Cooperative Oncology Group (ECOG) performance status 3, who suffered from orthostatic hypotension, and urinary retention needing a urethral balloon. Laboratory studies showed decreased levels of noradrenaline, and were positive for anti-ganglionic acetylcholine receptor antibody, type 1 antineuronal nuclear antibody, and sry-like high mobility group box 1 antibody. Nerve conduction evaluations and 123I-metaiodobenzylguanidine myocardial scintigraphy showed no abnormalities. Abdominal contrast-enhanced computed tomography revealed marked colonic distention. The patient’s autonomic symptoms resolved following integrated treatment (symptomatic treatment, immunotherapy, and additional chemotherapy) enabling the patient to walk, remove the urethral balloon, and endure further chemotherapy. ECOG performance status remained at 1, 10 months after admission.ConclusionsIntegrated treatment for autonomic PNS may improve autonomic symptoms and ECOG performance status of patients with cancer.

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Autoimmune paraneoplastic syndromes associated to lung cancer: A systematic review of the literature: Part 5: Neurological auto-antibodies, discussion, flow chart, conclusions

Cited by 10 publications

References 165 publications

Efficacy and Toxicity of Immune -Checkpoint Inhibitors in Patients With Preexisting Autoimmune Disorders

Efficacy and Toxicity of Immune -Checkpoint Inhibitors in Patients With Preexisting Autoimmune Disorders

Fatal enteric plexus neuropathy after one dose of ipilimumab plus nivolumab: a case report

Integrated treatment for autonomic paraneoplastic syndrome improves performance status in a patient with small lung cell carcinoma: a case report

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