Checkpoint-inhibitor induced Polyserositis with Edema.

BACKGROUND: As immune checkpoint inhibitors (ICI) are increasingly being used due to effectiveness in various tumor entities, rare side effects occur more frequently. Pericardial effusion has been reported in patients with advanced non-small cell lung cancer (NSCLC) after or under treatment with immune checkpoint inhibitors. However, knowledge about serositis and edemas induced by checkpoint inhibitors in other tumor entities is scarce. METHODS AND RESULTS: Four cases with sudden onset of checkpoint inhibitor induced serositis (irSerositis) are presented including one patient with metastatic cervical cancer, two with metastatic melanoma and one with non-small cell lung cancer (NSCLC). In all cases treatment with steroids was successful in the beginning, but did not lead to complete recovery of the patients. All patients required multiple punctures. Three of the patients presented with additional peripheral edema; in one patient only the lower extremities were affected, whereas the entire body, even face and eyelids were involved in the other patients. In all patients serositis was accompanied by other immune-related adverse events (irAEs). CONCLUSION: ICI-induced serositis and effusions are complex to diagnose and treat and might be underdiagnosed. For differentiation from malignant serositis pathology of the punctured fluid can be helpful (lymphocytes vs. malignant cells). Identifying irSerositis as early as possible is essential since steroids can improve symptoms.

Clinical determinants of fever in clozapine users and implications for treatment management: A narrative review.

OBJECTIVES: To identify the clinical determinants of fever in clozapine users and their impact on management of clozapine treatment. METHODS: Articles published in English or French identified with a MEDLINE, Web of Sciences, Cochrane Library and PsycINFO search, from inception through February 2019, using the term "clozapine" in combination with "fever" OR "hyperthermia" OR "body temperature" OR "pyrexia" OR "febrile" OR "heat" OR "thermoregulation". Information extracted for each medical condition were frequency, time to onset after initiation of clozapine treatment, characteristics of fever, associated symptoms, laboratory tests used for diagnosis, course, lethality, discontinuation of clozapine. Data were synthesized narratively. RESULTS: Our search yielded 394 unique hits published from 1993 to 2018. We included 73 articles in the review: two meta-analyses, 14 reviews, six epidemiological studies, 11 clinical studies and 40 case reports. During clozapine initiation, fever is most frequently benign and transient but should be closely monitored as it may be the first stage of potentially life-threatening adverse drug reactions (ADR) (agranulocytosis, neuroleptic malignant syndrome myocarditis, hepatitis, pancreatitis, nephritis, colitis, etc.). Other ADR associated with fever are independent of duration of exposure to clozapine (heat stroke, pneumonia, pulmonary embolism, necrotizing colitis). If fever is due to intercurrent infection, therapeutic drug monitoring is recommended to adjust clozapine daily dosage. CONCLUSION: Benign causes of fever are much more frequent than life-threatening ADR during clozapine treatment. Discontinuation should not be considered as automatic in the event of fever, especially during the early phase of clozapine initiation.

Severe polyserositis induced by the 13-valent pneumococcal conjugate vaccine: a case report.

BACKGROUND: The United States Advisory Committee on Immunization Practices recommends administration of the 13-valent pneumococcal conjugate vaccine in series with the 23-valent pneumococcal polysaccharide vaccine for prevention of pneumonia in the elderly. Reports of autoimmune or auto-inflammatory diseases as a result of pneumococcal vaccination, especially pneumococcal conjugate vaccine, are extremely rare. CASE PRESENTATION: We present a case of severe serositis in a 75-year-old Caucasian woman complicated by pericardial and pleural effusions in the setting of recent 13-valent pneumococcal conjugate vaccine vaccination and no other obvious etiology. Our patient required steroid treatment, thoracentesis, chest tube, and pericardial window and subsequently recovered to her baseline. CONCLUSIONS: To the best of our knowledge, no such reaction to the 13-valent pneumococcal conjugate vaccine has previously been documented. Although the benefits of vaccination outweigh the risks, knowledge of this potential side effect can help clinicians in diagnosis and treatment of similar patients.

Idiosyncratic drug reactions and membranous glomerulopathy.

An infant boy with steroid-resistant nephrotic syndrome (idiopathic membranous glomerulonephropathy) achieved remission with ciclosporin but developed eosinophilia and high IgE levels (max 19 000  iU/mL). Conversion to tacrolimus resulted in chronic diarrhoea (eosinophilic gastroenteritis), muscle weakness, polyserositis and failure-to-thrive. In contrast, a trial without tacrolimus resulted in a ciclosporin-responsive relapse, therapy-resistant focal seizures with generalised spikes, worsening muscle weakness and diarrhoea. The patient was weaned off of ciclosporin and completely normalised. In vitro testing demonstrated decreased viability of the patient's cells when incubated with calcineurin inhibitors (ciclosporin, 70%; tacrolimus, 80% compared to control cells), supporting their role in this adverse drug reaction.

Everolimus-Induced Systemic Serositis After Simultaneous Liver and Kidney Transplantation: A Case Report.

Although everolimus, a mammalian target of rapamycin inhibitor, has been used as a potent immunosuppressive agent in organ transplantation, data regarding its adverse effect profile compared with that of sirolimus in clinical circumstances are limited. A 50-year-old man who underwent simultaneous liver and kidney transplantation 14 months previously was admitted with large pleural effusion, pericardial effusion, and ascites. Laboratory findings and cultures for possible infectious causes were all negative. Pericardial window surgery with drainage of the pericardial fluid was performed on day 3. Pleural and pericardial biopsy revealed non-specific inflammation without evidence of malignant cells. Everolimus was discontinued and replaced by mycophenolate mofetil on day 4. Significant clinical improvement was observed after discontinuation of everolimus, and follow-up echocardiography and chest radiography showed no recurrence of the pericardial or pleural effusion after discharge.

Adalimumab-induced lupus serositis.

A 61-year-old man presented with a 1-month history of breathlessness, chest pain and lethargy. He had been taking adalimumab for ankylosing spondylitis for 2 years. Pleural and pericardial effusions were both found. A video-assisted thorascopic (VATS) pleural and lung biopsy were performed. The pleural pathology showed eosinophils, acute inflammatory cells and lymphoid aggregates. The patient was positive for antinuclear, antidouble-stranded and antihistone antibodies consistent with drug-induced lupus due to adalimumab. His serositis resolved on withdrawal of the drug. Drug-induced lupus can occur as a consequence of anti-TNF-α agents from induction of autoimmunity in a predisposed host.

Tumor necrosis factor inhibitor-induced serositis.

A 46-year-old man with a history of asthma and psoriatic arthritis on adalimumab presented with fever, tachycardia, and hypoxia. He was diagnosed with pleural effusion and started on antibiotics, as it was noted to be an exudative effusion. Patient failed to improve on multiple courses of antibiotics, and his blood and pleural fluid cultures were negative. He was then started on prednisone 1 mg/kg and showed remarkable recovery. He was diagnosed with adalimumab-induced serositis.

Clozapine-induced serositis: review of its clinical features, pathophysiology and management strategies.

Although the benefits of clozapine have been well demonstrated in resistant schizophrenia, the frequency of adverse events is of particular concern: up to 76% of patients to whom clozapine was prescribed experienced an adverse event, with a discontinuation rate of 17%. In addition to its major clinical side effect, agranulocytosis, clozapine is reported to induce inflammatory syndromes with polyserositis. Apart from sparse case reports, no study has yet addressed this particularly interesting issue. With the aim of improving the outcome of clozapine-treated patients, we undertook a review of the literature to characterize the clinical features of clozapine-induced serositis, its pathophysiology, and to propose strategies of clinical management.

Serosal inflammation (pleural and pericardial effusions) related to tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs) have dramatically changed the treatment of chronic myeloid leukemia (CML) and are increasingly used in other malignancies. Despite the apparent selectivity of these agents significant side effects can occur mainly due to off target kinase inhibition. Clinical consequences of serosal inflammation, including pleural and pericardial effusions, have emerged as a frequent adverse event associated with dasatinib while occurring much less frequently during imatinib and nilotinib therapy. The pathogenesis is uncertain but may involve inhibition of platelet derived growth factor or expansion of cytotoxic T and natural killer cells. The development of serosal inflammation with dasatinib poses a significant challenge to physicians, as it cannot be predicted, the time of onset is variable, and management frequently requires repeat invasive procedures.

[Chest pain, reduced physical activity, and polyserositis in a 35-year old patient with anticonvulsive medication]. / Leistungsknick, Thoraxschmerz und Polyserositis bei einem 35-jährigen Patienten mit antikonvulsiver Therapie.

We report on a rare case of a late-onset drug-induced lupus erythematosus. A 35 year old male patient complained about dyspnea, chest pain and reduced physical activity for three months. His medical history consisted of epilepsy treated with carbamazepine for 20 years. After diagnosis of a large pericardial effusion and percardiocentesis (1200 ml) the diagnosis of viral perimyocarditis was suspected. Under antiphlogistic treatment the symptoms vanished initially. Four weeks later the pericardial effusion recurred and a livedo reticularis became evident. A structural or infectious heart disease, in particular viral myocarditis, was ruled out invasively. Serologic testing revealed antinuclear antibodies and antibodies against histones without presence of antibody against ds-DNA, thereby confirming the diagnosis of carbamazepine-induced lupus erythematodes. After discontinuation of carbamazepine and immunosuppressive medication the patient recovered completely.

Pericarditis and polyserositis as a side effect of clozapine in an adolescent girl.

A case report describes an adolescent girl with a treatment-resistant bipolar disorder, who developed pericarditis and polyserositis while being treated with clozapine. The sparse literature about this rare, severe side effect of clozapine is discussed. Clinical recommendations with regard to monitoring are given. If myocarditis/polyserositis occurs, clozapine has to be discontinued immediately.