Cytomegalovirus and rheumatic diseases: cases-based review.

Cytomegalovirus (CMV) infection is a common and typically benign disease in immunocompetent individuals. However, immunocompromised patients are at a greater risk of reactivation, leading to more severe outcomes. Patients with rheumatic diseases have a particularly high risk of opportunistic infections due to both the inherent immunosuppressive state conveyed by the disease itself and the use of potent immunosuppressant drugs, such as glucocorticoids, cyclophosphamide, and rituximab. Limited data are available regarding prophylactic or preemptive treatment of CMV infection in patients with rheumatic diseases. In this article the authors present two cases of rheumatic conditions complicated by CMV infection. The first case describes a patient with eosinophilic granulomatosis with polyangiitis, previously treated with glucocorticoids and cyclophosphamide, who developed CMV colitis with bowel perforation. The second case involves a woman with systemic lupus erythematosus who was diagnosed with CMV meningitis. Both cases reinforce the importance of establishing guidelines for surveillance and prophylaxis of CMV infection in these patients.

Advances in the maintenance of ANCA vasculitis remission.

The maintenance treatment of ANCA-associated vasculitides (AAVs) has benefited from the results of several prospective clinical trials focusing on the evaluation of new drugs, therapeutic strategies, and adjuvant treatments. They also showed that rituximab was the most effective agent to maintain remission. However, because treatments can induce adverse events, including facilitating infections, therapeutic strategies should be adapted to find the optimal dose(s) and their administration duration(s) and to make them commensurate to the expected severity of relapse. That task is not easy to achieve because we have not yet been able to identify the clinical or biological parameters that can predict when a relapse will occur and its severity. Among AAVs, eosinophilic granulomatosis with polyangiitis (EGPA) has pathogenic and clinical specificities, and new drugs directly address those features. If rituximab could have a place such as in other AAVs, anti-IL5 biotherapies could also be prescribed successfully for maintenance. Another aim of vasculitis maintenance therapy is to control the disease with less prednisone than in the past. Herein, we emphasize the importance of individually devising a maintenance regimen adapted to the objectives of keeping the patient in remission without the adverse events related to the prescribed treatment(s).

Eosinophilic granulomatosis with polyangiitis developed after dupilumab administration in patients with eosinophilic chronic rhinosinusitis and asthma: a case report.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis, and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis (ECRS) in cases when there are no findings that suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as refractory asthma and chronic rhinosinusitis (CRS). Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with refractory asthma and CRS associated with dupilumab, few studies have examined the development of EGPA. CASE PRESENTATION: We report a case of a 61-year-old woman treated with dupilumab for refractory ECRS and eosinophilic otitis media (EOM) complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis before the initiation of dupilumab. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. A blood test showed an eosoinophilia and re-elevation of MPO-ANCA levels after the administration of dupilumab. Therefore, dupilumab was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy. CONCLUSION: To the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, measuring MPO-ANCA in patients with multiple eosinophilic disorders before the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with a previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.

Mepolizumab-Induced Posterior Reversible Encephalopathy Syndrome (PRES), a new patient report.

BACKGROUND: Posterior Reversible Encephalopathy Syndrome (PRES) is a neurotoxic state characterized by seizures, headache, vision change, paresis, and altered mental status. PRES has an important place in medicine due to the wide variety of causative diseases, infections, and medications that precipitate its mysterious onset. Although exposure to medications, particularly immunosuppressants, cancer chemotherapy, and biologic drugs, is a common occurrence in patients who develop PRES, Mepolizumab has never before been associated. CASE PRESENTATION: This report of a 67-year-old male patient outlines the first reported case of Mepolizumab-induced PRES in the literature. CONCLUSIONS: Treatment of severe asthma, asthma-exacerbations, and diseases such as eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss) with Mepolizumab is rapidly gaining popularity ever since the drug's recent FDA-approval. This report aims to raise awareness of this potentially life-threatening and previously unreported side effect of Mepolizumab since early identification of the causative agent is the key to preventing the severe neurologic disability and possible death that may occur from the delayed treatment of PRES.

Use of Systemic Corticosteroids for Reasons Other than Asthma in Subjects with Asthma.

BACKGROUNDS: Recent studies have reported increased risks of adverse events from systemic corticosteroids even with only low-dose or short-term use. Some patients with asthma experience complications requiring systemic corticosteroids. However, few studies have examined issues associated with administration of systemic corticosteroids for reasons other than asthma among subjects with asthma. OBJECTIVES: We investigated patterns of systemic corticosteroid exposure for reasons other than asthma in subjects with asthma. METHOD: We retrospectively reviewed the records of adult subjects with asthma followed up for >1 year at Yokohama City University Hospital from January 1, 2010, to December 31, 2019. We investigated patterns and reasons for systemic corticosteroid use during follow-up. In addition, factors related to systemic corticosteroid use for reasons likely other than asthma were investigated. RESULTS: Among the 568 subjects with asthma analyzed, 326 (57.4%) had received systemic corticosteroids for some reason. Among those 326 patients, 120 (36.8%) had received systemic corticosteroids for reasons likely other than asthma. Multivariable analysis revealed rheumatoid arthritis, eosinophilic granulomatosis with polyangiitis, other collagen vascular diseases, chronic rhinosinusitis, and malignancy as positively associated with systemic corticosteroid exposure for reasons likely other than asthma in subjects with asthma. CONCLUSIONS: About 40% of systemic corticosteroid use in subjects with asthma was for reasons likely other than asthma. Clinicians should be aware of their asthma patients' exposures to systemic corticosteroids for nonasthma reasons, to avoid missing adverse events or underestimating the severity of asthma, and to reduce systemic corticosteroid use.

Omalizumab-associated eosinophilic granulomatosis with polyangiitis: cause or coincidence?

Omalizumab is an anti-IgE monoclonal antibody used in severe allergic asthma. Herein, we describe a case of eosinophilic granulomatosis with polyangiitis, which manifested 3 months after initiation of omalizumab therapy, while maintenance corticosteroid therapy dose was unchanged.

Programmed cell death-1 blockade in kidney carcinoma may induce eosinophilic granulomatosis with polyangiitis: a case report.

BACKGROUND: Immune checkpoint inhibitors have potential applications in treating various cancers but are associated with immune-related adverse events, such as inflammation, in a wide range of organs; however, allergic inflammation caused by these agents has not been extensively studied. CASE PRESENTATION: A 65-year-old man was diagnosed with a kidney neuroendocrine carcinoma. Three months after kidney resection surgery, the tumor cells had metastasized to his liver and lymph nodes. Subsequently, the patient started chemotherapy; however, regardless of treatment, the tumor grew, and the patient experienced a series of adverse effects, such as taste disorder, anorexia, and general fatigue. Finally, he was administered a programmed cell death (PD)-1 inhibitor, nivolumab (biweekly, toal 200 mg/body), which was effective against kidney carcinoma. However, the patient had a bronchial asthma attack at 22 cycles of nivolumab treatment and chest computed tomography (CT) revealed an abnormal bilateral shadow after 37 cycles of nivolumab treatment. Bronchoscopy findings revealed eosinophil infiltration in the lungs along with severe alveolar hemorrhage. Paranasal sinus CT scanning indicated sinusitis and nerve conduction analysis indicated a decrease in his right ulnar nerve conduction velocity. Based on these findings, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis; he was treated with prednisolone, which alleviated his bronchial asthma. To restart nivolumab treatment, the dose of prednisolone was gradually tapered, and the patient was administered a monthly dose of mepolizumab and biweekly dose of nivolumab. To date, there have been no bronchial attacks or CT scan abnormalities upon follow up. CONCLUSIONS: We present a rare case in which a patient with cancer was diagnosed with eosinophilic granulomatosis with polyangiitis following treatment with a PD-1 inhibitor. Blockade of PD-1 and the programmed cell death ligand (PD-L) 1/PD-1 and PD-L2/PD-1 signaling cascade may cause allergic inflammation. Further studies are needed to identify the specific mechanisms underlying allergic inflammation after PD-1 blockade.

Case Report of Ipilimumab-Induced Diffuse, Nonnecrotizing Granulomatous Lymphadenitis and Granulomatous Vasculitis.

Ipilimumab is indicated for the treatment of melanoma in both the metastatic and adjuvant setting. Ipilimumab inhibits cytotoxic T-lymphocyte antigen 4, leading to the augmentation of T-cell activity and an antitumor immune system response. The side effect profile of ipilimumab consists of autoimmune-like events such as dermatitis, colitis, and thyroiditis. These immune-related adverse events can be serious, often resulting in the need for systemic immunosuppression with corticosteroids. We present a case of diffuse, nonnecrotizing granulomatous lymphadenitis and granulomatous vasculitis in a heavily pretreated patient with metastatic melanoma. After completion of 4 cycles of ipilimumab for the treatment of metastatic melanoma, our patient complained of increasing fatigue, drenching night sweats, and chills. Imaging revealed diffuse adenopathy involving several lymph nodes. Biopsy was positive for nonnecrotizing granulomatous lymphadenitis and granulomatous vasculitis. High-dose prednisone was initiated and tapered gradually over 6 weeks, resulting in complete resolution of the granulomatous disease.

Adverse drug reactions of montelukast in children and adults.

Montelukast, a selective leukotriene receptor antagonist, is recommended in guidelines for the treatment of asthma in both children and adults. However, its effectiveness is debated, and recent studies have reported several adverse events such as neuropsychiatric disorders and allergic granulomatous angiitis. This study aims to obtain more insight into the safety profile of montelukast and to provide prescribing physicians with an overview of relevant adverse drug reactions in both children and adults. We retrospectively studied all adverse drug reactions on montelukast in children and adults reported to the Netherlands Pharmacovigilance Center Lareb and the WHO Global database, VigiBase® until 2016. Depression was reported most frequently in the whole population to the global database VigiBase® (reporting odds ratio (ROR) 6.93; 95% CI: 6.5-7.4). In the VigiBase® , aggression was reported the most in children (ROR, 29.77; 95% CI: 27.5-32.2). Headaches were reported the most frequently to the Dutch database (ROR, 2.26; 95% CI: 1.61-3.19). Furthermore, nightmares are often reported for both children and adults to the Dutch and the global database. Eight patients with allergic granulomatous angiitis were reported to the Dutch database and 563 patients in the VigiBase® . These data demonstrate that montelukast is associated with neuropsychiatric adverse drug reactions such as depression and aggression. Especially in children nightmares are reported frequently. Allergic granulomatous angiitis is also reported, a causal relationship has not been established.

Pulmonary sarcoid-like granulomatosis induced by nivolumab.

The use of antibodies against programmed death (PD)1, such as nivolumab and pembrolizumab, has dramatically improved the prognosis of patients with advanced melanoma. Nivolumab is also approved in advanced squamous cell nonsmall-cell lung cancer. These immunotherapies are associated with a unique set of toxicities termed immune-related adverse events, which are different from toxicities observed with conventional cytotoxic chemotherapy. We report the case of a 56-year-old man who was diagnosed with metastatic melanoma and who received nivolumab. One week after the second infusion, he developed pulmonary symptoms, dry eye syndrome and a bilateral swelling of the parotid glands. Investigations were negative for infection. The bronchoalveolar lavage differential cell count showed 32% lymphocytes with an increased CD4 : CD8 ratio, and bronchial biopsies revealed noncaseating epithelioid granulomas, without malignant cells. The clinical and radiological courses were rapidly favourable with oral corticosteroid. This case illustrates that sarcoidosis can be induced by nivolumab treatment. With the increasing use of anti-PD1 inhibitors in patients with advanced melanoma and squamous cell nonsmall-cell lung cancer, clinicians should be aware of this potential associated immune-related adverse event.

Development of eosinophilic granulomatosis with poliangiitis (Churg-Strauss syndrome) and brain tumor in a patient after more than 7 years of omalizumab use: A case report.

Omalizumab is a monoclonal anti-immunoglobulin E antibody used for the treatment of severe perennial allergic asthma. Previous reports have suggested that omalizumab treatment can be associated with the development of eosinophilic granulomatosis with poliangiitis (EGPA) (formerly known as Churg-Strauss syndrome) and an increased risk of malignancy. Long-term risks of omalizumab treatment are not very well defined. Here, we report the case of a 75-year-old woman with concurrent occurrence of EGPA and brain tumor after more than 7 years of omalizumab treatment. The possibility of EGPA should be borne in mind during long-term treatment with omalizumab. Despite the absence of definitive data, an association may also exist between the development of malignancy and omalizumab use.

Systemic granulomatosis after surgical injection of silicone oil for retinal detachment in a child affected by Fisher-Evans syndrome.

UNLABELLED: Silicone oil is used for complicated retinal detachment, but it can be associated with relevant side effects. We report a 6-year-old South American female admitted to our hospital with steroid-resistant Fisher-Evans syndrome. She also had developed a retinal detachment, managed with intravitreal oil injection. During treatment for Fisher-Evans syndrome, she progressively developed recurrent and refractory bronchospasm, peaks of hypereosinophilia and orbital soft-tissue swelling. Despite the persistent negativity of all microbiologic tests, she was treated empirically with antibiotics. Failure of the treatment led to the execution of a biopsy of the periocular tissue that revealed an intense polymorphous infiltrate constituted by numerous monoclonal population (FR2 monoclonality) of plasma-cells. A diagnosis of lymphoma with plasmacytoid differentiation was suspected and cytotoxic treatment was started without response. For the appearance of swelling in left parotid and laterocervical region, an excisional biopsy was performed and a diagnosis of granulomatous reaction to ocular implant of silicone oil was made. In consideration of the clinical evolution, enucleation was considered, but parents did not consent to the procedure until the child developed cerebral lesions suspected to be silicone localizations. After enucleation, eosinophilic count normalized and the child no longer presented any new episode of fever or swelling. CONCLUSIONS: In this patient a granulomatous reaction is present at distance from the site of oil injection. This case suggests caution in using this substance even in ocular diseases, especially in immunocompromised patients.

Novel finding of carbamazepine induced gall bladder granulomatous vasculitis.

We report a 63-year-old male patient who presented with eosinophilic granulomatous vasculitis of the gall bladder secondary to carbamazepine drug therapy. Following commencement of carbamazepine for treatment of partial seizures, the patient developed an allergic cutaneous drug rash. He continued to take carbamazepine postdischarge despite cessation by the treating team. He represented 7 weeks later with acute pancreatitis and cholecystis. Gall bladder histopathology showed a granulomatous vasculitis.