Intravenous anakinra to curb cytokine storm in adult-onset Still's disease and in macrophage activation syndrome: A case series.

OBJECTIVE: Adult-onset Still's disease (AOSD) is an auto-inflammatory polygenic disorder, for which the diagnosis is essentially clinical. The exclusion of mimickers [such as common bacterial and viral infections, hematologic malignancies, and, more recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] is necessary to confirm the diagnosis. Anti-interleukin (IL)-1 therapy is considered a treatment milestone for AOSD. Herein, we present a short series of newly-diagnosed AOSD or upcoming macrophage activation syndrome (MAS) cases who received intravenous (IV) anakinra, an IL-1 receptor blocker. METHODS: Four patients with newly-diagnosed AOSD or upcoming MAS were treated with IV anakinra at the Rheumatology Unit of Padova University Hospital, Italy. We obtained informed consent from the patients for use of their cases and medical images for publication purposes. RESULTS: All patients presented with AOSD or MAS during the COVID-19 pandemic, making diagnosis challenging due to similar immunological and clinical characteristics across both pathologies. All patients presented with hyperpyrexia and elevated inflammatory markers; two patients had a skin rash typically seen in AOSD. IV anakinra slowed down AOSD progression in all patients, prevented severe outcomes and mitigated the risk of multiorgan failure. All cases improved within 24hours of anakinra administration. CONCLUSION: We found that administration of anakinra in patients with newly-diagnosed AOSD and/or upcoming MAS reduced hyperinflammation and prevented life-threatening complications. The IV route appears to be preferable in the hospital setting, where comorbidities such as coagulopathies and thrombocytopenia can complicate the use of other routes of administration.

Comprehensive description of adult-onset Still's disease after COVID-19 vaccination.

Cases of adult-onset Still's disease (AOSD) have been reported after COVID-19 vaccination. Here we provide a comprehensive description and analysis of all cases of AOSD reported in the literature and in pharmacovigilance databases through April 2022. Disproportionality analyses of pharmacovigilance data were performed in order to further explore the association between vaccination and AOSD. We included 159 patients, 144 from the World Health Organization pharmacovigilance database and 15 from the literature. Detailed clinical characteristics were described for the cases from the literature and from the French pharmacovigilance database (n = 9). The cases of AOSD after COVID-19 vaccination concerned women in 52.2% of cases. The median age was 43.4 years. More than 80% of AOSD reports occurred during the first three weeks and concerned mostly the BNT162b2 mRNA vaccine. We identified 14.5% of disease flare with a median time-to-onset of AOSD flare-up significantly shorter than for the new onset form. More than 90% patients received steroids. Although all cases were considered serious and required hospitalization, most cases presented a favorable outcome (67.1%) with a good response to corticosteroid therapy with a mean time to recovery of 7.2 days. Disproportionality analyses suggested that AOSD was associated with COVID-19 vaccines as well as other vaccines. AOSD was nearly five times more frequently reported with COVID-19 vaccines than with all other drugs. Clinicians should be informed about the potential risk of AOSD onset or flare following COVID vaccines and the importance of its early detection to optimize its management.

Adult-Onset Still's Disease-A Complex Disease, a Challenging Treatment.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with an unknown cause characterized by high-spiking fever, lymphadenopathy, hepatosplenomegaly, hyperferritinemia, and leukocytosis. The clinical course can be divided into three significant patterns, each with a different prognosis: Self-limited or monophasic, intermittent or polycyclic systemic, and chronic articular. Two criteria sets have been validated. The Yamaguchi criteria are the most generally used, although the Fautrel criteria offer the benefit of adding ferritin and glycosylated ferritin values. AOSD's pathogenesis is not yet completely understood. Chemokines and pro-inflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor α (TNFα), interleukin (IL)-1, IL-6, IL-8, and IL-18, play a crucial role in the progression of illness, resulting in the development of innovative targeted therapeutics. There are no treatment guidelines for AOSD due to its rarity, absence of controlled research, and lack of a standard definition for remission and therapy objectives. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CS), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are used in AOSD treatment. Biological therapy, including IL-1, IL-6, IL-18, and IL-17 inhibitors, as well as TNFα or Janus-kinases (JAKs) inhibitors, is administered to patients who do not react to CS and csDMARDs or achieve an inadequate response.

COVID-19 in a patient with new adult-onset Still disease: A case report.

RATIONALE: Adult-onset Still disease (AOSD) is a systemic autoinflammatory illness of unknown cause. Its manifestations comprise fever; arthritis or arthralgia; and skin rash with high inflammatory markers and ferritin levels. Coronavirus disease 2019 (COVID-19) shares several clinical features and laboratory markers of AOSD: making it challenging to differentiate between the 2 conditions. PATIENT CONCERNS: A 29-year-old woman presented with fever, skin rash, and polyarthritis 4 weeks before admission. Two weeks after illness onset, she had an infection with symptoms similar to those of COVID-19. She observed that her symptoms worsened, and new symptoms appeared including headache; vomiting; diarrhea; and loss of taste and smell. The patient tested positive for severe acute respiratory syndrome coronavirus 2 using polymerase chain reaction. DIAGNOSIS: The patient was diagnosed with AOSD complicated with COVID-19 after exclusion of other possible causes of her illness, such as infections, malignancy, or underlying rheumatological disease. INTERVENTIONS: The patient was administered corticosteroids and methotrexate. The patient responded quickly, particularly to corticosteroids. OUTCOMES: This is the second reported case of COVID-19 in a patient with AOSD. She experienced COVID-19 shortly after having AOSD, indicating that those with AOSD might have a higher risk of COVID-19 infection. Furthermore, she developed the most prevalent COVID-19 symptoms. However, distinguishing most of these symptoms from AOSD manifestations was difficult. LESSONS: Early diagnosis and differentiation between AOSD and COVID-19 and prompt initiation of treatment are required.

New-onset Adult-onset Still's disease-like syndrome after ChAdOx1 nCoV-19 vaccination-a case series with review of literature.

We report a series of 3 Adult-onset Still's disease (AOSD)-like presentations in previously healthy females following vaccination with the ChAdOx1 nCoV-19 vaccine, and also compare them with similar cases reported in literature through a PubMed database search. Our first patient had a high spiking bi-quotidian type of fever with myalgia, sore throat, and arthritis with onset 10-day post-vaccination, with laboratory features of hyper inflammation responding to only naproxen. She was off treatment after 2 months. The second patient, with onset 3-week post-vaccination, had a more severe illness, requiring high dose immunosuppression. In our third case, the onset of illness was slightly delayed i.e., 3-month post-vaccination, but she had the most severe disease with macrophage activation syndrome at presentation requiring immunosuppression and biologicals. The underlying mechanism may be linked to the activation of Toll-like receptors (TLR)-TLR-7 and TLR-9-leading to a robust immune response. These 3 cases highlight the immunogenicity of COVID-19 vaccines, with the possibility of occurrence of new-onset systemic hyper-inflammation illness which can happen a few days following the vaccination, sometimes even delayed to months, and can range in severity from mild to even life-threatening. More cases need to be studied to understand the profile and prognosis of these syndromes in the long run.

Adult-onset Still's Disease after BNT162b2 mRNA COVID-19 Vaccine.

The coronavirus disease 2019 (COVID-19) pandemic is being overcome by widespread inoculation with various COVID-19 vaccines, but concerns about the safety of the vaccines are a major hurdle to widespread vaccination. We report the first case of adult-onset Still's disease (AOSD) developing in a 36-year-old, previously healthy woman after the first dose of BNT162b2 mRNA COVID-19 vaccine (Pfizer). She visited our hospital due to high spiking fever and sore throat that developed 10 days after vaccination. Based on thorough investigations and changes in symptoms and signs after admission, she was diagnosed with AOSD and treated with high dose steroids and tocilizumab. This report suggests the possibility that AOSD could be triggered by COVID-19 vaccines through activation of the innate immune system.

A flare of Still's disease following COVID-19 vaccination in a 34-year-old patient.

Vaccination is a cornerstone for reducing the risk of COVID-19 infection during a pandemic. Although the currently used COVID-19 vaccine is considered safe, some concerns persist regarding the likelihood of flares of rheumatic diseases. Still's disease is a rare auto-inflammatory disorder of unknown etiology, and the data on the flare of Still's disease following COVID-19 vaccination are limited. Therefore, we hereby present the case of a 34-year-old female patient with Still's disease who experienced a flare after a ChAdOx1 nCoV-19 vaccination. The patient visited the emergency department complaining of fever, arthralgia, myalgia, pleuritic chest pain and macular salmon-pink rash on her back for the past 2 days. She had maintained low Still's disease activity with etanercept and low-dose glucocorticoid for 14 years. She received the ChAdOx1 nCoV-19 vaccine 7 days before the flare. Laboratory investigations revealed leucocytosis and elevated serum levels of erythrocyte sedimentation rate, C-reactive protein, and ferritin. Computed tomography showed no specific findings. She received methylprednisolone pulse therapy, etanercept, and methotrexate for treating the Still's disease flare. However, her symptoms were not fully controlled, and she developed pericarditis, pleuritis, fever and macular rashes expanding to her extremities. After excluding infectious conditions by blood culture and pleural fluid analysis, we administered tocilizumab with methotrexate and prednisolone. Her symptoms and laboratory findings improved significantly, and she was discharged without symptoms 7 days later. Although rare, this case of a patient with Still's disease undergoing a flare following vaccination suggests that close observation of disease activity is warranted following COVID-19 vaccination.

COVID-19 and adult-onset Still's disease as part of hyperferritinemic syndromes.

The coronavirus disease (COVID-19) is known to cause hyperferritinemia and haemophagocytic lymphohistiocytosis. Including this laboratory parameter, symptoms similar to COVID-19 have been observed in adult-onset Still's disease (AOSD), catastrophic antiphospholipid syndrome, macrophage activation syndrome, and septic shock, which has led to the proposal of a concept called 'hyperferritinemic syndromes'. High levels of some clinical markers in both COVID-19 and AOSD make them difficult to differentiate. While the efficacy of ciclesonide had been expected for mild pneumonia with COVID-19, the efficacy of tocilizumab (TCZ), which is a known treatment for AOSD, was not established. We report the first known occurrence of COVID-19 diagnosed in March 2020, preceded by the diagnosis of AOSD in April 2019. The patient was given prednisolone and TCZ, which led to remission. With the dyspnea and ground-glass appearance on chest computed tomography, PCR test revealed COVID-19 infection. Ciclesonide was started on Day 7 of the disease onset, which led to improved inflammatory markers. We infer that while TCZ is theoretically useful for COVID-19 due to its inhibition of interleukin 6. AOSD and COVID-19 may be differentiated by levels of ferritin, and appropriate treatment must be allocated.

Recurrent deep venous thromboses in a patient with adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is a rare inflammatory disorder affecting just over one in a million people. Due to its rarity, understanding of its pathophysiology and the spectrum of its clinical associations are limited. Improved case identification and creation of patient registries have begun to reveal sporadic reports of deep venous thromboses associated with AOSD. Herein, we report the first case of recurrent deep venous thrombosis in a patient with AOSD despite treatment with therapeutic dose anticoagulant medication. This case points for a judicious approach to the selection of an anticoagulation strategy for deep venous thromboses in the setting of active AOSD. This case is of contemporary interest in its clinical similarity with COVID-19 symptoms and pathophysiology for which a careful diagnostic approach with a broad differential should be considered given the limitations of SARS-CoV-2 testing and the risk associated with treatment in the event of misdiagnosis.