COVID-19 shares clinical features with anti-melanoma differentiation-associated protein 5 positive dermatomyositis and adult Still's disease.

OBJECTIVES: To investigate the similarities and differences between Coronavirus disease 2019 (COVID-19) and autoimmune and autoinflammatory rheumatic diseases characterised by hyperferritinaemia, such as antimelanoma differentiation-associated protein 5 (MDA5) autoantibody-positive dermatomyositis and adult Still's disease. METHODS: We reviewed consecutive, newly diagnosed, untreated patients with COVID-19, anti-MDA5 dermatomyositis, or adult Still's disease. We compared their clinical, laboratory, and radiological characteristics, including the prevalence of macrophage activation syndrome and lung involvement in each disease. RESULTS: The numbers of patients with COVID-19, anti-MDA5 dermatomyositis, and adult-onset Still's disease with hyperferritinaemia (serum ferritin ≥500ng/dL) who were included for main analysis were 22, 14, and 59, respectively. COVID-19 and adult Still's disease both featured hyperinflammatory status, such as high fever and elevated serum C-reactive protein, whereas COVID-19 and anti-MDA5 dermatomyositis both presented with severe interstitial lung disease and hypoxaemia. While two-thirds of the patients in each group met the criteria for macrophage-activated syndrome that is used in systemic juvenile idiopathic arthritis, the HScore, an indicator of haemophagocytic lymphohistiocytosis, was low in anti-MDA5 dermatomyositis and COVID-19 even in severe or critical cases. The findings of chest computed tomography were similar between COVID-19 and anti-MDA5 dermatomyositis. CONCLUSIONS: COVID-19 shared clinical features with rheumatic diseases characterised by hyperferritinaemia, including anti-MDA5 dermatomyositis and adult Still's disease. These findings should be investigated further in order to shed light on the pathogenesis of not only COVID-19 but also the aforementioned rheumatic diseases.

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.

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.

Expanding the spectrum of the hyperferritinemic syndrome, from pathogenic mechanisms to clinical observations, and therapeutic implications.

From the introduction of hyperferritinemic syndrome concept, a growing body of evidence has suggested the role of ferritin as a pathogenic mediator and a relevant clinical feature in the management of patients with inflammatory diseases. From a pathogenic point of view, ferritin may directly stimulate the aberrant immune response by triggering the production of pro-inflammatory mediators in inducing a vicious pathogenic loop and contributing to the occurrence of cytokine storm syndrome. The latter has been recently defined as a clinical picture characterised by elevated circulating cytokine levels, acute systemic inflammatory symptoms, and secondary organ dysfunction beyond that which could be attributed to a normal response to a pathogen It is noteworthy that the occurrence of hyperferritinemia may be correlated with the development of the cytokine storm syndrome in the context of an inflammatory disease. In addition to adult onset Still's disease, macrophage activation syndrome, catastrophic anti-phospholipids syndrome, and septic shock, recent evidence has suggested this association between ferritin and life-threatening evolution in patients with systemic lupus erythematosus, with anti-MDA5 antibodies in the context of poly-dermatomyositis, with severe COVID-19, and with multisystem inflammatory syndrome. The possible underlying common inflammatory mechanisms, associated with hyperferritinemia, may led to the similar clinical picture observed in these patients. Furthermore, similar therapeutic strategies could be suggested inhibiting pro-inflammatory cytokines and improving long-term outcomes in these disorders. Thus, it could be possible to expand the spectrum of the hyperferritinemic syndrome to those diseases burdened by a dreadful clinical picture correlated with hyperferritinemia and the occurrence of the cytokine storm syndrome. In addition, the assessment of ferritin may provide useful information to the physicians in clinical practice to manage these patients. Therefore, ferritin may be considered a relevant clinical feature to be used as biomarker in dissecting the unmet needs in the management of these disorders. Novel evidence may thus support an expansion of the spectrum of the hyperferritinemic syndrome to these diseases burdened by a life-threatening clinical picture correlated with hyperferritinemia and the occurrence of the cytokine storm syndrome.

Two flares of Still's disease after two doses of the ChAdOx1 vaccine.

We report the case of an 18-year-old male with Still's disease for the last 3 years, in remission, who developed two flares of his disease after receiving two doses of the ChAdOX1 nCoV-19 vaccine. While the first flare was mild requiring steroid initiation and resolved rapidly, the second flare after the second dose was much severe, requiring pulse steroid and tocilizumab. We also review three reported cases of flares of Still's disease after COVID-19 vaccination. The temporal association of the flares with both vaccine doses strengthens the association between the vaccine administration and the flare. The proposed mechanism may be due to activation of the innate immune system by the vaccine adjuvants. This review serves to inform the medical community regarding a possible role of the vaccine in producing a systemic inflammatory response. Early detection and treatment can help reduce morbidity in these cases.

Flare of adult-onset Still's disease following mRNA COVID-19 vaccination: a case report and review of literature.

The upheaval caused by the coronavirus disease 2019 (COVID-19) pandemic has allowed to large population to use new vaccines urgently. Although vaccine development programs and available epidemiological data reassure us, there are concerns about specific risks associated with vaccinations in patients with autoimmune-autoinflammatory diseases. These patients have the potential to decrease humoral and cellular immune responses caused by biologic agents and develop an acute flare of underlying disease following vaccination. We herein present a rare case of a 49-year-old female with a flare of adult-onset Still's disease (AOSD) after the first dose of BNT162b2 mRNA COVID-19 vaccination. She had been diagnosed with AOSD 7 years earlier and had achieved remission with tocilizumab. This patient came to the emergency room with fever and nausea that occurred 4 days after the first vaccination. Based on laboratory results and clinical manifestations, we suspected AOSD flare and was treated with steroid pulse therapy. In this report, we also discuss possible mechanisms linking vaccination with a flare of AOSD. Considering the close time relationship between COVID-19 vaccinations and a flare of AOSD, physicians should be aware of adverse events from this new vaccination and evaluate the benefits and risks of vaccination for each patient. KEY POINTS: • COVID-19 vaccination may cause an AOSD flare in patients who are in remission with tocilizumab.

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.