Complication Of Adult-onset Still Disease Research Articles

Intravenous Anakinra for Treating Macrophage Activation Syndrome in Adult-Onset Still's Disease.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease characterized by fever, rash, arthritis, and multi-organ involvement. Macrophage activation syndrome (MAS), a serious complication of AOSD, poses significant diagnostic and therapeutic challenges. A 32-year-old male was diagnosed with AOSD in 2020 after being hospitalized for a fever of unknown origin and elevated liver enzymes. The patient was initially treated with corticosteroids and methotrexate but subsequently discontinued both treatment and follow-up. In September 2023, he presented with fever, sore throat, and elevated inflammatory markers. After screening for infections, methylprednisolone (MP) treatment was initiated because of AOSD activation. The following day, the patient was admitted to the intensive care unit due to an altered state of consciousness. Brain magnetic resonance imaging revealed brainstem involvement. Empirical treatments were initiated, including intravenous MP, and immunoglobulin therapy. Due to suspected macrophage activation syndrome (MAS), anakinra (ANA) infusion was initiated. Significant improvement was observed after the ANA infusion. This case highlights the complex management of severe AOSD complications, emphasizing the role of early recognition, aggressive therapy, and multidisciplinary care in improving outcomes. Macrophage activation syndrome (MAS) is a serious complication of adult-onset Still's disease characterized by systemic inflammation. Early recognition and prompt initiation of treatment are crucial due to the high mortality rate associated with MAS, especially when neurologic symptoms are present.Clinicians should not delay treatment pending confirmatory diagnostic tests when MAS is suspected, as early intervention can significantly impact patient outcomes.Anakinra, an interleukin-1 inhibitor, is typically administered subcutaneously but has shown promise when administered intravenously, particularly in severe cases of MAS.

Clinicopathologic Features of Adult-onset Still's Disease Complicated by Severe Liver Injury.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder. Severe liver injury has rarely been reported, although liver enzyme elevation is a common complication of AOSD. We herein report four cases of relapsed AOSD with severe liver disorder by tapering or terminating corticosteroids. Liver specimens revealed robust infiltration of inflammatory cells throughout the lobule, especially cluster of differentiation (CD) 8-positive cells. Relapsed AOSD was refractory to corticosteroid reintroduction and required immunosuppressants. Severe liver injury with AOSD is pathologically characterized by extensive lobular infiltration of CD8-positive cells, and we should consider additive immunosuppressive agents on corticosteroids for treatment.

Rare, rarer, lung involvement in adult-onset Still's disease: A mini-review

Adult-onset Still's disease (AOSD) is a polygenic systemic autoinflammatory disease which is associated with increased morbidity and mortality. Pulmonary involvement is a rare, but serious complication of AOSD. As in AOSD, IL-1b, IL-18, and IL-6 dominate the molecular pathogenesis, which mediate a type 1 and type 3 inflammatory signature of the adaptive immune system. This is evidenced by the success of IL-1- and IL-6 inhibition in the management of AOSD. However, anaphylactic reactions to treatment with IL-1- or IL-6-inhibitors is currently being discussed as a potential trigger for lung involvement inf AOSD, while genetic risk factors have also been identified. Clinically, pulmonary involvement in AOSD can manifest in many different forms. Parenchymal inflammation with peripheral consolidations is the most frequent form while PAH is less common, but often very difficult to manage. This mini-review provides an overview of the pathophysiology as well as the clinical presentation and the diagnostic features of pulmonary involvement in AOSD.

Activation mechanisms of monocytes/macrophages in adult-onset Still disease.

Adult onset Still disease (AOSD) is a systemic inflammatory disorder characterized by skin rash, spiking fever, arthritis, sore throat, lymphadenopathy, and hepatosplenomegaly. Although the etiology of this disease has not been fully clarified, both innate and acquired immune responses could contribute to its pathogenesis. Hyperactivation of macrophages and neutrophils along with low activation of natural killer (NK) cells in innate immunity, as well as hyperactivation of Th1 and Th17 cells, whereas low activation of regulatory T cells (Tregs) in acquired immunity are involved in the pathogenic process of AOSD. In innate immunity, activation of monocytes/macrophages might play central roles in the development of AOSD and macrophage activation syndrome (MAS), a severe life-threating complication of AOSD. Regarding the activation mechanisms of monocytes/macrophages in AOSD, in addition to type II interferon (IFN) stimulation, several pathways have recently been identified, such as the pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)-pattern recognition receptors (PRRs) axis, and neutrophil extracellular traps (NETs)-DNA. These stimulations on monocytes/macrophages cause activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain (NLRP) 3 inflammasomes, which trigger capase-1 activation, resulting in conversion of pro-IL-1β and pro-IL-18 into mature forms. Thereafter, IL-1β and IL-18 produced by activated monocytes/macrophages contribute to various clinical features in AOSD. We identified placenta-specific 8 (PLAC8) as a specifically increased molecule in monocytes of active AOSD, which correlated with serum levels of CRP, ferritin, IL-1β, and IL-18. Interestingly, PLAC8 could suppress the synthesis of pro-IL-1β and pro-IL-18 via enhanced autophagy; thus, PLAC8 seems to be a regulatory molecule in AOSD. These findings for the activation mechanisms of monocytes/macrophages could shed light on the pathogenesis and development of a novel therapeutic strategy for AOSD.

Macrophage activation syndrome in neonates born to mothers with adult-onset Still's disease: Perinatal effect of maternal IL-18

Overproduction of interleukin (IL)-18 is closely related to the pathogenesis of adult-onset Still's disease (AOSD) and the development of macrophage activation syndrome (MAS), a life-threating complication of AOSD. We reported three cases of MAS occurring in infants born to mothers with AOSD. The infants developed MAS at age 13 and 8 days and at birth. Serum IL-18 levels were extremely elevated in all infants (147,000 pg/mL; 378,000 pg/mL; 95,000 pg/mL) as well as in their mothers (58,500 pg/mL; 367,000 pg/mL; 84,000 pg/mL). Physicians should be aware that infants born to mothers with AOSD are at a risk of developing MAS. Serum IL-18 levels in mothers with AOSD and their infants should be monitored.

Parvovirus-Induced Adult Onset Stills Disease Presenting With Elevated Liver Transaminases

Adult-onset Still's disease (AOSD) is an inflammatory disorder affecting multiple systems characterized by polyarthritis, rash, fever, and an elevated erythrocyte sedimentation rate. Macrophage activating syndrome is a severe complication of AOSD leading to pancytopenia, hypofibrinogenemia, elevated triglycerides, lactate dehydrogenase, soluble IL-2 receptor alpha chain (CD25), and ferritin. AOSD is a very rare cause of markedly elevated liver chemistries. A 50-year-old female with a past medical history of asthma developed sore throat, diffuse joint aches, muscle weakness, and a fever of 104° F. She was evaluated at an outside facility and noted to have positive Parvovirus IgM/IgG. She was started on Prednisone 30 mg and with a taper, she experienced a reticular erythematous rash, arthralgias involving the wrist and ankle, myalgias, and cyclic fevers with a temperature max of 100.8° F. She had an aspartate aminotransferase (AST) of 853, alanine transaminase (ALT) of 866, and total bilirubin of 1.5 from prior normal baseline. Complete evaluation for viral hepatitis and hereditary liver disease was negative. Ultrasound with doppler showed parenchymal liver disease with patent vascular flow. Within 48 hours, her AST increased to 2,452, ALT 2,213, and total bilirubin of 3.3. Ferritin was elevated >30,000 ng/mL. Transjugular liver biopsy showed hepatic parenchyma with acidophil bodies, Kupffer aggregates, and preserved architecture with patchy collections of acute and chronic inflammatory cells. No bridging necrosis or iron deposition was appreciated. She was treated with high dose Methylprednisolone 250 mg IV daily with downtrend in transaminases. As steroids were tapered, AST rose from 71 to 198 and ALT from 390 to 900. Percutaneous liver biopsy showed mildly increased inflammation and confluent necrosis. She was discharged on anakinra 100 mg, a recombinant interleukin 1 receptor antagonist, and prednisolone 60 mg twice daily with continued improvement in transaminases to AST of 59 and ALT of 380. The patient developed AOSD likely induced by parvovirus which was complicated by MAS and transaminase elevation >5 upper limit of normal. The pathogenesis of liver involvement of AOSD is unknown but it is presumed that sustained macrophage activation with cytokine production play a role. This is evidenced in this case as transaminases decreased with steroid dosing and increased with the initial taper.

Reactive hemophagocytic syndrome in adult-onset Still disease: clinical features, predictive factors, and prognosis in 21 patients.

Hemophagocytic syndrome (HPS) is a potentially life-threatening complication of systemic inflammatory disorders. Adult-onset Still disease (AOSD) is one of the systemic autoimmune diseases associated with reactive hemophagocytic syndrome (RHS). This study aimed to evaluate the characteristic findings, predictive factors, and prognosis of RHS in patients with AOSD.We retrospectively evaluated 109 patients diagnosed with AOSD and reviewed their clinical data and laboratory findings, including the biopsy results of 21 AOSD patients with RHS. Moreover, data from 17 hemophagocytic lymphohistiocytosis (HLH) patients evaluated during the same period were compared with those from the RHS patients.Twenty-one patients (19.3%) developed RHS during the course of AOSD, and only 7 patients (6.4%) were confirmed by bone marrow, liver, or lymph node biopsy. AOSD patients with RHS showed significantly higher frequencies of splenomegaly, hepatomegaly, and lymphadenopathy than did those without RHS. Moreover, patients with RHS showed significantly higher relapse rates than those without RHS (61.9% vs 18.2%, P < 0.001). Possible triggering factors inducing hemophagocytosis were detected in 16 of 21 RHS patients (76.2%): disease flare in 12 patients (75%), infection in 3 patients (18.8%), and drug use in 1 patient (6.3%). AOSD patients with RHS showed higher frequencies of leukopenia, anemia, thrombocytopenia, hypoalbuminemia, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, and elevated lactate dehydrogenase levels than did those without RHS. Multivariate logistic regression with forward selection procedure showed that low platelet count (<121,000/mm3), anemia, and hepatomegaly were independent predictors of RHS. Patients with definite RHS and those with probable RHS showed comparable results. Although RHS is a life-threatening complication of AOSD, long-term prognosis was observed to be similar in patients with and those without RHS. Compared to RHS patients, HLH patients had poor prognosis, such as higher death rates (52.9% vs 9.5%, P = 0.005).RHS can be considered when an AOSD patient shows at least 2 of the following 3 findings: low platelet count, anemia, and hepatomegaly. Diagnostic confirmation by biopsy may not be essential if typical clinical findings of RHS are present. Moreover, prognosis of RHS was better than that of HLH diagnosed by the presence of trilineage cytopenia at admission.

A novel therapeutic approach in pulmonary arterial hypertension as a complication of adult‐onset Still's disease: targeting IL‐6

Adult-onset Still's Disease (AOSD), often though as the adult variant of systemic juvenile idiopathic arthritis (JIA), has an incidence of 1-3 cases per 1 million. Cardinal manifestations include fever, arthritis, skin rash, sore throat, hepatosplenomegaly and lymphadenopathy. Prolongation in diagnosing this disease results from its similarity to infectious, malignant and rheumatic diseases and lack of biomarkers. Pulmonary arterial hypertension (PAH) is a rare pulmonary complication of AOSD, and we are aware of only six cases reported in literature to date. Here we present a patient with AOSD who has developed pulmonary hypertension as a complication. We report a case of AOSD complicated by PAH treated successfully with tocilizumab, a humanized monoclonal antibody to human interleukin (IL)-6 receptor. A Pubmed and Medline search for evidence of pulmonary hypertension in AOSD and use of IL-6 inhibition in management was performed. Data for this study was collected from the patient's chart records. No infectious or neoplastic cause of her disease was identified and after extensive diagnostic workup, the patient was diagnosed with AOSD fulfilling Yamaguchi criteria. After initiation of IL-6 therapy the patient was followed over time to monitor the hemodynamic changes in pulmonary vasculature. Following treatment with Tocilizumab, the patient showed dramatic improvement in her clinical symptoms and remains in remission, through combination of tocilizumab (8 mg/kg), methotrexate and prednisone. Improvement of systemic symptoms, right heart catheterization (RHC) findings and the VECTRA-DA score served as a measure of treatment response. Tocilizumab has been effective in demonstrating marked improvement in both the clinical and laboratory parameters. Tocilizumab is an effective novel treatment for AOSD with PAH. This is the first documented report of successful use of tocilizumab in AOSD patients presenting with PAH. Prospective comparative studies could help validate its efficacy and safety.

A Case of Adult Onset Still's Disease Complicated with Cryptogenic Organizing Pneumonia

Only a few pathologic reports exist describing adult onset Still's disease (AOSD) with pulmonary involvement. We report this very rare case of AOSD complicated with cryptogenic organizing pneumonia (COP). A 32-year-old woman was referred with high spiking fever, salmon-pink rash in her arms and legs, and polyarthralgia. The laboratory data showed marked increases in white blood cell count, an erythrocyte sedimentation rate, and C reactive protein, ferritin, and liver dysfunction. All cultures remained negative, as were autoantibodies and rheumatoid factor. The patient was strongly suspected of AOSD according to specific diagnostic criteria. However, chest X ray disclosed an infiltrative shadow accompanied by air bronchogram in the upper lobe of the right lung and therapy with antibiotics was initiated. As the patient did not respond to antibiotics and a remittent fever of over 38°C, a flexible bronchoscopy was performed. Organizing pneumonia was diagnosed by transbronchial lung biopsy (TBLB) histology and radiologically, and the lesions were thought to be due to pulmonary involvement of AOSD. Therefore, she was diagnosed with AOSD complicated with COP. Oral treatment with prednisolone (30 mg/day) resulted in rapid disappearance of the infiltrative shadow. Symptoms and markers of inflammation also improved. Clinicians should be aware that COP can be a complication of AOSD.

Two cases of acute respiratory distress syndrome resulting from adult-onset Still's disease

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown origin. Acute respiratory distress syndrome (ARDS) is a rare complication of AOSD, with only nine cases having been reported in the literature. Here, we describe two cases of AOSD complicated with ARDS that were successfully treated with immunosuppressive therapy, including corticosteroids. Although ARDS is a life-threatening complication in AOSD, early commencement of high-dose corticosteroids and mechanical ventilation improve the prognosis.