We report a rare long-term case in which systemic polyarteritis nodosa (PAN) was ultimately diagnosed in adulthood after childhood-onset recurrent inflammatory disease with atypical Still-like features. A Japanese man had recurrent febrile episodes from infancy and was diagnosed with juvenile idiopathic arthritis at 9 years of age. In early adulthood, he developed recurrent fever, rash, polyarthralgia, splenomegaly, neutrophilia, and elevated inflammatory markers, and was considered to have Still-spectrum disease. However, ferritin elevation remained modest despite marked systemic inflammation, suggesting that the early phenotype may not have represented typical Still's disease and may instead have reflected a broader autoinflammatory process. At 25 years of age, he developed digital ischaemia with necrosis, palpable nodules, and erectile dysfunction. Angiography demonstrated narrowing of the ulnar and palmar arteries, and skin biopsy showed necrotising vasculitis involving medium-sized vessels, leading to the diagnosis of systemic PAN. He subsequently developed fever, rash, inner-ear involvement, hypertrophic pachymeningitis, and tortuosity/dilatation of a right intercostal artery. A subtle suspected lesion of the right testicular artery later became a definite enlarging aneurysmal lesion on serial imaging. Systemic inflammatory manifestations were subsequently controlled during treatment that included glucocorticoids, azathioprine, and tocilizumab. However, serial imaging demonstrated gradual enlargement of the right testicular artery aneurysmal lesion despite the absence of fever, rash, or C-reactive protein elevation for 5 years. This clinical course suggests that vascular progression may not always be adequately reflected by C-reactive protein levels during interleukin-6 blockade. This case illustrates the diagnostic difficulty of childhood-onset recurrent inflammatory disease with atypical Still-like features that was ultimately recognized as systemic PAN in adulthood. Occult or under-recognized medium-vessel vasculitis may have been present earlier in the disease course. Long-term diagnostic reappraisal, vascular imaging when indicated, and continued follow-up across paediatric and adult rheumatology care may therefore be important in similar patients, particularly in the current biologic era.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disorder characterized by fever, rash, arthritis, and hyperferritinemia, often presenting as a diagnostic challenge due to its nonspecific manifestations. We report the case of a 35-year-old previously healthy male who presented with a 20-day history of pruritic erythematous skin lesions, high-grade fever, severe odynophagia, and symmetric inflammatory polyarthritis. Laboratory evaluation revealed leukocytosis with neutrophilia, elevated acute-phase reactants, liver enzyme abnormalities, and hyperferritinemia (1,050 ng/mL). Infectious, autoimmune, and neoplastic causes were excluded. During hospitalization, the patient developed chest pain with electrocardiographic changes and elevated troponin levels, consistent with acute pericarditis. Skin biopsy demonstrated nonspecific inflammatory dermatitis. A diagnosis of AOSD was established based on clinical findings and Yamaguchi criteria. Initial treatment with systemic corticosteroids resulted in partial improvement; however, early relapse required escalation to tocilizumab, achieving complete clinical remission at two months. This case highlights the importance of considering AOSD in patients with fever of unknown origin and elevated inflammatory markers, as well as the role of early targeted therapy in improving outcomes.

Trained immunity, an innate immunological memory induced by epigenetic and metabolic reprogramming, has changed the paradigm of host defense and pathogenesis of chronic inflammatory disease. Unlike adaptive immunological memory, trained immunity is characterized by the ability of innate immune cells and their progenitors to respond more robustly or differently to subsequent stimulations and contributes to chronic inflammatory conditions. Emerging data suggests that this process might be essential in autoinflammatory and immune-mediated inflammatory illnesses by enhancing sterile inflammation, decreasing activation thresholds, and boosting disease chronicity. This narrative review summarizes the existing evidence relating trained immunity to monogenic and polygenic autoinflammatory diseases. The greatest evidence in monogenic disease is for mevalonate kinase deficiency, where dysregulated mevalonate metabolism directly overlaps with conventional trained immunity pathways. Moderate evidence exists for familial Mediterranean fever, cryopyrin-associated periodic syndromes, and tumor necrosis factor receptor-associated periodic syndrome. For other rare hereditary autoinflammatory diseases, data are still inadequate. There is convincing evidence for a role of trained immunity in polygenic disorders like gout, atherosclerosis, obesity-associated "metaflammation", and type 2 diabetes and increasing evidence in Behçet's disease, adult-onset Still's disease, psoriasis, hidradenitis suppurativa, inflammatory bowel disease, and related inflammatory spectrum disorders. A major conceptual finding is that autoinflammatory illnesses may be a dynamic interplay between hereditary susceptibility and dysfunctional innate immune memory, rather than isolated static inflammatory abnormalities. However, information gaps still exist in reprogramming at the progenitor level, disease-specific epigenetic markers, and the reversibility of trained states. Understanding these systems may allow the development of therapeutic techniques to de-train abnormal innate immunological memory and obtain resilience for diseases.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory condition that presents with symptoms such as episodic fevers, a transient rash, inflammatory arthritis, and significant systemic inflammation. Diseases that have a relapsing-remitting clinical course can be challenging to diagnose and treat. We present a case of an 18 year old female with multiple flares over several years requiring stepwise escalation from conventional disease-modifying antirheumatic drugs (DMARDs) to targeted biologic therapy, highlighting the challenges of achieving durable remission. Our patient presented with recurrent episodes of high-grade fever (up to 40°C), evanescent salmon-pink rash, bilateral symmetrical inflammatory polyarthritis involving the wrists, metacarpophalangeal (MCP), proximal interphalangeal (PIP) joints, and knees with mild splenomegaly. After ruling out infectious, malignant, and other autoimmune diseases via biochemical, serological, autoimmune testing and biopsy, she was diagnosed with AOSD on the basis of the Yamaguchi criteria. Despite receiving treatment with corticosteroids and conventional disease-modifying antirheumatic drugs (DMARDs), including methotrexate, she suffered from multiple relapses, indicating a polycyclic disease pattern. The introduction of biologic therapy with tocilizumab provided temporary remission. However, her flares returned during the tapering of steroids, necessitating an increase in the dosage and the use of pulse corticosteroid therapy during the current admission. This case report illustrates the relapsing-remitting nature of AOSD. Escalation to IL-6 receptor inhibition (tocilizumab) is required in DMARDs refractory relapsing AOSD, with dose optimization to achieve sustained remission of disease activity of our patient.

Treatment strategies for pediatric rheumatic diseases have changed substantially over the past two decades, driven by the development of biologics and cytokine-targeted molecular therapy. Therapeutic approaches that modulate both innate and adaptive immune responses have improved prognosis in these immune-mediated disorders, and early diagnosis with timely intervention is associated with better outcomes. However, affected children often present with non-specific symptoms, and reliable biomarkers remain limited in juvenile idiopathic arthritis (JIA); thus, the diagnostic delay remains common. Imaging is an important adjunct in pediatric rheumatology; in selected scenarios, it can be pivotal for establishing a definitive diagnosis and for assessing disease subtype, complications, and treatment response. This review presents an imaging-focused overview of pediatric rheumatic diseases. We begin with a brief review of current immunologic concepts, including the autoinflammatory-autoimmune continuum, then illustrate typical imaging findings, discuss key differential diagnoses, and summarize the diagnostic strengths and limitations of major imaging modalities. We discuss in detail the major JIA subtypes based on the PRINTO classification, which aims to improve clinical coherence, facilitate risk stratification, and clarify relationships between pediatric and adult rheumatic entities. We also highlight interferonopathies-disorders characterized by a type I interferon signature-which provide a useful framework for understanding the mechanistic links between autoinflammation and autoimmunity along the continuum and for contextualizing selected autoimmune diseases, including systemic lupus erythematosus, juvenile dermatomyositis, and Sjögren's syndrome.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disorder that should be considered in patients presenting with fever of unknown origin (FUO). Diagnosis is challenging due to overlapping features with infectious, autoimmune, and hematological conditions. We report the case of a 19-year-old female presenting with a six-day history of persistent fever, later developing an evanescent rash and migratory polyarthralgia. Laboratory findings included cytopenias, elevated inflammatory markers, and markedly elevated ferritin levels. After ruling out infectious, autoimmune, and neoplastic etiologies, AOSD was diagnosed based on the Yamaguchi classification criteria. Initial treatment with corticosteroids led to partial clinical improvement, but persistent articular symptoms required escalation to anakinra, resulting in complete remission. This case reinforces that AOSD should be considered in the differential diagnosis of FUO, particularly in the presence of quotidian fever, rash, polyarthralgia, and marked hyperferritinemia. Early recognition and appropriate treatment, including biological therapy, are essential to control disease activity and prevent complications.