Host inflammatory responses contribute substantially to infection-related morbidity, and in severe cases such as sepsis, acute respiratory distress syndrome (ARDS) and haemophagocytic lymphohistiocytosis, immune-mediated tissue injury may exceed the direct effects of pathogens themselves. Although traditional wisdom has considered immunosuppression risky when antimicrobial therapy is required, modern insights into immune biology reveal a more nuanced landscape in which targeted immunomodulators can attenuate harmful inflammation without broadly compromising host defence. This evolution is particularly relevant in paediatrics, influenced by developmental stage, distinct exposure history and patterns of host response. The COVID-19 pandemic catalysed wider acceptance of immunomodulation in infection management, including corticosteroids in children and highlighted safe use of agents such as baricitinib. Platform trials of the hyperinflammatory syndrome (paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2) also identified benefits of methylprednisolone and tocilizumab in select groups. For other paediatric infections, including dengue, influenza and Epstein-Barr virus, the evidence remains sparse, with emerging mechanistic and early-phase clinical studies exploring interleukin (IL)-1 blockade, corticosteroids, immunoglobulin and anticytokine biologics. In paediatric sepsis, immunophenotype-guided trials represent a major conceptual advance. Adaptive studies, such as TRIPS and GRACE-2, aim to tailor immunomodulation to hyperinflammation or immunoparalysis, though definitive efficacy data are awaited. Parallel efforts in ARDS explore statins, IL-6 blockade and cell-based therapies, but robust paediatric evidence is still lacking. Collectively, evolving insights and trial designs offer renewed opportunities to use targeted immunomodulation in the management of paediatric infection. Large-scale, collaborative paediatric research networks will be essential to translate these advances and better integrate infection research into everyday paediatric practice.

BACKGROUND Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a strong predilection for women of reproductive age. Although uncommon, juvenile-onset SLE (jSLE) is usually associated with more severe disease than adult-onset SLE. The simultaneous occurrence of gastrointestinal and genitourinary manifestations, such as lupus enteritis, cystitis, and epididymo-orchitis, is exceedingly rare. We describe an unusual presentation of jSLE in an adolescent male patient with combined gastrointestinal and genitourinary involvement. CASE REPORT We report a previously healthy 16-year-old male patient who presented with a 2-month history of high-grade fever, weight loss, and lymphadenopathy, initially diagnosed as pyrexia of unknown origin. Further evaluation confirmed jSLE with multiorgan involvement, including lupus nephritis, enteritis, peritonitis, cystitis, and immune-mediated epididymo-orchitis. This was supported by imaging, which revealed small-bowel wall thickening, ascites, and diffuse bladder wall thickening on abdominal computed tomography, as well as bilateral epididymo-orchitis on scrotal ultrasonography, findings consistent with lupus enteritis, peritonitis, and cystitis. Clinical and biochemical responses were achieved after induction with intravenous methylprednisolone pulses, followed by gradual corticosteroid tapering and high-dose intravenous cyclophosphamide. Remission maintenance with hydroxychloroquine and mycophenolate mofetil enabled corticosteroid discontinuation and complete symptom resolution at follow-up. CONCLUSIONS This case demonstrates a rare occurrence of SLE in a male adolescent with concurrent gastrointestinal and genitourinary manifestations. Recognizing these atypical features is vital when evaluating abdominal pain and urinary symptoms in patients with SLE. Early diagnosis and prompt initiation of immunosuppressive therapy remain the cornerstone for minimizing the risk of long-term morbidity and are associated with a more favorable prognosis.

Myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) can present with diffuse alveolar hemorrhage (DAH), a life-threatening pulmonary complication, even in the absence of renal involvement. Relapse and steroid-related toxicity remain significant management challenges in such cases. Avacopan, a selective complement C5a receptor antagonist, has been introduced as a steroid-sparing agent; however, its role in pulmonary-dominant MPO-AAV remains underreported. Here, we describe a 24-year-old woman from Medina, Saudi Arabia, who presented with life-threatening DAH and acute hypoxemic respiratory failure secondary to MPO-AAV. She initially responded to pulse intravenous methylprednisolone and intravenous immunoglobulin but suffered an early relapse during treatment, and rituximab was therefore initiated. Due to steroid dependence and recurrent respiratory decline, avacopan 30 mg twice daily was started as an adjunctive therapy. Following sustained clinical remission for more than six months, corticosteroids were withdrawn, and the patient had no recurrence of DAH or further respiratory compromise. This case highlights the therapeutic value of avacopan as a steroid-sparing adjunct in MPO-AAV with severe pulmonary involvement. This is the first reported case from Saudi Arabia of avacopan use in MPO-AAV with predominantly pulmonary involvement, underscoring the need for regional real-world evidence to guide its optimal use in this challenging phenotype.

Recurrent polychondritis (RP) is a rare systemic autoimmune disorder that rarely involves the central nervous system (CNS). This report describes a 68-year-old male RP patient who was admitted with bilateral auricular swelling and pain that had lasted for one month, accompanied by limb weakness and pain that had lasted for ten days. Neurological assessment revealed sluggish responses, dysarthria, decreased limb muscle strength and urinary/bowel dysfunction, with a Montreal Cognitive Assessment (MoCA) score of 21/30. Laboratory tests showed elevated inflammatory markers, and autoantibodies in the serum and cerebrospinal fluid (CSF) were negative. CSF analysis revealed increased intracranial pressure and elevated protein levels, as well as decreased immunoglobulin and complement levels. A brain MRI revealed bilateral periventricular, centrum semiovale, and medial temporal lobe fluid-attenuated inversion recovery (FLAIR) hyperintensities. The diagnosis of RP was confirmed based on the Damiani-Levine criteria, alongside the diagnoses of autoimmune limbic encephalitis (LE) and secondary demyelinating encephalopathy (DE). Following treatment with methylprednisolone pulse therapy followed by cyclophosphamide, the patient's symptoms improved significantly. At the three-month follow-up, limb muscle strength had recovered, but urinary dysfunction persisted. This case demonstrates that RP can affect the CNS and the central-autonomic axis. Early recognition and initiation of immunotherapy can improve prognosis.

Leptospirosis is a zoonotic infection with a range of clinical findings, ranging from a mild, self-limited illness to a severe, life-threatening disease known as Weil's disease. The role of adjunctive corticosteroid therapy in severe leptospirosis remains controversial. We report a 41-year-old male with a history of intravenous drug use, regular alcohol consumption, and exposure to contaminated freshwater, who presented with fever, myalgia, vomiting, jaundice, thrombocytopenia, and acute kidney injury. Serological testing via the microagglutination test (MAT) was negative at admission, and empirical antibiotic therapy with ceftriaxone was initiated. Despite appropriate antimicrobial treatment and supportive care, including hemodialysis, the patient developed progressive hyperbilirubinemia and persistent thrombocytopenia. A repeat MAT performed one week later confirmed infection with Leptospira interrogans serovar Pomona. Due to ongoing clinical deterioration, methylprednisolone (1 mg/kg/day) was initiated, resulting in a dramatic clinical and laboratory improvement within 24 h. This rapid response suggests a potential role for corticosteroid therapy in selected patients with severe leptospirosis; however, further studies are required to establish its efficacy and safety.

Rare diseases are often overlooked due to their low prevalence and may be classified as "idiopathic" once more common etiologies have been excluded. Nevertheless, rare conditions do occur, and clinicians must remain vigilant in considering them. Pemphigus vulgaris is a well-established autoimmune blistering disorder involving the skin and mucous membranes, with recognized triggering factors such as medications, infections, paraneoplastic processes, and trauma. Postsurgical pemphigus, however, represents an exceptionally rare variant, arising specifically at sites of surgical scarring. Unfortunately, once initiated, the disease frequently extends beyond the scar, involving widespread cutaneous and mucosal surfaces. Although postsurgical pemphigus is trauma related, it must be distinguished from posttraumatic pemphigus, which is associated with blunt physical injury rather than surgical intervention. We present the case of a 49-year-old woman who developed postsurgical pemphigus beginning at the scar of a prior thyroidectomy. She achieved partial clinical improvement with systemic therapy consisting of methylprednisolone and azathioprine.

A 3-year-old boy with speech delay presented with fever and choreoathetosis, progressing to cardiogenic shock and respiratory failure. He met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C) and improved with treatment, which included intravenous immune globulin (IVIG), methylprednisolone, and anakinra per hospital protocol. Following sedation weaning, choreoathetosis recurred. Repeat brain MRI revealed new symmetric T2 hyperintensity and restricted diffusion in the globi pallidi. He was discharged with persistent developmental regression, hypotonia, and choreoathetosis. Four months later, he was readmitted with respiratory failure from a human metapneumovirus infection and died from refractory cardiogenic shock and multiorgan failure. Posthumous exome sequencing identified a homozygous variant of unknown significance in MDH2 (malate dehydrogenase 2). A sibling with chronic encephalopathy and myocarditis shared this genotype. MDH2 deficiency is associated with movement disorders and cardiomyopathy. MIS-C plausibly triggered clinical decompensation in our patient. Genetic or metabolic causes should be considered in children with a history of developmental delay, acute neurologic symptoms, and symmetric basal ganglia lesions.

Immune checkpoint inhibitors (ICIs) have been widely utilized in patients with cancer and established as a standard therapeutic modality for various solid tumors. Although generally well tolerated, ICIs can induce unique immune-related adverse events (irAEs) affecting systemic systems and organs, posing a significant challenge in clinical oncology practice. Neurological immune-related adverse events (N-irAEs) are relatively rare, but the clinical management of high-grade N-irAEs is extremely challenging and potentially life-threatening. Concurrently, the nonspecific manifestations and extensive differential diagnoses of N-irAEs render their diagnosis highly difficult, which may result in suboptimal clinical management. Herein, we report on a case of a patient with advanced breast cancer who developed severe adverse reactions subsequent to treatment with pucotenlimab and was diagnosed with anti-aquaporin 4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) following multidisciplinary discussion. Despite prompt administration of high-dose methylprednisolone and plasma exchange therapy, the patient's neurological symptoms progressively worsened, leading to multiple organ dysfunction syndrome and subsequent death. A literature review on N-irAEs is also presented.

A 73-year-old man with a 33-year history of primary progressive multiple sclerosis (PPMS) presented with subacute gait instability, confusion, dysarthria, and severe muscle spasms. Laboratory evaluation revealed severe acute kidney injury and hypercalcemia, while noncontrast brain MRI demonstrated chronic periventricular demyelinating changes without new inflammatory lesions; contrast-enhanced MRI was not obtained. The clinical picture was most consistent with a metabolically driven pseudoexacerbation precipitated by hypercalcemia from prolonged immobilization, nephrotoxic polypharmacy, and subtherapeutic gabapentin dosing, though concurrent inflammatory PPMS activity could not be excluded. Treatment with high-dose intravenous methylprednisolone, intravenous fluid resuscitation, and calcitonin resulted in normalization of renal function and serum calcium and meaningful improvement in neurologic symptoms. This case underscores the importance of thorough systemic evaluation before attributing acute neurologic deterioration in PPMS to inflammatory relapse.