ABSTRACT Myasthenia gravis (MG) is thought to be primarily caused by autoantibodies targeting proteins at the neuromuscular junction. It has been established that autoantibodies, primarily acetylcholine receptor (AChR) antibodies, act on the neuromuscular junction, impairing neuromuscular transmission or destroying the structure of the neuromuscular junction. However, cellular immunity also plays a significant role, activating various T‐cell subsets and stimulating B cells to produce antibodies, ultimately leading to disease onset. Immune responsiveness changes throughout life. The immune system develops and matures after birth, then declines with age. At each stage, mechanisms protect the body against pathogenic microorganism invasion. It can also lead to conditions where the immune response is insufficient, even against neoplasms formed within the body. This immune response fundamentally operates through the balance between effector T (Teff) cells and regulatory T (Treg) cells. Imbalances in this equilibrium can occur during the course of MG and various other pathologies. Treatment strategies and methods often achieve therapeutic effects by normalizing this balance. In this review, from the perspective of a pediatrician who has long treated patients with not only adult MG but also childhood MG, we would like to discuss the role Treg cells play in regulating this activation of cellular immunity.
Neonatal lupus erythematosus (NLE) is an autoimmune disorder in which maternal antibodies, particularly anti-Sjögren's-syndrome-related antigen A autoantibodies (anti-SS-A) or anti-SS-B antibodies, cause complications in foetal or neonatal cases. We report a case of NLE in an infant born to an asymptomatic mother, presenting with fever and elevated C-reactive protein despite the absence of maternal anti-double-stranded DNA (anti-dsDNA) antibodies. The patient was a 35-day-old male infant who presented with a rash and fever. Laboratory findings included elevated C-reactive protein and ferritin, soluble interleukin-2 receptor, hypocomplementaemia, and elevated D-dimer levels. NLE or urticarial vasculitis secondary to possible infantile-onset systemic lupus erythematosus was considered in the differential diagnosis. The infant and mother tested positive for anti-SS-A and anti-SS-B antibodies, with titres decreasing over time, leading to a final diagnosis of NLE. Although anti-dsDNA antibodies are typically maternal in origin, the mother in this case was repeatedly negative, making transplacental transfer unlikely and suggesting possible de novo antibody production by the infant. Although fever is rare in NLE, this case presented with systemic symptoms similar to systemic lupus erythematosus, including fever, elevated C-reactive protein, and hypocomplementaemia. In some cases of NLE, systemic symptoms similar to systemic lupus erythematosus may be observed in addition to the rash, and anti-dsDNA antibodies may also be positive serologically.
BACKGROUND Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterized by erythrocytosis resulting from the clonal overproduction of hematopoietic cells in the bone marrow and is closely associated with mutations in the Janus kinase 2 (JAK2) gene. Ruxolitinib, a selective JAK1/JAK2 inhibitor used to treat MPNs, predisposes patients to opportunistic infections. Herein, we report the case of a patient with PV treated with ruxolitinib who developed disseminated tuberculosis mimicking metastatic cancer. CASE REPORT A 71-year-old woman presented with imaging findings suggestive of metastases, elevated tumor markers, and a negative interferon-γ release assay. The diagnosis was confirmed by bone biopsy and a positive sputum Mycobacterium tuberculosis polymerase chain reaction test. The patient improved with standard 4-drug antituberculous therapy. In a focused review of 35 published cases of tuberculosis occurring during ruxolitinib therapy for MPNs, disseminated disease accounted for 50% of cases, whereas PV was reported in only 3 cases. Ruxolitinib-induced immunosuppression can lead to false-negative interferon-γ release assay results, and several tumor markers, including soluble interleukin-2 receptor, neuron-specific enolase, cancer antigen (CA)125, and CA15-3, are known to be elevated in tuberculosis. CONCLUSIONS Patients with PV treated with ruxolitinib can develop active tuberculosis, including disseminated forms. When tumor markers are elevated and imaging reveals lesions suggestive of metastases, clinicians should include disseminated tuberculosis in the differential diagnosis and pursue histopathological and microbiological investigations to enable timely diagnosis and appropriate treatment.
Atraumatic splenic rupture is a rare but potentially life-threatening complication of pancreatic disease. This report describes the case of a 62-year-old man with a prior history of chronic pancreatitis related to alcoholic pancreatitis who presented with left upper abdominal pain without any history of trauma. Contrast-enhanced computed tomography demonstrated splenomegaly, a large splenic laceration, and a perisplenic hematoma without active contrast extravasation, along with a pancreatic cystic lesion and narrowing of the splenic vein. Magnetic resonance imaging showed heterogeneous signal intensity within the spleen, and a neoplastic lesion could not be excluded. On admission, serum amylase was mildly elevated at 149 U/L, HbA1c was 4.8%, and formal pancreatic exocrine function testing had not been performed before surgery. Because he was hemodynamically stable, conservative management was initially selected. However, persistent diagnostic uncertainty and concern for re-bleeding led to surgery on hospital day 9. Distal pancreatectomy with splenectomy and partial diaphragmatic resection was performed. Intraoperatively, the pancreas was indurated, consistent with chronic inflammatory change. Histopathological examination of the resected distal pancreas demonstrated chronic pancreatitis with fibrosis, mild chronic inflammatory cell infiltration, fat necrosis, pseudolobular formation, and focal acute inflammation, with no evidence of malignancy. The final diagnosis was atraumatic splenic rupture secondary to splenic vein thrombosis associated with chronic pancreatitis. This case highlights the need to consider splenic complications in patients with chronic pancreatitis who present with left upper quadrant pain and supports surgical management when malignancy cannot be excluded or when the risk of re-bleeding remains a concern.
