Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a rare but relevant complication of long-term methotrexate (MTX) therapy that can closely mimic infection or disseminated malignancy. We report the case of a 65-year-old woman with a 10-year history of systemic lupus erythematosus (SLE) treated with MTX, who presented with progressive back pain, constitutional symptoms, pancytopenia, and extensive multiorgan disease. Fluorodeoxyglucose positron emission tomography (FDG PET) demonstrated widespread hypermetabolic lesions involving the lungs, liver, left adrenal gland, and skeleton, raising strong suspicion of disseminated metastatic malignancy. Two ultrasound-guided liver nodule biopsies were inconclusive, with no evidence of malignancy. Given the absence of histopathological confirmation and her prolonged MTX exposure, MTX-LPD was suspected, and MTX was discontinued. No oncologic treatment was initiated. Four months later, the patient had achieved complete clinical resolution of her symptoms, and follow-up imaging showed near-complete regression of the pulmonary, hepatic, adrenal, and most skeletal lesions.

A 65-year-old man presenting with pancytopenia and circulating large atypical cells was initially suspected of having acute leukemia. Flow cytometric analysis demonstrated a mature clonal B-cell phenotype, and the integrated findings supported a diagnosis of a CD5-positive mature B-cell neoplasm with large-cell morphology, predominant bone marrow involvement, and a leukemic peripheral blood presentation. Based on the available staging data, primary bone marrow DLBCL was suspected but could not be definitively confirmed. The neoplasm was characterized by CD5 expression, a BCL6 rearrangement, and a complex karyotype including monosomy 17. The patient received six cycles of R-CHOP followed by two cycles of systemic high-dose methotrexate as individualized central nervous system prophylaxis. A complete response was confirmed after treatment, with no evidence of recurrence 6 months after treatment completion.

Drug-induced lupus erythematosus is an autoimmune condition that resembles systemic lupus erythematosus and occurs after exposure to specific medications, including tumor necrosis factor alpha inhibitors. We report a rare case of golimumab-induced lupus erythematosus complicated by macrophage activation syndrome, angioedema, and severe dysphagia with anti-galactocerebroside antibodies detected. A 57-year-old woman with ulcerative colitis developed facial swelling, malar rash, arthritis, pancytopenia, hyperferritinemia, hypocomplementemia, and proteinuria after long-term treatment with tumor necrosis factor alpha inhibitors, most recently golimumab. Bone marrow examination demonstrated hemophagocytosis, confirming macrophage activation syndrome. Computed tomography and endoscopy revealed soft tissue and esophageal edema consistent with angioedema. Despite improvement of systemic inflammation following high-dose glucocorticoids and intravenous cyclophosphamide, severe dysphagia persisted. A videofluoroscopic swallowing study demonstrated pharyngeal muscle dysfunction, and serum testing detected anti-galactocerebroside immunoglobulin G antibodies. Neurological imaging and electrophysiological studies were unremarkable. Swallowing function gradually recovered after discontinuation of golimumab. This case highlights that golimumab-induced lupus erythematosus may trigger multiple autoimmune complications, including macrophage activation syndrome, angioedema, and antibody-associated neuromuscular dysphagia. Awareness of these potentially life-threatening manifestations is essential for early recognition and appropriate management in patients receiving tumor necrosis factor alpha inhibitors.

Pancytopenia is a diagnostic challenge due to its broad differential diagnosis, including infections and hematological malignancies. Parvovirus B19 infection is a recognized but uncommon cause of transient pancytopenia. However, positive viral serology or viremia may lead to diagnostic anchoring and delay the identification of underlying malignant disorders. We report the case of a 17-year-old previously healthy female presenting with persistent fever and tonsillitis. Laboratory investigations revealed pancytopenia with agranulocytosis. Blood serology and polymerase chain reaction (PCR) were positive for Parvovirus B19. The peripheral blood smear was normal. An initial diagnosis of virus-related pancytopenia was established. Despite supportive treatment, including granulocyte colony-stimulating factor, transfusions, and intravenous immunoglobulins, pancytopenia persisted. Bone marrow aspiration and biopsy were performed. The bone marrow aspiration showed a hypercellular marrow without abnormal cells by flow cytometry within the conventional blast gate. Subsequent pathological examination of the biopsy revealed massive blast infiltration consistent with acute promyelocytic leukemia. The patient rapidly developed disseminated intravascular coagulation, and atypical promyelocytes later appeared in the peripheral blood smear. Targeted treatment with all-trans retinoic acid and arsenic trioxide was initiated, leading to remission. This case highlights the risk of delayed diagnosis when pancytopenia is attributed to viral infection. Persistent cytopenia, even in the presence of positive Parvovirus B19 testing and a normal blood smear, should prompt early bone marrow examination to exclude underlying hematological malignancy.

X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by BTK gene mutations, characterized by hypogammaglobulinemia and recurrent infections. This study evaluates a long-term pediatric cohort to assess clinical spectrum, therapeutic outcomes, and molecular findings. We retrospectively reviewed clinical, immunological, treatment, and genetic data for 11 male XLA patients followed over 20 years at our center. Median age at symptom onset was 12.7 months (range: 3-60), while median age at diagnosis was 4.5 years (range: 1-10), revealing marked diagnostic delays in patients without family history. Severe complications included bronchiectasis, septic arthritis, and immune dysregulation (e.g., juvenile idiopathic arthritis, autoimmune hepatitis, pancytopenia, celiac disease). Immunoglobulin replacement and antibiotic prophylaxis significantly reduced median annual infections from 16.9 to 2.09. Six distinct BTK variants were identified, including three novel mutations: c.90del, c.1922_1924delGTC, and c.1589dup. Inter-sibling phenotypic heterogeneity was notable. In the absence of functional expression studies, pathogenic contributions of novel variants remain exploratory. XLA extends beyond recurrent infections to encompass significant immune dysregulation and phenotypic variability. Early diagnosis, family screening, genetic testing, and tailored immunoglobulin therapy are vital to improve long-term outcomes. Larger multicenter cohorts with functional testing are needed to validate genotype-phenotype associations.

Among pulmonary involvements of systemic lupus erythematosus (SLE), interstitial lung disease (ILD) is an infrequent but clinically significant complication, with fatal cases reported as "acute lupus pneumonitis" and associated with increased mortality. However, SLE-ILD remains insufficiently stratified according to clinical course, and no predictive factor for rapidly progressive (RP) SLE-ILD, including high-resolution computed tomography (HRCT) pattern, has yet been established. Here we report a 71-year-old man who presented with dyspnea, fever, pancytopenia, anti-double-stranded DNA antibody positivity, hypocomplementemia, proteinuria, and neuropsychiatric symptoms. HRCT initially showed bilateral consolidation predominantly in the peripheral lower lung zones, consistent with organizing pneumonia, followed by rapid extension with ground-glass opacities. He was diagnosed with RP-SLE-ILD with neuropsychiatric involvement and nephritis and improved after intensive combined immunosuppressive therapy. To characterize the HRCT findings of RP-SLE-ILD, we performed a systematic literature review and identified 27 patients with RP-SLE-ILD, including the present case. Organizing pneumonia (OP)-dominant patterns, defined as OP alone or OP combined with nonspecific interstitial pneumonia (OP+NSIP), were significantly more frequent than in the chronic reference cohorts (77.8% vs 10.0% or 14.6%). In contrast, isolated NSIP was significantly less frequent than in the chronic cohorts (3.7% vs 55.0% or 31.5%). These findings suggest that OP-dominant HRCT patterns and lower-lung-zone consolidation may be recurring radiological features among reported RP-SLE-ILD cases, although their predictive value requires validation in consecutive cohorts.

Plasmodium vivax (P. vivax) malaria, once regarded as a comparatively benign infection, is increasingly recognized as a cause of severe, potentially life-threatening multisystem disease. Concurrent secondary hemophagocytic lymphohistiocytosis (HLH), disseminated intravascular coagulation (DIC), and acute pancreatitis complicating P. vivax infection is exceptionally rare. A previously healthy 19-year-old Bangladeshi woman presented with a 5-day history of high-grade fever with rigors, generalized weakness, and upper abdominal pain. Laboratory evaluation demonstrated pancytopenia, markedly elevated ferritin (28,839 ng/mL), hypertriglyceridemia, hypofibrinogenemia, elevated transaminases, coagulopathy, and elevated pancreatic enzymes. Malaria rapid diagnostic testing (RDT) was positive for P. vivax; peripheral blood smear was negative and PCR was unavailable. The patient fulfilled six HLH-2004 diagnostic criteria, met International Society on Thrombosis and Hemostasis (ISTH) criteria for overt DIC, and satisfied revised Atlanta criteria for acute pancreatitis. Intravenous artesunate with multidisciplinary supportive care resulted in progressive clinical and biochemical improvement. HLH-directed immunosuppressive therapy was not required. She was transitioned to oral artemether-lumefantrine and primaquine for radical cure and remained asymptomatic at follow-up. This case illustrates the evolving recognition of P. vivax as a pathogen capable of triggering complex hyperinflammatory and multisystem complications. Early identification of underlying infection and prompt antimalarial therapy may be sufficient to achieve remission in infection-associated HLH without immunosuppression. Clinicians in endemic regions should maintain heightened vigilance for these rare but life-threatening complications.

Infantile malignant osteopetrosis is a rare autosomal recessive skeletal disorder caused by impaired osteoclast-mediated bone resorption, resulting in diffuse osteosclerosis, bone marrow failure, neurologic complications, and metabolic disturbances. Early diagnosis remains challenging, particularly when initial manifestations overlap with common neonatal conditions. Persistent neonatal hypocalcemia may be an early but underrecognized clue. We report a Saudi male infant with genetically confirmed TCIRG1-associated osteopetrosis who presented with persistent neonatal hypocalcemia and secondary hyperparathyroidism. Born at 36 weeks to a mother with insulin-dependent diabetes, he required neonatal intensive care for respiratory distress, hypoglycemia, and a right clavicular fracture following shoulder dystocia. Despite calcium supplementation, hypocalcemia persisted, prompting endocrinology evaluation. Laboratory investigations demonstrated recurrent hypocalcemia, elevated parathyroid hormone levels, and normal magnesium levels. Skeletal survey at three months of age revealed diffuse osteosclerosis with medullary cavity obliteration. Whole-exome sequencing identified a homozygous likely pathogenic TCIRG1 variant (c.1549G>A; p.Asp517Asn), confirming the diagnosis at three months of age. The disease subsequently progressed to pancytopenia, and the patient underwent hematopoietic stem cell transplantation at one year of age. At the most recent follow-up, 18 months post-transplant, the patient demonstrates adequate hematological recovery with stable blood counts and no significant neurological deficits. This case underscores the diagnostic challenge of infantile osteopetrosis when initial findings mimic common neonatal complications, particularly in infants of diabetic mothers. Persistent hypocalcemia with elevated parathyroid hormone, fractures, or unexpectedly increased skeletal density should prompt early skeletal evaluation and genetic testing to facilitate timely diagnosis and definitive treatment.