Glucocorticoids (GCs) affect the Wnt signaling pathway, which is a key mechanism underlying GC-induced osteoporosis (GIOP). The efficacy of romosozumab (ROMO), an antibody targeting sclerostin-an inhibitor of Wnt signaling-in treating GIOP remains unclear, as does its effectiveness when used sequentially after bisphosphonates (BP). In this prospective observational study, we aimed to evaluate the efficacy of ROMO as a sequential therapy following BP in patients with GIOP. Patients with rheumatic diseases receiving BP and GCs equivalent to 5 mg/d or more of prednisolone for at least 6 mo were enrolled and either switched from BP to ROMO (ROMO group) or continued on BP (BP group). BMD of the LS (L2-4), FN, and TH were measured every 6 mo, and bone turnover markers were assessed every 3 mo. Six patients in the ROMO group and 22 in the BP group were analyzed. Patients in the ROMO group were significantly older (78.5 vs 64.5 yr), had a higher history of vertebral fractures, had lower baseline BMD of the FN and TH, and tended to receive higher GC dose (8.0 mg vs 5.0 mg) compared with the BP group. The median (25th-75th percentile) BMD percent changes at 12 mo were numerically higher in the ROMO group compared to the BP group (LS 2.6 [0.8-3.4] % vs 1.6 [-1.9-4.3] %; FN 1.4 [-0.5-5.4] % vs 1.0 [-4.7-5.6] %; TH: 1.1 [-7.6-6.5] % vs -1.8 [-6.4-1.8] %), although their differences were not statistically significant. One new vertebral fracture was observed in the BP group, and 1 patient in the ROMO group experienced a cerebral infarction. These findings suggest that ROMO may be an effective sequential therapy for BP in patients with GIOP.

An 8-year-old spayed female domestic shorthair cat presented with anorexia and weight loss. A complete blood count revealed mild nonregenerative anemia, circulating blasts, dysplastic granulocytes, and basophilia. Both feline leukemia virus (FeLV) and feline immunodeficiency virus tested negative upon SNAP testing using peripheral blood and PCR using bone marrow. Bone marrow aspiration revealed an increased number of blast cells and basophils, and some blast cells were positive for MPO staining. Based on the basophilic lineages observed in the peripheral blood and bone marrow, acute myeloid leukemia with maturation (AML-M2) with basophilic differentiation was the most likely diagnosis in this case. This study reports the unique morphologic features of a rare case of AML-M2 with suspected basophilic differentiation in an FeLV-negative cat.

Sweet syndrome is characterized by tender erythematous plaques, histologically presenting as marked neutrophilic infiltration in the dermis. In general, this syndrome manifests in middle-aged adults, and given its extreme rarity in the pediatric population, it is rarely considered by pediatricians in routine clinical practice, which often leads to misdiagnosis. A 1-year-old girl had developed palpable purpura subsequent to experiencing upper respiratory symptoms, and at a previous hospital, she was preliminarily diagnosed with immunoglobulin A (IgA) vasculitis in the absence of skin biopsy evidence. The purpura developed into refractory hemorrhagic blisters and subsequently became ulcerated. Although intravenous glucocorticoid therapy was initiated, there was no discernable improvement. After being transferred to our hospital, she initially underwent a skin biopsy, which failed to lead to a diagnosis. We tapered the administration of intravenous glucocorticoid and performed a second skin biopsy, retrieving a specimen from a newly affected lesion. The histopathological findings for the second biopsy revealed marked neutrophilic infiltration extending from the dermis to the adipose tissue, with interstitial dermal edema, which met the diagnostic criteria of Sweet syndrome. This case highlights the importance of prioritizing early diagnostic biopsy prior to initiating empiric therapy when atypical cutaneous features are observed in suspected individuals.

A 77-year-old woman with a history of palindromic rheumatism and a previous episode of steroid-induced psychosis was treated with high-dose prednisolone for suspected giant cell arteritis because of the risk of irreversible visual loss. Within days, she developed recurrent psychotic symptoms requiring hospital admission. During her admission, she experienced profound hypovolaemic hyponatraemia complicated by a generalized tonic-clonic seizure. Following correction of her sodium level, brain magnetic resonance imaging unexpectedly demonstrated an acute left basal ganglia lacunar infarction despite the absence of focal neurological deficits. The coexistence of recurrent steroid-induced psychosis, severe electrolyte disturbance, seizure, and acute cerebral infarction created a significant diagnostic challenge, prompting multidisciplinary involvement from rheumatology, neurology, stroke medicine, psychiatry, endocrinology, and general internal medicine. Further investigations, including CT angiography, cerebrospinal fluid analysis, autoimmune screening, and fluorodeoxyglucose positron emission tomography, were undertaken to evaluate for possible systemic or central nervous system vasculitis. This case highlights the importance of maintaining a broad differential diagnosis in patients receiving glucocorticoid therapy, particularly when neuropsychiatric symptoms coexist with metabolic and neurological abnormalities. It also illustrates the value of multidisciplinary assessment in distinguishing medication-related adverse effects from alternative or concurrent pathology.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome with an inherited (Mendelian) form (primary HLH, pHLH), of which familial HLH (FHL) is most prevalent, and an acquired (non-Mendelian) form (secondary HLH, sHLH); both potentially rapidly fatal. As more patients survive, evaluating long-term morbidity, especially neurological complications, is important. Here we report on CNS involvement at onset, its impact on mortality and morbidity, and long-term follow-up in 365 children aged <18 years enrolled in the prospective multinational HLH-2004 study. This treatment included etoposide, dexamethasone, cyclosporin A, and, for selected patients, intrathecal methotrexate/prednisolone, followed by hematopoietic stem cell transplantation (HSCT) for pHLH. At diagnosis, 33% had neurological symptoms and 57% abnormal CSF; 33% and 73% in children with verified FHL, respectively. Elevated CSF protein was associated with inferior survival in univariate analyses, and multivariate analyses revealed reduced survival in children with both neurological symptoms and abnormal CSF. Altogether 32% of long-term survivors post-HSCT had neurological symptoms at last follow-up, more often in children with abnormal CSF at diagnosis; psychomotor retardation affected 25%, seizures 11%, and ADHD/autism 10% (at least). Seizures and psychomotor retardation were detected pre-HSCT in about half of the transplanted children, but, notably, at least 3 years post-HSCT in one third. The median time for reporting ADHD/autism was 5 years post-HSCT. Late neurological complications were reported in 7% of long-term survivors without HSCT. In conclusion, late neurological complications remain a major concern in pHLH, CSF evaluation at diagnosis is valuable, and long follow-up is important since complications may be diagnosed late. NCT00426101.

Zebra bodies-electron-dense lamellar lysosomal inclusions-are the renal hallmark of Fabry disease, caused by deficient α-galactosidase A (GLA) activity. However, several pharmacological agents with cationic amphiphilic properties produce morphologically indistinguishable deposits, resulting in drug-induced phospholipidosis. We describe a woman in her 50s referred to nephrology with non-nephrotic proteinuria and non-visible haematuria following an ischaemic stroke treated with prednisolone and methotrexate for concomitant medium-vessel vasculitis. Aetiological workup-including autoimmunity, anti-phospholipase A2 receptor and GLA gene sequencing-was negative. Renal biopsy revealed lamellated myelin bodies in podocyte cytoplasm on electron microscopy, alongside thin basement membrane disease. Given negative Fabry testing and chronic sertraline exposure-a selective serotonin reuptake inhibitor with known cationic amphiphilic properties-the drug was discontinued. Proteinuria fell from 2.8 g/24 hours to 0.13 g/24 hours at 6 months, with complete resolution of non-visible haematuria. This case underscores the importance of pharmacological review in Zebra body nephropathy.

A man in his late 50s with recently diagnosed chronic lymphocytic leukaemia (CLL) developed rapidly progressive bilateral, painless vision loss. Despite significant visual impairment, initial fundus examination, optical coherence tomography and neuroimaging were largely unremarkable. Further investigation revealed visual field defects, optic nerve dysfunction on visual evoked potentials and cerebrospinal fluid (CSF) infiltration by leukaemic cells, confirming bilateral leukaemic optic neuropathy (LON). The patient was treated with high-dose intravenous methylprednisolone followed by ibrutinib, resulting in marked visual recovery and normalisation of visual fields. Temporary discontinuation of ibrutinib due to neutropenia led to symptom recurrence and persistent central nervous system infiltration, which improved after treatment was resumed. This case highlights the diagnostic challenges of LON, particularly when ophthalmic and imaging findings are initially normal, and underscores the importance of CSF analysis and prompt CLL-directed therapy to prevent irreversible visual loss and achieve favourable outcomes.

BACKGROUND Severe Pneumocystis jirovecii pneumonia (PJP) in renal transplant recipients (RTRs) can rapidly progress to acute respiratory distress syndrome (ARDS) and is associated with high mortality. Glucocorticoids (GCs) play a paradoxical role, constituting a risk factor for infection and a trigger for immune reconstitution inflammatory syndrome upon withdrawal; they may also serve as a therapeutic agent for lung injury. We evaluated the efficacy of a standardized triple-therapy regimen designed to address this paradox. CASE REPORT We analyzed 7 RTRs admitted to the intensive care unit (ICU) with severe PJP-ARDS between June 2023 and September 2024. The cohort had a median age of 49 years; all patients had prior chronic low-dose GC maintenance therapy without PJP prophylaxis. All diagnoses were confirmed by metagenomic next-generation sequencing. After the onset of severe PJP-ARDS, all immunosuppressive agents were discontinued; patients were treated with trimethoprim-sulfamethoxazole and caspofungin. Early adjunctive intravenous methylprednisolone was administered to all patients, including 4 who received treatment upon ICU admission. The median starting dose was 80 mg/day (range, 40-120 mg/day), with a median treatment duration of 11 days (range, 5-17 days) and median cumulative dose of 580 mg (range, 200-840 mg). Following this triple-therapy regimen, the median duration of mechanical ventilation was 14 days, and the survival rate was 100% (7/7); no severe secondary infections or uncontrolled hyperglycemia occurred. CONCLUSIONS Despite constituting a predisposing factor for PJP, early adjunctive GC administration-combined with robust anti-Pneumocystis therapy-may be a safe and promising strategy for managing severe PJP-ARDS in RTRs.