Effective postoperative pain management following orthopedic surgery remains a challenge, particularly in the context of increasing opioid-related morbidity. Multimodal analgesic strategies incorporate adjuvant therapies such as ketamine to reduce opioid requirements while maintaining adequate pain control. This systematic review evaluated the efficacy and safety of perioperative ketamine as an adjunct to opioid therapy for acute postoperative pain management in adults undergoing orthopedic procedures. A PRISMA-guided search of Ovid MEDLINE, Embase, Web of Science, and Cochrane CENTRAL identified randomized controlled trials published between January 2014 and September 2024. Eligible studies included patients aged 18-65 years undergoing orthopedic surgery who received perioperative ketamine compared to opioid-based regimens. Primary outcomes included postoperative opioid consumption and patient-reported pain scores, while secondary outcomes included adverse events. Risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Randomized Controlled Trials. Due to heterogeneity in ketamine dosing, administration, and outcome reporting, a qualitative synthesis was performed. Eleven randomized controlled trials met the inclusion criteria. Adjunctive ketamine reduced postoperative opioid consumption in five of 11 studies, with the most consistent effects observed within the first 24 hours postoperatively. Four studies reported statistically significant improvements in patient-reported pain scores, while others demonstrated no significant differences despite reduced opioid use. Ketamine showed a safety profile comparable to opioid-only regimens, with no consistent increase in adverse events; several studies reported reductions in opioid-related side effects such as pruritus and sedation. Perioperative ketamine may reduce postoperative opioid consumption without increasing adverse events, although its effect on pain intensity remains variable. These findings support its use as part of multimodal analgesia strategies aimed at minimizing opioid exposure, though further research is needed to standardize dosing protocols and evaluate long-term outcomes.

Transient acantholytic dermatosis, also known as Grover's disease, is an acquired pruritic eruption commonly refractory to conventional therapies. We report a case of a 76-year-old male with Grover's disease presenting with persistent pruritus and skin lesions despite multiple treatments. Upadacitinib 15 mg once daily was initiated off-label and the patient reported marked improvement in pruritus within 2 days of treatment and substantial reduction in lesion burden after 1 month. The etiology of Grover's disease is unclear but is believed to be due in part to occlusion and damage to the sweat glands. Emerging responses to immunomodulatory therapies suggest immune dysregulation may contribute to select cases of Grover's disease. Upadacitinib, a selective Janus kinase 1 inhibitor, reduces pruritus and inflammation-associated cytokine signaling and represents a plausible therapeutic strategy. To our knowledge, this is the first reported case of Grover's disease successfully treated with Janus kinase inhibition.

Polycythemia vera (PV) is a clonal myeloproliferative neoplasm primarily caused by the JAK2V617F mutation, present in 95% of patients. It results in erythropoietin-independent hematopoietic proliferation, erythrocytosis, increased hematocrit (Hct), leukocytosis, thrombocytosis, and hyperviscosity, predisposing patients to thrombotic events and neurologic deficits, including erythromelalgia and pruritus. Neurologic manifestations can occur, such as transient ischemic attack (TIA) and stroke. We report an 83-year-old woman, PV patient who presented with chorea and magnetic resonance imaging (MRI) of her brain showed pachymeningeal enhancement (dural-arachnoid enhancement); this radiological finding is most commonly described in intracranial hypotension, autoimmune conditions, infection, and neoplastic processes and has not been reported in PV. Laboratory findings included complete blood count (CBC) showed severe erythrocytosis, moderate leukocytosis with moderate, mild thrombocytosis; bone marrow (BM) aspiration and biopsy showed hypercellular BM and marked megakaryocytic hyperplasia; and positive JAK2V617F mutation with 80% JAK2 DNA, suggestive of PV as the underlying cause. The patient underwent phlebotomy and was started on Aspirin. Following treatment, she showed dramatic improvement in choreiform movements. Hydroxyurea 500 mg three times daily was subsequently added, leading to complete hematologic response and resolution of pachymeningeal thickening on follow up MRI. This case suggested association between polycythemia vera and choreiform movements and a possible mechanism is proposed.

Primary sclerosing cholangitis (PSC) is a rare cholestatic disease that causes fibrosis and strictures of the bile ducts. It is primarily diagnosed in males between 30 and 40 years of age. Its presentation in elderly females is uncommon and represents a diagnostic challenge. The objective of this study is to present a clinical case of PSC with an atypical presentation in an elderly female with associated cholelithiasis. A 74-year-old female with no medical history presented with jaundice, dark urine, acholia, and pruritus. She was admitted to the emergency department with jaundice and a cholestatic pattern. Initial imaging studies identified cholecystitis and possible extrinsic compression of the bile duct by the gallbladder, mimicking Mirizzi syndrome. Magnetic resonance cholangiopancreatography identified a focal biliary stricture, but serological markers for PSC were negative. Due to persistent pain, a cholecystectomy and liver biopsy were performed. The liver biopsy was positive for PSC. PSC should be considered in elderly patients with persistent cholestatic jaundice despite concomitant gallstone disease. Characteristic cholangiographic findings, together with histopathological evaluation and exclusion of secondary causes, support the diagnosis in atypical presentations.

Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease diagnosed by the clustering of compatible biochemical, serological, and histological features after exclusion of competing causes. Concurrent biliary obstruction or drug-induced injury can obscure the underlying autoimmune process and misdirect the initial diagnosis toward a purely obstructive or toxic cause. A 65-year-old woman with a remote cholecystectomy presented with one week of painless jaundice, dark urine, fatigue, and pruritus on a background of a year of slowly progressive aminotransferase elevation. She had also completed an unprescribed two-week course of oral ivermectin shortly before presentation. Admission studies showed marked hepatocellular injury (aspartate aminotransferase (AST): 2,109 U/L, alanine aminotransferase (ALT): 1,652 U/L), conjugated hyperbilirubinemia (total bilirubin: 8.4 mg/dL), mildly elevated alkaline phosphatase (ALP) (253 U/L), hypergammaglobulinemia (globulin: 5 g/dL; subsequent immunoglobulin G (IgG): 2,925 mg/dL), and an international normalized ratio (INR) of 1.6. With a negative viral hepatitis panel, a normal acetaminophen level, and bland cross-sectional imaging, empiric intravenous corticosteroids were begun on hospital day 2. Aminotransferases and bilirubin fell briskly over the next 72 hours, before any mechanical relief of obstruction. Magnetic resonance cholangiopancreatography (MRCP) on hospital day 4 revealed a 7-mm common bile duct stone, extracted at endoscopic retrograde cholangiopancreatography on hospital day 5. Smooth muscle antibody (SMA) returned at a titer of ≥1:640, with negative antinuclear antibodies (ANA) and antimitochondrial antibodies (AMA), a profile consistent with type 1 AIH. By a simplified International Autoimmune Hepatitis Group (IAIHG) score of 6, the combination of high-titer SMA, markedly elevated IgG, and a corticosteroid response that preceded biliary decompression identified AIH as the most likely dominant driver of injury, with choledocholithiasis as a concurrent second insult and ivermectin as a possible contributor of indeterminate magnitude. Obstructive imaging findings can anchor clinicians away from a concurrent, treatable autoimmune process, and a corticosteroid response that precedes mechanical decompression carries genuine diagnostic weight. Because histology was not obtained during the index admission, the relative contributions of the biliary stone and ivermectin cannot be fully excluded; long-term follow-up, including confirmatory biopsy and a structured trial of corticosteroid withdrawal, will clarify whether the disease is best classified as idiopathic AIH unmasked by concurrent insults or as a drug-related variant.

We report the case of an 18-year-old female with cholestatic hepatopathy of unknown origin, presenting with therapy-resistant jaundice and pruritus following oral contraceptive use and gastrointestinal infections. In another hospital, drug-induced autoimmune hepatitis (DILI-AIH) was suspected, and corticosteroid therapy was initiated but remained unresponsive. Initiation of colestyramine led to a worsening of symptoms and increasing liver transaminases. After referral to our centre, a mini-laparoscopic liver biopsy was performed, and histopathology revealed cholestatic DILI and mild fibrosis, with no signs of AIH. After a repeated precise history from the mother, a hereditary fructose intolerance was highly suggestive, and genetic testing confirmed a homozygous mutation in the aldolase B gene (A149P). Additionally, no pathogenic mutations in genes encoding bile acid and phospholipid transporters were detected. The treatment was adjusted to sugar-free colestyramine, leading to complete resolution of symptoms. In the management of hereditary fructose intolerance, not only dietary ingredients but also the supplements and medications may contain fructose excipients that could exacerbate and aggravate liver injuries.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by intense pruritus, eczematous lesions, and significant impairment of quality of life. In severe or chronic cases, AD can present with diverse atypical phenotypes, among which prurigo nodularis (PN)-like lesions are clinically challenging due to their recalcitrance to conventional therapies. Patients with severe AD are also at an increased risk of comorbid immune-mediated diseases, such as alopecia areata (AA), a non-scarring hair loss disorder driven by aberrant immune responses. Ivarmacitinib, a highly selective oral Janus kinase 1 (JAK1) inhibitor, has been approved by the National Medical Products Administration (NMPA) of China for moderate-to-severe atopic dermatitis (April 2025) and alopecia areata (June 2025). Herein, we report a case of a 28-year-old male patient with a long-standing history of AD who developed generalized PN-like lesions and concurrent AA (with a 2-year disease duration) and androgenetic alopecia (AGA). Conventional therapies including topical corticosteroids and antihistamines failed to yield satisfactory outcomes. Following treatment with ivarmacitinib (8 mg once daily), the patient showed rapid improvements in skin lesions, pruritus, and hair regrowth. This case suggests that ivarmacitinib may be beneficial for complex AD phenotypes with comorbid immune-mediated hair loss.

Paraneoplastic syndromes (PNS) are frequently misdiagnosed as independent neurological, endocrine, cutaneous, or rheumatic immune disorders due to their low incidence, highly variable, and complex clinical presentations. Currently, when faced with clinically unexplainable phenomena, PNS is seldom considered in the differential diagnosis. A 68-year-old non-smoking Chinese male presented with insidious digital clubbing in 2021 and refractory cutaneous eruptions in 2023, which were initially diagnosed as granulomatous rosacea and erythroderma. However, treatment with ketotifen, cetirizine, and the immunosuppressant cyclosporine led only to partial regression of the rash, with persistent pruritus. Approximately 3 years after the insidious onset of digital clubbing and 1 year after the skin lesions flared, in April 2024, chest PET/CT scan revealed a mass in the left lower lobe and a nodule in the dorsal segment of the right lower lobe. A biopsy confirmed extensive-stage small cell lung carcinoma (SCLC).His dermatological manifestations, which progressed to edema and dysphagia, and ancillary examination results were subsequently attributed to a paraneoplastic dermatomyositis-like syndrome. Chemotherapy for SCLC resulted in resolution of the skin lesions and disease control. This case underscores the critical role of PNS as an early indicator of occult malignancy and highlights the therapeutic challenges in managing paraneoplastic dermatomyositis-like syndrome.