全身性アミロイドーシス

BACKGROUND: Presymptomatic genetic testing in relatives of hereditary transthyretin amyloidosis (ATTRv) index cases enables early carrier identification and timely treatment, but a confirmed pathogenic variant carries the risk of premature diagnostic closure when new symptoms arise. CASE PRESENTATION: A 25-year-old asymptomatic carrier of TTR: p.Val142Ile, whose father had neurological-predominant ATTRv, developed lower limb heaviness, burning pain, hyperesthesia, dysautonomia, and gastrointestinal symptoms. Cardiac work-up was unremarkable; electrochemical skin conductance testing was abnormal and gastric solid emptying scintigraphy was borderline. Before pursuing skin biopsy, a broad differential was investigated, revealing profoundly suppressed thyroid-stimulating hormone (TSH), elevated total triiodothyronine (T3), positive anti-thyroid peroxidase antibody (anti-TPO) and positive TSH receptor antibody (TRAb), confirming Graves' disease. Antithyroid treatment led to normalization of thyroid function and improvement of symptoms. CONCLUSION: Autoimmune thyroid disease may be an underrecognized, reversible cause of neuropathic symptoms. Systematic differential diagnosis is essential before attributing new symptoms to amyloidosis, preventing unnecessary initiation of disease-modifying therapy in patients with treatable alternative etiologies.

BACKGROUND: In wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM), increased left ventricular wall thickness reflects amyloid infiltration rather than myocyte hypertrophy, and QRS voltage may not rise proportionally. Whether this electrical-anatomical discordance marks myocardial dysfunction and adverse outcomes within established disease is uncertain. METHODS: We prospectively enrolled 220 consecutive patients with newly diagnosed wtATTR-CM in a single-centre cohort. LVH-voltage discordance was defined as maximum LV wall thickness ≥12 mm with a Sokolow-Lyon voltage < 3.5 mV. The primary outcome was absolute global longitudinal strain (GLS); secondary outcomes included impaired GLS (< 16%), serial GLS change, and clinical events. RESULTS: Discordance was present in 41.8%. Absolute GLS was lower with discordance (13.4 ± 2.8% vs. 17.3 ± 3.5%), including after multivariable adjustment (β -2.21, 95% CI -3.04 to -1.39; p< 0.001), without interaction by rhythm (p = 0.52). Impaired GLS was more prevalent (81.5% vs. 35.2%; adjusted prevalence ratio 1.66, 95% CI 1.28-2.15). The continuous QRS amplitude-to-wall-thickness index correlated with absolute GLS (ρ = 0.35; p< 0.001). Over a median 16.0 months, discordance was associated with cardiovascular death or first heart failure hospitalization (adjusted HR 3.88, 95% CI 1.43-10.52) and first heart failure hospitalization (adjusted HR 3.48, 95% CI 1.08-11.18); mortality estimates were imprecise. Among 142 patients with serial imaging, adjusted annual GLS decline was greater with discordance (-0.65 vs. -0.31 percentage points/year). CONCLUSIONS: In established wtATTR-CM, LVH-voltage discordance was associated with worse baseline GLS, a less favorable longitudinal GLS trajectory, and HF-related outcomes. It may provide a simple marker for within-disease phenotyping, but these findings require external validation.

HHV8-positive diffuse large B-cell lymphoma (HHV8+ DLBCL) is a rare and aggressive lymphoma frequently associated with multicentric Castleman disease. Population-based data remain limited. Using the National Cancer Database (2004-2023), we analyzed 262 patients with histologically confirmed HHV8+ DLBCL (ICD-O-3 9738/3), representing the largest cohort to date. The cohort was predominantly male (76.7%), White (66.0%), with a mean age of 52.6 years. The primary site was nodal in 78.6%. Systemic therapy was administered in 72.9% of patients. Median overall survival was 133 months, with 1-, 3-, and 5-year survival rates of 68.2%, 63.1%, and 59.9%, respectively. On multivariable Cox regression, age ≥60 years, Charlson-Deyo score ≥1, HIV-positive status, and lack of systemic therapy and surgery to the primary site were independently associated with worse overall survival. In a subgroup analysis restricted to patients with known HIV status (n = 113), HIV-positive status was the only variable significantly associated with worse overall survival on univariable analysis.

Anti-CD38 monoclonal antibodies have become a central immunotherapeutic platform in multiple myeloma, where they have reshaped treatment across relapsed or refractory disease, frontline therapy, maintenance intensification, and minimal residual disease-oriented management. Their success in multiple myeloma has also stimulated broader development in immunoglobulin light-chain amyloidosis, selected hematologic malignancies, and humoral immune-mediated disorders. CD38 functions both as a surface target and as an ectoenzyme involved in nicotinamide adenine dinucleotide metabolism, calcium signaling, immune-cell regulation, and microenvironmental remodeling, providing a mechanistic basis for antibody-mediated cytotoxicity, immune modulation, and broader humoral immune intervention. This Review critically evaluates CD38 biology, Fc-mediated immune-effector mechanisms, immune remodeling, clinical evidence, resistance, safety, laboratory interferences, biomarker evidence, and clinical positioning of anti-CD38 antibodies, with multiple myeloma as the central reference disease. In immunoglobulin light-chain amyloidosis, daratumumab-based therapy has moved beyond myeloma-derived extrapolation and established a disease-specific framework integrating hematologic response, organ response, and survival outcomes. Beyond multiple myeloma, anti-CD38-based strategies have been investigated in light-chain amyloidosis, selected hematologic malignancies, autoimmune cytopenias, transplant-related alloimmunity, and other antibody-driven diseases. However, the strength of evidence differs substantially across these settings, and CD38 expression alone does not establish clinical benefit. Outside established plasma cell disorders, further development should therefore rely on disease-specific prospective evidence and careful assessment of safety.