A 72-year-old Japanese man noticed a persistent fever 8 days before presentation. Cervical lymphadenopathy was detected at a local clinic. Laboratory examinations showed an elevated C-reactive protein (CRP) with a normal white-blood-cell count. Despite antibiotic therapy, the fever persisted, and he was referred to our department for further evaluation. He presented with tender erythema on his bilateral knees and cervical lymphadenopathy (Figure 1a). His past medical history included alcohol dependence. Laboratory examinations showed elevated white blood cell counts (10 400 /μL) and CRP (24.9 mg/dL), while ferritin was mildly elevated (308 ng/mL). Serologic tests for common viral infections, including HIV, were negative. Computed tomography scans demonstrated multiple enlarged lymph nodes in the cervical and bilateral femoral regions (Figure 1b,c). Histological examination of the painful erythema showed neutrophilic infiltration with abscess formation in the septal fat, consistent with a non-specific erythema nodosum-like septal panniculitis (Figure 1d). Histological and immunohistochemical examination of the femoral lymph-node biopsy revealed mixed hyaline-vascular and plasmacytic features, including prominent vascular proliferation with hyalinized vessel walls and interfollicular infiltration of CD138-positive plasma cells (Figure 1e,f). Taken together, we diagnosed him with multicentric Castleman disease (MCD), without anasarca, renal dysfunction, or hepatosplenomegaly. Serum CRP had already decreased spontaneously from 16 mg/dL to around 5 mg/dL, while fever persisted. Oral prednisolone 20 mg daily was initiated, resulting in defervescence. Several days after initiation of prednisolone, the platelet count rose to a peak of 453 × 109/L but then rapidly decreased to 79 × 109/L within approximately 10 days, while his pre-morbid platelet count was approximately 190 × 109/L. Findings at the platelet nadir were not suggestive of disseminated intravascular coagulation or thrombotic microangiopathy, no causative drug was identified and platelet-associated IgG was mildly elevated. Without additional therapy, the platelet counts spontaneously recovered to 110 × 109/L (Figure 1g). In MCD, platelet abnormalities can manifest either thrombocytopenia or thrombocytosis 1. Autoimmune cytopenias, including immune thrombocytopenia, have been reported in association with MCD, and a recent MCD cohort demonstrated that IL-6-mediated thrombocytosis and immune-mediated thrombocytopenia can coexist within the same disease spectrum 2-5. However, no literature describes a rapid swing from marked thrombocytosis to thrombocytopenia in the same disease episode. We report a case of MCD in which the platelet count initially rose to approximately 450 × 109/L, then decreased precipitously to below 80 × 109/L within 10–14 days. Taken together with the spontaneous decline in CRP before corticosteroid initiation and the relatively stable inflammatory markers during the subsequent platelet fall, this biphasic pattern may not be explained solely by reactive thrombocytosis and suggests a dynamic shift between platelet production and destruction. In the early phase, IL-6-driven thrombopoiesis may predominate over a concomitant, low-grade immune-mediated platelet destruction, resulting in marked thrombocytosis despite non-specific PA-IgG positivity. In contrast, partial control of inflammation later may reduce cytokine-driven production more than immune destruction, thereby unmasking a transient thrombocytopenia within the same MCD disease process. Clinicians should therefore consider not only classic causes of thrombocytopenia but also this under-recognized mechanism when confronted with a rapid platelet drop in MCD. The authors have nothing to report. The authors have nothing to report. Written informed consent was obtained from the patient for publication of this case report and accompanying images. The authors declare no conflicts of interest. The authors have nothing to report.
Kishimoto et al. (Mon,) studied this question.