Post-dialysis fever is commonly reported in patients undergoing hemodialysis (HD). However, it is often challenging to identify the underlying cause owing to the wide variety of potential factors that can lead to fever. In this case, a 66-year-old Japanese man experienced recurrent fever after HD treatment. Initially, antibiotics were prescribed to treat pneumonia, but it was later discovered that the pneumonia was an alveolar hemorrhage caused by cryoglobulinemic vasculitis. It is believed that cryoglobulin was sensitized by cold exposure owing to the dialysate temperature, which resulted in fever being experienced only after HD. Although treatment for vasculitis required prednisolone and rituximab, simple plasma exchange and a dialysate temperature of 37.5 °C dramatically suppressed the occurrence of post-dialysis fever. Cryoglobulinemia should be considered as a potential cause of fever, as it may be a common occurrence in patients undergoing HD and could be overlooked as a possible cause of localized fever following HD treatment.

Infective endocarditis is a rare but life-threatening condition, occasionally linked to diverse immunologic manifestations, including mixed cryoglobulinemia. This can lead to cryoglobulinemic vasculitis, which has the potential for widespread organ damage. Although some cases have highlighted the relationship between infective endocarditis and cryoglobulinemic vasculitis, no comprehensive epidemiological evaluation or optimal treatment strategies have been advanced for such a combination. We present a case of methicillin-sensitive Staphylococcus aureus infective endocarditis associated with cryoglobulinemic vasculitis and conduct a literature review to compare management and outcomes in similar cases. Our patient presented with classical Meltzer\'s triad and mild renal involvement. Cryoimmunofixation confirmed type III cryoglobulinemia, and serum cytokines showed elevated IL-6 levels. The differential diagnosis included infective endocarditis and chronic active hepatitis C virus infection. Rapid symptom resolution after antibiotic treatment identified infective endocarditis as the likely cause of cryoglobulinemic vasculitis. Our case and review of the literature highlight that early identification of the cause of cryoglobulinemic vasculitis is crucial for selecting appropriate treatment and preventing recurrence or morbidity.

A 75-year-old man with blurred vision and nasal bleeding was diagnosed with hyperviscosity syndrome and central retinal vein occlusion secondary to Waldenström macroglobulinemia. Serum total protein and IgM levels were undetectable. Because of the severe symptoms, we determined that immediate plasma-exchange treatment was required to decrease the blood viscosity. The initial plasma exchange was performed using the membrane isolation method with a predilution standby. A saline predilution replacement was prepared to decrease the total membrane pressure (TMP); however, the predilution protocol was not used because the planned treatment volume could be achieved without increasing the TMP. After two consecutive days of membrane plasma exchange, all serum biochemical tests were measurable, and IgM was below 4000 mg/dL. After chemotherapy, his visual symptoms improved, and he was discharged. Since it is difficult to assess the risk of elevated TMP prior to initial plasma exchange, membrane plasma exchange with a predilution standby may be a useful strategy for initial plasma exchange for hyperviscosity syndrome in terms of safety and efficiency.

This study presents two cases of type II mixed cryoglobulinemia. One case is essential, while the other is presumably associated with hepatitis B virus (HBV) infection. Both patients tested positive for monoclonal IgMκ, but negative for MyD88 mutation. They showed resistance to rituximab combined with a glucosteroid regimen, but responded positively to BTK inhibitors. These cases highlight the remarkable effectiveness of BTK inhibitors in treating refractory type II cryoglobulinemia without MyD88 mutation. The first patient achieved rapid complete remission of nephrotic syndrome within one month of starting ibrutinib, along with a significant reduction in cryoglobulin levels and abnormal clonal cells. The second patient had a rapid disappearance of rash within three days and accelerated wound healing within one week of initiating orelabrutinib, accompanied by a reduction in C-reactive protein. However, there was no reduction in cryoglobulin levels during the 12-month follow-up. These findings suggest varied mechanisms of action of BTK inhibitors in type II cryoglobulinemia through different mechanisms.

OBJECTIVE: Cryoglobulinemia is a pathological condition characterized by the presence of cryoglobulins in the blood, with cryoglobulinemic glomerulonephritis being the most frequent form of renal involvement. Fanconi syndrome presents as a generalized dysfunction of the proximal tubule, characterized by the presence of polyuria, phosphaturia, glycosuria, proteinuria, proximal renal tubular acidosis, and osteomalacia. We aimed to present five cases co-occurring with Fanconi syndrome and cryoglobulinemia.
METHODS: We retrospectively summarized the cases of five patients with Fanconi syndrome and cryoglobulinemia at Peking Union Medical College Hospital from January 2012 to June 2022. The clinical features, diagnosis, treatment, and prognosis were systematically analyzed.
RESULTS: All five patients exhibited typical features of Fanconi syndrome, and cryoglobulinemia was concurrently detected in all cases. These patients also exhibit positive anti-nuclear antibody spectrum and hyperglobulinemia, and IgM constitutes the predominant monoclonal component in cryoglobulins. In addition to supplemental treatment, timely immunosuppressive therapy may potentially benefit the long-term renal prognosis of patients with this condition.
CONCLUSIONS: Our findings highlight the rare co-occurrence of Fanconi syndrome and cryoglobulinemia in clinical practice. Despite the lack of causal evidence, the coexistence of Fanconi syndrome and tubulointerstitial injury is also noteworthy in patients with cryoglobulinemia, underscoring the importance of thorough evaluation and tailored management in patients presenting with overlapping renal manifestations. Key Points • Patients with mixed cryoglobulinemia can clinically present with tubulointerstitial injury, specifically manifesting as Fanconi syndrome. • In addition to typical symptoms of Fanconi syndrome, these patients also exhibit positive anti-nuclear antibody spectrum and hyperglobulinemia, while IgM constitutes the monoclonal component in cryoglobulins. • Timely immunosuppressive therapy may improve long-term renal prognosis in these patients.

Purpose: To highlight clinical and imaging features of 5 patients diagnosed with retinal vasculitis and cryoglobulins. Methods: This retrospective case series describes clinical and angiographic features of retinal vasculitis and serum cryoglobulins and is the most extensive series to our knowledge. Results: Five female patients were diagnosed with retinal vasculitis and serum cryoglobulins. The average age at time of cryoglobulin identification was 46 years (range, 28-72 years), although retinal vasculitis had been present for various durations. Fluorescein angiograms demonstrated large-vessel and small-vessel segmental leakage in 3 patients, only large-vessel segmental leakage in 1 patient, and only small-vessel segmental leakage in 1 patient. Treatment included topical steroids, intraocular steroid injections, oral corticosteroids, oral antimetabolites, and biologic therapy. At the time of this report, 4 of 5 patients had persistent angiographic leakage; however, none had retinal vascular occlusions. Conclusions: Various treatments were efficacious, although resolution was difficult. No patient experienced retinal vascular occlusions or other types of end-organ compromise.

BACKGROUND: Type 1 cryoglobulinemia is characterized by a large number of clinical signs. The lack of specificity of these signs can make diagnosis difficult. Ocular manifestations are rarely described across medical literature. Only 15 cases of ophthalmological involvement secondary to cryoglobulinaemia have been reported.
CONCLUSIONS: We report the case of a 69-year-old patient with cutaneous type 1 cryoglobulinaemia. He presented with bilateral anterior segment ischemia without retinal involvement with unilateral neovascularisation. Treatment of the B lymphocyte clone with rituximab and bendamustine and plasma exchange were initiated with successfully. Two similar cases describing ischaemic damage to the iris during type 1 cryoglobulinemia have been reported in the literature.
CONCLUSIONS: Irial ischaemia should be considered as a potential in type 1 cryoglobulinaemia.

Twenty-nine patients with HCV infection (HCV+) and mixed cryoglobulinemia (MC+) were retrospectively selected and matched for age and sex with 31 HCV+ MC- patients. Biomarkers of cholestasis (direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase), HCV-RNA and genotype, and plasma cryoprecipitates were measured before and after virus eradication; liver histology and plasma cells (aggregation and distribution), observed blinded by two pathologists, were analyzed. Sixty participants (mean age: 56.5; range: 35-77, males: 50%) with HCV infection were enrolled. Cholestasis (≥2 pathologically increased cholestasis biomarkers) was significantly higher in the MC group (p = 0.02) and correlated with cryoglobulinemia (OR 6.52; p = 0.02). At liver histological assessment, plasma cells were significantly increased in the MC+ group (p = 0.004) and tended to form aggregates more than the control group (p = 0.05). At multivariate analysis with MC, age, HCV-RNA, HBV diabetes, and cirrhosis, cholestasis was only significantly correlated to MC (OR 8.30; p < 0.05). In 25% patients, MC persisted after virus eradication with new antiviral treatment. Our study identified for the first time an association between MC, cholestasis, and an increased number of intrahepatic plasma cells in chronic hepatitis C (CHC) patients before virus eradication. Future studies are required to understand how MC contributes to liver damage and how its persistence affects the patients\' follow-up after antiviral therapies.

Cryoglobulinemia is a rare entity which frequently occurs in the setting of an underlying disease, with chronic hepatitis C virus infections and primary Sjogren syndrome being the most common underlying conditions. Cryoglobulinemic vasculitis (CV) is an immune-mediated type of small-vessel vasculitis with a broad spectrum of specific organ involvement, including renal, pulmonary, peripheral nerve, and cutaneous involvement and variable manifestations that can be life threatening. Moreover, a strong relationship between cryoglobulinemia and CV, with the future development of lymphoma, is well established. We present the case of a 72-year-old Caucasian male referred for nephrotic syndrome and acute renal injury. A diagnosis of Sjogren syndrome-associated CV was made, and he was successfully treated with rituximab and plasma exchange sessions.

Hyperviscosity syndrome (HVS) is a complication of monoclonal plasma cell tumors. The frequency of HVS depends on the type of monoclonal protein. Immunoglobulin M (IgM) is more closely associated with HVS than IgG, and among IgG subclass monoclonal proteins, IgG3 is most frequently associated with HVS. We herein report a 44-year-old woman with multiple myeloma (MM), HVS, and cryoglobulinemia. Her monoclonal protein and cryoglobulin were IgG1-lambda (λ). She developed HVS at a lower monoclonal protein level because of the properties of the IgG1-derived monoclonal protein and cryoglobulin. Our case highlights the fact that identifying the IgG subclass is useful in predicting the risk of complicating HVS.