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.

Paraproteinemias are a group of complex diseases associated with an overproduction of a monoclonal immunoglobulin that can cause a diversity of kidney disorders and end-organ damage. In this review, we focus on paraprotein-mediated glomerular diseases. Kidney biopsy plays a crucial role in diagnosing these disorders, enabling the identification of specific histological patterns. These lesions are categorized into organized (such as amyloidosis, immunotactoid glomerulopathy, fibrillary glomerulonephritis, cryoglobulinemic glomerulonephritis, and monoclonal crystalline glomerulopathies) and nonorganized deposits (such as monoclonal Ig deposition disease and proliferative glomerulonephritis with monoclonal Ig deposits) based on the characteristics of immunofluorescence findings and the ultrastructural appearance of deposits on electron microscopy. This review aims to provide an update, highlight, and discuss clinicopathological aspects such as definition, epidemiology, clinical manifestations, mechanisms of kidney injury, histological features, and diagnostic procedures.

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.

Mixed cryoglobulinemia vasculitis (MCV) is caused in ~90% of cases by chronic hepatitis C virus (HCVposMCV) and more rarely by hepatitis B virus (HBV) infection, or apparently noninfectious. HCVposMCV develops in only ~5% of patients with chronic hepatitis C (CHC), but risk factors other than female gender have not been identified so far. We conducted a retrospective case control study investigating whether past active HBV infection, defined by hepatitis B surface antigen (HBsAg) seroclearance and anti-core antibody (HBcAb) positivity, could be a risk factor for developing HCVposMCV. The prevalence of HBsAg seroclearance was 48% within 123 HCVposMCV patients and 29% within 257 CHC patients (p=0.0003). Multiple logistic regression including as variables gender, birth year, age at HBV testing, cirrhosis, and hepatocellular carcinoma, confirmed an association of HBsAg seroclearance with HCVposMCV [adjusted odds ratio (OR) 2.82, 95% confidence interval (95% CI) 1.73-4.59, p<0.0001]. Stratification by gender, however, showed that HBsAg seroclearance was associated with HCVposMCV in male [OR 4.63, 95% CI 2.27-9.48, p<0.0001] and not in female patients [OR 1.85, 95% 95% CI 0.94-3.66, p=0.076]. HBsAg seroclearance, and more likely occult HBV infection, is an independent risk factor for HCVposMCV in male CHC patients.

Waldenström macroglobulinemia (WM) is an infrequent variant of lymphoma, classified as a B-cell malignancy identified by the presence of IgM paraprotein, infiltration of clonal, small lymphoplasmacytic B cells in the bone marrow, and the MYD88 L265P mutation, which is observed in over 90% of cases. The direct invasion of the malignant cells into tissues like lymph nodes and spleen, along with the immune response related to IgM, can also lead to various health complications, such as cytopenias, hyperviscosity, peripheral neuropathy, amyloidosis, and Bing-Neel syndrome. Chemoimmunotherapy has historically been considered the preferred treatment for WM, wherein the combination of rituximab and nucleoside analogs, alkylating drugs, or proteasome inhibitors has exhibited notable efficacy in inhibiting tumor growth. Recent studies have provided evidence that Bruton Tyrosine Kinase inhibitors (BTKI), either used independently or in conjunction with other drugs, have been shown to be effective and safe in the treatment of WM. The disease is considered to be non-curable, with a median life expectancy of 10 to 12 years.

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.

BACKGROUND: Persistent cryoglobulinemia after the completion of antiviral treatment is an important consideration of clinical management in chronic hepatitis C patients. We aimed to investigate the occurrence of serum cryoglobulinemia in chronic hepatitis C patients without cryoglobulinemia at the initiation of antiviral treatment.
METHODS: In total, 776 patients without cryoglobulinemia were assessed for serum cryoglobulinemia after the completion of anti-HCV treatment. Serum cryoglobulinemia precipitation was assessed upon both the initiation and the completion of the treatment and analyzed for the clinical laboratory factors associated with chronic hepatitis C.
RESULTS: One hundred eighteen (118) patients were checked for serum cryo-precipitation after the completion of the treatment, and eight patients (4.6%) were positive for serum cryoglobulinemia. The patients who tested positive for cryoglobulinemia included a higher proportion of liver cirrhosis patients (4/50%, p = 0.033) and other organ cancer patients (5/62.5%, p = 0.006) than patients who showed no signs of cryoglobulinemia after treatment. In a multivariate analysis, liver cirrhosis (odds ratio [OR]-17.86, 95% confidence interval [95% CI]-1.79-177.35, p = 0.014) and other organ cancer (OR-25.17 95% CI-2.59-244.23, p = 0.005) were independently and significantly associated with positive cryoglobulinemia 3 months after antiviral treatment.
CONCLUSIONS: Three months after the antiviral DAA therapy had concluded, eight patients tested positive for cryoglobulinemia, representing a 6.7% prevalence. Liver cirrhosis and other organ cancer were independently and significantly associated with positive cryoglobulinemia after antiviral treatment. Further investigation into the causes of positive cryoglobulinemia after DAA antiviral therapy is warranted.

UNASSIGNED: We report an observation of a young patient presenting with severe type 1 cryoglobulinemic vasculitis revealing a monoclonal gammopathy of clinical significant. Treatment with Melphalan-Thalidomide Prednisone improved the symptoms. Early diagnosis would prevent serious tissue damage.
UNASSIGNED: Monoclonal gammopathy encompass diverse clinical forms. Only the cancerous form, multiple myeloma (MM), is treated based on specific diagnostic criteria. A new clinical entity, monoclonal gammopathy of clinical significance (MGCS), warrants special attention due to its need for specific treatment. It involves patients with signs of potentially severe organ involvement that do not meet MM criteria. We present the case of a 34-year-old Malagasy woman with severe type I cryoglobulinemic vasculitis associated with noncancerous monoclonal gammopathy, showing a favorable outcome after treatment with Thalidomide. Symptoms included toe necrosis, a severe ulcer on the left calf evolving for 3 months, and stocking-like dysesthesias. Investigations revealed monoclonal gammopathy at 30.1 g/L, proteinuria at 1 g/24 h, medullary plasma cell at 6%, and circulating cryoglobulin of Ig kappa type. CRAB criteria (anemia, hypercalcemia, renal insufficiency, and osteolysis) were absent. Treatment with Thalidomide, combined with corticosteroids and local care for 4 months, resulted in ulcer healing, disappearance of dysesthesias, and persistent normalization of gammaglobulin. Our case underscores the importance of specific treatment for MGCS.

The treatment of HCV and its sequelae are used to be predominantly based on Interferon (IFN). However, this was associated with significant adverse events as a result of its immunostimulant capabilities. Since their introduction, the directly acting antiviral drugs (DAAs), have become the standard of care to treat of HCV and its complications including mixed cryoglobulinemic vasculitis (MCV). In spite of achieving sustained viral response (SVR), there appeared many reports describing unwelcome complications such as hepatocellular and hematological malignancies as well as relapses. Prolonged inflammation induced by a multitude of factors, can lead to DNA damage and affects BAFF and APRIL, which serve as markers of B-cell proliferation. We compared, head-to-head, three antiviral protocols for HCV-MCV treatment As regards the treatment response and relapse, levels of BAFF and APRIL among pegylated interferon α-based and free regimens (Sofosbuvir + Ribavirin; SOF-RIBA, Sofosbuvir + Daclatasvir; SOF-DACLA). Regarding clinical response HCV-MCV and SVR; no significant differences could be identified among the 3 different treatment protocols, and this was also independent form using IFN. We found no significant differences between IFN-based and free regimens DNA damage, markers of DNA repair, or levels of BAFF and APRIL. However, individualized drug-to-drug comparisons showed many differences. Those who were treated with IFN-based protocol showed decreased levels of DNA damage, while the other two IFN-free groups showed increased DNA damage, being the worst in SOF-DACLA group. There were increased levels of BAFF through follow-up periods in the 3 protocols being the best in SOF-DACLA group (decreased at 24 weeks). In SOF-RIBA, CGs relapsed significantly during the follow-up period. None of our patients who were treated with IFN-based protocol had significant clinico-laboratory relapse. Those who received IFN-free DAAs showed a statistically significant relapse of constitutional manifestations. Our findings suggest that IFN-based protocols are effective in treating HCV-MCV similar to IFN-free protocols. They showed lower levels of DNA damage and repair. We believe that our findings may offer an explanation for the process of lymphoproliferation, occurrence of malignancies, and relapses by shedding light on such possible mechanisms.

Kidneys are often targets of systemic vasculitis (SVs), being affected in many different forms and representing a possible sentinel of an underlying multi-organ condition. Renal biopsy still remains the gold standard for the identification, characterization and classification of these diseases, solving complex differential diagnosis thanks to the combined application of light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM). Due to the progressively increasing complexity of renal vasculitis classification systems (e.g. pauci-immune vs immune complex related forms), a clinico-pathological approach is mandatory and adequate technical and interpretative expertise in nephropathology is required to ensure the best standard of care for our patients. In this complex background, the present review aims at summarising the current knowledge and challenges in the world of renal vasculitis, unveiling the potential role of the introduction of digital pathology in this setting, from the creation of hub-spoke networks to the future application of artificial intelligence (AI) tools to aid in the diagnostic and scoring/classification process.