Cryoglobulinemia indicates the reversible, cold-dependent precipitation of immunoglobulins (Ig), which may be monoclonal (MoC) or mixed IgG-IgM (MC). Although this in vitro phenomenon is relatively frequent, only a minority of cases develop clinically relevant manifestations, often falling within lymphoproliferative, autoimmune, or infectious disease domains. This complexity highlights the need for clearer nomenclature and definition systems. The term "cryoglobulinemia" is often used interchangeably to describe either simple laboratory finding, asymptomatic cryo-Ig precipitation (MoC or MC) or corresponding clinical syndromes (MoCs or MCs). This overlap creates ambiguity, hinders expert communication, and complicates the comparison of clinical studies. A standardized nomenclature is therefore essential to define disease subsets, establish boundaries with related conditions, and enable reliable data collection and multicenter analyses. When cryoglobulins are detected, the cryoprecipitate must be isolated and defined as MoC or MC, followed by a systematic clinical and laboratory assessment to identify potential underlying disorders. Immunoserological, microbiological, and pathological investigations are required to classify both MoC and MC as asymptomatic or symptomatic, and as essential or secondary. Asymptomatic individuals must be monitored over time for potential progression to overt clinical syndromes; similarly, those with essential forms require surveillance for the emergence of systemic diseases. Possible overlap with autoimmune conditions, particularly Sjögren's disease, should always be considered. Despite some shared features, MoCs and MCs represent distinct clinical entities. Accurate diagnosis relies primarily on cryoprecipitate analysis. MoCs are usually associated with thrombotic, non-inflammatory microangiopathy and lymphoproliferative disorders, whereas MCs are characterized by immune-complex-mediated leukocytoclastic vasculitis, complement consumption, and frequent association with viral infections, especially HCV and HBV. The introduction of new-generation antivirals in the last decade has markedly reduced the prevalence of virus-related MCs in more developed countries. A harmonized nomenclature and standardized definitions for various cryoglobulinemia subsets, supported by careful clinical-immunological and pathological characterization, are essential to improve diagnostic accuracy, ensure interobserver consistency, and enable the development of evidence-based, mechanism-driven therapies for major cryoglobulinemic syndromes.

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.

The aim: The purpose of the study is to improve the results of treatment of patients with acute intestinal obstruction of tumor origin by developing individualized surgical tactics considering the level of cryoglobulins. Materials and methods: 96 patients with ileus of tumor origin were studied. The mean age of patients was 54.7 ± 5.9 years. 30 patients were diagnosed with colorectal cancer, 35 patients - with sigmoid cancer, 13 patients - with cecum and ascending colon, 11 patients - with transverse colon cancer, and 7 patients with descending colon cancer. Isolation of cryoglobulins from blood serum was performed by the method of A. E. Kalovidoris with modifications. The content of Ig A, Ig M, Ig G, total Ig E in the serum was investigated using enzyme-linked immunosorbent assay systems "Granum-Ukraine", the content of allergen-specific Ig E was investigated using enzyme-linked immunosorbent assay systems produced by "Microgen". Results: As a result of treatment of 96 patients, it was found that the level of development of postoperative purulent complications was significantly influenced by the level of cryoglobulinemia and the volume of surgery (CMU, p <0.05). It was found that in patients with decompensated intestinal obstruction, the initial concentration of cryoglobulins was 16.4% higher than in the group with compensated intestinal obstruction (CMU, p <0,05). Conclusions: Determination of cryoglobulinemia on admission of patients with acute obstructive ileus of tumor origin is a simple and effective method for predicting the development of purulent-inflammatory complications in the postoperative period and can influence the choice of treatment tactics.

Diagnosis of pheochromocytoma can be simple when classic manifestations are present. It can also be challenging and complicated in some cases because of its wide array of faces and presentations. We present a case of a 30-year-old female patient who came with acute respiratory distress, chest pain, hemoptysis, asthenia, anorexia, weight loss of 20kg, and paresthesia in her lower limbs. Clinical examination found high blood pressure, accelerated heart and respiratory rates, signs of acute right heart failure with jugular venous distention and ankle edema, reticularis livedo in the four limbs, ulcers in both knees and in the 3rd metacarpo-phalangeal articulations and necrotic lesions in both calcaneal tendons and in the right toes. Further investigations concluded on myocarditis associated with alveolar hemorrhage, pericardic and pleuritic effusions and a segmental pulmonary embolism of the right inferior lobe. Neuro-muscular biopsy was suggestive of myositis. Cutaneous biopsy found nonspecific chronic dermatitis. ANCA antibodies were tested twice and were negative. Cryoglobulinemia was also negative. Thoraco-abdomino-pelvic scan was performed showing a large right adrenal mass suggestive of pheochromocytoma. Diagnosis of right adrenal pheochromocytoma was confirmed by MIBG-I123 hyperfixation findings and urinary normetanephrin levels. The patient was treated surgically. Postoperative outcomes were remarkably favorable with a complete regression of the cutaneous lesions and normalization of the blood pressure. Paresthesia significantly decreased. Control echocardiography at 3 months showed an improved heart function with a persistent apical and septal akinesis.

Hepatitis C Virus (HCV) is a well-known worldwide infection, responsible for hepatic and extrahepatic complications. Among extrahepatic manifestation, the rheumatologic are the most common ones. With the arrival of Direct Antiviral Agents (DAA), the treatment and the clinical perspective have rapidly changed, permitting to achieve a sustained virological response (SVR) and preventing complications of chronic infection. We performed on PubMed a literature search for the articles published by using the search terms "HCV infection," "HCV syndrome," "HCV-related rheumatologic disorders," "cryoglobulinemia," "cryoglobulinemic vasculitis" and "mixed cryoglobulinemia." Mixed cryoglobulinemia (MC) is the prototype of HCV-associated rheumatologic disorder. HCV-related MC is typically considered by physicians as a human model disease to linking infection with autoimmune diseases. Chronic HCV infection can lead to a multistep process from a simple serological alteration (presence of circulating serum cryoglobulins) to frank systemic vasculitis (cryoglobulinemic vasculitis [CV]) and ultimately to overt malignant B lymphoproliferation (such as non-Hodgkin lymphoma [NHL]). Antiviral therapy is indicated to eradicate the HCV infection and to prevent the complications of chronic infection. Immunosuppressive therapy is reserved in case of organ threatening manifestations of CV. In this review, we discuss the main clinical presentation, diagnostic approach and treatment of rheumatologic manifestations of HCV infection. Chronic HCV infection is responsible for complex clinical condition, ranging from hepatic to extra-hepatic disorders. Cryoglobulins are the result of this prolonged immune system stimulation, caused by tropism of HCV for B-lymphocyte.