This study represents the first demonstration that the incidence rates of cryoglobulinaemia and CryoVas are 1.5% in patients with AAV without chronic viral hepatitis or haematologic malignancies.
Key Findings
Results
Cryoglobulin was detected in the sera of only 2 out of 136 AAV patients, yielding a detection rate of 1.5%.
Of 324 total AAV patients diagnosed, 136 had available cryoglobulin test results and were included in the study.
Both patients with cryoglobulin positivity exhibited repeated cryoglobulinaemia, defined as cryoglobulin positivity on at least two occasions separated by an interval of ≥12 weeks.
The study excluded patients with chronic viral hepatitis or haematologic malignancies, which are common secondary causes of cryoglobulinaemia.
This is described as the first demonstration of incidence rates of cryoglobulinaemia in AAV patients without these common confounding conditions.
Results
Both patients with cryoglobulinaemia met classification criteria for CryoVas concurrent with microscopic polyangiitis (MPA), yielding a CryoVas concurrence rate of 1.5% among AAV patients.
Both patients presented with red skin spots, constitutional symptoms, articular involvement, and vascular involvement, enabling their classification as having CryoVas alongside MPA.
One patient additionally displayed peripheral neuropathy, reduced serum C4 levels, and rheumatoid factor positivity.
The CryoVas classification criteria were formally applied to all 136 AAV patients.
Both cases of concurrent CryoVas occurred specifically in patients diagnosed with MPA, not with GPA or eosinophilic GPA.
Methods
The study cohort consisted of 136 AAV patients with a median age of 61.0 years, of whom 41.2% were male.
The median age was 61.0 years with an interquartile range of 50.0–69.0 years.
41.2% of the 136 included patients were male.
Of the 136 patients, 75 were diagnosed with microscopic polyangiitis (MPA), 31 with granulomatosis with polyangiitis (GPA), and 30 with eosinophilic GPA.
Patients were drawn from an initial pool of 324 AAV-diagnosed patients, with inclusion contingent on availability of cryoglobulin test results.
Background
CryoVas and AAV share the characteristic of being small vessel vasculitides but exhibit significant differences in pathologic findings.
The study was motivated by the overlap in clinical presentation between CryoVas and AAV as both are small vessel vasculitides.
Despite clinical similarities, the two conditions have distinct pathological mechanisms and findings.
The study design required applying formal CryoVas classification criteria to all 136 AAV patients to assess true concurrence.
Repeated cryoglobulinaemia was specifically defined as positivity on at least two occasions separated by ≥12 weeks to avoid false-positive classification.
What This Means
This research investigated how often patients with a type of blood vessel inflammation called ANCA-associated vasculitis (AAV) also have a related but distinct condition called cryoglobulinaemic vasculitis (CryoVas). CryoVas is caused by abnormal proteins in the blood called cryoglobulins and is most commonly linked to chronic viral infections like hepatitis C or blood cancers. The researchers specifically looked at AAV patients who did NOT have these common causes, to see if the two conditions could occur together for other reasons. Out of 136 AAV patients tested, only 2 (1.5%) had detectable cryoglobulins, and both of those patients also met the formal criteria for CryoVas — specifically alongside a subtype of AAV called microscopic polyangiitis (MPA).
This research suggests that while CryoVas and AAV can co-occur, it is quite rare in the absence of hepatitis or blood cancers. Both patients who had both conditions showed overlapping symptoms such as skin spots, joint involvement, and vascular problems, making clinical distinction challenging. One patient also had nerve involvement, low complement C4 levels, and a positive rheumatoid factor — features more typical of CryoVas. The study is notable for being the first to formally measure the rate of this co-occurrence in a defined AAV population.
For clinicians, this research suggests that while cryoglobulin testing may be warranted in some AAV patients with atypical features, the overlap between the two conditions is uncommon when standard secondary causes are excluded. Understanding whether a patient has one or both conditions matters because the underlying causes and treatments can differ. The findings also raise questions about whether this co-occurrence is a true biological association or simply a coincidence in rare cases.
Whang J, Ha J, Chung J, Park Y, Song J, Park Y, et al.. (2026). Concomitant cryoglobulinaemic vasculitis alongside ANCA-associated vasculitis: concurrence or coincidental individual occurrence.. The Korean journal of internal medicine. https://doi.org/10.3904/kjim.2025.094