Skip to textbook content
Doctor’s PassportTextbook
QuestionsFlashcardsBriefsDashboardAccount
TopicsAll topics

Loading topic navigation…

Textbook navigation
TopicsAll topics

Loading topic navigation…
Educational draft · awaiting clinical reviewUse Rapid for revision, not patient-care decisions. Check current national and local guidance and the BNF or BNFC before acting.

Cryoglobulinaemic vasculitis

Rheumatology · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

RapidFull
!
Cryoglobulinaemic organ threat

Rapidly rising creatinine, pulmonary haemorrhage, mesenteric ischaemia, digital necrosis, severe motor neuropathy, hyperviscosity or widespread ulceration can progress before the causal laboratory work is complete.

Action: Admit under rheumatology with renal, haematology, hepatology or critical-care support as indicated; draw correctly handled cryoglobulin and infection samples, secure tissue diagnosis when safe, and begin severity-directed immunosuppression with cause-directed treatment without waiting for a delayed cryoglobulin result.

Synopsis

Recognise immune-complex vasculitis caused by circulating cryoglobulins, preserve specimen integrity, identify hepatitis, autoimmune and clonal drivers, and match antiviral, B-cell and plasma-exchange treatment to organ severity.

  • Cryoglobulinaemic vasculitis is a clinical syndrome, not simply a positive cryoglobulin test: look for palpable purpura, arthralgia, weakness, neuropathy, glomerulonephritis and acral ischaemia.
  • Type I disease is usually monoclonal and predominantly occlusive; mixed type II and III disease is immune-complex vasculitis associated with hepatitis C, autoimmunity or another chronic immune stimulus.
  • A false-negative cryoglobulin result is common when blood cools before clotting and serum separation; contact the laboratory before collection and keep the whole specimen at 37 degrees Celsius during pre-analytical handling.
  • Low C4, rheumatoid-factor activity and a compatible syndrome support mixed cryoglobulinaemia, but neither confirms the causal driver nor replaces skin, kidney or nerve tissue when organ-threatening disease needs classification.
  • Test every patient for HCV antibody with reflex HCV RNA, hepatitis B and HIV, and investigate autoimmune and B-cell or plasma-cell causes according to phenotype and immunofixation.
  • For HCV-associated glomerulonephritis with stable kidney function and no nephrotic syndrome, KDIGO supports direct-acting antiviral therapy before immunosuppression.
  • A cryoglobulinaemic flare, rapidly progressive glomerulonephritis or other major organ threat requires antiviral therapy plus specialist immunosuppression; plasma exchange is added selectively when rapid cryoprotein removal is needed.

Key red flags

Haemoptysis, falling haemoglobin, hypoxaemia or new bilateral alveolar shadowing suggests diffuse alveolar haemorrhage and requires immediate respiratory and vasculitis care.

Haematuria, proteinuria, oliguria, oedema, hypertension or a rapidly increasing creatinine indicates cryoglobulinaemic glomerulonephritis until a competing cause is established.

New foot drop, hand weakness, severe asymmetric neuropathic pain or rapidly extending sensory loss indicates ischaemic nerve injury and needs urgent specialist treatment.

Postprandial or severe abdominal pain, gastrointestinal bleeding, lactate elevation, digital infarction or skin necrosis suggests medium-vessel or severe small-vessel ischaemia.

Headache, visual change, mucosal bleeding, confusion or heart failure with a monoclonal protein may represent type I hyperviscosity and needs same-day haematology assessment.

Fever, rigors or an infected ulcer must trigger cultures and antimicrobial assessment because infection can drive immune complexes and can be worsened by glucocorticoid or rituximab.

Cryoglobulinaemic glomerulonephritis

Haematuria, proteinuria, hypertension, oedema and falling eGFR with complement consumption suggests an immune-complex membranoproliferative renal process.

Investigation priorities

01
Warm-handled cryoglobulin assay and immunotypingFirst step

Demonstrate a reversible cryoprotein and classify monoclonal or mixed composition.

Management branches

First diagnostic priorityPreserve the specimen and grade organs

Purpura, cold-related ischaemia, neuropathy or glomerular findings raise cryoglobulinaemic disease.

  1. Contact the laboratory before venepuncture, obtain a warm-handled cryoglobulin sample and simultaneously draw complement, infection, autoimmune and monoclonal-protein tests.
  2. Check urine, creatinine, pressure, oxygenation, haemoglobin, neurological power, perfusion and abdominal features to identify kidney, lung, nerve or bowel threat.
  3. Biopsy the safest active organ when classification will change treatment, but do not delay emergency organ rescue for a slow cryoglobulin result.
Cause-directed first stepEradicate active hepatitis C

HCV-associated disease is present with stable filtration and without nephrotic or rapidly progressive glomerulonephritis.

  1. Refer promptly to the regional hepatitis service and stage cirrhosis, kidney function, prior antiviral exposure, HBV status and medicine interactions.
  2. Start the selected pangenotypic direct-acting antiviral and monitor adherence, toxicity and HCV RNA according to the specialist eradication pathway.
  3. Track vasculitic organs after virological response because immune-complex or clonal disease can persist despite sustained viral clearance.

Key medicines

Glecaprevir 300 mg with pibrentasvir 120 mgGive three 100 mg/40 mg tablets orally together once daily with food; treatment is commonly 8 weeks in treatment-naive adults without decompensated cirrhosis, but duration and suitability must be set by the hepatitis service.Do not use in severe hepatic impairment or decompensated liver disease. Check every medicine for transporter and CYP interactions, especially statins, anticonvulsants, rifampicin and HIV drugs; screen HBV and verify duration for genotype, cirrhosis and prior treatment. Use is not recommended in pregnancy because data are limited; decide whether to discontinue breastfeeding or treatment by weighing benefits.
Rituximab intravenous infusionFor significant mixed cryoglobulinaemic vasculitis, a commonly studied specialist off-label regimen is 375 mg/m2 intravenously once weekly for 4 doses; an alternative protocol uses 1 g on days 1 and 15.Cryoglobulinaemic vasculitis is not a UK licensed rituximab indication. Screen HBsAg and anti-HBc and institute prophylaxis or monitoring, exclude active infection, check immunoglobulins and vaccines, premedicate and monitor infusion reactions. A high cryoglobulin burden can flare after infusion. Avoid pregnancy unless benefit outweighs risk and use effective contraception during treatment and for 12 months afterwards.
Open full textbook →Answer 2 questions
Sources and review status6 sources · checked 27 Aug 2026 · clinical review pending+
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

  • KDIGO 2022 hepatitis C in CKD guidelineHCV-associated glomerulonephritis, antiviral priority and severe cryoglobulinaemic flare treatment.
  • EASL recommendations on treatment of hepatitis C: final update of the seriesPangenotypic antiviral treatment and extrahepatic cryoglobulinaemic disease.
  • Italian Study Group consensus on rituximab in mixed cryoglobulinaemiaOrgan indications, studied rituximab schedules, relapse and infection safeguards.
  • Cryoglobulinaemic vasculitis diagnostic and treatment recommendationsClinical spectrum, laboratory handling, typing and severity-directed care.
  • MabThera UK product informationRituximab infusion, infection, HBV, vaccination and reproductive safety.
  • Glecaprevir and pibrentasvir UK product informationLicensed dose, treatment-duration tables, hepatic restrictions and interactions.

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

Authoring stateRapid draftClinical stateAwaiting reviewJurisdictionUnited Kingdom
Ischaemic neuropathy

Painful asymmetric sensory loss followed by weakness, foot drop or hand deficit reflects infarction of vasa nervorum and needs rapid treatment before axonal loss becomes fixed.

Hyperviscosity emergency

Headache, confusion, visual blurring, retinal change, mucosal bleeding or cardiopulmonary compromise with a large cryoprotein burden requires urgent haematology and plasma-viscosity assessment.