A 44-year-old was seen in the rheumatology clinic in December complaining of malaise, joint pains and tingling in the hands and feet. She had been diagnosed as having Raynaud’s phenomenon several years ago. The patient had consulted several doctors for intermittent malaise and joint pains. There was no history of night sweats, dyspnoea, or problems with swallowing. The patient took paracetamol on a PRN basis for joint pains. On examination she had palpable purpura on the thighs and arms. There was no obvious evidence of joint swelling. Abdominal examination revealed hepatomegaly palpable 3 cm below the costal margin. Neurological examination revealed decreased sensation in the hands and feet. The blood pressure was 110/80 mmHg.
Investigations are shown.
Hb 10 g/dl WCC 9 109/l Platelets 490 109/l ESR 90 mm/h Sodium 139 mmol/l Potassium 4.2 mmol/l Urea 9 mol/l Creatinine 140 mol/l Bilirubin 15 mmol/l AST 90 iu/l Alkaline phosphatase 122 iu/l Albumin 33 g/l Rheumatoid factor IgM Positive (titre 1/640) C3 0.2 g/l (NR 0.55–1.2 g/l) C4 0.09 g/l (NR 0.2–0.5 g/l) Hep C Virus AB Positive Hep B sAg Negative Urinalysis Blood + Protein ++
What is the best management of the patient’s illness?
a. Prednisolone.
b. Cyclophosphamide.
c. Chlorambucil.
d. Pegylated interferon- plus ribavarin.
e. Plasmapharesis.
Answer:
d. Pegylated interferon- plus ribavarin
This is a difficult question; however, the clue lies in the fact that the patient has evidence of current or previous infection with hepatitis virus and has Raynaud’s phenomenon, palpable purpura (vasculitis), neuropathy and hypocomplementaemia. The diagnosis is consistent
with mixed essential cryoglobulinaemia. Cryoglobulins are immunoglobulins that precipitate in the cold. They are associated with auto-immune haemolysis, Raynaud’s disease (in severe cases they can cause acronecrosis), vasculitis, peripheral neuropathy, glomerulonephritis and hepatosplenomegaly. Complement is reduced. HCV is thought to play an aetiological role in the development in type II and type III cryoglobulinaemia.
Types of cryoglobulinaemia Type Immunoglobulins Associated condition(s) I Monoclonal immunoglobulin Multiple myeloma Waldenstrom’s macroglobulinaemia II Polyclonal IgG and monoclonal Hepatitis C and hepatitis B rheumatoid factor IgM III Mixed IgG and polyclonal Chronic inflammation rheumatoid factor Hepatitis C Lymphoproliferative disease
The diagnosis is based upon history, skin biopsy (if purpura present), hypocomplementaemia and presence of cryoglobulins. Investigation for cryoglobulinaemia should always include serology for hepatitis C infection. Treatment for acute cryoglobulinaemia causing severe renal impairment or acronecrosis is plasmapharesis, though in less acute situations prednisolone and
cyclophosphamide are effective. Chlorambucil has also been used with success. When cryoglobulinaemia is secondary to HCV infection, the treatment of choice includes the combination of pegylated interferon-a and ribavarin. Ribavarin should be used with caution in patients with renal failure.