Serological tests for hepatitis B, hepatitis C, and human immunodeficiency virus, as well as cryoglobulin
, cold agglutinin, and C3 and C4 were all negative.
In children, pernio can be associated with the presence of cryoglobulins
, cold agglutinins, anorexia nervosa, and genetic interferonopathy; it may precede the diagnosis of chronic myelomonocytic leukemia and may occur as a presenting sign of a blast crisis in acute lymphoblastic leukemia.
Our patient also had associated mixed cryoglobulinemia, which was evidenced by a positive cryoglobulin
level with high rheumatoid factor levels.
While nonspecific inflammatory markers (C-reactive protein (CRP) of 55 mg/L and erythrocyte sedimentation rate (ESR) of 80 mm/hr) were elevated, multiple serologies associated with nephritic syndromes (peripheral and cytoplasmic antineutrophilic cytoplasmic antibodies (p- and c-ANCA): antimyeloperoxidase (MPO), antiproteinase 3 (PR3), complement levels, antinuclear antibody (ANA), anti-double-stranded DNA (dsDNA), rheumatoid factor (RF), hepatitis B and C panels, and cryoglobulins
) were all negative.
A detailed workup was performed (including ANA, ENA panel, RF, ANCA, serum protein electrophoresis and immunofixation, Lyme serology, muscle enzymes, ESR, CRP, ferritin, and cryoglobulins
The blood examinations at the baseline visit, prior to administer the IVIg cycle, were blood cell count, hepatic and renal function tests, plasma concentration of albumin and fibrinogen, lipid profile, routine urinalysis, serum levels of immunoglobulins specially IgA, rheumatoid factor, cryoglobulins
, and antibodies to hepatitis B, C, and human immunodeficiency viruses.
In view of the patient's presentation and absence of classical stroke risk factors, CT angiography and vasculitis work-up were sent including ANA, c-ANCA, p-ANCA, ESR, CRP, antiphospholipid antibodies, Factor V Leiden, prothrombin gene mutation, protein C, protein S, cryoglobulins
, and complement C3 and C4 levels.
The following investigations were done: complete haemogram, renal and liver function tests, urine analysis, antinuclear antibody (ANA), antineutrophilic cytoplasmic antibody (ANCA), Rheumatoid factor (RF), C-reactive protein (CRP), cryoglobulins
, lupus anticoagulant, HBsAg, anti-HCV antibody, antistreptolysin O (ASO) titre, throat swab for culture and sensitivity, Chest X-ray and Mantoux test.
It occurs when cryoglobulins
- abnormal proteins in the blood - thicken and clump together, restricting blood flow to surrounding organs and causing damage to blood vessels.
For example, regardless of their nature, it is important that substances that can lead to clumping of formed elements that might affect flow cytometric measurements, such as cryoglobulins
or other RBC agglutinins, elevated fibrinogen, macroglobulins, or naturally occurring factors that lead to platelet clumping, rouleaux, or other conditions such as polycythemia or thrombocytopenia, be recognized and corrected for by image analysis.
We believe that the low prevalence of mixed cryoglobulinemia is related to the referral of patients to other services and not due to error in detecting cryoglobulins
. Further studies are needed to better understand the natural history and to determine the best therapeutic approach for patients with these comorbidities.
A further workup was initiated to rule out any connective tissue disorders, and antinuclear antibody (quantitative), cytoplasmic antineutrophil cytoplasmic antibody, perinuclear antineutrophil cytoplasmic antibody, and serum cryoglobulins
were found to be normal.