Article Text


Cryoglobulinaemic vasculitis as presenting manifestation of infective endocarditis
  1. L La Civita1,
  2. P Fadda1,
  3. I Olivieri1,
  4. C Ferri2
  1. 1Rheumatology Department of Lucania, S Carlo Hospital, Contrada Macchia Romana, 85100 Potenza, Italy
  2. 2Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy
  1. Correspondence to:
    Dr Luca La Civita, Rheumatology Department of Lucania, Azienda Ospedaliera S Carlo, Contrada Macchia Romana, 85100 Potenza, Italy

Statistics from

Seroimmunological alterations, including antibodies and/or cryoglobulins, are common in infective endocarditis (IE)1; however, specific autoimmune disorders, such as cryoglobulinaemic vasculitis (CV) associated with IE have seldom been described.2–5 CV is related to the vascular deposition of circulating immune complexes, mainly cryoglobulins, and complement5,6; in 70–90% of patients with CV a triggering role of hepatitis C virus (HCV) has been suggested.7,8 We report the case of two patients who showed a typical CV with severe neurological involvement as the presenting manifestation of underlying IE.

Case 1

In November 1994 a 63 year old woman presented with fever, purpura, paraesthesias, and pseudoataxic gait. Her past clinical history was unremarkable except for a prosthetic implant of the left hip four years previously. Table 1 shows the main clinicoserological features. Repeated blood cultures were negative. Neurological examination showed abnormal tactile sensation in the arms and legs; mild ideomotor slowing down; shaky movements; and unsteady gait. An electrophysiological study recorded a moderate sensorimotor peripheral neuropathy, while ECG, chest x ray examination, abdominal echography, and echocardiography were normal. Cutaneous purpura biopsy disclosed a leucocytoclastic vasculitis. Truncoencephalic magnetic resonance imaging showed multiple, T2 weighted high signal intensity, punctiform lesions at the white matter consistent with brain vasculitis. Thus a central and peripheral neuropathy complicating CV was established, and prednisone (50 mg) combined with cyclophosphamide (100 mg) was given daily. However, the patient's clinical status progressively worsened and, finally, she died owing to cardiorespiratory failure during the following month of treatment. Necropsy disclosed coarse endocardial vegetations on the left sided valves infected by Kingella.

Table 1

Epidemiological, clinical, and seroimmunological features in two female patients with infective (bacterial) endocarditis, at the first visit

Case 2

In January 1999 a 75 year old woman with no risk factors for infections presented with fever, purpura, and acroparaesthesias. Table 1 shows the main clinical and laboratory features suggestive of CV. Prednisone (25 mg/day) was started, with a rapid clinical improvement. One month later, she had an exacerbation of purpura, arthralgias, acroparaesthesias, and impairment of distal muscle strength. An electrophysiological study confirmed a sensorimotor peripheral neuropathy. Thus a higher steroid dose (50 mg/day) was given. A week later fever persisted and the patient complained of precordial pain and cardiac murmurs were found. A chest x ray examination and transoesophageal echocardiography detected cardiomegaly and endocardial vegetations on the tricuspid valve; in addition, Staphylococcus aureus infection was shown by repeated blood cultures. Despite appropriate antibiotic treatment, the patient died one month later because of severe, refractory heart failure.


Our two patients show some interesting peculiarities: the unusual presentation of IE as CV with severe neurological involvement; and the difficulty of making a timely diagnosis of IE by routine investigations. In both cases, the clinically prevalent CV symptoms, together with their transient favourable response to corticosteroids (case 2), further delayed the detection of IE responsible for the fatal outcome. Previous reports (Medline) show that the association of IE with “asymptomatic” cryoglobulinaemia is not uncommon,9,10 but only a few studies report IE clinically presenting as CV.2–5 This latter presentation can mean a misdiagnosis; moreover, steroid treatment can contribute to masking and worsening of the underlying infectious disorder.4

In our patients we can reasonably exclude the possibility that IE represented a complication of the CV. In over 300 of our patients with CV, bacterial manifestations have rarely been seen, even in subjects undergoing steroid or immunosuppressive treatments, or both. Moreover, the CV seen in our two patients had quite unusual clinical and virological characteristics: absence of HCV or other hepatotropic viruses5–8; the presence of particularly severe skin purpura; and the presence of neuropathy as important organ involvement. The peripheral neuropathy, in one case associated with central nervous system vasculitis, was the only prevalent organ manifestation seen in our patients. This is one of the most common clinical manifestations in patients with CV,5,6,11 the aetiopathogenesis of which is still unclear. In a considerable number of patients with IE negative blood cultures have also been recorded,1,4 often when Gram negative bacteria are involved.1

In patient 1, the lack of timely recognition of Kingella by repeated blood cultures was probably due to different reasons, including slow growing of the agent, low microbial charge in the blood samples, and/or inappropriate use of growth media. However, the negative cultures together with clinical symptoms suggestive for CV, in the absence of relevant features at transthoracic echocardiography at the onset, were sufficient reasonably to exclude a suspicion of IE presenting as CV.

In conclusion, CV may represent the presenting manifestation of IE, a life threatening condition for which a timely correct diagnosis and adequate treatment are essential. In patients with CV unrelated to HCV infection and with fever unresponsive to steroids it is strongly recommended that other less common, infectious factors are excluded. IE, for example, should be excluded by repeated blood cultures and careful clinicomicrobiological evaluation, including transoesophageal echocardiography.


View Abstract

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.