Studies have demonstrated an increased infection-related mortality in rheumatoid patients.1 2
The addition of disease-modifying immunosuppressive drugs exacerbates the risk in this cohort3
and has led to the reporting of complications such as tuberculosis, bacterial pneumonia and septicaemia.4
Our case illustrates how a life-threatening and infective complication presented insidiously in an immunosuppressed patient. To our knowledge, this highly unusual course of events has not been reported previously.
The patient's illness began with a spontaneous rupture of the Achilles tendon. During the course of her illness, she ruptured two further tendons in each hand. Tendon rupture in rheumatoid patients is well recognised, although multiple ruptures are rare.5 6
Rheumatoid granulation tissue has previously been identified within ruptured tendons (and enthesis) on histological analysis.7
Hypoxia, angiogenesis and corticosteroid use have been implicated in pathogenesis.5 8
In this case, sepsis in the tenosynovium and leflunomide therapy are also possible contributory factors. The mechanism for tendon rupture is unclear with the latter – it is postulated that it may be due to an avascular effect.
In association with this patient's aggressive staphylococcal infection, a striking CRP of almost 500 mg/l was noted on presentation. A proportion of this CRP level was probably related to rheumatoid inflammation, although a rise of this degree is suggestive of superimposed infection. However, the CRP level fell rapidly with the initiation of antimicrobial therapy.
Staphylococcus is a common pathogen in the general population, and oral carriage has been shown to be higher in the rheumatoid patient. It has been suggested that combination immunosuppression may increase carriage.9
The progress of the infection was notably atypical and invasive. Metastatic complications are known to occur in a substantial proportion of cases of staphylococcal septicaemia, and common foci include the joints and heart valves.10
Despite appropriate therapy, multiple joint abscesses developed in our patient, all requiring surgical intervention.
CT imaging revealed septic destruction of the manubrium and resultant mediastinitis. The size and depth of the chest wall abscess had been previously underestimated on ultrasound, due to the presence of inflammatory debris as well as its retrosternal positioning. Such mediastinal pathology is rare in the rheumatoid patient.
Similarly, acute mediastinitis is another highly unusual feature. Seen most often in cases of open-chest surgery and oesophageal perforation, it rarely occurs as a result of direct infection from adjacent tissues.11
When the latter occurs, staphylococcus is frequently implicated and associated with significant rates of relapse and mortality.12
In this case, cross-sectional images provided the diagnosis of mediastinitis as well as the aetiology – displaying clear evidence of mediastinal invasion through a destroyed manubrium.
Prior to her acute illness, leflunomide was used with a view to combating severe and refractory rheumatoid disease. This immunomodulatory agent reduces activated lymphocyte and T cell proliferation as well as cytokine production. Its active metabolite (which has a long half-life) operates through mitochondrial enzyme and cell-cycle inhibition.13–15
Multiple trials have demonstrated safety and efficacy maintained over several years.16–18
Unsurprisingly for an immunosuppressive drug, however, infections are occasionally seen. In our case neither bone marrow suppression nor unusual pathogenic organisms were responsible. In the spectrum of infections seen, pneumonia is the commonest.14
Contradictory studies have been published commenting on postoperative infection rates.19 20
One long-term study reported an incidence of severe infection rate (requiring hospitalisation) as 3.3/100 patient years. This case-note audit included patients who varied in terms of disease status, co-morbidity and drug therapies. Therefore, a causative relationship could not be established.4
Most relevant to our patient's case are the reports of atypical and severe infections such as a paravertebral abscess (with vertebral erosions) as well as pyomyositis of the forearm in leflunomide treated patients. It was noted these extensive and striking lesions appeared in a relatively short period of time.21
In addition, leflunomide has been associated with abscess formation as well as tendon rupture – both relevant features here.
In summary, there are many factors likely to have contributed to this unusual course of events. Swelling of the joints (subsequently aspirated) may have initially gone unnoticed by the patient and been attributed to a flare up of her disease. It is possible that leflunomide and steroid therapy precipitated a staphylococcal septicaemia from this source. An abscess subsequently developed in the chest through haematogenous spread; metastases are a recognised phenomenon of staphylococcal infection.10
Finally, this abscess may have led to osteomyelitis of the manubrium through direct spread. Bony destruction which permitted this is rarely seen in the immunocompetent host and has been particularly noted in seropositive rheumatoid cases.22
Alternatively, the manubrium itself may have been the original source of infection. Here, underlying bone abnormality as well as trauma from the use of crutches may have been relevant factors. A bone scan was not performed at this stage, although, in retrospect, this may have been a useful examination to conduct in this context.
Irrespective of the sequence of events, diagnosis was complicated by a variety of factors. In terms of the patient's response, inflammatory markers and temperature fell despite underlying disease progression. Further difficulties were related to the nature of the diagnosis itself. Mediastinal infection is rare, and mediastinitis, when subacute, frequently presents in a subtle fashion.23 24
It is likely that that this response was further dampened by immunosuppression. Finally, the imaging modality used precluded the visualisation of retrosternal pathology.