Development of Oral Candidiasis Predicts Severe Infections in AAV Patients Receiving Immunosuppressants, Study Shows

ANCA-associated vasculitis patients who develop oral candidiasis during treatment with immunosuppressants have a significantly greater risk of severe infections compared to patients who never develop oral candidiasis, a study shows.

Together with use of methylprednisolone pulse therapy and higher serum albumin levels, oral thrush appears to be a significant predictor of future severe infections, emphasizing the need for increased surveillance in these patients.

These results were reported in the study “Oral Candidiasis is a Significant Predictor of Subsequent Severe Infections During Immunosuppressive Therapy in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis,” published in the journal BMC Infectious Diseases.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, or AAV, is an autoimmune condition characterized by inflammation of predominantly small blood vessels.

It includes three subtypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA). A common feature of the three diseases is their association with circulating ANCAs, which are self-reactive antibodies against neutrophils, a type of white blood cell.

Treatment with immunosuppressive agents, such as cyclophosphamide or Rituxan (rituximab), in addition to glucocorticoids, improves survival among AAV patients. However, it also increases the risk of infections, including severe ones, so it is important to be able to predict when they may occur.

Investigators at Aichi Medical University Hospital in Japan analyzed a group of 71 patients diagnosed with AAV and treated with immunosuppressive therapy from March 2013 to December 2018 to identify possible factors that might predict subsequent severe infections (defined as any infection requiring hospitalization). Of the 71 patients analyzed, 58 had MPA, one had GPA, and 12 had EGPA.

One factor they looked at was the development of oral candidiasis (an infection of the oral cavity caused by the Candida species, which is a type of yeast). It is common in people with suppressed immune systems. Of the 71 patients analyzed, 17 developed oral candidiasis after a average of 13 days of starting immunosuppressive therapy, while 54 never developed the condition.

During a median observation period of 23 months, 25 severe infection episodes occurred in 19 patients (26.8%). These included bacterial pneumonia (seven cases), Pneumocystis jiroveci pneumonia (one case), infection of the vertebrae (one case), methicillin-resistant Staphylococcus aureus (one case), invasive aspergillosis (a severe fungal infection, three cases), widespread tuberculosis infection (one case), presence of fungi or yeasts in the blood (one case), and bacterial infection of the kidney (four cases).

The investigators found that the proportion of patients who developed severe infection was significantly higher among those who developed oral candidiasis than in those who did not (64.7% vs. 14.8%).

The median time from starting immunosuppressive therapy to the first severe infection occurring also was shorter among those with oral candidiasis (13 months) compared to people who never developed candidiasis (16 months). In the candidiasis group, severe infections occurred shortly after the oral candidiasis episode (median 2.5 months).

In addition, results showed that the use of methylprednisolone pulse therapy — intermittent high doses of this glucocorticoid to achieve rapid immunosuppression with fewer side effects — and oral candidiasis were significant predictors of severe infection, increasing the risk by five-fold. Lower serum albumin, on the other hand, was a protective factor for severe infections, reducing the risk by 62%.

Although the researchers advised caution when interpreting and generalizing their results due to the limitations of their study — such as its retrospective nature, the single-center small group design and the short observation period — they concluded that physicians “should be careful in treating [oral candidiasis] patients, especially those under aggressive immunosuppressive treatment, to allow for earlier detection and better outcome.”