Abnormal Dihydrorhodamine Result in a Patient with Diabetes Mellitus, Recurrent Candida Liver Abscesses: Diagnostic Possibilities

Abstract

A 17-year-old female with type I diabetes mellitus (DM) and a history of recurrent candidal vaginal infections and liver abscesses was assessed fora potential neutrophil oxidative burst defect by DHR flow cytometry. The DHR result was abnormal with significantly decreased MFI (MFI = 9; ref. cutoff: >/ = 60) after stimulation with PMA though all of her neutrophils (99%; ref. cutoff >/ = 95%) showed respiratory burst. This DHR pattern has been previously observed in patients with complete myeloperoxidase deficiency (cMPO), p40phox deficiency and hypomorphic X-linked chronic granulomatous disease (CGD). Genetic evaluation of the genes commonly associated with CGD (CYBB, CYBA, NCF1, NCF2 and NCF4) was negative. It must be noted that many genetic laboratories either do not sequence the NCF1 gene or have limited sequencing to the most commonly observed pathogenic variant in exon 2. Most targeted genetic panels currently do not include MPO (myeloperoxidase) or CYBC1 (Eros). The clinical phenotype of Candida infection in the context of diabetes has been previously reported in 5% of cMPO deficiency. The patient underwent a partial hepatectomy and was initiated on an 8-month course of fluconazole. Three months later, there was a recurrence of hepatic abscesses (Figure 1), requiring treatment with a 12-week course of IV micafungin. Complete MPO deficiency can cause a false-positive result on the DHR assay but the pattern is different from that observed in typical XL- and autosomal recessive CGD. There are two ways of confirming cMPO deficiency, besides genetic testing: 1) staining for MPO in neutrophils in a peripheral smear, or 2) repeating the DHR assay and gating on eosinophils as eosinophil peroxidase can overcome the lack of MPO deficiency and demonstrate a normal oxidative burst. These studies are currently under investigation. In summary, cMPO deficiency should be included in the differential diagnosis of patients with diabetes and invasive Candida infections. Communication with the clinical laboratory is essential to identify the DHR pattern and obtain additional confirmatory testing. From a clinical perspective, cMPO-deficient patients do not require prophylactic antibiotics but they have a high rate of recurrence of fungal infections and require aggressive management with antifungal therapies. [Display omitted]