Burden of illness in hereditary periodic fevers: a multinational observational patient diary study.

OBJECTIVES: This study aimed to characterise the burden of illness of patients with inadequately controlled hereditary periodic fevers (HPFs), during and outside of flares. It was focused on the burden to the patients and also considered the wider impact on their caregivers and families. METHODS: The target population was patients or caregivers of patients with clinically/genetically confirmed colchicine resistant FMF (crFMF), mevalonate kinase deficiency/hyperimmunoglobinaemia D with periodic fever syndrome (MKD/HIDS) or TRAPS, who were expected to flare at least once in a 6-month period based on patient history. Disease burden was captured during and between flares using an electronic diary (e-diary) with questions on patient functioning, emotional/social well-being and pain, using validated instruments. RESULTS: HPF-related symptoms such as fever, joint, muscle or bone pain and tiredness and fatigue were reported by patients both during and outside of a flare. The SF-10 Health Survey (SF-10v2) (paediatric patients) and SF-12 Health Survey (SF-12v2) (adult patients) showed that flares negatively impacted patients' psychosocial and physical health. Negative effect of on-flare status on health utility index score assessed by the Short-Form Six-Dimension (SF-6D) was significant only for crFMF patients. Furthermore, the Sheehan Disability Score (SDSv3) showing the on-flare status resulted in significant functional impairment in all 3 disease cohorts through assessment of impact on work/school, social and family life. CONCLUSIONS: crFMF, MKD/HIDS and TRAPS negatively affected the quality of life (QoL) of adult and paediatric patients, including their physical, mental, psychosocial health, and social functioning. There remains, however, a high number of unmet needs for these patients to reduce their disease burden.

Misdiagnosing renal amyloidosis as minimal change disease.

BACKGROUND: Minimal change disease (MCD) accounts for 10-15% of all adult nephrotic syndrome cases and requires normal renal histology by light microscopy and negative immunohistology. Foot process effacement on electron microscopy (EM) is typical. Renal amyloid deposits demonstrate pathognomonic green birefringence when viewed under cross-polarized light after staining tissue with Congo red (CR) and may reveal fibrils on EM. Late diagnosis and delayed treatment of renal amyloidosis negatively impact on renal and patient survival. METHODS: A retrospective analysis was performed on 2116 patients referred to the National Amyloidosis Centre between 2001 and 2013, in whom renal amyloidosis was confirmed histologically. Twenty-seven of these patients had renal histology initially interpreted to be MCD. RESULTS: Among 26 patients in whom biopsy specimens and/or reports were retrieved, the median age at MCD diagnosis was 62 years and presenting proteinuria averaged 7.8 g/24 h. The median time period between the two diagnoses was 241 days (range: 20-2632 days). MCD was diagnosed without CR in 17/26 (65%) biopsies, but all specimens contained amyloid on retrospective CR staining. MCD was diagnosed without EM in 17/26 (65%) cases and all of 10 such biopsies subsequently demonstrated fibrils. Sixteen patients were subjected to two or more renal biopsies when their proteinuria proved steroid refractory. CONCLUSION: This study highlights the need to stain renal biopsies from proteinuric adults with CR, examine them under cross-polarized light and perform EM wherever possible. If the suspicion of renal amyloidosis remains high, despite apparent negative histology, specimens should be reviewed at specialist centres before undertaking a second kidney biopsy.