Drug-induced Fanconi syndrome associated with fumaric acid esters treatment for psoriasis: a case series

Abstract

BackgroundFumaric acid esters (FAEs), an oral immunomodulating treatment for psoriasis and multiple sclerosis, have been anecdotally associated with proximal renal tubular dysfunction due to a drug-induced Fanconi syndrome. Few data are available on clinical outcomes of FAE-induced Fanconi syndrome.MethodsDescriptive case series with two cases of Fanconi syndrome associated with FAE treatment diagnosed at two Dutch university nephrology departments, three cases reported at the Dutch and German national pharmacovigilance databases and six previously reported cases.ResultsAll 11 cases involved female patients with psoriasis. The median age at the time of onset was 38 years [interquartile range (IQR) 37–46]. Patients received long-term FAEs treatment with a median treatment duration of 60 months (IQR 28–111). Laboratory tests were typically significant for low serum levels of phosphate and uric acid, while urinalysis showed glycosuria and proteinuria. Eight (73%) patients had developed a hypophosphataemic osteomalacia and three (27%) had pathological bone fractures. All patients discontinued FAEs, while four (36%) patients were treated with supplementation of phosphate and/or vitamin D. Five (45%) patients had persisting symptoms despite FAEs discontinuation.ConclusionsFAEs treatment can cause drug-induced Fanconi syndrome, but the association has been reported infrequently. Female patients with psoriasis treated long term with FAEs seem to be particularly at risk. Physicians treating patients with FAEs should be vigilant and monitor for the potential occurrence of Fanconi syndrome. Measurement of the urinary albumin:total protein ratio is a suggested screening tool for tubular proteinuria in Fanconi syndrome.

Renal dysfunction in patients taking fumaric acid esters – a retrospective cross‐sectional study

“…One recent case series supports this trend. 12 This suggests that patients who develop PTD may have been treated more aggressively with higher doses of FAE used for a longer duration of time in the context of a lower bodyweight.…”

“…Common side‐effects of FAE include gastrointestinal upset, hot flushes and lymphopaenia. There are seven cases reported in the literature linking FAE with nephrotoxicity such as Fanconi syndrome and acute renal failure . One large retrospective study of 984 patients showed a favourable safety profile with no cases of renal toxicity but the presence of proteinuria was not commented upon.…”

“…There are seven cases reported in the literature linking FAE with nephrotoxicity such as Fanconi syndrome and acute renal failure. [9][10][11][12] One large retrospective study of 984 patients showed a favourable safety profile with no cases of renal toxicity but the presence of proteinuria was not commented upon. Six per cent of their patients were noted to have an elevated creatinine.…”

Fumaric acid esters in combination with a 6-week course of narrowband ultraviolet B provides an accelerated response compared with fumaric acid esters monotherapy in patients with moderate-to-severe plaque psoriasis: a randomized prospective clinical stud

“…Mild‐to‐moderate side‐effects (nausea, diarrhoea, cutaneous flushing) are not uncommon, particularly during the induction phase of treatment, and are usually reversible upon a temporary dose reduction. Severe side‐effects such as Fanconi syndrome or progressive multifocal leucoencephalopathy are very rare adverse events that almost exclusively occur in patients with a lack of regular laboratory monitoring …”

Acquired renal glucosuria in an undifferentiated connective tissue disease patient with a SLC5A2 heterozygous mutation

“…[1] The causes of renal glucosuria include a wide range of insults to proximal tubular cells, including genetic conditions, drugs, and poisons. [2] Mostly, the inherited form of this disorder is called familial renal glucosuria (FRG), which is a rare renal tubular disorder due to autosomal recessive mutations in the SLC5A2 gene located on human chromosome 16p11.2. [3,4] The SLC5A2 gene encodes the low-affinity sodium/glucose cotransporter SGLT2, which is responsible for most glucose reabsorption in the kidney.…”