Churg–Strauss syndrome with severe granulomatous angiitis and crescentic glomerulonephritis, which developed during therapy with a leukotriene receptor antagonist

Abstract

A 77-year-old Japanese female developed Churg-Strauss syndrome (CSS), showing fever and numbness in bilateral hands. She was being treated for bronchial asthma with combination inhalant of corticosteroid with beta(2)-agonist, and an oral leukotriene receptor antagonist (LTRA), montelukast, for 15 months. She presented fever up to 38°C with microscopic hematuria and proteinuria, serum creatinine level of 0.7 mg/dl, and C-reactive protein of 11 mg/dl. After referral to our hospital, eosinophilia and high myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) level were observed together with hematuria and proteinuria; renal biopsy examination was performed to clarify the disorder. Renal biopsy specimens showed necrotizing crescent formation, severe granulomatous angiitis in an interlobular artery, and interstitial eosinophilic infiltration. It was noted that nearly intact glomeruli were infiltrated with eosinophils. After treatment with oral prednisolone at initial dose of 40 mg (1 mg/kg body weight), urinary findings rapidly became normal with mild elevation of serum creatinine to 1.5 mg/dl and trace level of serum C-reactive protein in 1 month. Because she was previously treated with montelukast without oral corticosteroid, linkage between CSS and LTRA was highly suspected.

Churg-Strauss Syndrome Presenting with Acute Renal Insufficiency Accompanied by Eosinophilic Tubulointerstitial Nephritis

“…In described cases, extracapillary proliferation in more than 50% of glomeruli was present in 10 of 19 patients (53%). An eosinophil-rich interstitial infiltration was present in 18 of 31 patients (58%), 13 of them had eosinophilic tubulointerstitial nephritis (patients 5,6,7,8,15,17,20,21,22,23,24,28 and the present patient), including 2 eosinophilic tubulointerstitial nephritis cases without glomerular involve- . All patients were treated with corticosteroids, in association with immunosuppressive drugs.…”

Successful Multidrug Treatment of a Pediatric Patient with Severe Churg-Strauss Syndrome Refractory to Prednisolone

“…It has been postulated that the occurrence of CSS in some patients treated with leukotriene modifiers may be related to a residual underlying vasculitic syndrome (Boyer et al 2006;Salerno et al 2010). However, some case reports have suggested clear causal association between the use of leukotriene modifiers and CSS (Kobayashi et al 2003;Kanda et al 2010). In our patient, CSS occurred following significant hypereosinophilia, which developed after a 6-month course of pranlukast treatment, which is similar to a previous report by Kobayashi et al (2003).…”

“…Since massive use of corticosteroids increases the risk of intestinal perforation (Venditti et al 2011), we suggest that an aggressive immunosuppressive regimen including Tac is beneficial for children with refractory CSS like our case, although further studies are needed. Some previous reports have suggested a potentially causal relationship between treatment with leukotriene modifiers and the onset of CSS (Kobayashi et al 2003;Boyer et al 2006;Kanda et al 2010;Salerno et al 2010,). It has been postulated that the occurrence of CSS in some patients treated with leukotriene modifiers may be related to a residual underlying vasculitic syndrome (Boyer et al 2006;Salerno et al 2010).…”

“…From the clinical course of our patient, marked eosinophilia emerged 5 months after the start of pranlukast, as described in the case presentation. Recently, Kanda et al reported on an interesting adult patient with CSS, which occurred following a 15-month course of montelukast treatment (Kanda et al 2010). They speculated that leukotriene modifiers block the effects of the cysteinyl leukotrienes but not the effects of leukotriene B4, which is a chemoattractant for eosinophils and neutrophils, and this theory may be attributable to the onset of CSS in their patient (Kanda et al 2010).…”

“…Recently, Kanda et al reported on an interesting adult patient with CSS, which occurred following a 15-month course of montelukast treatment (Kanda et al 2010). They speculated that leukotriene modifiers block the effects of the cysteinyl leukotrienes but not the effects of leukotriene B4, which is a chemoattractant for eosinophils and neutrophils, and this theory may be attributable to the onset of CSS in their patient (Kanda et al 2010). Since our patient presented with HES/CSS possibly due to pranlukast administration, we postulate that the same mechanism may be applicable in our patient, although this remains speculative.…”