Strauss Syndrome Research Articles

Diagnosis and management of pulmonary vasculitis

The pulmonary vasculitides are a heterogeneous group of disorders characterized pathologically by vascular destruction with cellular inflammation and necrosis. These disorders can affect small, medium, and large vessels and may be primary or occur secondary to a variety of conditions. Vasculitis involving the lungs is most commonly due to primary, idiopathic, small-vessel antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides, which includes granulomatosis with polyangiitis (formerly Wegener's granulomatosis), Churg-Strauss syndrome, and microscopic polyangiitis. From a clinical perspective these remain among the most challenging of diseases both in terms of diagnosis and treatment. This review will focus on diagnosis and management of ANCA-associated vasculitides.

Churg–Strauss syndrome manifesting as cholestasis and diagnosed by liver biopsy

A 56-year-old woman was referred to our hospital due to fever and cholestatic liver dysfunction. Her eosinophil count was normal and she had no abdominal pain or neurological manifestations. We performed a liver biopsy and found fibrinoid necrosis of the hepatic artery with granulomatous reaction and eosinophilic infiltration in the portal area in the liver. Later, sensory abnormalities of the arms and legs appeared and the eosinophil count increased. Serum immunoglobulin E and immunoglobulin G4 were elevated and rheumatoid factor was strongly positive. Endoscopic retrograde cholangiopancreatography revealed no abnormality of the bile duct and pancreatic duct. We made a diagnosis of Churg-Strauss syndrome and began corticosteroid treatment. Fever and liver function immediately improved. In the present patient, Churg-Strauss syndrome manifested first in the liver, before hypereosinophilia and neural manifestations. We believe that Churg-Strauss syndrome is an autoimmune liver disease, and it is important to recognize that the liver may be involved in Churg-Strauss syndrome.

Parotid, breast, and fascial involvement in a patient who fulfilled the ACR criteria for Churg–Strauss syndrome

Churg–Strauss syndrome (CSS) is a rare, systemic, necrotizing vasculitis of small vessels that occurs in subjects with a background of asthma, allergic rhinitis, and/or nasal polyps (1). Lungs, ski...

Increased production of IL-5 and dominant Th2-type response in airways of Churg–Strauss syndrome patients

Churg-Strauss syndrome (CSS) is a rare systemic vasculitis associated with eosinophilia and asthma. We assessed the local immune response in airways of CSS patients with different activity of the disease. Concentration of IL-5, CCL17, CCL22 and CCL26 (ELISA) together with cell expression of T-helper-related genes (real-time PCR array) were measured in bronchoalveolar lavage fluid (BALF) sampled from 11 patients with active CSS, 11 patients with CSS in remission and 9 control subjects with bronchial asthma. In active CSS, both BALF and blood eosinophil counts were increased (P<0.01). BALF cells in active disease were characterized by an increased expression of Th2 and regulatory-type transcripts: STAT6, STAT3, GATA3, IL4, IL5 and IL10 as compared with asthmatics, and STAT5A, CCR4, FOXP3, IL4, IL5 and IL10 when compared with inactive CSS. There was significant increase in BALF concentration of IL-5 and CCL26 in exacerbation of CSS. CCR4-active chemokines were detected more frequently in active disease. We found a strong positive correlation between clinical parameters of disease activity (BVAS, eosinophilia) and expression of IL4, IL5, IL10 and STAT5A. These results indicate that as compared with asthma, active-CSS patients have much stronger local Th2 response in the airways. Airway cells may contribute to lung eosinophilia in CSS by producing IL-5 and eosinophil active chemokines.

Hypereosinophilic Syndrome, Churg-Strauss Syndrome and Parasitic Diseases: Possible Links between Eosinophilia and Thrombosis

Throughout the past decade, a possible role of eosinophils in blood coagulation and thrombosis has been suggested. We conducted a Pubmed (MEDLINE) search of case and series referring to any kind of thrombotic events described in three conditions characterised by persistent blood eosinophilia, i.e. the hypereosinophilic syndrome (HES), the Churg Strauss syndrome (CSS), and parasitic infestations from 1966 to date. One hundred and ninety-two articles were found regarding thrombotic events in HES and CSS, and 209 cases of thrombosis were extracted. One hundred and seventy- seven articles dealing with parasitic diseases and thrombosis were found, but only 15 manuscripts reporting thrombosis of unknown origin in 22 patients were selected. In HES, arterial thromboses were more frequent than in CSS (p=0.006), representing almost half of the cases (45%), while venous and mixed artero-venous thrombosis were respectively 28% and 27%. In contrast, in CSS there was a predominance of venous thrombosis (56%, p=0.006), with arterial thrombosis representing 38% of total thrombotic events, and mixed thrombosis being the least frequent (4%). The higher incidence of arterial thrombosis in HES patients can be explained by the common cardiac involvement (64% of patients). In the 22 patients with parasitoses and thrombosis, 15 had arterial thrombosis (68%) and 7 had venous thrombosis (32 %). Literature analysis shows that there are numerous reports of thrombotic events in patients with eosinophil-related disorders supporting a role for eosinophils in thrombosis. This observation raises the problem of prevention and treatment of thromboembolism particularly in HES and CSS patients.

Subarachnoid haemorrhage from PICA aneurysm rupture in a Churg–Strauss patient: A case report and a review of the literature

Churg–Strauss syndrome (CSS) is a systemic small vessel vasulitis, typically presenting as bronchial asthma, eosinophilia nd peripheral neuropathy and occasionally involving the cenral nervous system (CNS). CSS presenting with a subarachnoid emorrhage (SAH) is particularly rare. We report the case of a 64ear-old woman affected by CSS experiencing left Posterior Inferior erebellar Artery (PICA) aneurysm bleeding, requiring two-step ndovascular treatment due to aneurysm recurrence. We reviewed he literature and analyzed the potential correlations between a ecurrent, documented increase of vasculitis markers, aneurysm upture and aneurysm recurrence.

Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases

IgG4-related disease (IgG4-RD) is a novel disease entity that includes Mikulicz’s disease, autoimmune pancreatitis (AIP), and many other conditions. It is characterized by elevated serum IgG4 levels and abundant IgG4-bearing plasmacyte infiltration of involved organs. We postulated that high levels of serum IgG4 would comprise a useful diagnostic tool, but little information is available about IgG4 in conditions other than IgG4-RD, including rheumatic diseases. Several reports have described cutoff values for serum IgG4 when diagnosing IgG4-RD, but these studies mostly used 135 mg/dL in AIP to differentiate from pancreatic cancer instead of rheumatic and other common diseases. There is no evidence for a cutoff serum IgG4 level of 135 mg/dL for rheumatic diseases and common diseases that are often complicated with rheumatic diseases. The aim of this work was to re-evaluate the usual cutoff serum IgG4 value in AIP (135 mg/dL) that is used to diagnose whole IgG4-RD in the setting of a rheumatic clinic by measuring serum IgG4 levels in IgG4-RD and various disorders. We therefore constructed ROC curves of serum IgG4 levels in 418 patients who attended Sapporo Medical University Hospital due to IgG4-RD and various rheumatic and common disorders. The optimal cut-off value of serum IgG4 for a diagnosis of IgG4-RD was 144 mg/dL, and the sensitivity and specificity were 95.10 and 90.76%, respectively. Levels of serum IgG4 were elevated in IgG4-RD, Churg–Strauss syndrome, multicentric Castleman’s disease, eosinophilic disorders, and in some patients with rheumatoid arthritis, systemic sclerosis, chronic hepatitis, and liver cirrhosis. The usual cut-off value of 135 mg/dL in AIP is useful for diagnosing whole IgG4-RD, but high levels of serum IgG4 are sometimes observed in not only IgG4-RD but also other rheumatic and common diseases.

Churg–Strauss, a rare cause of intracerebral haemorrhage

Intracerebral haemorrhage (ICH) is a common and devastating condition. We describe a 43-year-old man with the rare Churg–Strauss syndrome, which was diagnosed after he presented with an ICH. He was managed initially neurosurgically with clot evacuation and craniectomy. Post-investigation and diagnosis of Churg–Strauss, treatment was with high dose methylprednisolone (then oral prednsiolone) and intravenous cyclophosphamide. Clinicians should be aware that Churg–Strauss syndrome can, rarely, be a cause of ICH. Given its high morbidity and mortality, it is important that patients are diagnosed promptly and managed appropriately.

CCR4-active chemokines contribute to blood and tissue eosinophilia in Churg–Strauss syndrome

CCR4-active chemokines contribute to blood and tissue eosinophilia in Churg–Strauss syndrome

Cardiac denervation procedure to treat refractory angina in a patient with Churg-Strauss syndrome and non-obstructive coronary lesions

Cardiac involvement in Churg-Strauss syndrome is common and represents the main cause of mortality. We report the case of a patient with Churg-Strauss vasculitis, mitral regurgitation with left ventricular dysfunction, paroxysmal atrial fibrillation and refractory angina with non-significant coronary lesions. Cardiac denervation was proposed as an associated procedure to treat angina. The total removal of peri-adventitial and adventitial tissue around the superior vena cava, ascending aorta and main pulmonary trunk was performed. After 3 months of follow-up, the patient was angina-free and could resume his normal lifestyle.

Occam’s razor reveals a hidden Churg-Strauss syndrome

Abstract A 28 year-old caucasian lady, with nine years of uncontrolled bronchial asthma, rhinosinusitis and mild upper limb paresthesia, came to our attention to be followed for coeliac disease (CD). She had a biopsy performed elsewhere which proved the diagnosis five years before. Since there was no clinical improvement on a strict gluten-free diet, we re-evaluated the slides of her duodenal biopsies and we found an overestimation of the duodenal lesions due to the wrong orientation of the specimens. Moreover, she had never had positive CD-related antibodies and she was negative for DQ2/DQ8 MHC Class II heterodimers. Months later, she referred she was suffering from diffuse joint pain, epistaxis and a substantial weight loss. A few days later she was hospitalized because of a sudden onset of dyspnea, peripheral edema and pleural effusion. Her echocardiogram showed global left ventricular hypokenesia with an ejection fraction of 24%. The patient was discharged with a diagnosis of dilated cardiomyopathy and NYHA Class II. After a large spectrum of haematological exams, the diagnosis of Churg Strauss Syndrome (CSS), a rare multisystemic small-vessel necrotizing vasculitis, was confirmed by the presence of four/five out of six diagnostic American College of Rheumatology classification criteria (Asthma, Eosinophilia &gt;10%, Neuropathy, Non-fixed pulmonary infiltrates, Paranasal sinus abnormality and Biopsy containing a blood vessel with extravascular eosinophils). Our patient had been under-diagnosed by pulmonologist and by gastroenterologists although she presented the criteria required for CSS diagnosis. Our case report emphasizes that often seemingly unrelated symptoms can be caused by a single rare clinical complex.

Combined Churg–Strauss syndrome and allergic bronchopulmonary aspergillosis – case report and review of the literature

A rare case of combined Churg-Strauss syndrome (CSS) and allergic bronchopulmonary aspergillosis (ABPA) was presented. A 41-year-old woman was diagnosed with CSS based upon asthma, eosinophilia (23%), chest radiographic findings, paranasal sinusitis, peripheral neuropathy and positive p- anti-neutrophil cytoplasmic antibodies (pANCA). The diagnosis of ABPA was established on the pathological findings of allegic mucin impaction and fungal hyphae on lung biopsy. It was further proved by positive serum IgE and IgG antibodies specific to afumigatus. The clinical investigation features were reviewed in the patients with combined CSS and ABPA. All patients had the time sequence of the development of CSS after ABPA uniformly, suggesting immunopathogenesis involving the emergence of CSS. The role of lung biopsy in the diagnosis of the condition was emphasized.

Vasculitis of the upper airways

Systemic vasculitides are rare and potentially life-threatening diseases. Granulomatosis with polyangiitis (GPA; formerly Wegener's granulomatosis) and Churg Strauss syndrome (possibly to be renamed eosinophilic granulomatosis with polyangiitis; EGPA) are the 2chief systemic vasculitides which may involve the upper respiratory tract. Chronic allergic rhinitis and nasal polyposis in EGPA, andrecurrent sinusitis and/or otitis in both conditions, are not specific and can thus represent real diagnostic challenges if they are the first manifestations of the disease. Nasal septum perforation, saddle nose deformity and/or subglottic stenosis (SGS), although not totally specific, are more suggestive of GPA. Because upper airway manifestations often tend to be refractory to systemic therapy and/or to linger, local treatment represents a major aspect of management of the condition, especially for patients with SGS.

Churg–Strauss syndrome: Case series

Churg–Strauss syndrome (CSS) is a systemic necrotizing vasculitis of the small and medium vessels, associated with extravascular eosinophilic granulomas, peripheral eosinophilia and asthma.This is a rare syndrome of unknown etiology, affecting both genders and all age groups.CSS patients usually respond well to steroid treatment, although relapses are common after it ends. Timely diagnosis and treatment generally lead to a good prognosis with a 90% survival rate at one year.A brief review of CSS is presented, with particular attention to diagnosis, therapy and recent developments in this area.The authors then report and discuss the clinical, laboratory and imaging characteristics of four patients admitted to an Internal Medicine Department with this diagnosis. The treatment, response and follow-up of the cases are also described.

Asymptomatic bilateral pulmonary embolism in Churg-Strauss syndrome

To the Editor: Churg–Strauss syndrome (CSS) is a systemic small-sized vessel vasculitis, characterised by severe asthma, transient pulmonary infiltrates, and blood and tissue eosinophilia [1]. CSS can affect several organs, including the lungs, heart, kidneys and peripheral nervous system. Anti-neutrophil cytoplasm autoantibodies (ANCA) mainly directed against myeloperoxidase (MPO) are detected in ∼40% of patients and are associated with renal involvement. Several studies have focused on venous thromboembolic events (VTE), which are an emerging clinical condition in ANCA-associated vasculitides (AAV) [2, 3]. Herein, we report the case of a patient with newly diagnosed CSS and totally asymptomatic pulmonary embolism, and discuss the features, pathogenesis and management of VTE in CSS. In February 2011, a 61-yr-old male was referred for recent asthenia, diffuse arthromyalgia and blood eosinophilia. His past medical history included high blood pressure treated with amlodipine. There were no other risk factors for VTE other than age and inflammatory state. His recent history included late-onset asthma, which started 1 yr earlier and required various combined inhaled corticosteroids, bronchodilators and several short courses of oral corticosteroids. In early December 2010, the patient complained of general weakness, weight loss and diffuse myalgia. In late December, another asthma flare-up was successfully treated with a course of oral prednisolone (1 mg·kg−1 per day for 5 days), which was effective for both myalgia and weakness. Unfortunately, muscle and joint pain immediately relapsed as soon as corticosteroids were discontinued, while respiratory symptoms had improved. In February 2011, a thoracic computed tomography (CT) scan was performed, focusing on the parenchyma not vessels. No lesions were reported. At the same time, distal paresthesia appeared and subsequently concerned the lower left and upper right limbs. Following this, the patient was referred to our department (Internal Medicine …

A break in the glomerular basement membrane in Churg–Strauss syndrome

Breaks in the glomerular basement membrane (GBM) have been focused on as a significant contributor to the leakage of fibrin and/or fibrinoid material into the Bowman’s space, thereby accelerating crescent formation in various types of glomerular disease [1]. We would like to show our serendipitous finding of a break in the GBM discovered during routine diagnostic transmission electron microscopy in a 52-year-old male patient presenting with Churg–Strauss syndrome (CSS). He was admitted to our hospital due to a protracted fever, fatigue, and muscle pain of the extremities that had lasted 2 months. More than two decades prior to admission, he was found to have bronchial asthma, for which he had received sporadic medical care including the administration of montelukast, a leukotriene receptor antagonist (LTRA). Laboratory analysis revealed a white blood cell count of 8700/ll with 8.9% eosinophils, serum creatinine of 1.01 mg/dl, and serum immunoglobulin (Ig) E of 6531 mg/dl. An increase in the titer of anti-myeloperoxidase anti-neutrophil cytoplasmic antibody (MPOANCA) of 12.1 U/ml (the positive cut-off value is 9.0 U/ml), but not in anti-proteinase 3 ANCA or anti-GBM antibodies, was also found. His urine demonstrated microscopic hematuria with red blood cell casts, and contained 0.2 g of protein in a 24 h specimen. The renal biopsy consisted of renal parenchyma with thirty-three glomeruli, five of which were globally sclerotic. The presence of cellular crescents with focal segmental necrotizing lesions was confirmed in seven of the remaining glomeruli (Fig. 1a). A granulomatous lesion associated with eosinophil infiltration was confirmed around the interlobular artery (Fig. 1b). Of note, transmission electron microscopy demonstrated a break in the GBM associated with fibrin and platelet extravasation in Bowman’s space; however, no evidence of immune complex deposition was confirmed (Fig. 1c). Consequently, he was diagnosed to have CSS, and intravenous methylprednisolone at a dose of 500 mg/day was given for three consecutive days, followed by oral administration of prednisolone at 30 mg/day. His clinical course was uneventful, and the prednisolone dose was gradually tapered. A potential association between LTRA and CSS has been proposed in several reports, while there is no information available regarding the casual impact of LTRA on the development of MPO-ANCA among patients with CSS [2]. Therefore, the pathogenesis of CSS with MPO-ANCA in the current case should be evaluated carefully. Nevertheless, it is reasonable to consider that MPO-ANCA might act by modifying in a subset of patients with CSS, and contribute directly to the development of glomerular injuries. Indeed, it has been reported that the association of ANCA positivity with a clinical phenotype including inflammation, necrosis of small vessels, and crescentic K. Iwazu T. Akimoto (&) E. Kusano Division of Nephrology, Department of Internal Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan e-mail: tetsu-a@jichi.ac.jp

PTPN22 R620W polymorphism in the ANCA-associated vasculitides

PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism (SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations. PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients [143 with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS)] and in 945 healthy controls. The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls [P = 0.005, χ(2 )= 7.858, odds ratio (OR) = 1.91], while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, χ(2 )= 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, χ(2 )= 7.258, OR = 1.98), lung involvement (P = 0.0060, χ(2 )= 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, χ(2 )= 16.567, OR = 3.73). The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset.

Patient with Churg Strauss Syndrome and Myocarditis Treated with Cyclophosphamide

Cardiac involvement in Churg Strauss Syndrome is common and a poor prognostic indicator. Myocarditis in Churg Strauss Syndrome can present in different ways. It has been shown that basic cardiac investigations including echocardiography can be normal even in symptomatic patients. More recently cardiac magnetic resonance imaging (MRI) has been shown to be more sensitive in its diagnosis. Our case report describes a 45 year old male who presented with palpitations and breathlessness. Echocardiography was normal but cardiac MRI demonstrated abnormalities consistent with Myocarditis. He was treated with Cyclophosphamide and follow up MRI imaging demonstrated complete resolution of these abnormalities which was accompanied by resolution of symptoms. This case therefore supports the use of cardiac MRI in Churg Strauss Syndrome as a sensitive diagnostic tool in and as a means of monitoring response to therapy. It also supports the therapeutic effectiveness of Cyclophosphamide therapy in Churg Strauss related Myocarditis, something that has yet to be assessed on a large scale.

Leukocytoclastic vasculitis: A window to systemic Churg Strauss syndrome

A twenty year old male presented with purpuric lesions with chronic painful ulcers over the lower extremities and a recurrent pruritic rash on the trunk for 10 years. He was diagnosed as idiopathic leukocytoclastic vasculitis (LCV) after investigations failed to reveal a systemic association. He was treated with immunosuppressants at each visit with partial remission. In 2004, he was diagnosed with bronchial asthma and allergic rhinitis. In his recent admission, he showed necrotic ulcers on legs and extensive shiny, truncal micropapules. Examination revealed maxillary sinus tenderness and loss of sensation on the medial aspect of the left lower limb. Biopsy of ulcer and the micropapules showed the presence of extravascular eosinophils, while hematological investigations showed peripheral eosinophilia of 18%, raised serum Immunoglobulin E (IgE), Anti nuclear antibody (ANA) positivity and negative antineutrophil cytoplasmic antibody (ANCA). Radiography confirmed maxillary sinusitis, nerve conduction studies revealed mononeuritis of the anterior tibial nerve and pulmonary function tests (PFT) were normal. Clinical examination and investigations pointed towards the diagnosis of Churg-Strauss syndrome (CSS). This report highlights the development of full-blown CSS over a period of 12 years in a patient initially diagnosed as idiopathic LCV, emphasizing the need for regular follow-up of resistant and recurrent cases of LCV.

Churg Strauss syndrome

The patient is a known case of Asthma with marked peripheral eosinophilia developed recurrent haemoptysis and lung infiltrates. Bronchoscopic lavage and FNAC of lung showed pulmonary eosinophilia. Due to raised IgE levels and strongly positive pANCA, the case was diagnosed as Churg Strauss syndrome. He responded well to corticosteroids with complete resolution and is presently on the tapering doses.