Churg-Strauss syndrome (allergic granulomatous antiitis) with multiple perforating ulcers of the small intestine,multiple ulcers of the colon,and mononeuritis multiplex

A case of Churg-Strauss syndrome with multiple perforations of the small intestine is described. A 31-year-old woman was admitted with a complaint of epigastric pain. She had a history of bronchial asthma. One week before admission, white blood cell count was 20 800/mm³ with 59% eosinophils. Neurological examination on admission disclosed mononeuritis multiplex with paresthesia in both the lower and upper extremities. At colonoscopy, there were scattered aphthous ulcers in the colon. Ophthalmological examination revealed allergic conjunctivitis. After admission, hypereosinophilia increased to as high as 36 000/mm³. Oral administration of prednisolone (60 mg/day) was begun. On the 3rd day of the treatment, the eosinophil count decreased dramatically, to 400/mm³, while severe abdominal pain developed. Since abdominal X-ray film revealed free air in the abdominal cavity, emergency laparotomy was performed and multiple intestinal ulcers with perforations were found. Partial ileectomy was performed. Pathological findings of the resected specimen were interpreted as a necrotizing angiitis with extravascular granuloma. Since the operation, the patient has been asymptomatic, except for neurological symptoms. Hypereosinophilia has decreased without treatment to counts averaging 270/mm³, within 3 months. On the basis of the clinical features and histopathological findings, a diagnosis of Churg-Strauss syndrome was established.     

A Case with Multiple Colonic Ulcers Simulating Churg-Strauss Syndrome

Abstract: Churg-Strauss syndrome (CSS), a relatively rare disorder which is associated with serious complications, has a highly variable course and several possible manifestations. We present the case of a 35-year-old woman with a history of bronchial asthma, admitted for evaluation of lower abdominal pain and melena, whose clinical course had certain features in common with CSS. On admission, the white blood cell count was 45,300/mm³ with 65% eosinophils, and the serum immunoglobulin E (5,300 u/ml) level was remarkably elevated. At colonoscopy, there were shallow ulcers, irregular in shape, throughout the large intestine. Abdominal pain and melena were relieved by oral administration of prednisolone. Most previously reported cases have not been recognized as having colonic involvement until surgery or autopsy. In only a few reports of CSS and related disorders were colonoscopic examination findings described.     

Early‐Stage Loeffler's Endocarditis with Isolated Right Ventricular Involvement: Management,Long‐Term Follow‐Up,and Review of Literature

Loeffler's endocarditis is a clinical condition characterized by combination of three key findings: unexplained prolonged and marked eosinophilia (>1500 eosinophils/mm³), absence of a primary cause of hypereosinophilia, and evidence of eosinophil‐mediated organ damage. We report a case of a 55‐year‐old African American male with symptoms of heart failure. Hematology showed white blood cell count of 17 670/mm³ with 63% eosinophils and an absolute eosinophil count of 11 133/mm³. Echocardiogram and computed tomography showed near complete obliteration of right ventricular cavity. Endomyocardial biopsy showed diffuse myocyte necrosis with extensive eosinophilic infiltration without fibrosis consistent with early Loeffler's endocarditis. Molecular and cytogenetic analyses of bone marrow cells were negative for FIP1L1‐PDGFRA fusion, PDGFRB mutation, abnormal myeloid maturation, or a lymphoproliferative disorder. Flow cytometry showed no clonality excluding chronic eosinophilic leukemia. There was a complete resolution of symptoms and eosinophilia after 1 month of steroid therapy.     

Colonoscopic and histologic features of colonic Crohn's disease in Chinese patients

OBJECTIVE: An attempt was made to provide a better insight into endoscopic and histological features and to enhance the understanding of the diagnostic value of colonoscopy combined with biopsy for colonic Crohn's disease. METHODS: As presented in our 27 cases of colonic Crohn's disease (Crohn's colitis), the endoscopic findings and histological changes of biopsy specimens were analyzed. As collated with correspondent results of biopsy and surgical specimens, the diagnostic accuracy of endoscopy was evaluated. RESULTS: Of these patients, 26 involvements of the colon (often combined with other sites of the bowel) were observed (96.3%). However, involvements limited to the colon alone were seen in only four cases (14.8%). Endoscopically, diverse patterns of multi‐staged‐segmental distributed and multi‐sited inflammatory lesions, both destructive and proliferative/regenerative changes were observed in the bowel of the same patient. The diaganostic accuracy of colonoscopy, as confirmed by the histological examination of biopsy and resected specimens, was 66.7%. The major characteristic features of mucosal biopsy were the focal distribution of inflammatory infiltration and lymphoid aggregate. Otherwise, it may include edematous and widened submucosa, deep fissuring ulcers and hyperplasia, fibrosis and granulomas (detected in 30% of the group), among others. CONCLUSION: The colonic involvement of Crohn's disease was common. Colonoscopy may be valuable in establishing a diagnosis and in assessing the extent and severity of such colonic involvement. Biopsy is helpful to confirm a diagnosis conducted by colonoscopy. Colonoscopy combined with biopsy may replace radiology as the initial test of choice in many clinical situations.     

Churg-Strauss syndrome with pulmonary eosinophilia and intrapulmonary lymph nodes 2 years before the onset of vasculitis]

We report a case of a 55-year-old man who had been treated for bronchial asthma diagnosed at the age of 51. One year following diagnosis, chest X-ray films disclosed nodular shadows. Biopsy specimens obtained by video-assisted thoracoscopic surgery were histopathologically identified as intrapulmonary lymph nodes. Three years after the initial diagnosis, the patient experienced sensory disturbance of the lower extremities, low-grade fever, and weight loss. At this point he was admitted to our hospital. On admission, physical examination and clinical investigations showed peripheral eosinophilia and signs of vasculitis. Specimens obtained by transbronchial lung biopsy and bronchoalveolar lavage showed strong evidence of tissue damage with infiltration of eosinophils but no evidence of necrotizing vasculitis or extra-vascular granuloma. Churg-Strauss syndrome (CSS) was diagnosed, and treatment was initiated with prednisolone at a dose of 60 mg/day. Except for the sensory disturbances in the lower extremities, after a few days of treatment the patient's symptoms subsided and his clinical data improved. This case was clinically important because pulmonary eosinophilic infiltration into vessel walls was confirmed a year after the diagnosis of bronchial asthma, and 2 years before the patient demonstrated signs of vasculitis. Further, it was a very rare case of CSS in which intrapulmonary lymph nodes had developed beneath the visceral pleura despite the absence of a history of heavy smoking, thus suggesting continuous stimulation by some as yet unknown antigen.     

Churg-Strauss syndrome complicated by colon erosion, acalculous cholecystitis and liver abscesses

We report on a case of Churg-Strauss syndrome (CSS) with colon erosion, cholecystitis and liver abscesses. A 21-year-old woman with a history of bronchial asthma for 3 years was admitted with a complaint of abdominal pain. Laboratory findings included remarkable leukocytosis and eosinophilia, and a colonoscopy revealed erosion from the rectum to the ileocecal region. In addition, a colonic biopsy specimen showed necrotizing vasculitis and marked eosinophilic infiltration. On the basis of the clinical features and histopathological findings, she was diagnosed with CSS and subsequently treated with oral prednisolone, after which the eosinophilia and abdominal pain disappeared. However, on the 15th d in hospital she developed cholecystitis and liver abscesses. She was therefore treated with antibiotics and as a result went into clinical remission.     

Churg-Strauss Syndrome with pleural involvement

A 51-year-old Japanese man with Churg-Strauss Syndrome (CSS) diagnosed by pleural biopsy is described. He was hospitalized because of high fever and bilateral knee, elbow and shoulder joint pain. Chest roentgenogram and chest computed tomography (CT) scan revealed bilateral massive pleural effusion. Pleural biopsy revealed eosinophilic infiltration and necrotizing granulomas. He was treated with oral prednisolone and his symptoms improved. This is the first report of CSS diagnosed by pleural biopsy.     

Pathogenesis of aphthoid ulcers in Crohn's disease: correlative findings by magnifying colonoscopy, electron microscopy, and immunohistochemistry.

BACKGROUND--The mechanism of ulceration in Crohn's disease remains unknown. AIMS--To clarify the role of the follicle associated epithelium (FAE) of colonic lymphoid nodules in the formation of ulcers in Crohn's disease. METHODS--After identification of colonic lymphoid nodules and aphthoid lesions by magnifying colonoscopy, 76 biopsy specimens were obtained from 10 patients with Crohn's disease and three patients with colonic lymphoid hyperplasia. This study correlated magnifying colonoscopic, electron microscopic, and immunohistochemical findings of biopsy specimens. RESULTS--In Crohn's disease, scanning electron microscopy of lymphoid nodules surrounded by a red halo without visible erosions by magnifying colonoscopy, showed surface erosions 150-200 microns in size. These lymphoid nodules with red halos had small erosions either light microscopically or electron microscopically in 18 of 21 specimens (86%). Correlation of scanning and transmission electron microscopy showed residues of FAE including M cells at the edges of the erosions. In immunohistochemical studies, HLA-DR antigen was limited in M cells of FAE in the patients with lymphoid hyperplasia without inflammatory bowel disease. In Crohn's disease patients in remission, however, HLA-DR antigen was strongly expressed over the entire FAE of lymphoid nodules with a red halo endoscopically, while the expression was weak and irregular in the mucosa surrounding the lymphoid nodules. HLA-DR was strongly expressed in the entire inflamed colonic mucosa in the active stage. CONCLUSION--The red halo appearance surrounding lymphoid follicles seems to precede visible aphthoid ulcers and suggests that ulcerations in Crohn's disease originate from FAE, possibly related to its physiological role as a portal of entry for potentially pathogenic agents.     

Discoidin domain receptor 1 contributes to eosinophil survival in an NF-kappaB-dependent manner in Churg-Strauss syndrome

Churg-Strauss syndrome (CSS) is a systemic disease that shows marked eosinophilia along with eosinophil infiltration in the tissue. Prolonged eosinophil survival plays an important role in the pathogenesis of CSS; however, its detailed molecular mechanism remains unclear. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase, and its ligand is collagen. DDR1 was expressed in human leukocytes and fibroblasts, and it plays an important role in leukocyte cytokine production and fibroblast survival in an NF-kappaB-dependent manner. In this study, we examined in vitro and in vivo eosinophil DDR1 expression and its function in CSS patients. The expression level of DDR1 was significantly higher in the eosinophils of CSS patients, and the predominant isoform was DDR1b. Immunohistochemical findings revealed that the tissue-infiltrating eosinophils expressed endogenous DDR1. In CSS patients, DDR1 activation inhibited Fas agonistic antibody-induced apoptosis and up-regulated Fas agonistic antibody-induced cytokine production of eosinophils in an NF-kappaB-dependent manner. Suppression of DDR1 expression in the eosinophils by using RNA interference and addition of the DDR1-blocking protein abolished these effects. We propose that DDR1 contributes to the eosinophil survival in the tissue microenvironment of CSS and that it might be involved in the development of CSS.     

Pulmonary involvement, pleural effusion, and electrocardiographic abnormality in hypereosinophilic syndrome]

A 47-year-old man was admitted to our hospital with complaints of cough and shortness of breath. Chest radiography showed infiltration of the right lung and left pleural effusion, the eosinophil count increased notably in the peripheral blood, sputum, and pleural effusion. Transbronchial lung biopsy revealed the invasion of eosinophils like eosinophilic pneumonia. Heart failure easily developed in this patient after the intravenous infusion. Myocardial involvement was suspected, and hypereosinophilic syndrome was diagnosed. After prednisolone was administered, the peripheral blood eosinophil count normalized rapidly, and subsequently, the pleural effusion and infiltration shadows in the lung disappeared.     

Case of eosinophilic granulomatous enterocolitis caused by Strongyloides stercoralis infection with marked hypoalbuminemia and ascites

We report a 10‐year‐old boy presenting with generalized pitting edema, ascites, abdominal pain, and chronic mucous diarrhea for 4 weeks. He had underlying diseases of hemoglobin E and juvenile rheumatoid arthritis and had been treated with immunosuppressive agents for a long period of time, including prednisolone and methotrexate. After extensive investigations, Strongyloides stercoralis infection, leading to protein‐losing enteropathy and eosinophilic granulomatous enterocolitis, was diagnosed. In the present report, we demonstrate early colonoscopic findings, revealing patchy erythema and small raised mucosal nodules with erosions at the cecum. Histopathological study showed open ulceration with cryptitis, intense infiltration of eosinophils and histiocytes with granuloma formation, in which Strongyloides stercoralis larvae were noted.     

Increased eosinophil infiltration and degranulation in colonic tissue from patients with collagenous colitis

OBJECTIVE: Eosinophils infiltrate the colonic mucosa of patients with collagenous colitis (CC), although the pathogenetic implications are unknown, including whether these eosinophils are activated and degranulate in situ. We examined eosinophil infiltration and degranulation in the intestines of patients with CC by immunofluorescence for eosinophil granule major basic protein (MBP). METHODS: We used both conventional histology (hematoxylin and eosin) and indirect MBP immunofluorescence histochemistry on colon biopsy specimens from patients with CC (n = 21) and from healthy controls (n = 9). Scoring of histological features was performed on hematoxylin and eosin-stained sections on a 0 to 3 scale. Eosinophil infiltration and degranulation, as quantified by extracellular MBP staining, were scored in each specimen on a 0 to 4 scale. RESULTS: The inflammatory infiltrate of the lamina propria, the thickness of the collagen band, the numbers of intraepithelial lymphocytes, and degree of epithelial cell damage were all significantly increased in patients with CC as compared to controls (p < 0.0001). Scores for both eosinophil infiltration and degranulation were also significantly higher in the CC group compared to controls (p < 0.0001). The degree of infiltrating eosinophils by hematoxylin and eosin was correlated with eosinophil infiltration and degranulation by MBP immunostaining; however, no other correlations were found between eosinophil infiltration or degranulation by immunofluorescence and any of the histological parameters measured in the CC group. CONCLUSIONS: Eosinophil infiltration and degranulation are increased in the colonic mucosa of patients with CC compared to healthy controls. Eosinophils and their cytotoxic granule proteins could be involved in the pathogenesis of CC. Further studies will be necessary to elucidate the mechanisms of eosinophil activation in CC.     

Bronchial biopsy and sequential bronchoalveolar lavage in atopic cough: In view of the effect of histamine H1-receptor antagonists

We have shown that some patients presenting with chronic bronchodilator-resistant non-productive cough have global atopic tendency, airway cough hyper-sensitivity without non-specific bronchial hyperresponsiveness and eosinophilic inflammation of the trachea and bronchi, abbreviated as atopic cough (AC). Histamine H₁ receptor antagonists are effective in relieving the cough in some patients with AC but not in others in whom corticosteroids are needed to improve the cough. The aim of the present study was to compare the intensity of eosinophil infiltration in biopsied bronchial submucosa and sequential bronchoalveolar lavage (SBAL) fluids between two subgroups of patients with AC: (i) group A, successfully treated with histamine H₁ receptor antagonists; and (ii) group B, requiring corticosteroids. Sequential BAL was performed using three 50 mL aliquots of physiologic saline solution and then bronchoscopic bronchial biopsy was performed in group A (n = 9) and B (n = 9) patients. Sequential BAL was also performed in normal controls (NC; n = 13). The first SBAL fraction was analyzed as bronchial lavage fluid (BLF) and the mixed fluid of the second and third SBAL fractions as bronchoalveolar lavage fluid (BALF). The number of eosinophils in the bronchial subepithelium was significantly (P = 0.0134) greater in group B patients (median 8.3 cells/mm²; range 3.6–21.9 cells/mm²) compared with group A (median 3.6 cells/mm²; range 0–10.0 cells/mm²). However, There were no significant differences in the number or percentage of eosinophils in BLF or BALF between group A, group B and NC subjects. These findings confirm that eosinophils do not infiltrate the peripheral airways of AC and suggest that corticosteroids are required to relieve the cough in more severe illness of AC, in which submucosal eosinophilic inflammation of the central bronchi is more intensive compared with the milder illness successfully treated with histamine H receptor antagonists.     

Eosinophilic pneumonia with eosinophilic gastroenteritis.

A 48-year-old man was admitted to our hospital with cough, fever and dysphagia. He had a past history of bronchial asthma and surgery for nasal polyp. Chest radiograph and computed tomography showed atelectasis in the right lower field and infiltrative shadow in the left lower field and overall thickening of the esophageal wall. Transbronchial lung biopsy (TBLB) specimens revealed infiltration of eosinophils and lymphocytes under the bronchial mucosa. Gastrointestinal tract biopsy specimens showed submucosal infiltration of eosinophils. These findings led to a definite diagnosis of eosinophilic pneumonia associated with eosinophilic gastroenteritis, a disease which has been rarely reported.     

A case of Jackhammer esophagus caused by eosinophilic esophagitis in which per-oral endoscopic myotomy resulted in symptom improvement

A 73-year-old female with a 6-month history of progressive dysphagia and chest pain was referred to our hospital. She underwent esophagogastroduodenoscopy, which revealed abnormally strong contractions in the distal esophagus. Esophageal biopsy specimens showed massive eosinophil infiltration into the epithelium, and high-resolution manometry (HRM) also demonstrated abnormally strong contractions in the distal esophagus. Based on these results, she was diagnosed with Jackhammer esophagus (JHE) due to eosinophilic esophagitis (EoE). Treatment was started with 5 mg/day of prednisolone (PSL), and the number of peripheral blood eosinophils quickly decreased without any improvement in the patient’s dysphagia. Esophageal biopsy specimens obtained after the PSL treatment showed the disappearance of eosinophils from the epithelium. However, abnormally strong contractions were still detected on HRM. Per-oral endoscopic myotomy (POEM) was performed to treat the JHE. Interestingly, the intraoperative esophageal muscle biopsy sample demonstrated massive eosinophil infiltration into the muscle layer. After the POEM, the patient’s symptoms improved, and abnormal contractions were no longer detected on HRM. The current case suggests that when EoE combined with an esophageal motility disorder are refractory to steroid therapy, clinicians should be aware that motility disorders can develop due to eosinophil infiltration deep into the esophageal muscularis propria.     

A case of Behçet's disease accompanied by colitis with longitudinal ulcers and granuloma

A 37‐year‐old female presenting with oral and genital ulcers and erythema nodosum on both arms was diagnosed as having Behçet’s disease. The symptoms resolved spontaneously. However, she was admitted to our hospital (Keio University Hospital) several months later because of fever, aphthous ulcers of the oral cavity, lower abdominal pain and frequent diarrhea. A colonoscopic examination revealed multiple ulcers including longitudinal ulcers in the ascending and transverse colon, and histological examination of biopsied specimens demonstrated non‐caseating epithelioid granuloma. Treatment with prednisolone and 5‐aminosalicylic acid was started, and the patient responded well clinically. One month later, a repeated colonoscopy confirmed that the lesions including longitudinal ulcers had disappeared. In this report, we describe our experience of this rare case of Behçet’s disease concomitant with colonic longitudinal ulcers and epithelioid granuloma, and discuss the difficulties in making a differential diagnosis, primarily with regard to Crohn’s disease.     

A case of eosinophilic cholangitis： Imaging findings of contrast-enhanced ultrasonography, cholangioscopy, and intraductal ultrasonography

A 38-year-old woman was referred to our institution due to epigastralgia. She presented with obstructive jaundice and eosinophilia. Endoscopic retrograde cholangiopancreatography showed diffuse narrowing from the distal common bile duct to the bifurcation of the hepatic ducts. An endoscopic plastic biliary stent was inserted; the specimen obtained from the common bile duct wall revealed dense infiltration by eosinophils. Treatment was started with prednisolone 60 mg daily. The patient＇s biliary stenosis and eosinophilia gradually improved. Eosinophilic infiltration in the lungs or stomach is relatively common, but it is rare in the common bile duct. Most of the reported cases of eosinophilic cholangitis presented with eosinophilia; our patient＇s eosinophil count was over 1000/mm^3. Since our patient had allergies to pollen and house dust, a relationship between the allergies and the eosinophilic cholangitis was suspected, but no cause was identified.     

Colonoscopy evaluation after short-term anti-tuberculosis treatment in nonspecific ulcers on the ileocecal area

AIM： TO evaluate the efficacy of colonoscopy follow-up after short-term anti-tuberculosis treatment in patients with nonspecific ulcers on ileocecal areas being suspicious of tuberculous colitis. METHODS： We prospectively analyzed the colonoscopic findings before and after short term anti- tuberculosis treatment in 18 patients with nonspecific ulcers on the ileocecal area and compared them with 7 patients of confirmed tuberculous colitis by acid-fast bacilli or caseating granuloma on colonic biopsy. RESULTS： Mean duration for short-term follow- up was 107.3 d with combined chemotherapy containing isoniazid, rifampicin, ethambutol and pyrazinamide. Seven patients with tuberculous colitis showed complete healing of active ulcers after short-term medication. After short-term anti-tuberculosis treatment, follow-up colonoscopy findings devided 18 patients with nonspecific ulcers into two groups by ulcer state. One is the ＂suspicious tuberculous colitis group＂ showing healing of ulcers and erosions and another is the ＂suspicious inflammatory bowel disease group＂ showing active ulcers with or without aggravation of the lesion. Finally, all 9 of the ＂suspicious tuberculous colitis group＂ were diagnosed as tuberculous colitis showing no recurrence of ulcers after termination of 9 mo of anti-tuberculosis medication. Patients of the ＂suspicious inflammatory bowel disease group＂ were finally diagnosed as Crohn＇ s disease or nonspecific colonic ulcers during long-term follow up, CONCLUSION： Follow-up colonoscopy shows a healing stage ulcer or scarring change without an active ulcer with just 2 mo to 3 mo of medication in patients with tuberculous colitis. Colonoscopy follow-up after short term anti-tuberculosis trial in patients with nonspecific ulcers on the ileocecal area is valuable in making early differential diagnosis of tuberculous colitis.     

CYTOMEGALOVIRUS‐ASSOCIATED GASTRIC ULCERS IN IMMUNOCOMPROMISED PATIENTS

Gastric ulceration is a rare manifestation of cytomegalovirus (CMV) infection in the immunocompromised host. Two cases with CMV‐associated gastric ulcers in immunocompromised patients are reported. Case 1 involved a 65‐year‐old male who underwent a cadaveric renal transplantation because of chronic renal failure. He was treated with immunosuppressive agents and steroids. After 3 months of the treatment, he developed CMV‐associated gastric ulcers with evidence of CMV inclusion bodies, CMV antigen and CMV–DNA in the gastric ulcers. After three courses of ganciclovir therapy for 5 months, endoscopic images revealed complete healing of the gastric ulcers. This case supports the use of ganciclovir, which can lead to complete healing of gastric ulcers caused by CMV. Case 2 involved a 69‐year‐old male with interstitial pneumonia who was admitted to hospital because of rapid progression of interstitial pneumonia. He was treated with repeated pulses of methylprednisolone and cyclophosphamide. He developed CMV‐associated gastric ulcers with evidence of CMV inclusion bodies, CMV antigen and CMV–DNA in the gastric ulcers after 1 month of the treatment with high doses of methylprednisolone and cyclophosphamide. Endoscopic images revealed multiple ulcers and erosions in the gastric antrum. Ganciclovir treatment was started, but he died of interstitial pneumonia. In this case, the ulcers were considered to be precipitated by CMV infection and the use of a high dose methylprednisolone. These cases emphasize the need for a careful histological examination for CMV in gastric ulcers in immunocompromised patients.     

9 Contemporary radiological examination of the lower gastrointestinal tract

The morphological spectrum of colonic disease is wide. Various treatment modalities may influence the macroscopic aspect of colonic lesions and render a pathological differential diagnosis occasionally difficult or impossible. Before starting therapy in patients suspected of having colonic disease, a physician should undertake a thorough radiological and endoscopic evaluation of the extent and severity of disease activity in the large bowel (Ruderman and Farmer, 1987).DCBE and colonoscopy are complementary imaging modalities, each test has its own intrinsic advantages and merits (Lichtenstein and Rothstein, 1991). DCBE remains the cornerstone in the detection of fistulas, strictures, perforations and estimating depth of ulcerations. Colonoscopy and biopsy remain the most sensitive imaging modalities to identify mucosal involvement (Dijkstra, 1992). The main clinically relevant discrepancies between colonoscopy and DCBE consist of inflammatory lesions without distortion of the mucosal relief and inflammation in the form of small, superficial erosions and ulcers (Dijkstra, 1992).