Spectrum of hypereosinophilia syndrome based on 2 clinical case reports

BACKGROUND: Two severe cases of hypereosinophilic syndrome with cardiopulmonary symptoms, erythema nodosum, eosinophilic ileocolitis and paresthesia are reported. Definition, etiology, pathophysiological mechanisms, types, complications and therapeutic approaches of this relatively rare clinical disorder are discussed on the basis of these two cases. The distinction between eosinophilia and hypereosinophilic syndrome is clearly defined. DIFFERENTIAL DIAGNOSIS: The 2 cases of hypereosinophilic syndrome demonstrate the difficulty to decide whether they represent the idiopathic or the reactive type of hypereosinophilic syndrome. If the assumption is made in favor of the reactive type of hypereosinophilic syndrome the assumed prognosis could eventually be too promising. In case of an assumed idiopathic type of hypereosinophilic syndrome the search for causing factors like allergens could be left out. The decision concerning the type of hypereosinophilic syndrome of the 2 cases reported was made with high probability. In the case of idiopathic hypereosinophilic syndrome, eosinophilic leukemia was excluded by bone marrow biopsy. CONCLUSION: In order to be able to make a diagnosis it is necessary to search carefully for causing and influencing factors of the hypereosinophilic syndrome such as allergens or medicaments and to eliminate them. The hypereosinophilic syndrome must be put under frequent control in order to avoid complications or to start with therapeutic approaches in time.     

Idiopathic and symptomatic hypereosinophilic syndromes (their comparative characteristics based on 14 cases)

Clinical, hematological, cytogenetic and pathohistological findings in 14 patients with high eosinophilia allowed the authors to distinguish 2 groups of patients: with symptomatic (secondary) and idiopathic hypereosinophilic syndromes (6 and 8 patients, respectively). The latter was characterized by hepato- and splenomegaly, specific cardiac lesion (thromboplastic endocarditis), non-infectious fever, anemia and thrombocytopenia, marked hypercellularity of the bone marrow with inhibition of erythro- and megakaryocytopoiesis. Ph'-chromosome occurred in 2 out of 8 cases. Biopsy and autopsy histology in all cases of idiopathic hypereosinophilic syndrome were typical for myeloproliferative diseases. In symptomatic hypereosinophilic syndrome the above features were not registered.     

Eosinophilic pulmonary arteritis in a full-term fetus with hypereosinophilia

The case refers to a term-fetus, small-for-date, with polydramnios, idiopathic hypereosinophilic syndrome and eosinophilic vasculitis of large, medium and small-size pulmonary arteries. The pulmonary arteritis was the only lesion observed in the fetus.     

Advised follow-up after emergency treatment of adolescents with violence-related injuries

INTRODUCTION: The finding of eosinophilic ascites is unusual. It requires the search for the main etiology, i.e., parasitic or malignant disease, vasculitis or hypereosinophilic syndrome. The diagnosis of exclusion is either mucosal, muscular or serous eosinophilic gastroenteritis. This last type, the most unusual--as less than 50 cases have been documented until now--is associated with eosinophilic ascites. EXEGESIS: We report a new case of serous eosinophilic gastroenteritis that occurred in a 23-year-old woman. This case was unusual because of its clinical history, as abdominal pain fits (along with the occurrence of ascites) were associated with urticaria fits. The lack of eosinophils in both the blood counts and the various digestive biopsies were unusual too. The disease evolution was favorable with corticosteroid therapy; however, a minimal dose of 8 mg/day was necessary to control the disease symptoms. CONCLUSION: Because of its association with urticaria fits, this case emphasizes the need for differential diagnosis in patients with hypereosinophilic syndrome and food allergy.     

Prostate cancer masquerading as a zygomatic posttraumatic mass

INTRODUCTION: Idiopathic hypereosinophilic syndrome is an uncommon disease often associated with diverse non-specific skin manifestations. Mucosal ulcerations suggest a myeloproliferative from with poor prognosis due to possible progression to malignant hemopathy or visceral complications. CASE REPORT: A 28-year-old man presented idiopathic hypereosinophilia with isolated mucosal ulcerations involving the buccal and genital areas. Laboratory results (hematology, CD25) suggested a myeloproliferative form. Treatment with alpha interferon (18 months) led to regression of the mucosal lesions and a decrease in the markers of eosinophil toxicity. There was no visceral involvement. DISCUSSION: Immunosuppression with/without high-dose alpha interferon is usually used for the treatment of hypereosinophilic syndrome. In our case favorable outcome was obtained with lower doses of alpha interferon than those reported in the literature. There was objective decrease in eosinophil toxicity (regular counts of hypodense eosinophils, CD25 or interleukin 2 soluble receptor) and no progression (malignant hemopathy, mortal visceral involvement).     

Idiopathic hypereosinophilic syndrome with eosinophilic myositis, peripheral neuropathy and central nervous system involvement

Idiopathic hypereosinophilic syndrome (HES) is a rare disorder marked by a sustained overproduction of eosinophils and a predilection for damage to multiple organ systems. Its neurologic involvement ranges from the central to the peripheral nervous system, and can be associated with eosinophilic myositis. We report a 68-year-old woman who had eosinophilia, eosinophilic dermatitis and eosinophilic pneumonia. She also suffered from numbness and weakness of the lower limbs. Because of long-lasting (> 6 mo) eosinophilia (> 1.5 x 10(9)/L) in the peripheral blood and the fact that no other underlying causes of eosinophilia and neurologic involvement could be identified, a diagnosis of idiopathic hypereosinophilic syndrome was made. The muscle biopsy showed infiltration of inflammatory cells, including a few eosinophils (Liu's stain). Magnetic resonance images, motor evoked potentials, somatosensory evoked potentials and nerve conduction velocities also showed abnormalities in the central and peripheral nervous systems. The pathogenesis and treatments of HES are discussed in this report.     

The hypereosinophilic variant of Ph''-positive chronic myeloleukemia

AIM: To confirm clonal nature of idiopathic hypereosinophilic syndrome (IHES), its relevance to Ph'-positive chronic myeloid leukemia. MATERIALS AND METHODS: 3 cases of idiopathic hypereosinophilic syndrome are reported with morphologic analysis of bone marrow cells and cytogenetic examinations. In one patient the presence of Ph'-chromosome was confirmed at fluorescent in situ hybridization (FISH) and molecular-genetic analysis (bcr/abl). Samples of bone marrow, spleen and liver were examined pathohistologically. RESULTS: The presence of chromosome anomaly t(9;22), i.e. Ph'-chromosome, associated with chronic myeloid leukemia (CML) was identified in all the 3 cases. There was also myeloid hyperplasia in the bone marrow (with primarily mature, eosinophilic granulocytes), spleen and liver, depression of megakaryocyto- and erythropoiesis. 2 patients had similar clinical symptoms which was not typical for CML in chronic phase: fever, elevated ESR, clear-cut anemia and thrombocytopenia. In the absence of hyperleukocytosis, blood and bone marrow eosinophils remained high (42.5, 21.5, 42.5% and 21.4, 7.1, 6.5%, respectively) due to "mature" forms. The number of blasts in the bone marrow was maximum 2.4%. CONCLUSION: The literature and the obtained data suggest closeness of idiopathic hypereosinophilic syndrome and Ph'-positive CML within myeloproliferative diseases.     

The interleukin-5 messenger RNA expression in a patient with idiopathic hypereosinophilic syndrome

Interleukin-5 has a specific role in various eosinophilic activities. It is the predominant cytokine produces by activated T-lymphocytes isolated from patients with idiopathic hypereosinophilic syndrome. We studied a young patient suffering from idiopathic hypereosinophilic syndrome who presented with Horner's syndrome, peripheral neuropathy and skin ulcers. The IL-5 gene expression by CD4+ T-lymphocytes and the peripheral eosinophil count were raised. The skin ulcers continued to deteriorate despite a swift reduction of the IL-5 gene expression and peripheral eosinophil count following systemic corticosteroid treatment. We suggest that peripheral eosinophilia may not be responsible for the damage in skin lesions and more aggressive treatment may be required.     

Cine-MRI-aided endomyocardectomy in idiopathic hypereosinophilic syndrome

The idiopathic hypereosinophilic syndrome is a leukoproliferative disorder marked by a predilection to damage specific organs, including the heart. This report describes a patient with extensive endocardial fibrosis accompanying this syndrome. Right ventricular endomyocardectomy with preservation of the tricuspid valve was performed. The procedure was aided by cine-magnetic resonance imaging for preoperative assessment and follow-up of surgical results.     

Eosinophilic cholecystitis, appendiceal inflammation, pericarditis, and cephalosporin-associated eosinophilia

A patient with eosinophilic cholecystitis and accompanying eosinophilic appendiceal inflammation, eosinophilic pericarditis, and peripheral eosinophilia is described. Review of the nine previously reported cases of eosinophilic cholecystitis suggests that this is the first case with closely associated eosinophilic appendiceal inflammation and pericarditis as manifestations of a systemic hypereosinophilic syndrome. The possible etiologic role of cephalosporin hypersensitivity is discussed.     

Hypereosinophilic syndrome with generalized myasthenia gravis

A patient with hypereosinophilic syndrome simultaneously had generalized myasthenia gravis. Ultrastructural and functional studies demonstrated an increase of the activated hypodense eosinophils. The eosinophilic cationic protein level in plasma and whole blood paralleled the severity of congestive heart failure. A high level of interleukin-5 was detected in both serum and in conditioned medium of T cells by interleukin-2 stimulation before therapy. The findings indicate that both diseases may be associated with a common T-cell abnormality.     

Allogeneic bone marrow transplantation for hypereosinophilic syndrome with advanced myelofibrosis

A 33-year-old man with an atypical course of hypereosinophilic syndrome including malignant hypercalcemia, osteolytic lesions and evolution into severe myelofibrosis was treated by allogeneic bone marrow transplantation after conditioning with cytoxan and total body irradiation. As the transplant was sex-mismatched, chimerism was studied by means of cytogenetic analysis and Y chromosomal DNA amplification by PCR assay. Long-term complete remission has been assessed by normalization of blood cell counts, magnetic resonance imaging and karyotypic analysis. A relapse was observed 40 months after transplantation. The patient remains alive 44 months post-BMT. This case report is compared with those reported in the literature.     

Incidence of ligament lesions and associated degenerative changes in the elderly wrist

As the carbohydrate lacto-N-fucopentaose III (CD15 antigen or X-determinant) and its sialylated derivative sialyl-Lewis X are involved in the adhesion of cells rolling along the surface of endothelial cells, experiments were done to study the presence of these molecules on human eosinophils from patients with the idiopathic hypereosinophilic syndrome. Normal-density eosinophils from some patients showed higher levels of expression for lacto-N-fucopentaose III than light-density eosinophils. In contrast, sialyl-Lewis X was highly expressed by light-density eosinophils. Activation of normal-density eosinophils with calcium ionophore A23187 resulted in increased expression of these molecules for a short time. Monoclonal antibodies to these carbohydrates stimulated eosinophils to secrete eosinophil cationic protein, but not eosinophil peroxidase, and acted as costimulatory signals for C3b-induced degranulation of eosinophil cationic protein. It was suggested that CD15 and sialyl-Lewis X might contribute to eosinophil-mediated tissue injury in patients with the idiopathic hypereosinophilic syndrome.     

Serious, prolonged hypoglycaemia with glibenclamide in a patient with Mendenhall''s syndrome

Mendenhall's syndrome, characterized by familial insulin resistant diabetes, pineal hyperplasia and multiple somatic abnormalities, is associated with defects involving the alpha-subunit of the insulin receptor. The associated insulin-resistant diabetes is extremely difficult to treat; insulin is required in very large doses to control hyperglycaemia and oral hypoglycaemic agents are ineffective. We report a case of severe, prolonged hypoglycaemia that occurred in a 24-year-old patient with Mendenhall's syndrome following therapy with glibenclamide. He had glibenclamide 10 mg daily for 1 week following which he was admitted to hospital in hypoglycaemic coma with blood glucose levels < 1.0 mmol/l. This subject had undergone hypophysectomy at the age of 11 years. Prior to pituitary ablation, oral hypoglycaemic agents did not improve glycaemic control. Thus, previous hypophysectomy in this patient appears to have made it possible for glibenclamide to exert its hypoglycaemic effect. The occurrence of hypoglycaemia in this patient suggests alternative mechanisms for insulin action in conditions characterized by severe insulin resistance due to insulin receptor defects.     

Rectal methohexital for sedation of children during imaging procedures

OBJECTIVE: Hypereosinophilic syndrome (eosinophilia without demonstrable cause) commonly involves eosinophilic infiltration of the liver and spleen, but few reports have described the imaging findings. Accordingly, we reviewed the imaging findings in five patients with this syndrome in whom the liver was involved. MATERIALS AND METHODS: Five patients who had hypereosinophilic syndrome with hepatic involvement were included in the study. The diagnosis of hepatic involvement was based on pathologic proof in two patients and on imaging and laboratory findings in the other three. Histologic examination of the hepatic lesions showed extensive eosinophilic infiltration in two patients and centrilobular necrosis in one. All patients had chest radiography, barium studies of the gastrointestinal tract, abdominal CT, and sonography. Four patients had hepatosplenic scintigraphy. All patients were followed up for 4-24 months. RESULTS: All patients had mild to marked hepatomegaly with multiple focal lesions. Focal lesions were detected on sonograms in three patients, on CT scans in four, and on scintigrams in three. On sonograms, the lesions were usually small (less than 2 cm in diameter), sharply or poorly defined nodules with varied echogenicity scattered throughout the liver. The lesions were hypodense with poorly defined margins on CT scans and appeared as variably sized areas of decreased radionuclide uptake on scintigrams. For each patient, the number, size, and shape of the lesions varied considerably from one imaging study to another. On follow-up studies 2-6 months after treatment, the appearance of the liver was normal. Other radiologic findings included transient pulmonary infiltrates (two patients), mild cardiomegaly (one patient), and mild lymphadenopathy (three patients). CONCLUSION: Hypereosinophilic syndrome is a cause of focal hepatic lesions seen on sonograms, CT scans, or scintigrams. The lesions are characterized by the varied appearance on the different types of images and the disappearance of the lesions with treatment.     

Cutaneous malakoplakia on the forehead

We report a single case of Weill-Marchesani syndrome, typically characterized by progressive joint stiffness, brachiymorphy, brachydactyly, and ectopia lentis. The clinical case appears particularly interesting as the patient also had primary osteoporosis, which until now has not been considered as a possible manifestation of Weill-Marchesani syndrome.     

Laparoscopic adrenalectomy

Between June and September 1993, laparoscopic adrenalectomy was indicated in five patients (three women, two men; aged 25-50 years). Three had a phaeochromocytoma, two had an adenoma (Conn's syndrome). Four of the five tumours were localized to the right adrenal gland, one to the left. Tumour diameter ranged from 3 to 5 cm. The laparoscopic procedure was successful in four of the patients (three right, one left). In the fifth case the operations had to be completed by conventional surgery, because of non-controllable haemorrhage. Duration of operation ranged between 165 and 360 min for right adrenalectomy and was 135 min for the left one. Rapid convalescence, lower dose of pain-killing drug required, short hospital stay and good cosmetic results characterized the postoperative course after the laparoscopic procedure. This technique thus opens up new perspectives for adrenal surgery.     

Musculocutaneous nerve palsy following traumatic spinal cord injury

Whipple's disease is a multisystem bacterial disease usually characterized by malabsorption, diarrhea and polyarthritis. Ocular manifestations include uveitis, vitreitis, retinis, myositis, papilledema and optic atrophy. We report a case of a chronic bilateral vitreitis in a 63 year-old man who had been treated for a Whipple's disease with gastrointestinal involvement 30 years before. The jejunal biopsy was negative but the polymerase-chain-reaction (PCR) revealed the presence of Trophyrema Whippelii in the vitreous prelevement of both eye. This new, original strategy of PCR is specific and more sensitive than histological diagnosis.     

Multiple primary cancers in families with Li-Fraumeni syndrome

BACKGROUND: Li-Fraumeni syndrome is a dominantly inherited disorder characterized by early-onset breast cancer, sarcomas, and other cancers in children and young adults. Members of families with this syndrome also develop multiple primary cancers, but the frequency is unknown. To approach this issue, we quantified the incidence of second and third primary cancers in individuals from 24 Li-Fraumeni kindreds originally diagnosed with cancer during the period from 1968 through 1986. METHODS: The relative risk (RR) of subsequent cancers and 95% confidence intervals (CIs) were calculated by use of population-based incidence data from the Connecticut Cancer Registry. Kaplan-Meier analysis was used to determine the cumulative probability (+/- standard error) of subsequent cancers. RESULTS: Among 200 Li-Fraumeni syndrome family members diagnosed with cancer, 30 (15%) developed a second cancer. Eight individuals (4%) had a third cancer, while four (2%) eventually developed a fourth cancer. Overall, the RR of occurrence of a second cancer was 5.3 (95% CI = 2.8-7.8), with a cumulative probability of second cancer occurrence of 57% (+/- 10%) at 30 years after diagnosis of a first cancer. RRs of second cancers occurring in families with this syndrome were 83.0 (95% CI = 36.9-187.6), 9.7 (95% CI = 4.9-19.2), and 1.5 (95% CI = 0.5-4.2) for individuals with a first cancer at ages 0-19 years, 20-44 years, and 45 years or more, respectively. Thirty (71%) of 42 subsequent cancers in this group were component cancers of Li-Fraumeni syndrome. CONCLUSIONS: Compared with the general population, members of Li-Fraumeni syndrome families have an exceptionally high risk of developing multiple primary cancers. The excess risk of additional primary cancers is mainly for cancers that are characteristic of Li-Fraumeni syndrome, with the highest risk observed for survivors of childhood cancers. Cancer survivors in these families should be closely monitored for early manifestations of new cancers.     

Cytomegalovirus iritis

We describe a case of focal cytomegalovirus iritis in a patient with acquired immunodeficiency syndrome (AIDS) who had CMV retinitis. The autopsy showed histologic evidence of focal iritis in the left eye. This iritis was characterized by infiltration of acute inflammatory cells mixed with cytomegalic cells, which was confirmed by CMV-specific immunohistochemical staining. The case suggested that cytomegalovirus could be a direct causative agent of infectious iritis in AIDS patients.