Hypereosinophilia: a diagnostic challenge.

Hypereosinophilia encompasses a broad differential diagnosis of atopy/allergic reactions, drug reactions, parasitic infections and paraneoplastic syndromes. Although mostly of limited clinical significance, hypereosinophilia can also be related to hematological malignancies. One has to be aware of the potential for secondary organ damage for example, in the case of hypereosinophilic syndrome. We present three cases with different underlying mechanisms of hypereosinophilia with a brief overview of causes, diagnostic work-up and treatment options.

Recurrent amebic liver abscesses over a 16-year period: a case report.

BACKGROUND: Amebic liver abscess is a rare disease in high-income countries. Recurrence of amebic liver abscess is even rarer with only a few previous reports. Here we present a patient who developed three subsequent amebic liver abscesses over a sixteen-year period. CASE PRESENTATION: A Caucasian male developed recurrent amebic liver abscesses, when aged 23, 27 and 39 years. Only on the first occasion did this coincide with a recent visit to the tropics. The patient received adequate treatment during each episode. Possible explanations are persistent asymptomatic carrier state, cysts passage in his family, re-infection or chance. CONCLUSION: We describe the unusual case of a healthy male who developed recurrent amebic liver abscesses over a long period despite adequate treatment. Possible pathophysiological explanations are explored.

Severe leptospirosis in a Dutch traveller returning from the Dominican Republic, October 2011.

In October 2011, a case of leptospirosis was identified in a Dutch traveller returning from the Dominican Republic to the Netherlands. The 51-year-old man had aspired muddy water in the Chavón river on 29 September. Twenty days later he presented with fever, nausea, vomiting, diarrhoea, arthralgia, headache, conjunctival suffusion and icterus. Leptospira serovar Icterohaemorrhagiae or Australis infection was confirmed ten days later by laboratory testing.

Two patients with ciguatera toxicity: a seafood poisoning in travellers to (sub) tropical areas.

Ciguatera toxicity is a type of seafood poisoning caused by the consumption of ciguatoxic reef fish. We describe two patients with characteristic gastrointestinal and neurological symptoms, both of whom had eaten local seafood. Although mortality is low, morbidity can be considerable due to debilitating symptoms. Most cases originate in the (sub)tropics but due to expanding tourism and fish exportation, it may be encountered in more temperate regions. Treatment is supportive, but some benefit from intravenous mannitol has been reported.

[Three patients with orf (ecthyma contagiosum)]. / Drie patiënten met orf (ecthyma contagiosum).

Orf was diagnosed in three patients: a 16-year-old Moroccan girl who had cut her finger in a butcher's shop, a 47-year-old Dutch woman who had allowed a lamb to suck on her finger on a children's farm, and a 50-year-old Dutch farm woman. Orf or ecthyma contagiosum is a well-known viral disease among sheep and goats. Transmission to humans as a zoonosis is rare but can take place via direct contact with infected animals or animal products. The clinical picture is usually characterized by a solitary lesion that develops on the dorsal side of the fingers or hands. This viral condition produces little or no systemic complaints and the lesions usually regress spontaneously without scar formation within 6 weeks (range 4-9 weeks). The correct diagnosis can usually be made on clinical grounds. The diagnosis may be confirmed by demonstration of the virus by electron microscopy or the polymerase chain reaction in fluid obtained from the skin lesions or by conventional histopathology. Early clinical recognition and knowledge of this benign, self-limiting viral condition is vital to avoid unnecessary surgical intervention. Proper information and reassurance of the infected patient are very important. All three patients recovered.

[Three patients with African sleeping sickness following a visit to Tanzania]. / Drie patiënten met Afrikaanse slaapziekte na een bezoek aan Tanzania.

Three Dutch tourists, a man aged 57 and two women aged 55 en 52 years, acquired African trypanosomiasis in the national parks of Tanzania. Two, without central nervous system involvement, were cured after treatment in the Netherlands, albeit one after having suffered a relapse. In the third patient, involvement of the central nervous system was diagnosed in Africa and she was treated with melarsoprol. After an apparently uneventful recovery she was readmitted with cerebral complaints and symptoms. While being treated with melarsoprol she lapsed into coma. She died following repatriation. An epidemic of trypanosomiasis is currently raging through Central Africa. In several western countries, trypanosomiasis has been diagnosed recently in tourists who visited Tanzania.

[Cholestatic hepatitis ascribed to the use of thiabendazole]. / Cholestatische hepatitis toegeschreven aan het gebruik van tiabendazol.

Two women, aged 27 and 42 years, both born in Surinam and both suffering from heterozygous thalassemia, developed cholestatic hepatitis three and two weeks respectively after the start of a two-day course of thiabendazol for Strongyloides stercoralis infection. Other causes of cholestasis were unlikely in view of the results of blood tests, echography and the endoscopic retrograde cholangiopancreaticography. The symptoms persisted for several months, and the liver function disorders for 7 years and one year, respectively. The incidence of thiabendazole-induced cholestatic hepatitis is unknown, but probably low.

[Invagination in adults]. / Invaginatie bij volwassenen.

Two adult patients with intussusception were both diagnosed by colonoscopic investigation. The first patient, a woman aged 39, suffered from persisting abdominal discomfort with nausea and vomiting. Ultimately an ileo-ileocolic intussusception caused by an inflammatory fibroid polyp of the ileum was found. The other patient, a man of 79 years, complained of subacute cramping pain in the right lower abdomen. This was due to an ileocolic intussusception caused by an adenocarcinoma of the cecum. Both patients underwent an ileocecal resection; their postoperative courses were uneventful.

[African sleeping sickness in The Netherlands]. / Afrikaanse slaapziekte in Nederland.

Of the four most dangerous protozoal infections acquired in (sub)tropical regions, falciparum malaria, amoebic abscess of the liver, visceral leishmaniasis (kala azar) and African trypanosomiasis (sleeping sickness) only the fourth was up to now unreported in the Dutch medical literature. Two case histories are presented: a Cameroonian woman, resident in the Netherlands for two years, suffering from West African type sleeping sickness, and a Dutch tourist who acquired East African trypanosomiasis while travelling through Zimbabwe. Although the parasites are morphologically identical, clinical and epidemiological characteristics are distinctly different. The West African type, rarely if ever observed in Europeans, has an insidious chronic course leading to the features of classical sleeping sickness. Differential diagnosis is difficult. The East African variety runs an acute course in Europeans leading to death within days due to myocarditis. It is therefore mandatory for the diagnosis to be made as soon as possible in order to initiate specific therapy. Both patients recovered after specific therapy.

[Glucose-6-phosphate dehydrogenase deficiency in an 81-year-old]. / Glucose-6-fosfaat-dehydrogenase-deficiëntie bij een 81-jarige.

In a 81-year-old woman, who for many years had been treated with iron and vitamin B12 injections because of a 'tendency to anaemia', congenital haemolytic anaemia on the basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency was diagnosed. The iron and vitamin medication was discontinued and after a blood transfusion because of signs of heart failure, the patient could leave the hospital in good condition. After instruction with regard to provocative factors, like eating of broad beans, no more haemolytic events occurred. Of her children and grandchildren, 2 sons and 1 granddaughter were G6PD deficient.

Humoral immune response to a yeast-derived hepatitis B vaccine in patients with type 1 diabetes mellitus.

The immune response following vaccination with a recombinant hepatitis B vaccine was investigated in 32 patients with Type 1 diabetes mellitus and compared with the outcome in 32 healthy age- and sex-matched volunteers. Participants were vaccinated at 0, 30, and 180 days and in vivo immune response was determined at 30, 60, 90, 180, and 210 days. The number of responders (anti-HBs greater than 1 IU l-1) was significantly lower (p less than 0.05) among patients at 30 (2 vs 11), 60 (17 vs 26), 90 (20 vs 28) and 180 (22 vs 29) days. The number of patients protected (anti-HBs greater than 10 IU l-1) was lower (p less than 0.05) than the number of protected volunteers at 60 (5 vs 14), 90 (10 vs 19), 180 (15 vs 24), and 210 days (24 vs 31). After the complete course of vaccination 8 out of 32 patients were still unprotected against hepatitis B (p less than 0.05). The anti-HBs titre of responders at 210 days was 251 (20, 3162) (geometric mean (-SD, +SD] IU l-1 in patients and 1259 (126, 12589) IU l-1 in control subjects (p less than 0.05). The HLA-antigen DQw1 frequency in the diabetic low responders (anti-HBs less than 100 IU l-1) was 0.27 compared with 0.86 in diabetic adequate responders. No relation between anti-HBs production and concentration of HbA1c could be demonstrated.

A prospective study of in vitro anti-HBs producing B cells (spot-ELISA) following primary and supplementary vaccination with a recombinant hepatitis B vaccine in insulin dependent diabetic patients and matched controls.

A prospective study of the immune response after hepatitis B vaccination was carried out in 32 insulin dependent diabetes mellitus (IDDM) patients and their age and sex matched healthy controls. A sensitive, immunoenzymatic technique was used, able to detect in vitro specific antibody production by mitogen stimulated individual B cells. In-vivo serologic response after vaccination with a standard scheme (0, 1 and 6 months) of 20 micrograms recombinant hepatitis B (HB) vaccine was significantly impaired in the IDDM patients both with respect to the number of nonresponders (25 versus 3%, P less than 0.05) and antibody titers reached (1,377 vs. 9,060 IU/L, P less than 0.05). The total number of in vitro IgM- and IgG-class immunoglobulin producing B cells as detected by the spot-ELISA, was found to be comparable in both groups. Specific IgG anti-HBs (and to a lesser extent IgM anti-HBs) showed impairment in the diabetic population as a whole. The number of IgG anti-HBs producing B cells was markedly depressed one month following vaccination, which is probably a reflection of homing of B cells outside the circulation. Responding subjects were identified early during their vaccination by the detection of in vitro anti-HBs production using the spot-ELISA. Non-responding healthy subjects and IDDM patients as a group showed a low number of IgG anti-HBs spots, suggesting a reduced specific memory B cell frequency. In 13 of 15 hypo- and nonresponders with positive IgG anti-HBs spots supplementary vaccination(s) resulted in improved anti-HBs levels.

[Tropical eosinophilia as an imported disease in The Netherlands]. / Tropische eosinofilie als importziekte in Nederland.

Tropical eosinophilia was diagnosed in two patients from India. This appears to be the first report on this exotic condition in the Netherlands. Tropical eosinophilia is characterised by hypereosinophilia, asthma-like attacks of wheezing and non-productive cough, non-specific findings on the chest X-ray in combination with general malaise, subfebrile temperatures, weight loss and lymphadenopathy. Although the syndrome is caused by an infection with Filaria, classical symptoms of filarial infection are characteristically absent. The main diagnostic criteria are hypereosinophilia and asthma-like attacks in subjects from regions where Filaria is endemic, high IgE titers, high antifilarial antibody titers and cure following one or more treatment courses with diethylcarbamazine. These case reports illustrate the importance of the assessment of the number of eosinophil cells in the peripheral blood in the diagnosis of tropical disease.

The spot-ELISA: a sensitive in vitro method to study the immune response to hepatitis B surface antigen.

We present our experience with a new sensitive in vitro method for the study of the immune response to hepatitis B surface antigen (HBsAg). This immunoenzymatic technique, called spot-ELISA, detects specific immunoglobulin production (e.g. IgG- or IgM-anti-HBs) by stimulated individual B cells in vitro. We have studied the immune response against HBsAg by mitogenic stimulation and subsequent spot-ELISA assay in 24 well-documented subjects with known immune status after either natural infection or vaccination with plasma-derived vaccine. Results indicate a good correlation between in vitro IgG anti-HBs spots and immune 'memory.' A possible predictive value in non-immunized and non-responder subjects awaits further confirmation.

Is booster injection with hepatitis B vaccine necessary in healthy responders? A study of the immune response.

Loss of protective anti-HBs levels (less than 10 IU/l) was noted in 5 (13%) of 38 well documented healthy responders to hepatitis B vaccine 30 months after completing the initial standard vaccination series. Revaccination with a single booster injection of 20 micrograms hepatitis B vaccine intramuscularly resulted in anti-HBs levels well above those initially obtained, thus confirming considerable immunological memory. Both decline prior to and rise after booster injection were proportional to the anti-HBs level obtained initially. The antibody production after a single booster injection was closely monitored in 13 individuals. A swift response was observed from day 4 onwards in all subjects. Based on passive immunization data and in vitro infection of human hepatocytes, this time delay is likely to permit infection of hepatocytes. Therefore, until further data on longterm follow-up of vaccinated in individuals in whom anti-HBs levels have dropped to less than 10 IU/l reveal compelling evidence to the contrary, booster injections remain mandatory for those individuals at risk.

Malaria chemoprophylaxis for multiple drug resistant Plasmodium falciparum in Africa: an increasing problem.

Resistance of P. falciparum to the two groups of antimalaria drugs commonly used for prophylaxis, i.e. folate antagonists and 4-aminoquinolines has become a matter of great concern, also in Africa. After 1978, P. falciparum developed resistance to the group of 4-aminoquinolines, which was first reported from East Africa. Chloroquine resistant infections are now spreading into Central Africa. Similar developments are now appearing with the combination sulfadoxine/pyrimethamine. With the increasing reports of multiple drug resistance in P. falciparum from Africa, no single drug or combination of drugs in use for chemoprophylaxis can give a complete protection under all circumstances any longer. Until new effective drugs become available, it is advised to use the combination of chloroquine or amodiaquine and proguanil; the traveller should be prepared for action in the event of a breakthrough. A written instruction is suggested to be inserted in the "International Certificate of Vaccination".