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In case of eosinophilia persisting for more than 6 months a diagnosis of hypereosinophilic syndrome (HES) should be considered if secondary causes of eosinophilia ca be ruled out. Recent studies on the pathogenesis of HES revealed that the syndrome previously coined "idiopathic HES" is comprised of pathogenetically distinct subtypes which are defined by molecular, immunophenotypic or clinical markers. Eosinophilia in HES can be caused by increased production or survival of eosinophils due to cytokines such as interleukin-5 (IL-5) or clonal expansion due to mutations. Distinction of these pathogenetically different subtypes of HES is clinically relevant as new targeted treatment approaches are available for some of these subtypes, such as tyrosine kinase inhibitors for the FIP1L1-PDGFRA-positive myeloproliferativer subtype, immunomodulators such as interferon-alpha or monoclonal antibodies against IL-5 for FIP1L1-PDGFRA-negative patients.

The diagnosis of ANCA-associated vasculitides (AAV) consists of clinical symptoms, results of technical procedures and a characteristic histology. The diagnostic workup should focus on the prominent clinical symptoms and should involve an interdisciplinary team of specialists. The therapy is divided into induction and maintenance treatment. Cyclophosphamid remains standard therapy for the induction of remission, whereas azathioprine, methotrexate and leflunomide are often used for maintenance therapy. The introduction of a stage-adapted treatment has contributed to a significant improvement of the long-time prognosis of patients with AAV.

History: A 27-year-old woman from Cameroon was admitted because of arthralgia, myalgia and severe thrombocytopenia (20,000/ micro l). She had been suffering from weakness, recurrent febrile episodes, generalized lymphadenopathy and pancytopenia for 2 years. Having a typical autoantibody constellation and fulfilling four (pleurisy, autoimmune-hemolytic anemia, antinuclear antibodies (ANA), anti-Sm antibodies) of the American College of Rheumatology (ACR) classification criteria, systemic lupus erythematosus (SLE) had been diagnosed at another hospital. Treatment with corticosteroids and azathioprine did not improve her condition., Investigations: Abnormal laboratory findings were pancytopenia, elevated markers of inflammation and extreme hypergammaglobulinemia (70 %) with polyclonal IgM (73 g/l). Antinuclear antibodies (ANA), anti-Sm-, anti-Scl 70-, anti-U1-RNP-, anti-histo-, anti-leukocyte- and IgM anticardiolipin antibodies were detected. A bone marrow biopsy showed polyclonal B-cell and plasma cell infiltrates. Examination of peripheral blood smears disclosed trypanosoma brucei infection., Diagnosis, Treatment and Course: After the diagnosis of stage 2 West African trypanosomiasis (sleeping sickness) specific treatment was initiated leading to subsequent remission of the disease., Conclusion: This case report underlines the importance of a thorough differential diagnosis in cases of suspected autoimmune disease. Induction of autoantibodies during infectious diseases may be misleading. The use of the ACR criteria for SLE must be restricted to the classification of proven connective tissue diseases.

Unlabelled: BACKGROUND AND QUESTION: The prognosis of patients with Wegener's granulomatosis (WG) refractory to standard treatment for the induction of remission (cyclophosphamide and steroids) has been poor so far. We report on the results of the follow-up of six patients refractory to the standard regimen (Fauci's scheme) with progressive, imminent visual loss, pulmonary and renal involvement, respectively. How long can remissions be successfully maintained with anti-TNF-alpha-antibody infliximab? What side effects occur?, Patients and Methods: Patients received infliximab (3 mg/kg) in addition to standard therapy with cyclophosphamide and steroids. Intervals between the first two infliximab infusions were 2 weeks, thereafter 4 weeks. Based on the impression of higher efficacy patients received 5 mg/kg infliximab for subsequent infusions., Results: Remission was induced after 4-6 infliximab infusions in five patients. Remission has been maintained in four patients for 16-26 months. After 12 months a pulmonary relapse occurred in one patient, who received azathioprine for the maintenance of remission. Infliximab was stopped in another patient because of a suspected infection. In the light of high cumulative cyclophosphamide doses (100 g/275 g) and cyclophosphamide induced hemorrhagic cystitis, infliximab was added to azathioprine in the two patients with a pulmonary relapse and protrusion of the eye with imminent visual loss, respectively. Remission was induced in both patients. A carcinoid of the bronchus was diagnosed in one patient after 12 months in remission., Conclusion: Infliximab means a new therapeutic option and offers better perspectives for a patient group with previously bad prognosis.

History and Admission Findings: A 72-year-old woman was admitted to hospital because of nonproductive cough, acrodistal sensorimotor axonal polyneuropathy, fatigue and 10 kg weight loss over the preceding 9 months., Investigations: Chest radiogram showed multiple round foci in both lungs. No organs other than the lungs and the peripheral nervous system were affected. Open lung biopsy revealed a pleomorphic angioinvasive lymphocytic infiltrations., Diagnosis, Treatment and Course: The findings indicated lymphomatoid granulomatosis (LG). Wegener granulomatosis was excluded on the basis of the clinical, serological and histopathological findings. Treatment with alpha-interferon (IFN-alpha) produced complete remission within 4 months. Interruption of treatment immediately resulted in a recurrence., Conclusion: Together with previously reported cases this patient's response to IFN-alpha suggests that IFN-alpha is a less toxic alternative to cyclophosphamide and corticosteroid administration in the early stages of LG.

A fasciitis-sclerodermia-eosinophilia syndrome developed in four female patients, aged between 55 and 75 years, after the ingestion of tryptophan, 1.5-6.0 g daily, for 13 months to 7 years. It began characteristically with hard oedema of the limbs, sometimes also of the trunk. Later there occurred diffuse indurations of the body surface with fixation of the skin to fascial planes. This was associated with mainly sensory peripheral neuropathy. Three of the patients had an eosinophilia (12-30%). Histological examination revealed a cell-poor fasciitis, fibrosis of the cutis and subcutis, perimyositis and epidermal atrophy of varying degree. Erythrocyte sedimentation rate was at most slightly increased. Antinuclear antibodies were demonstrated in one patient (1:80). Serum aldolase concentration was raised (3.4-5.4 U/l), while creatine kinase was normal. The disease progressed even after tryptophan was discontinued, in only one patient there was improvement during glucocorticoid treatment. In two cases the skin induration regressed slowly after administration of methotrexate (15 mg weekly) and hydroxychloroquine (400 mg daily).

Sera from 105 patients with Wegener's granulomatosis (WG) and 1,500 control subjects (with, among other diseases, primary or secondary vasculitis, collagen disease, glomerulonephritis or various granulomas) were examined with respect to sensitivity, specificity and importance of anticytoplasmic antibodies (ACPA) as markers of disease activity. The antibodies were demonstrated in 77 of the 105 patients (73%) with WG and six of the controls (less than 1%). They were always present in active WG (57 patients). In a prospective study of 21 closely followed patients with WG there was a close correlation between ACPA titre and the disease activity as measured by clinical and biochemical criteria. After induction of remission there was in all instances a clear fall in titre, while the titre rose again on exacerbation but remained unchanged during superinfection. Thus anticytoplasmic antibodies are useful both in primary diagnosis and in estimating disease activity of WG.

Immuno-augmentation with substances of bacterial origin was studied in vitro for its ability to induce polyclonal B-cell activation. Biostim, Broncho-Vaxom, Omnadin, Paspat and OK 432 were compared for their B-cell mitogenicity with classical polyclonal B-cell activators (Staph. aureus Cowan I, KlebsM, Pokeweed mitogen). B-cell mitogenicity, as measured by 3H-thymidine incorporation into proliferating blood B-cells, was not induced by any of the studied preparations. On the other hand, OK 432 produced a T-cell dependent and Biostim a T-cell independent blood B-cell differentiation in immunoglobulin producing cells. However, the extent of immunoglobulin production was clearly less than with the polyclonal B-cell activator KlebsM. These results demonstrate that, in some of the preparations, in vivo polyclonal B-cell activation can be expected to occur.