Pontus Harten

The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes

OBJECTIVE To develop a standardized nomenclature system for the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE). METHODS An international, multidisciplinary committee representing rheumatology, neurology, psychiatry, neuropsychology, and hematology developed case definitions, reporting standards, and diagnostic testing recommendations. Before and after the meeting, clinician committee members assigned diagnoses to sets of vignettes randomly generated from a pool of 108 NPSLE patients. To assess whether the nomenclature system improved diagnostic agreement, a consensus index was developed and pre- and postmeeting scores were compared by t-tests. RESULTS Case definitions including diagnostic criteria, important exclusions, and methods of ascertainment were developed for 19 NPSLE syndromes. Recommendations for standard reporting requirements, minimum laboratory evaluation, and imaging techniques were formulated. A short neuropsychological test battery for the diagnosis of cognitive deficits was proposed. In the postmeeting exercise, a statistically significant improvement in diagnostic agreement was observed. CONCLUSION The American College of Rheumatology (ACR) Nomenclature for NPSLE provides case definitions for 19 neuropsychiatric syndromes seen in SLE, with reporting standards and recommendations for laboratory and imaging tests. It is intended to facilitate and enhance clinical research, particularly multicenter studies, and reporting. In clinical settings, consultation with other specialists may be required. It should be useful for didactic purposes but should not be used uncritically or as a substitute for a clinical diagnosis. The complete case definitions are available on the ACR World Wide Web site: http://www.rheumatology .org/ar/ar.html.

Multiple Organ Manifestations in Thromboangiitis Obliterans (Buerger's Disease) A Case Report:

Thromboangiitis obliterans (TAO) occurs almost exclusively in young male smokers. Its involvement of the small and medium-sized arteries and veins leads to ischemic complaints and/or changes in the extremities. The possibility of organ involvement is a matter of controversy. The authors report a case of TAO with multiple organ involvement, including myocardial, splenic, and cerebral infarctions; pulmonary embolisms; and probable intestinal ischemia during a twenty-three-year course.

Disseminated histoplasmosis in a non-immunocompromised host.

Histoplasma infections in Europe are rare, and acute disseminated histoplasmosis has only been observed in immunocompromised persons. We describe a case of acute disseminated histoplasmosis in a young, nonimmunocompromised European woman. The probable source of infection was Sri Lanka or the Maldives. At presentation she was severely ill with fever, lymphadenopathy, anemia, thrombocytopenia, hepatosplenomegaly, and polyserositis. Histologically, myelofibrosis and osteosclerosis were observed with extramedullary hematopoiesis. Histoplasma capsulatum yeasts were detected in bone marrow trephine biopsy by methenamine silver staining. Treatment with conventional and liposomal amphotericin B and subsequent itraconazole led to rapid and complete recovery.

Thrombocytopenic thrombotic purpura : severe clinic with no CT minor MRI, but a SPECT correlate

A 28-year-old woman with primarily therapy refractory TTP was followed neuroradiologically over 6 months. Despite pronounced neurological and neuropsychiatric symptoms including hemiparesis and aphasia she had unremarkable CT scans on two occasions. Three MRI exams showed no correlate for her neurological symptoms except a small petechial cortical hemorrhage in the right parietooccipital gyrus which may account for her TTP-related anxiety disorder. A cerebral HMPAO-SPECT showed long-standing right-sided hypoperfusion compatible with residual vasculature changes. The possible causes for the clinico-neuroradiological discrepancies are discussed in view of the literature.

Hereditäres Angioödem@@@Hereditary angioedema. False diagnosis and therapy as systemic lupus erythematosus: Fehldiagnose und -behandlung als systemischer Lupus erythematodes

Zusammenfassung□ HintergrundDas autosomal-dominant vererbte hereditäre Angioödem geht mit intermittierenden Ödemen im Haut-, Abdominal-, Tracheolaryngealoder Zerebralbereich einher. Bei jedem fünften Patienten fehlt aufgrund einer Spontanmutation die Familienanamnese. Serologische Leitbefunde sind verminderte Spiegel des Komplementfaktors 4 und des C1-Esterase-Inhibitors. Die heterogene Symptomatik führt häufig zur Verzögerung oder Verwechslung der Diagnose.□ FalldarstellungBerichtet wird über einen 50jährigen Patienten mit schubförmigen Gelenkschwellungen, abdominellen Koliken, Pleuraergüssen, Aszites, Zephalgien und Bewußtseinsstörungen seit Adoleszenz. Die Diagnose lautete systemischer Lupus erythematodes. Nach mehrmonatiger erfolgloser Immunsuppression ergab die Diagnoseüberprüfung ein hereditäres Angioödem. Durch Anamnese und Laboruntersuchungen konnten in der Familie vier weitere Fälle aufgedeckt werden. Zwei davon waren ebenfalls seit Jahrzehnten erkrankt, aber fehleingeschätzt worden.□ SchlußfolgerungBei unklaren Hautschwellungen, abdominellen Koliken, Larynxödemen, Pleuraergüssen und Zephalgien sollte das hereditäre Angioödem in die Differentialdiagnose einbezogen werden. Bei früher Diagnose und adäquater Therapie ist die Prognose günstig. ACE-Hemmer können das Krankheitsbild verschlimmern, und sind daher kontraindiziert. In einem Literaturüberblick werden Diagnose, Pathogenese und Therapie diskutiert.Abstract□ BackgroundSymptoms of hereditary angioedema are intermittent edema of subcutaneous tissues, abdominal organs, upper airways, and brain. Because of spontaneous mutation, in 20% of patients a familial history is lacking. Serological hallmarks are diminished complement factor 4 and C1-esterase inhibitor. The heterogenicity of the clinical symptoms frequently leads to false or delayed diagnosis.□ Case ReportWe report on a 50-year-old male patient with intermittent joint swellings, abdominal complaints, pleural effusions, ascites and headaches with disturbances of consciousness since early adulthood. Diagnosis was systemic lupus erythematosus. Immunosuppressive therapy was ineffective over months. Careful re-evaluation of the patient’s clinical history and further laboratory examinations led to the diagnosis of an hereditary angioedema. Anamnestic and laboratory exploration of family members disclosed four other cases. Two of them also were symptomatic for decades without adaequate diagnosis.□ ConclusionIn case of intermittent swellings, abdominal complaints, laryngeal edema, pleural effusions or ascites, differential diagnosis should involve hereditary angioedema. With early diagnosis and adequate treatment, prognosis is good. Since ACE inhibitors can aggravate the disease they are contraindicated. Diagnosis, pathogenesis, and treatment are discussed by reviewing the literature.BACKGROUND Symptoms of hereditary angioedema are intermittent edema of subcutaneous tissues, abdominal organs, upper airways, and brain. Because of spontaneous mutation, in 20% of patients a familial history is lacking. Serological hallmarks are diminished complement factor 4 and C1-esterase inhibitor. The heterogenicity of the clinical symptoms frequently leads to false or delayed diagnosis. CASE REPORT We report on a 50-year-old male patient with intermittent joint swellings, abdominal complaints, pleural effusions, ascites and headaches with disturbances of consciousness since early adulthood. Diagnosis was systemic lupus erythematosus. Immunosuppressive therapy was ineffective over months. Careful re-evaluation of the patients clinical history and further laboratory examinations led to the diagnosis of an hereditary angioedema. Anamnestic and laboratory exploration of family members disclosed four other cases. Two of them also were symptomatic for decades without adequate diagnosis. CONCLUSION In case of intermittent swellings, abdominal complaints, laryngeal edema, pleural effusions or ascites, differential diagnosis should involve hereditary angioedema. With early diagnosis and adequate treatment, prognosis is good. Since ACE inhibitors can aggravate the disease they are contraindicated. Diagnosis, pathogenesis, and treatment are discussed by reviewing the literature.

Febrile Neutropenie: Praktische Aspekte

Zusammenfassung□ HintergrundInfektionen stellen eine bedeutende Mortalitätsursache bei neutropenischen Patienten dar. Sie führen zu langen Hospitalisierungsphasen und kostenintensiven therapeutischen Maßnahmen. In der vorliegenden Übersicht werden aktuelle Strategien zur Prophylaxe und Therapie der febrilen Neutropenie unter praktischen und pharmakoökonomischen Aspekten diskutiert.□ Prophylaxe und TherapieProphylaktisch eingesetzte hygienische und medikamentöse Maßnahmen reduzieren die Infektionsrate. Bei Neutropenie und Fieber unklarer Genese werden initial Kombinationen aus einem Aminoglykosid und einem Ureidopenicillin oder Cephalosporin der dritten Generation eingesetzt. Kombinationen zweier β-Lactam-Antibiotika sind bei gleicher Effektivität weniger toxisch, dafür aber meist kostenintensiver. Monotherapien mit Carbapenemen, Ceftazidim oder Cefepim bieten vergleichbare Ansprechraten. Versagt das Erstregime, wird nach drei bis vier Tagen die Kombination aus einem Carbapenem, einem Glykopeptidantibiotikum und Amphotericin B eingesetzt. Bei Nachweis von Lungeninfiltraten sollte Amphotericin B bereits initial hinzugefügt werden. Durch Vergleich von Tagestherapiekosten, Applikationsfrequenz und Toxizität der jeweiligen Antibiotika könnten die Gesamtaufwendungen verringert werden. Der prophylaktische oder interventionelle Einsatz von Wachstumsfaktoren wird nur bei speziellen Risikokonstellationen empfohlen.□ Schlußfolgerung und AusblickDas beschriebene Vorgehen führt bei der febrilen Neutropenie zu einer Ansprechrate von über 90%. Wichtig ist die kalkulierte Eskalation der empirischen Antibiotikatherapie zu definierten Zeitpunkten. Ob bei ausgewählten Patienten eine ambulante Therapie möglich ist, sollte noch weiter untersucht werden.Abstract□ BackgroundInfections are a major cause of mortality in neutropenic patients. They require long hospital stays and highly expensive therapeutic measures. In this review we discuss the practical and pharmaco-economic aspects of the management of febrile neutropenia.□ Prevention and TherapyPrevention of fever of unknown origin (FUO) demands hygienic and antimicrobiotic measures. First-line antibiotic therapy consists of an aminoglycoside combined with an ureidopenicillin or a 3rd-generation cephalosporin. Double ß-lactam antibiotic combinations are equally effective and less toxic, but more expensive. Monotherapy with carbapenems, ceftazidime, or cefepime appear to offer comparable efficacy. Lung infiltrates require immediate treatment with amphotericin B. If the initial therapeutic regime fails, a carbapenem plus a glycopeptide antibiotic and a parenteral antimycotic drug should be applied after 3 to 4 days. The prophylactic or interventional administration of hematopoietic growth factors is only indicated in special high-risk situations.□ ConclusionsUsing the described therapeutic procedure, the response rate exceeds 90%. Consistent, step-wise escalating administration of antibiotics is essential. More evaluation is needed to determine whether selected patients with febrile neutropenia can be treated on an outpatient basis.