[Pseudo-(venocuran-)lupus--a minor episode in the history of medicine]. / Pseudo-(Venocuran-)Lupus--eine kleine Episode Medizingeschichte.

Pseudolupus is a syndrome characterized by recurrent fever arthralgia, myalgia, involvement of lung and heart, high sedimentation rate, leukocytosis and lymphopenia. The diagnosis is established by the presence of circulating antimitochondrial antibodies. In 1975 it was found that the disease was due to prolonged treatment with Venocuran, a drug against venous disorders composed of phenopyrazone (pyrazolone derivative), horse-chestnut extract, and Miroton (glycosides extracted from white squill [Urginea maritima], convallaria, oleander and adonis). The drug was then withdrawn. No new cases have come to our attention since then. 15 patients with severe pseudolupus known to us in 1975 have now been followed up. In 6 of the patients all symptoms disappeared within weeks or a few months after withdrawal of the drug. However, the other 9 patients had at least 1 and often 2--3 relapses in the following months to years. In some patients, symptoms remained as long as 4--5 years. Antimitochondrial antibodies persisted in 4 patients for more than 3 years and in 1 patient are still detectable now. The pathomechanism of pseudolupus has not been elucidated.

[Chlamydia peritonitis: a disease of young females]. / Die Chlamydienperitonitis: eine Erkrankung junger Frauen.

Serological evidence of recent infection with Chlamydia trachomatis was found in 9 of 11 young women with acute peritonitis or perihepatitis proved by laparoscopy. High antibody titres to chlamydiae without laboratory evidence of gonococcal infection were present in 5 of these 9 patients, while the other 4 had evidence of simultaneous gonococcal infection. C. trachomatis may play an important part in peritoneal inflammation previously attributed only to gonococci.

[Therapy of Cronh's disease in the acute stage, using ornidazole (Tiberal). Preliminary results]. / Therapie des Morbus Crohn im akuten Schub mit Ornidazol (Tiberal). Vorläufige Resultate.

9 patients with acute exacerbations of Crohn's disease were treated over 2.5 months or longer with ornidazole (nitroimidazole). While 3 patients showed no response at all to 5 cycles of ornidazole treatment, 6 patients improved markedly within 2-3 months. In all but 1 patient, the improvement lasted during long-term therapy (average 9 months). Therapy was discontinued in 5 of these patients after 2.5-14 months; 2 patients had severe recurrences within 2-10 weeks, while 3 patients remained well during the follow-up (average 4.7 months). Ornidazole appears to be a promising alternative to steroid therapy in acute exacerbations of Crohn's disease and to deserve further evaluation by a double-blind study.

Chlamydia trachomatis as possible cause of peritonitis and perihepatitis in young women.

Of 11 young women with acute peritonitis proved by laparoscopy, seven of whom also had perihepatitis, nine had serological evidence of recent infection with Chlamydia trachomatis; In five of these nine patients high antibody titres to chlamydiae were found without laboratory evidence of gonococcal infection, while the other four had evidence of simultaneous gonococcal infection. C trachomatis may play an important part in peritoneal inflammation previously attributed only to gonococci.

[Vasculitis in hepatitis B infection]. / Vaskulitis bei Hepatitis-B-Infektion

Personal observations have confirmed the frequent association of HB-infection with certain forms of vasculitis. 4 of 11 patients with polyarteritis nodosa were repeatedly found to be HBs-Ag positive and had chronic hepatitis of varying severity. In patients with giant cell arteritis (polymyalgia rheumatica and temporal arteritis) anti-HBs was found more frequently than in controls, especially when examined within 6 months after onset of symptoms (7 of 20 equal 35% had anti-HBs, versus 6% of controls). Several lines of evidence point to the important role played by circulating HBs-Ag/anti-HBs complexes in the development of HB-associated vasculitis.

[Non-HL-A specific autoantibody against granulocytes, lymphocytes and thrombocytes in a patient with agranulocytosis due to pyrazolone]. / Nicht-HL-A-spezifischer Autoantikörper gegen Granulozyten, lymphozyten und Thrombozyten bei einer Patientin mit Agranulozytose nach Pyrazolon

An antibody of hitherto unknown specificity has been found in the serum of a patient who suffered three episodes of agranulocytosis after ingestion of aminopyrine derivatives. In vitro, the antibody reacts not only with homologous and autologous granulocytes and thrombocytes. It belongs to the IgM class and absorption of the serum with earlier leukocytes or platelets eliminates the activity against all three cell types. An HL-A specificity (LA or Four locus) can be ruled out, since all tests are positive with cells of individuals differing from the patient in all four HL-A specificities. Addition of the patient's serum results in marked reduction of thymidine uptake in the mixed leukocyte culture as well as during stimulation of lymphocytes with phytohemagglutinin or PPD; however, almost no effect is observed on stimulation with small amounts of Pokeweed mitogen. The rosette formation of lymphocytes with sheep erythrocytes or sensitized human erythrocytes is not influenced by this serum. This pattern is comparable to what is known for alpha-methyl-dopa-induced autoimmune hemolytic anemia insofar as the antibody does not require the presence of the offending drug for its action.

Drug-induced pseudolupus.

Of fifteen patients with pseudolupus (a syndrome characterised by recurrent fever, myalgia, arthralgia, pleuritis, pulmonary infiltrates, pericarditis, myocarditis, and by mitochondrial antibodies in the absence of nuclear antibodies), all had been treated with "Venocuran", one of a great number of drugs used for venous diseases. This drug, available in twenty countries under various names, contains phenopyrazone, horse-chestnut extract, and cardiac glycosides extracted from various plants. Further studies revealed that up to 90% of long-term users of venocuran acquired mitochondrial antibodies. This was not true for patients with venous diseases being treated with other drugs. About 30% of long-term users of venocuran might experience prodronal symptoms, such as myalgia and arthralgia, while more than 10% could develop the full disease.

Functional studies of Peyer's patches: evidence for their participation in intestinal immune responses.

The pattern of responsiveness of lymphocytes from Peyer's patches, spleen, mesenteric, and inguinal nodes of guinea pigs was compared after oral and parenteral immunization. After oral immunization with BCG, Peyer's patch lymphocytes showed the best in vitro proliferative responses to PPD (tuberculin). Responsiveness to Clostridia, normal constituents of the intestinal microflora, also was significant in Peyer's patches, and low or absent in the other lymphoid tissues examined. In animals immunized parenterally with heat-killed Mycobacterium tuberculosis, lymphocytes from the spleen reacted best to PPD and those from Peyer's patches least. Selective elimination of B or T cells from PPD-reactive Peter's patch lymphocyte populations showed that the T-cell-rich fraction remained responsive to PPD, the B cell-rich fraction became unresponsive; but both fractions reacted to Clostridia. We conclude from this experiment that a functional T cell population is present in these organs. Peyer's patches in the guinea pig are immunocompetent lymphoid organs which seem to be primarily engaged in immune responses to antigens presented from the intestinal lumen.

[Pseudolupus: a severe side effect of a varicose vein drug?]. / Pseudolupus: eine schwere Nebenwirkung eines Venenpräparats

Among 7 patients with "pseudolupus" (a lupus erythematodes-like syndrome with antimitochondrial antibodies) an unusual incidence of varicose veins was noted. Reexamination of their histories revealed that all had been taking the same rather uncommon drug "Venocuran" for a prolonged period before developing the typical symptoms of this disease (recurrent fever, perimyocarditis, myalgias). They appeared on average 7 months after initiation of drug therapy and lasted for weeks or months even when the drug was promptly withdrawn. It is probable, though by no means certain, that one or several components of this drug play an important role in the pathogenesis of this immunologically distinct disease.