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Das Muir-Torre-Syndrom (MTS), eine seltene, autosomal-dominant vererbte Erkrankung, ist klinisch durch Talgdrusenneoplasien und mindestens ein viszerales Malignom charakterisiert. Fur einen Teil der Patienten wurde ein genetischer Defekt, die sog. Mikrosatelliten-Instabilitat nachgewiesen. Ebensolche Mechanismen sind fur Patienten mit hereditaren nichtpolyposen kolorektalen Karzinomen (HNPCC) bekannt, weshalb zumindest bei einem Teil der MTS-Patienten die phanotypische Variante dieses Syndroms vermutet wird. Wir berichten uber eine 66-jahrige Patientin mit MTS, bei der sich im Verlauf von 32 Jahren multiple maligne viszerale und kutane Tumore manifestierten. Zusatzlich bestanden multiple Talgdrusenadenome. Mit 2 von 5 Markern wurde im Tumorgewebe eine Mikrosatelliten-Instabilitat nachgewiesen. In der Familienanamnese wiesen mehrere Verwandte mutterlicherseits maligne viszerale Tumore auf.

Cyclic neutropenia is a rare hematologic disorder of unknown origin. Periodic decreases in blood leukocytes with relative neutropenia and lymphocytosis are typical. These episodes appear in regular intervals of 15-35 days and last three to seven days. They are associated with physical weakness, fever, septic complications and necrosis of mucous membranes. Between the episodes, the patients are in complete clinical and laboratory remission. We report the case of a 34 year-old patient suffering from cyclic neutropenia with ulcerous lesions of the oral mucosa.

A 42- year-old atopic patient had suffered from disseminated verrucae since he was 14 years old. He had been treated with various, often expensive immunomodulatory agents for a long time without appreciable success. Laboratory tests revealed a striking T-cell defect. Topical treatment with imiquimod (Aldara 5% Cream) led to the regression of all verrucae.

Die Differentialdiagnostik der vernarbenden Alopezie umfast ein Spektrum unterschiedlichster Erkrankungen. Wir berichten uber den Fall einer 60jahrigen Patientin mit einer progredienten, bisher therapieresistenten Pseudopelade Brocq, bei der wir im Rahmen der atiologischen Abklarung eine Borreliose Stadium III diagnostizierten. Nach 3wochiger parenteraler Therapie mit Cefotaxim (Claforan®) zeigt die bisher uber ein Jahr bestehende Nachbeobachtungszeit ein Stillstand des Effluviums und vollstandige Abheilung der Entzundung. Diese Erstbeschreibung eines moglichen ursachlichen Zusammenhangs zwischen einer vernarbenden Alopezie und einer Borreliose Stadium III erweitert das differentialdiagnostische Spektrum zur Atiologie der Pseudopelade Brocq und bietet die Moglichkeit einer kausalen Therapie.

In an untreated 26-year-old female patient suffering from Neumann's pemphigus vegetans for 8 months (with neither preceding thymoma nor myasthenia gravis), several in vivo and in vitro phenomena of immunodeficiency involving both T and B cell system were disclosed. A diagnosis of defective immune state was established on the basis of the low IgG-serum level (though pemphigus antibodies were present), reduced T cell count in blood, weak PHA stimulation of lymphocytes, lack of skin reactivity to recall antigens and to most other bacterial antigens tested. Impaired chemotaxis and a deficient intracellular killing of Candida albicans by PMNL were also found. The conclusion is drawn that a combined disorder of both the B and T cell system is involved in the etiology of pemphigus vegetans, even when thymoma is ruled out.

A cellular immunodeficiency was revealed in a 39-year-old female patient suffering from Werner’s syndrome. Relevant findings were negative intracutaneous tests to candidin, trichophytin, tuberculin and bacterial antigens, reduced lymphocyte response to PHA, and impaired intracellular killing of Candida albicans by granulocytes. The inclination of patients suffering from Werner’s syndrome to develop neoplasms may be related to this immunodeficiency.

Apart from nonspecifically altered laboratory data, enhanced chemotaxis of polymorphonuclear leukocytes to chemotactic stimuli, HLA-B5 and circulating cytotoxic lymphocytes for oral epithelial cells were demonstrated in a 21-year-old patient suffering from Behçet’s disease (BD). Pathological liver function became indicative of concomitant hepatic involvement. The pathogenetic role cytotoxic lymphocytes have on the oral mucosa in BD is discussed.

The humoral and cellular immune status, the cutaneous pathergy, PMNL in vitro function tests as well as clinical and general laboratory examination were performed and evaluated on ten patients suffering from Behcet's disease (BD) and ten other patients with benign recurrent aphthosis (RA). The same set of in vitro tests (except PMNL exposure to solutions of copper sulfate or DDT) was carried out on a control group consisting of more than 100 healthy male and female individuals of various ages. Apart from general signs of inflammatory activity (leukocytosis, elevation of ESR, increased IgG serum levels), cutaneous pathergy to mild local highly injuries and marked enhancement of PMNL chemotaxis proved to be highly significant symptoms in acute phases of BD in contrast to benign RA. Both symptoms, in particular the hyperchemotaxis of PMNL, can be regarded as valuable diagnostic means in the early detection of beginning or atypical BD.

In a 21-year-old male patient afflicted with widespread recurrent pyoderma resistent to antimicrobial therapy since 3 years, a deficient state of cellular immunity including dysfunctions of both microphages and T lymphocytes was disclosed. After 6 weeks of systemic treatment with levamisole all lesions cleared completely, whereas appropriate long-term antibiotic therapy previously administered had failed to succeed. The immunological parameters, as far as being reexamined, also returned to normal levels during levamisole therapy.

In 20 patients with histologically confirmed pustular bacterid the immuno-logical status was checked including lymphocyte and granulocyte components of the cellular immune system as well as HLA typing. For comparison the same investigations were carried out in 20 healthy controls. In contrast to the controls, in the group of patients the chemotactic activity of polymorphonuclear leukocytes as well as their ability to engulf either vital or heat-inactivated Candida albicans cells was found to be slightly impaired (p ≤ 0.01 and 0.05, respectively). Killing of C. albicans cells by polymorphonuclear leukocytes was strikingly impaired (p ≤ 0.001). NADPH-dependent oxidase activity, however, was found to be normal. Impairment of chemotaxis and killing activity could not be substantiated in AB pool serum, thus a serum-dependent disorder of granulocyte function has to be assumed. Lymphocyte response to phytohemagglutinin was reduced in all patients, whereas intracutaneous test reactivity to microbial antigens was normal. T and B cell counts in peripheral blood were within normal range. HLA typing revealed a significantly increased prevalence rate of HLA-B14 as compared with the control group and other patients.

The function of microphages has been studied in two patients with chronic pyoderma vegetans by in vitro determination of phagocytosis as well as chemotaxis. The results showed a striking decrease in the chemotactic activity of the neutrophil granulocytes, a reduced phagocytosis of Candida albicans and Staphylococcus aureus, and a weakness of the intracellular killing of these microorganisms. However, the NADH-dependent oxidase activity appeared to be intact. No defect was found in the specific cellular or humoral immune system in either patient.

Typical signs and symptoms of type III allergy occurred in a 55-year-old diabetic during diabetes and diuretic treatment with glisoxepid, glibenclamide, furosemide and probenecid. Symptoms of this type of allergy unintentionally recurred with every subsequent therapeutic administration of each one of these drugs. The possibility of a cross allergy between sulphonamide diuretics, chemotherapeutic sulphonamides and sulphonyl-urea compounds has only rarely been described.

In an untreated 26-year-old female patient suffering from Neumann's pemphigus vegetans for 8 months (with neither preceding thymoma nor myasthenia gravis), several in vivo and in vitro phenomena of immunodeficiency involving both T and B cell system were disclosed. A diagnosis of defective immune state was established on the basis of the low IgG-serum level (though pemphigus antibodies were present), reduced T cell count in blood, weak PHA stimulation of lymphocytes, lack of skin reactivity to recall antigens and to most other bacterial antigens tested. Impaired chemotaxis and a deficient intracellular killing of Candida albicans by PMNL were also found. The conclusion is drawn that a combined disorder of both the B and T cell system is involved in the etiology of pemphigus vegetans, even when thymoma is ruled out.

The function of microphages has been studied in two patients with chronic pyoderma vegetans by in vitro determination of phagocytosis as well as chemotaxis. The results showed a striking decrease in the chemotactic activity of the neutrophil granulocytes, a reduced phagocytosis of Candida albicans and Staphylococcus aureus, and a weakness of the intracellular killing of these microorganisms. However, the NADH-dependent oxidase activity appeared to be intact. No defect was found in the specific cellular or humoral immune system in either patient.

Twenty-four patients suffering from longstanding severe recurrent herpes simplex, who had not responded to prior therapy, were treated with s.c. thymopentin injections 50 mg, three times weekly, over a period of six weeks. They were followed up at weekly intervals over this period and then six weeks later. Moreover, the longest relapse-free period observed in the year after the treatment was recorded in the investigator's documentation. Thirteen of the 14 patients with labial herpes simplex and 10 of the 13 patients with genital herpes simplex improved markedly as shown by a decrease in the relapse rate of at least 50%, shorter episodes of relapse and improvement of symptoms such as pain and itching. Fourteen of these 27 patients experienced no relapse for a period longer than four months after cessation of the therapy. No serious side-effects were observed. Laboratory examinations before, during and after thymopentin did not reveal significant alterations except for an increase in the T-helper/T-suppressor ratio. The effect of thymopentin is assumed to be due to T-helper cell activation resulting in enhanced interleukin-2 production with subsequent proliferation of cytotoxic T lymphocytes and natural killer cells which are capable of producing immune interferon.

Comparative in vivo examinations of skin (cutaneous pathergy test, skin window technique over 24 h according to Rebuck) were carried out in 12 patients with Behçet’s disease (BD) and in 13 healthy volunteers serving as controls. 10 out of 12 patients at active phases of BD showed a positive papular (-pustular) skin reactivity to needle prick or vene puncture. These 10 patients simultaneously revealed an increased chemotactic activity of polymorphonuclear leukocytes (PMNL) in vitro. In the controls all pathergy tests were negative and chemotaxis of PMNL was within normal range. The proportion of PMNL initially coming up to 100% in the skin window preparations, very rapidly decreased in patients with BD as compared to a distinctly slower drop in the controls. Conversely to the number of PMNL, the skin window cellular pattern was built up by monophagocytic cells replacing the PMNL. The phenomenon of ‘rapid depletion of PMNL’, from skin window can be considered an additional hint on the functional disturbance of the PMNL involved in the pathogenesis of BD.

Die Mikro- und Makrophagen spielen im Rahmen der Immunabwehr des Organismus eine sehr wichtige Rolle. Die Funktionen der Mikrophagen bzw. in Kultur gezuchteten Makrophagen sind bei verschiedenen Erkrankungen in vitro untersucht worden, wahrend dies bei frisch aus dem Blut isolierten Makrophagen (Monozyten) wegen methodischer Schwierigkeiten bisher nur sehr selten erfolgte [1, 9].

Die rezidivierende orale Aphthosis ist eine sehr haufige Erkrankung, die sich am meisten bei pradisponierten Personen im 2.–3. Lebensjahrzehnt manifestiert und bei etwa zweimal haufiger vorkommt als bei Mannern. An der Manifestation der Erkrankung sind nicht nur genetisch-familiare Komponenten, sondern auch verschiedene externe und interne sowie Umweltfaktoren beteiligt. HLA-Typisierungen an betroffenen Familienmitgliedern zeigen auch die genetische Disposition deutlich.

The present randomized, placebo-controlled double-blind multicenter study included a population of 36 subjects with frequent recurrences (at least once a month) of herpes labialis. Most of the patients had failed to respond adequately to previous treatment with other therapeutic tools, including acyclovir. Either 50 mg of thymopentin or of placebo was administered 3 times a week, by the subcutaneous route, for 6 weeks. Subsequently, the patients were observed for nearly 6 months on the average. The results achieved with thymopentin for the individual parameters were significantly superior to those obtained with placebo; thus significant improvement was seen in patients on thymopentin in the duration of the longest symptomfree period (prolonged from 2.1 weeks to 20.9 weeks, p = 0.000), in the number of relapses (reduced from 1.6 to 0.4 episodes/month, p = 0.001), and in the total duration of herpes symptoms per month (shortened from 2.0 to 0.3 weeks, p = 0.000). Placebo treatment also resulted in considerable improvement (p less than 0.05 or 0.01), but was significantly inferior to the improvement obtained with thymopentin. The longest symptomfree period in the placebo group was prolonged from 2.4 to 11.2 weeks. The number of relapses per month was reduced from 1.4 to 0.8, and the total duration of herpes symptoms per month from 2 to 0.9 weeks. The results of intergroup analyses, in which the observed parameters and the improvement achieved in either group were compared, significantly favored thymopentin treatment. The effect of thymopentin was in all but one parameters superior to that of placebo and highly significant (p less than 0.01).

SUMMARY The effect of blood lymphocytes on syngeneic oral epithelial cells was studied in twelve patients with Behcet's disease (BD) and twenty-one patients with recurrent aphthous ulcers (RAU). The control group consisted of twenty-five patients with non-aphthous skin disease and eight healthy individuals. Primary cell lines obtained from oral mucosa by suction blistering and subsequent enzymatic dissociation were used as target cells. Using a modified 51chromium release macro-assay, a significant lytic effect due to antibody-independent lymphocytotoxicity could be demonstrated in patients with BD, but no significant lysis of target cells was found in the RAU patients compared with the control group. These results provide further evidence that antibody-independent lymphocytotoxicity may play an important role in oral ulceration in BD.

Publisher Summary This chapter presents a study focusing on immunoglobulin demonstration in circumorificial plasmacytosis. Paraffin blocks of 22 biopsies of circumorificial plasmacytosis from different locations were available for this study. Sections were deparaffinized and treated with the peroxidase-antiperoxidase technique according to Sternberger (1979) with control serum, anti-IgA, anti-IgG, anti-IgM, and anti-lysozyme. Ig-containing plasma cells (PCs) were counted and graded as 1+:1–10 PC per medium power field, 2+: 10–15 PC, 3+:50–100, and 4+:more than 100. Lysozyme-immunoreactive polymorphonuclear leucocytes (PMNL) and monocytes/macrophages were similarly counted. In 20 out of the 22 biopsy specimens investigated, there were markedly more IgG PC than IGA PC. Very high numbers of IgM PC were only found in two biopsies and high numbers in another three specimens. Lysozyme-positive PMNL were found in 19 specimens; however, macrophages were demonstrated in only one biopsy. Folliclelike lymphocytic foci were found in four specimens. No clonal proliferation of PC producing only one Ig was seen in association with these lymphocytic infiltrates. Germinal centers within such foci were found in one biopsy.

Beim Morbus Behcet (MB) bzw. Behcet-Touraine handelt es sich um eine Systemvasculitis mit polytoper Organbeteiligung. Hinsichtlich der multifaktoriellen Manifestationsmechanismen der Erkrankung werden Klinik, Atiologie, Pathogenese, Epidemiologie und genetische Aspekte unter besonderer Berucksichtigung der immunpathologischen Vorgange, der cutanen Hyperreaktivitat und Therapie beschrieben. Anhand eigener Ergebnisse wird gezeigt, das es sich beim MB nicht um eine Immundefekterkrankung, sondern um eine Krankheit mit gesteigerter Immunreaktivitat handelt, wobei die Hyperchemotaxis der Granulocyten wahrend akuter Krankheitsschube dominiert. Zirkulierende Immunkomplexe und positive Lymphocytotoxicitat gegen autologe orale Mucosazellen weisen auf die wichtige Rolle der immunpathologischen Vorgange bei der Manifestation des MB hin. Die Untersuchung der Zellmorphologie der cutanen Pathergie mit Hilfe der Hautfenstermethode nach Rebuck zeigt semiquantitativ eine pathognomi- sche Zellkonstellation beim MB.

In 1977, we reported an increased phagocytotic activity in the semen of patients suffering from a varicocele. It was our assumption that this enhanced phagocytosis was caused by the varicocele [2].

Chemotactic, phagocytic and intracellular killing activities of polymorphonuclear leukocytes (PMNL) were investigated in vitro in 49 patients suffering from recurrent bouts of herpes simplex. A slight impairment of chemotactic activity and a markedly reduced capacity of killing Candida albicans blastospores were revealed. Phagocytic capacity and NADH-dependent oxidase activity of PMNL proved to be normal. The results point to an alteration of some PMNL functions in these patients.

This paper presents longitudinal clinical and immunological findings in a patient with a life-long history of pluriorificial pyoderma vegetans, a disease characterized by a distinct immunodeficiency of T lymphocytes. After treatment with thymopentin, 50 mg s.c. three times weekly for 12 weeks, the number of T lymphocytes in peripheral blood normalized, while other impaired immunological functions failed to improve, however. The most impressive observation was the significant clinical improvement of the patient's condition.

Es wurde die Oberflachenstruktur der polymorphkernigen neutrophilen Granulozyten (PMNL) bei der Phagozytose von Candida albicans (C. alb.) untersucht. Insbesondere interessierten etwaige Veranderungen der Morphologie bei Patienten mit zellularen Immundefekten. Ebenso wurde die Morphologie der Lymphozyten untersucht.

In a 21-year-old male patient afflicted with widespread recurrent pyoderma resistent to antimicrobial therapy since 3 years, a deficient state of cellular immunity including dysfunctions of both microphages and T lymphocytes was disclosed. After 6 weeks of systemic treatment with levamisole all lesions cleared completely, whereas appropriate long-term antibiotic therapy previously administered had failed to succeed. The immunological parameters, as far as being reexamined, also returned to normal levels during levamisole therapy.

The chemotactic microphage function in combating and eliminating microorganisms is one of the most important features of the cellular immune system. Using a modified Boyden method we studies in vitro the chemotactic activity of the granulocytes in 5 patients suffering from chronic muco-cutaneous candidosis (CMCC), 3 of the familial and 2 of the non-familial type. To obtain quantitative results comparable to those of a control group, we investigated the granulocytes of 55 clinically and immunologically healthy persons by the same way. So we found, in comparison with the results of the controls, a striking reduction of the chemotactic granulocyte activity in all CMCC patients. This impairment of chemotoxis is apparently due to an inborn defect of the microphages. It is pointed out, however, that a non-specific stimulation of the immune system might be a promising way in the treatment of patients affected by CMCC.

Twenty-seven patients suffering from long-standing, severe, recurrent herpes simplex (14 labial and 13 genital) who had not responded adequately to prior therapy were recruited for this open, monitored study. They were treated with thymopentin 50 mg subcutaneously three times weekly for a period of 6 weeks. Clinical controls were performed once a week and then again 6 weeks after cessation of therapy; laboratory investigations were done at time points 0, 3, and 6 weeks. Additionally, information was collected with regard to the clinical course during the following year. Thirteen of 14 patients with labial infection and 10 of the 13 with genital herpes improved markedly (p less than 0.05) as shown by decrease in the relapse rate of at least 50%, shorter relapse episodes, and improvement of symptoms such as pain and itching. Fourteen of these 27 patients experienced no relapse for a period longer than 4 months after cessation of therapy. These favorable results were paralleled by a statistically significant increase in the T cell helper/suppressor ratio. This finding indicates that thymopentin acts as an immunodomulator; it is assumed that the activation of T helper cells induces-presumable via interleukin 2-the proliferation of cytotoxic T lymphocytes and natural killer cells which play a major role in the natural immune defense. No serious side effects of thymopentin were recorded.

There is now a great deal of evidence to prove that monocytes are formed in the bone marrow. After circulating for a certain time these cells leave the vascular tree and migrate into the tissue. Here they give rise to tissue macrophages (1–12).

The frequencies of HLA-class I antigens were studied in 39 patients with Adamantiades-Behçet's disease and were compared with those in 1415 [corrected] healthy controls; both patients and controls were of German origin. Moreover, the correlations of HLA antigens with onset, various clinical features and the course of the disease were investigated and the familial clustering of the disease was examined. We found an increased frequency of the HLA-B5 antigen in these series (P0.05, relative risk 2.6, confidence interval 1.2-5.5). The presence of HLA-B5 was more frequently detected in male (41%, relative risk 4.9, confidence interval 1.8-13.1) than in female patients (9%; P0.05). A significantly higher frequency of HLA-B5 was found in male patients with severe vascular involvement, including blindness and thrombosis, than in HLA-B5-positive male patients without these features. Incidences of genital ulcers, ocular involvement, cutaneous features, positive pathergy test and of secondary symptoms as well as the age of onset and the duration of development of the complete clinical picture were all found not to be significantly correlated with any of the HLA-A, -B, -C alleles. Familial clustering was also not found in German patients. Because of the low relative risk in the presence of HLA-B5 and the lacking familial clustering, it seems likely that there is a weak immunogenetically determined predisposition for Adamantiades-Behçet's disease in Germany. HLA-B5-positive male persons of German origin show a higher relative risk to develop or acquire Adamantiades-Behçet's disease than female ones.(ABSTRACT TRUNCATED AT 250 WORDS)