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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.

The differential diagnosis of cicatricial alopecia includes a wide variety of diseases. A 60-years-old woman was admitted to the hospital because of an unsuccessfully treated, progressive pseudopelede of Brocq. Further examination revealed an borreliosis (Stage III). After 3 weeks of treatment with intravenous Cefotaxime (Claforan), follow-up examination one year later show an complete arrest of the alopecia. This first description of cicatricial alopecia to be causally related to borreliosis Stage III extends the differential diagnosis of pseudopelede of Brocq and offers a curative therapy.

In a 20-year-old women having suffered from Crohn's disease for many years, we found granulomatous fistular ulcerations on her right distal lower leg. After histological verification of the clinical diagnosis, she was orally treated with metronidazole for 6 weeks with excellent results: The cutaneous lesions healed completely.

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.

Polymorphonuclear leucocytes (PMNL) or microphages resp. are essentially involved, on account of their ubiquity within the entire organism as well as their phagocytic and intracellular killing properties, in the complex organization of the antimicrobial and antitumoral protective capacity of man. Positive chemotaxis triggers the migration of PMNL to the specific danger area and thus initiates an immune reaction. An either inborn or acquired defect or functional weakness of PMNL may entail a state of persisting viral, fungal and/or bacterial infections. Impairment of various PMNL functions may result from different metabolic disorders, internal malignancies, and/or immunosuppressive therapy. Disturbances of various PMNL functions can be especially analysed in vitro. After delineation of different techniques available to check the immunological defense system of the human organism, we report on our results of PMNL function analysis in patients suffering from chronically recurrent pyoderma (n = 22), oral precancer and cancer (n = 13), chronic mucocutaneous candidosis (n = 10), recurrent aphthous ulcers (n = 33), as well as Behcet's disease (n = 20).

Five patients suffering from recurrent oral aphthae and one patient with Behçet's disease were treated with thymopoetin pentapeptide injections for 6 weeks. Although some immune parameters showed a tendency toward normalization no clinical improvement was observed.

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.

Recurrent oral aphthosis, a very frequent disease, is encountered most often in predisposed individuals in their second to third decade, and found twice as often in females than in males. Not only genetic but a variety of different other factors participate in the manifestation of the disease, many of them controversial as far as their significance is concerned. Polymorphonuclear leukocyte (microphage) function is unimpaired. HLA-studies in affected families indicate a genetic disposition.

Various micro- and macrophage functions were studied in vitro in 21 patients suffering from lichen ruber planus and in 100 healthy individuals. A slight impairment of chemotactic activity of microphages (12/21) and a reduced capacity of intracellular inactivation of microorganisms in both systems (14/21; 3/12) were found.

22 patients (10 female, 12 male) aged between 60 and 76 were tested in vitro with regard to granulocyte function (i.e., leucotaxis, chemotaxis, capability of phagocytosis, intracellular killing of bacteria, and oxidase reaction). Most of the patients showed reduced chemotactic activity of the granulocytes, although the motility of these cells was normal. With regular phagocytosis of candida albicans cells--either active or heat-inactivated the intracellular killing rate of bacteria was clearly decreased in all cases. The intracellular oxidase activity of granulocytes always showed normal function.

The granulocytes which are distributed by blood circulation close to the extern and intern body surfaces as well as in all organs protect the organism from microbial perils by phagocytosis and intracellular killing of bacteria and fungi so constituting a very important component of the granulocytic functions seriously impairs the host resistance and may entail a state of persisting infectious disease. As chronic mucocutaneous candidosis (CMCC) represents such a persistent generalized infection, we studied in vitro several functional activities of the granulocytes of 5 patients suffering from CMCC. 2 of them presented a non-familiar type of CMCC, the remaining 3 patients (father and 2 daughters) were subject to the hereditary type of CMCC. For comparison, by the same way we investigated the granulocytic functions of 51 clinically and immunologically healthy adult persons. Each of our 5 patients exhibited a reduced ability of the granulocytes to phagocytize and kill Candida albicans. In the CMCC family, the father had a marked deficiency of the oxidase activity of the granulocytes whereas in his daughters, the oxidase deficiency proved to be of a minor grade. In the sera of both daughters a phagocytosis inhibiting factor could be assumed to exist in addition to the granulocytic abnormalities. When heat-inactivated Candida albicans cells, however, were used for experiments, the granulocytes of each patient were able to phagocytize the germs at the same rate as did the granulocytes taken from the controls. With regard to alterations of the T cell function previously reported in CMCC, in all patients we also could demonstrate various symptoms of a T cell-dependent immunodeficiency. The results of the present in vitro-experiments furnish good evidence of a state of fundamental deficiency of the microphages in patients with CMCC, which may be the dominating cellular factor in the aetiopathogenesis of CMCC.

25 patients (2 females, 23 males, 20 to 40-year-old) suffering from condylomata acuminata (19 genital, 2 anal, and 4 genitoanal lesions) were locally treated with salicylic acid containing 5-fluorouracil (Verrumal) once a day. This therapy resulted in complete healing within 12 days on an average. 5 patients showed a relaps after 2 weeks to 5 months and were treated again. The treatment failed in a 40-year-old patient suffering from condylomata acuminata genitalis.

25 patients suffering from recurrent herpes simplex infection were orally treated with acyclovir 5 X 200 mg daily for 5 days. Control examinations were carried out on the 1st, 3rd, 5th, and sometimes on the 7th day of treatment. All patients treated showed a significantly shortened course of the disease and quick decrease of the symptoms. If acyclovir was applied during the prodromal phase, we additionally found inhibited vesicular eruption. There were not observed any dangerous side effects.

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.

Specific infiltrations in myelogenous leukemia are rare and occur mostly in the course of an acute blast crisis often representing the terminal phase of the disease. A 50 year-old female patient is described who developed specific cutaneous lesions during such a blast crisis. The infiltrates consisted to a major part of eosinophilic myelocytes although the peripheral blood smear showed only relatively few mature eosinophils.

Polymorphonuclear leukocyte (PMNL) function tests were performed in 20 patients suffering from chronic recurrent pyogenic skin infections and, in addition, in 20 healthy individuals. As for in vitro tests, investigations of chemotaxis, intracellular killing and NADH dependent oxidase activity were included. Compared to the control group, a marked impairment of chemotaxis but totally normal microphage motility, a significantly decreased intracellular killing of ingested microorganisms by these phagocytes and an almost phagocytosis of viable and heat-inactivated Candida albicans cells could be detected in the examined patients. These results once again demonstrate the extraordinary importance of PMNL in the body's primary defense mechanisms.

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.

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 five patients with either familial or non-familial type of chronic mucocutaneous candidosis some properties of phagocytic function of the polymorphonuclear leucocytes (PMNL) have been studied in vitro. In each of the patients there were found: a) a decreased chemotactic activity of PMNL, b) a weakness of intake and of intracellular destruction of Candida albicans cells by PMNL, c) an impairment of phagocytosis and intracellular killing of Candida albicans as well of Staphylococcus aureus by PMNL. The rate of phagocytosis of heat-inactivated Candida albicans cells by PMNL was normal in each case. In the serum of two patients a phagocytosis inhibiting factor is supposed to exist. In PMNL of 3 patients a defective activity of NADH-dependent oxidase was found. The occurrence of hereditary CMCC in a father and his two daughters points to an autosomal dominant trait, whereas in most cases of familiar CMCC hitherto described an autosomal recessive mode of transmission was found.

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).

There is a variety of immunologic and etiologic phenomena in Lupus Erythematosus Disseminatus (LED) sive Visceralis particularly when induced by drugs ("Pseudo-LE-Syndrom"). In this report a patient (age 22 y.) is presented suffering from LED in whom the disease exacerbated under treatment with Ethambutol. Various drugs known to either cause a "pseudo-LE-Syndrom" or to induce or aggravate a LED have been compiled in this paper and listed in tablets; Ethambutol apparently represents a new addition to the drugs listed.

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.

82 of 203 patients with malignant melanoma and other skin diseases suitable for DNCB-immunotherapy were re-exposed to standard test substances, chloramphenicol, and another four p-nitrocompounds similar to DNCB by epicutaneous patch tests 6-15 months after primary sensitization with DNCB. The DNCB sensitizaton threshold proved to be unchange. No cross allergy with chloramphenicol was observed However, two patients showed sensitization against picric acid not seen before. A group allergy may be suggested in both cases. Immunotherapy with DNCB is briefly discussed. Apart from a very low rate of group sensitization, topical treatment with threshold concentrations of DNCB has neither toxic effect nor produces scarring nor generalized eczema.

Report on a 55-year-old female patient developing skin-colored papules on her back and shoulders after sun exposure and later on typical lupus erythematosus (LE) lesions. During therapy with chloroquine there was regression of LE and annular extension of peripherally developed mucinous papules which did not vanish entirely. Histochemically, dense reticular deposits of metachromatic mucinous material was found in the mid cutis.