[Adamantiades-Behçet disease: necrotizing systemic vasculitis with a fatal outcome]. / Morbus Adamantiades-Behçet: nekrotisierende Systemvaskulitis mit letalem Ausgang.

Vascular involvement in Behçet's disease was first mentioned by Adamantiades and occurs in addition to the classic symptom triad. In the present work an unusually fulminant course of Adamantiades-Behçet disease with a lethal outcome is reported in a 43-year-old male patient of German origin. The first symptoms were painful oedemas of the joints, followed 1 year later by bipolar aphthous lesions and by multiple progressive ulcers of the skin and the oral mucosa. Histologically, pustule formation with underlying vasculitis was diagnosed. In spite of systemic treatment with azathioprine and high-dosed prednisolone, the course was progressive with multiple necrotizing ulcers, and the patient died 18 months after the onset of the disease with signs of heart insufficiency and cachexia. The autopsy findings revealed multiple lesions of ulcerating systemic vasculitis of the skin and other visceral organs, including the lungs and the central nervous system, and also endocarditis verrucosa ulcerosa of the mitral valve.

[Chronic erosive, therapy-resistant perianal herpes (type II) with herpes proctitis in AIDS]. / Chronisch-erosiver, therapierefraktärer perianaler Herpes (Typ II) mit Herpes-Proktitis bei AIDS.

In an AIDS patient who had repeated successful treatment with acyclovir in his history, erosive herpes perianalis with herpes proctitis appeared, which persisted over several weeks. High-dose intravenous administration on of acyclovir (500-750 mg, 3 x daily, over 7 weeks) did not reveal any beneficial effects: However, almost complete clearing of the lesions occurred within 3 weeks of intravenous administration of Foscarnet (50 mg/kg body wt., 3 x daily). No relapse was seen in a follow-up period of 4 months. HSV type II was isolated by culture from the erosive lesions before treatment, but no virus was found 1 week after application of Foscarnet. The unusual chronic refractory course of a severe HSV type II infection in AIDS suggests the presence of an acyclovir-resistant HSV strain in this case. This is the first observation indicating acyclovir-resistance in the Federal Republic of Germany and a warning against the unlimited use of acyclovir in AIDS patients. Foscarnet may be beneficial in some of these cases.

Long-term therapy of HIV-associated Kaposi's sarcoma with recombinant interferon alpha-2a.

Five young male patients with HIV-associated Kaposi's sarcoma (KS) were treated with recombinant interferon alpha 2a (rIFN-alpha-2a) over a period of 2-2.5 years. An IFN dose of 18 x 10(6) IU was given subcutaneously every day during the first 3 months of treatment and then on alternate days. Additional treatment with radiotherapy and laser therapy was given and, in some cases, isolated skin nodules were excised. Within 7 months of initiation of therapy one patient had a complete remission of his tumours, however, tumour progression recurred after the patient discontinued treatment. In another patient the tumour cleared within 9 months of rIFN therapy, and after 52 months he is still free of KS. The condition of a third patient tended to become stabilized during the first 6 months of therapy, but after 60 months there has been a slow progression. The fourth and fifth patients died 25 and 28 months, respectively, after the histological diagnosis of KS and the initiation of treatment. While on therapy with rIFN-alpha-2a, no life-threatening opportunistic infections occurred. The side-effects were mostly well tolerated, and no severe changes in haematological parameters were caused by the therapy.

Long-term combined rIFN-alpha-2a and zidovudine therapy for HIV-associated Kaposi's sarcoma: clinical consequences and side effects.

Interferon alpha (IFN-alpha) has been shown to be effective in treating HIV-associated KS in at least 30% of patients, and Zidovudine has proved beneficial for AIDS patients. Moreover, both drugs have demonstrated an inhibitory effect on HIV replication. Based on the above, we combined IFN-alpha and zidovudine for treatment of HIV-associated KS in order to evaluate tolerance and clinical efficacy. Twenty-one homosexual men with histologically proved HIV-associated KS were treated in an open trial with rIFN-alpha-2a 18 X 10(6) IU every second day and zidovudine 800-1200 mg/d. Treatment was discontinued within the first month in six patients: three of them developed subjective intolerance, and three others contracted severe opportunistic infections or HIV-cachexia. Fifteen evaluable patients received combination treatment over a period of 2-20 months (average 10 months). The dosage was reduced as required based on drug-induced cytotoxicity. Complete remission was observed in four patients, partial remission in three, stable disease in two, and progression in six, resulting in an overall response rate of 46%. Negative p24 expression prior to treatment was a positive predictor. Although extracutaneous involvement had a negative influence on tumor remission, even patients with a mean initial T-helper cell count below 100 mm3 responded positively. In conclusion, combination therapy of rIFN-alpha-2a with AZT may effectively control HIV-related Kaposi's sarcoma in more than 40% of patients. In contrast to monotherapy with IFN-alpha, patients with severely reduced immune systems will also benefit from combined treatment.

Plasma glucose and free fatty acids modulate the secretion of growth hormone, but not prolactin, in the rhesus and Java monkey.

In 11 freely moving rhesus and 5 Java monkeys the plasma GH, PRL, and cortisol responses to suppression and elevation of plasma glucose and FFA concentrations were studied. Blood was sampled and infusions given via chronic jugular catheters, extended via a swivel into the adjacent room. In the rhesus monkeys, the mean plasma GH concentration rose during insulin-induced hypoglycemia from 4.7 +/- 1.9 to 17.4 +/- 2.5 micrograms/L at 60 min (P less than 0.001), and the mean plasma cortisol concentration from 320 +/- 55 to 700 +/- 133 nmol/L at 90 min (P less than 0.001). The mean plasma PRL concentration (basal value, 5 +/- 2.3 micrograms/L) did not change significantly. During glucose-induced hyperglycemia, the mean plasma GH concentration oscillated between 2.0-5.2 micrograms/L from 60-360 min (no significant change). Large GH secretory episodes occurred during hyperglycemia in individual animals. During nicotinic acid-induced plasma FFA suppression, the mean plasma GH concentration increased from 3.7 +/- 0.6 to 17.9 +/- 2.3 micrograms/L at 270 min (P less than 0.001). During lipid-induced plasma FFA elevation, the mean plasma GH concentration decreased consistently from 6.5 +/- 1.0 micrograms/L to values between 1.3 +/- 0.2 and 2.6 +/- 0.6 micrograms/L from 60-360 min (P less than 0.01). Plasma PRL and cortisol concentrations were not affected by plasma FFA changes. Compared with the spontaneous plasma GH pattern in a previously studied group of rhesus monkeys, the mean plasma GH concentration was increased during hypoglycemia and plasma FFA suppression. It was strongly suppressed during plasma FFA elevation and slightly suppressed during hyperglycemia. Similar effects were observed in the Java monkeys, although hyperglycemia tests were not performed. We conclude the following. 1) In rhesus and Java monkeys, as in man, GH secretion is stimulated by plasma FFA suppression and is inhibited by plasma FFA elevation. In both species, acute hypoglycemia stimulates the secretion of GH and cortisol. 2) These nonhuman primates differ from man in that hyperglycemia only weakly inhibits GH secretion in the rhesus monkey, if at all (Java monkeys had no hyperglycemia tests), and in neither species does acute hypoglycemia stimulate the secretion of PRL. 3) Both primate species can serve as models for the metabolic modulation of GH secretion in man, although a suppressive effect of hyperglycemia remains to be proven.

[Borrelia burgdorferi-induced pseudolymphoma with pathogen cultivation in an HIV-1 positive patient]. / Borrelia-burgdorferi-induziertes Pseudolymphom mit Erregeranzüchtung bei einem HIV-1-positiven Kranken.

Cutaneous symptoms and skin diseases are common findings in almost all HIV-1-positive patients. In many cases the clinical presentation and course of the skin diseases are atypical, and occasionally the development of the appropriate circulating antibodies is lacking or impaired. In this report we present a patient seen in our multidisciplinary outpatient clinic for HIV patients. This patient had a Borrelia burgdorferi infection with an unusual course. The acute inflammatory phase of the arthropod reaction was maintained over a period of 9 months with development into pseudolymphoma showing unusual cytological characteristics. Immunohistological evaluation revealed an almost complete lack of T-helper and Langerhans cells, but an increased number of activated cytotoxic cells with class II antigen expression. A marked serological response was observed on IgG-ELISA and in the IgG-immunofluorescence test. Borrelia burgdorferi was cultured in vitro from a skin biopsy of the involved area. To our knowledge this is the first reported case of skin borreliosis in an HIV-1-positive patient.

Interferons in dermatology.

Interferons are a large family of proteins and glycoproteins, naturally occurring or artificially produced by recombinant biotechnology. Their antiviral, antiproliferative, antitumoral, and immunomodulatory activities are induced by alterations in cell metabolism after binding to specific membrane receptors. Interferons have been used for the treatment of viral papillomas (e.g., verruca vulgaris and condyloma acuminatum), human immunodeficiency virus (HIV)-associated Kaposi's sarcoma and cutaneous tumors (e.g., melanoma, cutaneous T cell lymphoma, and basal cell carcinoma), and inflammatory dermatoses (e.g., Behçet's syndrome and psoriatic arthropathy). Clinical trials have been performed worldwide with various regimens and have not always led to conclusive results. In our experience long-term therapy with high doses of subcutaneously injected, recombinant interferon-alpha-2a in patients with HIV-associated Kaposi's sarcoma induces a remission or stabilization of the disease. In malignant melanoma a low response rate is obtained in metastatic disease with the use of interferon as a single therapeutic agent. Combined with other antitumor agents, however, interferon seems to be a useful drug. Excellent control of Behçet's disease has been obtained, and the treatment of condylomata acuminata has been effective.

[Acute primary stage of HIV infection and progression to AIDS with Kaposi sarcoma 24 months later]. / Akutes Primärstadium einer HIV-Infektion und Ubergang in AIDS mit Kaposi-Sarkom 24 Monate danach.

The case is reported of a 31-year-old homosexual male who developed distinct maculopapular and papulovesicular exanthema with aphthous-like, painful lesions of the oral mucosa, together with marked general symptoms (fever, diarrhoea, lymphadenopathy). This clinical picture suggested the primary acute phase of an initial HIV infection; during this phase the HIV-ELISA and Western blot test were negative. One year later the patient was found to be HIV-positive, showing oral candidosis, generalized lymphadenopathy, seborrhoeic eczema and zoster infection (L5/S1). A further year later, the patient developed full-blown AIDS with disseminated Kaposi's sarcoma. This observation underlines the acute inflammatory character of the primary phase of HIV infection with initial exanthema and documents the appearance of AIDS-associated Kaposi's sarcoma in a time period of maximally 2 years thereafter.

[Therapy of AIDS-induced Kaposi sarcoma and malignant melanoma with interferons]. / Therapie des AIDS-induzierten Kaposi-Sarkoms und des malignen Melanoms mit Interferonen.

Since 1980, disseminated Kaposi's sarcoma has been occurring in new epidemic proportions with a rapid clinical course in risk populations. Sixteen cases were under therapy and close surveillance from 1982 to 1986. Eight are still under therapy. In disseminated Kaposi's sarcoma with acquired immune deficiency syndrome (AIDS) our experience was encouraging. Following systemic, long-term treatment with recombinant alpha 2a interferon we observed complete remission of the lesions in 2 cases, partial remission and stabilization of the disease in 3 cases, at least temporary stabilization of the disease in 3 cases and progressive disease in 8 cases. Systemic rIFN-alpha 2a therapy was well tolerated; its long-term administration in patients with a relatively good immune status has an obviously beneficial effect on the course of Kaposi's sarcoma. In metastatic malignant melanoma Stage IV the results were only moderately encouraging. Regression of cutaneous metastases in 1 case and long-term stabilization of the disease in another patient point to antitumor activity of interferon in disseminated malignant melanoma. However, the administration of rIFN-alpha 2a in earlier stages appears more promising.

[Acute primary phase as an indicator of HIV-1 infection. The general symptoms and polymorphic exanthema with mouth mucosal involvement 2 to 6 weeks before seroconversion]. / Akute Primärphase als Indikator der HIV-1-Infektion. Allgemeine Symptomatik und polymorphes Exanthem mit Mundschleimhautbeteiligung 2-6 Wochen vor der Serokonversion.

The initial symptoms of an HIV-1 infection were observed in four patients. The following were characteristic for the acute primary phase: (a) initial maculopapular exanthema, especially of the trunk, with occasional transition into a papulovesical appearance; (b) involvement of the oral mucosa, often of aphthous character; and (c) general malaise with fever and lymphadenopathy. The observed cutaneous changes had, on one hand, features of a Coxsackie or mononucleosis exanthema, on the other of secondary syphilis. In three patients seroconversion occurred within 2-6 weeks, the fourth failed to return for follow-up. The listed acute primary symptoms can be used as the earliest indicators of an HIV-1 infection having occurred.

[Pulmonary complications in acquired immunodeficiency syndrome. Results of a prospective study]. / Pulmonale Komplikationen beim erworbenen Immundefektsyndrom. Ergebnisse einer prospektiven Untersuchung.

Between 1983 and 1987, a stepwise diagnostic programme was undertaken prospectively in 37 of 100 HIV-positive patients with 40 bronchopulmonary infections. It consisted chiefly of flexible bronchoscopy combined with lavage, transbronchial biopsy and/or removal of bronchial brush cells. Taking into account all examinations performed in life and at autopsy, 25 of the 37 patients had Pneumocystis carinii pneumonia (67.5%), 13 had bacterial pneumonia, six of these were mycobacterial infections (atypical mycobacteria in four), eight had neoplasms (pulmonary Kaposi's sarcoma in five, squamous-cell carcinoma in two, and Hodgkin's disease in one), and four patients had cytomegalovirus infection. Total diagnostic success of bronchoscopy was 78%; related to Pneumocystis pneumonia it was 91%.

Disseminated Kaposi's sarcoma in AIDS: histogenesis-related populations and influence of long-term treatment with rIFN-alpha A.

Lesions (n = 19) of cutaneous Kaposi's sarcoma in different stages of development were obtained from 13 patients with acquired immunodeficiency syndrome (AIDS), and studied by light and electron microscopy. Six additional biopsies from 4 patients treated with recombinant alpha A interferon were obtained after treatment. Varying amounts of two proliferating cell populations were found: (1) Large cells showing cytologic and histochemical characteristics of endothelial cells. They were seen in close proximity to normal vessels, forming new vascular structures and large aggregates found in papular and nodular lesions. (2) Smaller spindle-shaped cells, probably of pericytic origin. They appeared in bundles and fascicles in the papillary dermis of the cutaneous Kaposi's sarcoma lesions and, in part, gave origin to thin-walled, bizarre-shaped vessels that show incomplete lumina proliferating from the upper to the deep dermis and are surrounded by extravasate erythrocytes and siderophages. After long-term systemic treatment with recombinant alpha A interferon, the endothelial type of tumor cell aggregates mostly disappeared, whereas most of the spindle-shaped pericytic-like cells were still present. Our findings lead us to suggest that some cellular product may, as a promoter factor, induce the proliferation and growth of endothelial cells. This factor may be blocked by alpha A interferon and cause regression of endothelial cell proliferation observed in AIDS patients undergoing long-term systemic therapy.

[Therapeutic use of alpha interferon in metastasizing malignant melanoma, disseminated Kaposi sarcoma and severe Behçet disease]. / Therapeutischer Einsatz von alpha-Interferon bei metastasierendem malignem Melanom, disseminiertem Kaposi-Sarkom und schwerem Morbus Behçet.

Three types of human interferons (IFNs) are differentiated: alpha-interferon (with about 20 subtypes), beta-interferon, and gamma-interferon. In addition to their antiviral properties, these IFN types exert numerous other biological effects, which are increasingly exploited for therapeutic purposes. From 1982 to 1985 long-term recombinant alpha 1-interferon (rIFN-alpha A) was administered systemically in 39 patients with various severe dermatoses. In this study we report our preliminary experiences with systemic administration of rIFN-alpha A in malignant melanoma (MM, 9 patients), in disseminated Kaposi's sarcoma (KS, 8 patients), and in severe Behçet's disease (2 patients). In metastatic MM (clinical stage IV) the result was only moderate; the administration of IFN in earlier stages, for instance as a postoperative adjuvant therapy, appears more promising. In disseminated KS with acquired immune deficiency syndrome (AIDS) our experience was encouraging. In 7/8 patients the general condition was stabilized and partial remission of skin lesions was observed. In Behçet's disease both patients had good or excellent responses to IFN treatment. The side effects of systemic rIFN-alpha A were moderate, dose-dependent, and tolerable.

[Skin reaction to dithranol and its modification by the addition of tar (LCD)]. / Hautreaktion auf Dithranol und ihre Beeinflussung durch Teerzusatz (LCD).

In spite of 70 years' continuous use of dithranol for the topical treatment of psoriasis, there are few reports of contact hypersensitivity reactions to this compound. A male patient with psoriasis had an adverse skin reaction to the traditional topical dithranol treatment; patch tests revealed contact dermatitis in response to 0.02% dithranol in petrolatum, which was characterized by marked erythema and severe bullous reaction to 0.1% dithranol in acetone. A control group of ten volunteers tested under similar conditions did not react with marked erythema until a concentration of 0.1% dithranol in petrolatum was applied. When liquid tar (5% liquor carbonis detergens, LCD) was added to the patch test solutions concentrations that were clearly one or two steps higher were needed before the erythematous skin reaction was induced. Since minimal erythema generally appears in patch tests with greater than or equal to 0.05% dithranol in petrolatum, we believe that in the patient reported here contact hypersensitivity to dithranol was present. The development of large perilesional erythematous areas with accompanying edema during topical dithranol treatment supports this suggestion. It seems that the addition of liquid tar elevates the reaction threshold to dithranol in hypersensitive patients with psoriasis.

[Disseminated mucocutaneous Kaposi sarcoma in AIDS. Clinical and therapeutic experiences in 13 patients]. / Disseminiertes mukokutanes Kaposi-Sarkom bei AIDS. Klinische und therapeutische Erfahrungen an 13 Patienten.

Since 1980 a new epidemic form of disseminated mucocutaneous Kaposi's sarcoma (KS) with a progressive clinical course has been observed in populations at risk. Since 1982, 13 cases of AIDS-associated KS have been seen in our department; all of them were in young homosexual males with circulating HIV antibodies and a reduction in the ratio of T-helper to T-suppressor lymphocytes (0.05-1.3). Following systemic treatment with recombinant alpha A-interferon (rIFN-alpha A) over a period of 6 months (18 million IU/day for 3 months; later 18 million IU/3 X weekly) together with other concomitant measures (superficial X-ray radiation, argon laser radiation, surgical excision of isolated lesions) we registered complete remission of the remaining lesions in 2 cases, progression of the disease in 4 cases, and at least temporary stabilization of the disease in 7 cases. In 4 patients opportunistic infections occurred during rIFN treatment: Pneumocystis carinii pneumonia (PCP) with lethal outcome in 2 cases, atypical mycobacteriosis in 2 cases, and Legionella pneumoniae infection in 1 case. Two additional deaths were registered due to PCP appearing during the post-treatment period. Life-threatening virus infections were not observed during rIFN treatment. Out of 9 patients receiving prophylactic trimethoprim/sulfamethoxazole medication, only 1 developed allergic exanthema as a result of this drug combination. Occasionally, rIFN-induced leukopenia was seen and pronounced thrombocytopenia appeared in 1 patient during treatment. Overall, systemic rIFN therapy was well tolerated; its long-term administration in patients with AIDS-associated mucocutaneous KS seems to be well justified according to these preliminary observations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Behçet disease and exogenous interferon. A successful treatment study using recombinant alpha-A-IFN]. / Morbus Behçet und exogenes Interferon. Erfolgreicher Behandlungsversuch mit rekombiniertem alpha-A-IFN.

Up till now no standard therapy for Behçet syndrome has existed. Long-term corticoid therapy is often necessary, although side-effects cannot be avoided. Recent investigations have shown a correlation between high endogenous gamma-interferon serum levels and low activity of the syndrome. A 20-year-old male with severe Behçet's syndrome was therefore treated with recombinant alpha-A-interferon (IFN). The general condition of the patient improved rapidly, together with rapid clearing of the skin lesions. Over a 10.5 week-period the patient received a total dose of 792 million IU recombinant alpha-A-interferon.