Hans W. Kreysel

Antipsoriatic effect of fumaric acid derivatives: Results of a multicenter double-blind study in 100 patients

BACKGROUND Psoriasis vulgaris may benefit from treatment with fumaric acid and/or its derivatives; however, because different preparations have been used, results have been contradictory and difficult to interpret. OBJECTIVE The purpose of this clinical trial was to evaluate the therapeutic value of fumaric acid derivatives. METHODS A randomized double-blind study was carried out in patients with psoriasis, comparing a well-characterized formulation of fumaric acid derivatives with placebo. RESULTS The results indicated statistically significant superiority of the fumaric acid derivatives over placebo. Adverse events (flush, gastrointestinal disturbances) were initially relatively frequent, but decreased thereafter. CONCLUSION Fumaric acid derivatives were found to be effective and safe in the treatment of psoriasis.

Systemic interferon gamma treatment in severe atopic dermatitis

BACKGROUND Recent results suggest decreased interferon gamma (IFN-gamma) but high interleukin 4 (IL-4) production in patients with atopic dermatitis (AD). Because the relative activities of IL-4 and IFN-gamma seem to regulate the amplitude of the IgE response we suggested a role for IFN-gamma in the treatment of AD. OBJECTIVE The purpose of this study was to assess the efficacy of systemic IFN-gamma treatment in patients with severe AD. METHODS Patients with severe AD (n = 14) were treated with recombinant IFN-gamma for 6 weeks. During the study only basic local therapy with steroid-free hydrophilic or emollient ointments was allowed. RESULTS Eight patients (57%) showed marked clinical improvement during systemic IFN-gamma therapy. Four of these patients showed continuous improvement 3 months after treatment was discontinued. Mean total and antigen-specific serum IgE concentrations were not statistically different during and after treatment, whereas mean spontaneous IgE production in vitro was significantly lower after 6 weeks of IFN-gamma therapy. CONCLUSION Our results suggest that IFN-gamma treatment may represent a novel therapeutic approach in patients with severe AD.

Topical acetylsalicylic, salicylic acid and indomethacin suppress pain from experimental tissue acidosis in human skin

&NA; Topically applied acetylsalicylic acid (ASA), salicylic acid (SA) and indomethacin were tested in an experimental pain model that provides direct nociceptor excitation through cutaneous tissue acidosis. In 30 volunteers, sustained burning pain was produced in the palmar forearm through a continuous intradermal pressure infusion of a phosphate‐buffered isotonic solution (pH 5.2). In 5 different, double‐blind, randomized cross‐over studies with 6 volunteers each, the flow rate of the syringe pump was individually adjusted to result in constant pain ratings of around 20% (50% in study 4) on a visual analog scale (VAS). The painful skin area was then covered with either placebo or the drugs which had been dissolved in diethylether. In the first study on 6 volunteers, ASA (60 mg/ml) or lactose (placebo) in diethylether (10 ml) was applied, using both arms at 3‐day intervals. Both treatments resulted in sudden and profound pain relief due to the cooling effect of the evaporating ether. With lactose, however, the mean pain rating was restored close to the baseline within 6–8 min while, with ASA, it remained significantly depressed for the rest of the observation period (another 20 min). This deep analgesia was not accompanied by a loss of tactile sensation. The further studies served to show that indomethacin (4.5 mg/ml) and SA (60 mg/ml) were equally effective as ASA (each 92–96% pain reduction) and that the antinociceptive effects were due to local but not systemic actions, since ASA and SA did not reach measurable plasma levels up to 3 h after topical applications. With a higher flow rate of acid buffer producing more intense pain (VAS 50%), ASA and SA were still able to significantly reduce the ratings by 90% or 84%, respectively. On the other hand, by increasing the flow rate by a factor of 2 on average, during the period of fully developed drug effect it was possible to overcome the pain suppression, which suggests a competitive mechanism of (acetyl‐) salicylic antinociception.

Cutaneous angiomyxoma: a benign neoplasm distinct from cutaneous focal mucinosis.

We describe a cutaneous angiomyxoma on the head of a 38-year-old man without evidence of Carneys complex. Complete excision of the tumor appeared to be curative. Histologic examination revealed fibroblast-like cells embedded in a well-demarcated, lobulate, mucinous, and vascularized stroma with a delicate reticulin network. Immunohistologically, the stromal cells were consistently positive for vimentin and focally positive for smooth muscle A-actin but were negative for desmin, KP1, MAC387, factor XIIIa, CD34, Leu-7, and S-100. Cutaneous angiomyxoma appears to represent a myofibroblastic neoplasm that should be distinguished from cutaneous focal mucinosis.

Dose-dependent competitive block by topical acetylsalicylic and salicylic acid of low pH-induced cutaneous pain.

&NA; In a human acid pain model, which uses continuous intradermal pressure infusion of a phosphate‐buffered solution (pH 5.2) to induce localized non‐adapting pain, the flow was adjusted to result in constant pain ratings of about 20% or 50% on a visual analog scale (VAS). Six volunteers in each group participated in 4 different placebo‐controlled double‐blind cross‐over studies to measure rapidly evolving cutaneous analgesia from topically applied new ointment formulations of acetylsalicylic acid (ASA) and salicylic acid (SA) as well as of commercial ibuprofen and benzocain creams. Similar, log‐linear dose‐response curves were found for both ASA and SA, significant in effect at 3 g/ kg and higher drug contents and reaching saturation level at 15 or 30 g/ kg, respectively, which, 20 min after application, caused a mean pain suppression of 95% using ASA and 80% using SA. Half‐maximal effects were achieved using 3 g/kg ASA or 15 g/kg SA. The SA action was also clearly slower to develop. With an increased flow of the acidic buffer, producing lower effective tissue pH and more intense pain, the effect of ASA and SA decreased to 73% pain suppression. A competitive mechanism of both drug effects was suggested by the fact that, with 15 g/kg ASA and SA, pain reduction could be reversed by increasing the buffer flow by a factor of 1.75., on average. Commercial ibuprofen (50 g/kg) and benzocain creams (100 g/kg) were comparably as effective as ASA and SA, but the local anesthetic caused a loss of all cutaneous sensations while the touch threshold (von Frey) under the specific analgesics was the same as under the placebo ointment. Thus, topical applications of non‐steroidal anti‐inflammatory drugs (NSAIDs) dissolved in different ointment formulations have proven dose‐dependently effective and specific in suppressing experimental acidotic pain by a local and competitive mechanism.

Hailey-Hailey disease and bipolar affective disorder in three members of the same family

Zusammenfassung. Wir berichten über eine Kosegregation von Morbus Hailey-Hailey (MHH) und bipolarer affektiver Erkrankung bei drei Mitgliedern einer Familie. Mit dem Fortschritt molekularbiologischer Techniken ist die Genlokalisation bei Erkrankungen mit einfachem Vererbungsmuster, wie dem autosomal-dominant vererbten MHH, eine Frage der Zeit. Die chromosomale Region des MHH-Gens wird dann auch Kandidatenregion für Kopplungsanalysen bei affektiven Erkrankungen sein.Summary. We report on three family members suffering from both autosomal dominant Hailey-Hailey disease and bipolar affective disorder. As molecular biology techniques have made the localization of genes causing simple Mendelian traits possible as a routine task, the gene for Hailey-Hailey disease will presumably be localized in the foreseeable future. The Hailey-Hailey gene and its chromosomal surrounding will then be a region of interest for linkage studies in bipolar affective disorder.

Differential expression of major histocompatibility complex class II antigens on human keratinocytes

Skin biopsies from 136 patients with 30 different dermatoses and eight biopsies of normal skin were investigated with the avidin-biotin-peroxidase complex method with regard to the expression of major histocompatibility complex class II antigens human leukocyte antigen (HLA) HLA-DR, HLA-DQ, HLA-DP on keratinocytes. In normal skin the expression of these antigens was restricted to acrosyringia and Langerhans cells. In the dermatoses investigated HLA-DR was found in 51.5% (70 of 136), HLA-DQ in 24.3% (33 of 136), and HLA-DP in 20.5% (8 of 39). In 37 cases (27.2%) only HLA-DR could be detected, whereas in 33 cases (24.3%) HLA-DR was expressed jointly with HLA-DQ. Coexpression of HLA-DR and HLA-DQ was found especially often in cutaneous T cell lymphomas, skin tumors, and inflammatory dermatoses.

Reaction of human keratinocytes with the monoclonal antibody anti-Leu-11: An immunohistologic study

Biopsy specimens from skin of 99 patients with 26 different dermatoses and 17 specimens from normal skin were labeled with regard to the reactivity of keratinocytes with the monoclonal natural killer-associated antibody anti-Leu-11b by means of the avidin-biotin-peroxidase complex method. Reactivity occurred in 64.7% of the preparations from normal skin and in 84.8% of the preparations from diseased skin. The membranes of the subcorneal keratinocyte layers were labeled regularly. In some of the preparations cytoplasmic reactivity and labeling of the basement membrane zone occurred in addition. Most labeled preparations and the highest labeling intensities were shown in the skin tumors and in the infectious dermatoses. The biologic significance of this finding is discussed.

NATURAL KILLER CELL AND CYTOTOXIC/SUPPRESSOR T CELL DEFICIENCY IN PERIPHERAL BLOOD IN SUBJECTS WITH ALOPECIA AREATA

The previously observed reduction in peripheral cytotoxic/suppressor T cell populations in subjects with alopecia areata (AA) was confirmed (p<0.001). Moreover, a hitherto undescribed decrease in circulating natural killer cells was noted (p<0.01).

Das epitheloidzellige Histiozytom

ZusammenfassungWir berichten über sieben Beobachtungen dieses seltenen, erst kürzlich beschriebenen, gutartigen Tumors, der klinisch in allen Fällen als solitärer leicht erhabener Knoten von 0,6 bis 1,1 cm Durchmesser an der unteren (n=5) und oberen (n=2) Extremität imponierte. Histologisch zeigte sich in allen Fällen eine gut umschriebene Läsion mit charakteristischer epidermaler Manschette. Überwiegend (60–80%) epitheloide Zellen mit reichlich Zytoplasma, vesikulärem Kern und kleinem Nukleolus sowie zahlreiche erweiterte Blutgefäße kamen zur Darstellung. Diese Zellen reagierten nicht mit Monozyten/Makrophagen Antikörpern (KP1, MAC387). Auch fanden sich keine Hinweise für eine myofibroblastische Differenzierung (Alpha-smooth muscle actin und Desmin negativ). Mit Hilfe immunhistologischer Marker können daher andere Tumoren differentialdiagnostisch abgegrenzt werden, jedoch geben sie keine Information über die Differenzierung epitheloidzelliger Histiozytome. – Unsere hier präsentierten Fälle entsprechen der primär beschriebenen Variante. Kürzlich wurde auch über ähnliche Läsionen im tieferen Korium sowie zellreichere Formen berichtet. So stellt das epitheloidzellige Histiozytom eine charakteristische, bisher wenig bekannte Variante im Spektrum gutartiger fibröser Histiozytome dar, die klinisch und histopathologisch insbesondere vom Nävus Spitz abzugrenzen ist.SummaryWe report on seven examples of this rare, only recently described benign tumor, which presented clinically as solitary elevated nodules on the lower (n=5) and upper (n=2) extremity, measuring between 0.6 and 1.1 cm in diameter. Histologically, all tumors were well-defined with a characteristic epidermal collarette. There were abundant (60–80%) epithelioid cells with prominent cytoplasm, a vesicular nucleus and inconspicuous nucleolus, as well as a number of dilated blood vessels. Immunohistologically, tumor cells did not react with monocyte/macrophage antibodies (KP1, MAC387). In addition, there was no evidence of myofibroblastic differentiation (alpha-smooth muscle actin and desmin negative). Thus, while immunohistological markers are helpful to exclude the diagnosis of other tumors, they do not shed light on the differentiation of epithelioid cell histiocytomas. The present cases are identical to those described originally. Recently similar lesions have been described in deeper parts of the corium as well as more cellular forms. Epithelioid cell histiocytoma represents a characteristic, poorly known variant within the spectrum of benign fibrous histiocytomas; it needs to be distinguished clinically and histopathologically especially from Spitz nevus.