Bernd Algermissen

Interferon treatment of patients with chronic urticaria and mastocytosis

REFERENCES 1. Maycock RL, Bertrand P, Merrison CEo Manifestations of sarcoidosis: analysisof 145 patients with a review of nineseries selected from the literature. Am J Moo 1963;36:67-89. 2. Von Lichtenberg F. Infectious diseases: fungal, protozoal, and helminthic diseases and sarcoidosis. In: Robbins SL, Cotran RS, Kumar V, eds.Pathologicbasisofdisease.Philadelphia: WB Saunders, 1984:390-2. 3. Mitchell ON, Scadding JG, Heard BE, et al. Sarcoidosis: histopathology and clinical diagnosis. J Clin Pathol 1977; 30:395-408. Journal of the American Academy of Dermatology March 1994

Chemosensitivity testing of human malignant melanoma. A retrospective analysis of clinical response and in vitro drug sensitivity.

Background. Clinical response rates in the treatment of patients with disseminated malignant melanoma are low and unpredictable. Several reports have documented that clonogenic assay systems for in vitro drug testing are capable of predicting resistance to therapy in vivo and might provide guidelines to improve clinical response rates.

Phenotypic evaluation of cultured human mast and basophilic cells and of normal human skin mast cells

In order to evaluate various markers for human mast cells, two human mast/basophilic cell lines (HMC-1/KU812), cultured mast cells from the peripheral blood monocytic fraction and peripheral blood monocytes were compared with mast cells in tissue sections from normal skin, using histochemistry, enzyme histochemistry and immunohistochemistry. All reagents stained normal skin mast cells, with toluidine blue, tryptase reactivity and antibodies against the FcεRI and the stem cell factor receptor (c-kit) being most active. The cell lines and mast cells cultured from peripheral blood were negative for avidin, safranin and chymase, strongly positive for c-kit and variably reactive with all other reagents. All antibodies except AA1 against tryptase also stained one or several epidermal and dermal cell types or blood monocytes. Histochemical stains (toluidine blue, avidin) and reagents for the enzymes tryptase and chymase are thus specific markers for mast cells. The frequent reactivity of antibodies against mast cells with other cell types indicates interesting functional and ontogenetic relationships between these cells.

Analysis of mast cell subpopulations (MCT, MCTC) in cutaneous inflammation using novel enzyme-histochemical staining techniques

Abstract In order to gain insights into the dynamics of mast cell subpopulations in normal and diseased skin, a novel enzyme‐histochemical double and triple staining method was employed that allowed the detection of metachromasia (toluidine blue) and the mast cell proteases tryp‐tase and chymase within the same cell. Cryostat sections were used of skin biopsies from the following specimens: normal skin (N=4), psoriasis (N=13), atopic eczema (N=7), lichen planus (N=6), interferon α2a injection sites (N=l) of a leukemic infiltrate and corresponding normal skin of the same patient before and after treatment. (i) Equal numbers of tryptase‐and chymase‐positive mast cells (MCTC) were obtained in all normal and diseased specimens in papillary and reticular dermis, with threefold increases around appendages, (ii) Tryptase‐positive mast cells (MCT) were absent in normal skin, but were markedly increased in a disease‐specific pattern within the papillary dermis, the inflammatory infiltrate and around appendages, (iii) Marked increases of MCT were also noted at interferon injection sites within the leukemic infiltrate, but not in the normal skin of the same patient. These data suggest that disease‐dependent mast cell dynamics involve only MCT in cutaneous inflammation and that MCT numbers are controlled by distinct, disease‐specific local tissue factors.

Amelanotic malignant melanoma presenting as malignant schwannoma

A 78‐year‐old woman presented with a 14‐month history of a nodule on the sole of her left foot. It had been increasing in size, and had become ulcerated. Histological, immunochemical and ultrastructural studies of the primary tumour revealed melanocytic and Schwannian characteristics, and posed diagnostic difficulties. The final diagnosis of a malignant melanoma with Schwannian differentiation was established on the basis of the clinical course, with the development of metastases in the subcutis, lymph nodes, liver and brain, as well as a shift in differentiation of the metastases towards cells containing giant melanosomes, typical of melanoma.

Laser-induced weal and flare reactions: clinical aspects and pharmacological modulation

Summary Background Among the adverse effects of cutaneous laser therapy, weal and flare reactions immediately after treatment have received little attention, and the pathomechanisms are unclear.

Phenotypic characterization of skin lesions in urticaria pigmentosa and mastocytomas

In order to identify possible cellular abnormalities in human mastocytosis, sections from 13 urticaria pigmentosa lesions and 5 mastocytomas were compared with 5 normal skin specimens using histochemical, enzyme histochemical and immunohistochemical techniques. All toluidine blue-positive mast cells also reacted with FcεRI and c-kit antibodies, almost all stained for tryptase, many for chymase and the myeloid workshop mast cell antibodies, few for FcεRII and none for the proliferation marker Ki-67. Urticaria pigmentosa lesions contained fewer epidermal Langerhans cells and a lower percentage of avidin-positive mast cells than mastocytomas and normal skin. Mastocytomas exhibited generally weaker staining for mast cell markers and mostly lacked FcεRI-bound IgE on mast cells and Langerhans cells, although the receptor was able to bind IgE in tissue sections. Most of the mast cell antibodies also reacted with other cell types. Only toluidine blue, avidin, tryptase and chymase stains were mast cell specific. Mast cells in mastocytosis thus differed only to a minor degree from normal mast cells, although distinct pathomechanisms may play a role in urticaria pigmentosa and mastocytosis.

Acute monoblastic leukemia with skin nodules in an adult

An 18-year-old man had a 3-week history of malaise, a 1-week history of a papular eruption, and increasingly severe multisystem neurologic symptoms. A diagnosis of acute monoblastic leukemia was made. Immunophenotypic characterization of peripheral blood, bone marrow, and cutaneous infiltrates revealed a predominant myelomonocytic phenotype with the coexpression of intercellular adhesion molecule type 1, IgE receptor, terminal deoxynucleotidyl transferase, and some T-cell markers. These findings may have important clinical and pathogenetic implications regarding the biologic and pathologic behavior of the myelomonocytic leukemic cells. They also explain in part the impressive presentation of the disease in the skin.

A pilot study on the effect of interferon alpha in atopic eczema

Zusammenfassung. Im Rahmen einer Pilotstudie wurde bei 12 Patienten mit mittelgradig bis schwer ausgeprägtem atopischen Ekzem eine Therapie mit 3×2 Mio. I.E. rekombinantem Interferon α 2a (Roferon A)/Woche durchgeführt. Die Behandlungsdauer betrug 8 Wochen, die Nachbeobachtungszeit 10 Wochen. Bei 2 Patienten zeigte sich eine deutliche Besserung des Hautzustandes, 9 Patienten besserten sich gering- bis mittelgradig, und ein Patient verschlechterte sich. Der Juckreiz nahm unter der Therapie nicht ab bzw. verschlechterte sich bei einigen Patienten, und die Serum-IgE-Konzentrationen änderten sich nicht signifikant während des Studienzeitraumes. Alle Patienten hatten milde, vorübergehende, primär grippeartige Nebenwirkungen. Unter dem hier verwendeten Therapieschema ist die klinische Wirksamkeit von Interferon α beim atopischen Ekzem als nur unzureichend einzustufen.Abstract. In this pilot study 12 patients with moderate to severe atopic eczema were treated with 2 million IU interferon alpha 2a (Roferon A) three times weekly for 8 weeks and followed up for a further 10 weeks: 2 patients showed clear and 9 a slight to moderate reduction of their skin lesions; 1 patient got worse. Pruritus did not decrease and even increased in a few patients, and IgE levels showed no change during and after treatment. All patients noted mild, transient, flu-like symptoms. The efficacy of interferon alpha in the present therapeutic design for the treatment of atopic eczema must thus be classified as only moderate.