Urticaria Pigmentosa Lesions Research Articles

Immunohistochemical Demonstration of Migration Inhibitory Factor in Different Types of Urticaria

Because urticarial lesions can persist for extended periods of time, we have investigated the histochemical expression of an antibody against the cytokine macrophage inhibitory factor in 23 patients with different types of urticaria. Positive staining of upper and middermal dendritic cells was noted in sections from all three biopsy specimens of acute urticaria, eight of chronic urticaria, and all six of urticaria pigmentosa lesions. In all but one biopsy specimen, endothelial cells reacted as well. In three sections (two chronic urticaria, one urticaria pigmentosa), luminal lining cells of sweat glands were also noted to stain positively. In contrast, lesional skin from all eight patients with pressure urticaria was negative, as was the clinically normal skin of all patients, with the exception of one patient with urticaria pigmentosa. The data suggest that cytokines may be involved in lesions of acute type immunologic processes and that they need not be expressed in delayed type reactions.

Mechanisms for Hyperpigmentation in Postinflammatory Pigmentation, Urticaria pigmentosa and Sunburn

Our in vitro studies demonstrate that normal human epidermal melanocytes become swollen and more dendritic with an increase in amount of immunoreactive tyrosinase when they are cultured for several days with arachidonic acid metabolites, vitamin D3 or histamine. From these data we propose the following possible mechanisms for hyperpigmentations noted at postinflammatory sites and suntanned areas as well as at skin lesions of urticaria pigmentosa. Arachidonic acid metabolites and histamine, which are found in increased amounts in inflammatory skin, are thought to play a key role in the induction of postinflammatory hyperpigmentation. In sunburnt skin the increased proinflammatory mediators, particularly arachidonic acid metabolites, are also thought to stimulate melanocytes in the production of hyperpigmentation. Thus tanning after sun exposure may be induced not only by the effect of vitamin D3 and direct UV irradiation on the melanocytes but also by the effect of various arachidonic acid metabolites which are increased in sunburnt skin. Mast cells massively proliferate in the skin lesions of urticaria pigmentosa. Thus hyperpigmentation in the skin lesions of urticaria pigmentosa is quite likely to be induced by the chemical mediators, including histamine and leukotrienes, that are released from these cells.

Differences between basophils and mast cells: failure to detect Charcot-Leyden crystal protein (lysophospholipase) and eosinophil granule major basic protein in human mast cells.

Human eosinophils contain several distinctive proteins including eosinophil granule MBP and the membrane-associated CLC protein (lysophospholipase). Human basophils also contain these proteins, indicating biochemical similarities between eosinophils and basophils. To determine whether MBP or CLC protein is present in connective tissue mast cells, we studied human lung and cutaneous mast cells by immunofluorescence by utilizing specific antibodies to CLC and MBP. Cytocentrifuge slides of enriched lung mast cells and mast cells in sections of formalin-fixed, paraffin-embedded cutaneous tissue from urticaria pigmentosa lesions were stained for CLC and MBP. Neither pulmonary nor cutaneous mast cells stained for CLC protein or MBP. In contrast, lung and cutaneous eosinophils in the same preparations showed bright staining for both proteins. The failure to find CLC protein and MBP in mast cells provides additional evidence of dissimilarity between mast cells and basophils, and an immunochemical means to distinguish between them.

Fatal anaphylaxis in systemic mastocytosis.

A 42-year-old woman died after an episode of anaphylaxis associated with a raised serum histamine level. A diagnosis of systemic mastocytosis was established, with lymphadenopathy and hepatosplenomegaly, not associated with the usually pre-existing skin lesions of urticaria pigmentosa.

Atypical diffuse cutaneous mastocytosis.

A 19-month-old boy was found to have atypical diffuse cutaneous mastocytosis. Although severe dermographism and pressure urticaria were present from early infancy, his disease remained undiagnosed because he lacked the characteristic bullous and pigmented lesions of urticaria pigmentosa and the pebbly skin texture usually found in diffuse cutaneous mastocytosis. A skin biopsy from clinically normal skin disclosed a dense infiltrate of mast cells in the upper dermis. Since involvement of other organ systems is frequent in this form of mastocytosis, the patient was studied for internal lesions but none was found at this time. Parents of affected children should be informed that trauma to the skin such as brisk toweling after a bath, and drugs such as aspirin, codeine, and polymyxin B sulfate may precipitate episodes of histamine shock due to degranulation of the mast cells.

Cytodiagnosis of Inflammatory Dermatoses

The smear technique of cytodiagnosis is of distinct value in the study of lesions of urticaria pigmentosa, herpes simplex, eczema herpeticum, herpes zoster, varicella, and vaccinia. The method has certain advantages as a rapid aid to the diagnosis of pemphigus vulgaris and pemphigus erythematosus, but pitfalls are encountered because of the presence of acantholytic and Tzanck-like cells in other diseases. Proteolytic enzymes liberated from polymorphonuclear leukocytes or bacteria probably account for the acantholytic cells observed in several of the vesiculobullous and pustular diseases studied. Cytodiagnosis of inflammatory dermatoses is an adjunct to routine histologic study and clinical evaluation of the disease.

Mastocytosis with coagulation defects induced by biopsy.

Mast cell disease has seldom been associated with hemorrhagic accidents1,2or with coagulation abnormalities such as prolonged coagulation time, prolonged bleeding time, abnormal prothrombin concentration in tolerance test for heparin. Some of the above anomalies have been explained by an associated liver alteration3; others by the presence in plasma of inhibitors of the coagulation process.4-9In most instances, however, the laboratory findings have been minimal or the cases did not show clinical manifestations. Urbach, Bell, and Jacobson10by local friction on cutaneous lesions of urticaria pigmentosa demonstrated a temporary increase of blood heparin in their cases. Berlin11found in blood obtained from a cutaneous lesion an abnormal coagulation process. We have had the opportunity to observe a child with nodular urticaria pigmentosa with severe bleeding from the biopsy site, who required a whole blood transfusion. The coagulation defect was due to the presence of a

Urticaria pigmentosa with systemic lesions and otosclerosis.

Urticaria pigmentosa both with and without systemic involvement has been well reviewed. 1,2 Recently Davis et al. 3 reported the case of an adult with cutaneous but no demonstrable systemic lesions of urticaria pigmentosa, who had flushing of the face, neck, and upper thorax. Analysis of the skin containing mast-cell infiltrates showed large amounts of histamine. We should like to report another interesting patient with urticaria pigmentosa and flushing, who also had systemic signs of mast-cell disease and otosclerosis. A 29-year-old white married mother of two children was hospitalized at the Yale-New Haven Medical Center from Dec. 13, 1955, to Dec. 17, 1955, for evaluation of possible metabolic disease of the bone. During the preceding summer, the patient had fallen on a waxed floor and subsequently experienced low back pain. X-rays of the pelvic bones showed a granular appearance due to disseminated minute areas of increased density separated by cystic-appearing

The Remarkable Tissue Mast Cells

The importance of those remarkable cytological units, the tissue mast cells, has soared in recent years. This paper reviews briefly some of the newer concepts of these cells and reports on the author's experience with histological techniques for the study of mast cell acid polysaccharides in the cutaneous lesions of urticaria pigmentosa. Some Newer Concepts of Tissue Mast Cells Although the distribution of mast cells varies from species to species, their characteristic location in warm-blooded vertebrates is the loose fibrillary tissue which surrounds small blood vessels and underlies epithelial, serous and synovial membranes. 1,13 In general, parenchymatous organs are poor in mast cells, a noteworthy exception being the widespread distribution of mast cells throughout the parenchyma of the dog's liver. 1 Urticaria pigmentosa, the lesions of which are featured by agglomerations of mast cells, has been known for many years. Only recently, however,

Generalized flushing of the skin with urticaria pigmentosa.

In 1869, Nettleship 1 described an unusual type of urticaria which bears the name urticaria pigmentosa. For the next 80 years it was regarded as a comparatively rare skin condition characterized by yellow or brown macules or nodules, which, when rubbed vigorously, produced a whealing or urtication localized to the pigmented areas. Apart from the occasional report of rare solitary nodular and bullous lesions, the only other significant observation during this period was the finding of Unna, 2 in 1887, that the skin manifestations of urticaria pigmentosa were characterized by a marked infiltrate of tissue mast cells. In 1949, Ellis 3 reported the first case of urticaria pigmentosa in which an autopsy was performed. This one-year-old Negro girl had the typical skin lesions of urticaria pigmentosa from birth, associated with gastrointestinal upsets and hepatosplenomegaly. The autopsy revealed increased numbers of mast cells in the areas of portal

Nodular urticaria pigmentosa of the vulva in siblings.

Since Nettleship¹first described urticaria pigmentosa in 1869, the literature has abounded with discussions of various aspects of this uncommon, yet well-defined, clinical entity. The present report of the unusual, and perhaps even unique, occurrence of lesions of urticaria pigmentosa in identical sites solely on the vulva of two sisters demonstrates the need for considering this disease in the differential diagnosis of genital lesions in young children. Report of Cases An 8-month-old white girl with an erythematous, raised, slightly firm, pruritic nodule measuring 1 by 1 cm. on the right labium majus was seen at Charity Hospital of Louisiana at New Orleans on July 26, 1955. According to the patient's mother, the lesion had been present for at least three months. The top of the mass had become edematous and excoriated as a result of frequent scratching of the area. Physical examination yielded no significant findings except for the presence of pediculosis capitis. Results of peripheral blood studies, fasting test for blood glucose, serologic test for syphilis, urinalysis, liver function tests, fecal examinations, tuberculin tests, and complete roentgenographic studies of the bones were all within normal limits.

Negative test for heparin in mast cells of urticaria pigmentosa.

SINCE it became known that mast cells contain heparin or heparin-like material, speculation arose about the concentration of these potent enzymes in the skin of subjects with urticaria pigmentosa. It is said the same cells contain histamine, too, which would readily account for the ability of the skin to react by whealing on stroking or rubbing. Recently investigators studied intensively the so-called clearing factor the body develops somewhere within itself when one injects heparin intravenously. This clearing factor removes the milky appearance of blood serum following a fat meal. However, the oldest and best-known property of heparin is its ability to interfere with coagulation of blood. Accordingly, a simple and direct test for the presence of heparin concentrates in the skin at the site of lesions of urticaria pigmentosa would be interference with the blood coagulation reaction by extracts of such skin. A positive test (interference) could be interpreted

Bullous urticaria pigmentosa: report of an unusual case.

Bullous lesions in association with urticaria pigmentosa have been observed occasionally since recognition of the disease in 1869. Finnerud, 1 in 1923, in a summary of all reported cases of urticaria pigmentosa found that 8 cases out of a total of 308 had vesicles and bullae. Since 1923, a number of references to bullous lesions in urticaria pigmentosa have appeared in various society transactions. The vesicles and bullae were described as being in association with the usual urticaria pigmentosa. In each case reviewed, the classical lesions of urticaria pigmentosa— macules and nodules—were the outstanding feature, although some lesions were bullous. The following case presentation is made because of itsunusual nature. It represents the only reported bullous eruption having the classical histologic picture of urticaria pigmentosa, without a single macule, papule, or other lesion typical of the disease. REPORT OF CASE K. M.—A 6-month-old white girl, was first seen by the