Localization of eosinophil granule major basic protein in chronic urticaria.

The role of the eosinophil in the pathogenesis of cutaneous diseases is not known. The eosinophil granule major basic protein (MBP), constituting the core and accounting for greater than 50% of the eosinophil granule, is toxic to helminths and mammalian cells. To determine whether eosinophil degranulation occurs in lesions of chronic urticaria, we performed an indirect immunofluorescence assay on sections of formalin-fixed, paraffin-embedded tissue, utilizing affinity chromatography-purified antibody to MBP. Twelve of 28 biopsies showed evidence of degranulation as judged by the deposition of MBP outside the eosinophil. The positive staining was of 3 types: (1) small blood vessel walls (5 patients), (2) dispersion of granular material (9 patients), and (3) focal or diffuse immunofluorescence of connective tissue fibers (11 patients). These results suggest a possible role for the cytotoxic molecule MBP in the evolution of lesions of chronic urticaria.

Immunodermatology update: the immunologically mediated vesiculobullous diseases.

Before a specific diagnosis of an immunologically mediated blistering disease can be made, the clinical and histologic features and the results of direct and indirect immunofluorescence studies (with use of multiple substrates in some cases) must be assessed. For both subepidermal and intraepidermal groups of blistering diseases, direct immunofluorescence testing of perilesional tissue is critical for diagnosis. For these conditions, indirect immunofluorescence testing of serum is important for diagnosis and has a role in management of selected diseases. In dermatitis herpetiformis, indirect testing of serum for IgA antiendomysial antibodies is useful for both diagnosis and management. Indirect testing of serum for IgG antibodies to intercellular substance is important for diagnosis and, in conjunction with the clinical findings, can be used as a guide for monitoring disease activity in patients with pemphigus. Immunoelectron microscopy, immunoprecipitation, and immunoblotting studies have identified the sites of immune deposits and the specific antigens in most of the immunologically mediated bullous diseases. From a practical standpoint, however, direct and indirect immunofluorescence testing, in conjunction with clinical and histologic evaluations, is a simple, rapid, and relatively inexpensive tool for diagnosis and management.

Efficacy of vitamin D3 derivatives in the treatment of psoriasis vulgaris: a preliminary report.

The efficacy of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and the new analogue calcipotriene (MC 903) in the treatment of psoriasis was investigated. Eight patients with psoriasis were enrolled in a pilot study with systemically administered vitamin D3 and were given 1,25(OH)2D3 (Rocaltrol; Hoffmann-La Roche) in dosages from 0.5 microgram to 2 micrograms/day for a 6-month trial. In one patient, the psoriatic plaques resolved within 2 months after treatment (0.5 microgram/day) was initiated. Moderate improvement was noted in one other patient (1 microgram/day). The serum level of 1,25(OH)2D before treatment was not less than the normal range of the adult population. Side effects of systemically administered 1,25(OH)2D3 included a dose-dependent increase in the 24-hour urinary calcium excretion and a decrease in the total number of platelets. Seven patients with symmetric plaque-type psoriasis were treated topically with 2 micrograms/g of 1,25(OH)2D3 in petrolatum. During 3 months of follow-up, mild improvement was noted in three patients. Five patients in the calcipotriene study were part of a nationwide double-blind placebo-controlled trial by Bristol-Myers Squibb. Moderate to marked improvement was noted in the two patients who received 50 micrograms/g of calcipotriene topically. The three patients who received placebo showed no response. We conclude that a subset of patients with psoriasis responds well to 1,25(OH)2D3. Calcipotriene is efficacious and an excellent alternative to topically applied corticosteroids.

Atypical fibroxanthoma. A study with antibody to S-100 protein.

Fourteen biopsy specimens from ten patients with atypical fibroxanthoma were studied with the peroxidase-antiperoxidase method for binding of S-100 antibody. Six specimens from four patients were minimally positive. The S-100-positive cells were observed in greatest concentrations at the periphery of the lesions and were associated with perivascular inflammatory cells. By this method, it appears that there is not a Langerhans' cell type of atypical fibroxanthoma. The S-100 antibody can help differentiate desmoplastic juvenile melanoma and malignant melanoma from atypical fibroxanthoma.

Localized lipoatrophy (atrophic connective tissue disease panniculitis).

Four patients with localized lipoatrophy were observed. All were female, and three were children. Lymphocytic panniculitis was observed in early biopsy specimens of all four cases, with focal histiocytic granulomas in one case. Later biopsy specimens in three patients showed that the inflammation was transient. These pathologic findings and reports of lipodystrophies associated with nephritis, hypocomplementemia, and other inflammatory or immunologic disorders offer an opportunity for histologic and immunologic study of such patients. Localized lipoatrophy may represent the end stage of panniculitis in a localized expression of connective tissue disease.

Amyloid elastosis. A new cutaneous and systemic pattern of amyloidosis.

A patient with papulonodular cutaneous disease was studied until his death from progressive systemic disease. The elastic fibers in the skin, subcutaneous tissue, and serosae were coated with an amyloid-staining material in a unique pattern, as demonstrated by special stains and electron microscopy. Visceral and cutaneous blood vessels from autopsy tissue also showed amyloidosis, particularly in relation to the elastic fibers. These findings seem to represent a unique syndrome of amyloid disease.

Factitial leg ulcers associated with an unusual sleep disorder.

A 19-year-old woman presented with a 14-month history of multiple, factitially induced, full-thickness leg ulcers. Nocturnal polysomnography with video monitoring revealed a short sleep latency and frequent sleep stage changes. Rapid eye movement sleep was absent. All stages of non-rapid eye movement sleep were associated with leg rubbing. After treatment that included avoidance of daytime naps and administration of chlorpromazine at bedtime, affect, daytime behavior, nocturnal sleep, and the ulcers improved markedly. To our knowledge, there are no reports of factitial dermatosis associated with disordered sleep. Our findings suggest that abnormal sleep may play a role in initiating or perpetuating factitial dermatoses. This case illustrates that polysomnography and video monitoring may be indicated in the evaluation of patients with factitial dermatoses.

Mast cells, neutrophils, and eosinophils in prurigo nodularis.

BACKGROUND AND DESIGN: Prurigo nodularis is a disease of unknown cause. To characterize the involvement of mast cells, neutrophils, and eosinophils in lesional tissue, we analyzed seven skin biopsy specimens by an indirect immunofluorescence technique for localization of mast cell tryptase, neutrophil elastase, and eosinophil granule major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin. RESULTS: Mast cells were detected in all of the specimens, with prominent numbers of mast cells in three specimens; there was minimal or no extracellular deposition of tryptase in any of the tissues. Neutrophil infiltration was observed in all specimens, but few cells were observed in four; extracellular elastase was minimal or absent in all but one specimen in which prominent dermal elastase deposition was found. Scanty eosinophil infiltration was present in all specimens; however, extracellular deposition of the eosinophil granule proteins including major basic protein, eosinophil-derived neurotoxin, and eosinophil cationic protein was present in all but one specimen and striking deposition of at least one eosinophil granule protein was present in six of the seven specimens. CONCLUSIONS: These studies suggest that mast cell numbers are increased in prurigo nodularis and that eosinophil degranulation as evidenced by striking extracellular deposition of granule proteins is prominent in lesions. In contrast, extracellular deposition of mast cell and neutrophil proteins is absent. The distinctive proteins of the eosinophil granule have potent effects on tissues; the toxicity of these proteins and their deposition in lesional tissue suggest a pathogenic role for the eosinophil in prurigo nodularis.

Lupus erythematosus panniculitis.

LE panniculitis is an uncommon but distinctive subset of LE. It may develop in patients with discoid LE or SLE or may occur as an isolated phenomenon. The typical clinical presentation is that of multiple indurated nodules or plaques (or both), often associated with lipoatrophy, there being a predilection for the proximal extremities and trunk. Because the clinical and histologic findings of LE panniculitis overlap with those of other connective tissue diseases, evaluation of patients suspected of having LE panniculitis should include a complete history and physical examination as well as serologic studies, determination of peripheral blood counts, and tests of renal function. A deep excisional biopsy rather than punch biopsy should be performed for diagnosis. The characteristic histologic pattern includes hyaline necrosis of fat; lymphoid nodules, often with germinal centers; and lymphocytic lobular panniculitis. Direct immunofluorescence testing of skin may help confirm the diagnosis in patients who have less than classic histologic features. LE panniculitis tends to have a chronic course marked by recurrent nodules or plaques (or both). Antimalarial agents, with or without courses of systemic steroids, are beneficial in most patients.

The eosinophil.

The eosinophil has characteristic granules containing a variety of mediators that may be important in the pathogenesis of cutaneous disease. Although numerous cutaneous diseases may be associated with tissue infiltration with eosinophils, in very few disorders, including Wells' syndrome, angiolymphoid hyperplasia with eosinophilia, and granuloma faciale, does the pattern of eosinophil infiltration contribute to the characteristic histopathologic picture. Immunofluorescence studies demonstrating eosinophil degranulation in the skin, particularly in urticaria and angioedema, have provided evidence to support a role for eosinophil mediators in the pathogenesis of certain cutaneous diseases.

Gene rearrangement analysis in lymphoid neoplasia.

Current uses for gene rearrangement analysis in clinical dermatology are listed in Table 3. This technique is useful for determining the existence of clonal populations within a background of polyclonal lymphoid cells; therefore, it is helpful in the diagnosis and staging of patients with CTCL and PTCL. Although dual genotypes do occur, this technique is usually capable of determining lineage in a clonal lymphoid infiltrate and elucidating and characterizing the etiopathogenesis of certain neoplasms. On the basis of this review of the literature and our own experience, we conclude that gene rearrangement analysis shows great promise for monitoring response to therapy and detecting progression or relapse in patients with CTCL and PTCL. With the recent technology of PCR, it is possible to amplify specific sequences of DNA, detect molecular alterations in individual malignant T cells, and even identify exogenous retroviral gene sequences in tissues of patients with CTCL. Although gene rearrangement analysis has supported or established the clonal nature of lymphomatoid papulosis, pre-Sézary syndrome, granulomatous slack skin syndrome, and follicular mucinosis, the clinical significance of these findings is not yet clear. In the case of primary cutaneous B-cell lymphoma and its benign counterpart, B-cell pseudolymphoma, further investigation will be needed to determine the clinical significance of clonal rearrangements.

Panniculitis.

An accurate assessment of subcutaneous lesions can be made by joining the differential diagnoses generated by clinical and histologic features. Anatomic location of lesions, presence or absence of ulceration, occurrence of lipoatrophy, history of trauma, association with immunologic or metabolic disorders, and age of the patient are important clinical data to consider in conjunction with the microscopic features. Individual histologic features such as calcification, cytophagic histiocytes, pseudocysts, lymphoid nodules, and crystals should be evaluated in conjunction with the inflammatory infiltrate (i.e., granulomatous, neutrophilic, lymphocytic, or combined); presence and type of necrosis (e.g., basophilic, hyaline, lobular, or septal); and presence and extent of sclerosis. For optimal management of patients, it is important to consider the differential diagnosis generated by the dominant histologic features as well as the clinical and histologic abnormalities.

T-cell receptor gene rearrangement analysis in the early diagnosis of cutaneous T-cell lymphoma.

The authors describe the techniques of T-cell gene rearrangement in the diagnosis and early detection of cutaneous T-cell lymphoma. Current and future applications of these techniques are discussed.

Diacylglycerol-enhanced electrical activation of porcine oocytes matured in vitro.

This study was undertaken to examine the effect of second messengers added to the electroporation medium on electric pulse-induced artificial activation of meiotic Metaphase II porcine oocytes. Six separate experiments evaluated second messengers added to electroporation medium. When added to electroporation medium, neither phospholipase C (PLC: 0 to 2.5 Units/ml), D-myo-inositol triphosphate (IP(3): 0 to 10,000 muM), nor guanosine 5'-O-(3-thiotriphosphate; GTP-gamma-S: 0 to 100 muM) had any effect (P> 0.05) on activation rates. However, addition of 1,2-dioctanoyl-sn-glycerol (DiC(8)) increased activation rates in a dose-dependent response. At a level of 1,000 muM, DiC(8) resulted in a higher activation rate (P< 0,05) than 0.0, 0.1, 1 or 10 muM of DiC(8) with a pulse, and the 1,000 and 10,000 muM of DiC(8) no-pulse control groups. Effects of DiC(8) (1,000 muM) and IP(3) (100 muM) in combination or individually were investigated. At 1,000 muM, DiC(8) caused a higher rate of activation (P< 0.05) than 100 muM IP(3), but the result was not different from DiC(8) + IP(3). In another experiment, no difference (P> 0.05) was observed between DiC(8), GTP-gamma-S and IP(3), but DiC(8) + GTP-gamma-S + IP(3) + PLC yielded a higher (P< 0.05) activation rate than PLC or the rate of the controls. No significant development (blastocyst) was observed after 5 days of culture in any of the experiments. Protein profiles of activated oocytes, determined by 1D SDS-PAGE, were characteristic of pronuclear-stage embryos. These data indicate that the addition of DiC(8) to the electroporation medium synergistically enhances the rate of activation of electrically stimulated in vitro-matured porcine oocytes.

Pyoderma gangrenosum and adrenocortical carcinoma.

Systemic disorders that have been associated with pyoderma gangrenosum include inflammatory bowel disease, rheumatoid arthritis, paraproteinemias, and hematologic malignancies. We report the case of a 55-year-old woman with pyoderma gangrenosum, IgA monoclonal gammopathy, and a cortisol-secreting adrenocortical carcinoma. Review of the literature revealed one previous case of pyoderma gangrenosum associated with a solid tumor; at autopsy, a carcinoid tumor and an adrenocortical adenoma were found. Our patient's rapid improvement after the carcinoma was resected and her subsequent disease-free course suggests that the two conditions were related. This case suggests that evaluation for underlying malignancy should be considered in patients with pyoderma gangrenosum.

Hospitals respond to water loss during the Midwest floods of 1993: preparedness and improvisation.

The Midwest floods of 1993 presented multiple emergency preparedness challenges to the six metropolitan medical centers in Des Moines, Iowa. As floodwaters overcame the Des Moines Water Treatment Plant, medical centers were faced with the task of responding to imminent water loss and its associated impact on patient care services and facility operations. Many clinical services were cancelled or diverted to alternate facilities. Ancillary resources were identified and implemented to maintain essential operations. Through effective emergency preparedness and creative improvisation, medical centers were able to overcome the initial crisis, sustain primary services, and ensure continued quality patient care. The article describes how sudden and prolonged water loss affected Des Moines hospitals. It also discusses aspects of hospital emergency preparedness that contributed to successful response.

The Midwest flood of 1993: surviving prolonged water loss.

The Midwest Flood of 1993 was one of the most devastating and challenging disasters in Iowa's history. The city's water supply became contaminated, leaving more than 250,000 residents and all seven metropolitan medical centers without water. Despite heroic sandbagging efforts, floodwaters invaded the Des Moines water treatment plant's filtration system. The major strategies used at this facility during the disaster provide a framework for effective, coordinated emergency response.