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PubMed2002

Clinical responses to undiluted and diluted smallpox vaccine.

BACKGROUND: To evaluate the potential to increase the supply of smallpox vaccine (vaccinia virus), we compared the response to vaccination with 10(8.1), 10(7.2), and 10(7.0) plaque-forming units (pfu) of vaccinia virus per milliliter. METHODS: In this randomized, single-blind, prospective study, 680 adults who had not been previously immunized were inoculated intradermally with undiluted vaccine (mean titer, 10(8.1) pfu per milliliter), a 1:5 dilution, or a 1:10 dilution of vaccinia virus with use of a bifurcated needle, and the site was covered with a semipermeable dressing. Subjects were monitored for vesicle formation (an indicator of the success of vaccination) and adverse events for 56 days after immunization. RESULTS: Success rates did not differ significantly among the groups and ranged from 97.1 to 99.1 percent after the first vaccination. Both the undiluted and diluted vaccines were reactogenic. In addition to the formation of pustules, common adverse events included the formation of satellite lesions, regional lymphadenopathy, fever, headache, nausea, muscle aches, fatigue, and chills consistent with the presence of an acute viral illness. Generalized and localized rashes, including two cases of erythema multiforme, were also observed. CONCLUSIONS: When given by a bifurcated needle, vaccinia virus vaccine can be diluted to a titer as low as 10(7.0) pfu per milliliter (approximately 10,000 pfu per dose) and induce local viral replication and vesicle formation in more than 97 percent of persons.

Adolescent↗
PubMed2000

Potassium iodide in dermatology: a 19th century drug for the 21st century-uses, pharmacology, adverse effects, and contraindications.

Potassium iodide (KI) is a useful drug in the dermatologic armamentarium. It is successfully used for inflammatory dermatoses, most notably erythema nodosum, subacute nodular migratory panniculitis, nodular vasculitis, erythema multiforme, and Sweet's syndrome. KI is also successfully used for cutaneous and lymphocutaneous sporotrichosis. The precise mechanism by which KI acts is unknown. Although many minor side effects are common with this drug, major side effects can occur in pregnant patients and those with a history of kidney or thyroid disease. This article reviews the pharmacology, mechanism of action, indications, contraindications, and adverse effects of KI as a therapeutic agent.

Humans↗
PubMed2003

Bullous autoimmune estrogen dermatitis.

We report a case of bullous eruption secondary to exogenous estrogen. Histology mimicked erythema multiforme. Lesions cleared with discontinuation of estrogen.

Autoimmune Diseases↗
PubMed2003

Dermatologic side effects of thalidomide in patients with multiple myeloma.

BACKGROUND: Thalidomide, an antiangiogenic agent, was approved by the Food and Drug Administration in 1998 for the treatment of erythema nodosum leprosum. Although its teratogenic and neurologic side effects are well known, its dermatologic side effects continue to be defined. OBJECTIVE: We report the dermatologic side effects in 87 patients with multiple myeloma enrolled in a comparative, open-label, clinical trial treated with thalidomide alone (50 patients) or thalidomide and dexamethasone (37 patients). METHOD: We reviewed the records of all patients enrolled in the clinical trial. The frequency, type, severity, and time of onset of all skin eruptions that were temporally related to thalidomide treatment were recorded. RESULTS: Minor to moderate skin eruptions were noted in 46% of patients taking thalidomide alone and in 43% of those taking thalidomide and dexamethasone. These included morbilliform, seborrheic, maculopapular, or nonspecific dermatitis. Severe skin reactions (exfoliative erythroderma, erythema multiforme, and toxic epidermal necrolysis) that required hospitalization and withdrawal of thalidomide developed in 3 patients receiving thalidomide and dexamethasone. CONCLUSION: The prevalence of dermatologic side effects of thalidomide appear to be higher than previously reported. Although in most patients they were minor, in a few patients they were quite severe, particularly when given in conjunction with dexamethasone for newly diagnosed myeloma. Further studies are needed to verify the extent of the interaction between thalidomide and dexamethasone in this group of patients.

Adult↗
PubMed2003

Scar-localized argyria secondary to silver sulfadiazine cream.

Silver sulfadiazine cream is a topical antibacterial agent that combines the antibacterial effects of both silver and sulfadiazine. Its reported cutaneous side effects include hypersensitivity reactions, allergic contact dermatitis, erythema multiforme, and systemic argyria. We report the case of a patient who had localized argyria develop in a scar after the use of silver sulfadiazine cream. In this case, the silver sulfadiazine cream was applied to and argyria developed within a postsurgical wound and area of severe contact dermatitis.

Administration, Cutaneous↗
PubMed1998

Subacute cutaneous lupus erythematosus: two cases of delayed diagnosis.

Two cases of subacute cutaneous lupus erythematosus are described. Features which delayed diagnosis are discussed. The potential clinical and histopathological overlap between this condition and erythema multiforme is emphasized, drawing attention to the histological features which allow distinction. The possibility that some cases of Rowell's syndrome may be manifestations of subacute lupus erythematosus is discussed.

Aged↗
PubMed1999

Mast cells in developing subepidermal bullous diseases: emphasis on tryptase, chymase and protease inhibitors.

The possible involvement of mast cell tryptase and chymase in subepidermal bullous diseases was studied enzyme-histochemically in specimens from erythematous and vesicular skin and from non-involved skin of patients with dermatitis herpetiformis, bullous pemphigoid, erythema multiforme, infective bullous eruption and linear IgA dermatosis. Patients with pemphigus were biopsied for comparison. The immunoreactivity of chymase inhibitors, alpha1-proteinase inhibitor (alpha1-PI) and alpha1-antichymotrypsin (alpha1-AC), in mast cells was demonstrated using the sequential double staining method. Tryptase-positive mast cells were unchanged or only slightly increased in number in erythematous lesions and slightly decreased in blistering skin compared with healthy-looking skin. Only occasionally were mast cells seen in apparent contact with the basement membrane zone. Chymase-positive mast cells and the chymase/tryptase ratio steadily decreased during the development of the lesions in each subepidermal bullous disease. The percentage of alpha1-PI+ and/or alpha1-AC+ mast cells increased simultaneously, which could explain the disappearance of chymase activity. Similar results were obtained regardless of the bullous disease. The results were also similar in pemphigus, which is an intraepidermal bullous disease. In conclusion, these results show significant alterations in mast cell chymase and protease inhibitors in a range of different bullous diseases, suggesting mast cell involvement. The apparent inactivation of chymase could be due to the action of chymase inhibitors detected in numerous mast cells. However, these alterations probably reflect general inflammation rather than a specific reaction in a certain bullous disease.

Adolescent↗
PubMed1995

A retrospective evaluation of adverse reactions to trimethoprim-sulphonamide combinations in dogs and cats.

Adverse reactions to various trimethoprim-sulphonamide (T-S) combinations were studied retrospectively in dogs and cats referred to the Utrecht University Department of Clinical Sciences of Companion Animals during the period 1985-1994. Dermatological and systemic reactions were observed in 19 dogs and 2 cats. Specific histological reaction patterns were seen in 3 dogs with toxic epidermal necrolysis, in 1 dog and 1 cat with erythema multiforme, and in 1 dog with pemphigus foliaceus. Diagnostic criteria used in humans proved to be reliable in dogs and cats as well. Adverse reactions were observed within 7-14 days after administration and were most often due to sulphadiazine (76%) and sulphatroxazole (14%). The incidence of adverse reactions to T-S was 0.25%.

Animals↗
PubMed2006

Paraneoplastic autoimmune multiorgan syndrome: review of the literature and support for a cytotoxic role in pathogenesis.

Paraneoplastic autoimmune multiorgan syndrome (PAMS), first described as paraneoplastic pemphigus in 1990, is an autoimmune blistering disease associated with neoplasia. Patients with this rare disorder have severe blistering and painful erosions of the oral cavity and various other cutaneous findings ranging from classic pemphigus vulgaris-like erosions to targetoid lesions resembling erythema multiforme and papular to more confluent lichenoid eruptions. This syndrome involves multiple organ systems, and its high rate of mortality often stems from constrictive bronchiolitis obliterans. The histologic findings are as diverse as the clinical presentation, often making diagnosis difficult initially. Immunodermatologic and serologic laboratory findings typically establish the diagnosis. These results can be confirmed with immunoprecipitation profiling of specific molecular weight protein markers. The proposed pathogenesis of PAMS continues to evolve, and recent reports implicate the involvement of cell-mediated, cytotoxic immunity, in addition to humoral autoantibodies. This review characterizes and summarizes the clinical, pathologic, and immunohistologic features of PAMS and outlines the possible role of cytotoxic T lymphocytes in the pathogenesis of this syndrome.

Autoimmune Diseases↗
PubMed2006

Autoimmune progesterone dermatitis.

Autoimmune progesterone dermatitis (APD) is a rare disorder characterized by recurrent polymorphous skin manifestations, which appear or are exacerbated during the luteal phase of the menstrual cycle. The hallmarks for diagnosis include premenstrual flare, its prevention with the inhibition of ovulation, and positive skin reaction to intradermal injection of progesterone. The mainstay of treatment is to inhibit the secretion of endogenous progesterone by suppressing ovulation. Bilateral oophorectomy may be necessary in patients with severe and refractory symptoms. We report herein the case of a 38-year-old woman who developed recurrent and cyclic vesiculobullous eruptions clinically suggestive of erythema multiforme or autoimmune bullous diseases. The skin manifestations turned out to be APD. The patient was treated with tamoxifen 20 mg daily with complete symptom remission after 4 months.

Adult↗
PubMed1986

Expression of HLA-DR molecules by keratinocytes, and presence of Langerhans cells in the dermal infiltrate of active psoriatic plaques.

Immunoperoxidase staining of skin sections and immunofluorescence analysis of keratinocyte suspensions obtained from suction blisters of psoriatic plaques were performed using an mAb, Josh 524.4.1, and Fab'2 fragments of a rabbit antiserum, both of which are directed against nonpolymorphic determinants of HLA-DR molecules. HLA-DR+ keratinocytes were present in plaques, but not normal-appearing skin, from a significant portion of patients with active psoriasis. Double-labelling immunofluorescence experiments with either the monoclonal or polyclonal anti-HLA-DR antibody, in conjunction with the mAb OKT6, which identifies DR+ Langerhans cells, demonstrated that HLA-DR molecules were present on OKT6- keratinocytes. The dermal infiltrate of psoriatic plaques contained T cells expressing the activation antigens, IL-2 receptor (Tac) and HLA-DR, as well as macrophages and OKT6+ cells. There was little difference in the characteristics of the dermal infiltrate between the lesions with or without HLA-DR+ keratinocytes. OKT6+ presumptive Langerhans cells were also found in the dermal infiltrates of patients with lichen planus, contact dermatitis, spongiotic dermatitis, erythema multiforme, basal and squamous cell carcinoma. Studies of keratinocyte suspensions showed that 7-84% of keratinocytes were HLA-DR+. Flow cytometry experiments showed that keratinocytes at all stages of differentiation were HLA-DR+. However, the stem cell-enriched population contained the highest proportion of HLA-DR+ cells. HLA-DR expression by keratinocytes correlated with disease activity. The expression was reversible with successful medical therapy. HLA-DR+ keratinocytes may activate T cells directly or may present an as yet unknown antigen to T cells. These studies provide further support for the hypothesis that immunological mechanisms play an important role in the pathogenesis of psoriasis.

Dermatitis↗
PubMedDate not supplied

Cutaneous and soft-tissue manifestations of sepsis due to gram-negative enteric bacilli.

Four patterns of tissue involvement can be distinguished in sepsis due to gram-negative enteric bacilli. When intense local inflammation predominates, cellulitis or thrombophlebitis results, often with venous or arterial obstruction. Bacteria are present in the affected tissues, but not in sufficient numbers to be seen microscopically. When bacterial proliferation is unchecked by an appropriate leukocyte response, ecthyma gangrenosum, erythema multiforme, or diffuse bullous lesions may occur with minimal clinical or histologic signs of inflammation. In symmetric peripheral gangrene associated with disseminated intravascular coagulation, bland fibrinous deposits are seen in small vessels but neither inflammatory cells nor bacteria are present. The fourth kind of lesion is that seen in bacterial endocarditis. In all four patterns a vascular component is prominent clinically and histologically. The pathogenesis of these lesions is multifactorial; in each individual case the interaction between bacterial and host factors probably determines which clinical picture will result. The appearance of symmetric soft tissue lesions of the extremities in the absence of predisposing local conditions suggests the possibility of sepsis due to gram-negative bacilli, especially if other clinical features indicate that sepsis might be present.

Bacterial Infections↗
PubMed1995

Spectrum of parvovirus B19 infection: analysis of an outbreak of 43 cases in Cadiz, Spain.

In the spring of 1993, an epidemic of infection with human parvovirus B19 occurred in Cadiz, Spain. Evaluation of the 43 patients in whom this diagnosis was confirmed revealed four groups of predominant manifestations: (1) hematologic manifestations in six cases (13.9%), including four of aplastic crisis and two of pancytopenia; (2) dermatologic manifestations in 23 cases (53.4%), including 10 of erythema infectiosum and one of erythema multiforme ampullosum; (3) arthralgias/arthritis in nine cases (20.9%), including two with a chronic course; and (4) infection during pregnancy in three cases (7.0%), including two that ended in abortion. Of the 43 patients, 37.2% presented with fever and adenopathies, and these were the only manifestations in two cases. The appearance of clinical disease correlated with modifications in isotype and serum level of specific antibodies to parvovirus B19; the disappearance of IgM antibodies coincided with the resolution of clinical manifestations. Although their presence did not correlate with the course of the disease, the detection of circulating immune complexes in 81.6% of cases supports the possibility that some manifestations were immune mediated.

Adolescent↗
PubMed1995

Safety, plasma concentrations, and efficacy of high-dose fluconazole in invasive mold infections.

A trial of the antifungal triazole fluconazole was conducted in cancer patients with presumed or proven mold infection. Groups of patients received fluconazole at four dosages (800, 1200, 1600, or 2000 mg/day). Adverse events, plasma levels, and clinical response were examined. Thirty-nine patients were enrolled. The 28 evaluable patients had presumed (13 patients) or proven (15) mold infection with Aspergillus (4) and Fusarium (3) species, Zygomycetes organisms (1), or nonspeciated mold (7). Adverse effects included elevated liver function test results (8 patients), nausea and vomiting (2), and erythema multiforme (1). Neurologic toxicity occurred in 3 patients receiving 2000 mg/day. Average steady-state peak plasma concentrations were 51.8, 74.4, and 91.8 mg/L for dosages 1200, 1600, and 2000 mg/day, respectively. Seven of 28 evaluable patients responded. Response did not appear to be related to dose. Fluconazole is well tolerated at total daily doses up to 1600 mg. The data suggest a linear plasma concentration-dose relationship. The activity of fluconazole in refractory mold infections seems to be limited.

Adolescent↗
PubMed1985

Toxic shock syndrome. I. Clinical exclusion of other syndromes by strict and screening definitions.

Several clinical definitions of toxic shock syndrome have been proposed and used in extensive epidemiologic and clinical studies. Most of these definitions suggest (but usually do not require) that there be sufficient laboratory studies to exclude other potentially similar syndromes. Simplified definitions which broaden the spectrum of toxic shock syndrome illness have also been proposed but not validated. In this study, clinical findings of consecutive hospitalized patients were compared: nine with toxic shock syndrome (confirmed by a modification of the collaborative strict case definition) and 120 with potentially similar diagnoses (bacteremia with shock, meningococcemia, Staphylococcus aureus bacteremia, scarlet fever, toxic epidermal necrolysis, acute rheumatic fever, leptospirosis, Rocky Mountain spotted fever, rubeola, Kawasaki syndrome, erythema multiforme, and Stevens-Johnson syndrome). None of the 120 controls satisfied the clinical criteria of the modified strict definition of toxic shock syndrome, demonstrating its exclusionary properties even in the absence of additional laboratory data. A "simplified" screening definition was constructed which might be applied early in illness (i.e., at admission) and this definition distinguished all the patients with toxic shock syndrome from all but three (2.5%) of the 117 analyzable patients with other mucocutaneous or potential infectious shock syndromes. Applied prospectively in the state of Colorado passive/active reporting system, the screening definition identified 24 potential toxic shock syndrome cases of which 19 (76%) eventually were confirmed as toxic shock syndrome. Before being adopted and widely used, clinical syndrome definitions should be documented to exclude other potentially overlapping syndromes or should require additional mandatory exclusionary laboratory data.

Adolescent↗
PubMed1980

Hodgkin's disease with specific bullous lesions.

A variety of bullous eruptions have been reported in patients with Hodgkin's disease, among them erythema multiforme, herpesvirus infections, bullous impetigo, prurigo-like papules with vesicles, drug eruptions, bullous pemphigoid, dermatitis herpetiformis, and acquired epidermolysis bullosa. We now describe a patient whose bullous eruption was thought initially to be bullous pemphigoid. However, histopathologic examination of a bulla showed a lymphomatous infiltrate beneath an intraepidermal and subepidermal blister. These pathological findings seem to be unique and we interpret them to be those of bullous Hodgkin's disease.

Diagnosis, Differential↗
PubMed1987

Enhanced binding of peripheral blood mononuclear leukocytes to gamma-interferon-treated cultured keratinocytes.

Dermatopathologists observe mononuclear leukocytes in close apposition to keratinocytes (KCs) in graft versus host disease and in other lymphocyte-mediated skin diseases, such as lichen planus, erythema multiforme, and lupus erythematosus. Since the KCs are Class II histocompatibility antigen (HLA-DR) positive in these diseases (indicating local production of gamma interferon, IFN-gamma, by activated T-cells), we sought to determine whether IFN-gamma treatment of KCs would influence the ability of allogeneic peripheral blood mononuclear leukocytes (PBMLs) to adhere to cultured KCs in vitro. The adherence of PBMLs to KC monolayers was determined by the three following methods: (a) methanol fixation of the washed KCs (after PBML incubation), followed by hematoxylin-eosin staining and direct counting of adherent PBMLs; (b) fluorescein isothiocyanate (FITC) labeling of PBML, followed by measuring the amount of FITC-PBML bound to KCs after washing either by direct visualization with a fluorescence microscope; or by (c) quantitative fluorescence spectroscopy following lysis of the adherent cells. While untreated KCs bound allogeneic PBMLs minimally 15-120 min at 37 degrees C, pretreatment of the KCs with IFN-gamma (300 U/ml, 3 days) produced significantly increased binding of the PBMLs by approximately fivefold. By contrast, IFN-alpha and IFN-beta (10(3) U/ml) had no effect. Also, despite the induction of HLA-DR on cultured human fibroblasts, no increased binding of PBMLs after IFN-gamma treatment was observed. The selective ability of IFN-gamma to produce a marked increase in adherence between KCs and PBMLs suggests a new role for IFN-gamma in the immunobiology of the skin.

Cell Adhesion↗
PubMed1991

Lichenoid histopathologic changes in patients with clinical diagnoses of exfoliative dermatitis.

Among 30 patients who received a clinical diagnosis of exfoliative dermatitis and were biopsied between 1982 and 1990, nine showed microscopic features of lichenoid dermatitis. Clinical information was available in eight of these cases. Possible etiologic factors included lymphoma, herpes simplex infection, connective tissue disease, and (in five cases) reactions to drugs. In each instance, microscopic features included a superficial perivascular lymphocytic infiltrate involving the dermal-epidermal interface, vacuolar alteration of the basilar layer, and individually necrotic keratinocytes at all levels of the epidermis. Such microscopic changes are not usually described in connection with exfoliative dermatitis, with the possible exception of those cases related to lichen planus or lupus erythematosus. Disseminated lichenoid drug eruption is one possible interpretation of the drug-induced cases. Erythema multiforme is another condition that has similar microscopic features and has been associated with drugs (many of which also cause exfoliative dermatitis), infectious agents, neoplasms, and connective tissue diseases. Lichenoid dermatitis can become generalized and clinically mimic and exfoliative dermatitis. Many, but not all, of these eruptions may be triggered by drugs.

Adult↗