[Elastosis perforans serpiginosa in a patient with pseudoxanthoma elasticum]. / Elastosis perforans serpiginosa en una enferma afecta de pseudoxantoma elástico.

A 34-year-old female previously diagnosed of pseudoxanthoma elasticum developed an annular plaque with serpiginous borders of 42 by 30 mm in diameter on the inner left arm. A similar lesion later appeared on the inner right arm. Histopathological examination of a papule showed short, fragmented, granular, basophilic and calcified elastic fibers in the mid-reticular dermis. The epidermis showed hyperplasia surrounding degenerated and normal elastic fibers. Transepidermal elimination channels of these elastic fibers were also observed. These findings were consistent with the diagnosis of elastosis perforans serpiginosa. Abundant multinucleated giant cells were observed surrounding the area of epidermal hyperplasia and in the reticular dermis. The patient was treated with tazarotene, and the plaques disappeared in 9 months.

Interleukin-1 increases 15-hydroxyeicosatetraenoic acid production in human dermal fibroblasts.

Inhibition of the formation of pro-inflammatory eicosanoids such as leukotrienes and 12-hydroxyeicosatetraenoic acid by 15-hydroxyeicosatetraenoic acid (15-HETE) has been reported. Psoriatic dermis synthesizes reduced levels of 15-HETE and it has been postulated to play a role in the pathophysiology of this disease. Interleukin-1 stimulates the production of prostaglandin E2 in fibroblasts, but its effect on the synthesis of 15-HETE is at present unknown. The aim of this study was to investigate the modulation of 15-HETE formation by interleukin-1 in dermal fibroblasts. Cells were treated with recombinant interleukin-1 alpha or beta prior to incubation with exogenous 14C-arachidonic acid, and eicosanoids were analyzed by HPLC. Interleukin-1 significantly increased the production of 15-HETE, but also 12-hydroxy-heptadecatrienoic acid, 11-hydroxyeicosatetraenoic acid, and prostaglandins, in a concentration- and time-dependent fashion. No significant differences between the two types of interleukin-1 were found. Dexamethasone (10 nM), and the protein synthesis inhibitors actinomycin D (1 microM) and cycloheximide (3 micrograms/ml) completely abolished the effect of interleukin-1 on 15-HETE formation. Whereas indomethacin (0.5-25 microM) strongly inhibited the synthesis of 15-HETE, aspirin (100-1000 microM) was unable to significantly inhibit its formation in both untreated and interleukin-treated fibroblasts. Aspirin inhibited the 15-HETE produced by cyclooxygenase from ram seminal vesicles, although to a lesser extent than indomethacin. In cell-free extracts, the activity concerning the synthesis of 15-HETE was associated with the microsomal fraction (100,000 x g pellet). Overall, these results strongly suggest that interleukin-1 increases 15-HETE formation mainly through the expression of new cyclooxygenase.

Occurrence of hepoxilins and trioxilins in psoriatic lesions.

We recently found that normal human epidermis produces relatively high amounts of hepoxilins and trioxilins in vitro. Therefore, the aim of this study was to demonstrate the presence of these compounds in psoriatic lesions. Extracts from scales of patients with chronic stable plaque psoriasis were analyzed by a combination of high performance liquid chromatography and gas chromatography-mass spectrometry techniques. We found that the levels of hepoxilin B3 were more than 16-fold higher in psoriatic scales than in normal epidermis (3.2+/-2.3 and < 0.2 ng per mg, respectively), whereas hepoxilin A3 was not detected in any sample. Trioxilins were semiquantitated and referred to 12-hydroxyeicosatetraenoic acid, ratios of trioxilins A3 and B3 12-hydroxyeicosatetraenoic acid in psoriatic lesions were 0.65+/-0.23 and 0.32+/-0.28, respectively, and they were not detected in normal epidermis. The presence of a great amount of trioxilin A3 strongly suggests that hepoxilin A3 was present in psoriatic lesions and it was totally degraded to trioxilin A3 during the analysis procedure. Our results demonstrate that hepoxilins and trioxilins are produced by human skin in vivo and that the levels of these compounds are increased in psoriasis. The reported biologic activities of hepoxilins indicate that they could amplify and maintain the inflammatory response. Our results reinforce the idea that these compounds could play a role as mediators in the inflammatory response in skin, particularly in psoriasis.

Cyclooxygenase activity is increased in platelets from psoriatic patients.

The aim of the present study was to ascertain the relationship between in vitro hyper-aggregability and alterations in arachidonic acid metabolism in platelets from psoriatic patients. We have studied the response to several concentrations of ADP, collagen, and arachidonic acid of intact platelets from psoriatic patients and normal subjects, with and without irreversible inhibition of platelet cyclooxygenase by aspirin. Apparent kinetic constants (apparent Michaelis constant [Km] and apparent maximum velocity [Vmax]) of cyclooxygenase in platelets from both controls and psoriatic patients were also studied. The maximum percentage and slope of aggregation induced by collagen or sodium arachidonate were significantly greater (p less than 0.05) in platelets from psoriasis patients, whereas lag time was significantly shorter in the psoriasis group in response to arachidonic acid only when compared to controls. Cyclooxygenase pathway blockade inhibited the response to aggregation inducers in the following order: sodium arachidonate greater than collagen greater than ADP. When platelets were pre-treated with aspirin no significant differences were observed between controls and psoriasis patients. We also found a significant increase of the apparent Vmax value (p less than 0.05) for cyclooxygenase activity in platelets from psoriatic patients in comparison with controls. Our results indicate that platelet hyperaggregation in psoriatic patients is related to enhanced cyclooxygenase activity in their platelets.

Epidermal cell-polymorphonuclear leukocyte cooperation in the formation of leukotriene B4 by transcellular biosynthesis.

The cellular origin of Leukotriene B4, a potent pro-inflammatory agent that is present in psoriatic lesions, has not been completely ascertained. The present study was performed in order to assess the possible contribution of epidermal cells to leukotriene B4 synthesis through 5-lipoxygenase or by means of transcellular metabolism of the epoxide intermediate leukotriene A4 from activated polymorphonuclear leukocytes. The metabolism of exogenous arachidonic acid in fresh human epidermal cell, polymorphonuclear leukocyte or mixed suspensions was determined by means of high-performance liquid chromatography. Epidermal cells transformed arachidonic acid mainly into 12-hydroxy-eicosatetraenoic acid and prostaglandin E2. Formation of prostaglandins F2 alpha and D2, 12-hydroxy-eptadecatrienoic acid, and 15- and 11-hydroxy-eicosatetraenoic acids was also detected. We did not detect any eicosanoid derived from 5-lipoxygenase pathway. Mixed suspensions of polymorphonuclear leukocytes and epidermal cells (ratio 1:4) produced 1.72 times more leukotriene B4 than leukocytes alone under the same experimental conditions. Epidermal cells incubated with 5 microM authentic leukotriene A4 for 3 min yielded 2.954 +/- 0.27 pmoles/10(6) cells of leukotriene B4, which was characterized by co-elution with authentic standard and its ultraviolet absorption spectrum. These data demonstrate the existence of a leukotriene A4 epoxide hydrolase activity in human epidermal cells. Our results suggest that epidermal cells could cooperate in leukotriene B4 biosynthesis by transcellular metabolism of leukotriene A4 in lesions of psoriasis, and possibly other inflammatory dermatoses characterized by increased leukotriene B4 levels and prominent polymorphonuclear leukocyte infiltrates.

Prostaglandin H-synthase-2 is the main enzyme involved in the biosynthesis of octadecanoids from linoleic acid in human dermal fibroblasts stimulated with interleukin-1beta.

This study was focused on the characterization of the metabolism of linoleic acid by human dermal fibroblasts and the effect of interleukin-1 on the biosynthesis of octadecanoids. Dermal fibroblasts untreated and treated with recombinant IL-1beta were incubated with exogenous labeled linoleic acid. A combination of high performance liquid chromatography and gas chromatography-mass spectrometry was used as the analytic technique. We found that dermal fibroblasts convert linoleic acid mainly into 13-hydroxy-9-cis,11-trans-octadecadienoic acid (13-HODE) and 9-hydroxy-10-trans,12-cis-octadecadienoic acid (9-HODE), 13(S)-HODE and 9(R)-HODE being the predominant enantiomers. IL-1beta increased the formation of both 13-HODE and 9-HODE in a concentration-dependent manner with similar EC50 values as for prostanoid formation. This effect of IL-1beta on HODEs formation was concomitant with the expression of prostaglandin H-synthase-2. Formation of octadecanoids was inhibited in a concentration-dependent manner by acetylsalicylic acid and indomethacin. Dexamethasone, actinomycin D, and cycloheximide abolished the effect of IL-1beta on HODEs biosynthesis. Octadecanoid biosynthetic activity was associated with the microsomal fraction. Dermal fibroblasts incorporated [14C]-9-HODE and [14C]-13-HODE into phospholipids, mainly into phosphatidylcholine. IL-1beta increased significantly the esterification of 13-HODE in all glycerophospholipids, the major increase being observed in phosphatidylinositol. These results indicate that prostaglandin H-synthase-2 is the enzyme responsible for the increase in the ability to form HODEs of dermal fibroblasts stimulated with IL-1beta.

Cutaneous alternariosis treated with miconazole.

A 40-year-old man had had a chronic, slowly spreading inflammatory process in the skin over the right knee of ten years' duration. Culture of a biopsy specimen grew Alternaria sp. Antimycotic susceptibility testing with flucytosine, amphotericin B, and miconazole nitrate was performed. The Alternaria was highly sensitive to the last two drugs. Miconazole nitrate, 1.2 g daily intravenously for 31 days, did not induce a clinical response. The lesions were then infiltrated with 10 mg of miconazole nitrate in 10 mL of polyethoxylated castor oil (Cremophor EL) twice weekly, with clearing of the lesions during a several-month period.

Congenital ichthyosiform dermatosis with linear keratotic flexural papules and sclerosing palmoplantar keratoderma.

Four members of a consanguineous family showed a congenital disorder characterized by an ichthyosiform dermatosis, sclerosing palmoplantar keratoderma, and multiple keratotic papules arranged in bands with a linear, cordlike distribution. This association seems to represent a distinct entity. The differential diagnosis is described.

The use of levamisole in atopic dermatitis: a prospective study.

Levamisole hydrochloride, a nonspecific immunostimulant, was given to 30 children with atopic dermatitis (AD) in a double-blind manner during an eight-month period. Clinical course findings, including intradermal reactions to tuberculin, candidin, and streptokinase-streptodernase; sensitization to dinitrochlorobenzene; periphal blood T- and B-lymphocytes; in vitro lymphocyte transformation with phytohemagglutinin; and serum levels of IgM, IgG, IgA, and IgE, were noted every two months. Fifteen children completed the study. Neither the clinical course nor the immunologic values showed substantial differences between the levamisole-treated and the placebo group. Our experience with levamisole in AD is disappointing.

Septal granulomatous panniculitis in Sweet's syndrome. Report of two cases.

Two patients had Sweet's syndrome (acute febrile neutrophilic dermatosis) with subcutaneous lesions resembling erythema nodosum. In both, the erythema nodosum--like lesions histologically showed a septal granulomatous panniculitis with numerous Miescher's granulomas. This type of subcutaneous involvement in Sweet's syndrome should be differentiated from panniculitis caused by deep subcutaneous neutrophilic infiltration. Involvement of the panniculus in Sweet's syndrome may then occur in two different patterns: a septal granulomatous panniculitis, as in our two cases, or a neutrophilic lobular panniculitis, as has been previously reported.

Detection of Mycobacterium tuberculosis DNA in lobular granulomatous panniculitis (erythema induratum-nodular vasculitis).

OBJECTIVE: To determine, using polymerase chain reaction (PCR) amplification, if Mycobacterium tuberculosis complex DNA is present in the skin biopsy specimens of lobular granulomatous panniculitis. DESIGN: A retrospective descriptive study. SETTING: A university-based hospital. PATIENTS: From the 65 patients included in the study, we examined 72 paraffin-embedded skin biopsy specimens with a histologic diagnosis of erythema induratum or nodular vasculitis. The biopsy specimens were from the histopathological archives of the Departments of Dermatology and Pathology of the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, from 1976 to 1994. Twenty-two biopsy specimens were excluded from the final analysis because we could not amplify the internal control. MAIN OUTCOME MEASURES: Detection of a 123-base pair fragment of the IS6110 insertion sequence specific for M tuberculosis complex. RESULTS: The results of PCR amplification were positive for M tuberculosis complex DNA in 77% of the skin biopsy specimens. No significant difference could be detected with respect to the age of the patients, ulceration of the nodules, reactivity to purified protein derivative, abnormal results of a chest x-ray examination, personal and family history of tuberculosis, and PCR results. The presence and degree of necrosis on histologic examination were significantly higher in the PCR-positive group (P = .04). None of the following variables were associated with PCR results: presence of vasculitis, degree of granulomatous infiltrates, number of giant cells, and presence of well-organized granulomas. CONCLUSIONS: The DNA of M tuberculosis can be detected in a considerable number of skin biopsy specimens of lobular granulomatous panniculitis. None of the clinical and histologic variables evaluated could accurately predict the results of PCR amplification.

Apolipoprotein E phenotypes, lipoprotein composition, and xanthelasmas.

The different types of serum lipoproteins, including apolipoprotein E phenotypes, were measured in 50 patients with xanthelasma. Half of them were found to be hyperlipemic. The normolipemic and hyperlipemic groups with xanthelasma were compared with two control groups (one a group of normolipemic patients and another a group of hyperlipemic patients without xanthelasma) selected as homogeneously as possible with regard to age, sex, degree of obesity, and hyperlipemic phenotype. The only significant differences found among the groups, regardless of the presence of hyperlipemia, were the increased levels of total and high-density lipoprotein phospholipids, and lower levels of apolipoprotein B, found in the group with xanthelasmas. The distribution of apolipoprotein E phenotypes was the same in both groups, with slight differences between the normolipemic and hyperlipemic groups. Patients with xanthelasmas showed slight deviations in the metabolism of lipoproteins that require further clarification.

Persistent subcutaneous nodules in patients hyposensitized with aluminum-containing allergen extracts.

BACKGROUND: The development of persistent nodules that cause pain and itching at a vaccination or hyposensitization injection site is a rare event. These lesions have been mainly attributed to a hypersensitivity reaction to aluminum hydroxide, which is used as an absorbing agent in many vaccines and hyposensitization preparations. Patch tests with standard antigens and aluminum compounds and histopathologic and ultrastructural studies were performed on 10 patients with persistent subcutaneous nodules on the upper part of their arms after injection of aluminum-adsorbed dust and/or pollen extracts. OBSERVATIONS: The nodules appeared 1 month to 6.5 years after injections. The results of patch tests with 2% aluminum chloride were positive in five patients. Histopathologic examination revealed two different patterns: some biopsy specimens (from lesions of less than 9 months' duration) showed a pure foreign body histiocytic reaction characterized by extracellular amorphous dermal basophilic deposits with a histiocytic-macrophagic reaction; others showed a delayed hypersensitivity granulomatous reaction in association with an histiocytic foreign body response. The lesions were characterized by a unifocal or multifocal unencapsulated granulomatous reaction in the deep dermis and/or subcutaneous tissue. Eosinophilic necrotic areas surrounded by dense fibrous bands and a massive inflammatory infiltrate (lymphoid follicles, large histiocytic cells, abundant eosinophils, and some plasma cells) were observed. A granular basophilic material in extracellular spaces and within the cytoplasm of some histiocytes was also noted. Electron microscopic studies revealed intracytoplasmic and extracellular deposits of a fibrillar electron-dense material. CONCLUSIONS: Persistent subcutaneous nodules that develop after the administration of aluminum-containing preparations may show two characteristic histopathologic patterns. A pure histiocytic foreign body reaction was observed in early lesions, and a delayed hypersensitivity granulomatous reaction was seen in older lesions. No relationship between histopathologic pattern and patch test results was observed. Aluminum-free preparations should be used in patients in whom these nodules develop.

Metabolism of exogenous arachidonic acid by polymorphonuclear leukocytes from psoriatic patients.

We evaluated the metabolism of exogenous arachidonic acid in polymorphonuclear leukocytes from psoriatic patients in comparison with those from normal subjects. The leukocytes were incubated with 10 microM labelled arachidonic acid and 5 microM A23187 for varying periods of time. We evaluated all the compounds derived from the 5-lipoxygenase activity, including the products of non-enzymatic transformation of leukotriene A4 and w-oxidized leukotriene B4. In the experimental conditions used, there was no significant difference in the formation of any compound at any time of incubation. These results indicate that there is no intrinsic alteration either in 5-lipoxygenase activity or in w-oxidation ability of circulating polymorphonuclear leukocytes in psoriatic patients.

Familial leiomyomatosis cutis et uteri (Reed's syndrome).

We report a large family with leiomyomatosis cutis et uteri. Sixty-four percent of the females were involved; 18% had only uterine myomas, 10% had only cutaneous piloleiomyomas, and 36% had both. Five patients (45%) had to have an hysterectomy before age 35. Management of female patients having leiomyomatosis cutis should include a periodical gynecological examination in order to rule out the presence of uterine myomas.

Prurigo gravidarum.

Prurigo gravidarum is an infrequent dermatologic condition in pregnant patients that has been found to be associated with an increased incidence of perinatal and obstetric complications. We present ten cases of this finding and review the pathogenesis, therapy, and complications of prurigo gravidarum. The recognition of this entity by dermatologists, obstetricians, and general practitioners should prompt referral of these patients for high-risk obstetric care.

Masson's intravascular papillary endothelial hyperplasia mimicking Stewart-Treves syndrome: report of a case.

Masson's intravascular papillary endothelial hyperplasia, also called Masson's pseudoangiosarcoma, represents a benign vascular proliferation, presently considered as a peculiar histopathologic reaction pattern of the endothelium to diverse stimuli. Differentiation from angiosarcoma represents the main diagnostic concern. We report a case of Masson's intravascular papillary endothelial hyperplasia presenting in a 55-year-old woman with ipsilateral lymphedema secondary to surgery and radiation therapy for breast carcinoma. The diagnosis was intravascular papillary endothelial hyperplasia. This is the first description of Masson's pseudoangiosarcoma in this clinical context, to our knowledge. We believe it represents a peculiar morphologic pattern of endothelium proliferation secondary to venous stasis and thrombosis due to lymphedema.

Amelanotic lentigo maligna melanoma: report of a case and review of the literature.

Amelanotic lentigo maligna melanoma (ALMM) is an infrequent presentation of lentigo maligna melanoma, less than thirty cases having been reported to date. Hypopigmented or erythematous macules on the face of older women, resembling Bowen's disease or eczema, are the most common clinical presentation. We report a case of ALMM in a 73-year-old woman. Therapeutic trials with cryotherapy, 5-fluorouracil, and azelaic acid were unsuccessful, and the lesions were eventually cured by surgical excision. ALMM requires early clinical suspicion and histopathologic confirmation of diagnosis in every patient presenting with a slowly enlarging erythematous or hypopigmented macule, especially when located on the face of an older woman with a light complexion.

Petechial glove and sock syndrome caused by parvovirus B19.

The petechial glove and sock syndrome is a recently described febrile dermatosis characterized by acral edema, petechiae in a characteristic distribution, and enanthem, which has been associated in several cases with parvovirus B19 seroconversion. We report an additional case of petechial glove and sock syndrome that further corroborates the role of parvovirus B19 as a causative agent of this syndrome in adults.