Enhanced expression of human metalloelastase (MMP-12) in cutaneous granulomas and macrophage migration.
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Accumulation of inflammatory cells such as macrophages may lead to degeneration of connective tissue matrix in various skin diseases. Macrophage metalloelastase, is a matrix metalloproteinase (MMP-12) capable of degrading elastin as well as various basement membrane components. To investigate the role of human macrophage metalloelastase in skin, we assessed by in situ hybridization and immunohistochemistry 66 specimens representing skin diseases characterized either by changes in elastic fibers or by pronounced infiltrations of extravasating and migrating macrophages. CD68 immunostaining was performed to identify the human macrophage metalloelastase-positive cells and Weigert's Resorcin-Fuchsin staining to reveal the status of elastic fibers. We found abundant expression of human macrophage metalloelastase mRNA in macrophages in areas devoid of normal elastic fibers in granulomatous skin diseases sarcoidosis, necrobiosis lipoidica diabeticorum, and granuloma annulare. Positive cells for human macrophage metalloelastase protein could be detected in the same regions as well as positive immunostaining for urokinase plasminogen activator. Of the other matrix metalloproteinases capable of degrading elastin, 92 kDa gelatinase colocalized with human macrophage metalloelastase, while 72 kDa gelatinase was produced by surrounding fibroblast-like cells. Furthermore, human macrophage metalloelastase was expressed by macrophages in areas with disrupted basement membrane, as assessed by type IV collagen staining, in pityriasis lichenoides and dermatitis herpetiformis. Specimens of anetoderma, acrodermatitis chronica atrophicans and pseudoxanthoma elasticum showed no signal for human macrophage metalloelastase. Matrilysin was not detected in any of the samples investigated. Our study suggests that human macrophage metalloelastase may contribute to elastin degradation occurring in granulomatous skin diseases and may aid macrophage migration through the epidermal and vascular basement membranes in inflammatory disorders. (+info)
Penile granuloma annulare.
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A case of granuloma annulare (GA) localised to the shaft of the penis is reported with a brief review of the current literature. We concluded that penile GA, although rare, should be considered in the differential diagnosis of granulomatous lesions of the penis and that histopathological examination of the lesion is essential for the diagnosis. (+info)
Papulonecrotic tuberculide and stenosis of the abdominal aorta.
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Papulonecrotic tuberculide (PNT) is a rare form of skin tuberculosis affecting predominantly young adults, with a history of immunity to Mycobacterium tuberculosis. We report a case of a young Caucasian female with PNT who was also documented to have a stenotic segment in the abdominal aorta. The difficulty in clarifying and treating the primary disease and the association between a tuberculous infection and Takayasu's arteritis are discussed. (+info)
Subcutaneous granuloma annulare of the extremities in children.
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OBJECTIVE: To familiarize surgeons to the natural history and treatment of granuloma annulare of the extremities in children. DESIGN: Case review and follow-up by appointment and questionnaire. SETTING: The Children's Hospital of Eastern Ontario, a tertiary referral centre. PATIENTS: Twenty-seven children (23 girls, 4 boys) seen between 1983 and 1998 with subcutaneous granuloma annulare, proven pathologically. The mean age at initial presentation was 8.3 years (range from 1.8 years to 16.7 years). The mean follow-up was 45 weeks (range from 1 week to 5 years). INTERVENTION: Biopsy excision of the lesions. OUTCOME MEASURES: The incidence multiple lesions, the commonest site of occurrence and the incidence of recurrence. RESULTS: Six children presented with multiple lesions for a total of 46 lesions. The anterior pretibial area was the most frequently affected site (16 lesions), followed by the ankle (6 lesions) and the long finger (4 lesions). Five patients suffered recurrence of the lesion, with a total of 7 lesions recurring. CONCLUSIONS: Subcutaneous granuloma annulare is a benign inflammatory skin lesion occurring most frequently in the anterior pretibial area in children, predominantly girls. The incidence of recurrence and of multiple lesions is high. Biopsy is required for definitive diagnosis. The lesion resolves spontaneously without treatment. (+info)
Treatment of disseminated granuloma annulare with fumaric acid esters.
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BACKGROUND: Granuloma annulare is a granulomatous disease of unknown etiology. Various therapies have been tried in disseminated granuloma annulare (DGA), including corticosteroids, several variants of psoralen plus ultraviolet-A radiation, ultraviolet- A1 radiation, systemic retinoids, and dapsone, with variable success. We report a patient with recalcitrant DGA who was treated with fumaric acid esters (FAE). CASE PRESENTATION: A 40-year old Caucasian woman presented with a 25-year history of recalcitrant DGA. On both legs and the abdomen there were erythematous annular plaques. She was treated with FAE in tablet form using two formulations differing in strength (low strength tablets: 30 mg dimethylfumarate, 67 mg monoethylfumarate Ca salt, 5 mg monoethylfumarate Mg salt, 3 mg monoethylfumarate Zn salt; high strength tablets: 120 mg dimethylfumarate, 87 mg monoethylfumarate Ca salt, 5 mg monoethylfumarate Mg salt, 3 mg monoethylfumarate Zn salt). After three-month therapy, an almost complete clearance of skin lesions was achieved. With the exception of temporary lymphopenia, no adverse effects were observed. The patient remained in remission during a six-month follow up period. CONCLUSIONS: Our observation has demonstrated that FAE is a potentially beneficial therapeutic option for patients with recalcitrant DGA. However controlled trials are necessary to fully explore the efficacy, optimal dosage, and safety of FAE in the management of DGA. (+info)
T-cell receptor repertoire and cytokine pattern in granuloma annulare: defining a particular type of cutaneous granulomatous inflammation.
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Granuloma annulare is a common granulomatous infiltration of the skin of unknown etiopathogenesis. We analyzed granuloma annulare biopsies in 11 patients and could find in all patients significant numbers of CD4-T cells. These cells showed a broad usage of the different T cell receptor Vbeta families and a rather unbiased repertoire when the complementary determining region 3 spectra were analyzed by the Immunoscope technique. Comparison with the peripheral blood mononuclear cell repertoire, however, identified in all patients few skin-specific expansions, which were for one patient also present in two distinct skin sites. Extensive sequence analysis of the complementary determining region 3 region confirmed the presence of a limited number of skin-specific expansions together with various nonspecific T cell infiltrations. Analysis of the intralesional cytokine expression revealed abundant production of interleukin-2, which was not dominant in granulomas from leprosy patients and was not reflected by the cytokine profile in peripheral blood mononuclear cells. These results demonstrate the capacity of the granulomatous response to recruit T cells in high numbers with only few clones expanding specifically. The high local production of interleukin-2 might thereby play an important role in the nonspecific attraction of T cells to the granulomatous site. (+info)
Is granuloma annulare related to intermediate uveitis with retinal vasculitis?
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AIM: To report on eight patients with severe idiopathic intermediate uveitis (IU) and granuloma annulare (GA), a self limiting cutaneous condition of unknown aetiology. METHODS: Retrospective case series. Clinical ophthalmic and dermatological data were studied and fluorescein angiography and skin biopsies were reviewed. RESULTS: All patients with idiopathic IU had similar ocular features (eight with vitritis, seven with retinal vasculitis) and developed complications such as cystoid macular oedema (n=5), cataract (n=4), and glaucoma (n=3). Systemic diseases were not found, but a localised type of GA was observed in all. CONCLUSION: Seven out of eight patients with IU and GA developed severe retinal vasculitis. Further studies are needed for a better understanding of this association, a common pathogenesis, and its eventual clinical consequences. (+info)
Granuloma annulare of the penis.
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Granuloma annulare is an uncommon skin condition, most often found on the extremities of young females. A case of granuloma annulare occurring on the penis of a 61 year old man is reported and the current literature associating granuloma annulare and conditions likely to present to genitourinary clinics is reviewed. (+info)