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Tear fluid levels of MMP-8 are elevated in ocular rosacea--treatment effect of oral doxycycline.

BACKGROUND: Ocular rosacea (OcR) is a chronic inflammatory disease especially affecting lid margins. Previous studies have shown that it is accompanied by increased levels and activation of tear fluid gelatinases. Matrix metalloproteinase 8 (MMP-8; collagenase 2) levels and activation are commonly elevated in many inflammatory conditions. Therefore we studied here whether MMP-8 concentration and activation in tear fluid are increased also in OcR, and if an oral doxycycline regimen could rectify the situation. METHODS: Tear fluid samples were collected from 22 OcR patients and 22 healthy controls. The OcR patients were then treated with an oral doxycycline regimen for 8 weeks and tear fluid samples collected again after 4 and 8 weeks. Conjunctival brush cytology and patients' subjective symptoms were scored. MMP-8 concentrations in the tear fluid were assessed by immunofluorometric assay and the molecular forms and isoenzyme expression of MMP-8 were studied by Western immunoblotting. RESULTS: The mean MMP-8 concentration was statistically significantly higher in OcR (156.8+/-207.4 mug/ml) than in the normal subjects (53.5+/-66.7 mug/ml) (P=0.036), but decreased to 79.2+/-141.6 mug/l and 53.6+/-75.2 mug/l after 4 and 8 weeks doxycycline treatment, respectively. There was a statistically significant difference between the untreated OcR and the MMP-8 results after 4 or 8 weeks of oral doxycycline (P=0.041 and 0.069, respectively) and the OcR patients experienced statistically significant relief of their subjective symptoms (P=0.0001) after the doxycycline regimen. Both the normal and OcR tear fluid contained the larger, 60-80 kDa highly- glycosylated polymorphonuclear leukocyte-type MMP-8 isoform in Western immunoblotting, but not the 45-55 kDa less glycosylated mesenchymal-type isoform. MMP-8 activation was in practice present only in the OcR samples, and was inhibited by oral doxycycline. CONCLUSIONS: MMP-8 concentration and activation degree in tear fluid are increased in OcR, probably reflecting increased inflammatory activity. Doxycycline effectively reduces these pathologically excessive levels and activation of MMP-8, and relieves patients' subjective symptoms.

Administration, Oral↗

Evolutionary analysis of S-RNase genes from Rosaceae species.

Eight new cDNA sequences for S-RNases were cloned and analysed from almond (Prunus dulcis) cultivars of European origin, and compared to published sequences from other Rosaceae species. Insertions/deletions of 10-20 amino acid residues were detected in the RC4 and C5 domains of S-RNases from almond and sweet cherry. The S-RNases of the Prunus species and those of the genera Malus and Pyrus formed two distinct groups on phylogenetic analysis. Nucleotide substitutions were analysed in the S-RNase genes of these species. The S-genes of almond and sweet cherry have a lower Ka/Ks value than those of apple, pear and wild apple do. The fact that there is no fixed difference between the S-RNase genes of almond and sweet cherry, or between apple and pear, suggests that nucleotide substitutions only introduce transient polymorphism into the two groups, and rarely became fixed and contribute to divergence. Through the comparative study of 17 S-RNase genes from the genus Prunus and 18 from the genera Malus and Pyrus, some fixed nucleotide differences between the two groups were identified. These differences do not appear to be the result of selection for adaptive mutations, since the number of replacement substitutions is not significantly greater than the number of synonymous substitutions. S-RNase genes of almond and sweet cherry, and of apple and pear, showed little heterogeneity in nucleotide substitution rates. However, heterogeneity was observed between the two groups of S-alleles, with the Prunus alleles exhibiting a lower rate of non-synonymous substitutions than alleles from Malus and Pyrus. The evolutionary relationships between these species are discussed.

Amino Acid Sequence↗

The ocular manifestations of atopic dermatitis and rosacea.

Atopic dermatitis and rosacea are chronic diseases that have both dermatologic and ocular manifestations. The occurrence of ocular disease is often proportionately higher than that of dermatologic disease. Even if the skin abnormalities appear well controlled, these patients require ophthalmic evaluation as well. Optimal management usually requires a team approach that includes internists, dermatologists, and ophthalmologists. Both disorders are characterized by acute exacerbations and require maintenance therapy for control. Exacerbations need aggressive treatment to limit ocular signs and symptoms and to reduce ocular inflammation that can lead to permanent visual loss. Topical corticosteroid use, although at times needed, should be minimized for both disorders. Future research will continue to emphasize the use of steroid-sparing and immune-modulating agents that have the potential to provide long-lasting anti-inflammatory control with a more favorable side-effect profile.

Adrenal Cortex Hormones↗

Rosacea: the battle goes on.

Rosacea presents an enigma to patients and physicians alike. Although new insights and a plethora of therapies provide hope, the underlying etiology remains unknown. This assures a certain amount of frustration as available treatments temporize rather than cure the disease. This article examines the current state of knowledge regarding this fascinating entity.

Anti-Infective Agents↗

Ocular rosacea.

Ocular rosacea was diagnosed in 49 patients. The most common signs and symptoms were foreign body sensation, burning, superficial punctate erosions, chalazia, and belpharitis. Less common but dangerous to the vision was corneal thinning, vascularization, and infiltrates. Three new associated symptoms were found. These were mapdot subepithelial opacities, recurrent erosions, and moderately severe foreign body sensation, pain or burning with minimal associated signs. Of the 49 patients, 37 were treated with 250 mg of oral tetracycline four times a day, which resulted in improvement in almost all patients from four to 17 days after initiation of therapy. Most of the patients have been able to taper, or taper and stop therapy without recurrence of their symptoms. Those patients with foreign body sensation, burning, and pain required the most prolonged therapy in order to taper or stop treatment with tetracycline.

Adolescent↗

Delusions of disfigurement in a woman with acne rosacea.

A 36-year-old woman with newly diagnosed acne rosacea is presented. Her skin changes were noticeable only under closest scrutiny, but she quit her job, became despondent about her acne, and developed suicidal ideation. The diagnosis and treatment of this patient allow a broader discussion of the somatically focused patient whose ideation reaches delusional intensity.

Adult↗

Demodicosis and rosacea: epidemiology and significance in daily dermatologic practice.

BACKGROUND: Demodicoses are thought to be rare, occurring mainly for patients with immunosuppression. OBJECTIVE: We sought to demonstrate the high frequency of demodicoses and the overlapping with papulopustular rosacea (PPR) . METHODS: We conducted a prospective epidemiologic study among 10 dermatologists. High Demodex density (Dd) was confirmed by standardized skin surface biopsy. RESULTS: In all, 4372 diagnoses, in which 115 were demodicoses, were collected among 3213 patients. Demodicosis was the 9th most frequent diagnosis (13th new). Each dermatologist observed an average of 2.4 demodicoses a week (1.2 new). The proportion of demodicoses varied greatly according to the dermatologist. The general status was good in 110 patients; only 3 had known immunodeficiency. The most frequent symptoms were follicular scales (71%) and telangiectasia (63%). The mean Dd was higher in pityriasis folliculorum (m = 61 D/cm 2 ) than in PPR (m = 36 D/cm 2 ; P = .04); 42 patients with PPR had a high Dd, 6 had a low Dd. CONCLUSION: Demodicoses are frequent and occur among patients who are immunocompetent. PPR with normal Dd are rare.

Adult↗

Acne and rosacea.

The diagnosis of acne and rosacea are reviewed in this article, and specific therapeutic strategies are discussed for these extremely common diseases.

Acne Vulgaris↗

Diagnosis and treatment of ocular rosacea.

Eighteen patients with ocular rosacea were treated with oral tetracycline which resulted in marked improvement in all patients. Approximately one half of the patients were able to taper and stop the medication without recurrence of symptoms. The remaining have tapered their medication but could not stop without recurrence of symptoms. The majority of the patients in the series had Staphylococcus aureus on their conjunctiva and lids before and after surgery.

Adult↗

[Pseudokeratoconus and ocular rosacea].

Photokeratoscopy analysis of the anterior curve of the cornea can detect keratoconus, particularly in the early stages of the disease. Nevertheless, all irregular astigmatisms are not related to keratoconus. We report here several cases of patients presenting high asymmetric astigmatism with features of keratoconus, although the clinical examination suggests corneal disease related to rosacea.

Adult↗

Cutaneous lymphoplasmacytoid lymphoma (immunocytoma) with Waldenström's macroglobulinemia mimicking rosacea.

A 50-year-old woman presented with a 2-year history of facial lesions that were resistant to rosacea therapy. Evaluation of histology, immunohistochemistry, gene rearrangement study, bone-marrow biopsy specimen, and systemic workup revealed the findings of lymphoplasmacytoid lymphoma (immunocytoma) in both the skin lesions and bone marrow, and IgM kappa paraprotein. Lesions cleared after chemotherapy.

Bone Marrow Cells↗

Action of isotretinoin in acne rosacea and gram-negative folliculitis.

Good to excellent clinical results have been obtained in the treatment of severe inflammatory acne (acne conglobata, acne fulminans, and acne conglobata with hidradenitis and dissecting cellulitis of the scalp) with orally administered isotretinoin (13-cis-retinoic acid). Similar promising results have been obtained in patients with severe rosacea and gram-negative folliculitis. Isotretinoin probably has multiple modes of action, including (1) inhibition of sebaceous gland activity, (2) inhibition of the growth of Propionibacterium acnes within the follicle, although the retinoid is not antibacterial, (3) inhibition of inflammation, and (4) alteration of the pattern of keratinization within the follicle, as demonstrated by light and ultrastructural studies.

Acne Vulgaris↗

Effect of nadolol on flushing reactions in rosacea.

The effect of nadolol versus placebo on both flushing provoked in a laboratory setting and spontaneous flushing was studied in 15 patients with erythematous telangiectatic rosacea. The intensity of the flushing reactions was assessed in the laboratory by the cutaneous perfusion index method with laser-Doppler velocimetry. No effect of nadolol on the flushing reactions provoked in the laboratory was detected.

Adult↗

Unilateral demodectic rosacea.

A unilateral rosacea-like chronic dermatitis of the right side of the face was shown to harbor innumerable Demodex folliculorum and D. brevis. Treatment with oral metronidazole suppressed the dermatitis but did not significantly reduce the Demodex population. Treatment with topical crotamiton eliminated the Demodex and was curative. These observations support the view that D. folliculorum and D. brevis may be pathogenic when they are present in extremely large numbers.

Adult↗

Treatment of rosacea-like demodicidosis with oral ivermectin and topical permethrin cream.

A 32-year-old man presented with a chronic rosacea-like dermatitis of the facial skin and the eyelids. The skin disorder had been present for 4 years and was unresponsive to multiple previous treatment attempts. Skin scrapings and a histologic examination of a biopsy specimen from the affected area revealed the presence of numerous Demodex mites. The patient was treated with oral ivermectin and subsequent topical permethrin resulting in complete and rapid clearing of the folliculitis. We believe that this case supports the view that Demodex mites may be pathogenic when they are present in large numbers. Oral treatment with 200 microg/kg ivermectin with subsequent weekly topical permethrin showed impressive treatment efficacy in a case refractory to conventional treatment.

Administration, Oral↗

An unusual case of a relationship between rosacea and dental foci.

Rosacea is a chronic disorder affecting the facial convexities, characterized by frequent flushing, persistent erythema, and telangiectases. During episodes of inflammation, additional features are swelling, papules, and pustules. The exact etiology of this dermatitis is unknown, and theories abound. Infectious foci, especially dental foci, seem to be rarely associated with the onset and progression of this disease. Dermatologic treatments are determined by the severity of the disease. But eradication of infectious foci, and in this case eradication of dental foci, may generate a significant improvement and may lead to a recovery.

Adult↗

Topical application of NADH for the treatment of rosacea and contact dermatitis.

Among many important physiological functions played by NADH (the reduced form of beta-nicotinamide adenine dinucleotide) its antioxidative properties are remarkable. Acting directly as an antioxidant, NADH can effectively protect the cell and its membrane from destruction by free radicals. NADH can be stabilized as a suspension in hydrophobic ointments prepared in a way that prevents contact with atmosphere containing oxygen and water. We present the first report of NADH as a treatment for some inflammatory dermatoses. It was found that topical application of 1% NADH diluted in Vaseline ointment can be very effective in the treatment of rosacea and contact dermatitis. Since no adverse effects were observed, therapy with NADH can be viewed as a potential alternative to other established treatments.

Adult↗

Case report. Rosacea-like Tinea incognito.

We report a case of dermatophytosis of the face due to Microsporum canis that was exacerbated and altered clinically by a long-term application of topical corticosteroids. We considered this case a rosacea-like tinea incognito of the beard area.

Adrenal Cortex Hormones↗