The cytokine and chemokine network in psoriasis

Creation and maintenance of psoriatic plaques require a multicellular conspiracy by which prepsoriatic skin becomes infiltrated by a variety of immunocytes triggering changes in the behavior of epidermal keratinocytes and endothelial cells. These complex cellular events require coordination in space and time to achieve the mature plaque. Key molecular coordinators dictating behavior and movement of cells within plaques include cytokines as well as chemokines. These mediators of inflammation play fundamentally important roles in the pathophysiology of psoriasis. The purpose of this chapter is to provide an updated review of cytokine and chemokine networks in psoriatic skin lesions.     

Keratinocyte cytokine and chemokine receptors

Chemokines are a superfamily of small, secreted proteins that regulate cell traffic in homeostatic and inflammatory conditions. Keratinocytes synthesize many chemokines, including members of the CC and CXC subfamilies, such as regulated on activation of normal T-cell expressed and secreted, gamma-interferon inducible protein-10, monokine induced by gamma-interferon, and thymus- and activation-regulated chemokine. They also express some chemokine receptors that mediate the inflammatory or immune response by attracting various kinds of leukocytes.     

Rosacea: an update

Rosacea is a common chronic cutaneous disorder of unknown etiology which occurs most commonly in middle-aged individuals. Cutaneous manifestations include transient or persistent facial erythema, telangiectasia, edema, papules and pustules that are usually confined to the central portion of the face. The National Rosacea Society's Expert Committee on the Classification and Staging of Rosacea identified four subtypes of rosacea: erythematotelangiectatic, papulopustular, phymatous and ocular. Recently, a standard grading system for assessing gradations of the severity of rosacea has been reported. Little is known about the cause of rosacea. Genetic, environmental, vascular, inflammatory factors and microorganisms such as Demodex folliculorum and Helicobacter pylori have been considered. Topical metronidazole and azelaic acid have been demonstrated to be effective treatments for rosacea. Severer or persistent cases may be treated with oral metronidazole, tetracyclines or isotretinoin.     

Rosacea and rhinophyma

Rosacea is a common and chronic inflammatory cutaneous disease with unknown etiology. The pathophysiology of rosacea is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been detected yet. Recent molecular studies propose that an altered innate immune response is involved in the pathogenesis of the rosacea disease. Signs of rosacea are indicated by the presence of characteristic facial or ocular inflammation involving both the vascular and tissue stroma. A wide range of drug options is available for the treatment of rosacea, including several topical ones (metronidazole, antibiotics, azelaic acid, benzoyl peroxide, sulfacetamide/sulfur, retinoids) and oral ones (mainly tetracyclines, metronidazole, macrolides, isotretinoin). This review highlights the recent clinical and pathophysiological developments concerning rosacea.     

Rosacea: II. Therapy

Despite an incomplete understanding of the pathogenesis of rosacea, therapeutic modalities continue to expand. The principal subtypes of rosacea include erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea. These phenotypic expressions are probably caused by divergent pathogenic factors and consequently respond to different therapeutic regimens. A subtype-directed approach to therapy is discussed in part II of this review. We provide an overview of the available topical, oral, laser, and light therapies in the context of these cutaneous subtypes, review the evidence that supports their use, and outline their therapeutic approach. Suggestions for future areas of study also are provided. Learning objective At the completion of this learning activity, participants should be familiar with the subtype-directed approach to therapy for rosacea including available topical, oral, laser, and light therapies.     

Rosacea: a clinicopathological approach

BACKGROUND: There are few reports of the histological changes in rosacea, and little attempt has been made to correlate such changes with clinical findings. In the present study, we describe in detail the histopathological features of rosacea in a large number of patients and simultaneously investigate the aetiopathogenesis of the disease based on the comparative assessment of epidemiological, clinical and histological findings. METHODS: The study included 73 patients with rosacea. A skin biopsy with a 4-mm punch was performed in each case. All biopsy specimens included subcutaneous tissue. In 10 randomly selected patients, facial biopsy specimens were obtained from both involved and uninvolved (non-lesional) skin. Demodex mite presence was estimated semi-quantitatively under light microscopy. Patients with self-reported gastro-intestinal symptoms were submitted to upper gastro-intestinal endoscopy, and a rapid urease test was performed. Serological antibodies, IgG and IgA, against Helicobacter pylori were also detected. RESULTS: The patients had a broad clinical spectrum of lesions. No specific histological features associated with either erythematous-telangiectatic or papulopustular clinical forms were noticed. Histological examination showed that there is no histological pattern unique to rosacea. Three different types of granulomas were observed: small palisaded ones around altered collagen and other granulomas of elastolytic and non-specific epithelioid type, all coexisting in 5 cases. The deep dermis and subcutis were frequently involved. Comparative study in 10 rosacea patients between lesional and non-lesional skin biopsies revealed almost the same histological changes to the latter biopsies, to a lesser degree though. CONCLUSION: Rosacea seems to be a reaction pattern to which a variety of pathogenetic routes may lead.     

The Role of Tetracyclines in Rosacea

There is a great deal of evidence to support the use of tetracycline and doxycycline in the treatment of papulopustular rosacea. Nevertheless, these agents have shared and unique adverse effects and relative contraindications. Recently, subantimicrobial-dose doxycycline was demonstrated to be an effective treatment for rosacea, due to its inherent anti-inflammatory properties. Furthermore, subantimicrobial-dose doxycycline has a more preferable tolerability profile and a lower occurrence of bacterial resistance than traditional-dose doxycycline. To further elucidate the role of tetracycline agents in rosacea, clinical trials that compare these agents with each other as well as with other effective rosacea treatments are called for. Adherence studies comparing oral tetracycline treatment with topical metronidazole treatment may also enhance clinical decision making.     

Rosacea and its management: an overview

BACKGROUND: Rosacea is a chronic inflammatory disorder that affects 10% of the population. The prevalence of rosacea is highest among fair-skinned individuals, particularly those of Celtic and northern European descent. Since a cure for rosacea does not yet exist, management and treatment regimens are designed to suppress the inflammatory lesions, erythema, and to a lesser extent, the telangiectasia involved with rosacea. OBJECTIVES: This review outlines the treatment options that are available to patients with rosacea. METHODS: Published literature involving the treatment or management of rosacea was examined and summarized. RESULTS: Patients who find that they blush and flush frequently, or have a family history of rosacea are advised to avoid the physiological and environmental stimuli that can cause increased facial redness. Topical agents such as metronidazole, azelaic acid cream or sulfur preparations are effective in managing rosacea. Patients who have progressed to erythematotelangiectatic and papulopustular rosacea may benefit from the use of an oral antibiotic, such as tetracycline, and in severe or recalcitrant cases, isotretinoin to bring the rosacea flare-up under control. Treatment with a topical agent, such as metronidazole, may help maintain remission. Patients with ocular involvement may benefit from a long-term course of an antibiotic and the use of metronidazole gel. A surgical alternative, laser therapy, is recommended for the treatment of telangiectasias and rhinophyma. Patients with distraught feelings due to their rosacea may consider cosmetic camouflage to cover the signs of rosacea. CONCLUSIONS: With the wide variety of oral and topical agents available for the effective management of rosacea, patients no longer need to feel self-conscious because of their disorder.     

Rosacea: current thoughts on origin

Rosacea is a clinical pattern beginning and evolving in the genetically susceptible individual in response to a host of exposures. It produces a variety of clinical presentations, which vary over time and with age. Recently, many specific mediators of rosacea development have been described. A primary genetic cause for rosacea is suggested as single genes often control such mediators: enzymes, neuroendocrine transmitters, and cytokines are found in pathways to rosacea signs and symptoms. Currently, neither a specific cause nor a laboratory indicator of rosacea has been suggested. However, broadening interest in rosacea portends future increase in knowledge.