Topische Therapie der Rosazea

Metronidazole and azelaic acid are the only topical medications approved for rosacea. All other topical treatments for rosacea and its special forms are used off-label. Topical steroids are not indicated in rosacea, because of their side effects (induction of steroid rosacea, high risk of facial skin atrophy, and high risk of rebound after cessation of therapy). Topical as well as systemic steroids are allowed only as initial and short term therapy for acute forms of rosacea (e.g. rosacea fulminans). Papular and pustular rosacea is the major indication for topical therapy. Sebaceous gland and connective tissue hyperplasia in glandular-hypertrophic rosacea as well as erythema in erythematous rosacea do not respond well to topical measures. A new active substance, the alpha-2-adrenoreceptor agonist brimonidine, will be approved soon for the topical treatment of erythema in rosacea. All severe forms of rosacea should initially be treated with a combination of topical and systemic agents. After improvement of the clinical symptoms, topical treatment alone is usually adequate to maintain the control.     

Rosazea

Systemic isotretinoin has been known for decades as an effective and safe therapeutic option in the treatment of severe and refractory forms of rosacea. It can also be used in special treatment-resistant forms of rosacea, e.g. granulomatous rosacea, as efficacious second-line therapy. Previously, the effect of isotretinoin in rosacea has been mainly studied in small cohorts or anecdotal reports. Recently, a big randomized double-blind dose-response and comparative study revealed that an optimized dosage of 0,3 mg/kg was superior to other dosages and non-inferior to doxycycline as gold standard of systemic rosacea treatment and proved effective and safe in papulopustular and phymatous subtypes. However, the substance is still not licensed for this indication The efficacy of isotretinoin in rosacea is probably mainly related to anti-inflammatory mechanisms as well as anti-oxidative, anti-angiogenic and antifibrotic properties. The classical antiseborrheic effect of isotretinoin might play a role in special subtypes like the phymatous type or rosacea fulminans.     

Klinik und Klassifikation der Rosazea

Rosacea is a frequent chronic dermatological disorder mainly affecting the face. Since it affects the appearance, it can be very distressing for the patient leading to psychosocial disturbances. Rosacea occurs in adults, peaking between 40 and 50 years of age. The course of rosacea is quite variable and the disease may stop at any stage. Generally, three main stages are differentiated: erythemato-teleangiectatic rosacea (rosacea stage I), papulopustular rosacea (rosacea stage II), hyperglandular-hypertrophic rosacea (rosacea stage III). Besides these main manifestations numerous special forms exist, which often lead to difficulties in the differential diagnoses and require specific therapeutic strategies. These include rosacea conglobata, rosacea fulminans, granulomatous rosacea, persisting edema, (Morbihan disease), gram negative rosacea, ocular rosacea, and steroid rosacea. Recently increasing numbers of patients have been observed, whose rosacea was were induced by inhibitors of epidermal growth factors (cetuximab, geftinib) used as chemotherapy in patients with different malignancies. These side effects have been described as acneiform eruptions but at least some of the described patients have a rosacea-like appearance; therefore, this form can be classified as a subset of drug induced rosacea.     

Roaccutan in acne and rosacea

Isotretinoin (Accutane) is a lately developed synthetic oral retinoid for treatment of severe forms of cystic acne resistant to therapy. Its pharmacological effect principally consists in decreased size of the sebaceous glands, reduced sebum production, as well as alteration of the bacterial micropopulation. At a dosage of 0.5 mg up to 1.0 mg/kg body weight daily, isotretinoin led to significant reduction of the inflammatory skin eruptions and long-lasting remission after discontinuation of the drug. With regard to 18 patients suffering from rosacea, the application of Accutane brought about satisfactory results, as well. Mucocutaneous side-effects were almost compulsory, but did never lead to discontinuation of the treatment. Because of its teratogenity, isotretinoin must not be applied in case of gravidity. Accutane offers new modes of therapy with respect to patients suffering from nodulocystic acne or severe rosacea which did not respond to common forms of treatment.     

Use of permethrin in the treatment of rosacea fulminans during pregnancy: One case report

Rosacea fulminans (RF) is a rare dermatological condition which occurs exclusively in women and it is characterized by a sudden onset of painful papules, pustules, cysts, and nodules on the face. A 28‐year‐old woman was referred to our clinic due to a painful facial eruption within the 13th week of her second pregnancy. After physical examination, the diagnosis of RF during pregnancy was established. Several treatments were used: mupirocin ointment, topical zinc oxide, topical erythromycin, oral erythromycin, metronidazole gel, oral metronidazole, oral amoxiciline, and oral prednisone. Finally, the patient was started on 5% permethrin cream with complete clearing of the lesions. Nowadays, a wide range of treatments for rosacea is available: topical metronidazole, oral metronidazole, topical ivermectin, oral tetracyclines, oral isotretinoin, systemic steroids, photodynamic therapy, or pulsed dye laser. However, in pregnant patients, the treatment alternatives are limited. We consider that 5% permethrin cream could be an effective, cheap, and safe treatment not only in regular patients with rosacea but also in pregnant women, representing an important alternative in the context of pregnancy when therapeutic options are limited. To our knowledge, this is the first case of rosacea treated with 5% permethrin cream in monotherapy during pregnancy.     

Treatment of aseptic facial granuloma as a manifestation of pediatric rosacea with oral macrolides

Aseptic facial granuloma is a rare pediatric disease, presenting with asymptomatic facial nodules on the cheeks or the eyelids and may represent a form of granulomatous rosacea in children. In this retrospective case series, 12 children with aseptic facial granuloma were treated with oral macrolides (erythromycin or roxithromycin) resulting in a healing of the lesions within a mean treatment time of 5.25 months with no recurrences. The treatment was mainly well tolerated. Oral macrolides may be effective in the treatment of patients with aseptic facial granuloma.     

A rare case of lupoid leishmaniasis defying diagnosis for a decade

Cutaneous leishmaniasis (CL) is a common disease affecting millions in endemic areas worldwide. We present a case of lupoid leishmaniasis, a rare variant of CL, which clinically mimicked sarcoidosis and/or granulomatous rosacea for 10 years until ultimate diagnosis. An 82-year-old U.S. citizen with an extensive travel history presented with a 10-year history of facial plaques on the cheeks and was previously diagnosed and treated as sarcoidosis. Multiple biopsies (previously and at presentation) revealed tuberculoid granulomas with negative special stains for microorganisms and negative sterile tissue cultures for acid-fast bacilli, bacteria, and fungal organisms. A diagnosis of granulomatous rosacea was rendered and multiple medical therapies were attempted, none with sustained improvement. Repeat biopsy of a new lesion revealed intracellular organisms consistent with leishmaniasis, which was confirmed by polymerase chain reaction (PCR). Lupoid leishmaniasis is a rare presentation of CL including facial plaques that can mimic granulomatous diseases affecting the face including sarcoidosis and granulomatous rosacea. CL can sometimes be challenging to diagnose through standard histopathologic examination; immunohistochemistry for CD1a can be used to augment tissue-based examination and PCR should be sent early in cases with sufficient concern.     

A case of granulomatous rosacea successfully treated with pimecrolimus cream

A 43-year-old male attended with lesions on his face that had been present for 3 months. On dermatological examination, multiple papules and pustules were seen on the forehead, nose, bilateral cheeks and lower eyelids. The patient used systemic clindamycin and doxycycline and topical benzoyl peroxide therapies, but the lesions did not regress. Routine laboratory tests were normal. Histopathological examination of the lesions confirmed the diagnosis of granulomatous rosacea. Pimecrolimus cream 1% was applied to the lesions. The regression of lesions began in the first month and complete improvement was observed at the end of the fourth month of therapy. Rosacea is a chronic, inflammatory skin disorder characterized by remissions and relapses. Although it is known that the disease is a treatable disorder, it may be resistant to standard therapies and there is a need for new therapy alternatives in some patients. We present a case of granulomatous rosacea successfully treated with pimecrolimus cream and believe that pimecrolimus may be a good alternative for the treatment of granulomatous rosacea.     

Rosacea. Clinical features, pathogenesis and therapy

Rosacea is a common facial dermatosis, which may have detrimental effects on the patient's psychological and social interactions. It is a disease of the middle aged, skin types I and II are more often affected than darker skin types. Clinically, pre-rosacea, and rosacea grade I-III may be distinguished. Pre-rosacea is characterized by flushing and blushing, grade I to III by erythemato-teleangiectasies, papulopustules, and inflammatory nodules. Especially severe subtypes include rosacea conglobata and rosacea fulminans. Hyperglandular subtypes lead to different forms of phyma, of which Rhinophyma is the most frequent. Pathogenetically destruction of the dermal vessels and connective tissue seems to be decisive for the development of a chronic inflammation, which leads to the phenotype of the various forms of rosacea. Mild forms can be treated exclusively by topical medication. Antibiotics (erythromycin, clindamycin, tetracyclin), metronidazol, azelaic acid, and the retinoid adapalene have been shown to be effective in well controlled randomized studies. The best evaluated topical medication is metronidazol. In severe forms systemic therapy must be applied. Systemic antibiotics are effective and especially isotretinoin has shown a very good response even in low dose regimens. Rhinophyma must be treated surgically.     

Rosacea Fulminans in Pregnancy

Rosacea fulminans is a rare disease of unknown cause which occurs exclusively in women years after adolescence. Although the etiology is unknown, immunologic, hormonal, and vascular factors have been suggested. When rosacea fulminans occurs during pregnancy and in women taking oral contraceptive pills, hormonal factors may be a trigger. Rosacea fulminans is localized specifically to the face, with the chin, cheeks, and forehead bearing the brunt of the attack. A dull red, cyanotic erythema of all involved facial areas, extending beyond the inflammatory nodules, is typical. We present the case of a 31-year-old pregnant woman who had rosacea fulminans during the first trimester of her second pregnancy. She had multiple erythematous papules, pustules, nodules, and purulent discharging cysts on the face. Conventional therapeutic approaches with systemic corticosteroids were associated with clear improvement within 2 months, and subsequently only 0.75% metronidazole topical cream was used during the second trimester.     

Lupus miliaris disseminatus faciei: A resistant case with response to cyclosporine

Lupus miliaris disseminatus faciei (LMDF) is a chronic, inflammatory dermatosis of unknown etiology, characterized by multiple, monomorphic, symmetrical, reddish‐brown papules over forehead, cheeks, and eyelids. Histopathology shows perifollicular epitheloid cell granuloma. Though numerous therapies, ranging from cyclines, macrolides, dapsone tranilast, isotretinoin, steroids, and tacrolimus have been tried, the results are inconsistent, except with systemic steroids. One approach is to administer therapies based on the histological findings and the corresponding mode of action of drugs, thus antibiotics and dapsone are effective in the early inflammatory stage while clofazamine can be used in the granulomatous stage of the disease. A case of LMDF, recalcitrant to multiple systemic therapies, who responded dramatically to cyclosporine (50 mg twice daily), which probably was due to the specific effect on T_H1 cell response which mediates cell mediated immunity responsible for granulomatous changes on histology has been reported. This case highlights that LMDF is an independent granulomatous entity (not a variant of rosacea or tuberculosis).     

Therapeutic hotline: Successful treatment of Morbihan's disease with oral prednisolone and doxycycline

Persistent facial swelling can occur as a rare complication of rosacea. This finding is referred to as lymphedematous rosacea or Morbihan's disease. We report a case of a 45-year-old male with no previous history of rosacea who developed bilateral periorbital swelling associated with facial erythema and edema that responded to a combination of oral corticosteroids and doxycycline. Biopsy revealed changes of granulomatous 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.     

Pathogenese,Klinik und aktuelle Therapie der Rosazea

Rosacea is a common chronic inflammatory disease, especially in patients with fair skin and positive family history. Typical locations are forehead, nose, cheeks and chin; the periorbital region is usually not involved. Clinical features can be very heterogeneous. Besides different subtypes (erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea), which often overlap, various special forms of rosacea exist. Up to 60?% of patients with cutaneous rosacea suffer from ocular rosacea. In Germany, brimonidine, metronidazol, azelaic acid, and ivermectin are approved for topical therapy of rosacea; for systemic therapy, doxycycline at a subantimicrobial dose (40 mg/day) is the only approved substance. In case of resistance to this therapy, contraindications or side effects, various alternative therapies are available, however off-label.     

Pediatric rosacea

Rosacea is a condition most commonly associated with adults; however, various forms exist in the pediatric population and need to be considered when a child presents with a facial rash. Acne rosacea, steroid rosacea, granulomatous periorificial dermatitis, and other variants of rosacea are presented here and are distinguished from their numerous mimickers. Various topical and systemic therapeutic options exist for the treatment of rosacea with several adjustments and considerations that must be taken into account when treating a child.     

Clinical presentations and classification of rosacea

Rosacea is a chronic skin disease affecting up to 10% of the population in some European countries. Rosacea manifests as various combinations of characteristic signs and symptoms in a centrofacial distribution. At present, there is no consensus about the definition or classification of the clinical patterns of rosacea. Initially, four stages were differentiated (pre-rosacea then stages I through III), with several variants (e.g., persistent erythema and edema, rosacea conglobata, and rosacea fulminans). The National Rosacea Society (NRS) in the USA has classified rosacea into four subtypes (erythematotelangiectatic, papulopustular, phymatous, and ocular) and one variant (lupoid or granulomatous rosacea). This classification scheme does not mention progression from one type to another and makes no reference to pathophysiological considerations. It uses major and minor diagnostic criteria based on the physical findings and symptoms. The NRS has also developed criteria for grading disease severity. The classification of rosacea into stages or subtypes, without considering the possibility of progression from one to another, will probably remain controversial until additional knowledge on the pathophysiology of rosacea is obtained.     

Pyoderma faciale. A review and report of 20 additional cases: is it rosacea?

BACKGROUND AND DESIGN--Pyoderma faciale was originally described by O'Leary and Kierland in 1940. It is characterized by the sudden onset of monstrous coalescent nodules and confluent draining sinuses confined to the face of young women in their early 20s. This report summarizes our results in 20 cases. The women were 15 to 46 years old (mean, 25 years). RESULTS--All women were flushers and blushers. Histopathologic examination revealed a dense perivascular and periadnexial infiltrate, including granulocytes, eosinophils with epithelioid granulomas, and septal and lobular panniculitis. No consistent laboratory abnormalities were found. After much therapeutic experimentation, we developed an effective treatment plan, based on a combination of oral isotretinoin and corticosteroids. CONCLUSION--We regard it as an extreme form of rosacea and suggest it be renamed rosacea fulminans in analogy with its counterpart, acne fulminans.     

Childhood granulomatous periorificial dermatitis: lupus miliaris disseminatus faciei in children?

BACKGROUND: Childhood granulomatous periorificial dermatitis (CGPD) is a granulomatous disease characterized by monomorphous, small papular eruptions around the mouse, nose and eyes, and is thought to be closely related to perioral dermatitis. This condition has always been believed to occur more commonly in dark-skinned patients; however, recent observations have revealed CGPD to occur also in white patients. OBSERVATION: We report an 11-year-old Japanese boy with the characteristic features of CGPD. Although sarcoidosis and acne/granulomatous rosacea could be differentiated from CGPD, we could find no essential differences between CGPD and lupus miliaris disseminatus faciei (LMDF). The cases of LMDF in children, which were recorded in the Japanese literature, had highly similar clinicopathological features to those of CGPD. This case responded dramatically to topical tacrolimus in combination with the oral administration of minocycline. CONCLUSIONS: The entity 'facial idiopathic granulomas with regressive evolution' is considered to include LMDF (a common adult form), CGPD (a rare childhood form) and perioral dermatitis (a peculiar form exacerbated by topical corticosteroids). Topical tacrolimus may be recommended as one of the therapies for LMDF as well as CGPD.     

Rosacea fulminans triggered by high-dose vitamins B6 and B12

Rosacea fulminans is a rare variant of rosacea conglobata that occurs almost exclusively in women well past adolescence. The aetiology is unknown, although immunological, hormonal, and vascular factors have been suggested. We report the case of a 17-year-old girl with rosacea fulminans that was temporally associated with daily ingestion of high-dose vitamin B supplements. The onset was sudden and cosmetically disabling. The eruption improved when the vitamin supplement was discontinued and a therapeutic regimen including isotretinoin and methylprednisolone was introduced. It seems appropriate to consider the possibility of such a vitamin B-triggered condition in cases of subjects presenting new or exacerbating facial eruptions.     

New antibiotic therapies for acne and rosacea

Acne and rosacea compromise a substantial portion of the dermatology clinical practice. Over the past century, many treatment modalities have been introduced with antibiotics playing a major role. Today, both oral and topical antibiotics are used in the management of acne and rosacea, with several novel formulations and/or combination regimens recently introduced. The latest studies suggest anti-inflammatory actions to be the most likely mechanism of antibiotics in acne and rosacea, shifting the focus to subantimicrobial-dose oral antibiotics and/or topical antibiotic regimens as the preferred first-line agents. Here we will discuss the most recent oral and topical antibiotic therapies available for treatment of acne and rosacea, with special focus on efficacy data, indication, dosing, and mechanism of action.