Morbus Morbihan als Sonderform der Rosazea

Morbihan disease is classified as a special form of rosacea, which presents with persistent facial erythema and solid edema because of marked involvement of the lymphatic vessels. The cheeks, nose and forehead are particularly affected. Currently, the treatment options of this cosmetically very disturbing disease are limited. However, every attempt should be made to provide treatment because of the great emotional suffering of the patients. We review some new currently available therapeutic options for Morbihan disease. In our patient, we were able to achieve a significant improvement with systemic isotretinoin 30 mg/day over a period of 12 months.     

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.     

Persistent lymphoedema in Morbihan disease: formation of perilymphatic epithelioid cell granulomas as a possible pathogenesis

Morbihan disease is a rare complication of rosacea, characterized by persistent lymphoedema on the upper half of the face, occurring during the chronic clinical course of rosacea. This refractory condition has been also designated as 'rosacea lymphoedema' and 'solid persistent facial oedema of rosacea'. We report a patient with Morbihan disease showing persistent lymphoedema on the upper half of the face accompanied by unique histological findings of striking dermal dilated lymphatics and damage of the lymphatics at the site of the adjacent epithelioid cell granulomas, with histiocytes bulging into the lymphatic lumen. The marked epithelioid cell granulomas forming around dermal lymphatic vessels with subsequent lymphatic damage and luminal obstruction by histiocytic infiltration may account for the development of lymphoedema in this patient.     

Four cases of Morbihan disease successfully treated with doxycycline

Morbihan disease (MD) is rosacea‐like disease characterized by persistent lymphedema on the upper half of the face. Currently, there is no established standard treatment for MD. Recently, MD has been reported to be associated with the infiltration of mast cells. The aim of this study was to investigate the association of treatment response and mast cell infiltration in MD. We report four cases of MD that were successfully treated with long‐term oral doxycycline therapy.     

Etiopathogenesis, classification, and current trends in treatment of rosacea

Rosacea is a common chronic dermatosis characterized by varying degrees of flushing, erythema, telangiectasia, edema, papules, pustules, ocular lesions, and phymas. Etiology and pathogenesis of rosacea are still unknown. Many possible causes have been described as inducing the disease or contributing to its manifestation, such as genetic predisposition, abnormal vascular reactivity, changes in vascular mediating mechanisms, Helicobacter pylori infection, Demodex folliculorum infestation, seborrhea, sunlight, hypertension, and psychogenic factors. However, none of these factors has been proved. Rosacea shows a wide spectrum of clinical presentations, which vary over time and with age. Successful management of rosacea requires careful patient evaluation and individualized therapy with appropriate variations and modifications, as the severity of the disorder fluctuates. In mild cases of rosacea, patients are instructed to avoid sun, to apply sun-protective creams, and to avoid facial irritants and other triggers that provoke symptoms. At later stage, drug therapy is often necessary. The disease commonly requires long-term treatment with topical or oral medicaments. Surgical correction may be required for rhinophyma and telangiectasia. We reviewed the current literature on the aspects of the pathogenesis, diagnostic criteria, and treatment options for rosacea.     

Case Series of Morbihan Disease (Extreme Eyelid Oedema Associated with Rosacea): Diagnostic and Therapeutic Approaches

Morbihan disease (MD) is a rare form of rosacea that presents with chronic erythema and solid oedema on the upper half of the face. A diagnosis of MD can be made only after eliminating diseases that are similar in terms of clinical and histopathological presentation. The cause of MD remains unclear and no standardised treatment is yet available. MD often tends to be recalcitrant to therapies commonly used to treat rosacea, including systemic corticosteroids, antibiotics, isotretinoin, and topical regimens. Thus, surgical interventions have been attempted but most cases have exhibited unsatisfactory responses. We treated six patients with extreme eyelid lymphoedema without any other cutaneous manifestation. Surgical eyelid reduction was performed in all patients, because ptosis and narrowing of the visual field were the major complaints. Histopathological tests revealed various extents of perivascular and perifollicular inflammation, and dermal oedema. After surgery, patients with severe inflammatory cell infiltration (including mast cells) exhibited a tendency toward recurrence. Other patients with severe dermal oedema exhibited better responses to surgical reduction, and thus no recurrence. We propose that MD should be included in the differential diagnosis of persistent, chronic eyelid oedema even if eyelid oedema is the only manifestation; the histological features may aid in the selection of appropriate therapeutic strategies. We suggest that eyelid reduction surgery can be a useful treatment option for MD patients when there is no massive mast cell infiltration.     

Combined effects of silymarin and methylsulfonylmethane in the management of rosacea: clinical and instrumental evaluation

Objective   This study aims to evaluate a topical treatment based on silymarin/methylsulfonilmethane (S-MSM) to improve erythematous-telangiectactic rosacea.
Methods    Forty-six patients affected by stage I–III rosacea entered this double-blind, placebo-controlled study. Subjects were treated for 1 month. Clinical and instrumental evaluations were done at baseline, after 10 and 20 days, and at the end of the study. Itching, stinging, erythema, and papules were investigated clinically as well as hydration and erythema instrumentally with capacitance and color measurements.
Results    A statistically significant improvement was observed in many clinical and instrumental parameters investigated ( P <  0.001). In particular, improvement of skin redness, papules, itching, hydration, and skin color occurred.
Conclusions    The combination of silymarin and S-MSM can be useful in managing symptoms and condition of rosacea skin, especially in the rosacea subtype 1 erythemato-telangiectatic phase. The action can be considered multicentric and multiphase because of the direct modulating action on cytokines and angiokines normally involved and up-regulated in the case of such skin condition.     

Neurovascular and neuroimmune aspects in the pathophysiology of rosacea

Rosacea is a common skin disease with a high impact on quality of life. Characterized by erythema, edema, burning pain, immune infiltration, and facial skin fibrosis, rosacea has all the characteristics of neurogenic inflammation, a condition induced by sensory nerves via antidromically released neuromediators. To investigate the hypothesis of a central role of neural interactions in the pathophysiology, we analyzed molecular and morphological characteristics in the different subtypes of rosacea by immunohistochemistry, double immunofluorescence, morphometry, real-time PCR, and gene array analysis, and compared the findings with those for lupus erythematosus or healthy skin. Our results showed significantly dilated blood and lymphatic vessels. Signs of angiogenesis were only evident in phymatous rosacea. The number of mast cells and fibroblasts was increased in rosacea, already in subtypes in which fibrosis is not clinically apparent, indicating early activation. Sensory nerves were closely associated with blood vessels and mast cells, and were increased in erythematous rosacea. Gene array studies and qRT-PCR confirmed upregulation of genes involved in vasoregulation and neurogenic inflammation. Thus, dysregulation of mediators and receptors implicated in neurovascular and neuroimmune communication may be crucial at early stages of rosacea. Drugs that function on neurovascular and/or neuroimmune communication may be beneficial for the treatment of rosacea.     

Treatment of early-stage erythematotelangiectatic rosacea with a Q-switched 595-nm Nd:YAG laser

Erythematotelangiectatic rosacea presents as persistent erythema and telangiectasia with frequent flushing and blushing on the facial and extrafacial skin. Additionally, papulopustular rosacea shows acneiform papules, pustules, and nodules with persistent plaque-form edema. Despite garnering only grade-C or -D level recommendations, a 585-nm or 595-nm flashlamp-pumped pulsed-dye laser can be considered as an effective therapeutic modality for the treatment of rosacea in patients who are refractory to topical and/or systemic treatments. In this report, treatment with a Q-switched 595-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser with low non-purpuragenic fluence proved to be safe and effective in treating early-stage erythematotelangiectatic rosacea in two female Korean patients. Laser treatment for rosacea was delivered with the settings of pulse energy of 0.4–0.5 J/cm², pulse duration of 5–10 ns, 5-mm spot size, 5 Hz, and 500 shots. Additionally, we found that remarkable therapeutic effects were achieved for both rosacea and melasma by combining Q-switched quick pulse-to-pulse 1,064-nm Nd:YAG and Q-switched 595-nm Nd:YAG laser treatments, which required only the changing of handpieces equipped with solid dye. In conclusion, we suggest that treatment with a Q-switched 595-nm Nd:YAG laser with low fluence may provide an additional therapeutic option for treating early-stage erythematotelangiectatic rosacea.     

Granulomatous rosacea: unusual presentation as solitary plaque

A 45-year-old male presented with a 6 month history of an enlarging smooth, erythematous plaque over the central part of his face. Mild erythema of both eyes was present. Sarcoidosis, Hansen disease, lupus vulgaris, cutaneous leishmaniasis, pseudolymphoma, foreign body granuloma, granuloma faciale, discoid lupus erythematosus, and granulomatous rosacea were considered in the differential diagnosis. CBC, urinalysis, renal function tests, liver function tests, serum electrolytes, and blood sugar were all normal. Chest X-ray and ECG revealed no abnormality. Serology for syphilis and HIV, and mantoux test were negative. Slit-skin smear, tissue smear and culture for AFB and fungi were negative. Skin biopsy revealed multiple non-caseating epitheloid granulomas around the pilosebaceous unit suggestive of granulomatous rosacea. Granulomatous rosacea, a rare entity comprising only about 10 percent of cases of rosacea can mimic many granulomatous conditions both clinically and histologically making the diagnosis an enigma. It usually presents as yellowish brown-red discrete papules on the face; non-caseating epithelioid granulomas are seen on histology examination. We herein report the case because it presented in atypical fashion, as a solitary indurated plaque on the nose, likely representing Morbihan's disease or solid persistent facial edema of rosacea (rosacea lymphedema).     

Aktuelles Verständnis der Pathophysiologie der Rosazea

Rosacea is a chronic inflammatory skin disease mainly affecting the face. Four major clinical subtypes of rosacea can be identified: erythemato-telangiectatic, papulopustular, phymatous and ocular rosacea. Still, it is currently unclear whether these subtypes develop consecutively or if any subtypes may occur individually as part of a syndrome. Rosacea is characterized by facial flushing, erythema, chronic inflammation, edema and fibrosis. Several trigger factors can worsen the disease or cause recurring episodes of inflammation. Although some aspects in the pathophysiology of rosacea have been characterized in more detail during the past years, the precise interplay of the various dysregulated systems is still poorly understood. In early disease manifestations and milder stages, dysfunction of neurovascular regulation and the innate immune system seem to be driving forces in rosacea pathophysiology. A disturbed chemokine and cytokine network further contributes to disease progression. This current review highlights some of the recent findings in rosacea pathophysiology and points out novel targets for therapeutic intervention.     

The management of rosacea

Rosacea is a multiphasic disease which is associated with flushing, erythrosis, papulopustular rosacea and phymas; each phase is likely to have its own treatment. Flushing is better prevented rather than treated, and its etiology investigated. Beta-blockers, atenolol in particular, are worthy of prophylactic trials examining their efficacy in treating the flushing associated with rosacea. Currently, clonidine is the only drug available for the treatment of flushing. Treatment for erythrosis includes topical and systemic therapies. Metronidazole 1% cream and azelaic acid 20% cream have been reported to reduce the severity score of erythema. The systemic treatment of erythrosis is based on the association of Helicobacter pylori with rosacea. However, this role is still being debated. Eradication of H. pylori can be achieved using a triple therapy regimen lasting 1 to 2 weeks [omeprazole and a combination of two antibacterials (a choice from clarithromycin, metronidazole or amoxicillin)]. Both the flashlamp-pumped long-pulse dye laser and the potassium-titanyl-phosphate laser may be used in the treatment of facial telangiectases. Both systemic and topical remedies may be used to treat the papulopustules of rosacea. Systemic treatment includes metronidazole, doxycycline, minocycline, clarithromycin and isotretinoin, while topical treatment is based on metronidazole cream and gel. The presence of Demodex folliculorum is important in the inflammatory reaction, whether it is pathogenetic or not. Crotamiton 10% cream or permethrin 5% cream may be useful medications for papulopustular rosacea, although they are rarely successful in eradicating D. folliculorum. Oral or topical ivermectin may also be useful in such cases. Ocular involvement is common in patients with cutaneous rosacea and can be treated with orally administered or topical antibacterials. Once rhinophyma starts to be evident, the only way to correct it is by aggressive dermatosurgical procedures. Decortication and various types of lasers can also be used. Associated conditions, such as seborrheic dermatitis and possible contact sensitizations, deserve attention.     

Comorbidity of rosacea and depression: an analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey--Outpatient Department data collected by the U.S. National Center for Health Statistics from 1995 to 2002

BACKGROUND: Psychogenic factors have been considered to be important in the exacerbation and possibly the onset of rosacea. However, there are very few studies that have reported conclusive findings. OBJECTIVES: To examine the association between rosacea and major depressive disease, a common and usually treatable psychiatric disorder. METHODS: Data from 1995 to 2002, collected by the National Ambulatory Medical Care Survey and the outpatient component of the National Hospital Ambulatory Care Survey, which are both nationally representative surveys of healthcare visits in the U.S.A., were studied. The basic sampling unit in both surveys is the patient visit or encounter. A "Rosacea" variable was created by grouping all rosacea (ICD-9-CM code 695.3) visits and a "Depression" variable was created by grouping the patient visits related to major depressive disorder (ICD-9-CM codes 296.2, 296.3 and 311). As alcohol abuse has been implicated in rosacea, and alcohol can confound symptoms of depression, an "Alcohol" variable was created by grouping all ICD-9-CM codes related to alcohol dependence and abuse (codes 303, 303.0, 303.9 and 305.0). All analyses were conducted using the Complex Samples module of SPSS version 13, to account for the multistage probability sampling design used to collect the data. RESULTS: The weighted data were representative of over 608 million dermatology visits between 1995 and 2002. Logistic regression analysis using "Rosacea" as the dependent variable and age, sex, "Alcohol" and "Depression" as independent variables revealed that the odds ratio for depressive disease in the rosacea group was 4.81 (95% confidence interval 1.39-16.62). The association between "Alcohol" and "Rosacea" was not significant. CONCLUSIONS: The comorbidity between major depressive disease and rosacea may have important clinical implications. Alcohol abuse does not appear to play a significant role in this association.     

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.     

Childhood ocular rosacea: Considerations for diagnosis and treatment

Rosacea in children is not as well described as it is in adults. Ocular signs may be a dominant feature and some children with what has previously been called periorificial dermatitis may in fact have rosacea. We report three cases of paediatric ocular rosacea responding to prolonged treatment with oral erythromycin. Our cases demonstrate the close association of periorificial dermatitis with childhood rosacea, and highlight the importance of eye signs in its diagnostic criteria.     

Treatment of rosacea with doxycycline monohydrate

Rosacea is one of the most commonly occurring inflammatory dermatoses treated by dermatologists today. Estimates suggest that at least 13 million Americans have recognized rosacea, and the clinical experience of most practitioners would add considerably more to that number. Rosacea is an inflammatory condition of the skin, classically presenting with a history of flushing and/or blushing along with the clinical findings of erythema, edema, telangiectasia, papules, pustules, and nodules of the face. Severity and distribution vary considerably. A patient may have only a few scattered papules and pustules of the central third of the face or there may be numerous inflammatory, painful, tender, large nodules. In some cases, only the face may be affected. In other cases, there may be lesions of the scalp, neck, and/or torso. Although the exact etiology is unknown, rosacea is thought by most experts to be an inflammatory process incited by vascular instability with subsequent leakage of fluid and inflammatory mediators into the dermis.     

Rosacea – global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group

Background The absence of specific histological or serological markers, the gaps in understanding the aetiology and pathophysiology of rosacea, and the broad diversity in its clinical manifestations has made it difficult to reach international consensus on therapy guidelines. Objectives The main objective was to highlight the global diversity in current thinking about rosacea pathophysiology, classification and medical features, under particular consideration of the relevance of the findings to optimization of therapy. Methods The article presents findings, proposals and conclusions reached by the ROSacea International Expert group (ROSIE), comprising European and US rosacea experts. Results New findings on pathogenesis provide a rationale for the development of novel therapies. Thus, recent findings suggest a central role of the antimicrobial peptide cathelicidin and its activator kallikrein‐5 by eliciting an exacerbated response of the innate immune system. Cathelicidin/kallikrein‐5 also provide a rationale for the effect of tetracyclines and azelaic acid against rosacea. Clinically, the ROSIE group emphasized the need for a comprehensive therapy strategy – the triad of rosacea care – that integrates patient education including psychological and social aspects, skin care with dermo‐cosmetics as well as drug‐ and physical therapies. Classification of rosacea into stages or subgroups, with or without progression, remained controversial. However, the ROSIE group proposed that therapy decision making should be in accordance with a treatment algorithm based on the signs and symptoms of rosacea rather than on a prior classification. Conclusion The ROSIE group reviewed rosacea pathophysiology and medical features and the impact on patients and treatment options. The group suggested a rational, evidence‐based approach to treatment for the various symptoms of the condition. In daily practice this approach might be more easily handled than prior subtype classification, in particular since patients often may show clinical features of more than one subtype at the same time.     

Rosazea 2009

Rosacea is one of the most common dermatoses of adults. In recent years many studies have contributed to a better understanding of the pathophysiology of rosacea. They suggest that an altered innate immune response is involved in the vascular and inflammatory manifestations seen in rosacea. A good understanding of the disease and its special features is necessary for the differential diagnosis of the many clinical subtypes and for a stage- and phase-specific treatment approach. Topical treatments that are widely accepted are metronidazole and azelaic acid; agents under investigation that show promise include permethrin, calcineurin inhibitors and sulfur compounds. For systemic therapy antibiotics (tetracyclines, macrolides) and recently doxycycline in anti-inflammatory rather than anti-microbial dosages are used, as well as isotretinoin in severe cases. Findings such as rhinophyma and telangiectases can be treated using different laser systems or dermabrasion. This article gives an overview regarding rosacea, a challenging condition with multiple therapeutic options.     

Granuloma aséptico facial idiopático: hallazgos clínicos y ecográficos de 3 casos

Idiopathic facial aseptic granuloma is a typical childhood disease characterized by the presence of one or more asymptomatic nodules on the cheek. Although pathogenesis remains unclear, the disease is thought to be a type of childhood rosacea. It resolves spontaneously, yet it could be confused with other lesions that require treatment.We present clinical and ultrasound findings and outcome from 3 new cases. In 2 cases, the lesion presented as childhood rosacea. Ultrasound revealed a characteristic pattern, with variations depending on the stage of development.High-frequency ultrasound can facilitate the differential diagnosis and thus obviate unnecessary biopsy or excision.     

Syndrome in question

Morbihan Syndrome is a rare entity with unknown etiology. It is clinically characterized by chronic erythematous edema on the face - especially in the middle and upper third of the face - and creates abnormal facial contours that are initially intermitent but become permanent with the development of the syndrome. The histopathology is nonspecific and its therapy is a major challenge due to poor response to the various treatment options. We present the case of a male patient with a five-month-history of disease.