Morbihan disease is a lymphangitic complication of Rosacea, characterized by solid and persistent oedema of the upper face [1], with no spontaneous remission [2]. It is often associated with frequent episodes of flushing, fixed erythema, spider veins, papules and pustules [3]. In most cases, it has a bilateral presentation, but there are some case reports about unilateral Morbihan Syndrome [4,5]. The pathogenesis of this disease is still unknown, but it is probably linked to recurrent episodes of vasodilation and inflammation. These result in damage, remodeling and formation of epithelioid granulomas and lympho-histiocytic infiltrates around lymphatic vessels, with consequent drainage alteration [1,6,7]. The disease more commonly appears in the third and fourth decades, with greater incidence in women [2].

Symptoms are usually minimal, but, when eyelids involvement is present (as in our patient was), aesthetic alterations of facial features and visual field limitations can occur [8,9], with a considerable worsening patients’ quality of life.

A suspicion of Morbihan Syndrome should arise in patients with a chronic, refractory oedema, without any specific abnormalities to lab tests nor histological examinations [10-12]; a few patients show infiltration consistent with a mast cells inflammation [6,13]. Morbihan Syndrome is a diagnosis of exclusion, so it is mandatory to consider any other differential diagnosis, such as oro-facial granulomatosis, sarcoidosis, Hansen's disease, Systemic Lupus Erythematosus, cutaneous leishmania, foreign body granulomatosis, facial granuloma, superior vena cava syndrome, Buschke’s scleredema, pseudolymphoma, Melkersson-Rosenthal’s syndrome, dermatomyositis, chronic actinic dermatitis, chronic contact dermatitis, angioedema or thyroid disease and drug reactions (barbiturates, chlorpromazine, diltiazem and isotretinoin) [2,3,6,13].

In our patient, the presence of rosacea and the typical presentation drove us to the suspicion of t Morbihan disease. Furthermore, anti-DSF70 antibodies in a patient with ANA-positivity made the presence of immune-rheumatologic diseases unlikely [14].

The therapy we chose was supported by the studies published in literature [12]:

• Treatment of basic rosacea: since our patient had a papulo-pustular rosacea, we decided to start therapy with a topical anti-inflammatory agent (Metronidazole cream 0.75%). It works altering neutrophil chemotaxis and inactivating ROS, in order to reduce erythema, papules and pustules. We also added an oral antibiotic at reduced doses (Doxycycline 40 mg) [15];
• Isotretinoin: Isotretinoin at a dose of 10-80 mg for 3-6 months has proved to be effective in most studies carried out on patients with massive mast cells infiltration [2,8,9], leading to disease-free intervals of about 9 months [6,16]. Also a long term therapy with ultra-low dose of Isotretinoin (10 mg) and Desloratadine 5 mg given for 12-16 month seems to be effective [17]. However, in 15-20% of patients this drug is ineffective: in these cases, the disease course is uncertain, with possible chronic evolution or exacerbations [7];
• Deflazacort: corticosteroids are used thanks to their anti-inflammatory power that inhibits mast cells activation, migration, proliferation and cytokine production and neutrophils recruitment [6], but steroid use in monotherapy must be carefully evaluated, as it could be related to the disease recurrence or progression, since it does not act on pathogenetic mechanisms at its base [1]. Steroids intralesional administration appears effective, safe and minimally invasive and could have more satisfactory results, as the effects would not be impaired by persistent lymphedema and perivascular inflammation. For this reason, our patient was referred to the plastic surgery department, where, in addition to performing a biopsy, he was treated with to local injection of Triamcinolone;
• Doxycycline: the use of tetracyclines is emerging in patients with Morbihan disease, thanks to the ability of the drug in inhibition of cytokines production (in particular, antimicrobial peptide LL37 and metalloproteases that have vasodilatory effects) [16] by mast cells [8,12]; different from the previous therapy, however, the duration of antibiotic treatment relates with the degree of response obtained [1]. In particular, Doxycycline given at a reduced dose (40 mg/day in the prolonged release formulation) for 4-12 months seems to be effective in inducing complete remission, as it improves cellular metabolism in damaged tissues and reduces the damage of the extracellular dermal matrix, with antiproliferative effect on fibroblast activity; furthermore, at these doses, it is not associated with side effects or onset of resistance [11,16];
• Blepharoplasty: when medical therapy results inadequate, surgical therapy could be a choice; however, after this procedure, disease outcomes or relapses cannot be ruled out [10].

Other therapies that have been studied: facial draining massage [18], blepharoplasty with CO2-laser [2], Minocycline (in countries where Isotretinoin is not on the market) [8,19], IFN-gamma injection [3], Thalidomide (with poor results) [3,9], Tripterygium wifordii (extracted from a traditional Chinese herb and having anti-inflammatory and immunosuppressive properties) [19] and Omalizumab at initial dose of 450 mg and consecutive maintenance doses of 300 mg every 4-6 week for 2 months [20].

Despite several available drugs, capable of acting on factors apparently triggering the phenomenon, we must remember that they may be ineffective in case of excessive accumulation of fluids in the interstice and the reduced perfusion of the fibrous and collagenous thickness, which prevent the correct drugs distribution in involved areas [10]. Moreover, in patients presenting with a low mast cell infiltrate those drugs would have fewer targets to act on.

Currently, combined therapy with antibiotics and steroids seems to be the most commonly used, but it is necessary to consider adverse effects [1].