Blepharochalasis syndrome H02.3

The first report of this syndrome was written by the Austrian ophthalmologist Joseph Beer in 1807, but Ernst Fuchs was the first to use the term "blepharochalasis" (from the Greek: "drooping of the eyelids") in 1896.

Blepharochalasis syndrome (BS) is a rare disorder characterized by recurrent episodes of periocular edema.

Due to the rarity of this syndrome, no precise epidemiological data is available. The available information is mainly based on case reports or small case series.

There are several theories for the etiology of blepharochalasis syndrome. However, the final clarification is still pending. Although the majority of cases are confined to the eyelid, there are reports of blepharochalasis in association with other systemic abnormalities. Some authors have therefore suggested that blepharochalasis may be part of a more complex systemic disorder (Ortiz-Perez S et al. 2024).

Hormonal influences, allergies, localized forms of cutis laxa and idiopathic angioedema are discussed. Histopathological studies suggest an immunological process with deposits of immunoglobulin (IgA ) (Motegi S et al. 2014; Paul M et al. 2017; Grassegger A et al. 1996).

The pathophysiology of BS has not yet been clarified. Histopathological examinations show only fluid extravasation in the acute stage. Repeated episodes of skin stretching lead to fragmentation and eventual loss of elastic fibers. However, the presence of Ig A deposits in the dermis and perivascular inflammatory cells, which have been described in several studies, indicate a possible immune reaction.

Blepharochalasis syndrome usually begins in childhood or puberty. The average age of onset is 11.4 years (Koursh DM et al. 2009). The flare-ups recur every 3 to 4 months for several years and become less frequent with increasing age. Finally, the inflammatory episodes cease and the disease enters a dormant stage.

The acute phase lasts from hours to days (on average 2 days). In this phase there is painless edema, usually combined with erythema. The patient may also complain of a "red eye" and lacrimation. Repeated episodes of eyelid swelling lead to a very characteristic appearance of the eyelids and the periocular area with upper eyelid pontosis, wrinkled, discolored and atrophic skin with dilated visible subcutaneous vessels.

In the late stages of the disease, the insertion of the ligamentous structures of the lateral canthus may be disrupted, resulting in a rounded lateral angle and even a shortening of the horizontal palpebral fissure (known as acquired blepharophimosis). With the progression of levator aponeurosis dehiscence, upper eyelid ptosis becomes more evident, especially in the medial region, and the weakening of the orbital septum favors prolapse of the orbital fat and lacrimal gland in some patients.

Blepharochalasis can also occur as part of a systemic disease. The most common association is with Ascher syndrome (blepharochalasis, double lip and non-toxic thyroid enlargement) or acquired cutis laxa (redundant skin, skeletal abnormalities and multi-organ impairments).

Blood tests, including blood count, circulating Ig, C-reactive protein, C3, C4 and C1 esterase inhibitor, were reported as normal in these patients.

The common finding in these samples is the loss of elastic fibers of the dermis. IgA antibody deposits can be detected by immunofluorescence. Positive immunohistochemical staining for the metalloproteinases MMP-3 and MMP-9 was also detected. Other findings include atrophy of various structures of the dermis, increasing number and diameter of skin capillaries, perivascular inflammatory infiltrates and pigmentation in the papillary and upper reticular dermis (Koursh DM et al. 2009).

Various entities may resemble BS. In the acute phase, the differential diagnosis can be difficult, especially when inflammatory episodes occur, as all the different causes of acute and acute-chronic eyelid swelling need to be considered:

• Allergic reactions (contact allergic dermatitis)
• Local infection/inflammation of the eyelid (e.g. chalazion)
• Inflammation of the eye socket
• Angioedema (acquired)
• Melkersson-Rosenthal syndrome

In the resting phase:

• Dermatochalasis
• Droopy eyelid syndrome
• Upper eyelid ptosis
• Acquired cutis laxa
• Eyelid/orbital tumors

There are no well-defined protocols for the treatment of inflammatory flare-ups. Several authors report good results with the use of steroids, both systemically and topically. Other immunosuppressants, such as tacrolimus, have been used for topical treatment (Razmi T M et al. 2018).

Karakonji et al. reported improvement of the acute stage in two patients with NB by oral doxycycline based on its properties as a matrix metalloproteinase inhibitor. Finally, oral acetazolamide was reported in two case series with good results. The rationale for the use of this diuretic is based on the assumption that BS is a localized form of angioedema of the eyelid (Lazaridou MN et al. 2007).

The treatment of BS is usually based on surgery to correct the complications. Surgical techniques should be combined depending on the case. Blepharoplasty, ptosis surgery and canthus surgery are the methods of choice in these patients due to the particular changes in the periocular tissue.

The natural history of BS is well established, although a wide variety of presentations have been described in terms of the number of swelling attacks and the duration of the early stage. Depending on this, the number and severity of complications may vary from patient to patient. The impact of surgery on the possibility of recurrence is also unknown (Ortiz-Perez S et al. 2024).

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