Disease Entity
Blepharochalasis is a rare syndrome consisting of recurrent bouts of upper eyelid edema associated with thinning, stretching, and fine wrinkling of the involved skin. The lower eyelids are not commonly involved. These episodes often result in eyelid skin redundancy. This condition was initially described by GJ Beer in 1817, and was named blepharochalasis by Ernst Fuchs in 1896. [1] The term blepharochalasis originates from the Greek words: blepharon (eyelid) and chalasis (a relaxing). [2, 3, 4]
Bilateral lacrimal gland prolapse in the quiescent stage of blepharochalasis syndrome. Courtesy of Kathleen Duerksen, MD.
Upper and lower eyelid edema in blepharochalasis syndrome. Notice the left pseudoepicanthal fold. Courtesy of Kathleen Duerksen, MD.
Various disease stages have been observed. In 1926, WL Benedict described a swelling stage and a subsequent stage characterized by thinning skin. [5] Others have suggested an active, intumescent phase that precedes a quiescent, atrophic phase. [6]
Epidemiology
Blepharochalasis is an uncommon disorder with a typical initial presentation in adolescence or young adulthood. A study by Koursh et al that describes 22 male and 45 female cases reports an average age of onset as 11 years. [2] Blepharochalasis is a rare disorder and thus has no clear gender predilection; however, many case studies often report more female patients than male patients. [2, 7] The intermittent attacks occur less commonly as the person ages. [6]
Etiology
Although the exact cause of this syndrome is unknown, several associations have been noted. A relationship with Ascher syndrome, consisting of upper lip edema and nontoxic thyroid enlargement, has been suggested by multiple cases. [8, 9] One case of blepharochalasis associated with dermatomyositis and lymphocytic leukemia has been reported. [10] Others have proposed that blepharochalasis is exacerbated by hormonal influences (may explain the common onset with puberty), menstrual cycles, upper respiratory tract infections, and allergies. In several individuals, systemic abnormalities (eg, vertebral anomalies, renal agenesis, congenital heart disease) have been found. [11]
Tissue biopsy in an affected patient has revealed the presence of matrix metalloproteinase, indicating a potential immune mechanism. [12]
A hereditary form of the disease may exist; Panneton observed varying degrees of the syndrome in many members of a large family. [13] Autosomal dominance with incomplete penetrance and variable expressivity is possible. [13]
Pathophysiology
Blepharochalasis may be a form of chronic angioedema with localized vascular dilation and proteinaceous fluid extravasation. An orbital component has been suggested because, in patients with the syndrome, orbital fat has been noted to contain increased vascularity with dilated capillaries. Multiple triggers have been described, including immune reactions and environmental factors. [14]
The finding of immunoglobulin A (IgA) deposits in lesional skin has implicated immunopathogenic causes. [15] Elevated immunoglobulin E (IgE) levels in one case report supports the involvement of atopy in blepharochalasis. Perivascular infiltrates in patients with active disease, along with degradation of both elastin and collagen in the dermis, suggest inflammatory influences. Elastin messenger RNA (mRNA) expression has been shown to be normal compared to controls, indicating an environmental cause of breakdown, such as postinflammatory enzymatic action. [16]
Matrix metalloproteinase 3 (MMP-3) and MMP-9 may play a role in the development of this disease. One recent study by Browning et al reported a case of blepharochalasis stemming from episodes of nighttime crying, linking the presence of MMP-9 in human tears to the onset of blepharochalasis. [17]
Relevant Anatomy
The eyelid skin is extremely thin and distensible, which may promote vulnerability to further thinning and wrinkling after an episode of severe edema. The levator aponeurosis, the tendonous continuation of the levator palpebrae superioris muscle, attaches to the anterior surface of the tarsus in the upper eyelid. This structure may similarly undergo thinning and stretching during edematous attacks, leading to aponeurotic upper blepharoptosis. Likewise, stretching of the orbital septum allows prolapse of the tissues behind (including orbital fat and lacrimal gland). [18]
Indications for Surgical Intervention
Surgery is primarily indicated for correction of sequelae in those who have achieved a stable course later in the disease, and usually follows a 6 month to 1 year interval of quiescence to prevent, delay and/or minimize post-operative complications. [6] Corrective procedures may include levator aponeurosis dehiscence repair, canthal tendon reattachment, eyelid tightening, blepharoplasty, and fat grafting (please see Treatment sectin for additional details). [19]
Contraindications to Surgical Intervention
Those experiencing active episodes of edema should not undergo surgery. Surgical candidates should have displayed at least 6 months to 1 year of quiescence. [6] Systemic steroids, topical steroids, antihistamines, and anti-inflammatory agents have not been shown to alter the course of the disease or to alleviate the symptoms associated with acute episodes. [2]
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Bilateral lacrimal gland prolapse in the quiescent stage of blepharochalasis syndrome. Courtesy of Kathleen Duerksen, MD.
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Upper and lower eyelid edema in blepharochalasis syndrome. Notice the left pseudoepicanthal fold. Courtesy of Kathleen Duerksen, MD.
