Dermatologic literature frequently reiterates the dictum that blepharochalasis is a very localized form of cutis laxa,⁶,⁷,⁸,⁹ and indeed the clinical as well as the histopathological features of blepharochalasis may partly resemble the elastolytic features of type I (but not type II) acquired cutis laxa.¹⁰ Nevertheless, the pathophysiology of blepharochalasis remains largely unknown, although several theories have been proposed. The postpubertal onset may suggest a hormonal cause,⁴ while an underlying vascular etiology is strongly supported by the redness and hyperemia of the skin during the attacks.² This vascular etiology is further reinforced by the clinical features of the disease.¹ An onset without an identifiable cause followed by spontaneous resolution is reminiscent of idiopathic angioedema.¹

An immunologic mechanism that involves matrix metalloproteinases (MMPs) has long been suspected.¹¹ Postinflammatory release of MMPs hypothetically upregulates elastolytic and collagenolytic activity in blepharochalasis patients.¹¹,¹² This immunologic mechanism is supported by several recent studies that demonstrate that blepharochalasis patients have immunoglobulin A (IgA) antibodies directed against elastic fibers in the dermis,¹,⁸,⁹,¹³ although a recent study failed to detect dermal IgA staining.¹² A reduction in the blood levels of complement C4 lends further credibility to an immunologic mechanism.⁸ Yet it is still difficult to comprehend why a purported immune mechanism against elastic fibers would lead only to such localized disease. Because several familial cases have been reported,⁴ and because no one knows exactly why elastic fibers are still not reassembled in the dermis, or why IgA staining persists even after prolonged periods of quiescence of the disease, the occurrence of a yet unknown hereditary factor cannot be excluded.⁶

What exactly triggers the inflammatory response in the first place is also a matter of debate, and a recent literature review failed to identify a verifiable inciting factor in more than half the patients.¹ A large number of poorly documented trigger factors have been reported in the literature, including menstruation, upper respiratory tract infection, a beesting, sports, crying, fever, wind, emotional or psychological stress, and even minor eyelid trauma.¹ However, what complicates matters further is the loose definition of blepharochalasis, as some of the reported cases even in recent literature may not be patients with blepharochalasis after all.¹,³,¹⁴

Because of the rarity of blepharochalasis, robust demographic data are lacking. However, the typical presentation is between the ages of 10 and 20 years.⁴ Although previously thought to be more common in females,¹ the reported male-to-female ratio is 1:1.¹,²,⁴,⁷ The active stage of blepharochalasis is characterized by recurrent episodes
of nonpainful, nonerythematous, and nonpitting edema of both upper eyelids (Figure 27.1), and this edema is relatively resistant to antihistamines and corticosteroids.¹,⁴,⁵ Unilateral involvement and involvement of the lower eyelids is less common,¹,²,⁸ but in more severe cases, the attacks may occasionally be observed in the lower eyelids.¹,² The frequency of the episodic attacks varies from one patient to the other, but initially, it occurs around three to four times a year and then gradually declines as the patient grows older until the attacks completely subside.¹,⁴ However, the frequency and nature of the attacks are too variable for any meaningful analysis or standardization.² They can occur monthly or annually, lasting from several hours to several weeks, and can persist for only a year or 2, or recur over several decades.² After multiple attacks of eyelid edema, the eyelid suffers significant damage and enters a chronic phase of the disease, which is defined as the cessation of any episodic attacks for 2 years.² After the acute phase, the eyelid acquires either an atrophic or a hypertrophic appearance.⁴ However, based on a series of 30 cases, Collin² rejected this classification scheme and questioned the existence of a hypertrophic type in the quiescent or chronic phase of the disease. Instead, he proposed that the hypertrophic phase is a misnomer that occurs when patients are observed by clinicians while they are still in an acute phase, which may indeed be quite prolonged in some patients. He further argued that all patients would invariably progress to atrophy. The authors’ experience does not fully support these findings, as older patients are occasionally seen with recalcitrant hypertrophic changes that can persist for decades (Figure 27.1C).