Pemphigus is a life-threatening autoimmune disease in which autoantibodies are directed against desmosomal adhesion molecules resulting in blistering in the suprabasal layers of the cutaneous epidermis and mucosa.¹,²,³,⁴ The disease is classified as pemphigus vulgaris or foliaceus depending upon the histologic layer of blistering, and as paraneoplastic pemphigus.

Paraneoplastic pemphigus, mostly presenting as pemphigus vulgaris (PV) with severe mucosal involvement,⁵ is often associated with lymphoproliferative neoplasms and carcinomas of the colon, lung, breast, pancreas, prostate, uterus, liver, and kidney.⁵,⁶,⁷,⁸,⁹,¹⁰ It may be related to an altered immunologic state and immunologic cross-reactivity between the tumor and the skin.²,⁵ Paraneoplastic pemphigus is characterized by painful erosions and ulcerations affecting the mucous membranes of the oropharynx, tongue, lips, and conjunctiva.⁶,¹¹,¹² Skin lesions vary in appearance from blisters to lichenoid-like² and are seen most often on the head, neck, upper trunk, and proximal extremities.

Induced or triggered pemphigus is a condition in which an exogenous factor induces the onset of the disease.² Triggers can include drugs, viral infections, contact allergens, physical agents, and foods.¹³ Viral infections, especially herpes virus infections, have been linked to pemphigus, and herpes virus DNA has been detected in lesions of some patients with PV.²,¹⁴ Dietary factors have been implicated as triggers for pemphigus in genetically predisposed individuals, including thiol-allyl compounds present in garlic, leeks, and onions; and polyphenolic compounds present in black pepper, red chili pepper, cherry, cranberry, blackberry, red wine, and tea.²,¹³ Physical agents, such as thermal burns, ultraviolet radiation, and surgical procedures have also been shown to trigger pemphigus in genetically predisposed individuals.¹³,¹⁵,¹⁶,¹⁷ Contact allergens such as pesticides of the organophosphate group can serve as potential triggers.¹³ Drugs capable of inducing pemphigus include non-thiol angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, calcium channel blockers, and some vaccines and interferons.²

PV accounts for approximately 80% of all types of pemphigus and is the most common form. It occurs more frequently in individuals of Mediterranean and Jewish descent³,¹⁸,¹⁹ and is seen most often in the fourth or fifth decades of life. Some reports have shown a slight predilection for females at about 66%,²⁰,²¹ whereas others have shown no gender predominance.²² The incidence of PV varies from 1 to 16 new cases per million persons per year.²³,²⁴

PV is typically seen in previously normal skin as a blister caused by the separation of the superficial epidermal layers from its basal layer.² In nearly half of cases, the oral mucosa is initially involved, but later, lesions spread to involve the skin and other mucous membranes including the pharynx, esophagus, conjunctiva, urethra, cervix, and rectum.¹⁹,²²,²⁵,²⁶ Bacterial infection can be seen following the sloughing of the fragile blister walls.²⁷,²⁸ The disease is characterized by repeated exacerbations, fluid and protein loss, and opportunistic infections,² and even with treatment, these can lead to death in 10% of cases.³,¹³

Ocular PV is uncommon but well-known.⁴,¹⁹,²⁹,³⁰,³¹,³²,³³,³⁴,³⁵,³⁶,³⁷,³⁸,³⁹,⁴⁰,⁴¹,⁴² It is reported to occur in approximately 7% to 26% of pemphigus cases,¹⁹,²²,⁴³ but ocular findings are unpredictable and their presence does not correlate with the general severity
of the disease.²,³,⁴,¹⁹ Ocular involvement involves the conjunctiva in most cases (88%), the eyelid skin or margin in 67% of cases,²² and may be unilateral or bilateral. It usually presents as chronic blepharitis and conjunctivitis,⁴,¹⁹,²⁹,⁴²,⁴³ associated with conjunctival injection, foreign body sensation, photophobia, dry eye, and epiphora. Inflammation, blisters, and eyelid margin mucosal papillomas can be seen.²⁹,³⁰,⁴⁴,⁴⁵ Conjunctival bullae can be seen, but are unusual.⁴⁶ PV can rarely present with a distinct conjunctival inflammatory mass without associated typical findings such as conjunctivitis, mucous discharge, blisters, or erosions.⁴⁷ Other rare findings include cicatricial contraction of the eyelid skin or conjunctiva,² cobblestone-like conjunctival papillae,⁴⁸ sicca keratoconjunctivitis, eyelid ectropion or entropion, and trichiasis.²,³,⁴²,⁴⁹,⁵⁰,⁵¹

While eye involvement has been reported as an early manifestation of PV,⁴,³⁷ most patients develop the ocular lesions 1 to 3 years after the diagnosis of PV.¹⁹,²²