by Edward Tenner, M.D.
The autoimmune bullous skin diseases, pemphigus (with major subsets pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus) and the more common bullous pemphigoid (with variant disease phenotypes of cicatricial pemphigoid and gestational pemphigoid) each may have ocular manifestations.
Diagnosis of PV is made by a characteristic clinical presentation, histological suprabasilar intraepithelial acantholysis, IgG autoantibodies on the cell surface by direct immunofluorescence testing of a biopsied lesion and the presence of circulating antiepithelial autoantibodies.1 The incidence of PV varies between 1/million in the general population to over 1/100,000 among Ashkenazi Jews in Israel. This variability correlates to a strong association of PV in individuals with selected class II MHC genes. For instance, 90% of Ashkenazi Jews with PV carry the gene allele DRB1 *0402.
New advances in characterization of the antigen and autoantibodies involved in autoimmune bullous diseases have helped elucidate the mechanism of the epithelial damage. Pathophysiologically, PV is caused by autoantibodies against desmoglein 3 (Dsg 3), a glycoprotein that localizes to the core of desmosomes. These autoantibodies cause acantholysis in the deeper suprabasal epidermis which is where Dsg 3 is mainly located. Dsg 3 is also located throughout the oral and other mucous membranes including the conjunctiva where blisters also occur in PV.2 ELISA tests for autoantibodies against desmoglein 1 (Dsg 1) and Dsg 3 are recently available that differentiate pemphigus vulgaris (anti-Dsg 3 IgG detected) from pemphigus foliaceus (only anti-Dsg 1 IgG detected), and the clinical subtypes of PV i.e. mucosal dominant (anti-Dsg 3 IgG detected) and mucocutaneous (anti-Dsg 3 IgG and anti-Dsg 1 IgG detected).
While almost uniformly fatal before the advent of corticosteroid treatment, PV can now be controlled in most patients and the mortality rate is less than 5%. Along with prednisone, an immunosuppressive drug is often needed. Azathioprine and mycophenolate mofetil are the most commonly used but in unresponsive patients cyclophosphamide, cyclosporine, or chlorambucil can be substituted.
After seeing a patient with active PV and ocular involvement, a search of the medical literature was sparse concerning ocular involvement in PV. In cooperation with the International Pemphigus Foundation a survey was undertaken to determine the prevalence and extent of ocular involvement in this rare disease.
Questions relating to the eye were part of an International Pemphigus Questionnaire that appeared in the Foundation's website, discussion group and quarterly newsletter. A total of 158 responses were collected in 1999. Of these, 134 were from patients with PV and only those responses were considered.
The general disease parameters from the survey approximate what is generally known about PV, such as average age at onset in the sixth decade and equal occurrence in males and females (Table 1). Questions were framed to differentiate between prior eye problems and new ones appearing during the course of PV. New eye problems after being diagnosed with PV were reported in 62% (83 out of 134 persons). Cataract, glaucoma or both developed in 32% (43 out of 134 persons). Since most of these patients were on high dose glucocorticoid treatment, this ocular involvement most likely was treatment related and not due to PV. Although there are reports of cataract formation in pemphigus foliaceus, there is little about cataract with PV in the medical literature.
Disease related ocular involvement excluding cataract and glaucoma was noted by 40% (53 out of 134 persons), which is detailed in Table 2. It is noteworthy that blisters occurred not only on lid margins and conjunctiva but also on the eyelids themselves.3 While past reports indicate that conjunctivitis is the most common ocular involvement in PV4, the survey indicates that eyelid involvement is equally common.
The importance of careful ophthalmologic care for patients with PV as their disease is being treated is apparent with almost two-thirds of those surveyed having ocular problems at some time. Also because tearing and foreign body sensation due to conjunctival involvement can precede the appearance of mouth and skin lesions in PV as noted in an article by Hodak5, ophthalmologists may be among the first to see patients with this often misdiagnosed disease. Early care should minimize ocular morbidity.
- Nousari HC, Anhalt GJ. Pemphigus & bullous pemphigoid. The Lancet 1999; 354: 667-672.
- Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J Clin Invest.1999; 103: 461-468.
- Seishima M, Oyama Z, Shimizu H, Naganawa Y, Yoshimura T, Yamazaki F. Pemphigus of the eyelids. Eur J Dermatol. 2001; 11: 141-143.
- Ekong AS, Foster CS, Roque MR. Eye involvement in autoimmune blistering diseases. Clin Dermatol. 2001; 19: 742-749.
- Hodak E, Kremer I, David M, et al. Conjunctival involvement in pemphigus vulgaris: a clinical, histopathological and immunofluorescence study. Br J Dermatol. 1990; 123: 615-620.
TABLE I. General findings in 134 PV patients
|Sex||79 (59%) Female||55 (41%) Male|
|Clinical presentation||40 (30%) Mucosal||94 (70%) Mucocutaneous|
|Average age, yrs||50.3 At onset of disease||55.5 At time of report|
TABLE II. Ocular finding in 134 PV patients
|Periocular skin & eyelid involvement||18 (13%)|
|Corneal problem||7 (5%)|
|Misc. (iritis, dry eyes, herpes simplex, blurred vision, blisters on eyes)||23 (17%)|
|Total with eye problems (some had more than one type of involvement)||83 (62%)|