A 31-year-old woman presented highly inflammatory
conjunctivitis for several months associated with bilateral symblepharons and superficial punctuate
keratitis around the left eye refractory to treatment. The patient had a history of
mouth ulcers and sores on the scalp. Examination showed scalp lesions with crusts. Histological examination of these lesions revealed dermal-epidermal cleavage. Direct immunofluorescence showed sub-membrane deposits. Anti-basal membrane
antibodies were positive. Immunotransfer confirmed the presence of circulating
antibodies. This condition was controlled following administration of three courses of
cyclophosphamide as a bolus. However, the symblepharons persisted in both eyes. Improvement lasted 4 years. The patient again consulted for inflammatory
conjunctivitis and superficial punctate
keratitis resulting in invalidating loss of visual acuity, associated with
hypereosinophilia.
Cortisone eye drops alone resulted in no improvement. Treatment was initiated with topical
tacrolimus (Protopic) 0.03% comprising once-daily application to the conjunctiva in the evening. This
therapy was well tolerated, and 2 daily applications could be given, followed by a dosage of 0.1%. Improvement was rapid and spectacular, with frank amelioration of visual acuity and resolution of the patient's
keratitis. Treatment was continued for 4 months and gradually reduced to the 0.03% dosage level, with increasingly wide intervals between applications. There has been no relapse within the 12 months following the end of treatment.
DISCUSSION: Standard treatment of pharmacological
cicatricial pemphigoid involves systemic immunosuppression since topical
anti-inflammatories are ineffective. The mortality associated with this disease is due to iatrogenic complications.
Tacrolimus exhibits extremely good penetration of the conjunctiva. Following administration at a concentration of 0.06% 3 times daily in 15 patients with inflammatory disease of the conjunctiva or the cornea, improvement was seen in 10 of these patients at 26 weeks.
Tacrolimus appears to act through immunomodulatory and anti-inflammatory mechanisms. It induces local inhibition of T lymphocyte activation and reduces production of pro-inflammatory
lymphokines. Oral
tacrolimus cannot be used to control
cicatricial pemphigoid refractory to standard
immunomodulators. However, 3 three other cases involving topical treatment of
cicatricial pemphigoid showed marked efficacy of treatment given for 2 to 6 months, with complete tolerability. Thus, topical
tacrolimus appears to constitute an interesting alternative treatment in
cicatricial pemphigoid.