- Email: [email protected]
Topical tacrolimus 0.03% for the treatment of ocular psoriasis
a r c h s o c e s p o f t a l m o l . 2 0 1 6;9 1(1 0):505–507
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia
Short communication
Topical tacrolimus 0.03% for the treatment of ocular psoriasis夽 P. Rodríguez-Ausín a,∗ , D. Antolín-Garcia a , M. Ruano del Salado b , C. Hita-Antón a a b
Departamento de Oftalmología, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain Departamento de Dermatología, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain
a r t i c l e
i n f o
a b s t r a c t
Article history:
Objective/methods: Cases are presented of 4 patients suffering from severe symptoms due to
Received 7 August 2015
ocular psoriasis and who were treated with off-label 0.03% tacrolimus once a day.
Accepted 19 March 2016
Results/conclusions: All four patients had a mixed blepharitis and keratitis. Pseudopterygium
Available online 6 July 2016
and corneal opacities were present in three of them. All of them experienced an improvement of their itching and ocular surface. They all referred to a marked improvement of their
Keywords:
quality of life in a follow-up period ranging from six months to two years. Therefore, topical
Tacrolimus
tacrolimus could be considered an option in the treatment of ocular psoriasis.
Ocular psoriasis
˜ ˜ S.L.U. All rights © 2016 Sociedad Espanola de Oftalmolog´ıa. Published by Elsevier Espana, reserved.
Psoriasis Blepharitis Pseudopterygium
Tacrolimus tópico al 0,03% en el tratamiento de la psoriasis ocular r e s u m e n Palabras clave:
Objetivo/método: Presentamos una serie de 4 pacientes afectos de psoriasis ocular con sin-
Tacrolimus
tomatología severa, a los que se indicó tratamiento off label con tacrolimus tópico al 0,03%
Psoriasis ocular
una vez al día.
Psoriasis
Resultados/conclusión: La blefaritis mixta y queratitis es común a los 4, y en 3 casos hay seu-
Blefaritis
dopterigión y opacidades corneales. Se apreció mejoría subjetiva del prurito en 2 semanas,
Seudopterigión
y al mes mejoría de la superficie. Todos manifiestan mejoría significativa de su calidad de ˜ vida tras un rango de seguimiento de 6 meses a 2 anos. El tacrolimus tópico puede ser considerado una opción en el tratamiento de la psoriasis ocular. ˜ ˜ S.L.U. Todos © 2016 Sociedad Espanola de Oftalmolog´ıa. Publicado por Elsevier Espana, los derechos reservados.
夽 Please cite this article as: Rodríguez-Ausín P, Antolín-Garcia D, Ruano del Salado M, Hita-Antón C. Tacrolimus tópico al 0,03% en el tratamiento de la psoriasis ocular. Arch Soc Esp Oftalmol. 2016;91:505–507. ∗ Corresponding author. E-mail address: [email protected] (P. Rodríguez-Ausín). ˜ ˜ S.L.U. All rights reserved. 2173-5794/© 2016 Sociedad Espanola de Oftalmolog´ıa. Published by Elsevier Espana,
506
a r c h s o c e s p o f t a l m o l . 2 0 1 6;9 1(1 0):505–507
Introduction Psoriasis is a relatively frequent inflammatory skin disease, affecting up to 2% of the population and diminishing quality of life in 80% de patients.1 Ocular psoriasis rates are not precisely determined but range between 10 and 67% according to different authors.2 A series of 4 patients with ocular psoriasis is presented, who experienced quality of life improvement after beginning treatment with 0.03% topical tacrolimus.
Clinic case reports Patients Four patients, 2 males and 2 females, with a mean age of 72 ± 2.82 years, with psoriasis since youth and experiencing pruritus and chronic ocular discomfort. All four exhibited mixed blepharitis (Fig. 1) and inferior keratitis punctata, while 3 had circumferential pseudopterygium (Fig. 2) and corneal opacities. In one of the patients (Fig. 3), the right eye (RE) exhibited severe thinning and topographic signs of secondary ectasia. Palpebral hygiene measures for blepharitis
Fig. 1 – Mixed blepharitis, the most frequent finding in psoriasis.
Fig. 3 – Chronic corneal involvement with a nasal pseudo-pterygium over stromal thinning and leukomae.
and oral doxycycline were insufficient, with a patient experiencing relapse after suspending said treatment. Topical 0.5% cyclosporine in oily carrier (middle chain triglycerids) was applied although intolerance arose in all cases. After obtaining the authorization of the pharmacy committee of the hospital and requesting the patient to sign an informed consent, off label utilization of 0.03% topical tacrolimus was prescribed in a preparation with vaseline, supplied by the hospital pharmacy. The prescription established 2 daily applications for the first 15 days, followed by an indefinite single nocturnal maintenance application. Subjective improvement appeared in 2 weeks, and after one month pruritus and keratitis diminished, while lacrimal film stabilized. In one case, keratitis disappeared at month 3. Gradual reduction of applications up to one weekly application at 6 months follow-up was considered. Follow-up ranged between 3 months and 3 years, without adverse effects. All patients referred substantial changes in their quality of life and none required systemic treatment for psoriasis.
Discussion
Fig. 2 – Circumferential pseudo-pterygium with small vessels and whitish line parallel to the limbus.
Psoriasis is a chronic disease, the elementary lesion of which is a scale-covered erithematous papula with highly variable clinic and evolution. Ocular symptoms as frequently underestimated in psoriasis patients, with doctors or patients failing to appreciate the possible connection with the base disease. Extracutaneous expressions are infrequent although, due to the epithelial nature of psoriasis, ocular involvement must be considered in addition to the possible existence of psoriasis plaque on the skin of the eyelids.1 In a review on ocular psoriasis, Rehal et al.2 described mixed blepharitis as the most prevalent ocular finding, with burning and itching as the most frequent symptoms. Psoriasis tends to respect the face and therefore the appearance of facial lesions is considered a severity marker. Psoriasis plaque rarely appears on the eyelids and is treated on the basis of corticoids and equivalent medications such as
a r c h s o c e s p o f t a l m o l . 2 0 1 6;9 1(1 0):505–507
tacrolimus. Nonspecific chronic conjunctivitis and/or yellowreddish plaque can appear on the palpebral conjunctiva and in addition 18% of patients suffer dry eye due to lacrimal gland involvement as in other selfimmune systemic diseases.2 Corneal disease is very rare, normally secondary to dry eye and trichiasis. The most common finding is keratitis punctata, although the clinic range comprises opacities, sterile infiltrates, neovascularization, cicatrization and severe peripheral ulcerative keratitis.3 Additional ocular involvement of psoriasis includes anterior uveitis and Birdshot chorioretinopathy. The side effects of psoriasis treatments cannot be dismissed, such as isotretinoin and methotrexate, with possible involvement of the ocular posterior pole by the former (neuropathy, maculopathy) and keratitis and dry eye by the latter. Doxycycline should not be utilized simultaneously with isotretinoin as it increases its neurological toxicity. The 4 patients of the series have chronic blepharitis, 3 with a significant corneal involvement that indicates chronicity such as circumferential pseudopterygium. The main symptom is ocular and palpebral pruritus, which improves slightly with palpebral hygiene, heat and massage and more with oral doxycycline and corticoids. Relapse upon suspension of this treatment indicates an efficient anti-inflammatory therapy with less side effects than corticoids. Tacrolimus, Protopic® (Astellas Pharma, Pozuelo de Alarcón, Madrid, Spain), is a calcineurin inhibitor generally used at 0.03% for atopic dermatitis. The presence of excipients (propylene carbonate) in the skin cream gives rise to doubts about ocular surface toxicity although literature references report goods tolerance in anterior segment diseases refractory to
507
corticoid treatment.4–6 To date, local or systemic side effects attributable to the use of tacrolimus on the ocular surface have not published. By way of conclusion, 0.03% topical tacrolimus could be an efficient and well tolerated therapeutic option for ocular psoriasis when it has a negative repercussion on the quality of life of patients.
Conflict of interests No conflict of interests was declared by the authors.
references
1. Sousa LB, Bass LJ. Psoriasis. In: Mannis MJ, Macsai MS, Huntley AC, editors. Eye and skin disease. Philadelphia: Lippincot-Raven Publishers; 1996. p. 319–26. 2. Rehal B, Modjtahedi BS, Morse LS, Schwab IR, Maibach HI. Ocular psoriasis. J Am Acad Dermatol. 2011;65:1202–12. 3. Huynh N, Cervantes-Castaneda RA, Bhat P, Gallagher MJ, Foster CS. Biologic response modifier therapy for psoriatic ocular inflammatory disease. Ocul Immunol Inflamm. 2008;16: 89–93. 4. Miyazaki D, Tominaga T, Kakimaru-Hasegawa A, Nagata Y, Hasegawa J, Inoue Y. Therapeutic effects of tacrolimus ointment for refractory ocular surface inflammatory diseases. Ophthalmology. 2008;115:988–92. 5. Kymionis GD, Klados NE, Kontadakis GA, Mikropoulos DG. Treatment of superior limbic keratoconjunctivitis with topical tacrolimus 0.03% ointment. Cornea. 2013;32:1499–5015. 6. Wang C, Lin A. Efficacy of topical calcineurin inhibitors in psoriasis. J Cutan Med Surg. 2014;18:8–14.
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia
Short communication
Topical tacrolimus 0.03% for the treatment of ocular psoriasis夽 P. Rodríguez-Ausín a,∗ , D. Antolín-Garcia a , M. Ruano del Salado b , C. Hita-Antón a a b
Departamento de Oftalmología, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain Departamento de Dermatología, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain
a r t i c l e
i n f o
a b s t r a c t
Article history:
Objective/methods: Cases are presented of 4 patients suffering from severe symptoms due to
Received 7 August 2015
ocular psoriasis and who were treated with off-label 0.03% tacrolimus once a day.
Accepted 19 March 2016
Results/conclusions: All four patients had a mixed blepharitis and keratitis. Pseudopterygium
Available online 6 July 2016
and corneal opacities were present in three of them. All of them experienced an improvement of their itching and ocular surface. They all referred to a marked improvement of their
Keywords:
quality of life in a follow-up period ranging from six months to two years. Therefore, topical
Tacrolimus
tacrolimus could be considered an option in the treatment of ocular psoriasis.
Ocular psoriasis
˜ ˜ S.L.U. All rights © 2016 Sociedad Espanola de Oftalmolog´ıa. Published by Elsevier Espana, reserved.
Psoriasis Blepharitis Pseudopterygium
Tacrolimus tópico al 0,03% en el tratamiento de la psoriasis ocular r e s u m e n Palabras clave:
Objetivo/método: Presentamos una serie de 4 pacientes afectos de psoriasis ocular con sin-
Tacrolimus
tomatología severa, a los que se indicó tratamiento off label con tacrolimus tópico al 0,03%
Psoriasis ocular
una vez al día.
Psoriasis
Resultados/conclusión: La blefaritis mixta y queratitis es común a los 4, y en 3 casos hay seu-
Blefaritis
dopterigión y opacidades corneales. Se apreció mejoría subjetiva del prurito en 2 semanas,
Seudopterigión
y al mes mejoría de la superficie. Todos manifiestan mejoría significativa de su calidad de ˜ vida tras un rango de seguimiento de 6 meses a 2 anos. El tacrolimus tópico puede ser considerado una opción en el tratamiento de la psoriasis ocular. ˜ ˜ S.L.U. Todos © 2016 Sociedad Espanola de Oftalmolog´ıa. Publicado por Elsevier Espana, los derechos reservados.
夽 Please cite this article as: Rodríguez-Ausín P, Antolín-Garcia D, Ruano del Salado M, Hita-Antón C. Tacrolimus tópico al 0,03% en el tratamiento de la psoriasis ocular. Arch Soc Esp Oftalmol. 2016;91:505–507. ∗ Corresponding author. E-mail address: [email protected] (P. Rodríguez-Ausín). ˜ ˜ S.L.U. All rights reserved. 2173-5794/© 2016 Sociedad Espanola de Oftalmolog´ıa. Published by Elsevier Espana,
506
a r c h s o c e s p o f t a l m o l . 2 0 1 6;9 1(1 0):505–507
Introduction Psoriasis is a relatively frequent inflammatory skin disease, affecting up to 2% of the population and diminishing quality of life in 80% de patients.1 Ocular psoriasis rates are not precisely determined but range between 10 and 67% according to different authors.2 A series of 4 patients with ocular psoriasis is presented, who experienced quality of life improvement after beginning treatment with 0.03% topical tacrolimus.
Clinic case reports Patients Four patients, 2 males and 2 females, with a mean age of 72 ± 2.82 years, with psoriasis since youth and experiencing pruritus and chronic ocular discomfort. All four exhibited mixed blepharitis (Fig. 1) and inferior keratitis punctata, while 3 had circumferential pseudopterygium (Fig. 2) and corneal opacities. In one of the patients (Fig. 3), the right eye (RE) exhibited severe thinning and topographic signs of secondary ectasia. Palpebral hygiene measures for blepharitis
Fig. 1 – Mixed blepharitis, the most frequent finding in psoriasis.
Fig. 3 – Chronic corneal involvement with a nasal pseudo-pterygium over stromal thinning and leukomae.
and oral doxycycline were insufficient, with a patient experiencing relapse after suspending said treatment. Topical 0.5% cyclosporine in oily carrier (middle chain triglycerids) was applied although intolerance arose in all cases. After obtaining the authorization of the pharmacy committee of the hospital and requesting the patient to sign an informed consent, off label utilization of 0.03% topical tacrolimus was prescribed in a preparation with vaseline, supplied by the hospital pharmacy. The prescription established 2 daily applications for the first 15 days, followed by an indefinite single nocturnal maintenance application. Subjective improvement appeared in 2 weeks, and after one month pruritus and keratitis diminished, while lacrimal film stabilized. In one case, keratitis disappeared at month 3. Gradual reduction of applications up to one weekly application at 6 months follow-up was considered. Follow-up ranged between 3 months and 3 years, without adverse effects. All patients referred substantial changes in their quality of life and none required systemic treatment for psoriasis.
Discussion
Fig. 2 – Circumferential pseudo-pterygium with small vessels and whitish line parallel to the limbus.
Psoriasis is a chronic disease, the elementary lesion of which is a scale-covered erithematous papula with highly variable clinic and evolution. Ocular symptoms as frequently underestimated in psoriasis patients, with doctors or patients failing to appreciate the possible connection with the base disease. Extracutaneous expressions are infrequent although, due to the epithelial nature of psoriasis, ocular involvement must be considered in addition to the possible existence of psoriasis plaque on the skin of the eyelids.1 In a review on ocular psoriasis, Rehal et al.2 described mixed blepharitis as the most prevalent ocular finding, with burning and itching as the most frequent symptoms. Psoriasis tends to respect the face and therefore the appearance of facial lesions is considered a severity marker. Psoriasis plaque rarely appears on the eyelids and is treated on the basis of corticoids and equivalent medications such as
a r c h s o c e s p o f t a l m o l . 2 0 1 6;9 1(1 0):505–507
tacrolimus. Nonspecific chronic conjunctivitis and/or yellowreddish plaque can appear on the palpebral conjunctiva and in addition 18% of patients suffer dry eye due to lacrimal gland involvement as in other selfimmune systemic diseases.2 Corneal disease is very rare, normally secondary to dry eye and trichiasis. The most common finding is keratitis punctata, although the clinic range comprises opacities, sterile infiltrates, neovascularization, cicatrization and severe peripheral ulcerative keratitis.3 Additional ocular involvement of psoriasis includes anterior uveitis and Birdshot chorioretinopathy. The side effects of psoriasis treatments cannot be dismissed, such as isotretinoin and methotrexate, with possible involvement of the ocular posterior pole by the former (neuropathy, maculopathy) and keratitis and dry eye by the latter. Doxycycline should not be utilized simultaneously with isotretinoin as it increases its neurological toxicity. The 4 patients of the series have chronic blepharitis, 3 with a significant corneal involvement that indicates chronicity such as circumferential pseudopterygium. The main symptom is ocular and palpebral pruritus, which improves slightly with palpebral hygiene, heat and massage and more with oral doxycycline and corticoids. Relapse upon suspension of this treatment indicates an efficient anti-inflammatory therapy with less side effects than corticoids. Tacrolimus, Protopic® (Astellas Pharma, Pozuelo de Alarcón, Madrid, Spain), is a calcineurin inhibitor generally used at 0.03% for atopic dermatitis. The presence of excipients (propylene carbonate) in the skin cream gives rise to doubts about ocular surface toxicity although literature references report goods tolerance in anterior segment diseases refractory to
507
corticoid treatment.4–6 To date, local or systemic side effects attributable to the use of tacrolimus on the ocular surface have not published. By way of conclusion, 0.03% topical tacrolimus could be an efficient and well tolerated therapeutic option for ocular psoriasis when it has a negative repercussion on the quality of life of patients.
Conflict of interests No conflict of interests was declared by the authors.
references
1. Sousa LB, Bass LJ. Psoriasis. In: Mannis MJ, Macsai MS, Huntley AC, editors. Eye and skin disease. Philadelphia: Lippincot-Raven Publishers; 1996. p. 319–26. 2. Rehal B, Modjtahedi BS, Morse LS, Schwab IR, Maibach HI. Ocular psoriasis. J Am Acad Dermatol. 2011;65:1202–12. 3. Huynh N, Cervantes-Castaneda RA, Bhat P, Gallagher MJ, Foster CS. Biologic response modifier therapy for psoriatic ocular inflammatory disease. Ocul Immunol Inflamm. 2008;16: 89–93. 4. Miyazaki D, Tominaga T, Kakimaru-Hasegawa A, Nagata Y, Hasegawa J, Inoue Y. Therapeutic effects of tacrolimus ointment for refractory ocular surface inflammatory diseases. Ophthalmology. 2008;115:988–92. 5. Kymionis GD, Klados NE, Kontadakis GA, Mikropoulos DG. Treatment of superior limbic keratoconjunctivitis with topical tacrolimus 0.03% ointment. Cornea. 2013;32:1499–5015. 6. Wang C, Lin A. Efficacy of topical calcineurin inhibitors in psoriasis. J Cutan Med Surg. 2014;18:8–14.