Intralesional cyclosporine for psoriasis. Relationship of dose, tissue levels, and efficacy

Burns, Michael K.; Ellis, Charles N.; Eisen, Drore; Duell, Elizabeth A.; Griffiths, C.E.M.; Annesley, Thomas M.; Hamilton, Ted A.; Birnbaum, Jay E.; Voorhees, John J.

doi:10.1001/archderm.128.6.786

Cited by 25 publications

(9 citation statements)

References 20 publications

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“…Topical CyA is ineffective in psoriasis, probably because of inadequate absorption, as intralesional CyA induces local clearance. 33 However, preliminary studies with FK506 suggest that topical therapy is effective in atopic eczema. 34 Taken together, these studies suggest that keratinocyte immunophilins may be playing a part in the therapeutic action of CyA and FK506 in inflammatory skin disease.…”

Section: Discussionmentioning

confidence: 99%

Cyclosporin A inhibits 12-O-tetradecanoyl-phorbol-13-acetate-induced cutaneous inflammation in severe combined immunodeficient mice that lack functional lymphocytes

1998

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A single application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to mouse skin results in an acute inflammatory response, with an influx of neutrophils and lymphocytes, epidermal hyperplasia and abnormal keratinocyte differentiation. This response is significantly inhibited by topical cyclosporin A (CyA). Although CyA is known to inhibit T-cell activation, the role of T cells in TPA-induced cutaneous inflammation is not well understood. In this study, we have used severe combined immunodeficient (SCID) mice, which carry a spontaneous mutation resulting in the absence of functional T and B lymphocytes, to examine whether lymphocytes are required for the TPA response in mouse skin and whether CyA inhibits the TPA response in SCID mice. A significant increase in epidermal and deep dermal inflammation was observed in both SCID and CB-17 mice 24 h after a single application of TPA (10 nmol) compared with vehicle (P < 0.05, n = 5-7). Simultaneous application of CyA (1.7 mumol) plus TPA resulted in a significant reduction in epidermal and deep inflammation at 24 h compared with TPA alone in SCID and CB-17 mice (P < 0.05, n = 7). In contrast to hairless mice, a variable increase in epidermal thickness was observed in both SCID and CB-17 mice after treatment with TPA at 24 and 72 h, which was not significantly affected by CyA. These data indicate that TPA-induced inflammation in mouse skin does not depend on lymphocytes. In addition, the inhibition of TPA-induced epidermal and deep dermal inflammation by CyA in SCID mouse skin suggests that CyA exerts effects on cutaneous inflammation in mice in the absence of functioning T cells.

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Section: Discussionmentioning

confidence: 99%

Cyclosporin A inhibits 12-O-tetradecanoyl-phorbol-13-acetate-induced cutaneous inflammation in severe combined immunodeficient mice that lack functional lymphocytes

1998

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“…Although intralesional cyclosporine has shown good effects in the treatment of cutaneous psoriasis,[7677] there are no reports on the use of intralesional cyclosporine in the treatment of nail psoriasis. However, keeping in mind its efficacy in the treatment of skin psoriasis, it can prove to be a very useful tool in the treatment of nail psoriasis.…”

Section: Treatment Of Nail Psoriasismentioning

confidence: 99%

Nail psoriasis: The journey so far

Dogra

Arora

2014

Indian J Dermatol

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Nail involvement is an extremely common feature of psoriasis and affects approximately 10-78% of psoriasis patients with 5-10% of patients having isolated nail psoriasis. However, it is often an overlooked feature in the management of nail psoriasis, despite the significant burden it places on the patients as a result of functional impairment of manual dexterity, pain, and psychological stress. Affected nail plates often thicken and crumble, and because they are very visible, patients tend to avoid normal day-to-day activities and social interactions. Importantly, 70-80% of patients with psoriatic arthritis have nail psoriasis. In this overview, we review the clinical manifestations of psoriasis affecting the nails, the common differential diagnosis of nail psoriasis, Nail Psoriasis Severity Index and the various diagnostic aids for diagnosing nail psoriasis especially, the cases with isolated nail involvement. We have also discussed the available treatment options, including the topical, physical, systemic, and biological modalities, in great detail in order to equip the present day dermatologist in dealing with a big clinical challenge, that is, management of nail psoriasis.

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“…However, data are available on use of intralesional CYA injections in plaque type psoriasis, which are statistically significant when used three times a week for 4 weeks. 15,16…”

Section: Psoriasismentioning

confidence: 99%

Cyclosporin in dermatology: A practical compendium

Amber

Tabassum

2020

Dermatologic Therapy

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Cyclosporine A (CYA) belongs to calcineurin inhibitor family, which has the ability to selectively suppress T cells. Owing to its immune-modulatory effects, it had been in use for graft vs host diseases and organ transplant rejection for many years, but in dermatology, it was first approved for use in 1997 in the treatment of psoriasis. Other off-label indications for skin diseases include atopic dermatitis, chronic spontaneous urticaria, lichen planus, pyoderma gangrenosum, alopecia areata, granuloma annulare, and several others. A thorough search of Medline-PubMed database, Google Scholar, and Uptodate was performed for evidence-based and peer-reviewed information. We have summarized the use of cyclosporine in dermatological diseases with respect to its, dosage, safety considerations, and monitoring guidelines. Furthermore, brief overview of its pharmacology, drug interactions, use in pregnancy, and lactation has been discussed. Despite of its common adverse effects like nephrotoxicity and hypertension, cyclosporine offers good safety profile when used in skin diseases. Decision to start cyclosporine therapy is individualized and it should be based on analysis of risk vs benefit. Nevertheless, CYA is preferred over other immunosuppressants in dermatology because of early therapeutic response and less myelosupression. This article offers concise but detailed summary of this beneficial immune-suppressive agent in skin diseases. K E Y W O R D S cyclosporine, dermatology, practical use 1 | INTRODUCTION Cyclosporine A (CYA) is a lipophilic cyclic polypeptide produced by fungal species (Tolypocladium inflatum), which was initially identified as antifungal agent but later found to have immense immunosuppressive properties. It inhibits T-cell activation by selectively inhibiting calcineurin phosphatase, thus suppressing production of IL-2. It has been in clinical practice for more than 30 years. It was initially employed primarily for the treatment of graft vs host diseases and organ transplant rejection but in 1997 U.S. Food and Drug Administration (FDA) approved its use in dermatology for the treatment of psoriasis. 1 Other off-label indications for skin diseases include atopic dermatitis, chronic spontaneous urticaria (CSU), lichen planus (LP), pyoderma gangrenosum (PG), alopecia areata (AA), and granuloma annulare. We used various search engines to get updated information, namely, Medline-PubMed database, Google Scholar, and Uptodate for evidence-based and peer-reviewed publications till April 2020. Systematic reviews, randomized controlled trials, and observational studies were screened and short-listed for critical evaluation of evidence. 2 | PHARMACOLOGY CYA binds with cytoplasmic proteins known as cyclophilins and this complex competitively binds and inhibits calcineurin. This leads to reduction in transcription of interleukin (IL)-2, tumor necrosis factor alpha (TNF-α), IL-3 and IL-4, interferon gamma, and granulocyte-Authors declare that the contents of this article are their own original and unpublished work.

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Intralesional cyclosporine for psoriasis. Relationship of dose, tissue levels, and efficacy

Cited by 25 publications

References 20 publications

Cyclosporin A inhibits 12-O-tetradecanoyl-phorbol-13-acetate-induced cutaneous inflammation in severe combined immunodeficient mice that lack functional lymphocytes

Cyclosporin A inhibits 12-O-tetradecanoyl-phorbol-13-acetate-induced cutaneous inflammation in severe combined immunodeficient mice that lack functional lymphocytes

Nail psoriasis: The journey so far

Cyclosporin in dermatology: A practical compendium

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