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Topical Immune Response Modifiers: Antiinflammatories

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Clinical and Basic Immunodermatology

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Abstract

In recent years, major findings such as blockade of the calcineurin pathway in T lymphocytes led to the identification of novel targets for the treatment of inflammatory skin diseases. The first systemic specific calcineurin inhibitor (CI) for the treatment of inflammatory skin diseases was cyclosporin A (CsA), which demonstrated efficacy both in psoriasis and atopic dermatitis (AD). Because of its systemic adverse effects and the inability to generate a topical CsA compound, there still exists a need for better immunomodulatory agents. Later, the calcineurin inhibitor tacrolimus (FK506) was successfully approved as an efficient topical drug. Subsequently a second calcineurin inhibitor (pimecrolimus, ASM 981) was developed and approved for the topical treatment of atopic dermatitis. Both CIs have been shown to function as effective inhibitors of inflammatory responses in the skin. In addition to T cells, they appear to target other inflammatory cells including mast cells, eosinophils and basophils, blocking cytokine production and reducing associated pruritus. This chapter focuses on topical CIs and briefly discusses recent promising developments of topical antiinflammatory agents.

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Author information

Authors and Affiliations

  1. Department of Dermatology, University Hospital Münster, Von-Esmarch-Str. 58, Münster, D-48149, Germany

    Thomas A. Luger MD

  2. Department of Dermatology, University College Dubin, Charles Institute of Dermatology, Dublin, Ireland

    Ian McDonald MB, BCh, BAO

  3. Department of Dermatology and UCD Charles Institute for Dermatology, University College Dublin, Dublin, Ireland

    Martin Steinhoff MD, PhD, FRCPI

Authors
  1. Thomas A. Luger MD
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  2. Ian McDonald MB, BCh, BAO
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  3. Martin Steinhoff MD, PhD, FRCPI
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Corresponding author

Correspondence to Thomas A. Luger MD .

Editor information

Editors and Affiliations

  1. School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA

    Anthony A. Gaspari

  2. Department of Dermatology, University of Texas Health Science Center, Houston, Texas, USA

    Stephen K. Tyring

  3. Department of Dermatology and Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Daniel H. Kaplan

Questions

Questions

  1. 1.

    The following statements describe the actions of calcineurin inhibitors except for?

    1. A.

      Calcineurin inhibitors inhibit the effect of T1 and T2 cytokines in addition to the generation of granulocyte-macrophage colony-stimulating factor

    2. B.

      In contrast to topical glucocorticosteroids, the use of Calcineurin inhibitors is not associated with tachyphylaxis

    3. C.

      Calcineurin inhibitors have a direct affect on fibroblast function including collagen synthesis resulting in skin atrophy

    4. D.

      Unlike glucocorticoids pimecrolimus does not affect the density of epidermal Langerhans cells or affect the keratinocyte or endothelial cell expression of cell adhesion molecules

  2. 2.

    Regarding systemic absorption of calcineurin inhibitors which of the following is NOT true?

    1. A.

      Penetration and permeation of CIs is limited by their molecular weight

    2. B.

      In vitro and pharmacokinetic studies demonstrate that topical application of pimecrolimus results in significant risk of systemic exposure and side effects

    3. C.

      Their lipophilic properties show higher affinity for skin and less potential for systemic absorption compared with other agents

    4. D.

      The concentration of CIs required for a systemic anti-inflammatory affect is 10–15 ng/ml

  3. 3.

    Local adverse affects to TCIs include all of the following except?

    1. A.

      Stinging sensation

    2. B.

      Burning sensation

    3. C.

      Transient itching

    4. D.

      Increased risk of bacterial skin infections

    5. E.

      Onset in the first few days of treatment

  4. 4.

    Which of the following is NOT true regarding the effect of TCIs on itch?

    1. A.

      They are effective in significantly reducing atopic dermatitis associated pruritus within 1 week

    2. B.

      They are effective in treating pruritus associated with nodular prurigo

    3. C.

      Tacrolimus has shown superior efficacy over pimecrolimus with regard to itch scores and onset of action

    4. D.

      Itchy lesions that are often treatment resistant on the face and neck have been shown to respond well to pimecrolimus

    5. E.

      While they have effective antipruritic effects in nodular prurigo they have no effect on the prurigo nodules

  5. 5.

    Which of the following statements regarding the safety of TCIs is NOT true?

    1. A.

      The FDA issued a black box warning regarding a theoretical risk of malignancy including lymphoma with topical CI use in 2006

    2. B.

      There has been no conclusive proof to date to link TCI with malignancy

    3. C.

      Patients should be advised to use UV-protective measures while using TCIs

    4. D.

      Concomitant UV therapy should be avoided

    5. E.

      Animal studies have demonstrated an increased incidence of epidermal and melanocytic skin tumors when topical application of Pimecrolimus was combined with UV-irradiation

  6. 6.

    Which of the following statements is true regarding TCIs?

    1. A.

      Pimecrolimus is available as a 1 % ointment

    2. B.

      Both tacrolimus and pimecrolimus have no effect on rosacea, lichen planus, psoriasis or lichen sclerosis et atrophicans

    3. C.

      Tacrolimus has demonstrated superior and comparable efficacy to topical GCs in the treatment of atopic dermatitis

    4. D.

      Tacrolimus is approved for the treatment of moderate and severe atopic dermatitis in adults only

    5. E.

      Treatment should be stopped once symptomatic control has been achieved

Answers

  1. 1.

    C

  2. 2.

    B

  3. 3.

    D

  4. 4.

    E

  5. 5.

    E

  6. 6.

    C

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Luger, T.A., McDonald, I., Steinhoff, M. (2017). Topical Immune Response Modifiers: Antiinflammatories. In: Gaspari, A., Tyring, S., Kaplan, D. (eds) Clinical and Basic Immunodermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-29785-9_46

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  • DOI: https://doi.org/10.1007/978-3-319-29785-9_46

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  • Online ISBN: 978-3-319-29785-9

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