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Cells to Surgery Quiz: November 2021

  • Author Footnotes
    4 These authors contributed equally to this work.
    Brian Cheng
    Footnotes
    4 These authors contributed equally to this work.
    Affiliations
    School of Medicine, University of South Carolina, Columbia, South Carolina, USA
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  • Author Footnotes
    4 These authors contributed equally to this work.
    Surya Veerabagu
    Footnotes
    4 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, School of Medicine, Tulane University, New Orleans, Louisiana, USA
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  • H. William Higgins II
    Correspondence
    Correspondence: H. William Higgins II, University of Pennsylvania, 3400 Civic Blvd, Philadelphia, Pennsylvania 19104, USA.
    Affiliations
    Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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  • Author Footnotes
    4 These authors contributed equally to this work.

      What is Your Diagnosis?

      Figure thumbnail gr1
      Figure 1
      Image reprinted from
      • Leducq S.
      • Caille A.
      • Le Cleach L.
      • Samimi M.
      • Tavernier E.
      • Maruani A.
      • et al.
      Research techniques made simple: randomized controlled trials for topical drugs in dermatology: when and how should we use a within-person design?.
      with permission from Elsevier.
      Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image shown, while additional questions concern the findings reported in a JID article by
      • Zhai S.
      • Xu M.
      • Li Q.
      • Guo K.
      • Chen H.
      • Kong M.G.
      • Xia Y.
      Successful treatment of vitiligo with cold atmospheric plasma–activated hydrogel.
      (
      • Zhai S.
      • Xu M.
      • Li Q.
      • Guo K.
      • Chen H.
      • Kong M.G.
      • Xia Y.
      Successful treatment of vitiligo with cold atmospheric plasma–activated hydrogel.
      ) (https://doi.org/10.1016/j.jid.2021.04.019).
      Detailed answers and a list of relevant references are available following the Quiz Questions below.

      Quiz Questions

      • 1.
        The picture above pertains to a specific diagnosis mentioned in the study. What is the most likely diagnosis?
        • a.
          Pityriasis versicolor
        • b.
          Psoriasis
        • c.
          Tuberous sclerosis
        • d.
          Vitiligo
        • e.
          Pityriasis alba
      • 2.
        Which of the following is NOT one of the mechanisms through which Cold Atmospheric Plasma (CAP) treatments are hypothesized to treat vitiligo?
        • a.
          CAP treatment induces low-level transient reactive oxygen species that can promote antioxidant mechanisms.
        • b.
          CAP treatment can inhibit excess T-cell activation.
        • c.
          CAP treatment can downregulate proinflammatory genes.
        • d.
          CAP treatment can upregulate anti-inflammatory genes.
        • e.
          CAP treatment can upregulate melanocyte production genes.
      • 3.
        Which of the following statements regarding CAP treatments on vitiligo is false?
        • a.
          Both CAP-activated hydrogel and CAP jet reduced mRNA expression levels for IFN-γ and CXCL10, which are both crucial for vitiligo development.
        • b.
          CAP treatments generate small amounts of transient free radicals, which reduce overall oxidative stress by upregulating endogenous antioxidant expression and downregulating proinflammatory genes.
        • c.
          Only the CAP-activated hydrogel showed a statistically significant reduction in the infiltration of vitiligo lesions by dendritic cells and CD3+ and CD8+ T-cells.
        • d.
          After treatment with either CAP-activated hydrogel or CAP jet, tissue levels of inducible nitric oxide synthase (iNOS) mRNA and protein expression were reduced, although serum levels of iNOS showed no significant difference.
      See following pages for detailed answers

      Detailed Answers

      • 1.
        The picture above pertains to a specific diagnosis mentioned in the study. What is the most likely diagnosis?
      • CORRECT ANSWER: d. Vitiligo
        • Discussion of incorrect answers:
        • a.
          Pityriasis versicolor: Although similar in appearance, pityriasis versicolor is most commonly seen on the chest and upper back. Pityriasis versicolor patches typically also have fine scaling.
        • b.
          Psoriasis: Plaque psoriasis is the most common subtype of psoriasis. The lesions shown in this picture noticeably lack inflammation or scale, both of which are the hallmark characteristics of psoriasis. In addition, plaque psoriasis classically presents on extensor surfaces, not on the lower trunk.
        • c.
          Tuberous sclerosis: Ash leaf spots are a cutaneous manifestation of tuberous sclerosis. These lesions are present at birth and are associated with a wide range of neurological, endocrine, and vascular anomalies. In contrast, vitiligo is an acquired condition that is not present at birth
        • e.
          Pityriasis alba: Pityriasis alba is a mild form of atopic dermatitis (AD) typically seen in children. The condition depicted earlier is not in the typical regions associated with AD, namely the face and extensor surfaces. In addition, pityriasis alba lesions are hypopigmented, not entirely depigmented as shown earlier.
      • 2.
        Which of the following is NOT one of the mechanisms through which Cold Atmospheric Plasma (CAP) treatments are hypothesized to treat vitiligo?
      • CORRECT ANSWER: e. CAP treatment can upregulate melanocyte production genes.
      • There is no mention of melanocyte production genes in this study.
        • Discussion of incorrect answers:
        • a.
          CAP treatment induces low-level transient ROS that can promote antioxidant mechanisms: Option A is true.
        • b.
          CAP treatment can inhibit excess T-cell activation: CAP treatment can inhibit excess T-cell activation through a variety of mechanisms, including by decreasing chemokines that promote T-cell chemotaxis and inhibiting abnormal oxidative stress response.
        • c.
          CAP treatment can downregulate proinflammatory genes: Inducible nitric oxide synthase (iNOS) is a proinflammatory gene that was downregulated in skin lesions treated with CAP.
        • d.
          CAP treatment can upregulate anti-inflammatory genes: Nrf-2 is a transcription factor that is bound under normal conditions and is inactivated. When tissue undergoes an oxidative stress reaction, such as CAP treatment, Nrf-2 is released and induces the production of antioxidant genes, thus making Nrf-2 an important contributor to the anti-inflammatory pathway.
      • 3.
        Which of the following statements regarding CAP treatments on vitiligo is false?
      • CORRECT ANSWER: a. Both CAP-activated hydrogel and CAP jet reduced mRNA expression levels for IFN-γ and CXCL10, which are both crucial for vitiligo development.
      • In the study, it was noted that CAP-activated hydrogel produced a significant reduction in IFN-γ and CXCL10, but this effect was not significant in mice treated with CAP jet.
      • Previous studies using mouse models for vitiligo have noted the importance of IFN-γ and CXCL10 in both progression and maintenance of the diseased state. In one study, CXCL10 neutralization in mice with established, widespread disease showed repigmentation (
        • Rashighi M.
        • Agarwal P.
        • Richmond J.M.
        • Harris T.H.
        • Dresser K.
        • Su M.W.
        • et al.
        CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo.
        ). In another study, autoreactive CD8+ T-cell accumulation was shown to be dependent on IFN-γ production. Neutralization of IFN-γ in these mice prevented CD8+ T-cell accumulation and significantly reduced depigmentation scores (
        • Harris J.E.
        • Harris T.H.
        • Weninger W.
        • Wherry E.J.
        • Hunter C.A.
        • Turka L.A.
        A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8+ T-cell accumulation in the skin.
        ). Taken together, these studies underscore the importance of both IFN-γ and CXCL10 in vitiligo.
        • Discussion of incorrect answers:
        • b.
          CAP treatments generate small amounts of transient free radicals, which reduce overall oxidative stress by upregulating endogenous antioxidant expression and downregulating proinflammatory genes: True. ROS generation in small, physiological quantities is thought to upregulate Nrf-2, a transcription factor for genes related to responding to oxidative stress (
          • Ma Q.
          Role of nrf2 in oxidative stress and toxicity.
          ). This is in contrast to supraphysiological levels, which produce the deleterious effects commonly associated with high oxidative stress (
          • Sies H.
          • Jones D.P.
          Reactive oxygen species (ROS) as pleiotropic physiological signalling agents.
          ).
        • c.
          Only the CAP-activated hydrogel showed a statistically significant reduction in the infiltration of vitiligo lesions by dendritic cells and CD3+ and CD8+ T cells: True. Whereas the CAP-activated hydrogel group showed a significant reduction in dendritic cells and CD3+ and CD8+ T cells compared with control, the CAP jet group only showed a significant reduction in CD8+ T-cell infiltration.
        • d.
          After treatment with either CAP-activated hydrogel or CAP jet, tissue levels of inducible nitric oxide synthase (iNOS) mRNA and protein expression were reduced, although serum levels of iNOS showed no significant difference: True. In both the CAP-activated hydrogel and CAP jet groups, mRNA and protein levels of iNOS were significantly reduced. The generation of peroxynitrite by iNOS is thought to be involved in the pathogenesis of vitiligo, and iNOS expression is elevated in vitiligo lesions (
          • Glassman S.J.
          Vitiligo, reactive oxygen species and T-cells.
          ).

      References

        • Glassman S.J.
        Vitiligo, reactive oxygen species and T-cells.
        Clin Sci (Lond). 2011; 120: 99-120
        • Harris J.E.
        • Harris T.H.
        • Weninger W.
        • Wherry E.J.
        • Hunter C.A.
        • Turka L.A.
        A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8+ T-cell accumulation in the skin.
        J Invest Dermatol. 2012; 132: 1869-1876
        • Leducq S.
        • Caille A.
        • Le Cleach L.
        • Samimi M.
        • Tavernier E.
        • Maruani A.
        • et al.
        Research techniques made simple: randomized controlled trials for topical drugs in dermatology: when and how should we use a within-person design?.
        J Invest Dermatol. 2020; 140: 931-938.e1
        • Ma Q.
        Role of nrf2 in oxidative stress and toxicity.
        Annu Rev Pharmacol Toxicol. 2013; 53: 401-426
        • Rashighi M.
        • Agarwal P.
        • Richmond J.M.
        • Harris T.H.
        • Dresser K.
        • Su M.W.
        • et al.
        CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo.
        Sci Transl Med. 2014; 6: 223ra23
        • Sies H.
        • Jones D.P.
        Reactive oxygen species (ROS) as pleiotropic physiological signalling agents.
        Nat Rev Mol Cell Biol. 2020; 21: 363-383
        • Zhai S.
        • Xu M.
        • Li Q.
        • Guo K.
        • Chen H.
        • Kong M.G.
        • Xia Y.
        Successful treatment of vitiligo with cold atmospheric plasma–activated hydrogel.
        J Invest Dermatol. 2021; 141: 2712-2721