Advertisement

SnapshotDx Quiz: January 2016

  • Alyx Rosen
    Affiliations
    Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida
    Search for articles by this author
  • Mariya Miteva
    Correspondence
    Correspondence: Mariya Miteva, Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, 1600 NW 10th Ave, RMSB 2023A, Miami, Florida 33136, USA.
    Affiliations
    Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida
    Search for articles by this author
      Editorial note: Welcome to the Journal of Investigative Dermatology (JID) SnapshotDx Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image found below, while additional questions concern the findings reported in a JID article by Alexander Egeberg et al. (http://dx.doi.org/10.1038/JID.2015.350).
      Figure 1
      Figure 1
      Image courtesy of Mariya Miteva, University of Miami

      References

      • Arnason B, Jacobs G, Hanlo M, Clay B, Noronha A, Auty A. TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. Neurology 1999;53:457–65.
      • Blaževski J, Petković F, Momčilović M, Jevtić B, Stojković MM, Miljković D. Tumor necrosis factor stimulates expression of CXCL12 in astrocytes. Immunobiology 2015;220:845–50.
      • Broadley SA, Deans J, Sawcer SJ, et al. Autoimmune disease in first-degree relatives of patients with multiple sclerosis. A UK survey. Brain 2000;123:1102–11.
      • Cargill M, Schrodi Steven J, Chang M, Garcia V, Brandon R, Callis K, et al. A Large-Scale Genetic Association Study Confirms IL12B and Leads to the Identification of IL23R as Psoriasis-Risk Genes. Am J Hum Genet 2007;80:273–390.
      • Egeberg A, Mallbris L, Gislason GH, Skov L, Hansen PR. Risk of Multiple Sclerosis in Patients with Psoriasis: A Danish Nationwide Cohort Study. J Invest Dermatol 2016;136:93–8.
      • Elder JT, Nair RP, Henseler T, Jenisch S, Stuart P, Chia N, et al. The genetics of psoriasis 2001: the odyssey continues. Arch Dermatol 2001;137:1447–54.
      • Farley E, Masrour S, McKey J, Menter A. Palmoplantar psoriasis: a phenotypical and clinical review with introduction of a new quality-of-life assessment tool. J Am Acad Dermatol 2009;60:1024–31.
      • Gilliam JN, Sontheimer RD. Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol 1981;4:471–5.
      • Gupta AK, Chaudhry M, Elewski B. Tinea corporis, tinea cruris, tinea nigra, and piedra. Dermatol Clin 2003;21:395–400.
      • Koch M, Baurecht H, Ried JS, Rodriguez E, Schlesinger S, Volks N, et al. Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures. J Invest Dermatol 2015;135:1283–93.
      • Kumar B, Saraswat A, Kaur I. Palmoplantar lesions in psoriasis: a study of 3065 patients. Acta Derm Venereol 2002;82:192–5.
      • Le Cleach L, Chosidow O. Clinical practice. Lichen planus. N Engl J Med 2012;366:723–32.
      • Lee HJ, Sinha AA. Cutaneous lupus erythematosus: understanding of clinical features, genetic basis, and pathobiology of disease guides therapeutic strategies. Autoimmunity 2006;39:433–44.
      • Lieb W, Vasan RS. Brief Review: Genetics of coronary artery disease. Circulation 2013;128:1131–8.
      • Lynde CW, Poulin Y, Vender R, Vender R, Bourcier M, Khalil S. Interleukin 17A: toward a new understanding of psoriasis pathogenesis. J Am Acad Dermatol 2014;71:141–50.
      • Mansouri B, Horner ME, Menter A. Tumor Necrosis Factor-alpha inhibitor use in psoriasis patients with a first-degree relative with multiple sclerosis. J Drugs Dermatol 2015;14:876–8.
      • Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008;58:826–50.
      • Momcilovic M, Mostarica-Stojkovic M, Miljkovic D. CXCL12 in control of neuroinflammation. Immunol Res 2012;52:53–63.
      • Mu Z, Zhao Y, Liu X, Chang C, Zhang J. Molecular biology of atopic dermatitis. Clin Rev Allergy Immunol 2014;47:193–218.
      • Mullooly C, Higgins SP. Secondary syphilis: the classical triad of skin rash, mucosal ulceration and lymphadenopathy. Int J STD AIDS 2010;21:537–45.
      • Nunez C, Dema B, Cenit MC, Polanco I, Maluenda C, Arroyo R, et al. IL23R: a susceptibility locus for celiac disease and multiple sclerosis? Genes Immun 2008;9:289–93.
      • Patton ME, Su JR, Nelson R, Weinstock H. Primary and secondary syphilis--United States, 2005-2013. MMWR Morb Mortal Wkly Rep 2014;63:402–6.
      • Rossi S, Motta C, Studer V, Barbieri F, Buttari F, Bergami A, et al. Tumor necrosis factor is elevated in progressive multiple sclerosis and causes excitotoxic neurodegeneration. Mult Scler 2014;20:304–12.
      • Sachdeva S, Sachdeva S, Kapoor P. Wickham Striae: etiopathogenensis and clinical significance. Indian J Dermatol 2011;56:442–3.
      • Shahwan KT, Kimball AB. Psoriasis and cardiovascular disease. Med Clin North Am 2015;99:1227–42.
      • Sharief MK, Hentges R. Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis. N Engl J Med 1991;325:467–72.
      • Shy R. Tinea corporis and tinea capitis. Pediatr Rev 2007;28:164–74.
      • Taoufik E, Tseveleki V, Chu SY, Tselios T, Karin M, Lassman H, et al. Transmembrane tumour necrosis factor is neuroprotective and regulates experimental autoimmune encephalomyelitis via neuronal nuclear factor-kappaB. Brain 2011;134:2722–35.
      • Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, et al. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 2008;172:146–55.
      • Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 2007;8:950–7.
      • Wtccc, Tasc. Association scan of 14,500 nsSNPs in four common diseases identifies variants involved in autoimmunity. Nat Genet 2007;39:1329–37.
      Detailed answers and a list of relevant references are available following the Quiz Questions below.

      Quiz Questions

      • 1.
        What is your diagnosis?
        • a)
          Lichen planus
        • b)
          Tinea corporis
        • c)
          Psoriasis
        • d)
          Subacute cutaneous lupus erythematosus
        • e)
          Secondary syphilis
      • 2.
        Which one of the following statements is TRUE?
        • a)
          Psoriasis and atopic dermatitis are characterized by an altered Th1/Th17 immunological response.
        • b)
          Patients with psoriasis do not have a higher prevalence of metabolic syndrome compared to the general population.
        • c)
          It has been shown that psoriasis shares genetic risk loci with type 2 diabetes and myocardial infarction.
        • d)
          The American Academy of Dermatology currently recommends not to use TNF-α inhibitors in patients with psoriasis who have second degree relative(s) with MS.
        • e)
          TNF produced in central nervous system plays a protective role in neuroinflammation by increasing the expression of CXCL12 in astrocytes.
      • 3.
        Based on the current study by Egenberg et al., which one of the following statements is FALSE?
        • a)
          Psoriasis carries an independent disease severity-dependent risk for developing MS.
        • b)
          Patients with mild psoriasis have significantly increased risk of MS.
        • c)
          Both psoriasis and MS share genetic similarities such as polymorphism of the IL23 R gene on chromosome 1.
        • d)
          Increased levels of IL17 have been detected in psoriasis plaques but not in MS plaques.
        • e)
          Patients with MS have shown immune activation and disease exacerbation following treatment with anti-TNF-α agents in trials.
      See following pages for detailed answers.

      Detailed Answers

      • 1.
        What is your diagnosis?
      The correct answer is: (c) Psoriasis.
      Psoriasis is a chronic, inflammatory, hyperproliferative disease of the skin and joints that affects 2% of the US population (
      • Elder J.T.
      • Nair R.P.
      • Henseler T.
      • et al.
      The genetics of psoriasis 2001: the odyssey continues.
      ). It has a variety of clinical presentations, with the most classic appearance demonstrated in the clinical photograph. Multiple well-demarcated erythematous plaques with adherent micaceous scale can be appreciated. The most common sites affected are the scalp, elbows, knees, and presacrum, in addition to the palms and soles. In the photograph, thick hyperkeratotic plaques on the right heel can also be appreciated. The morphology of palmoplantar psoriasis is often classic sharply demarcated, red scaling plaques that stop at the palm-wrist junction (
      • Kumar B.
      • Saraswat A.
      • Kaur I.
      Palmoplantar lesions in psoriasis: a study of 3065 patients.
      ). Predominantly pustular lesions to thick, hyperkeratotic plaques, with a spectrum of overlap can also occur (
      • Farley E.
      • Masrour S.
      • McKey J.
      • et al.
      Palmoplantar psoriasis: a phenotypical and clinical review with introduction of a new quality-of-life assessment tool.
      ).
      Discussion of Incorrect Answers
      • a)
        Lichen planus is a mucocutaneous inflammatory disease of unknown origin (
        • Le Cleach L.
        • Chosidow O.
        Clinical practice. Lichen planus.
        ). The genitalia, esophagus, conjunctiva, hair and nails can also be affected. Cutaneous lichen planus often presents as erythematous to violaceous, pruritic, flat-topped papules that may have a polygonal form. The flexural areas are preferentially involved, especially the flexural aspect of the wrist. Wickham striae are seen as fine, white or grey lines on top of the purple papules (
        • Sachdeva S.
        • Sachdeva S.
        • Kapoor P.
        WICKHAM STRIAE: ETIOPATHOGENENSIS AND CLINICAL SIGNIFICANCE.
        ).
      • b)
        Tinea is a group of fungal infections caused by dermatophyte species: Trichophyton, Epidermophyton, and Microsporum (
        • Gupta A.K.
        • Chaudhry M.
        • Elewski B.
        Tinea corporis, tinea cruris, tinea nigra, and piedra.
        ). In the US, it is the second most frequently reported skin disease after acne. Infection occurs through contact with infected humans, animals, soil, or inanimate objects. Tinea corporis presents on glabrous skin as annular, red, scaly plaques with active erythematous borders and central clearing (
        • Shy R.
        Tinea corporis and tinea capitis.
        ).
      • d)
        Cutaneous findings in lupus erythematosis encompass a broad spectrum and can appear with or without systemic involvement (
        • Lee H.J.
        • Sinha A.A.
        Cutaneous lupus erythematosus: understanding of clinical features, genetic basis, and pathobiology of disease guides therapeutic strategies.
        ). Subacute cutaneous lupus erythematosis (SCLE) typically presents in the third or fourth decade, and women are 3-4 times more likely to be affected than men. Clinically, it appears as erythematous macules or papules that develop into annular, polycyclic or psoriasiform plaques (
        • Gilliam J.N.
        • Sontheimer R.D.
        Distinctive cutaneous subsets in the spectrum of lupus erythematosus.
        ), mostly distributed over the sun exposed sites of the neck, upper trunk and arms.
      • e)
        Syphilis is a sexually transmitted infection caused by Treponema pallidum. After years of declining rates in developed countries, syphilis has re-emerged as a major public health problem over the past decade (
        • Patton M.E.
        • Su J.R.
        • Nelson R.
        • et al.
        Primary and secondary syphilis--United States, 20052013.
        ). Clinically, syphilis occurs in multiple stages, with secondary syphilis resulting from widespread vascular and lymphatic dissemination of the spirochete. It can affect the skin, lymph glands, and mucosal membranes. The rash of secondary syphilis tends to be symmetrical and generalized. Papular lesions involve the palms, soles, and face. They are rounded and brownish and measure a few millimeters up to a centimeter in size. Often a collarette scale may appear at the margins (
        • Mullooly C.
        • Higgins S.P.
        Secondary syphilis: the classical triad of skin rash, mucosal ulceration and lymphadenopathy.
        ).
      • 2.
        Which one of the following statements is TRUE?
      The correct answer is choice (e) TNF produced in central nervous system plays a protective role in neuroinflammation by increasing the expression of CXCL12 in astrocytes.
      Tumor necrosis factor (TNF) is a pluripotent cytokine that has a dual role in the pathogenesis of multiple sclerosis (MS). On the one hand it mediates harmful inflammatory effects on the CNS tissue (
      • Rossi S.
      • Motta C.
      • Studer V.
      • et al.
      Tumor necrosis factor is elevated in progressive multiple sclerosis and causes excitotoxic neurodegeneration.
      ), but on the other, it provides neuroprotection and remyelination in MS and its animal model experimental autoimmune encephalomyelitis (EAE) (
      • Taoufik E.
      • Tseveleki V.
      • Chu S.Y.
      • et al.
      Transmembrane tumour necrosis factor is neuroprotective and regulates experimental autoimmune encephalomyelitis via neuronal nuclear factor-kappaB.
      ). The divergent effects are based on interactions with different TNF receptors. Astrocytes are major cell components of the blood-brain barrier, and they play an important role in the pathogenesis of MS and EAE. They also produce several cytokines and chemokines, including CXCL12 (
      • Blaževski J.
      • Petković F.
      • Momčilović M.
      • et al.
      Tumor necrosis factor stimulates expression of CXCL12 in astrocytes.
      ). Within the central nervous System specifically, CXCL12 prevents leukocyte egress into the CNS parenchyma and promotes immunoregulatory mechanisms (
      • Momcilovic M.
      • Mostarica-Stojkovic M.
      • Miljkovic D.
      CXCL12 in control of neuroinflammation.
      ). Recently, TNF has been positively correlated with CXCL12 expression in astrocytes, thus contributing to a protective role in neuroinflammation (
      • Blaževski J.
      • Petković F.
      • Momčilović M.
      • et al.
      Tumor necrosis factor stimulates expression of CXCL12 in astrocytes.
      ).
      Discussion of Incorrect Answers
      • a)
        Atopic dermatitis (AD) and psoriasis are both chronic immune-mediated inflammatory disorders. T lymphocytes are critical for the development of cell-mediated immune responses, mainly through secretion of specific effector cytokines. Molecular, immunohistochemical, and clinical data have demonstrated that T helper (Th)-1 and more so Th17 cells drive the inflammatory pathways in psoriasis with interleukin (IL)-17A as the principal effector cytokine of Th17 cells (
        • Lynde C.W.
        • Poulin Y.
        • Vender R.
        • et al.
        Interleukin 17A: toward a new understanding of psoriasis pathogenesis.
        ). In contrast, a predominant early Th2 cell phenotype with increased levels of Th2 cytokines, including IL4, IL-5, and IL-13, is considered a primary reason for AD pathogenesis (
        • Mu Z.
        • Zhao Y.
        • Liu X.
        • et al.
        Molecular biology of atopic dermatitis.
        ).
      • b)
        Epidemiologic data regarding the association of psoriasis and cardiometabolic disease are inconsistent. Koch et al recently demonstrated in a combined cross-sectional and prospective cohort study that psoriasis was statistically significantly associated with type 2 diabetes, myocardial infarction, and waist circumference, but not with hypertension, metabolic syndrome, angina pectoris, or peripheral arterial disease (
        • Koch M.
        • Baurecht H.
        • Ried J.S.
        • et al.
        Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures.
        ). However, contrary to this report, metabolic syndrome, which includes central obesity, dyslipidemia, hypertension, and insulin resistance, has long been associated with psoriatic disease (
        • Shahwan K.T.
        • Kimball A.B.
        Psoriasis and Cardiovascular Disease.
        ). Psoriasis is a systemic inflammatory disease, and its association with metabolic derangements and adverse cardiovascular outcomes continues to be a significant focus of research.
      • c)
        Results from candidate gene studies have previously suggested that some genetic variants associated with inflammatory disease may also predispose to cardiovascular and metabolic disease (
        • Lieb W.
        • Vasan R.S.
        Brief Review: Genetics of coronary artery disease.
        ). In a recent German cross-sectional study and prospective cohort study, investigators used genome-wide association studies and Metabochip® custom arrays to identify a potential genetic overlap between psoriasis and cardiometabolic disease. Results demonstrated insignificant association between established psoriasis risk polymorphisms and coronary artery disease risk. Additionally, validated genetic loci for cardiometabolic traits did not impact psoriasis risk (
        • Koch M.
        • Baurecht H.
        • Ried J.S.
        • et al.
        Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures.
        ).
      • d)
        The American Academy of Dermatology (AAD), European S3, and British Association of Dermatologists recommend avoidance of TNF-α inhibitor in patients with MS due to the well- established increase in MS exacerbations in patients on anti-TNF-α therapy (
        • Mansouri B.
        • Horner M.E.
        • Menter A.
        Tumor Necrosis Factor-alpha Inhibitor Use in Psoriasis Patients With a First-degree Relative With Multiple Sclerosis.
        ). The AAD also recommends avoidance of anti-TNF-α therapy in patients with first-degree relatives with MS (
        • Menter A.
        • Gottlieb A.
        • Feldman S.R.
        • et al.
        Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 3. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics.
        ). The AAD working group cites a United Kingdom survey, which showed an increased risk of psoriasis in families of patients with MS. The association with psoriasis was even higher in families with more than one case of MS (
        • Broadley S.A.
        • Deans J.
        • Sawcer S.J.
        • et al.
        Autoimmune disease in first-degree relatives of patients with multiple sclerosis. A UK survey.
        ). However, there are no recommendations regarding the use of TNF-α inhibitors in patients with psoriasis and second-degree relatives with MS.
      • 3.
        Based on the current study by Egenberg et al., which one of the following statements is FALSE?
      The correct answer is choice d) Patients with MS have shown immune activation and disease exacerbation following treatment with anti-TNF-α agents in trials.
      Using the EAE animal model for experimental MS, expression of IL-17 mRNA and protein is demonstrated in astrocytes and oligodendrocytes and correlated with increased labeling of IL-17 in both CD4+ and CD8+ T cells in active areas of MS lesions (
      • Tzartos J.S.
      • Friese M.A.
      • Craner M.J.
      • et al.
      Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis.
      ). Similarly, Wilson et al demonstrate significantly higher expression of IL-17 in plaque lesions of patients with psoriasis compared with non-lesional or healthy skin (
      • Wilson N.J.
      • Boniface K.
      • Chan J.R.
      • et al.
      Development, cytokine profile and function of human interleukin 17-producing helper T cells.
      ).
      Discussion of Incorrect Answers
      • a & b)
        Recent findings of a nationwide Danish population-based study with >5,000,000 individuals demonstrate that psoriasis is an independent risk factor for MS. Both patients with mild and severe psoriasis in the study demonstrated a significantly increased risk of MS with incidence rate ratios of 1.84 and 2.61 for patients with mild and severe psoriasis, respectively. Moreover, the risk of MS was significantly different between patients with mild and severe psoriasis overall and when separated between males and females, thus demonstrating a disease severity-dependent risk of MS. In the study, severe psoriasis was defined as receiving systemic treatment consistent with severe disease, including biologic therapies such as TNF inhibitors, cyclosporine, hydroxyurea, psoralens, retinoids, or methotrexate (
        • Egeberg A.
        • Mallbris L.
        • Gislason G.H.
        • et al.
        Risk of Multiple Sclerosis in Patients with Psoriasis: A Danish Nationwide Cohort Study.
        ).
      • c)
        IL23 is a proinflammatory cytokine that plays a key role in several chronic immune-mediated inflammatory diseases, including psoriasis. The IL23R gene encodes a unique protein subunit of the IL23 receptor, which pairs with the IL12Rβ1 subunit, and triggers downstream signaling when IL23 is bound (
        • Wtccc
        • Tasc
        Association scan of 14,500 nsSNPs in four common diseases identifies variants involved in autoimmunity.
        ). IL23R is located on chromosome 1 at position 31.3. Genetic polyphormisms in IL23R have been documented in several diseases including Crohn's Disease, psoriasis, and ankylosing spondylitis. Specifically, in psoriasis the single- nucleotide polymorphism (SNP) rs11209026, in combination with rs7530511, is associated with increased psoriasis risk (
        • Cargill M.
        • Schrodi Steven J.
        • Chang M.
        • et al.
        A Large-Scale Genetic Association Study Confirms IL12B and Leads to the Identification of IL23R as Psoriasis-Risk Genes.
        ). Separately, the same rs11209026 SNP may increase susceptibility to MS and Crohn's Disease (
        • Nunez C.
        • Dema B.
        • Cenit M.C.
        • et al.
        IL23R: a susceptibility locus for celiac disease and multiple sclerosis?.
        ).
      • e)
        MS has a significant autoimmune T cell-mediated component, and studies have shown that patients with chronic progressive MS have significantly higher cerebrospinal fluid (CSF) levels of TNFα than serum levels. Additionally, CSF levels of TNFα correlate with MS disease severity and progression of disease (
        • Sharief M.K.
        • Hentges R.
        Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis.
        ). In contrast, a randomized, double-blind, placebo-controlled phase II study in patients mostly with relapsing-remitting MS treated with lenercept versus placebo showed that patients treated with lenercept experienced a greater number of and earlier MS exacerbations and more severe neurologic deficits, compared with placebo-treated patients. Lenercept is a TNF receptor fusion protein (
        • Arnason B.
        • Jacobs G.
        • Hanlo M.
        • et al.
        TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study.
        ). Therefore, anti-TNFα agents are contraindicated in patients with preexisting demyelinating disease, and the American Academy of Dermatology working group recommends avoidance of anti-TNFα therapy in patients with MS (
        • Menter A.
        • Gottlieb A.
        • Feldman S.R.
        • et al.
        Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 3. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics.
        ).

      Supplementary Material

      Referenecs

        • Arnason B.
        • Jacobs G.
        • Hanlo M.
        • et al.
        TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study.
        Neurology. 1999; 53: 457-465
        • Blaževski J.
        • Petković F.
        • Momčilović M.
        • et al.
        Tumor necrosis factor stimulates expression of CXCL12 in astrocytes.
        Immunobiology. 2015; 220: 845-850
        • Broadley S.A.
        • Deans J.
        • Sawcer S.J.
        • et al.
        Autoimmune disease in first-degree relatives of patients with multiple sclerosis. A UK survey.
        Brain : a journal of neurology. 2000; 123: 1102-1111
        • Cargill M.
        • Schrodi Steven J.
        • Chang M.
        • et al.
        A Large-Scale Genetic Association Study Confirms IL12B and Leads to the Identification of IL23R as Psoriasis-Risk Genes.
        American Journal of Human Genetics. 2007; 80: 273-390
        • Egeberg A.
        • Mallbris L.
        • Gislason G.H.
        • et al.
        Risk of Multiple Sclerosis in Patients with Psoriasis: A Danish Nationwide Cohort Study.
        J Invest Dermatol. 2015;
        • Elder J.T.
        • Nair R.P.
        • Henseler T.
        • et al.
        The genetics of psoriasis 2001: the odyssey continues.
        Archives of dermatology. 2001; 137: 1447-1454
        • Farley E.
        • Masrour S.
        • McKey J.
        • et al.
        Palmoplantar psoriasis: a phenotypical and clinical review with introduction of a new quality-of-life assessment tool.
        Journal of the American Academy of Dermatology. 2009; 60: 1024-1031
        • Gilliam J.N.
        • Sontheimer R.D.
        Distinctive cutaneous subsets in the spectrum of lupus erythematosus.
        Journal of the American Academy of Dermatology. 1981; 4: 471-475
        • Gupta A.K.
        • Chaudhry M.
        • Elewski B.
        Tinea corporis, tinea cruris, tinea nigra, and piedra.
        Dermatologic clinics. 2003; 21 (v): 395-400
        • Koch M.
        • Baurecht H.
        • Ried J.S.
        • et al.
        Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures.
        The Journal of investigative dermatology. 2015; 135: 1283-1293
        • Kumar B.
        • Saraswat A.
        • Kaur I.
        Palmoplantar lesions in psoriasis: a study of 3065 patients.
        Acta dermato-venereologica. 2002; 82: 192-195
        • Le Cleach L.
        • Chosidow O.
        Clinical practice. Lichen planus.
        The New England journal of medicine. 2012; 366: 723-732
        • Lee H.J.
        • Sinha A.A.
        Cutaneous lupus erythematosus: understanding of clinical features, genetic basis, and pathobiology of disease guides therapeutic strategies.
        Autoimmunity. 2006; 39: 433-444
        • Lieb W.
        • Vasan R.S.
        Brief Review: Genetics of coronary artery disease.
        Circulation. 2013; 128https://doi.org/10.1161/CIRCULATIONAHA.113.005350
        • Lynde C.W.
        • Poulin Y.
        • Vender R.
        • et al.
        Interleukin 17A: toward a new understanding of psoriasis pathogenesis.
        Journal of the American Academy of Dermatology. 2014; 71: 141-150
        • Mansouri B.
        • Horner M.E.
        • Menter A.
        Tumor Necrosis Factor-alpha Inhibitor Use in Psoriasis Patients With a First-degree Relative With Multiple Sclerosis.
        Journal of drugs in dermatology : JDD. 2015; 14: 876-878
        • Menter A.
        • Gottlieb A.
        • Feldman S.R.
        • et al.
        Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 3. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics.
        Journal of the American Academy of Dermatology. 2008; 58: 826-850
        • Momcilovic M.
        • Mostarica-Stojkovic M.
        • Miljkovic D.
        CXCL12 in control of neuroinflammation.
        Immunologic research. 2012; 52: 53-63
        • Mu Z.
        • Zhao Y.
        • Liu X.
        • et al.
        Molecular biology of atopic dermatitis.
        Clinical reviews in allergy & immunology. 2014; 47: 193-218
        • Mullooly C.
        • Higgins S.P.
        Secondary syphilis: the classical triad of skin rash, mucosal ulceration and lymphadenopathy.
        International journal of STD & AIDS. 2010; 21: 537-545
        • Nunez C.
        • Dema B.
        • Cenit M.C.
        • et al.
        IL23R: a susceptibility locus for celiac disease and multiple sclerosis?.
        Genes Immun. 2008; 9: 289-293
        • Patton M.E.
        • Su J.R.
        • Nelson R.
        • et al.
        Primary and secondary syphilis--United States, 20052013.
        MMWR Morbidity and mortality weekly report. 2014; 63: 402-406
        • Rossi S.
        • Motta C.
        • Studer V.
        • et al.
        Tumor necrosis factor is elevated in progressive multiple sclerosis and causes excitotoxic neurodegeneration.
        Multiple sclerosis (Houndmills, Basingstoke, England). 2014; 20: 304-312
        • Sachdeva S.
        • Sachdeva S.
        • Kapoor P.
        WICKHAM STRIAE: ETIOPATHOGENENSIS AND CLINICAL SIGNIFICANCE.
        Indian Journal of Dermatology. 2011; 56: 442-443
        • Shahwan K.T.
        • Kimball A.B.
        Psoriasis and Cardiovascular Disease.
        The Medical clinics of North America. 2015; 99: 1227-1242
        • Sharief M.K.
        • Hentges R.
        Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis.
        The New England journal of medicine. 1991; 325: 467-472
        • Shy R.
        Tinea corporis and tinea capitis.
        Pediatrics in review / American Academy of Pediatrics. 2007; 28: 164-174
        • Taoufik E.
        • Tseveleki V.
        • Chu S.Y.
        • et al.
        Transmembrane tumour necrosis factor is neuroprotective and regulates experimental autoimmune encephalomyelitis via neuronal nuclear factor-kappaB.
        Brain : a journal of neurology. 2011; 134: 2722-2735
        • Tzartos J.S.
        • Friese M.A.
        • Craner M.J.
        • et al.
        Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis.
        The American journal of pathology. 2008; 172: 146-155
        • Wilson N.J.
        • Boniface K.
        • Chan J.R.
        • et al.
        Development, cytokine profile and function of human interleukin 17-producing helper T cells.
        Nature immunology. 2007; 8: 950-957
        • Wtccc
        • Tasc
        Association scan of 14,500 nsSNPs in four common diseases identifies variants involved in autoimmunity.
        Nature genetics. 2007; 39: 1329-1337