- 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.
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- Gilliam JN, Sontheimer RD. Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol 1981;4:471–5.
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- 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.
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- 1.What is your diagnosis?
- a)Lichen planus
- b)Tinea corporis
- 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.
- 1.What is your diagnosis?
- a)Lichen planus is a mucocutaneous inflammatory disease of unknown origin (Le Cleach and Chosidow, 2012). 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 et al., 2011).
- b)Tinea is a group of fungal infections caused by dermatophyte species: Trichophyton, Epidermophyton, and Microsporum (Gupta et al., 2003). 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, 2007).
- d)Cutaneous findings in lupus erythematosis encompass a broad spectrum and can appear with or without systemic involvement (Lee and Sinha, 2006). 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 and Sontheimer, 1981), 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 et al., 2014). 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 and Higgins, 2010).
- 2.Which one of the following statements is TRUE?
- 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 et al., 2014). 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 et al., 2014).
- 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 et al., 2015). However, contrary to this report, metabolic syndrome, which includes central obesity, dyslipidemia, hypertension, and insulin resistance, has long been associated with psoriatic disease (Shahwan and Kimball, 2015). 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 and Vasan, 2013). 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 (
Brief Review: Genetics of coronary artery disease.Circulation. 2013; 128https://doi.org/10.1161/CIRCULATIONAHA.113.005350Koch et al., 2015).
- Lieb W.
- Vasan R.S.
- 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 et al., 2015). The AAD also recommends avoidance of anti-TNF-α therapy in patients with first-degree relatives with MS (Menter et al., 2008). 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 et al., 2000). 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?
- 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 et al., 2015).
- 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 and Tasc, 2007). 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 et al., 2007). Separately, the same rs11209026 SNP may increase susceptibility to MS and Crohn's Disease (Nunez et al., 2008).
- 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 and Hentges, 1991). 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 et al., 1999). 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 et al., 2008).
- SnapshotDx Quiz: January 2016: Answers
- Quiz Answers
- TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study.Neurology. 1999; 53: 457-465
- Tumor necrosis factor stimulates expression of CXCL12 in astrocytes.Immunobiology. 2015; 220: 845-850
- Autoimmune disease in first-degree relatives of patients with multiple sclerosis. A UK survey.Brain : a journal of neurology. 2000; 123: 1102-1111
- 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
- Risk of Multiple Sclerosis in Patients with Psoriasis: A Danish Nationwide Cohort Study.J Invest Dermatol. 2015;
- The genetics of psoriasis 2001: the odyssey continues.Archives of dermatology. 2001; 137: 1447-1454
- 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
- Distinctive cutaneous subsets in the spectrum of lupus erythematosus.Journal of the American Academy of Dermatology. 1981; 4: 471-475
- Tinea corporis, tinea cruris, tinea nigra, and piedra.Dermatologic clinics. 2003; 21 (v): 395-400
- Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures.The Journal of investigative dermatology. 2015; 135: 1283-1293
- Palmoplantar lesions in psoriasis: a study of 3065 patients.Acta dermato-venereologica. 2002; 82: 192-195
- Clinical practice. Lichen planus.The New England journal of medicine. 2012; 366: 723-732
- Cutaneous lupus erythematosus: understanding of clinical features, genetic basis, and pathobiology of disease guides therapeutic strategies.Autoimmunity. 2006; 39: 433-444
- Brief Review: Genetics of coronary artery disease.Circulation. 2013; 128https://doi.org/10.1161/CIRCULATIONAHA.113.005350
- Interleukin 17A: toward a new understanding of psoriasis pathogenesis.Journal of the American Academy of Dermatology. 2014; 71: 141-150
- 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
- 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
- CXCL12 in control of neuroinflammation.Immunologic research. 2012; 52: 53-63
- Molecular biology of atopic dermatitis.Clinical reviews in allergy & immunology. 2014; 47: 193-218
- Secondary syphilis: the classical triad of skin rash, mucosal ulceration and lymphadenopathy.International journal of STD & AIDS. 2010; 21: 537-545
- IL23R: a susceptibility locus for celiac disease and multiple sclerosis?.Genes Immun. 2008; 9: 289-293
- Primary and secondary syphilis--United States, 20052013.MMWR Morbidity and mortality weekly report. 2014; 63: 402-406
- Tumor necrosis factor is elevated in progressive multiple sclerosis and causes excitotoxic neurodegeneration.Multiple sclerosis (Houndmills, Basingstoke, England). 2014; 20: 304-312
- WICKHAM STRIAE: ETIOPATHOGENENSIS AND CLINICAL SIGNIFICANCE.Indian Journal of Dermatology. 2011; 56: 442-443
- Psoriasis and Cardiovascular Disease.The Medical clinics of North America. 2015; 99: 1227-1242
- Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis.The New England journal of medicine. 1991; 325: 467-472
- Tinea corporis and tinea capitis.Pediatrics in review / American Academy of Pediatrics. 2007; 28: 164-174
- 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
- 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
- Development, cytokine profile and function of human interleukin 17-producing helper T cells.Nature immunology. 2007; 8: 950-957
- Association scan of 14,500 nsSNPs in four common diseases identifies variants involved in autoimmunity.Nature genetics. 2007; 39: 1329-1337
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