Dermatology Online Journal

Letter: Psoriasis and Down syndrome: A report of three cases and a potential pathophysiologic link
Shana Marmon¹ MD PhD, Aieska De Souza¹ MD, Bruce E Strober² MD PhD
Dermatology Online Journal 18 (6): 13

1. Department of Dermatology, New York University, New York
2. Department of Dermatology, University of Connecticut, Farmington, Connecticut

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Abstract

Psoriasis is thought to result from an influx of Th1 and Th17 cells driven by the production of cytokines such as interferon (IFN)-gamma, IL-2, and tumor necrosis factor (TNF)-alpha elicited by skin immunocytes. We report three cases of patients with chronic plaque psoriasis and concomitant Down syndrome. Although there is no direct link between Down syndrome and the Th17 pathway, there are data supporting a dysregulation of the IFN system in this patient population. The percentage of Th1 lineage cells (IFN-gamma producing CD4+ and CD8+ T cells) is substantially higher in patients with Down syndrome and serum levels of IFN-gamma in patients with Down syndrome are significantly elevated when compared to healthy controls. We propose that people with Down syndrome have a greater prevalence of psoriasis secondary to both high serum levels of and an enhanced sensitivity to IFN-gamma.

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Introduction

We report 3 cases of patients with chronic plaque psoriasis and concomitant Down syndrome. None of these patients had a family history of psoriasis.

Case 1. A 16-year-old boy presented with chronic plaque psoriasis (CPP) since age 6, Down syndrome, diabetes, and hypothyroidism. Examination revealed erythematous, hyperkeratotic patches and plaques involving 10 percent of the body surface area (BSA). The patient was treated with topical calcipotriene and tacrolimus 0.1 percent ointment with marked improvement.

Case 2. A 12-year-old boy presented with CPP since age 9, asthma, and gastroesophageal reflux. Examination revealed erythematous, hyperkeratotic patches and plaques involving 10 percent of the BSA. Adalimumab 40 mg subcutaneous injections every other week was prescribed and after 4 weeks there was marked clinical improvement: physician global assessment (PGA)=1, BSA=1 percent. Adalimumab was continued for 2-years with good disease control.

Case 3. A 20-year-old man presented with a 5-year history of severe CPP, Down syndrome, and tetralogy of Fallot. Examination revealed erythematous scaly patches and plaques covering 25 percent of the BSA, with marked disease activity (PGA=4). The patient was successfully managed by a combination of methotrexate 15 mg weekly and etanercept 50 mg once weekly for 9 months. Owing to lack of efficacy, etanercept was substituted for adalimumab 40 mg every other week, with significantly sustained improvement for the next 3 years.

Down syndrome, which results from an additional copy of chromosome 21, is the most common autosomal chromosomal disorder and one of the leading genetic causes of mental retardation [1]. The incidence of psoriasis in North America is 2-3 percent, whereas it has been reported as high as 8 percent in patients with Down syndrome [2, 6]. Additionally, the concomitant presence of the two disease states has been noted in a number of case studies [3, 4, 5]. Whereas there are numerous cutaneous manifestations associated with Down syndrome – notably palmoplantar hyperkeratosis, xerosis, and seborrheic dermatitis – the link between Down syndrome and psoriasis remains poorly defined [6].

The clinical phenotype of psoriatic lesions is thought to result from an influx of Th1 and Th17 cells driven by the production of cytokines from skin immunocytes [1]. Examination of the cytokine profile of infiltrating CD4 cells isolated from the affected skin of psoriasis patients reveals a heavy predominance of Th1 cytokines such as interferon (IFN)-γ, IL-2, and tumor necrosis factor (TNF)-α [1]. More recent work has suggested a large role for interleukin (IL)-23R and IL17 in the pathogenesis of psoriasis, with psoriatic skin showing elevated levels of IL-23, a cytokine that helps drive Th17 differentiation [7].

Although there is no direct link between Down syndrome and the Th17 pathway, there are data supporting a dysregulation of the IFN system in this patient population [8]. The percentage of Th1 lineage cells (IFN-γ producing CD4+ and CD8+ T cells) is substantially higher in patients with Down syndrome and serum levels of IFN-γ in patients with Down syndrome are significantly elevated when compared to healthy controls [9]. Aberrant regulation of IFN-γ in Down syndrome derives from the genotype of the disease. Signal transduction in response to IFN-γ requires the binding to its receptor IFNGR-1, the gene of which is located on the long arm of chromosome 6, and an accessory factor, IFNGR-2, encoded on chromosome 21. In fact, chromosome 21 ploidy results in increased responsiveness to IFN, with additional copies of chromosome 21 conferring increased IFN sensitivity [10]. We propose that people with Down syndrome have a greater prevalence of psoriasis secondary to both high serum levels of and an enhanced sensitivity to IFN-γ. Further research is necessary to test this hypothesis.

References

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10. Maroun LE: Interferon effect on ribosomal ribonucleic acid related to chromosome 21 ploidy. Biochem J (179): 221-225, 1979. [PubMed]

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