JEADV

LETTERS TO THE EDITOR

Hyaluronic acid in psoriasis Editor I read with interest the research article by Chladek et al.1 in the August issue of 2013, which suggested that serum hyaluronic acid levels reflected psoriasis activity rather than the marker of liver fibrosis, apart from N-terminal propeptide of collagen type III (PIIINP) and Fibrotest. Previously, we reported that serum hyaluronic acid concentrations were significantly elevated in patients with severe cutaneous psoriasis such as generalized pustular psoriasis.2 The patients we examined had neither been treated with methotrexate nor suffered from liver fibrosis, which indicate that serum hyaluronic acid are attributed to the cutaneous inflammation, not liver damage. Additionally, recent studies have also suggested that serum hyaluronic acid did not correlate with joint inflammation in psoriatic arthritis.3 Recent progress has demonstrated that hyaluronan is an important immune regulator in various diseases. In particular, low molecular weight hyaluronan is a ligand for toll-like receptors (TLRs), and induces inflammatory cytokine gene expression. TLRs play an important role in the innate immune responses, and in psoriasis, activation of TLR7 and TLR9 via autoimmune plasmacytoid dendritic cell activation releases interferon-a, which further stimulates Tip-DC (tumour necrosis factor-a and inducible nitric oxide synthase-producing dendritic cell) to secret IL-23. Additionally, other TLRs, i.e. TLR2 and TLR4, are also involved in the pathogenesis of psoriasis of plaque and guttate type,4, 5 as well as psoriatic arthritis.6 Hyaluronic acid is abundant in the psoriatic skin and hyaluronan fragments signal through TLR4 and TLR2. CD44, a major cell-surface hyaluronic acid binding protein, is expressed on T cells. Ligation of CD44 on T cells and neutrophils induces IL-6 secretion and inflammation.7 Although role of TLRs in pustular psoriasis is still unclear, triggering factors of pustular psoriasis such as infection, drug and pregnancy may activate TLRs expression. Alternatively, CD44-hyaluronan interactions may lead to systemic inflammation in pustular psoriasis. T. Yamamoto* Department of Dermatology, Fukushima Medical University, Fukushima, Japan *Correspondence: T. Yamamoto. E-mail: [email protected]

References

1 Chladek J, Simkova M, Vaneckova J et al. Assessment of methotrexate hepatotoxicity in psoriasis patients: a prospective evaluation of four serum fibrosis markers. J Eur Acad Dermatol Venereol 2013; 27: 1007– 1014.

JEADV 2015, 29, 2487–2499

2 Yamamoto T, Matsuuchi M, Irimajiri J et al. Elevated circulating hyaluronan in patients with generalized pustular psoriasis. Eur J Dermatol 1997; 7: 409–411. 3 Lindqvist U, Pihl-Lundin I, Engstr€ om-Laurent A. Dermal distribution of hyaluronan in psoriatic arthritis: coexistence of CD44, MMP3 and MMP9. Acta Derm Venereol 2012; 92: 372–377. 4 Seung NR, Park EJ, Kim CW et al. Comparison of expression of heat-shock protein 60, Toll-like receptors 2 and 4, and T-cell receptor gammadelta in plaque and guttate psoriasis. J Cutan Pathol 2007; 34: 903–911. 5 Garcia-Rodriguez S, Arias-Santiago S, Perandres-L opez R et al. Increased gene expression of Toll-like receptor 4 on peripheral blood mononuclear cells in patients with psoriasis. J Eur Acad Dermatol Venereol 2013; 27: 242–250. 6 Carrasco S, Neves FS, Fonseca MH et al. Toll-like receptor (TLR) 2 is upregulated on peripheral blood monocytes of patients with psoriatic arthritis: a role for gram-positive inflammatory trigger? Clin Exp Rheumatol 2011; 29: 958–962. 7 Noble PW, Liang J, Jiang D. Hyaluronan as an immune regulator in human diseases. Physiol Rev 2011; 91: 221–264. DOI: 10.1111/jdv.12581

Testing for levamisole and cocaine in hair samples for the diagnosis of levamisole-related panniculitis Editor Levamisole has been used as a cutting agent in cocaine, as it enhances its euphoric effect at a lower cost. More than 70% of the cocaine from the USA or Canada contain levamisole. Since 2009, several cases of vasculitis due to levamisole contained in cocaine have been reported, and most of these (94%) were ANCA-positive vasculitides.1 The dosage of levamisole is usually tested in urine and serum; however, its half-life is short (5.6 h),2 therefore only very recent consumption can be detected using this method. We have previously reported the interest of measuring levamisole and cocaine in hair samples in a patient presenting an atypical panniculitis with some features of vasculitis and positive ANCA testing.3 Herein, we report additional data that reinforce the link between levamisole exposure and development of systemic vasculitis. In May 2011, a 39-year-old female cocaine addict (previously reported3) consulted for recurrent (six stereotypic episodes per year) painful panniculitis with erythematous

© 2014 European Academy of Dermatology and Venereology

Hyaluronic acid in psoriasis.

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