Letters to the Editor removed from the peripheral blood of the patients. REFERENCES One round of cytapheresis removed approximately 1RuoccoE,SangiulianoS,GravinaAG,MirandaA,Nico- 3.9 · 109 WBC from approximately 2000 mL blood. letti G. Pyoderma gangrenosum: an updated review. Short-term rapid removal of leukocytes from periph- J Eur Acad Dermatol Venereol 2009; 23: 1008– eral blood may cause some kind of alteration of phe- 1017. notype, particularly the expression of the homing 2CallenJP.Pyodermagangrenosum.Lancet 1998; 351: 581–585. receptors of leukocytes to the skin, such as leukocyte 3KanekuraT,MaruyamaI,KanzakiT.Granulocyteand adhesion molecule (LCAM)-1.8 Furthermore, IL-8, a adsorption apheresis for pyoderma gangre- potent leukocyte chemotactic agent, which is mainly nosum. J Am Acad Dermatol 2002; 47: 320–321. produced by , is overexpressed in PG 4FujimotoE,FujimotoN,KurodaK,TajimaS.Leuko- ulcers;1 however, the serum level of IL-8 did not cytapheresis treatment for pyoderma gangrenosum. Br J Dermatol 2004; 151: 1090–1092. increase in our case. LCAP using both leukocyte- 5KohgoY,HibiH,ChibaTet al. Leukocyte apheresis absorbing filter and CCS may be more effective than using a centrifugal cell separator in refractory ulcerative GCAP alone, because the former can remove not colitis: a multicenter open label trial. Ther Apher 2002; only but also IL-8-producing mono- 6: 255–260. cytes.5 The clinical efficacy of LCAP using CCS was 6HidakaT,SuzukiK,MatsukiYet al. Filtration leukocyta- equivalent to that of LCAP using leukocyte-absorbing pheresis therapy in rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum filter in the treatment of IBD, but its efficacy in the 1999; 42: 431–437. treatment of PG remains to be investigated.8 7MillerFW,LeitmanSF,CroninMEet al. Controlled trial of In conclusion, LCAP using CCS can serve as an plasma exchange and leukapheresis in polymyositis important and new treatment option for patients with and dermatomyositis. N Engl J Med 1992; 326: 1380– steroid and immunosuppressant-resistant PG, and 1384. 8KohgoY,AshidaT,MaemotoA,AyabeT.Leukocytaph- the efficacy of this treatment is similar to that of GCAP eresis for treatment of IBD. J Gastroenterol 2003; or LCAP using a leukocyte-absorbing filter. 38(Suppl 15): 51–54. 9RembackenBJ,NewbouldHE,RichardsSJ et al. Takaaki HANAFUSA,1 Hiroaki AZUKIZAWA,1 apheresis in inflammatory bowel disease: Noriko UMEGAKI,1 Mamori TANI,1 possible mechanisms of effect. Ther Apher 1998; 2: Yuji YAMAGUCHI,2 Ichiro KATAYAMA1 93–96. 1Department of Dermatology, Osaka University Graduate School of Medicine, 10 Sawada K, Ohnishi K, Kosaka T et al. Leukocytaphere- Osaka, and 2Department of Geriatric and Environmental Dermatology, sis with leukocyte removal filter as new therapy for Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan . Ther Apher 1997; 1: 207–211.

Rosacea (erythematotelangiectatic type) effectively improved by topical xylometazoline

Dear Editor, occasionally with telangiectasias, is one of the most Rosacea is a common chronic cutaneous disorder common types of rosacea in patients of Korean des- that primarily occurs on the convex surfaces of the cent. A number of medications, including metronida- central face and is often characterized by exacerba- zole, sodium sulfacetamide with sulfur, azelaic acid tions and remissions.1 Erythematotelangiectatic type gel, oral tetracycline and isotretinoin, have been used rosacea, characterized by centrofacial erythema in various combinations to treat rosacea. However,

Correspondence: Sung Ku Ahn, M.D., Ph.D., Department of Dermatology, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju 220-701, Korea. Email: [email protected]

510 Ó 2010 Japanese Dermatological Association Letters to the Editor these treatments are less effective in the erythematot- vate clinic prior to presentation and had been treated elangiectatic type than in the papulopustular type of with a topical application of metronidazole and p.o. rosacea. Reported here is a case of erythematotelan- administration of minocycline for several months. In giectatic type rosacea which was controlled by topi- addition, two rounds of laser treatment with intense cal application of xylometazoline 0.05%, with a brief pulsed light were not effective. Physical examination review of the relevant published work. revealed diffuse erythema with telangiectasias in the A61-year-oldpostmenopausalwomanpresented centrofacial area, including both cheeks. There were with a history of several months of moderate centro- no definite papules or pustules noted. These findings facial erythema. She complained of multiple episodes were more prominent on cross-polarizing photo- of flushing with occasional pruritus in the erythema- graphs (Fig. 1a). Laboratory studies, including com- tous area. She was diagnosed with rosacea in a pri- plete blood cell count, blood chemistry, anti-nuclear

(a) (b)

Figure 1. Baseline cross-polarizing photographs of the patient immediately prior to application of xylometazoline 0.05% solution (a) and 3 h after topical application (b), demonstrating improvement in macular erythema and fine telangiectasias.

Ó 2010 Japanese Dermatological Association 511 Letters to the Editor and thyroid function tests, were within Xylometazoline is one of the imidazoline-type sym- normal limits, except a total cholesterol level of pathomimetic agonists. It acts as a highly selective

275 mg ⁄dL (normal <200), a triglyceride level of agonist for the a1A-adrenergic receptor and is also 240 mg ⁄dL (normal <200) and an alanine aminotrans- partially selective for the a2A-adrenergic receptor that ferase level of 46 U ⁄L(normal<35).Onthebasisof produces vasoconstrictive effects. Worldwide, there medical history and clinical findings, the patient was are multiple preparations containing xylometazoline. diagnosed with erythematotelangiectatic type rosa- Two xylometazoline preparations, 0.1% (1 mg ⁄mL) cea. We prescribed Otrivin (xylometazoline) (Novartis, and 0.05% (0.5 mg ⁄mL), are commercially available Sweden) 0.05% (0.5 mg ⁄mL), which possesses vaso- in Korea. These have been shown to reduce ery- constrictive effects. She was instructed to apply this thema, edema and congestion through the vasocon- solution 0.5 mL ⁄day to both cheeks after washing strictive properties of the medication when applied to without any other cosmetics. Three hours after appli- the skin and mucosa. Xylometazoline has been pre- cation of xylometazoline 0.05% (0.5 mg ⁄mL), the skin scribed for the treatment of allergic rhinitis to reduce lesions had significantly improved (Fig. 1b) and sub- congestion of nasal mucosa due to the same proper- jective symptoms such as flushing and itching were ties. In addition, there have been reports of treatment also reduced. These improvements persisted for of ocular hypertension and glaucoma using selective hours following application. Eight months after a2A-adrenergic receptor agonists. However, there initiating daily application of xylometazoline, her facial have been few reports of using adrenergic receptor erythema and telangiectasias were significantly agonists in the dermatological field, especially in the reduced, and the patient suffered no side-effects treatment of rosacea.8 related to the medication. As mentioned above, one possible mechanism of While the pathogenesis of rosacea remains the therapeutic effects of xylometazoline in the eryt- unknown, several factors have been implicated, hematotelangiectatic type of rosacea is due to the including inherent abnormalities in cutaneous vascu- vasoconstrictive properties of this medication. In lar homeostasis and thermal dysregulation. There are addition, recent studies have demonstrated that sev- various cutaneous signs of rosacea such as flushing, eral a-adrenergic receptor agonists also have anti- erythema, telangiectasias, edema, papules and pus- inflammatory properties. In upper respiratory tract tules. Among them, persistent erythema and abnor- infections, oxymetazoline and xylometazoline have mal flushing have been known to arise from been shown to reduce the levels of pro-inflammatory abnormalities in cutaneous vascular homeostasis by inhibiting themigrationofneutrophils triggered by many factors such as neurogenic, hor- and the oxidative burst of .9 Moreover, monal, thermal and topical stimuli.2,3 The complex oxymetazoline affects arachidonic acid metabolism regulation of cutaneous vascular circulation is medi- and reduces leukotriene B4.9 These results suggest ated by systemically and locally excreted catechol- that reducing inflammation may be another therapeu- amines. There are two types of adrenergic receptors tic mechanism of xylometazoline in erythematotelan- that modulate cutaneous vascular responses to cate- giectatic type rosacea. cholamines.4 One is the a-adrenergic receptor, acti- There are some side-effects related to the long- vation of which causes vasoconstriction. The other is term use of a-adrenergic receptor agonists on the the b-adrenergic receptor, which antagonizes the nasal mucosa. Tachyphylaxis caused by desensiti- actions of the a-receptor, causing vasodilation. In zation is a well-known side-effect of these medica- in vivo and in vitro studies, contraction of peripheral tions. Another complication of treatment is a vascular smooth muscle was primarily mediated by rebound phenomenon that produces vasodilation 8 a1A-anda1D-receptors, which are two subtypes of with recurrent flushing. In the general population, a-adrenergic receptors.5–7 In studies of the actions of the incidences of tachyphylaxis and rebound phe- the a2-receptor subtypes, a2A ⁄ D-anda2B-receptors nomenon were increased with increased duration of are responsible for the contraction of the arterial com- treatment and a larger cumulative dose of the medi- 10 ponent, while a2A ⁄ D-anda2c-receptors regulate con- cation. Fortunately, in this case, neither of these traction of the venous component.5–7 adverse effects were observed during the 8-month

512 Ó 2010 Japanese Dermatological Association Letters to the Editor treatment period. In addition, there were no other Expert Committee on the classification and staging of side-effects related to the medication. Further inves- rosacea. J Am Acad Dermatol 2002; 46: 584–587. tigations with larger numbers of subjects and a 2CrawfordGH,PelleMT,JamesWD.Rosacea:I.Etiol- ogy, pathogenesis, and subtype classification. J Am longer follow-up period are needed to evaluate the Acad Dermatol 2004; 51: 327–341. (quiz 342-4) efficacy of xylometazoline in erythematotelangiectat- 3PelleMT,CrawfordGH,JamesWD.Rosacea:II. ic type rosacea. Therapy. J Am Acad Dermatol 2004; 51: 499–512. In summary, we report a case of a 61-year-old (quiz 513-4) woman who presented with moderate, centrofacial 4AhlquistRP.Theadrenotropicreceptor-detector.Arch Int Pharmacodyn Ther 1962; 139: 38–41. erythema with telangiectasias, which was controlled 5GuimaraesS,MouraD.Vascularadrenoceptors:an by topical application of xylometazoline solution once update. Pharmacol Rev 2001; 53: 319–356. aday.Thiscasestudydemonstratesthattopical 6CivantosCalzadaB,Aleixandre de Artinano A. Alpha- application of a-adrenergic receptor agonists could adrenoceptor subtypes. Pharmacol Res 2001; 44: 195– be a new treatment option for the erythematotelan- 208. giectatic type of rosacea. 7LeechCJ,FaberJE.Differentalpha-adrenoceptorsub- types mediate constriction of arterioles and venules.

1 1 1 Am J Physiol 1996; 270: H710–H722. Jae-Hong KIM, Yoon Seok OH, Jae Hong JI, 8ShanlerSD,OndoAL.Successfultreatmentoftheery- 2 1,3 Hana BAK, Sung Ku AHN thema and flushing of rosacea using a topically applied 1 Department of Dermatology and selective alpha1-adrenergic receptor agonist, oxymetaz- 3Institute of Basic Medical Science, Yonsei University 2 oline. Arch Dermatol 2007; 143: 1369–1371. Wonju College of Medicine, Wonju, and Asan Medical Center, 9Beck-SpeierI,DayalN,KargEet al. Oxymetazoline University of Ulsan College of Medicine, Seoul, Korea inhibits proinflammatory reactions: effect on arachidonic acid-derived metabolites. J Pharmacol Exp Ther 2006; REFERENCES 316: 843–851. 10 Graf P. Long-term use of oxy- and xylometazoline nasal 1WilkinJ,DahlM,DetmarMet al. Standard classification sprays induces rebound swelling, tolerance, and nasal of rosacea: report of the National Rosacea Society hyperreactivity. Rhinology 1996; 34: 9–13.

Erysipelas-like erythema with familial Mediterranean fever

Dear Editor, phenomenon and subcutaneous nodules are non- Familial Mediterranean fever (FMF) is an autosomal specific skin problems seen in FMF.1-3 Vasculitic skin recessive disease, characterized by recurrent and lesions related to Henoch–Scho¨ nlein purpura and self-limited attacks of fever and peritonitis, pleuritis, polyarteritis nodosa can also occur.1,4 Erysipelas-like arthritis or erysipelas-like skin disease. These erythema (ELE) is an unusual but well-known and attacks are usually short-lived and subside within pathognomonic skin manifestation of FMF.3 Lesions 24–72 h.1 are characterized by tender, erythematous plaques, Cutaneous manifestations in FMF were noted in usually located on the joints, lower legs and dorsal 25–47% of cases in different reports.1,2 Diffuse ery- aspect of the feet. They may be triggered by physical thema of the face and ⁄or trunk, angioneurotic edema, effort and subside spontaneously within 48–72 h of diffuse erythema of the palms and soles followed by bedrest. Fever, arthritis and leukocytosis may accom- mild desquamation of the skin, pyoderma, Raynaud’s pany this condition.

Correspondence: Fatma Aydin, M.D., Ondokuz Mayis University School of Medicine, Department of Dermatology, TR-55139 Kurupelit, Samsun, Turkey. Email: [email protected]

Ó 2010 Japanese Dermatological Association 513