units without the prolonged use of corticosteroids. J Am Coll Surg. 1995; 180(3):340-342. 5. Araki Y, Sotozono C, Inatomi T, et al.

Successful treatment of StevensJohnson syndrome with steroid pulse therapy at disease onset. Am J Ophthalmol. 2009;147(6):1004-1011, 1011, e1. 6. Sotozono C, Ueta M, Koizumi N, et al. Diagnosis and treatment of StevensJohnson syndrome and toxic epidermal necrolysis with ocular complications. Ophthalmology. 2009;116(4):685-690.

(HDAC) inhibitor approved for the treatment of cutaneous T-cell lymphoma.1 Report of Cases. Case 1. Patient 1 was a 70-year-old white woman with stage IVA MF treated previously with methotrexate, interferon alfa, bexarotene, topical nitrogen mustard, and psoralenUV-A therapy (PUVA). She had been taking vorinostat, 300 to 400 mg/d, for 6 months when diffuse leukonychia of the fingernails was noted (Figure 1). Vorinostat treatment was discontinued after 10 months owing to persistent disease, and by 10 months later, her nails had returned to normal. Case 2. Patient 2 was a 70-year-old white man with stage IIB MF previously treated with interferon alfa, bexarotene, local and total-body electron beam irradiation, and PUVA. The patient had taken vorinostat, 400 mg/d, for 40 weeks when leukonychia totalis of all fingernails was noted (Figure 2). Four months after discontinuing vorinostat treatment, the leukonychia had completely resolved. Case 3. Patient 3 was a 44-year-old African American man with stage IIB MF previously treated with interferon alfa, denileukin diftitox, methotrexate, bexarotene, local and total-body electron beam irradiation, etoposide, topical nitrogen mustard, topical carmustine, and PUVA. Six months after treatment with vorinostat, 400

Linking Publication About Efalizumab Effectiveness With Safety Concerns

he Cutting Edge article by Mun tos-Santos et al,1 Response of Keratosis Lichenoides Chronica to Efalizumab Therapy, published in the August 2009 issue of the Archives, was accepted on August 12, 2008, which is prior to the recognition of the safety concerns of efalizumab. As noted by Korman et al2 in the commentary in the same issue, reports of progressive multifocal leukoencephalopathy (PML) in patients treated with efalizumab in the absence of other immunosuppressive agents led the manufacturers to voluntarily withdraw the drug from the market. At the time the drug was withdrawn from the market, the Archives ceased considering manuscripts discussing the dermatologic indications of this drug. The final manuscript in our inventory of manuscripts accepted prior to withdrawal of the drug was published in the same issue as the commentary by Korman et al2 to alert our readers to concerns about using efalizumab for dermatologic indications. On February 19, 2009, both the European Medicines Agency and the US Food and Drug Administration issued safety concerns regarding the risk of PML with the use of efalizumab for the treatment of psoriasis.3 This letter to the editor ensures that the National Library of Medicine links the article by Mun oz-Santos et al1 to articles discussing the reasons for withdrawal of the drug.2,3 June K. Robinson, MD Correspondence: Dr Robinson, Northwestern University Feinberg School of Medicine, 132 E Delaware Pl, No. 5806, Chicago, IL 60611 (june-robinson@northwestern.edu). Additional Information: Dr Robinson is Editor of the Archives of Dermatology.
1. Mun oz-Santos C, Ye benes M, Roman J, Luelmo J. Response of keratosis lichenoides chronica to efalizumab therapy. Arch Dermatol. 2009;145(8):867-869. 2. Korman BD, Tyler KL, Korman NJ. Progressive multifocal leukoencephalopathy, efalizumab, and immunosuppression. Arch Dermatol. 2009;145(8):937942. 3. Nijsten T, Spuls PI, Naldi L, Stern RS. The misperception that clinical trial data reflect long-term drug safety: lessons learned from efalizumabs withdrawal. Arch Dermatol. 2009;145(9):1037-1039.

Figure 1. Clinical comparison of the fingernails of patient 1 after 6 months of vorinostat treatment (top, 2 hands) with normal fingernails (bottom, 1 hand).

VIGNETTES

Leukonychia Related to Vorinostat

e herein describe a new clinical finding of leukonychia occurring in 3 patients with mycosis fungoides (MF) being treated with vorinostat (Zolinza; Merck & Co Inc, Whitehouse Station, New Jersey), a zinc-dependent histone deacetylase

Figure 2. Clinical appearance of the fingernails of patient 2 after 10 months of vorinostat treatment.

(REPRINTED) ARCH DERMATOL/ VOL 145 (NO. 11), NOV 2009 1338

WWW.ARCHDERMATOL.COM

Downloaded from www.archdermatol.com at Duke University, on October 13, 2010 2009 American Medical Association. All rights reserved.

mg/d, was initiated, leukonychia totalis of all fingernails was noted. No follow-up information is available. All 3 patients denied a personal or family history of abnormal nails or trauma or chemical exposures to the nails. None of the other medications the patients were taking have been associated with leukonychia. On examination, all 3 patients lacked onychodystrophy, onycholysis, nail thickening, or pitting of the nails, and no obvious peripheral vasoconstriction was present. Toenails were not involved. None of the 3 patients had hypocalcemia, hypoalbuminemia, or anemia. Creatinine levels had slightly increased in 2 patients who were taking vorinostat. Comment. Leukonychia can be classified into true or apparent subtypes.2,3 In the true subtype, a defect in the nail matrix causes an abnormal keratinization of the nail plate. In contrast, apparent leukonychia involves a pathologic process in the subungual tissue or nail bed and includes changes in adherence of the nail plate to the nail bed or changes in the translucence of the nail bed epithelium or its vasculature status.4 The present cases best represent apparent leukonychia as manifested by (1) persistence of opacity as the nail grew; (2) rapid improvement once treatment with the presumed causative agent was stopped; and (3) resolution starting distally and moving proximally (the opposite from what is generally seen with true leukonychia). Diffuse or total apparent leukonychia has been seen with medical illnesses such as liver cirrhosis (Terrys nails), anemia, hypocalcemia, hypoalbuminemia, and zinc deficiency. To our knowledge, this is the first report of diffuse leukonychia secondary to treatment with an HDAC inhibitor, a condition that resolved once treatment with the drug was halted. Although the arrest of cell growth and apoptosis in a wide range of cells is the primary effect of HDAC inhibitors in cancer cells, it may be their effect on repression of endothelial nitric oxide synthase and the resultant compromise of endothelial cell function in vasorelaxation and angiogenesis that best explains the mechanism in apparent leukonychia.5 Kyle A. Anderson, MD Holly L. Bartell, MD Elise A. Olsen, MD Correspondence: Dr Olsen, Division of Dermatology, Duke University Medical Center, PO Box 3294, Durham, NC 27710-0001 (olsen001@mc.duke.edu). Financial Disclosure: Dr Olsen is a consultant for Merck and Co Inc and has been an investigator for Mercksponsored studies.
1. Olsen EA, Kim YH, Kuzel TM, et al. Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous Tcell lymphoma. J Clin Oncol. 2007;25(21):3109-3115. 2. Grossman M, Scher RK. Leukonychia: review and classification. Int J Dermatol. 1990;29(8):535-541. 3. Stevens KR, Leis P, Peters S, Baer S, Orengo I. Congenital leukonychia. J Am Acad Dermatol. 1998;39(3):509-512. 4. Daniel CR III, Zaias N. Pigmentary abnormalities of the nails with emphasis on systemic diseases. Dermatol Clin. 1988;6(2):305-313. 5. Rssig L, Li H, Fisslthaler B, et al. Inhibitors of histone deacetylation downregulate the expression of endothelial nitric oxide synthase and compromise endothelial cell function in vasorelaxation and angiogenesis. Circ Res. 2002; 91(9):837-844.

An Association of Idiopathic Chronic Eosinophilic Pneumonia With Pemphigoid Nodularis: A Rare Variant of Bullous Pemphigoid

Report of a Case. In October 2006, a 70-year-old Japanese woman came to our hospital for evaluation of her severe itching accompanied by nodular skin lesions on the trunk and extremities (Figure 1A), symptoms that clinically suggested prurigo nodularis. There were no blister formations at the time of initial presentation, but several small blisters sometimes appeared on the extremities during the course of the disease (Figure 1B). Her medical history included (1) idiopathic chronic eosinophilic pneumonia (ICEP) confirmed by chest radiography and computed tomography, (2) pulmonary eosinophilia in bronchoalveolar lavage fluid (BALF), and (3) a transbronchial lung biopsy 6 years previously. She had no atopic diathesis and was taking prednisolone, 2 mg/d, to control ICEP. Laboratory investigations revealed an elevated white blood cell count (15 700/L) and serum IgE titer (1160 g/L). (To convert white blood cells to number of cells 109 per liter, multiply by 0.001; to convert IgE to milligrams per liter, multiply by 0.001.) Other results of blood tests were within the normal range. Histopathologic examination of a nodular lesion specimen revealed irregular acanthosis with pseudoepitheliomatous hyperplasia and infiltration of many lymphocytes and a few eosinophils (Figure 2A). Direct immunofluorescence of perilesional skin specimens demonstrated linear deposits of IgG and C3 at the basement membrane zone (BMZ) of the epidermis (Figure 2B). On indirect immunofluorescence with normal human skin as substrate, circulating IgG anti-BMZ autoantibodies were detected. Immunoblot analysis using BP180-NC16a domain recombinant protein demonstrated that the patient had circulating IgG but not IgE autoantibodies. Enzyme-linked immunosorbent assay detected IgG anti-BP230 (49.45 index) and anti-BP180 (75.60 index) autoantibodies. These immunologic pro-

Figure 1. Prurigo nodularislike lesions are present on the lower limb (A), and a bulla and erosion are found on the forearm (B).

(REPRINTED) ARCH DERMATOL/ VOL 145 (NO. 11), NOV 2009 1339

WWW.ARCHDERMATOL.COM

Downloaded from www.archdermatol.com at Duke University, on October 13, 2010 2009 American Medical Association. All rights reserved.