Seborrheic keratosis

Abstract

Pemphigus Foliaceus (PF) is an antibody-mediated autoimmune disease. IgG directed against desmoglein-1 induces acantholysis in the superficial epidermis, leading to the classic presentation of crusted erosions in a seborrheic distribution. We report a case of a 51-year-old African-American man with an 8-year history of PF, who developed multiple hyperpigmented, 'stuck-on' appearing verrucous papules and plaques on the back, chest, and neck. Skin biopsy and direct immunofluorescence from the seborrheic keratosis-like lesions was consistent with pemphigus foliaceus. The patient was treated by adding oral gold (auranofin) to his regimen of prednisone and discontinuing hydroxychloroquine. After six months of follow-up his erosions healed. This is the first report of treating pemphigus foliaceus with oral gold.

Introduction

Pemphigus foliaceus is a cutaneous autoimmune disorder, sparing the oral mucosa. Antibodies against desmoglein-1, a 160-kDa transmembrane glycoprotein of desmosomes, are thought to be the underlying cause of epidermal acantholysis, mainly at the granular layer. (1) Despite various clinical manifestations, the histopathology and immunofluorescent microscopy of these lesions are quite typical.

We report a patient with longstanding pemphigus foliaceus who later developed seborrheic keratoses-like lesions. Biopsy of these lesions was consistent with PF.

Case Report

A 51-year-old African-American male patient had an eight-year history of pemphigus foliaceus. The lesions initially presented as generalized crusted erosions, mainly on the upper chest and back. Skin biopsy of initial presentation revealed subcorneal bulla with acantholysis. Previous therapies included tetracycline and nicotinamide, prednisone and methotrexate, azathioprine, and hydroxychloroquine without complete clearing. When he came to the clinic for routine follow-up he was on prednisone 20 mg and hydroxychloroquine 200 mg a day.

On physical examination he had developed multiple sharply demarcated, hyperpigmented, "stuck-on" appearing verrucous plaques and papules on the back, chest, and neck (figure 1). Most lesions were clinically indistinguishable from seborrheic keratosis. There were few crusted erosions on the back and central face. No oral lesions were identified.

Routine laboratory studies such as CBC, Electrolytes, LFT, and Urinalysis were normal. Skin biopsy of one of these hyperkeratotic plaques from the back revealed orthokeratosis, papillomatosis, and acantholysis in the granular layer (figure 2). Direct immunofluorescence from perilesional skin revealed intercellular IgG deposition within the epidermis (figure 3). Diagnosis of PF resembling eruptive seborrheic keratosis was made. He was treated by continuing his prednisone 20 mg, stopping hydroxychloroquine, and adding oral gold (auranofin) 3 mg twice daily. Within 3 weeks he stopped developing new erosions. The seborrheic keratosis-like lesions started drying and decreasing in number up to his six-month follow up, at which point he did not have any evidence of gold toxicity.

Discussion

There are two other citations in the literature describing seborrheic keratosis-like pemphigus foliaceus (2,3). In the two previous case reports, the patients' lesions resolved after prednisone therapy. The mechanism of developing seborrheic keratosis-like lesions in PF remains elusive. Possibly a certain unique subset of autoantibodies induces hyperproliferation of keratinocytes, leading to hyperkeratosis. On the other hand, eruptive seborrheic keratosis might indicate the "sign of Leser-Trelat" and possible internal malignancy (4). Therefore, in order to distinguish this sign from unusual presentations of pemphigus foliaceus, biopsy confirmation is recommended.

Parental gold has been successfully used for the treatment of pemphigus foliaceus and pemphigus vulgaris (5-8). Gold is thought to act as an immune-modulating and anti-inflammatory agent (9). In a recent study, 22 out of 26 (85%) patients with pemphigus responded to intramuscular gold (Myochrysine), while 9 out of 26 (38%) developed toxic side effects requiring discontinuation of therapy (5). Long-term follow-up studies show successful outcome of intra-muscular chrysotherapy for pemphigus (10).

To the best of our knowledge this is the first report of oral gold treatment for pemphigus foliaceus. One previous report describes three patients treated with oral gold (auranofin) for pemphigus vulgaris (9). In that report two of the patients showed slight clinical improvement and only one achieved short-term remission, while all three patients had significant oral pain relief.

Auranofin is used in rheumatology as a steroid-sparing agent for treatment of rheumatoid arthritis. Its pharmacokinetic and pharmacodynamic properties are different from intramuscular gold thiomalate (9). The long-term side effects are minor compared to intramuscular gold, and the administration is more convenient (11). Further studies are necessary to determine the efficacy of oral gold in Pemphigus.

References

(1.) Eyre RW, Stanley JR. Human autoantibodies against a desmosomal protein complex with a calcium-sensitive epitope are characteristics of pemphigus foliaceus patients. J Exp Med 1987; 165:1719.

(2.) Kahana M, Trau H, Schewach-Millet M, et al. Pemphigus foliaceus presenting as multiple giant seborrheic keratoses. J Am Acad Dermatol 1984; 11:299-300.

(3.) Bruckner N, Katz RA, Hood AF. Pemphigus foliaceus resembling eruptive seborrheic keratoses. Arch Dermatol 1980; 116(7): 815-6.

(4.) Dantzig PI. Sign of Lesar-Trelat. Arch Dermatol 1973; 108:700-1.

(5.) Pandya AG, Dyke C. Treatment of pemphigus with gold. Arch Dermatol 1998; 134:1104-07.

(6.) Walton S, Keczkes K. Pemphigus foliaceus-successful treatment with adjuvant gold therapy. Clin and Exp Dermatol 1987; 12:364-365.

(7.) Penneys NS, Eaglstein WH, Indgin S, et al. Gold sodium thiomalate treatment of pemphigus. Arch Dermatol 1973; 108:56-60.

(8.) Sutej PG, Jorizzo JL, White W. Intramuscular gold therapy for young patients with pemphigus vulgaris: a prospective, open, clinical study utilizing a dermatologist/ rheumatologist team approach. J Eur Acad Dermatol Venereol 1995; 5:222-28.

(9.) Salomon D, Saurat J. Oral gold therapy (Auranofin) in pemphigus vulgaris. Dermatologica 1986; 172:310-14.

(10.) Penneys NS, Eaglstein WH, Frost P. Management of pemphigus with gold compounds: a long-term follow-up report. Arch Dermatol 1976; 112:185-87.

(11.) Chaffman M, Brogden RN, Heel RC, et al. Auranofin. A preliminary review of its pharmacological properties and therapeutic use in rheumatoid arthritis. Drugs 1984; 27:378-424.

ADDRESS FOR CORRESPONDENCE:

Mehran Alagheband, MD

17-31 Seagirt Boulevard

Far Rockaway, NY 11691

Phone: 718-539-0059

MOHAMMED M. BAGHERI, MD (A) MEHRAN ALAGHEBAND, MD (A) OMEED M. MEMAR, MD, PHD (B) DAVID B. EILER, MD (C)

FROM THE DEPARTMENTS OF DERMATOLOGY, NEW YORK MEDICAL COLLEGE (A), VALHALLA, NEW YORK; THE UNIVERSITY OF ILLINOIS (B), AND LOYOLA UNIVERSITY (C), CHICAGO, IL

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