Dyskeratosis of the Face: A Quiz
Valérie Vuong1, Gentiane Monsel1, Bénedicte Cavelier-Balloy1,2, Maxime Battistella2, Evelyne Collet3, Martine Bagot1, Nicole Basset-Seguin1 and Manuelle Viguier1*
1Dermatology and 2Pathology Department, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, 1 avenue Claude-Vellefaux, FR-75475 Paris, and 3Dermatology Department, Hôpital du Bocage, Dijon, France. *E-mail: manuelle.viguier@ aphp.fr
A 53-year-old woman presented with a 10-month history of verrucous and hyperkeratotic plaques on the forehead, which had extended progressively to the cheekbones (Fig. 1A).
An initial skin biopsy was taken on the cheek, with pathological findings consistent with a diagnosis of warty dyskeratoma (Fig. 1B). In situ human papilloma virus (HPV) hybridization was negative on this biopsy. No improvement was shown after 2 months of acitretin, 25 mg/day. Additional biopsies on the extended lesions of the face identified dyskeratotic cells with some vacuolated keratinocytes evocative of HPV infection. Viral papilloma was suspected and she was treated with shaving, followed by topical application of imiquimod. Four months later, physical examination revealed emaciation, hyperkeratotic, superinfected plaques on the face with a lupoid distribution, erosive lesions on the gums, and vegetant vulvar and perianal lesions. The usual laboratory tests were normal.
Fig. 1. (A) Verrucous and hyperkeratotic plaques on the forehead and cheekbones. (B) Pathological findings from a skin biopsy on the cheek showing hyperkeratosis and papillomatosis with some acantholysis and dyskeratosis (haematoxylin and eosin (H&E) staining; original magnification × 50). A written permisison from the patient is given to publish these photos.
What is your diagnosis? See next page for answer.
Dyskeratosis of the Face: A Comment
Acta Derm Venereol
Diagnosis: Pemphigus vegetans
The patient’s facial appearance after imiquimod application is shown in Fig. 2A. New biopsy from the cheek showed more pronounced suprabasal acantholysis with slight dyskeratosis in a hyperplastic epidermis (not shown). Direct immunofluorescence on lesional skin revealed suprabasal intercellular staining of IgG and C3, without staining on the basement membrane zone (Fig. 2B). Indirect immunofluorescence was negative on rat bladder substrate, but showed positive circulating intercellular IgG autoantibodies on monkey oesophagus substrate (1/100). Western immunoblotting, using epidermal extract antigen, detected autoantibodies to 130 kDa. This confirmed pemphigus vegetans (PV) initially misdiagnosed as warty dyskeratoma.
Oral prednisone therapy (1 mg/kg/day) for 3 months provided only partial improvement. The patient then received 2 infusions of rituximab (1 g each, at 15 days interval) that were efficient after 3 months. She was still in remission at one year with 2 supplementary infusions of rituximab (500 mg each) and 10 mg prednisone daily. Four years after the first lesions, the patient now receives 5 mg prednisone daily and topical corticosteroid because of the recurrence of a few vegetant lesions on the face, but all the mucosae are healed.
Fig. 2. (A) Four months later, after imiquimod application, hyperkeratotic, superinfected plaques on the face with a lupoid distribution. (B) Direct immunofluorescence: suprabasal intercellular staining of the epidermis with anti-IgG (original magnification × 400).
PV represents less than 2% of all cases of pemphigus vulgaris (1). Two clinical subtypes are described: the Neumann type is the most common, beginning with bullae and having a poor prognosis, whereas the Hallopeau type usually begins with pustules and has an excellent response to treatment (2). Both types are characterized by vegetant plaques in the skin folds (mainly the axillary, the inguinal and the perianal folds) (3–5) and on the mucosae (2, 6). Some cases of Hallopeau type PV have been described on the foot or on the scalp (7, 8).
Our patient’s facial involvement with hyperkeratotic plaques following a lupoid distribution is unique in the literature, as is the absence of folds involvement. Another clinical particularity is the huge extended mucosal involvement with vegetant and erosive lesions on the gum, the vulva, and the oesophagus. The absence of eosinophilic microabsesses on skin biopsy is also notable.
Warty dyskeratoma is also characterized by location on the face, mucosal involvement, presence of epidermal hyperplasia and acantholysis on skin biopsy (9). However, epidermal hyperplasia is more pronounced and, clinically, the lesion is usually unique, with only a dozen cases of multiple warty dyskeratoma reported previously (9). Signs evocative of cytopathic HPV on the second biopsies misled us to diagnose viral papilloma. Shaving followed by topical application of imiquimod were then attempted but failed. Retrospective examination of the pathological slides identified that koïlocytes corresponded rather to clarified keratinocytes. Some cases of imiquimod-induced pemphigus have been reported presumably caused by a potential stimulation of the production of inflammatory cytokines and induction of Th1-driven autoimmune conditions (10).
The authors declare no conflicts of interest.