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HPV 29-associated spotted hyperpigmentation of the face


European Journal of Dermatology. Volume 12, Number 2, 189-90, March - April 2002, Cas cliniques


Summary  

Author(s) : Susanne JACOBS, Jens Malte BARON, Albert RUBBEN, Elke-Ingrid GRUSSENDORF-CONEN, Department of Dermatology, University Hospital RWTH Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany..

Summary : A healthy immunocompetent 40-year-old man presented with spotted hyperpigmentation of the face. Skin-biopsies taken from these lesions revealed slight acanthosis of the epidermis with vacuolization within the keratinocytes in the upper malpighian layer similar to HPV-induced cytopathic viral effects. Polymerase chain reaction analysis and subsequent direct DNA sequencing could clearly demonstrate the presence of HPV 29 DNA in the hyperpigmented macules. To our knowledge, this is the first report of facial hyperpigmented lesions induced by HPV 29.

Keywords : hyperpigmentation, humanpapillomavirus type 29, polymerase chain reaction.

Pictures

ARTICLE

Human papillomaviruses (HPV) are small DNA tumor viruses affecting epidermal (cutaneous) and epithelial (mucosal) tissues. They are associated with a large variety of different clinical lesions, ranging from benign common (cutaneous) warts to malignant tumors of the anogenital area. The number of HPV types analyzed is steadily increasing. Among these, HPV 29 is identified only on rare occasions.

Case report

A healthy, human immunodeficiency virus (HIV)-negative, 40-year-old white man presented with a 4-year history of hyper macules on the cheeks and forehead (Fig. 1). Local treatment with aceleic acid and retinoid cream brought no improvement. Skin-biopsies taken from these lesions revealed slight acanthosis of the epidermis with vacuolization within the keratinocytes in the upper malpighian layer similar to HPV-induced cytopathic viral effects (Fig. 2). The basal cell layer showed moderate hyperpigmentation. DNA was extracted from the paraffin embedded material and polymerase chain reaction (PCR) was performed with the "general'' primer pair RK91, which is able to amplify viral DNA of approx. 230 bp length of the following HPV types: 1-4,10,11,15,16,26, 27,29,30,53,56,57,65. Sense primer sequence: 5'ACHCCTAGTGGBTCTWTRGTDWC3'; antisense primer sequence: 5'HHTCAWAYTCCTCYAYATGYCT3' (B = C or G or T, H = A or C or T, W = A or T, Y = C or T). PCR was performed in a total volume of 50 mul with 2.5 U of the Taq-polymerase AmpliTaq Gold (Perkin Elmer, Roche Diagnostics, Basel, Switzerland) according to the manufacturer's recommendations (35 cycles: 1 min 94° C, 1 min 52° C, 1 min 72° C) using the DNA Thermal Cycler 960 (Perkin Elmer, Roche Diagnostics, Basel, Switzerland). The purified PCR product was then sequenced by dye terminator cycle sequencing according to the manufacturer's recommendations (Perkin Elmer Applied Biosystems, Warrington). The sequence comparison with DNA from HPV types 1-70 demonstrated a > 96.3% homology with HPV 29 DNA. In contrast a comparison with other cutaneous HPV-types revealed a 43% homology for HPV3 and a 50% homology for HPV10.

Discussion

Spotted hyperpigmentation on sun-exposed sites such as the face can be quite common. In young people simple freckles must be distinguished from solar lentigines. The later have a more intensive color and do not darken or increase in number on sun exposure as freckles do. Simple freckles show no morphological abnormality on biopsy. Solar lentigines are histologically characterized by a linear increase in the number of melanocytes at the dermoepidermal junction without any cytological atypia and no budding down of these melanocytes into the underlying dermis. Pigmented actinic keratoses and the flat type of seborrhoeic warts show characteristic changes within the epidermis.

In 1988 and in 1999, we reported two cases of pigmented bowenoid papulosis of the neck containing HPV 16 in the first and HPV 18 in the second patient [1, 2]. Clinically, the lesions on the face of the patient we describe in this report resembled those found in our patients with extragenital bowenoid papulosis. However, the microscopic examination of the facial skin lesions did not show bowenoid features within the epidermis. Nevertheless, on the basis of finding intracellular vacuolization within the cells of the upper epidermal layers, we suspected that the lesions could have been induced by viral infection [3-5]. Using PCR and DNA sequencing we clearly identified HPV 29 DNA.

HPV 29 was first described by Favre et al. in 1989, and appears to be related to HPV types associated with common as well as with flat warts [6]. Later on, HPV 29 was also found in benign proliferations and in carcinomas of the skin in immunosuppressed patients [7].

Altogether, the occurrence of HPV 29 is only rarely mentioned within the extensive HPV-literature. We find it very interesting to detect this virus type in the unusual lesions of our male immunocompetent patient. To our knowledge, this is the first case of HPV 29-induced spotted hyperpigmentation of the face. Our findings suggest that HPV could cause more varied skin lesions than is generally assumed.

Article accepted on 15/10/01

REFERENCES

1. Baron JM, Rübben A, Grussendorf-Conen EI. HPV 18-induced pigmented bowenoid papulosis of the neck. J Am Acad Dermatol 1999; 40: 633-4.

2. Grußendorf-Conen EI. HPV 16-induzierte pigmentierte bowenoide Papulose am Hals. Akt Dermatol 1988; 14: 317-9.

3. Egawa K. New types of human papillomaviruses and intracytoplasmatic inclusion bodies: a classification of inclusion warts according to clinical features, histology and associates HPV types. Br J Dermatol 1994; 130: 158-66.

4. Egawa K, Inaba Y, Yoshimura K, Ona T. Varied clinical morphology of HPV-1-induced warts depending on an anatomical factors. Br J Dermatol 1993; 128: 271-6.

5. Grußendorf EI. Lichtmikroskopische Untersuchungen an typisierten Viruswarzen (HPV-1 und HPV-4). Arch Dermatol Res 1980; 268: 141-8.

6. Favre M, Croissant O, Orth G. Human papillomavirus type 29 (HPV 29), an HPV type cross-hybridizing with HPV-2 and with HPV-3-related types. J Virol 1989; 63: 4906.

7. Shamanin V, Glover M, Rausch C, Proby C, Leigh IM, zur Hausen H, et al. Specific types of human papillomavirus found in benign proliferations and carcinomas or the skin in immunosuppressed patients. Cancer Res 1994; 54: 4610-3.


 

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