3
British Journal of Dermatology 2001; 144: 1067–1069. Successful topical treatment of focal epithelial hyperplasia (Heck’s disease) with interferon-b M.STEINHOFF, D.METZE, E.STOCKFLETH* AND T.A.LUGER Department of Dermatology, University of Mu ¨nster, von-Esmarch-Str. 56, 48129 Mu ¨nster, Germany *Department of Dermatology, University of Kiel, 24105 Kiel, Germany Accepted for publication 26 December 2000 Summary We report the successful topical treatment of focal epithelial hyperplasia (Heck’s disease) with interferon-b (Fiblaferon gel w ). Topical treatment with interferon-b appears to be an effective, simple, non-invasive, cheap and low-risk alternative to other invasive or surgical therapeutic modalities. Key words: focal epithelial hyperplasia, interferon Focal epithelial hyperplasia (FEH, Heck’s disease) is a rare skin disease caused by human papillomavirus (HPV), which mainly affects the oral mucosa, and rarely the genital mucosa, of children. FEH is a chronic disease and can be associated with a significant reduction in quality of life. Unfortunately, most treatments such as surgical, cryosurgical, electro- coagulatory or laser procedures or systemic treatment with interferon-a are invasive and expensive, with many potential side-effects. We report the successful topical treatment of FEH with interferon-b . Case report A 4-year-old boy of Turkish origin presented with a 1-year history of enlarging papillomatous skin lesions on the lips and oral mucosa. Owing to severe pain the child had developed significant loss of body weight, sleep deficiency and general malaise. Inspection of the ears, nose and throat revealed verrucous skin lesions on the lips, tongue and hard palate. These consisted of multiple solitary or aggregated, roundish, skin-coloured or pink papules and nodules (Fig. 1). Local treatment with antiseptics and glucocorticosteroids was ineffective. There was no history of infectious, immunosuppressive or metabolic diseases. Routine laboratory parameters as well as immune parameters (B cells, T cells, CD41, CD81 and HLA- activated T cells, natural killer cells, IgE, immuno- globulins, skin test for recall antigens) were normal before therapy and during follow-up. Histological examination of a biopsy from the lip showed a parakeratotic hyperplastic epidermis with some vacuolated and dyskeratotic epithelia. The rete ridges showed some clubbing and were occasionally turned inwards. The papillary dermis expressed dilated capillaries and a discrete perivascular lymphocytic infiltrate. HPV 32 DNA was clearly detected in biopsy material using polymerase chain reaction (PCR). Analysis of HPV DNA was carried out using two different sets of L1 consensus primers in a nested PCR assay. PCR conditions for amplification of mucosal HPVs using primers MY9/MY11 have been published recently. 1 Primers CP65/CP70 and CP66/CP69 were used in a nested PCR to detect the complete set of epidermo- dysplasia verruciformis-associated HPV types. 2 Typing of amplified HPV DNA was performed by restriction fragment length polymorphism analysis and subsequent hybridization with a generic oligonucleotide probe as described previously. 3 The clinical and histological features, and the molecular detection of HPV 32 DNA, were typical of FEH. Interferon-b (Fiblaferon gel w , Biosyn, Fellbach, Germany) was applied topically five times daily (100,000 IE g 21 ; approximately 2·5 g weekly). This agent is currently licensed for condyloma acuminatum but, because of its consistency, it is suitable for the treatment of oral as well as anogenital mucosal diseases. Improvement of the verrucous skin lesions was observed within 2 weeks. Neither systemic nor local adverse effects occurred and periodic checks on blood parameters remained normal. Treatment with interferon-b was continued for 12 weeks until total q 2001 British Association of Dermatologists 1067 Correspondence: Martin Steinhoff. E-mail: [email protected]

Successful topical treatment of focal epithelial hyperplasia (Heck’s disease) with interferon-β

Embed Size (px)

Citation preview

Page 1: Successful topical treatment of focal epithelial hyperplasia (Heck’s disease) with interferon-β

British Journal of Dermatology 2001; 144: 1067±1069.

Successful topical treatment of focal epithelial hyperplasia(Heck's disease) with interferon-b

M.STEINHOFF, D.METZE, E.STOCKFLETH* AND T.A.LUGER

Department of Dermatology, University of MuÈnster, von-Esmarch-Str. 56, 48129 MuÈnster, Germany

*Department of Dermatology, University of Kiel, 24105 Kiel, Germany

Accepted for publication 26 December 2000

Summary We report the successful topical treatment of focal epithelial hyperplasia (Heck's disease) with

interferon-b (Fiblaferon gelw). Topical treatment with interferon-b appears to be an effective, simple,non-invasive, cheap and low-risk alternative to other invasive or surgical therapeutic modalities.

Key words: focal epithelial hyperplasia, interferon

Focal epithelial hyperplasia (FEH, Heck's disease) is arare skin disease caused by human papillomavirus

(HPV), which mainly affects the oral mucosa, and

rarely the genital mucosa, of children. FEH is a chronicdisease and can be associated with a significant

reduction in quality of life. Unfortunately, most

treatments such as surgical, cryosurgical, electro-coagulatory or laser procedures or systemic treatment

with interferon-a are invasive and expensive, with

many potential side-effects. We report the successfultopical treatment of FEH with interferon-b .

Case report

A 4-year-old boy of Turkish origin presented with a

1-year history of enlarging papillomatous skin lesionson the lips and oral mucosa. Owing to severe pain the

child had developed significant loss of body weight,

sleep deficiency and general malaise. Inspection of theears, nose and throat revealed verrucous skin lesions

on the lips, tongue and hard palate. These consisted of

multiple solitary or aggregated, roundish, skin-colouredor pink papules and nodules (Fig. 1). Local treatment

with antiseptics and glucocorticosteroids was ineffective.

There was no history of infectious, immunosuppressiveor metabolic diseases.

Routine laboratory parameters as well as immune

parameters (B cells, T cells, CD41, CD81 and HLA-activated T cells, natural killer cells, IgE, immuno-

globulins, skin test for recall antigens) were normal

before therapy and during follow-up.

Histological examination of a biopsy from the lipshowed a parakeratotic hyperplastic epidermis with

some vacuolated and dyskeratotic epithelia. The rete

ridges showed some clubbing and were occasionallyturned inwards. The papillary dermis expressed dilated

capillaries and a discrete perivascular lymphocytic

infiltrate.HPV 32 DNA was clearly detected in biopsy material

using polymerase chain reaction (PCR). Analysis of

HPV DNA was carried out using two different sets of L1consensus primers in a nested PCR assay. PCR

conditions for amplification of mucosal HPVs using

primers MY9/MY11 have been published recently.1

Primers CP65/CP70 and CP66/CP69 were used in a

nested PCR to detect the complete set of epidermo-

dysplasia verruciformis-associated HPV types.2 Typingof amplified HPV DNA was performed by restriction

fragment length polymorphism analysis and subsequent

hybridization with a generic oligonucleotide probe asdescribed previously.3 The clinical and histological

features, and the molecular detection of HPV 32

DNA, were typical of FEH.Interferon-b (Fiblaferon gelw, Biosyn, Fellbach,

Germany) was applied topically five times daily

(100,000 IE g21; approximately 2´5 g weekly). Thisagent is currently licensed for condyloma acuminatum

but, because of its consistency, it is suitable for the

treatment of oral as well as anogenital mucosaldiseases. Improvement of the verrucous skin lesions

was observed within 2 weeks. Neither systemic nor

local adverse effects occurred and periodic checks onblood parameters remained normal. Treatment with

interferon-b was continued for 12 weeks until total

q 2001 British Association of Dermatologists 1067

Correspondence: Martin Steinhoff.

E-mail: [email protected]

Page 2: Successful topical treatment of focal epithelial hyperplasia (Heck’s disease) with interferon-β

1068 M.STEINHOFF et al.

q 2001 British Association of Dermatologists, British Journal of Dermatology, 144, 1067±1069

remission was achieved (Fig. 2), and the patient has

remained disease free during 7 months of follow-up.

Lesion-associated pain cleared about 2 weeks aftertherapy with topical interferon-b, appetite was restored

and the child gained weight 3 weeks after therapy was

started.

Discussion

FEH (Heck's disease) is a rare but potentially seriousdisease of the mucosae. In 1965, Archad et al.

described Inuit and Indian children from North and

South America suffering from verruciform papules andnodules on the oral mucosa, sometimes also affecting

the anal and/or genital mucosa.4 Since then, FEH has

been described from most continents. The incidencevaries from 0´11% (Sweden) up to 17´3% (Greenland).5

In Germany, children of Turkish, rather than German,

origin are predominantly affected.6±8

Owing to association with certain ethnic groups,

a genetic (co)-factor is probable. An increased

incidence in close communities and genetically

unrelated family members favours an infectious

pathogenesis. HPV types 1,9 11, 13,10 3211,12 and248 have been isolated from biopsies of mucosal

material in patients with FEH, HPV 32, 13 and 11

being the most common.13

In contrast to other HPV-induced papillomas, FEH is

only rarely associated with detectable immuno-

deficiency or immunosuppression. The immune statusof our patient was normal. However, an increased

association of FEH in immunosuppressed or human

immunodeficiency virus-positive patients has recentlybeen observed,12,14,15 underlining the importance of

early diagnosis of FEH.Spontaneous remission of FEH is occasionally

observed.10 However, papillomas in FEH can develop

in such considerable proportions that they are veryresistant to successful therapy,14 and may lead, as in

our patient, to significant functional disturbance. Thus,

a reliable long-term treatment of FEH with low risks orside-effects is desirable.

Figure 1. Focal epithelial hyperplasia in a 4-year old boy beforetherapy with topical interferon-b. (a) Lips and oral mucosa, and (b)

tongue.

Figure 2. Focal epithelial hyperplasia after interferon-b therapy(12 weeks). Almost complete remission of verrucous skin lesions of

(a) lips and oral mucosa, and (b) tongue.

Page 3: Successful topical treatment of focal epithelial hyperplasia (Heck’s disease) with interferon-β

TOPICAL INTERFERON TREATMENT OF HECK'S DISEASE 1069

q 2001 British Association of Dermatologists, British Journal of Dermatology, 144, 1067±1069

First-line therapies of FEH include surgical, cryo-

surgical, electrocoagulatory or (carbon dioxide) laserprocedures.16 However, these therapies are invasive

and are associated with well-known risks and side-

effects as compared with topical treatments. Intra-lesional treatment with interferon-a has been

recommended; Niebrugge et al.8 used a combination

of systemic acitretin and intralesional/subcutaneousinterferon-a. Systemic treatment with retinoids has

been reported in a Turkish family, but no data about

the therapeutic response were given.3 Treatment withinterferon-b appears to be an effective, simple, non-

invasive, cheap and low-risk alternative to other

invasive or surgical therapeutic modalities. Moreover,as we did not observe any local or systemic side-effects of

topically applied interferon-b it appears to be superior

to intralesional/subcutaneous interferon treatment.

References

1 Meyer T, Arndt R, Stockfleth E et al. Strategy for typing human

papillomaviruses by RFLP analysis of PCR products and

subsequent hybridization with a generic probe. Biotechniques

1995; 19: 632±9.

2 Stockfleth E, Rowert J, Arndt R et al. Detection of human

papillomavirus and response to topical 5% imiquimod in a case of

stucco keratosis. Br J Dermatol 2000; 143: 846±50.

3 Berkhout RJ, Bouwes-Bavinck JN, ter Schegget J. Persistence ofhuman papillomavirus DNA in benign and (pre)malignant skin

lesions from renal transplant recipients. J Clin Microbiol 2000; 38:

2087±96.

4 Archad HO, Heck JW, Stanley HR. Focal epithelial hyperplasia: anunusual mucosal lesion found in Indian children. Oral Surg 1965;

20: 201±12.

5 Axell T, HammerstroÈm L, Larsson A. Focal epithelial hyperplasiain Sweden. Acta Odontol Scand 1986; 39: 201±5.

6 Rechmann P, Florack M. Focal epithelial hyperplasia (Heck's

disease) of oral mucosa in a three-year-old German girl.

Dtsch Zahnarztl Z 1988; 43: 379±82.

7 Weidner F. Focal epithelial hyperplasia in a Turkish family.

Hautarzt 1994; 47: 927±9.

8 Niebrugge B, Villiers E, Gerlach K et al. Demonstration of HPV 24in long-standing Heck's disease with malignant transformation.

Eur J Dermatol 1999; 9: 477±9.

9 Petzold D, Pfister H. HPV 1 DNA in lesions of focal epithelial

hyperplasia Heck. Arch Dermatol Res 1982; 268: 313±16.

10 Pfister H, Hettich I, Runne U et al. Characterisation of human

papillomavirus type 13 from focal epithelial hyperplasia Heck

lesions. J Virol 1983; 47: 363±70.

11 Garlick JA, Calderon S, Buchner A, Mitrani-Rosenbaum S.Detection of human papillomavirus (HPV) DNA in focal epithelial

hyperplasia. J Oral Pathol Med 1989; 18: 172±7.

12 Greenspan D, de Villiers EM, Greenspan JS et al. Unusual HPVtypes in oral warts in association with HIV infection. J Oral Pathol

1988; 17: 482±8.

13 Padayachee A, van Wyk CW. Human papillomavirus (HPV) DNA

in focal epithelial hyperplasia by in situ hybridization. J Oral PatholMed 1991; 20: 210±14.

14 Vilmer C, Cavelier-Belloy B, Pinquier L et al. Focal epithelial

hyperplasia and multifocal human papilloma-virus infectionin an HIV-positive man. J Am Acad Dermatol 1994; 30:

497±508.

15 Marvan E, Firth N. Focal epithelial hyperplasia in an HIV positive

man. An illustrated case and review of the literature. Aust Dent J1998; 43: 305±10.

16 Bassioukas K, Danielides V, Georgiou I et al. Oral focal epithelial

hyperplasia. Eur J Dermatol 2000; 10: 395±7.