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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]
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.
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.
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