A Unique Case? Darier’s Disease Presented as Porcupine-Like Appearance and the Observation on Acitretin Treatment

doi:10.4236/jcdsa.2012.23027

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Journal of Cosmetics, Dermatological Sciences and Applications, 2012, 2, 136-140

http://dx.doi.org/10.4236/jcdsa.2012.23027 Published Online September 2012 (http://www.SciRP.org/journal/jcdsa)

A Unique Case? Darier’s Disease Presented as

Porcupine-Like Appearance and the Observation on

Acitretin Treatment*

Xi-Bao Zhang1#, Chang-Xing Li2, Xue-Mei Li1, Yu-Qing He1, Xiao Xu,1 Quan Luo1

1Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, China; 2Department of Dermatology, Dongguan

Hospital of Chronic Disease, Dongguan, China.

Email: #[email protected]

Received May 6th, 2012; revised June 10th, 2012; accepted June 29th, 2012

ABSTRACT

Dyskeratosis follicularis (Darier’s disease, DD) is rare autosomal dominant disease characterized by hyperkeratotic

papules that coalesce into plaques and occur primarily in seborrheic or intertriginous areas. Associated findings include

nail abnormalities. A 3-year-old boy presented with porcupine-like appearance for 2 years. The lesion from the back

was taken for light microscopy and electron microscopy. He was treated with acitretin (0.31 mg/d to 0.66 mg/d) for 8

years. Light microscopy and electron microscopy showed that the typical features of DD. The patient show good re-

spond to the treatment. During 8 years treatment, the patient had dry mouth and pruritus. The skeletal abnormalities

didn’t happen in the patient. Evaluation of the serum lipid profile, liver function and renal function were within normal

lever after treatment. Our findings showed that porcupine-like appearance is a unique pattern of DD. Acitretin may be a

useful therapeutic agent in children with DD and less likely to cause skeletal problems.

Keywords: Darier’s Disease; Acitretin

1. Introduction

The prevalence of DD has been estimated vary from one

in 36,000 to one in 100,000 [1]. Clinically, the distinctive

lesion is characterized by hyperkeratotic papules that

coalesce into plaques and occur primarily in seborrheic,

but also in intertriginous areas [1,2]. Coalescence of the

papules produces irregular warty plaques or papilloma-

tous masses, which, in the flexures, become hypertrophic,

and malodorous with painful fissured. Associated ab-

normalities include nail abnormalities characterized by

nail fragility, red and white longitudinal stripes and v-

shaped notches at the free margin of the nails [2]. In this

article, we describe a case of DD with porcupine-like ap-

pearance. The patient showed good respond to the treat-

ment of acitretin therapy.

2. Case Report

A 3-year-old boy had healthy skin at birth. At the age of

1 year, a brownish-red, keratotic papules and plaques

appeared in his scalp, ears, perianal and genital areas. A

biospy taken from his lesion revealed DD in the local

hospital. He showed no signifficant respond to the treat-

ment of 0.025% retinoc acid cream or 0.1% mometasone

furoate cream. The keratotic skin lesions worsened gra-

dually as she grew. At 3 years of age, roughening, thick-

ening and dryness of the keratotic skin lesions increased

progressively to most parts of the body. Mentally the

patient was normal and he had done well in school. His

general health had been good. No other family members

were affected.

On physical examination, the erythematous, keratotic,

follicular papules were over his scalp, face and ear (Fig-

ure 1(a)). The disseminated heavy papillomatous hy-

perkeratosis was dark gray-brown and thickest on the

legs, arms and trunk (Figures 1(b) and (c)). Nail involve-

ment was subungual hyperkeratosis, dystrophy of the

free margin of the nail and v-shaped notches at the free

margin of the nails (Figure 1(d)).

3. Materials and Methods

Biopsy specimens were taken from affected skin on his

back before treatment. The tissue specimens were studied

under the light microscope as paraffin sections stained

with hematoxylin-eosin or as l μm epoxy resin-fixed sec-

tions. For electron microscopy, the tissue was fixed 2

*Authors Xi-Bao Zhang and Chang-Xing Li contributed equally to this

work.

#Corresponding author.

A Unique Case? Darier’s Disease Presented as Porcupine-Like Appearance and the Observation on Acitretin Treatment 137

Figure 1. (a) The erythematous, keratotic, follicular papules were over his scalp, face and ear; (b) and (c) The disseminated

heavy papillomatous hyperkeratosis was dark gray-brown and thickest on the legs, arms and trunk; (d) Nail involvement was

subungual hyperkeratosis, dystrophy of the free margin of the nail and v-shaped notches at the free margin of the nails; (e)

and (f) The patient’s condition showed great improvement.

hours to 4 hours in 3% glutaraldehyde and postfixed in

1% osmium tetroxide. The specimens were stained en

bloc with uranyl acetate-lead citrate, dehydrated in a

graded alcohol series, and embedded in epoxy resin

(Epon812). Ultrathin sections were cut on an ultramicro-

tome, stained with uranyl acetate-lead citrate solutions,

and examined with an electron microscope.

Assessment of efficacy:

The definitions of efficacy used in the present investi-

gation were: 1) Cured in clinically. The improvement of

skin lesions comes to over 90% been cured; the kerato-

derma is totally desquamated or light coarse remains on

the skin. The patients can normally study and live in the

society without any handicap; the life quality was im-

proved completely; 2) Marked improvement. The im-

provement of skin lesions comes to 60% - 90% and the

patients can normally study and live, the life quality was

improved remarkable; 3) Improvement. The improve-

ment of skin lesions comes to 30% - 60% and the pa-

tients can nearly study and live as normal the life quality

was improved; 4) Failure. The skin improvement is less

than 30% and the patients can’t live in a normal life, the

life quality was improved in a little.

Safety evaluation: Evaluate the safety according to the

clinical side effects, changes in body weight and height,

examination results of routine blood tests, liver and renal

function, blood lipids and selective X-ray check for those

cases been treated more than one year.

4. Results

Biopsies taken from back showed hyperkeratosis, para-

keratosis, follicular plugging, irregular acanthosis, acan-

tholytic keratinocytes forming corp ronds and corp grains

(Figure 2), and an upward proliferation of papillae into

the clefts. The direct immunofluorescence was negative.

Electron microscopic studies have demonstrated cell

membrane damage, cytoplasmic vacuolization, dissolu-

tion of desmosome-keratin filament complexes and ag-

gregation of keratin filaments around cell nucle. In the

granular layer, the abnormality is cytoplasmic vacuoliza-

tion. The affected cells display a spectrum of vacuoliza-

A Unique Case? Darier’s Disease Presented as Porcupine-Like Appearance and the Observation on Acitretin Treatment

138

tion ranging from a predominantly perinuclear distribu-

tion giving a foamy or cytolytic appearance. The tono-

filaments and keratohyaline granules appear compressed

into dense rings without attachments with neighboring

cells (Figure 3(a)). Cells of the prickle layer, which are

within lacunae, are separated from each other, having

smooth rounded plasma membranes devoid of microvilli

and desmosome attachments, and increasing aggregation of

tonofilaments with perinuclear ditriution (Figures 3(b) - (d)).

Acitretin was used in the treatment of the case. The

start treatment dose was 5 mg/day (0.38 mg/kg/d). The

response was good and the patient’s condition showed

great improvement within 1 year. After 1 year, the dose

of acitretin was increased to 10 mg/day (0.66 mg/kg/d),

and the skin remained in good condition. After 2 years,

the dose of acitretin was reduced to 6 mg/day (0.31 mg/

kg/d), and the skin remained in good condition within 2

years. After 4 years, the dose of acitretin was reduced to

5 mg/day (0.31 mg/kg/d), and the skin remained in good

condition (Figures 1(e)-(f)) (Table 1).

During 8 years treatment, our patient had dry mouth

and pruritus. The skeletal abnormalities didn’t happen in

the patient. Evaluation of the serum lipid profile, liver

function and renal function were within normal lever

after treatment.

5. Discussion

The clinical expression of IH (Curth-Macklin) varies from

palmoplantar keratoderma to a severe generalized involve-

ment [3]. Histopathology shows granular cells with peri-

nuclear oedema and shell formation, and binuclear cells,

and the most prominent feature ultrastructurally are

Figure 2. Histology showed hyperkeratosis, parakeratosis,

follicular plugging, irregular acanthosis, acantholytic kera-

tinocytes forming corp ronds and corp grains.

(a)

(b)

(c)

(d)

Figure 3. (a) The tonofilaments and keratohyaline granules appear compressed into dense rings without attachments with

neighboring cells; (b-d) Cells of the prickle layer, which are within lacunae, are separated from each other, having smooth

rounded plasma membranes devoid of microvilli and desmosome attachments, and increasing aggregation of tonofilaments

with perinuclear ditriution.

A Unique Case? Darier’s Disease Presented as Porcupine-Like Appearance and the Observation on Acitretin Treatment 139

Table 1. Dose, improvement and side effects of acitritin.

Age (y) Height (cm) Weight (kg) Dose (mg/d) improvement skinmucosa bones nerves laboratory

3 90 13 5 C ++ ++ - - -

4 97 15 10 C ++ ++ - - -

5 103.5 17.5 10 C ++ ++ - - -

6 108 19 6 B ++ ++ - - -

7 114 22 6 B + + - - -

8 121.5 24.5 5 B + + - - -

9 126 26 5 B + + - - -

10 131 28 5 A + + - - -

+: Mild pruritus and dry; ++: Moderate pruritus and dry.

segregation of cytoplasmic components, perinuclear to-

nofilament shells and binuclear keratinocytes [3-5].

The clinical condition generalized epidermolytic hy-

perkeratosis, or bullous congenital ichthyosiform eryth-

roderma, is characterized at birth and in the neonatal pe-

riod by erythroderma, widespread bullae, and desqua-

mation resulting in denuded skin. Focal hyperkeratosis

may accompany these clinical findings. In infancy and

into adulthood, the erythema and bullae are replaced

with widespread hyperkeratosis, most prominent over

joints, leading to a characteristic cobblestone appearance.

Histologically, epidermolytic hyperkeratosis is charac-

terized by vacuolization of the mid and upper spinous

layer, large keratohyaline granules in vacuolated ex-

panded granular cytoplasm of the keratinocytes con-

taining an increased number of small and large irregu-

larly shaped keratohyaline and trichohyaline-like bodies,

and hyperkeratosis. The most prominent feature ultra-

structurally in epidermolytic hyperkeratosis, is the supra-

basal cells showed vacuolated cytoplasm and clumped

keratin tonofilaments as in epidermolysis bullosa Dowl-

ing-Meara [6,7].

Our patient presented with disseminated dark gray-

brown and thickest heavy papillomatous hyperkeratosis

on the legs, arms and trunk. The erythematous, keratotic,

follicular papules were over his scalp, face and ear. Nail

involvement was subungual hyperkeratosis, dystrophy of

the free margin of the nail and v-shaped notches at the

free margin of the nails. The clinical condition of our

patient is resemblance to a porcupine and similar with IH

(Curth-Macklin) and epidermolytic hyperkeratosis. It is

difficult to distinguish these three disorders by clinical

expression; however, the light microscopy and electron

microscopic features are different. Histologic examina-

tion showed dyskeratosis with typical “corps ronds and

grains,” suprabasilar acanthosis, and hyperkeratosis, of-

ten with formation of papillae. The ultrastructural studies

reveal breakdown of the desmosome-keratin filament

complexes between keratinocytes. The light microscopy

and electron microscopic features of our patient showed

that the typical features of DD. Our patient was diag-

nosed as DD.

Despite much progress in understanding of the under-

lying abnormality in DD, disappointingly little has changed

in our treatment armoury. Many patients with mild disease

require no treatment other than simple emollient-like soap

substitutes and moisturizers (in particular, those contain-

ing urea or lactic acid can reduce scaling and irritation)

[8], with advice about the effects of sunshine. For those

with more severe disease, oral retinoids (etretinate, aci-

tretin, isotretinoin) are the most effective prescription.

Most patients tolerate 0.6 mg/kg of acitrecin daily, but 10-

25 mg daily is a reasonable starting dose and the dose

can be increased gradually [8]. The clinical response is

good in 90% of patients: Hyperkeratosis is reduced and

papules are flattened, while malodour may also improve.

However, retinoids are teratogenic and pregnancy must

be avoided during and for a while after treatment. Reti-

noids treatment may cause skeletal abnormalities in chil-

dren including osteoporosis, periosteal plucking, slender

long bones and premature epiphyseal closure. A starting

dose of acitretin of 0.38 - 0.66 mg/kg/d was recom-

mended and good responses were seen within 1 - 3 years.

The maintenance dose was titrated down to the 0.31

mg/kg/d. During 8 years treatment, our patient had dry

mouth and pruritus. The skeletal abnormalities didn’t

happen in the patient. Evaluation of the serum lipid pro-

file, liver function and renal function were within normal

lever after treatment.

In conclusion, the present study has demonstrated that

porcupine-like appearance is a unique pattern of DD.

Acitretin may be a useful therapeutic agent in children

with DD and less likely to cause skeletal problems.

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