ARTICLE
Auteur(s) : Ichiro KATAYAMA Minako HIRAYAMA Kumiko
EISHI
Department of Dermatology, Nagasaki University School of
Medicine, 1‐7‐1Sakamoto, Nagasaki, 852‐8501 Japan
Reprints: I. Katayama
Article accepted on 14\7\03 Key words: Milia are
common benign keratinous cysts which are subgrouped into primary
and secondary milia [1]. Primary milia are occasionally observed at
birth, occurring mostly on the face particularly around the eyelids
and the cheeks and thought to be of follicular origin while
secondary milia usually occur after blistering skin disorders [2]
or topical steroids [3] and are thought to be of eccrine origin.
Eruptive milia without any underlying diseases or limited use of
topical steroid has been previously reported [4, 5]. In contrast to
these common or eruptive milia, several genodermatosis have been
reported to be accompanied by multiple eruptive milia and basaloid
follicular hamartoma or basal cell epithelioma [6, 9]. These
dermatosis showed several common characteristics such as hair
abnormality, hypohidrosis or keratinizing disorders such as palmar
pit in addition to milia. However quantitative measurement of
sweating has not been reported in the previous literature. An
8 year‐old Japanese girl presented with multiple tiny white
and comedo like papular eruptions on the face and extremities. Her
mother had noticed such cutaneous manifestations and bilateral
bluish macular lesions consistent with nevus of Ota at birth.
Papular eruptions gradually increased in number and spread over the
extremities especially on the sun‐exposed areas. Physical
examination revealed tiny white papules 2‐3 mm in diameter and
comedo‐like lesions distributed on the face (Fig. 1), dorsal aspect of
the hand and lateral aspect of the extremities (Fig. 2). Fading bluish
macular lesions with bluish sclera were observed on the bilateral
nasolabial folds (after dyelaser treatment). Thyroid goiter was
also present at the first visit which was later diagnosed as simple
goiter by an endocrinologist. Other mucocutaneous manifestations
such as hair or nail abnormalities, palmar and sole pit or
dermatosis papulosa nigra‐like eruptions were not observed. Family
history was not contributory and no similar cases were documented
in her pedigree at the time of first visit..
. She noticed hypohidrosis especially on the sun‐exposed areas,
where multiple milia were present after the progression of the
disease. To evaluate her sweating function, we performed QSART as
described previously [10]. Briefly the patients or normal
volunteers were asked to keep quiet for 60 minutes before
measurement in a climatic chamber (24 ± 0.5°C chamber
temperature and 40 + 0.3% relative humidity with less
than 1 m\sec air velocity). Iontophoretically applied
acetylcholine into the skin from the outer compartment stimulates
the underlying sweat glands directly (DIR sweating) while the
glands of the skin in the central compartment of the capsule are
activated indirectly via axon reflex (AXR sweating). The middle
compartment separates the outer and central compartments to avoid
diffusion of acetylcholine. Sweating rates were measured by a
hygrometer (H211, Technol Seven, Yokohama, Japan). Sweat
onset‐time, latent period for sweating after current loading
(latency), and sweat volume for 5 min, area under the sweating
curve, 0‐5 min for AXR and 6‐11 min DIR were used for the
analyses. Reduced sweating was observed after iontophoretically
applied acetylcholine on the forearm (direct sweating) (Figure 3). The results from
QSART analysis suggest that reduced sweating seen in this case
might be attributable to the possible presence of morphological
abnormality or obstruction of sweat ducts which might be
responsible for the induction of milia. Because not only direct
sweating but also axon reflex‐induced sweating were impaired in
this case.
. Histopathologically, the keratotic cyst showed trichilemmal
keratinization with a homogenous horny layer, swelling of the cells
close to the cyst and connection with tinyx vellus hair cysts
(Fig. 4).
Milia‐like small trichilemmal cysts (Fig. 5 right) and
projection of basaloid cells with a sprouting hair germ‐like
structure in connection with fibrous stroma around the bland
basaloid cells without clefting (Fig. 5 left) were
observed adjacent to milia shown in Fig. 4 in the serial
sections of white papules. These histopathological findings suggest
that the milia seen in this case might be derived from the
infundibular portion of the hair follicle. So the histopathological
diagnosis is rudimentary basaloid follicular hamartoma. No
histopathological finding of basal cell epithelioma or
trichoepithelioma could be demonstrated in this specimen. We
diagnosed this case as sporadic generalized basaloid follicular
hamartoma syndrome with hypohidrosis and positive anti‐nuclear
antibody. Our case might be categorized into the spectrum of
ectodermal dysplasia proposed by Patrizi et al. [11].
Similar diseases and their differential diagnoses are summarized in
Table I.
.
.
Table I. Summarized data of generalized
basaloid follicular hamartoma ‐ spectrum diseases
|
Mode of inheritance |
BFHs |
Milia |
Comedo |
Hypohidrosis |
Hypotrichosis |
Palmar, Planar pit |
Other skin lesions |
Positive ANAs |
| present case |
Sporadic |
+ |
+ |
+ |
+ |
+\‐‐ |
‐‐ |
‐‐ |
+ |
| GBFHS* |
Autosomal dominant |
+ |
+ |
+ |
+\‐‐ |
+ |
+ |
Acrochordons |
‐‐ |
| BDCS** |
X‐linked dominant |
+ |
+ |
+ |
+ |
+ |
‐‐ |
BCEs |
‐‐ |
| BCS*** |
N.D. |
+ |
‐‐ |
‐‐ |
‐‐ |
+ |
‐‐ |
Acrochordons |
+ |
| Rhombo syndrome |
Autosomal dominant |
‐‐ |
+ |
‐‐ |
‐‐ |
+ |
‐‐ |
BCEs |
‐‐ |
| Oley syndrome |
N.D. |
N.D. |
+ |
N.D. |
N.D. |
+ |
N.D. |
BCEs |
N.D. |
| Patritzi syndrome |
N.D. |
N.D. |
+ |
N.D. |
N.D. |
N.D. |
‐‐ |
Steatocystoma multiplex Eruptive vellus hair cyst |
N.D. |
| BCNS**** |
Autosomal dominant |
‐‐ |
+ |
+ |
N.D. |
N.D. |
+ |
BCEs |
N.D. |
GBFHS* Generalized basaloid follicular hamartoma syndrome BDCS **
Bazex‐Dupre‐Christol syndrome BCS*** Brown‐Crounse syndrome
BCNS**** Basal cell naevus syndrome ND**** Not described . The
milia in our case are still progressing and basal cell epithelioma
has not developed two years after the first visit. Topical peeling
with salicylic acid or vitamin D3 ointment were
unsuccessful.
Discussion
Milia are common benign keratinous cysts which are subgrouped
into primary and secondary milia. Primary milia are occasionally
observed at birth, occurring mostly on the face particularly the
eyelids and the cheeks and thought to be of follicular origin while
secondary milia usually occur after blistering skin disorders and
are thought to be of eccrine origin. In contrast to these common
milia, several genodermatosis have been reported to be accompanied
by multiple eruptive milia with or without the histopathological
features of basaloid follicular hamartoma or basal cell
epithelioma. These dermatosis show several common characteristics
such as hair abnormality, hypohidrosis or keratinizing disorders in
addition to milia.
Recently Wheeler et al. proposed a new clinical entity on
the basis of the observation about a North Carolina family and
termed it "Generalized basaloid follicular hamartoma syndrome"
[12]. Affected siblings in the family developed multiple eruptive
milia, comedo‐like lesions, dermatosis papulosa nigra‐like
eruptions with diffuse scalp hypotrichosis and pinpoint palm\sole
pits in early childhood that showed autosomal dominant inheritance.
This new entity is clearly differentiated from previously described
diseases such as Bazex‐Dupre‐Christol syndrome, Brown‐Crouse
syndrome and Rombo syndrome on the basis of their clinical and
histopathological findings and the mode of inheritance as described
in their article. Although common clinical features such as
multiple milia with the basaloid follicular hamartoma or
hypertrichosis are observed in these genodermatosis, the patients
with this new genodermatosis never develop basal cell epithelioma
and distinct palm\sole pits are complicated in most of the
patients. From these observations, they concluded this new
genodermatosis could be categorized into the same clinical entity
that has in common a continuous gene syndrome or a different
allelic form of the same gene mutation. The major problems left
unsettled in this new entity are the degree of hypohidrosis,
presence of palm\sole pits and the transformation of basaloid
hamartoma into basal cell epithelioma.
Our case presented multiple milia, comedo‐like eruptions and
basaloid follicular hamartoma like features without any
histopathological findings of basal cell epithelioma or
trichoepithelioma. Palm\sole pits and hypotrichosis were not
apparent at the time of consultation. Vermiculate atrophoderma seen
in Rombo syndrome or follicular atrophoderma seen in
Bazex‐Dupre‐Christol syndrome were not observed in our case. Mode
of inheritance was not confirmed in this study because it was
difficult to see the pedigrees other than her parents and sister.
Other siblings might have similar clinical features. Reduced
sweating was observed after iontophoretically applied acetylcholine
on the forearm by quantitative QSART analysis, which is the first
report in eruptive milia and a possible complication with basaloid
follicular hamartoma. Complications of thyroid goiter, nevus of Ota
and positive ANA have not been documented in basaloid follicular
hamartoma syndrome‐spectrum genodermatosis in the previous reports
except for positive ANA in Brown‐Crounse syndrome [7] or
complication with SLE [13], of which the significance are not
clarified at present. Based on these findings, our current
diagnosis was made as eruptive milia with hypohidrosis. Although
the genes linked for these genodermatosis have been reported in the
recent literature [14], mechanisms of impaired sweating other than
obstruction of sweat ducts, possible transformation of basal cell
epithelioma, and mode of inheritance and new mutated alleles should
be confirmed in future studies.
References
1 . Epstein W, Kligman AM. The pathogenesis of milia and
benign tumors of the skin. J Invest Dermatol 1956; 26:
1‐11.
2 . Leppard B, Sneddon IB. Milia occurring in lichen
sclerosis et atrophicus. Br J Dermatol 1975; 92: 711‐4.
3 . Tsuji T, Kadoya A, Tanaka R, Kono T, Hamada T. Milia
induced by corticosteroids. Arch Dermatol 1986; 122:
139‐40.
4 . Heard MG, Horton WH, Hambrick GW. The familial
occurrence of multiple eruptive milia. Birth Defects 1971;
7: 333‐7.
5 . Langley RGB, Walsh NMG, Ross JB. Multiple eruptive
milia: Report of a case, review of the literature and a
classification. J Am Acad Derm 1997; 37: 353‐6.
6 . Bazex A, Dupre A, Christol B. Atrophodermie
Folliculaire, proliferations baso‐cellulaires et hypotrichose.
Ann Dermatol Syphilgr (Paris) 1966; 93: 241‐54.
7 . Brown AC, Crounse RG, Winkelmann RK. Generalized
hair‐follicle hamartoma: associated with alopecia, aminoaciduria
and myasthenia gravis. Arch Dermatol 1969; 99: 478‐93.
8 . Brownstein MH. Basaloid follicular hamartoma: solitary
and multiple. J Am Acad Dermatol 1992; 27: 237‐40.
9 . Oley CA, Sharpe H, Chenevix‐Trench G. Basal cell
carcinomas, coarse sparse hair, and milia. Am J Med Genet
1992; 43: 799‐804.
10 . Eishi K, Lee JB, Bae SJ et al. Impaired
sweating function in adult atopic dermatitis: results of the
quantitative sudomotor axon reflex test. Br J Dermatol
2002
; 147: 683‐8.
11 . Patrizi A, Neri I, Guerrini V et al. Persistent
milia, steatocystoma multiplex and eruptive vellus hair cysts:
variable expression of multiple pilosebaceous cysts within an
affected family. Dermatology 1998; 196:392‐6.
12 . Wheeler Jr CE, Carroll M, Groben PA et al.
Autosomal dominantly inherited generalized basaloid follicular
hamartoma syndrome: Report of a new disease in a North Carolina
family. J Am Acad Dermatol 2000; 43: 189‐206.
13 . Morton S, Stevens A and Powell RJ. Basaloid follicular
hamartoma, total body hair loss and SLE. Lupus 1998; 7:
207‐9.
14 . Vabres P, Lacombe D, Rabinowitz LG, Augert G, Anderson
CE, Taibe A et al. The gene for Bazex‐Dupre‐Christol
syndrome maps to chromosome Xq. J Invest Dermatol 1995; 105:
87‐91.
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