ARTICLE
Auteur(s) :, E Paul
Scheidegger1,*, Peter Itin1, Werner
Kempf2
1Dept. of Dermatology Kantonsspital Aarau 501.1 Aarau
Switzerland Fax: (+41) 62 28 38 69 52
2Department of Dermatology, University Hospital Zürich,
Switzerland
accepté le 12 Juillet 2004
Idiopathic cutaneous mucinosis is classified into various
clinicopathologic subsets (for review of an updated classification
see Rongioletti [1]). According to these authors the criteria for
localized lichen myxoedematosus (or papular mucinosis, PM) are as
follows: 1) papular or nodular/plaque eruption; 2) mucin deposition
with variable fibroblast proliferation; and 3) the absence of both
monoclonal gammopathy and thyroid disease. Atypical or intermediate
forms of PM, not meeting the criteria for either scleromyxedema or
the localized form, include cases of 1) scleromyxedema without
monoclonal gammopathy, 2) localized forms with monoclonal
gammopathy and/or systemic symptoms, 3) localized forms with mixed
features of the 5 subtypes, and 4) not well-specified cases.In this
report we describe a family with papular mucinosis of the axillary
pits. The unique features of these cases are 1) an unequivocal
autosomal dominant pattern of inheritance, 2) a disease association
with a concurrent autoimmune thyroiditis in one of the family
members (mother) and 3) the unusual location (arm pits),
distribution (bilateral symmetric) and number (innumerate) of the
skin lesions. This report also raises the question whether the
distinction between typical (i.e. absence of both monoclonal
gammopathy and thyroid disease) and atypical forms of PM is
universally justified.
Case report
A 43-year-old woman came for the assessment of incidental cutaneous
lesions in both of her arm pits ( (figure 1A) ). The papules
had first appeared during puberty and increased in number and
density over the last 20 years. No symptoms were reported by the
patient and thus she requested no further treatment. Her medical
history was remarkable for an autoimmune thyroiditis 5 years prior
to her presentation. Currently the patient is euthyroid and she is
taking no medication. On physical examination multiple tiny white
soft papules densely distributed throughout both arm pits were
found ( (figure
1A) ). Otherwise the physical and laboratory examinations
were unremarkable. In particular, no endocrinopathies (eg, hypo-
and hyperthyroidism), malignancy (mycosis fungoides), connective
tissue disorders (lupus erythematosus, myopathy or
dermatomyositis), and infectious diseases (scleredema associated
with upper respiratory tract infection or HIV) were found [2, 3].
A biopsy of an axillary papule was performed. Histopathological
examination revealed ( (figure 2) ) a
predominantly perifollicular deposition of mucin (Alcian-blue
staining) in the upper dermis and a sparse superficial perivascular
lymphocytic infiltrate. No obstruction of the intraepidermal
apocrine duct was found and spongiosis was absent, ruling out
Fox-Fordyce disease. No histiocytes were found. Follicular
mucinosis was not present. Otherwise the laboratory assessment for
thyroid function (TSH), thyroid antibodies and monoclonal
gammopathy was unremarkable.
The family history was most striking for the presence of
identical skin lesions in the mother’s identical twin 14-year-old
daughters ( (figure
1B) ). The skin lesions had appeared during the last two
years. The laboratory assessment for thyroid function (TSH) and the
protein electrophoresis (for monoclonal gammopathy) was
unremarkable
Discussion
For the first time an unequivocal autosomal dominant pattern of
inheritance with three affected family members for this unusual
manifestation of localized papular mucinosis can be established. We
could identify only three other publications [4-6] where a
hereditary pathogenesis is proposed. One case report [4] involved
two young sisters who are described as having an asymptomatic
papular eruption on the forearms, the clinical, histopathological
and ultrastructural features of which were consistent with acral
persistent papular mucinosis. The other case report [5] describes a
girl presenting with a childhood dermal mucinosis, whose father
reported having had similar lesions when he was a child, which
completely disappeared during adolescence. Alves et al. [6]
performed a histopathological investigation in patients with
mucinosis and they included two families, one with manifestation in
a father and daughter and in the other family a brother and a
sister were affected [6]. However no details of the clinical
aspects were given in this histopathological study. A search on the
Online Mendelian Inheritance of Man (OMIM) data base generated no
known molecular mutations for this skin disease.
Other unusual features of the present case report are the
atypical location (arm pits), distribution (bilateral symmetric)
and number (innumerate) of the skin lesions. This circumstance
makes a strong case for a genetic factor being responsible for this
peculiar presentation. Alternatively the location and distribution
of the skin lesions may by attributed to a Koebner phenomenon. This
has previously been reported in a patient with isomorphic response
in scleromyxoedema [7]. The distribution (bilateral) of the
lesions, however, make this hypothesis rather unlikely. A
symmetrical pattern of well-circumscribed mucin containing papules
designated “hereditary progressive mucinous histiocytosis” has
previously been reported [8]. The location (dorsum of hands, sides
of fingers, extensor aspect of forearms) as well histology (dermal
nodules composed of epithelioid hisitocytes) are very different
from our observation.
None of these characteristics fit into the known typical pattern
or current classification systems of papular mucinosis or localized
lichen myxoedematosus. Only two other case reports were found in
the literature with an aberrant (i.e. non-acral) distribution
pattern [9, 10] One case involved a patient with multiple papules,
grouped but not confluent, asymptomatic, skin-coloured or slightly
erythematous and located on the lumbar area [9]. In the other
report a 26-year-old female patient experienced a papular eruption,
involving the scalp, face, neck and trunk, accompanied by
periarticular papules on the hands and arthralgias [10].
Interestingly in the study by Alves et al. [6] the four familial
cases all had numerous lesions also on the trunk. Secondary causes
of mucinosis (endocrinopathies, malignancy, connective tissue
disorders, and infectious causes [2, 3, 11, 12]) were ruled out by
immune serology (i.e. lupus erythematosus, thyroid function), case
history as well as clinical assessment.
Finally we strongly believe that the occurrence of concurrent
autoimmune thyroiditis in one of the affected individuals (mother)
was not merely coincidental but causal. This notion is supported by
many previous publications on disease associations with this
particular skin disease [13].
This has practical implications for the euthyroid daughters
since a serial (once yearly) follow-up of thyroid function is – in
our opinion – mandatory.
The circumstances of this case also allow for speculation on the
pathogenesis of this rare skin disease: a mutational event may
allow for mucin-like material to accumulate (much like a “storage
disease”) upon which an “appropriate” immune response is mounted
crossreacting with thyroid epitopes. Support for this notion can be
derived from reports of papular mucinosis [14, 15] in patients with
Hunter syndrome (a hereditary mucopolysaccharidosis), particularly
in the mild form presenting with normal development and growth.
Alternatively, an inappropriate activation of the immune system
constitutes the primary event after which mucin is deposited in the
interstitial tissue as a secondary event. Either way this case
demonstrates the strong genetic (or hereditary) role in the
pathogenesis of this particular skin disease.
References
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