ARTICLE
Auteur(s) : Naoyuki
Higashi, Seiji Kawana
Department of Dermatology, Nippon Medical School, 1-1-5,
Sendagi, Bunkyo-ku, Tokyo, 1138603, Japan
accepté le 3 Mars 2005
A topic diseases entail a hyperreactivity towards environmental
antigens [1], whereas autoimmune diseases show hyperreactivity
towards endogenous antigens. Therefore the two conditions could be
mutually exclusive. So far there have only been a few case reports
of patients displaying both atopic eczema (AE) and systemic lupus
erythematosus (SLE). Both diseases express an enhanced Th2 cytokine
profile [2]. Also, several autoantibodies have been detected in
patients with AE [3, 4]. And 20 to 30% of AE patients show positive
antinuclear antibodies (ANA) [5], but their significance is
unclear. Recent reports have indicated that the incidence of AE in
SLE is comparable to persons without SLE [6, 7]. Here, we present
two patients with AE who developed SLE.
Case reports
Case 1
A 25-year-old man was admitted complaining of fever (37.5°C) and
butterfly erythema ( (figure 1A) ). He had no
active symptoms of AE at admission, but had suffered from mild to
moderate AE since 5 years of age. His elder sister had also
suffered from AE. He had been treated with topical steroids,
moisturizing cream and oral anti-histamine in our outpatient clinic
3 years previously. Poikiloderma-like changes in his neck were
observed as a clinical appearance of chronic AE. In addition he had
Raynaud’s phenomenon. Five years before admission he was found to
have increased anti-RNP antibodies (> 500 U/ml), but was
not diagnosed as having mixed connective tissue disease (MCTD).
Three years before the present admission he was diagnosed with
nephritic syndrome (membranous nephropathy, stage II~III). On this
admission, blood tests were normal except for increased lactate
dehydrogenase (LDH) 648 IU/l (normal range 180-460 IU/l).
Urinalysis revealed proteinuria (0.3 g/day). His immunological
findings are summarized in table 1. A facial skin biopsy showed
hyperkeratotic changes, follicular plugging, thinning of epidermis,
slight degeneration of the basal layer, edema in upper dermis and a
predominantly lymphocytic infiltration around hair follicles and
appendages compatible with LE ( (figure 1B) ). The lupus
band test revealed a moderate granular deposition of IgG, C3 in the
dermis-epidermis junction. A new renal biopsy showed membranous
nephropathy stage III. He was diagnosed as suffering from SLE, and
steroid therapy (30 mg/day) [8] was effective in controlling
his symptoms. His AE was treated with only moisturizing cream due
to the treatment with systemic steroids.
Case 2
A 27-year-old man had suffered from mild AE since childhood. His
elder brother had also AE. He was admitted complaining of facial
edema and an acne-like eruption ( (figure 2) ) but without
eczema. His past history besides AE was allergic rhinitis. Blood
tests showed slight leukopenia, slightly elevated GOT, BUN and
creatinine, increased total cholesterol and decreased total protein
and albumin. Urinalysis revealed proteinuria (4.1 g/day),
50-99 erythrocytes, and 20-29 granular and hyaline casts per
high-power field. The main immunological findings are summarized in
table 1. A skin biopsy from a chilblain-like lesion showed changes
compatible with LE. A renal biopsy showed lupus nephritis IV b. He
was started on prednisolone 60 mg/day with much improvement.
Discussion
We present two patients with AE, who developed SLE. Case 1
fulfilled four of the revised American Rheumatism Association (ARA)
criteria for SLE [8]. He had manifestations of MCTD, but did not
strictly fulfill the criteria for a diagnosis of MCTD [9]. Case 2
satisfied five of the revised ARA criteria for SLE [8]. He was
treated for AE in childhood. He had normal IgE, but a positive RAST
to pollen. Histologically there was slight liquefaction
degeneration of the basal layer of the epidermis and the lupus band
test was positive in both cases. It is noteworthy that both were
males, as 90% of patients with SLE are females. Interestingly, Case
1 developed SLE during treatment of mild AE in our department. Case
2 did not have any active symptoms of AE, but had a past history of
AE.
Recently, Sekigawa et al. reported 2 cases of AE associated with
MCTD-like immune abnormalities [10]. Although both cases had a high
titer of anti-RNP Ab, they did not fulfill the criteria for a
diagnosis of MCTD [9]. Only 4 patients with AE have been reported
to develop SLE in conference abstracts in Japan. The 4 reported
patients were female, unlike our cases. The reason why there are
few case reports of AE with SLE is unknown. It is unlikely that two
morbid conditions, AE and SLE, simultaneously exist in an
individual. Another conceivable reason may be the difference of
developmental age between AE and SLE. When a patient developed SLE,
no symptom of AE was generally found, due to self-healing in AE,
like our case 2. Thus we considered case 1 a very rare status.
Sekigawa reported that the incidence of AE was 6% in SLE
patients, comparable to that in healthy control (15%) [7]. In
accordance with this report, among 33 patients with SLE in our
department, four had suffered from AE (12.1%). There was only 1
case who developed SLE during treatment of active symptoms of AE.
Thus we reconsidered case 1 as a very rare patient, because Morton
and Sekigawa referred the past history of AE in SLE.
Several autoantibodies have been detected in patients with AE
[3, 4]. Between 20 to 30 % of AE patients have ANA ranging in
titer between 1:40 and 1:1280 [5]. Nineteen percent of patients
with AE in our department had positive ANA (range 1:40 to 1:640).
We do not know whether ANA (+) patients with AE will develop
autoimmune disease or not. Case 1 had a high titer of anti-RNP Ab
before development of SLE. Thus it is necessary to measure various
autoantibodies in ANA (+) patients with AE and to carefully monitor
those AE patients for a long period for development of SLE
symptoms, if other autoantibodies are positive in ANA (+) patients
with AE.
Becker described a relationship between AE and other autoimmune
disease such as SLE, Crohn’s disease and rheumatoid arthritis, as
there is an overlap of autoimmune/inflammatory loci on 1p22.3-p22.1
(TGFbRIII), on 3q21-q22.2 (CD80, CD86) and on 19p13 suggesting that
underlying genetic components may not be disease or tissue
specific, but may share basic mechanisms of immune regulation
[11].
Further investigations should clarify the relationship between
AE and SLE and thus contribute to reveal pathophysiological
features of AE and SLE.
Acknowledgments
This work was supported in part by grants-in-aid 14770433 (NH) from
the Ministry of Education, Science and Culture of Japan. We thank
Dr. Kristian Thestrup-Pedersen for his helpful comments during the
preparation of this manuscript.
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