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© 2007 Acta Dermato-Venereologica. ISSN 0001-5555
DOI: 10.2340/00015555-0217
Acta Derm Venereol 87
261
Letters to the Editor
Sir,
Palmoplantar pustulosis (PPP) is considered to be a
variant of psoriasis, although recently it has been shown
to be genetically different from psoriasis vulgaris (1). The
majority of patients with PPP are women and smokers.
The nal target for inammation in this condition is
the palmoplantar sweat duct (2, 3), but the mechanisms
underlying the inammation are poorly characterized.
PPP patients have co-morbidity, with an increased pre-
valence of autoimmune thyroid disease, coeliac disease
(4), abnormal calcium homeostasis and a greatly increased
risk for diabetes type 2 (5).The possibility that PPP might
be an autoimmune disease has recently been suggested by
us, as sera from 47% of PPP patients reacted with papil-
lary endothelium in palmar skin from healthy subjects, as
assessed by indirect immunouorescence (IIF) (6).
The main purpose of this study was to determine
whether PPP sera also show immunoreactivity against
non-palmar skin and non-dermal tissues. In addition, the
immunoreactivity of PPP sera against cultured dermal
endothelial cell and palmar skin proteins was studied
using a Western blot technique.
Sera were obtained from 43 women and 1 man with
typical PPP on the palms and/or soles. Twenty-one of
these 44 new sera (47.7%) induced IIF staining of the
endothelium in the palmar skin from a healthy woman,
which is in agreement with our rst study (6).
Sera from 18 PPP patients studied previously
(6) were
obtained 1–6 years after the rst samples and were used
for follow-up screening of the IIF pattern in palmar skin.
With 16 of these 18 PPP sera the staining results were
the same as in the rst sample (7 were still negative, 9
still positive). The positive staining had the same pattern
(chain-like) and intensity as before. Two sera previously
giving weak IIF staining were now negative. There had
been only mild changes in the clinical conditions in the
majority of these patients.
Two patients who had stopped smoking had un-
changed, strong endothelial IIF, despite almost total
clearance of the PPP lesions in one of them and marked
improvement in the other. The IIF pattern induced by
PPP sera in palmar skin thus persists over time regard-
less of variation in clinical activity.
With the intention of screening for IIF in non-palmar
skin and non-dermal tissues, sera from 10 PPP patients,
5 healthy non-smokers and 5 patients with eczema on
the hands, were used. Five of the PPP sera had previ-
ously produced strong endothelial IIF on palmar skin
and 5 were negative.
The former positive sera showed endothelial stain-
ing also in skin from the ngertips, elbow, forearm and
back, but not in scalp skin, from healthy non-smokers.
However, the most widespread endothelial immunoreac-
tion was seen in palmar skin.
The most pronounced IIF staining with PPP sera in the
non-dermal tissues was seen on the endothelium in the
richly vascularized parathyroid gland (Fig. 1a). These PPP
sera also induced a staining in the endothelium between
the thyroid follicles (Fig. 1d), and in the pancreas strong
IIF staining was seen on the endothelial cells lining the
lumen of some larger blood vessels (Fig. 1e). All other sera
were negative (Fig. 1b). Double staining with endothelial
cell antibodies veried the location (Fig. 1c). No specic
staining was observed in the liver or duodenum.
Sera from Patients with Palmoplantar Pustulosis Show Immunoreactivity Against Endothelial Cells
Eva Hagforsen1, Håkan Hedstrand1, Johan Rönnelid2, Bo Nilsson2 and Gerd Michaëlsson1
Departments of 1Medical Sciences, Dermatology and 2Clinical Immunology, University of Uppsala, Uppsala, Sweden. E-mail: eva.hagforsen@medsci.uu.se
Accepted November 3, 2006.
Fig. 1. Immunoreactivity as assessed by indirect immunouorescence with
sera in non-dermal tissues. (a–c) The parathyroid gland: (a) serum from a
palmoplantar pustulosis (PPP) patient with endothelial immunoreaction;
(b) serum from a healthy non-smoking person, no endothelial staining; (c)
double staining (PPP serum and endothelial cell antibodies), yellow colour
demonstrates that PPP serum reacts with endothelial cells; (d) thyroid gland
– immunoreactivity in the endothelium between the follicles; (e) pancreas
– strong staining of the endothelial cells lining the lumen of a larger blood
vessel. Scale bars: (a–c) 10 µm; (d) 20 µm; (e) 10 µm.
262 Letters to the Editor
Acta Derm Venereol 87
When PPP sera were used for IIF on cultured endothelial
cells some of them seemed to stain the nucleus. Therefore,
34 sera from PPP patients were analysed for the pres-
ence of anti-nuclear antibodies by a standardized routine
method (IF on HEp-2 cells). Three sera (with nucleus IIF)
were anti-nuclear antibodies positive, but none of them
showed any antibodies to native DNA or to the extractable
nuclear antigens Sm, RNP, SSA, SSB, Scl -70 and Jo-1.
Endothelial cell proteins were separated on sodium do-
decyl sulphate polyacrylamide gel electrophoresis (SDS-
PAGE) and the numbers of sera used for Western blot
were: PPP patients with IIF 18; PPP without IIF 6; healthy
non-smokers 6; healthy smokers 3; eczema patients 7. A
larger number of bands and also stronger bands were seen
with sera from PPP patients than with sera from healthy
controls and patients with eczema of the hand (Fig. 2a).
One band of 59 kDa was seen with sera from 8 of 24 PPP
patients (33%). Six of these 8 sera produced the endothe-
lial IIF staining pattern. Only one of 16 sera from healthy
control subjects showed reactivity with an endothelial
antigen of 59 kDa (p-value = 0.044, χ
2
-test).
When palmar skin proteins were similarly studied, a
heterogeneous pattern with bands of different molecular
weights (between 32 and 47 kDa) was seen with sera
from PPP patients but not with control sera (Fig. 2b).
DISCUSSION
These IIF results show that sera from patients with
PPP have reactivity in particular against endothelial
cells in palmar skin, but also against endothelium in
non-palmar skin and in some non-dermal tissues. The
fact that PPP sera induce stronger and more widespread
endothelial IIF staining in normal palmar skin than in
skin from other areas may reect a different antigenic
prole, which may be of pathogenetic relevance. None
of the sera from patients with hand eczema showed IIF,
which rules out the possibility of a reaction from PPP
sera associated with an inammation in palmar skin.
The pronounced IIF staining of the parathyroid gland
endothelium was of particular interest as we have found
an abnormal calcium homeostasis in PPP (5). This
nding indicates that palmoplantar and parathyroid
endothelium might have some properties in common.
The clinical relevance of the endothelial staining in the
thyroid gland and pancreas is not yet known.
The Western blot results show that patients with PPP
have antibodies against several endothelial and palmar
skin antigens and that the antigens to which they react
vary between the patients. Analogously, several studies
of systemic lupus erythematosus using Western blotting
and immunoprecipitation have shown that endothelial
reactive sera recognize a number of proteins present in
endothelial cell preparations (7–9).
Although the clinical relevance of the reactivity
against endothelium is not yet known, these results
indicate that PPP is a complex autoimmune disease in-
volving not only the skin but also other organs. As most
patients with PPP are smokers, the possible link between
smoking, reactivity against endothelial components and
inammation in PPP deserves further investigation.
REFERENCES
1. Asumalahti K, Ameen M, Suomela S, Hagforsen E,
Michaëlsson G, Evans J, et al. Genetic analysis of PSORS1
Fig. 2. (a) Western blot on endothelial cell lysate, separated on 7.5–12.5% gradient sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE)
showing a larger number of bands and also stronger bands with sera from palmoplantar pustulosis (PPP) patients (lanes 5–8) than with sera from controls
(lanes 1–2) and patients with hand eczema (lanes 3–4). Arrow indicates a 59 kDa band seen with 33% of the PPP sera. (b) Western blot on palmar skin
homogenates from a healthy smoker, separated on 10% SDS-PAGE, showing several bands of different molecular weights with PPP sera (lanes 1–6), which
were not observed with control sera (lanes 7–8) or with sera from patients with hand eczema (lanes 9–10).
263
Letters to the Editor
Acta Derm Venereol 87
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