Correspondence 773

Figure 1 summarizes the findings of S100b levels in mel-

anocyte supernatants after 05, 6, 24, 48 and 72 h. A slight
increase in S100b can be observed even in the controls, but
the difference between control and irradiated cells increases
over time after irradiation and is also dose dependent. We
consider the slight increase of S100b level in controls to be
caused either by the fact that cells could not be prepared in
the total absence of light, resulting in melanocyte activation,
or possibly by a cumulative increase of cell depletion. The cell
doubling time was 456 h in both controls and irradiated
cells, resulting in similar cell counts after each measurement.
To our knowledge, we show for the first time that S100b
levels in extracellular fluid derived from normal human skin
melanocytes increase after irradiation with suberythemal as
well as erythemal UVB doses. Taking this finding together
with the observations of Tronnier et al., who found elevated
serum S100b levels after UVB exposure in some individuals
of a small group of volunteers, we conclude that UVB
exposure of skin cells can indeed influence serum S100b
levels. Further investigation is needed to provide correct
interpretation of elevated S100b levels in dermatology as well
as in neurology.
Acknowledgments
The authors thank I. Nuyken for excellent technical assistance.
Bundeswehr Institute of Radiobiology, J. VITZTHUM
Munich, Germany H . D . D O R R
E-mail: jannisvitzthum@bundeswehr.org V. MEINEKE
References
1 Moore BW. A soluble protein characteristic of the nervous system.
Biochem Biophys Res Commun 1965; 19:73944.
2 Cotena S, Piazza O, Storti M. The S100B protein and traumatic brain
injury. J Neurosurg 2006; 104 (Suppl. 6):4356.
3 Gupta SK, Nigam S, Mandal AK, Kumar V. S-100 as a useful auxi-
liary diagnostic aid in tuberculoid leprosy. J Cutan Pathol 2006;
33:4826.
4 Weiss T, Weber L, Scharffetter-Kochanek K, Weiss JM. Solitary cuta-
neous dendritic cell tumor in a child: role of dendritic cell markers
for the diagnosis of skin Langerhans cell histiocytosis. J Am Acad
Dermatol 2005; 53:83844.
5 Jury CS, McAllister EJ, MacKie RM. Rising levels of serum S100 pro-
tein precede other evidence of disease progression in patients with
malignant melanoma. Br J Dermatol 2000; 143:26974.
6 Acland K, Evans AV, Abraha H et al. Serum S100 concentrations are
not useful in predicting micrometastatic disease in cutaneous
malignant melanoma. Br J Dermatol 2002; 146:8325.
7 Domingo-Domenech J, Molina R, Castel T et al. Serum protein s-100
predicts clinical outcome in patients with melanoma treated with
adjuvant interferon comparison with tyrosinase rtPCR. Oncology
2005; 68:3419.
8 Tronnier M, Missler U, Grotrian K, Kock N. Does ultraviolet radi-
ation exposure influence S100b protein plasma levels? Br J Dermatol
1998; 138:1098100.
Conflicts of interest: none declared.
Erythema gyratum repens-like eruption in a
patient with epidermolysis bullosa acquisita
associated with ulcerative colitis
DOI: 10.1111/j.1365-2133.2006.07746.x
SIR, Epidermolysis bullosa acquisita (EBA) is an acquired auto-
immune bullous disease of the skin and mucous membranes
characterized by IgG autoantibodies to type VII collagen,
the main constituent of the anchoring fibrils of the dermal
epidermal juction.1,2 Inflammatory bowel diseases (IBD) may
be associated with autoimmunity to type VII collagen.3,4 Ery-
thema gyratum repens (EGR), an obligate paraneoplastic syn-
drome, may occur in patients with pemphigoid diseases.59
To the best of our knowledge, EGR has not been previously
described in EBA. We report a most unusual clinical manifest-
ation of EGR-like lesions in a patient with EBA and ulcerative
colitis (UC).
A 35-year-old woman presented with 2-year history of
bullous skin lesions on the trunk and extremities and ero-
sions on the oral mucosa. In addition, 6 months before her
first visit to our department, she developed progressive diar-
rhoea and asthenia. Following further investigation by endo-
scopy with biopsy of colonic mucosa a diagnosis of UC was
made. A computed tomographic scan ruled out the presence
of a neoplastic process. Physical examination revealed wide-
spread blistering, erosions, scarring and milia formation on
her hands (Fig. 1a), feet (Fig. 1b), legs and arms. In add-
ition, erythematous lesions with a wood-grained appearance
were observed on the thighs and trunk (Fig. 1c). Bullous
lesions were associated with figurate erythematous lesions on
the knees and legs (Fig. 1d). Examination of the oral cavity
revealed erosions and scarring of jugal and lingual mucosa.
Histopathological examination of a blister showed a subepi-
dermal split and a massive infiltrate mainly consisting of
neutrophils in the upper dermis (Fig. 2a). Direct immuno-
fluorescence (IF) of the perilesional skin demonstrated linear
deposits of IgG and C3 at the basement membrane zone.
Indirect IF on NaCl-split skin revealed circulating IgG auto-
antibodies binding to the dermal side (titre 1 : 320). These
antibodies belonged to the IgG1, IgG3 and IgG4 subclasses
(Fig. 2b). By immunoblotting using a recombinant form of
the noncollagenous (NC) 1 domain of type VII collagen,10
our patients serum demonstrated type VII collagen-specific
IgG4 autoantibodies (data not shown). Serum tumoral mark-
ers, including s-CA 199, s-CA 125 and s-CEA, were within
the normal range. Enzyme-linked immunosorbent assay
analysis using recombinant antigen did not reveal reactivity
against the immunodominant XVII NC domain of BP180.
Our patient was started on a regimen of prednisone 40 mg
daily, oral sulfasalazine 2 g daily and mycophenolate mofetil
2 g daily. Under this treatment, an important clinical and
serological improvement was noted at the follow-up visit
3 months later.

 2007 The Authors

Journal Compilation  2007 British Association of Dermatologists British Journal of Dermatology 2007 156, pp748791
774 Correspondence

Fig 1. Blisters, erosions, scarring and milia formation on (a) patients left hand and (b) feet. (c) On thighs, erythematous lesions with a wood-
grained appearance were observed. (d) Figurate erythematous lesions accompanied the bullous eruption.

Fig 2. (a) Subepidermal blistering and a neutrophil-rich inflammatory infiltrate were observed within the upper dermis (haematoxylin and eosin;
original magnification 40). (b) Circulating autoantibodies of IgG1, IgG3 and IgG4 subclasses binding to the dermal side of 1 mol L)1 NaCl-split
skin were detected by indirect immunofluorescence microscopy.

Several clinical manifestations of EBA are described, includ-
ing the classic mechanobullous, the generalized inflammatory,
and the cicatricial pemphigoid-like types.2 Interestingly, our
patient presented features of both the mechanobullous and the
inflammatory forms of EBA, with acral lesions, scarring, milia
formation and an erythematous inflammatory eruption on the
trunk. Nevertheless, the figurate eruption resembling EGR rep-
resents a particular clinical feature of this patient that has not
yet been reported in patients with EBA. EGR may be very
rarely associated with pemphigoid diseases.59 Although EGR

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Journal Compilation  2007 British Association of Dermatologists British Journal of Dermatology 2007 156, pp748791

usually represents an ominous sign heralding an associated
neoplasm, our patient as well as several previously reported
cases6,7,9 clearly demonstrate that in patients with autoim-
mune blistering diseases such figurate erythema may occur in
the absence of neoplasia.
Irrespective of its clinical manifestation, EBA is associated
with autoantibodies to type VII collagen.1,3 Patients autoanti-
bodies belonging to different IgG subclasses mainly target epi-
topes within the NC1 domain of type VII collagen.1 IgG
autoantibodies to type VII collagen mainly belong to the IgG1
and IgG4 and to the IgG3 subclasses in EBA and IBD, respect-
ively. Consistent with these findings, our patient presented
IgG1, IgG3 and IgG4 autoantibodies to type VII collagen.
While the blister-inducing potential of autoantibodies to type
VII collagen is established,2 their contribution to the patho-
genesis of IBD and EGR-like lesions is still unclear. IBD occur
in approximately 30% of patients with EBA. Thus EBA is
mainly associated with Crohns disease, but rarely with UC.4,7
The causes and pathomechanisms underlying the association
of EBA with IBD are poorly understood. The detection of type
VII collagen expression in the colonic mucosa led to the hypo-
thesis that, in the context of chronic inflammation and dam-
age to the overlying mucosa, antigenic epitopes of the type
VII collagen molecule are exposed. These newly exposed anti-
genic epitopes may invoke production of autoantibodies,
which, in some patients, also cross-react with type VII colla-
gen and trigger blister formation in the skin.7 Why EBA asso-
ciates more often with Crohns disease compared with UC is
even less clear.
When IBD and EBA are associated, the onset of IBD usually
precedes by several years the first manifestations of the blister-
ing disease. Interestingly, in our patient, the onset of EBA
clearly predated the manifestations of UC.
In conclusion, we report that an EGR-like eruption may occur
in EBA associated with UC. Our results emphasize the notion
that EBA is clinically a heterogeneous disease and suggest EGR
to be one of its possible manifestations. Therefore, the differ-
ential diagnosis in patients with EGR-like eruptions should
also include EBA and other autoimmune blistering skin diseases.
Department of Dermatology, University Clinic of A . E S P A N A
Navarra, University of Navarra, School of Medicine, C. SITARU*
PO Box 4209, Pamplona 31080, Navarra, Spain M. PRETEL
*Department of Dermatology, University of Lubeck, L. AGUADO
Germany J. JIMENEZ
Department of Gastroenterology, Hospital of
Navarra, Pamplona, Navarra, Spain
E-mail: aespana@unav.es
References
1 Sitaru C, Zillikens D. Mechanisms of blister induction by autoanti-
bodies. Exp Dermatol 2005; 14:86175.
2 Hallel-Halevy D, Nadelman C, Chen M, Woodley DT. Epidermo-
lysis bullosa acquisita: update and review. Clin Dermatol 2001;
19:71218.
 2007 The Authors
Journal Compilation  2007 British Association of Dermatologists British Journal of Dermatology 2007 156, pp748791
Correspondence 775
3 Chen M, OToole EA, Sanghavi J et al. The epidermolysis bullosa
acquisita antigen (type VII collagen) is present in human colon
and patients with Crohns disease have autoantibodies to type VII
collagen. J Invest Dermatol 2002; 118:105964.
4 Oostingh GJ, Sitaru C, Zillikens D et al. Subclass distribution of type
VII collagen-specific autoantibodies in patients with inflammatory
bowel disease. J Dermatol Sci 2005; 37:1824.
5 Graham-Brown RA. Bullous pemphigoid with figurate erythema
associated with carcinoma of the bronchus. Br J Dermatol 1987;
117:3858.
6 Caputo R, Bencini PL, Vigo GP et al. Eruption resembling erythema
gyratum repens in linear IgA dermatosis. Dermatology 1995;
190:2357.
7 Breathnach SM, Wilkinson JD, Black MM. Erythema gyratum
repens-like figurate eruption in bullous pemphigoid. Clin Exp Dermatol
1982; 7:4016.
8 Hauschild A, Swensson O, Christophers E. Paraneoplastic bullous
pemphigoid resembling erythema gyratum repens. Br J Dermatol
1999; 140:5502.
9 Wozniak K, Kowalewski C, Hashimoto T et al. Penicillin-induced
anti-p200 pemphigoid: an unusual morphology. Acta Derm Venereol
(Stockh) 2006; 86:4436.
10 Sitaru C, Kromminga A, Hashimoto T et al. Autoantibodies to type
VII collagen mediate Fcgamma-dependent neutrophil activation
and induce dermalepidermal separation in cryosections of human
skin. Am J Pathol 2002; 161:30111.
Conflicts of interest: none declared.
Blindness due to the IgA variant of
epidermolysis bullosa acquisita, and treatment
with osteo-odonto-keratoprosthesis
DOI: 10.1111/j.1365-2133.2006.07739.x
SIR, We describe a woman who initially presented in 1994, at
age 47 years, with numerous groups of blisters in an annular
arrangement on the trunk, strongly suggestive of linear IgA
disease (LAD). Biopsy with immunofluorescence confirmed
intense linear dermoepidermal IgA deposition which was felt
to support the diagnosis of LAD, although recent re-evaluation
using indirect immunofluorescence and salt-split skin has
shown that the binding of IgA is predominantly dermal, thus
suggesting that she actually has IgA-epidermolysis bullosa
acquisita (IgA-EBA). No cause or associated disease have
become apparent over 12 years of follow-up.
Some therapeutic aspects of this patient were included in an
earlier report of vitamin E prophylaxis for dapsone-induced
headache1 (her initial treatment was with dapsone) but her
treatments and response are further documented here as they
are remarkable for the lack of efficacy. Treatments (individually
or in combination) have included dapsone (with vitamin E);
sulfapyridine; numerous topical (including ocular, buccal and
vaginal) and systemic (oral and pulsed intravenous) cortico-