BJD
British Journal of Dermatology
_ 2011 The Authors
BJD _ 2011 British Association of Dermatologists 2011 164, pp1107–1124 1107
Successful treatment of classic Kaposi sarcoma
with low-dose intramuscular immunoglobulins
DOI: 10.1111/j.1365-2133.2010.10188.x
MADAM, Kaposi sarcoma (KS), a malignant multilocular angioproliferative
disease, is aetiologically linked to human herpes
virus (HHV)-8 infection and immune dysfunction.1 There is
no standard therapy.1,2 Various local treatments, including
cryotherapy, radiotherapy, intralesional chemotherapy, laser
therapy and topical alitretinoin may be effective but limited in
patients with multiple lesions.1,2 Systemic treatment options
including interferon alfa, antiangiogenic strategies such as
thalidomide or sirolimus, and cytotoxic therapies, such as
vinca alkaloids, bleomycin, etoposide, taxanes and anthracyclines
are used in palliative settings.1–4 Especially, liposomal
anthracyclines may be beneficial in widespread disease.2,5
However, chemotherapy may aggravate pre-existing immunosuppression
and may be limited by side-effects.
A 63-year-old Turkish woman presented with various manifestations
of classic KS on the lower legs, ears, lower back and
palms that had developed 6 months previously, the largest
with a size of 8 ? 4 cm on the right lower leg (Fig. 1a). Histology
showed patch, plaque and nodular lesions of KS. The
tumours were characterized by proliferation of atypical spindle
cells lining vascular slits containing erythrocytes, and a sparse
infiltrate of lymphocytes and plasma cells (Fig. 2a, b). As
demonstrated by immunohistochemistry, the spindle cells
expressed the lymphatic endothelium marker podoplanin
(Fig. 2c). In addition, HHV-8 was detected in the tumour cells
immunohistochemically (Fig. 2d) and by polymerase chain
reaction (PCR). In the patient’s serum, HHV-8 DNA was
detectable by PCR analysis and highly positive anti-HHV-8 IgG
levels by fluorescent antibody tests. Further laboratory and
radiology diagnostics were within normal limits and excluded
human immunodeficiency virus or extracutaneous involvement.
The patient refused radiation therapy of the lower leg or
other suggested conventional therapy. We started a therapeutic
attempt with intramuscularly administered Beriglobin_ (BG;
CSL Behring, Marburg, Germany), a preparation of globulins
containing antibodies normally present in adult human blood.
We injected 5 mL BG (800 mg immunoglobulin) according
to the dose recommended for pre-exposure prophylaxis of
hepatitis A infection. Four weeks after the first administration
a marker lesion on the right lower leg had already lightened
significantly (Fig. 1b). We continued the treatment with seven
more injections every 4 weeks. After 6 months, complete
remission was achieved (Fig. 1c) and confirmed histologically.
As demonstrated by podoplanin stainings only a few residual
lymphatic vessels without formation of spindle cells were
present (Fig. 2e) and HHV-8 was no longer detectable immunohistochemically.
Five months later, the disease recurred on
the left lower arm and the right ear (Fig. 1d). Another course
of intramuscular immunoglobulin injections was started, again
resulting in complete remission within 6 months (Fig. 1e, f).
Therapy was continued for another 3 months. The patient
continued to have high anti-HHV-8 titres, but HHV-8 DNA
became undetectable in the patient’s serum.
The batch of BG that was used was analysed for HHV-8-
specific IgG by indirect immunofluorescence applying fluorescein–
isothiocyanate-conjugated antihuman IgG1–4 monoclonal
mouse antibodies. Surprisingly, the immunoglobulin preparation
contained a high concentration of anti-HHV-8 IgG1 (titre
1 : 600) and IgG3 (titre 1 : 600) antibodies. This was unexpected,
as the donors originated from Germany, Austria and
the U.S.A. For Germany and other Western European countries
HHV-8-seroprevalences of only 2–3% have been reported.6
After a disease-free interval of 4 years without any treatment
the patient relapsed with KS manifestations on the lower
legs, the right ear and the tip of the nose (Fig. 1g). Remarkably,
together with the clinical relapse HHV-8 DNA again
became detectable in the patient’s serum. Again, we administered
intramuscular BG. The tumours responded considerably
within 5 weeks after the first injection (Fig. 1h) and completely
resolved after 3 months (Fig. 1i). As complete response
was achieved again this batch of BG was not analysed for anti-
HHV-8 antibodies. During the whole time of immunoglobulin
treatment, no side-effects were observed.
As reported earlier, a patient with polymyositis and iatrogenic
KS reached stable regression after shifting from immunosuppressive
therapy to high-dose intravenous immunoglobulins.
7 However, it remained unclear whether this was due to
discontinuation of the immunosuppression or a direct therapeutic
effect of the immunoglobulins. In patients with
iatrogenic KS, tumour regression has been observed after the
withdrawal of immunosuppressive therapy.8,9 In addition, the
development of KS under combined therapy with immunosuppressive
drugs and immunoglobulins has been reported.10
To our knowledge, successful therapy of KS using low-dose
intramuscular immunoglobulins, an immunological approach
presumably targeting the HHV-8 infection as a major aetiopathological
factor, has not yet been described. BG, which in
contrast to many other potential treatments does not lead to
further immunosuppression, might be a well-tolerated and relatively
low-priced therapeutic option. At present in Germany,
one dose (5 mL) of BG costs about €60. In our patient, HHV-
8 DNA became undetectable in the blood during clinical
remission, whereas recurrence was accompanied by viraemia.
Because our patient had high titres of anti-HHV-8 antibodies,
one might speculate that BG had substituted a lack of sufficiently
working antibodies. In any case, the response of KS to
low-dose immunoglobulin has to be confirmed by further
investigations.
K.-M. THOMS
S . HEL LRIEGEL
B. KRONE*
I . BECKMANN
K. RITTER_
M. P. SCHO¨ N
H. P. BERTSCH
L. KRETSCHMER
Departments of Dermatology, Venerology and
Allergology and *Virology,
Georg-August-University Go¨ttingen,
D-37075 Go¨ttingen, Germany
_Division of Virology, Institute of Medical
Microbiology, University Hospital Aachen, D-52074
Aachen, Germany
Correspondence: Lutz Kretschmer.
E-mail: lkre@med.uni-goettingen.de