A case of Sweet's syndrome developed after the treatment of herpes simplex infection in a metastatic breast cancer patient.
ABSTRACT Sweet's syndrome or acute febrile neutrophilic dermatosis is associated with several systemic diseases such as malignancies and infectious diseases.
We present a 34-year-old woman with Sweet's syndrome associated with both herpes infection and metastatic disease.
Skin biopsy showed neutrophilic infiltrates in the dermis confirming the diagnosis of Sweet's syndrome.
To our knowledge, this is the second case of Sweet's syndrome associated with herpes simplex infection in the literature. Further observations are required to determine the relationship between Sweet's syndrome and herpetic infection.
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ABSTRACT: A patient with aplastic anaemia developed Sweet's syndrome (a febrile neutrophilic dermatosis) during granulocyte colony-stimulating factor (G-CSF) therapy. Three repeated episodes of appearance and disappearance of erythematous nodules after administration and withdrawal of G-CSF confirmed that G-CSF induced Sweet's syndrome in the patient. Sweet's syndrome has been reported in patients with myelodysplastic syndrome and acute leukemia, but not in patients with aplastic anaemia. This is the first report of a patient with aplastic anaemia who developed G-CSF-induced Sweet's syndrome.British Journal of Haematology 04/1994; 86(3):645-8. · 4.94 Impact Factor
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ABSTRACT: A 33-year-old male was referred with a two-week history of fevers to 40 degrees C and painful, erythematous skin and oral mucosal eruptions that had failed to respond to multiple anti-infectious agents. He had a recent diagnosis of a "myeloproliferative disorder with myelodysplastic features" on bone marrow biopsy, with associated pancytopenia. Two weeks before admission, he had been treated with a course of granulocyte colony-stimulating factor (G-CSF) at a dose of 300 microg/day in an attempt to improve his neutropenia. After four days of treatment, the fever and lesions developed. Infectious evaluation was negative; however, biopsies of the skin and oral mucosal lesions revealed histology consistent with Sweet's syndrome. Intravenous methylprednisolone (30 mg/day) was started with prompt defervescence and resolution of the lesions within days. With the increasing use of G-CSF, Sweet's syndrome is becoming more commonly recognized as an adverse effect. This is the first case of G-CSF-induced Sweet's syndrome to demonstrate gingival involvement.American Journal of Hematology 07/1999; 61(2):126-9. · 4.00 Impact Factor
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ABSTRACT: A 55-year-old woman developed Sweet's syndrome (acute febrile neutrophilic dermatosis, AFND) 5 years after a diagnosis of chronic lymphocytic leukemia (CLL). Two months later she developed a scirrhous carcinoma of the breast. The patient died 7 months later from sepsis. To our knowledge, this is the first case of an association among a cancer of the breast, CLL and Sweet's syndrome.Haematologica 75(2):173-5. · 5.94 Impact Factor
J CutanPatho l 2002: 29: 301–304
Blackwe ll Munksgaard. Printe dinDe nm ark
Copyright C Blackwell Munksgaard 2002
Background: Sweet’s syndrome or acute febrile neutrophilic
dermatosis is associated with several systemic diseases such as
malignancies and infectious diseases.
Methods: We present a 34-year-old woman with Sweet’s syndrome
associated with both herpes infection and metastatic disease.
Results: Skin biopsy showed neutrophilic infiltrates in the dermis
confirming the diagnosis of Sweet’s syndrome.
Conclusions: To our knowledge, this is the second case of Sweet’s
syndrome associated with herpes simplex infection in the literature.
Further observations are required to determine the relationship
between Sweet’s syndrome and herpetic infection.
Ugur Coskun1, Nazan Gunel1,
Esin Senol2, Nilsel Ilter3,
Ayse Dursun4and Dilek Tuzun5
Gazi University Medical School, Departm ents of
1Medical Oncology,2Infectious Diseases,
3Derm atology,4Pathology and5Internal
Correspondence: Ugur CoskunMD, Fellow , Gazi
Universitesi, TipFakultesi, Medical Onkoloji, Besevler/
Ankara, 06500 Turkey
Tel:π903122141000 ext: 5828
E-m ail: ugurcos/hotm ail.com
Coskun U, Gunel N, Senol E, Ilter N, Dursun A, Tuzun D. A case
of Sweet’s syndrome developed after the treatment of herpes simplex
infection in a metastatic breast cancer patient.
J Cutan Pathol 2002; 29: 301–304. C Blackwell Munksgaard 2002.
Accepted28 Septem ber 2001
Sweet’s syndrome is characterized by fever, neutro-
philic leukocytosis and multiple painful cutaneous
plaques.1Thecause of Sweet’ssyndromeisnot clear,
butahypersensitivity reactiontoantigenic stimulation
issuspected in thepathogenesis.2,3It hasbeen associ-
atedwith several diseasesincluding variousinfections,
autoimmune diseases and malignancies, especially
myeloproliferative diseases.4Recently, several cases
with exogenous G-CSF-induced Sweet’s syndrome
have been reported.5,6We report a breast cancer pa-
tient with Sweet’s syndrome associated with herpes
A 34-year-old woman was found to have infiltrating
ductal left breast carcinoma (T2N1M0) in March
1999. Treatment modality included modified left rad-
ical mastectomy, local regional radiation therapy and
five courses of adjuvant chemotherapy containing 5-
fluorouracil, cyclophosphamideanddoxorubicin. She
could not receive a sixth course of chemotherapy be-
cause of neutropenia. In February 2001, progressive
bonepain wasshown tobecausedby bonemetastasis
in the lumbar column and pelvis. She received radi-
ation therapy to the T10-S1 and pelvis. One month
after radiotherapy, shecomplainedoftypical vesicular
lesions for herpetic infection on her lips and the
lesions then spread all over the face (Fig.1). The pa-
tient’s temperature was 38æC. Her hemoglobin was
5.8g/dl and platelet count was 25.000/mm3. The
whitebloodcell count was4400/mm3with 78% neu-
trophils. Herpes simplex infection was suspected and
intravenous acyclovir (30mg/kg/day in three doses)
was started. Three days later, leukocyte count de-
creased to 2300/mm3with 35% neutrophils. G-CSF
or GM-CSF were not administrated to the patient.
Bone marrow examination showed diffuse infiltration
by tumor cells. Three unitsof erythrocyte suspension
were administered. Following 14days’ treatment of
acyclovir, all theherpetic lesionsimproved. Thetem-
peraturewasnormal. At theendof thetreatment, the
leukocycte count was 9000/mm3with 88% neutro-
phils, hemoglobin was8.9g/dl and platelet count was
Coskun et al.
Fig.1. Clustersof small vesicleson an erythematousbase with pus-
tules and crusts which started on the wemillion border of the lip
and spread all over the face is typical for herpetic infection.
Fig.2. (A) Red or bluish red plaques, nodules and some bullae on
thehandandforearmofthepatients. (B) Redor bluishredplaques,
nodules and some bullae on the right leg of the patients.
19,000/mm3. Two days later, she developed papules
at the sitesof drug injectionswhich can be evaluated
asthepathergy phenomenon. After a short while, the
lesionsspread rapidly all over the body, especially on
the extremities. The skin lesions were red or bluish
red papulesand nodules. They showed a tendency to
coalesce and form irregular,sharply bordered
plaques. Therewaspronounced inflammatory edema
and some bullae on some of the lesions. The lesions
were tender and painful (Fig.2A,B). At this time, the
patient’s fever increased again. The erythrocyte sedi-
mentation rate was 120mm/h. The biopsy obtained
fromoneof thefully developed lesionswasevaluated.
There were large nodular infiltrates of neutrophils,
lymphocytes and nuclear dust in a top-heavy fashion
within the dermis. There was edema in the papillary
dermisand some small subcorneal collectionsof neu-
Fig.3 (A, B, C). Microscopic examinationsof theSweet’ssyndrome
lesions show large nodular infiltrates of neutrophils, lymphocytes
and nuclear dust in a top-heavy fashion within the dermis and
some small subcorneal collectionsof neutrophilswithin the epider-
mis (¿ 40,200).
Sweet’s syndrome associated with herpes simplex and breast carcinoma
findings, Sweet’s syndrome was considered. There-
fore, stains for organisms were not performed on the
biopsyspecimen. Prednisolone 80mg/day
started. After 7days of treatment, the lesions im-
proved. ESR decreased to 7mm/h and the tempera-
ture was normal. There was no change in leukocyte,
platelet counts and hemoglobin levels in the patient’s
Sweet’s syndrome was first described by Sweet in
1964.7The following diagnostic criteria were pro-
posed in 1986.
1. Abrupt onset of tender or painful erythematousor
violaceous plaques or nodules.
2. Predominant neutrophilic infiltration in thedermis
without leukocytoclatic vasculitis.
1. Preceded by fever or infections.
2. Accompanied by fever arthralgia, conjunctivitis or
4. Good responsetosystemic steroidsand not toanti-
Three years later, increased sedimantation rate was
added as a fifth minor criterion.8It has been sug-
gested that, to allow a definite diagnosis of Sweet’s
syndrome, both of the major criteria and at least two
of the minor criteria must be fulfilled.1In this case,
two major and four minor criteria (except leuko-
cytosis) were determined. However, an elevated neu-
trophil level was detected at a normal range just be-
fore skin lesions appeared.
Aproximately 10–15% of the reported cases of
Sweet’ssyndromeassociatedwith a malignancy, espe-
cially myeloproliferative diseases.9Several cases as-
sociated with metastatic breast carcinoma as a para-
neoplastic syndrome have been reported to date. In
all thecasesrelated to breast cancer in literature, it is
detected that Sweet’s syndrome appeared before or
at the same time as metastasis.10–13The association
between Sweet’ssyndromeand infectiousdiseasesare
well known.3,4However, only one case associated
with herpeszoster hasbeen reported in theliterature.
Fivedaysafter therecovery, using acyclovir treatment
of this patient with systemic lupus erythematosus,
neutrophil count elevated and Sweet’s syndrome oc-
curred. Thiscasewasvery similar to our case.14Her-
pes zoster-like Sweet’s syndrome has also been re-
portedintheliterature. Their patient withacutemye-
logenous leukemia had not improved by acyclovir
treatment, but had a good response to steroid treat-
ment.15In the differential diagnosis, we considered
whether theherpetic infection at thebeginning of the
history was an unusual variant of Sweet’s sydrome.
However, because of the good response to acyclovir
and thetypical featureof herpetic lesions, werejected
this idea. Although we could not rule out varicella
zoster infection without performing viral typing or
culture, weconsidered that it wasmost probably her-
pes simplex infection. Because of the normal levels
of leukocyte count before herpetic infection and the
improvement of leukocyte count after antiviral treat-
ment, we concluded that decreased leukocyte count
may be due to suppression of bone marrow by her-
petic infection in spite of bone marrow invasion by
known, but a hypersensitivity reaction to a bacterial,
viral or tumor antigen is suspected in the etiology.
This mechanism is supported by the rapid response
tosystemic corticosteroids.2,3Elevated levelsof serum
granulocyte colony-stimulating factor (G-CSF) and
interleukin 6 (IL-6) in comparison with other cyctok-
ines during acute exacerbations of Sweet’s syndrome
to consideration that G-CSF and IL-6 may be in-
volved in the pathogenesis of disease by stimulating
the production, activation and chemotaxis of neutro-
phils.19The rise in G-CSF is considered to stimulate
peripheral neutrophilsand neutrophilic infiltration of
thedermis.17Moreover, several caseswith exogenous
G-CSF-induced Sweet’s syndrome have been re-
ported.6,7In our case, Sweet’ssyndrome exacerbated
after herpetic infection improved after 14days’ acy-
clovir treatment. We consider that while the herpetic
infection was recovering, bone marrow suppression
by herpetic infection dissappeared, and in this way
neutrophilic stimulation began without using C-CSF
or GM-CSF. During this period the absolute neutro-
phil count rose from 800/mm3to 7900/mm3. The
trigger mechanism of Sweet’s syndrome in this case
may be the elevated neutrophil levels after the treat-
ment of herpetic infection. This suggestion may be
connected with the theory related to G-CSF and IL-
6. If we were able to measure G-CSF and IL-6 levels
during herpetic infection and Sweet’s syndrome, we
would have an opportunity to clarify this suggestion.
In this case, it is not possible to distinguish clearly
whether Sweet’s syndrome is related or not to meta-
static breast carcinoma. However, it can be con-
sidered that both herpetic infection and breast carci-
noma areassociatedwith Sweet’ssyndrome. Herpetic
infection may bea trigger event for theoccurrenceof
breast carcinoma. It ispossible that viral infectionsin
particular may be playing a role in the etiology of
Coskun et al.
Sweet’s syndrome with malignant diseases. Sweet’s
syndrome may be aggravated after transient bone
morrow suppression by viral infections. Asviral infec-
tionsaresometimesnotmanifestinother cases, unlike
ours, they may not be noticed. In conclusion, it is
essential to investigate viral infections, especially her-
pes infections, in the etiology of Sweet’s syndrome.
Further observations are necessary to determine the
relationship between Sweet’s syndrome and herpetic
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