Hindawi Publishing Corporation
Case Reports in Rheumatology
Volume 2011, Article ID 242681, 6 pages
Associationof Sweet’s Syndromeand
J. L.Barton, L.Pincus,J. Yazdany,N. Richman,T. H.McCalmont,
L.Gensler,M. Dall’Era,andK. H.Fye
Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA 94143, USA
Correspondence should be addressed to J. L. Barton, email@example.com
Received 9 August 2011; Accepted 29 August 2011
Academic Editors: A. Chalmers and J. C. Nossent
Copyright © 2011 J. L. Barton et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sweet’s syndrome is an acute febrile neutrophilic dermatosis which usually presents as an idiopathic disorder but can also be
drug induced, associated with hematopoetic malignancies and myelodysplastic disorders, and more, infrequently, observed in
autoimmune disorders. Sweet’s syndrome has been reported in three cases of neonatal lupus, three cases of hydralazine-induced
lupus in adults, and in nine pediatric and adult systemic lupus erythematosus (SLE) patients. We describe three additional adult
cases of Sweet’s associated with SLE and provide a focused review on nondrug-induced, nonneonatal SLE and Sweet’s. In two of
three new cases, as in the majority of prior cases, the skin rash of Sweet’s paralleled underlying SLE disease activity. The pathogen-
esis of Sweet’s remains elusive, but evidence suggests that cytokine dysregulation may be central to the clinical and pathological
changes in this condition, as well as in SLE. Further research is needed to define the exact relationship between the two conditions.
Sweet’s syndrome represents an acute neutrophilic dermati-
tis, often with associated fever , first described by Sweet
in 1964 . Although the syndrome often presents in
idiopathic fashion, it can also be induced by medications and
has been associated with hematopoietic malignancies and
myelodysplastic disorders. It has also been observed in asso-
ciation with certain autoimmune disorders, such as Sjogren’s
syndrome. Nine patients with both Sweet’s syndrome and
systemic lupus erythematosus (SLE) have been previously
reported [3–10]. Because the diagnosis of Sweet’s syndrome
can be challenging, particularly when associated with other
connective tissue disorders such as SLE, a set of diagnostic
criteria were proposed initially by Su and Liu  and then
revised by Von den Driesch . The diagnosis is based
upon the presence of two major and two of the four minor
erythematous plaques or nodules and (2) histopathologic
include (1) fever >38 degrees centigrade; (2) presence of
a malignancy or connective tissue disease; (3) dramatic
response to corticosteroids or potassium iodide therapy; (4)
an elevated erythrocyte sedimentation rate or leukocytosis.
We herein report our experience with Sweet’s syndrome
among adult patients in the Lupus Clinic at the University
of California, San Francisco, along with a review of the
A 26-year-old previously healthy Japanese female presented
with nine days of myalgias, subjective fevers, and soaking
night sweats. Four days prior, she developed multiple zer-
ythematous nodules on her face, chest, abdomen, and
upper and lower extremities bilaterally. She complained of
sore throat, nonproductive cough, painless oral ulcers, hand
swelling, Raynaud’s phenomenon, erythroderma, and ab-
dominal bloating. She denied illicit or prescribed drug use,
drug allergies, alcohol, or tobacco. She emigrated from Japan
at age eight and received a BCG vaccination as a child. She
reported recent travel to Europe and was sexually active with
2 Case Reports in Rheumatology
Figure 1: Multiple 2-3cm tender, erythematous, subcutaneous nodules were present over (a) the face and (b) lower extremities.
On physical examination, the patient was normotensive
and afebrile. There was a tender right submandibular node
and diffuse swelling of the hands without synovitis. Multiple
2-3cm tender, erythematous, subcutaneous nodules were
present over the face, chest, abdomen, and upper and lower
extremities bilaterally (Figures 1(a) and 1(b)). She sub-
sequently developed a fever of 39.5 Celsius. Initial labo-
ratory tests included a hematocrit of 30.9%, an LDH of
329iu/L, a positive Coombs antibody assay, an erythrocyte
sedimentation rate of 58mm/hr Westergren, a c-reactive
protein of 182mg/L (normal <6.3mg/L), and a prolonged
partial thromboplastin time of 38.7sec (normal 20.9–33.6).
Histochemical staining of the skin biopsy did not reveal
organisms. A CT scan of the chest revealed interlobular
septal and bronchial wall thickening of multiple lobes and
or atypical or viral pneumonia. Further laboratory testing
revealed an antinuclear antibody titer >640, speckled with
positive anti-Smithandanti-Sm/RNPantibody assays.Com-
plement levels and urinalysis were normal. A tuberculin skin
test was positive to 14mm at 48 hours. A quantiferon gold
assay was indeterminate. A skin biopsy from her left thigh
showed a relatively sparse interstitial inflammatory infiltrate
composed of neutrophils, lymphocytes, and histiocytes. In
addition, there were some foci of leukocytoclastic vasculitis.
Neutrophils were also found in the subcutaneous tissue.
The patient was treated with prednisone 40mg and
hydroxychloroquine 400mg daily with a dramatic response.
Dapsone was later added in an effort to taper the prednisone.
She was also treated for latent tuberculosis with four months
A 23-year-old Asian-American female with a history of SLE
presented to the emergency department with a five-day
history of diffuse myalgias, fatigue, dizziness, and three days
side of the face and then spread to the upper trunk, arms and
legs. On presentation, temperature was 38.9 Celsius. Routine
erythrocyte sedimentation rate was 54mm/hr Westergren.
The patient was instructed to follow up in the lupus clinic.
Manifestations of SLE diagnosed at age 20 included malar
rash, arthritis, pericarditis, Raynaud’s, Coombs positive
autoimmune hemolytic anemia, antinuclear antibody titer
>640 speckled, and elevated titers of anti-dsDNA antibodies.
She was a nursing student, denied tobacco, alcohol, or illicit
drug use, and was sexually active with one partner. Medi-
cations included hydroxychloroquine 400mg, prednisone
3mg, and calcium with vitamin D.
The following day in clinic, the patient complained of
painful erythematous papules and plaques as well as inter-
mittent discomfort over the left chest which worsened with
deep inspiration, palpitations, and Raynaud’s phenomenon.
new medications. Physical examination revealed an afebrile,
normotensive female with tachycardia (pulse 114), cobble-
exudate, and shotty cervical lymphadenopathy. Cardiac and
chest exam were normal. Skin exam revealed large erythe-
matous, tender, and indurated papules and plaques over the
face with smaller lesions scattered over the upper chest, back,
upper legs, and arms.
Repeat laboratories and skin biopsy were performed.
Hemoglobin dropped from 13.7g/dL to 10.9g/dL over two
days. A skin biopsy of the right upper arm revealed an
extensive interstitial infiltrate of neutrophils and histiocytes
syndrome. A skin biopsy over the chin 17 months later
showed neutrophilic dermatitis with leukocytoclasis. Treat-
ment with higher dose prednisone and azathioprine resulted
in a good response. However, as indicated by the repeat
biopsy, the rash recurred as prednisone was tapered.
A 23-year-old Asian male with a history of SLE diagnosed
at age 16 presented for followup with his nephrologist.
He complained of persistent right facial swelling for 12
months. The swelling was limited to the skin over the right
parotid gland and was associated with intermittent pruritic
vesicles. Manifestations of SLE included a discoid rash and
Case Reports in Rheumatology3
lupus nephritis. Abnormal serologies included antinuclear
antibody titer >640 diffuse and elevated titers of anti-dsDNA
antibodies. Medications included prednisone 5mg, enalapril
5mg, and tacrolimus 2mg twice daily. The patient was an
engineer, used tobacco and alcohol occasionally, and was not
sexually active. On examination, the patient was normoten-
sive and afebrile. He had slight warmth and erythema over
the right parotid gland without tenderness. Laboratory data
revealed an elevated anti-dsDNA antibody titer of 271iu/mL
(250iu/mL one month prior). Complete blood count, com-
plement levels, creatinine, urinalysis, and c-reactive protein
were all normal. A fine needle aspiration of the parotid
gland revealed a mixed population of lymphocytes with scat-
tered lymphoepithelial islands, diagnostic of lymphoepithe-
lial sialadenitis. Skin biopsy of the right cheek showed a
diffuse infiltrate of neutrophils and leukocytoclastic debris
consistent with Sweet’s syndrome (Figures 2(a) and 2(b)).
The patient was started on hydroxychloroquine 400mg and
prednisone with an excellent response.
While Sweet’s syndrome can occur in idiopathic fashion, it
can also be drug induced, associated with malignancy ,
or connective tissue diseases. Concurrent Sweet’s disease and
SLE are exceedingly rare. Only two other papers reported
Sweet’s syndrome as an initial presentation in adult SLE [6,
8]. Our Case 1 is the third. Three cases of Sweet’s syndrome-
like nonbullous neutrophilic dermatosis and neonatal lupus
have been reported [14, 15], as well as three cases of hy-
dralazine-induced SLE and Sweet’s [16–18], but will not be
discussed here. In addition, cases with some features of SLE
The skin lesions in Sweet’s syndrome typically start as
erythematosus papules, plaques, and nodules. The lesions
lesions are usually painful, and typical sites include the head,
neck, and upper extremities, although lesions can be found
anywhere. Lesions usually develop abruptly, resolve over 1–3
months, and can recur in 30% of patients . One of the
two major criteria as outlined by Von den Driesch is a typical
cutaneous rash . Indeed, all three patients described
herein had a rash compatible with Sweet’s syndrome. Both
Cases 1 and 2 had lesions on the face, upper trunk, arms,
and legs. Patient 3 had erythematosus swelling on his right
face with vesicles within it for 12 months. Although the time
course of this patient’s lesion was atypical for Sweet’s, the
vesicles waxed and waned, suggesting resolution and recur-
rence, as can be seen.
The prototypical histopathologic findings in Sweet’s
syndrome include a diffuse dermal infiltrate of neutrophils
accompanied by leukocytoclasis with overlying papillary
dermal edema and, in some cases, extending into the subcu-
taneous septa. Although older studies reported that leukocy-
toclastic vasculitis is not seen , more recent reports have
convincingly demonstrated that leukocytoclastic vasculitis
Figure 2: (a) Low magnification showing a diffuse dermal infiltrate
of neutrophils accompanied by leukocytoclastic debris. (b) High
magnification highlighting the neutrophils.
can occasionally be found . The skin biopsies from
all patients described herein were compatible with Sweet’s
syndrome as they exhibited a dermal neutrophilic infiltrate
accompanied by leukocytoclasis (Table 1). In Cases 2 and 3,
in Case 1 it was relatively sparse. Additional histopathologic
findings in Case 1 included extension of the neutrophilic
infiltrate into subcutaneous septa and accompanying leuko-
As posited by Gleason and colleagues , infiltrates that
are less dense than what is typically observed in Sweet’s
disease may be classified as “neutrophilic dermatosis of LE
(lupus erythematosus).” In fact, our Case 1 probably best fits
into this classification. It seems most plausible that Sweet’s
syndrome and neutrophilic dermatosis of LE are related
and on a spectrum. It is important for rheumatologists and
dermatologists to recognize the possibility, as suggested by
Gleason, that what appears to be a distinct entity (Sweet’s
syndrome) may in fact be a variant of cutaneous LE and may
represent the first manifestation of the systemic disease, as in
These new cases, combined with nine others in the
literature, raise several important questions. Does Sweet’s
syndrome occur as an independent process, or is it merely
a manifestation of the underlying autoimmune disease and
an underrecognized variant of cutaneous LE? In two out of
three new cases, the rash consistent with Sweet’s syndrome
4 Case Reports in Rheumatology
Table 1: Demographic and clinical characteristics of SLE patients at time of presentation with Sweet’s.
PatientGender Age Race/ethnicity
SLE at time of
1 Female26 Asian
2 Female23 Asian
3 Male23 Asian ANA, dsDNANeutrophilic
Goette 1985 Male67NA
Arthritis, malar, and
Choi and Chung,
Malar rash, oral
Cron, 2005 
Arthritis, oral ulcer,
Marked edema of
Hou et al., 2005
Gleason et al.,
Gleason et al.,
(lupus nephritis on
Camarillo et al.,
Fernandes et al.,
Gollol-Raju et al.,
Malar rash (lupus
Case Reports in Rheumatology5
paralleled underlying SLE activity. In Case 1, the patient had
concomitant oral ulcerations, hand swelling, and a Coombs
and a Coombs positive hemolytic anemia. The nine other
cases in the literature reflect a similar pattern of Sweet’s
presenting along with manifestations of active SLE.
Although the pathogenesis of Sweet’s syndrome remains
elusive, evidence suggests that cytokine dysregulation may be
central to the clinical and pathological changes. Studies have
implicated a variety of cytokines, including IL-1, IL-3, IL-6,
and IL-8 and G-CSF, GM-CSF and interferon gamma [22,
23]. Some of these cytokines, such as IL-6, may also play a
role in SLE through a variety of mechanisms, including B cell
ilarly, interferon gamma may be involved in the pathogenesis
of SLE. In one series of experiments, NZB mice treated with
interferon developed hemolytic anemia earlier and had a
renal failure . This preliminary evidence suggests that
be that in certain patients during a SLE flare, some cytokines
implicated in eliciting Sweet’s syndrome are released, result-
ing in clinical manifestations on the spectrum of Sweet’s syn-
drome and Sweet’s syndrome-like neutrophilic dermatitis.
Like other cases in the literature, our patients responded
dramatically to corticosteroids, which are the mainstay of
therapy for Sweet’s syndrome. Other immunosuppressive
treatments, including cyclosporine, have also been used suc-
cessfully. Additional treatments include potassium iodide,
dapsone, colchicine, indomethacin, and clofazimine.
In summary, Sweet’s syndrome is a neutrophilic der-
matoses that may be more commonly associated with SLE
than previously suspected because of the role of cytokine
dysregulation in the pathogenesis of both conditions. Sweet’s
disease observed in the setting of lupus may also be classified
as “neutrophilic dermatosis of LE” and may be the first
manifestation of SLE. Further research is needed to define
the exact relationship between the two conditions and to
enhance awareness among both rheumatologists and derma-
The authors would like to dedicate this paper to the memory
of their senior author and beloved teacher, Dr. Kenneth H.
Fye, who died on March 28, 2010.
Dr. J. L. Barton’s work was supported by a Physician
Scientist Development Award from the American College of
Rheumatology Research and Education Foundation. Drs. J.
L. Barton, J. Yazdany, N. Richman, L. Gensler, M. Dall’Era
and K. H. Fye’s work was supported by the Rosalind
Russell Medical Research Center for Arthritis, University
of California, San Francisco. Dr. J. Yazdany also received
support from the Arthritis Foundation Arthritis Investigator
Award, and Dr. N. Richman received support from NIH T32
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