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“Drug-induced Sweet’s Syndrome
Masquerading as ANCA-associated
Vasculitis”
Melissa R. Bussey, M.D.
Rheumatology Fellow
Division of Allergy, Immunology, and Rheumatology
Loyola University Medical Center
2160 S. First Ave, Bldg 54, Rm 153
Maywood, Illinois 60153
Ph: 708-216-2012
RWCS 2014
Clinical Case
• A 59 year-old male with congenital solitary kidney and
squamous cell cancer of the lung complicated by
myelodysplastic syndrome (MDS) was admitted from a long
term care facility with fevers and cough. He was started on
broad spectrum antibiotics to treat healthcare associated
pneumonia and his respiratory status initially improved.
One dose of GM-CSF (Neulasta) was given for significant
neutropenia related to his known MDS. Six days after his
Neulasta dose, the patient was noted to have worsening
anemia, new onset hematuria and proteinuria, acute renal
failure (creatinine increase from 1.2 to 5.0), worsening
respiratory status (hemoptysis, hypoxia) and fevers. He
also developed a painful purpuric rash on hands, forearms,
and left thigh.
Clinical Case (Cont.)
• Laboratory workup revealed elevated
inflammatory markers, negative infectious
workup, positive ANA 1:160, and high titer
myeloperoxidase and proteinase-3 antibodies.
• The primary service was initially concerned for
ANCA-associated vasculitis with pulmonary, renal,
and skin involvement. The patient subsequently
underwent skin biopsy, additional lung imaging,
and bronchoscopy to help confirm the diagnosis
Rash
Dermatology noted palpable
purpura on both hands, left
antecubital region, and left
proximal medial thigh; also
noted were coalescing petechiae
and ecchymosis on left foot.
**The patient’s written consent was obtained regarding the use of photographs.
Biopsy of Skin Rash (low and high power views)
•
Within the dermis is a sharply localized collection of neutrophils and neutrophilic debris
admixed with extravasated red blood cells. Focal epidermal spongiosis is noted. No fibrinoid
necrosis of vessels is seen. No eosinophils are present.
•
The pathologist felt these findings were more consistent with Sweet’s Syndrome than vasculitis.
Chest CT
Chest CT showed development of new coalescing alveolar infiltrates
throughout the right lower lobe and patchy nodular infiltrates scattered
throughout the left lung along with new small left pleural effusion.
Bronchoscopy Images
Nodules
Mainstem bronchi notable for multiple white nodules
thought to be tracheo-bronchial Sweet’s nodules;
unfortunately lesions could not be biopsied safely due to
thrombocytopenia (platelets <50k). Bronchoalveolar
lavage fluid was noted to have 76% neutrophils.
Diagnosis and Clinical Course
• Final Diagnosis: Drug-induced Sweet’s syndrome with
cutaneous and extracutaneous involvement
(bronchopulmonary, renal)
• Clinical Course: Once a diagnosis of Sweet’s syndrome was
made, the patient was started on high dose prednisone.
The patient’s fevers, oxygen requirements, and rash
improved dramatically with steroids. The infiltrates on his
chest CT resolved completely and his renal function
stabilized, but unfortunately did not return to baseline.
Kidney biopsy was not performed due to ongoing
thrombocytopenia.
Sweet’s Syndrome
• Sweet’s syndrome was initially described by Dr. Robert Douglas
Sweet in 1964 when he reported a case of “An acute febrile
neutrophilic dermatosis”1
• Since then, Sweet’s syndrome has been described in three different
clinical settings2,3
– Classic (or idiopathic) Sweet’s syndrome
• Primarily seen in women
• Associated with infection, inflammatory bowel disease, or pregnancy
• Recurrence in up to 1/3 of patients
– Malignancy-associated Sweet’s syndrome
• Equal rates in men and women
• Most commonly seen with Acute Myelogenous Leukemia
• Also reported with solid tumors – GU, breast, GI
– Drug-Induced Sweet’s syndrome
• Most frequently observed following G-CSF (Neulasta)
• Rechallenge is typically associated with recurrence
1. Cohen PR and Kurzrock R. Int J Derm. 2003;42:761-778
2. Anzalone CL and Cohen PR. Curr Opin Hematology. 2013;20(1):26-35.
3. Cohen PR. Orphanet J Rare Dis. 2007;2:34.
Diagnostic Criteria for Drug-Induced
Sweet’s Syndrome
• All five criteria are required for diagnosis of drug-induced Sweet’s syndrome:
1.
2.
3.
4.
5.
Abrupt onset of painful erythematous plaques or nodules
Histopathologic evidence of a dense neutrophilic infiltrate without evidence of
leukocytoclastic vasculitis
Pyrexia >38C
Temporal relationship between drug ingestion and clinical presentation, OR
temporally-related recurrence after oral challenge
Temporally-related resolution of lesions after withdrawal or treatment with
systemic corticosteroids
• Our patient satisfied all 5 of these criteria.
Cohen PR. Orphanet J Rare Dis. 2007;2:34.
Sweet’s Syndrome - Histopathology
• Characteristic histopathology of a Sweet’s
syndrome skin lesion reveals a dense, diffuse
infiltrate of mature neutrophils in the superficial
dermis. In addition, one may see lymphocytes,
histiocytes, and eosinophils along with edema of
the dermal papillae and papillary dermis.
• A subcutaneous variant has also been described
with characteristic neutrophilic inflammation in
the subcutaneous fat.
Cohen PR and Kurzrock R. Int J Derm. 2003;42:761-778
Sweet’s Syndrome – Clinical Manifestations
• Cutaneous Manifestations
– Skin lesions are described as painful red or purple papules which may
become plaques. The lesions are often asymmetrically distributed and
are most typically found on the upper extremities, face, and neck. The
lesions often resolve without scarring. Pathergy has been described in
association with Sweet’s syndrome skin lesions.1
• Pulmonary Manifestations
– Interestingly, pulmonary involvement was the first described
extracutaneous manifestation of Sweet’s syndrome. Symptoms of
pulmonary involvement include dyspnea, dry cough, fevers, and
interstitial infiltrates or pulmonary opacities which can appear
excavated. These findings often appear simultaneously with skin
lesions; however, skin lesions can also precede the lung findings by
months or years. Histology of lung tissue shows dense alveolar
neutrophilic infiltrate.2
– There are a few cases of tracheo-bronchial involvement described in
the literature.3,4
1.
2.
3.
4.
Cohen PR. Orphanet J Rare Dis. 2007;2:34.
Astudillo L et al. Int J Derm. 2006;45:677-80.
Tanimura K et al. Thorax. 2010;65:1119-20.
Thurnheer R et al. Eur Respir J. 1998;11:978-990.
Sweet’s Syndrome – Clinical Manifestations
• Renal Manifestations
– Renal manifestations of Sweet’s syndrome are not
as well described in the literature, however,
proteinuria, hematuria, and mesangiocapillary
glomerulonephritis have been reported.1,2
• Manifestations of Sweet’s syndrome have also
been reported in nearly every other organ
system including bone, central nervous
system, intestines, liver, heart, muscle, and
spleen.1,2
1. Cohen PR. Orphanet J Rare Dis. 2007;2:34.
2. Vignon-Pennamen MD. Clin Derm. 2000;18:339-347.
Sweet’s Syndrome - Treatment
• In drug-induced Sweet’s syndrome, symptoms may remit with
withdrawal of the offending agent.
• In malignancy-associated Sweet’s syndrome, treatment of the
underlying malignancy may result in resolution of the dermatosis as
well.
• Systemic steroids are the first-line therapy for Sweet’s syndrome
and typically symptoms will improve promptly after initiation of
treatment. The initial prednisone dose is 1mg/kg/day with tapering
to 10mg daily within 4 to 6 weeks. Low dose prednisone therapy
may need to be continued for several months, however.
• There is some discussion in the literature of successful treatment of
Sweet’s syndrome with colchicine using total daily doses of about
1.5mg. Other second-line agents include cyclosporine, dapsone,
and indomethacin.
Cohen PR. Orphanet J Rare Dis. 2007;2:34
References
• Anzalone CL and Cohen PR. Acute febrile neutrophilic dermatosis
(Sweet’s syndrome). Curr Opin Hematology. 2013;20(1):26-35.
• Astudillo L et al. Pulmonary involvement in Sweet’s syndrome: a
case report and review of the literature. Int J Derm. 2006;45:67780.
• Cohen PR. Sweet’s syndrome – a comprehensive review of an acute
febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34.
• Cohen PR and Kurzrock R. Sweet’s syndrome revisited: a review of
disease concepts. Int J Derm. 2003;42:761-778.
• Tanimura K et al. Tracheo-bronchial involvement in Sweet
syndrome. Thorax. 2010;65:1119-20.
• Thurnheer R et al. Bronchial manifestation of acute febrile
neutrophilic dermatosis. Eur Respir J. 1998;11:978-990.
• Vignon-Pennamen MD. The extracutaneous involvement in the
neutrophilic dermatoses. Clin Derm. 2000;18:339-347.