Sweet Syndrome


Article Author:
Priyanka Vashisht


Article Editor:
Michelene Hearth Holmes


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David Wood
Andrew Wilt
Mary Cataletto


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Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
1/20/2019 9:12:50 AM

Introduction

Sweet syndrome, first described in 1964 by Robert Douglas Sweet, is an acute febrile neutrophilic dermatosis. It is a severe dermatologic disorder and patients presenting with the syndrome demonstrate an abrupt onset of tender plaques or nodules, fever, arthralgias, ophthalmologic manifestations, headaches and, rarely, oral or genital lesions.[1][2][3]

Sweet syndrome has four described features:

  • Fever
  • Leukocytosis
  • Acute tender red plaques
  • Papillary dermal infiltrate of neutrophils

Fever and neutrophilia are not consistently present. The diagnosis is based on the two constant features:

  • Typical eruption
  • Characteristic histologic features

The goals of pharmacotherapy in acute febrile neutrophilic dermatosis (Sweet Syndrome) is to reduce morbidity and complications. The best first-line option is systemic or topical corticosteroids if the lesions are limited. If corticosteroids are contraindicated, anti-inflammatory medications such as colchicine or dapsone can be used.

Etiology

Although its etiology is unknown, Sweet syndrome has been associated with many conditions. It can broadly be classified into four categories: idiopathic (the most common), para-inflammatory, paraneoplastic, and pregnancy-associated.[4][5]

Several autoimmune and other inflammatory conditions have been linked as underlying etiologies; these include systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, inflammatory bowel disease and Sjogren syndrome. It has been associated with several infectious processes, including infections with bacterial pathogens (e.g., atypical mycobacteria) and viral organisms (e.g., cytomegalovirus and human immunodeficiency virus). The drug-induced Sweet syndrome also has been reported; the medications most commonly associated with the drug-induced form are all trans retinoic acids, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor. Finally, Sweet syndrome may represent the early presentation of a neoplastic disease; the two most common neoplastic presentations are acute myelogenous leukemia and lymphoma.

Epidemiology

Sweet syndrome has no racial predilection. It is more common in females than males by a ratio of 3:1. Most cases have occurred between the ages of 30 and 50 years, however, reported age groups range from 2 to 75 years.

Pathophysiology

Sweet syndrome is an idiopathic disorder. Dysregulation of immune function or an immunomediated hypersensitivity to an eliciting bacterial, viral, or tumor antigen may trigger the development or promotion of Sweet syndrome. Laboratory studies show the presence of various cytokines, circulating autoantibodies, immune complexes, human leukocyte antigen serotypes, dermal dendrocytes, and leukotactic mechanisms which may be playing a role in the pathogenesis of Sweet syndrome.[6][7]

Histopathology

The classic histopathologic pattern of acute febrile neutrophilic dermatosis (Sweet Syndrome) consists of a diffuse dense neutrophilic infiltrate in the reticular dermis. Leukocytoclastic nuclear debris presents interstitially, and papillary dermal edema is common. True vasculitic changes usually are absent, although subtle vasculitic changes may occur. Eosinophils and lymphocytes may be present, but neutrophils predominate.

The epidermis typically is spared, although spongiosis and subcorneal pustule formation can be seen.

Direct immunofluorescence testing is not contributory. In rare instances, the inflammation may extend to involve the subcutis. In most instances, cases with subcutaneous involvement show extensive involvement of the reticular dermis.

Histiocytoid Sweet syndrome has been described as a variant and includes histiocytoid cells, which are immature myeloid cells that are commonly mistaken as histiocytes. The most important differential diagnosis for this variant is leukemia cutis.

History and Physical

Patients present with an abrupt onset of multiple tender, erythematous plaques or nodules. The lesions may be vesicular, bullous, or targetoid, and they may present on the face, neck, chest, back, and extremities. In rare cases, oral or genital lesions are present. Other manifestations include ophthalmologic involvement (6% to 72% of cases), fever (65%), and arthralgias and myalgias. Joint involvement may occur (33% to 62%), as well as lung, eye, kidney, liver, or central nervous system compromise.

Clinical diagnostic criteria have been proposed. The two major findings include the presence of (1) tender, painful eruptions of plaque-like nodules and (2) neutrophilic infiltrates in the dermis. Both must be present to establish a diagnosis of Sweet syndrome. To confirm the diagnosis of Sweet Syndrome, there should be at least two minor clinical features present; these include (1) illness preceded by an infection or fever (2) illness with arthralgia, fever, an underlying malignancy, or conjunctivitis (3) elevated white cell count, and (4) a positive response to corticosteroids.

Evaluation

Laboratory findings in patients with Sweet syndrome include an elevated erythrocyte sedimentation rate, peripheral leukocytosis, and neutrophilia. The diagnosis can be supported by biopsy findings of dense infiltrates in the superficial dermis composed primarily of polymorphonucleocytes and marked edema of the dermal papillae. Lymphocytes may also be present in the inflammatory infiltrate.

Treatment / Management

First-line treatment for Sweet syndrome is prednisone at 0.5 to 1.5 mg/kg/day tapered over 2 to 4 weeks. A corticosteroid injected into the lesions or applied topically also may be used. There are literature reports of successful use of potassium iodide and colchicine. Second-line agents for treating Sweet syndrome include indomethacin, clofazimine, cyclosporine, and dapsone.[8][9][10]

Differential Diagnosis

Diagnostic considerations include:

  • Acute hemorrhagic edema of childhood
  • Acral erythema
  • Bowel-associated dermatitis-arthritis syndrome
  • Halogenoderma
  • Neutrophilic rheumatoid dermatitis
  • Leukocytoclastic vasculitis
  • Leukemia cutis
  • Rosacea fulminans

The Differential Diagnoses includes:

  • Allergic Contact Dermatitis
  • Cellulitis
  • Dermatologic aspects of Behcet Disease
  • Dermatologic manifestations of Herpes Simplex
  • Drug Eruptions
  • Erythema Multiforme
  • Erythema Nodosum
  • Pyoderma Gangrenosum

Prognosis

Most cases resolve, although some persist indefinitely and can cause chronic pain and skin breakdown. Because this condition can be associated with other diseases, including malignancy, the prognosis depends on the underlying cause. Recurrence may occur in up to 50% of patients, usually in cases associated with drug reactions or hematologic malignancy.

Pearls and Other Issues

Differential diagnosis includes bullous pyoderma gangrenosum, erythema multiforme, urticarial vasculitis, rheumatoid neutrophilic dermatosis, and bacterial, mycobacterial, and deep fungal infections.

Sweet syndrome can present typically and atypically, so assess the overall clinical picture. It is important to be mindful of the association with hematologic malignancy. Patients with underlying myelodysplastic syndrome may have the classical cutaneous lesions of Sweet syndrome, but with lymphocytic infiltrate and atypical mononuclear infiltrate rather than neutrophils.

In some patients with classical Sweet syndrome, the signs and symptoms of Sweet syndrome may spontaneously resolve without any type of medical intervention. However, the lesions often persist for many weeks or months in others. Successful management of any malignancy will result in clearing the related dermatosis in patients with the malignancy-associated Sweet syndrome. Similarly, spontaneous improvement and subsequent resolution of the syndrome typically follows discontinuation of the associated medication in patients with drug-induced Sweet syndrome.

Enhancing Healthcare Team Outcomes

Sweet syndrome is a rare disorder of the skin. However, patients may usually present to the primary care provider or nurse practitioner with abrupt onset of tender plaques or nodules, fever, arthralgias, ophthalmologic manifestations, headaches and, rarely, oral or genital lesions. It is important to refer these patients to the dermatologist for further management, but the followup can be done by the primary caregiver.

The goals of pharmacotherapy in acute febrile neutrophilic dermatosis (Sweet Syndrome) is to reduce morbidity and complications. The best first-line option is systemic or topical corticosteroids if the lesions are limited. If corticosteroids are contraindicated, anti-inflammatory medications such as colchicine or dapsone can be used.

Sweet syndrome is a chronic disorder with relapses and remissions. While the symptoms do respond to treatment, there is no cure. Many patients have a poor quality of life because of continued treatment and side effects from medications. (Level II)


  • Image 474 Not availableImage 474 Not available
    Contributed by Scott Jones, MD
Attributed To: Contributed by Scott Jones, MD

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Sweet Syndrome - Questions

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In some patients who develop Sweet syndrome, the disorder may be an early presentation of which malignancy?



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Sweet Syndrome - References

References

Bhat AG,Siddappa Malleshappa SK,Pasupula DK,Duke W,Shaaban R, Bullous Variant of Sweet's Syndrome as a Consequence of Radioiodine Contrast Exposure. Cureus. 2018 Oct 24;     [PubMed]
Vettakkara KMN,Banerjee S,Mittal A,Goel P,Kumar P,Baitha U,Jorwal P,Soneja M,Biswas A, Not so sweet; severe Sweet's syndrome presenting as SIRS and pleural effusion. Journal of family medicine and primary care. 2018 Nov-Dec;     [PubMed]
Stevens G J,Yutronic H J,Pizarro O J,Velozo P L, Sweet Syndrome in Pediatrics. A case report. Revista chilena de pediatria. 2018 Aug;     [PubMed]
Nelis S,Azerad MA,Drowart A,Lewalle P,Efira A, [Sweet's syndrome induced by pegfilgrastim during a myelodysplastic syndrome AREB2: A case report]. La Revue de medecine interne. 2018 Dec 11;     [PubMed]
Arun Kumar AU,Elsayed ME,Alghali A,Ali AA,Mohamed H,Hussein W,Hackett C,Leonard N,Stack AG, Sweet syndrome: a rare feature of ANCA-associated vasculitis or unusual consequence of azathioprine-induced treatment. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2018;     [PubMed]
Gurnari C,Franceschini L,Anemona L,Passarelli F,Vaccarini S,Pupo L,Provenzano I,Nasso D,Rizzo M,Cantonetti M, Recurrent Sweet's syndrome in a patient with multiple myeloma. Clinical case reports. 2018 Oct;     [PubMed]
Das A,Burmeister R,Chhaya R,Eisenga B,Kumar A, Sweet Syndrome in a Patient With Systemic Lupus Erythematosus. Journal of clinical rheumatology : practical reports on rheumatic     [PubMed]
Sanchez IM,Lowenstein S,Johnson KA,Babik J,Haag C,Keller JJ,Ortega-Loayza AG,Cohen J,McCalmont TH,Demer AM,Mansh MD,Hylwa SA,Liu J,Shinkai K, Clinical Features of Neutrophilic Dermatosis Variants Resembling Necrotizing Fasciitis. JAMA dermatology. 2018 Oct 31;     [PubMed]
Corbeddu M,Pilloni L,Pau M,Pinna AL,Rongioletti F,Atzori L, Treatment of Sweet's syndrome in pregnancy. Dermatologic therapy. 2018 Jul;     [PubMed]
Kinser KN,Panach K,Dominguez AR, Recurrent Malignancy-Associated Atypical Neutrophilic Dermatosis With Noninfectious Shock. The American journal of the medical sciences. 2017 Dec;     [PubMed]

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