Sweet syndrome
Encyclopedia
Sweet's syndrome or acute febrile neutrophilic dermatosis is a skin disease characterized by the sudden onset of fever
, leukocytosis
, and tender, erythematous, well-demarcated papules and plaques which show dense infiltrates
by neutrophil granulocyte
s on histologic
examination.
The syndrome was first described in 1964 by Dr Robert Douglas Sweet. It was also known as Gomm-Button disease in honour of the first two patients Dr Sweet diagnosed with the condition.
disease (including leukemia
), and immunologic
disease (rheumatoid arthritis
, inflammatory bowel disease
).
A genetic association has been suggested, but no specific genetic link has been identified.
in 1964, described a disease with four features: fever; leukocytosis; acute, tender, red plaques; and a papillary dermal
infiltrate of neutrophils
. This led to the name acute febrile neutrophilic dermatosis. Larger series of patients showed that fever and neutrophilia are not consistently present. The diagnosis is based on the two constant features, a typical eruption and the characteristic histologic features; thus the eponym "Sweet's syndrome" is used.
There is now good evidence that treatment with hematopoietic growth factors, including granulocyte colony-stimulating factor
, which is used to treat acute myelogenous leukemia, and granulocyte-macrophage colony-stimulating factor, can cause SS. Lesions typically occur when the patient has leukocytosis and neutrophilia but not when the patient is neutropenic. However, G-CSF may cause SS in neutropenic patients because of the induction of stem cell proliferation, the differentiation of neutrophils, and the prolongation of neutrophil survival.
Acute, tender, erythematous plaques, nodes, pseudovesicles and, occasionally, blisters with an annular or arciform pattern occur on the head, neck, legs, and arms, particularly the back of the hands and fingers. The trunk is rarely involved. Fever (50%); arthralgia or arthritis (62%); eye involvement, most frequently conjunctivitis or iridocyclitis (38%); and oral aphthae (13%) are associated features. Differential diagnosis includes erythema multiforme, erythema nodosum, adverse drug reaction, and urticaria. Recurrences are common and affect up to one third of patients.
Vasculitis occurs secondary to noxious products released from neutrophils. Blood vessels in lesions of longer duration are more likely to develop vasculitis than those of shorter duration because of prolonged exposure to noxious metabolites. Therefore, vasculitis does not exclude a diagnosis of SS.
) produce rapid improvement and are the “gold standard” for treatment. The temperature, WBC count, and eruption improve within 72 hours. The skin lesions clear within 3 to 9 days. Abnormal laboratory values rapidly return to normal. There are, however, frequent recurrences. Corticosteroids are tapered within 2 to 6 weeks to zero. Resolution of the eruption is occasionally followed by milia and scarring. The disease clears spontaneously in some patients. Topical and/or intralesional corticosteroids may be effective as either monotherapy or adjuvant therapy.
Oral potassium iodide
or colchicine
may induce rapid resolution. Patients who have a potential systemic infection or in whom corticosteroids are contraindicated can use these agents as a first-line therapy.
In one study, indomethacin, 150 mg per day, was given for the first week, and 100 mg per day was given for 2 additional weeks. Seventeen of 18 patients had a good initial response; fever and arthralgias were markedly attenuated within 48 hours, and eruptions cleared between 7 and 14 days. Patients whose cutaneous lesions continued to develop were successfully treated with prednisone (1 mg/kg per day). No patient had a relapse after discontinuation of indomethacin.
Other alternatives to corticosteroid treatment include dapsone
, doxycycline
, clofazimine
, and cyclosporine. All of these drugs influence migration and other functions of neutrophils.
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, leukocytosis
Leukocytosis
Leukocytosis is a raised white blood cell count above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, and is observed in certain parasitic infections...
, and tender, erythematous, well-demarcated papules and plaques which show dense infiltrates
Infiltration (medical)
Infiltration is the diffusion or accumulation of substances not normal to it or in amounts in excess of the normal. The material collected in those tissues or cells is called infiltrate.-Classification:...
by neutrophil granulocyte
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
s on histologic
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
examination.
The syndrome was first described in 1964 by Dr Robert Douglas Sweet. It was also known as Gomm-Button disease in honour of the first two patients Dr Sweet diagnosed with the condition.
Associations
Although it may occur in the absence of other known disease, SS is often associated with hematologicHematology
Hematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...
disease (including leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
), and immunologic
Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...
disease (rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
).
A genetic association has been suggested, but no specific genetic link has been identified.
Definition
Sweet, working in PlymouthPlymouth
Plymouth is a city and unitary authority area on the coast of Devon, England, about south-west of London. It is built between the mouths of the rivers Plym to the east and Tamar to the west, where they join Plymouth Sound...
in 1964, described a disease with four features: fever; leukocytosis; acute, tender, red plaques; and a papillary dermal
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...
infiltrate of neutrophils
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
. This led to the name acute febrile neutrophilic dermatosis. Larger series of patients showed that fever and neutrophilia are not consistently present. The diagnosis is based on the two constant features, a typical eruption and the characteristic histologic features; thus the eponym "Sweet's syndrome" is used.
Etiology
SS can be classified based upon the clinical setting in which it occurs: classical or idiopathic SS, malignancy-associated SS, and drug-induced SS.Systemic diseases
SS is a reactive phenomenon and should be considered a cutaneous marker of systemic disease. Careful systemic evaluation is indicated, especially when cutaneous lesions are severe or hematologic values are abnormal. Approximately 20% of cases are associated with malignancy, predominantly hematological, especially acute myelogenous leukemia. An underlying condition (streptococcal infection, inflammatory bowel disease, nonlymphocytic leukemia and other hematologic malignancies, solid tumors, pregnancy) is found in up to 50% of cases. Attacks of SS may precede the hematologic diagnosis by 3 months to 6 years, so that close evaluation of patients in the “idiopathic” group is required.There is now good evidence that treatment with hematopoietic growth factors, including granulocyte colony-stimulating factor
Granulocyte colony-stimulating factor
Granulocyte colony-stimulating factor is a colony-stimulating factor hormone. G-CSF is also known as colony-stimulating factor 3 ....
, which is used to treat acute myelogenous leukemia, and granulocyte-macrophage colony-stimulating factor, can cause SS. Lesions typically occur when the patient has leukocytosis and neutrophilia but not when the patient is neutropenic. However, G-CSF may cause SS in neutropenic patients because of the induction of stem cell proliferation, the differentiation of neutrophils, and the prolongation of neutrophil survival.
Clinical manifestations
Laboratory studies
Studies show a moderate neutrophilia (less than 50%), elevated ESR (greater than 30 mm/hr) (90%), and a slight increase in alkaline phosphatase (83%). Skin biopsy shows a papillary and mid-dermal mixed infiltrate of polymorphonuclear leukocytes with nuclear fragmentation and histiocytic cells. The infiltrate is predominantly perivascular with endothelial-cell swelling in some vessels, but vasculitic changes (thrombosis; deposition of fibrin, complement, or immunoglobulins within the vessel walls; red blood cell extravasation;inflammatory infiltration of vascular walls) are absent in early lesions.Vasculitis occurs secondary to noxious products released from neutrophils. Blood vessels in lesions of longer duration are more likely to develop vasculitis than those of shorter duration because of prolonged exposure to noxious metabolites. Therefore, vasculitis does not exclude a diagnosis of SS.
Treatment
Systemic corticosteroids (prednisonePrednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
) produce rapid improvement and are the “gold standard” for treatment. The temperature, WBC count, and eruption improve within 72 hours. The skin lesions clear within 3 to 9 days. Abnormal laboratory values rapidly return to normal. There are, however, frequent recurrences. Corticosteroids are tapered within 2 to 6 weeks to zero. Resolution of the eruption is occasionally followed by milia and scarring. The disease clears spontaneously in some patients. Topical and/or intralesional corticosteroids may be effective as either monotherapy or adjuvant therapy.
Oral potassium iodide
Potassium iodide
Potassium iodide is an inorganic compound with the chemical formula KI. This white salt is the most commercially significant iodide compound, with approximately 37,000 tons produced in 1985. It is less hygroscopic than sodium iodide, making it easier to work with...
or colchicine
Colchicine
Colchicine is a medication used for gout. It is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum...
may induce rapid resolution. Patients who have a potential systemic infection or in whom corticosteroids are contraindicated can use these agents as a first-line therapy.
In one study, indomethacin, 150 mg per day, was given for the first week, and 100 mg per day was given for 2 additional weeks. Seventeen of 18 patients had a good initial response; fever and arthralgias were markedly attenuated within 48 hours, and eruptions cleared between 7 and 14 days. Patients whose cutaneous lesions continued to develop were successfully treated with prednisone (1 mg/kg per day). No patient had a relapse after discontinuation of indomethacin.
Other alternatives to corticosteroid treatment include dapsone
Dapsone
Dapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for the treatment of Mycobacterium leprae infections . It is also second-line treatment for prophylaxis against Pneumocystis pneumonia caused by Pneumocystis jiroveci Dapsone...
, doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
, clofazimine
Clofazimine
Clofazimine is a fat-soluble riminophenazine dye used in combination with rifampicin and dapsone as multidrug therapy for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients and...
, and cyclosporine. All of these drugs influence migration and other functions of neutrophils.