NORD gratefully acknowledges Philip R. Cohen, MD, Department of Dermatology, University of California San Diego, for assistance in the preparation of this report.
Sweet syndrome is a rare disorder characterized by fever and the sudden onset of a rash, which consists of multiple tender, red or bluish-red bumps or lesions. These lesions usually occur on the arms, legs, trunk, face or neck. In some cases, additional systems of the body can become involved including the musculoskeletal system such as inflammation of the joints (arthritis), the eyes such as inflammation of the conjunctiva or the membrane that lines the eyes (conjunctivitis), and the internal organs. In the majority of affected individuals, the disorder occurs by itself for no known reason (idiopathic Sweet syndrome); this is also known as classical Sweet syndrome. Less often, the disorder can be associated with an underlying cancer (malignancy), usually a blood (hematologic) cancer such as certain types of leukemia; this is known as malignancy-associated Sweet syndrome. The disorder can also result as a reaction to taking certain drugs, especially a drug known as granulocyte-colony stimulating factor; this is known as drug-induced Sweet syndrome. Sweet syndrome is treated with corticosteroids.Introduction
Sweet syndrome was first described in the medical literature in 1964 by Dr. Robert Douglas Sweet. The disorder is classified as a neutrophilic dermatosis, which is a general term for a group of skin disorders characterized by the accumulation of neutrophils in the skin. Neutrophils are a specific type of white blood cell that is instrumental in fighting off infection by surrounding and destroying bacteria that enter the body. In Sweet syndrome neutrophils accumulate in the dermis, the thick layer of tissue just below the outer layer of the skin (epidermis).
The major symptom of Sweet syndrome is the sudden onset of tender or painful bumps (nodules or papules) on the arms, legs, face or neck. They may also occur on the thighs and trunk. Papules are solid, raises lesions; nodules are slightly larger and may extend deeper into the skin. These initial lesions are usually several millimeters to centimeters in diameter, but sometimes up to an inch in diameter, flat or slightly elevated, irregularly-shaped, and inflamed. They tend to grow slowly, eventually joining together (coalescing) to form larger, irregular plaques. Small pus-filled blisters (pustules) may develop.
In some individuals, neutrophils may accumulated in the fatty layer of tissue just below the skin (subcutaneous fat) rather than in the dermis. Affected individuals often develop reddish (erythematous) discoloration of the skin and small bumps (nodules) on the skin. The arms and legs are most often affected.
Individuals with Sweet syndrome also experience fever, fatigue, headaches, a general feeling of ill health (malaise), muscle pain (myalgia), and inflammation and pain of the joints (arthritis and arthralgia). Fever can precede the development of skin symptoms by days or weeks.
Sweet syndrome can potentially affect most organ systems of the body. The most common organ system involved outside of the skin is the eyes. Affected individuals can develop inflammation of the conjunctiva, the delicate membrane that lines the eyes (conjunctivitis) or inflammation of the thin layer of tissue (episclera) covering the whites of the eyes (episcleritis). Less often, additional symptoms can occur including the formation of bumps on the limbus, which is the border of the cornea and the whites of the eyes (limbal nodules), glaucoma, inflammation of the iris, which is the colored portion of the eye (iritis), and inflammation and ulceration of the cornea (peripheral ulcerative keratitis).
In most individuals, Sweet syndrome occurs without any underlying disorder. In these individuals with classic Sweet syndrome, onset of the disorder usually follows an infection of the upper respiratory tract or gastrointestinal system.
Less often, Sweet syndrome is associated with a malignancy, most often a malignancy that affects the blood (hematologic malignancies), such as certain types of leukemia and, rarely, cancers of the genitourinary and gastrointestinal tracts. In some cases, individuals with malignancy-associated Sweet syndrome may have lesions affecting the mucous membranes of the mouth (oral mucosa).
Drug-induced Sweet syndrome has skin (cutaneous) symptoms are similar to those seen in the classical form.
The exact cause of Sweet syndrome is not fully understood. Most likely, the disorder results from multiple, complex factors including immunological, and environmental factors. Some researchers speculate that Sweet syndrome occurs as an allergic reaction (reactive process) to an unknown agent. In such instances, there is an oversensitive, or hypersensitivity, reaction by the immune system to a specific agent such as a bacterial or viral infection, cancer or certain type of drug.
Cytokine dysregulation may also play a role in the development of the disorder. Cytokines are specialized proteins secreted from certain immune system cells that either stimulate or inhibit the function of other immune system cells. If these cytokines malfunction, it can result in overstimulation of the immune system in response to a specific agent.
Many people with classic Sweet syndrome experience an upper respiratory infection, gastrointestinal infection, or influenza-like illness that precedes their skin lesions by one to three weeks. In women, classic Sweet syndrome may occur during pregnancy. Pregnancy-associated Sweet syndrome typically presents in the first or second trimester. There does not appear to be any fetal risk, and the syndrome may recur with subsequent pregnancies.
In some cases, classic Sweet syndrome may also be associated with autoimmune and inflammatory disorders such as inflammatory bowel disease: ulcerative colitis or Crohn’s disease. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
Drug-induced Sweet syndrome develops after using certain medications, the most commonly associated drug is known as granulocyte-colony stimulating factor. This drug is used to stimulate the production of neutrophils. A wide variety of additional drugs have been associated with Sweet syndrome, although less often.
Malignancy-associated Sweet syndrome is most commonly associated with blood cancers such as leukemia and lymphoma and solid tumors including breast cancer.
More research is necessary to determine the exact underlying mechanisms that contribute to and ultimately cause the development of Sweet syndrome.
Classical Sweet syndrome in adults affects women more often than men by as much as 15:1 by some estimates. This female preponderance has not been seen in malignancy-associated or drug-induced Sweet syndrome. Classical Sweet syndrome usually affects women between the ages of 30-50, but can be seen in individuals of any age including children. There is no gender predominance seen in children. Several hundred individuals of Sweet syndrome have been reported in the medical literature. Only approximately 80 children have been reported in the medical literature.
A diagnosis of Sweet syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of classic symptoms, and a variety of specialized tests. In many cases, surgical removal (biopsy) and microscopic examination of small samples of skin tissue may reveal the infiltrate of neutrophils in the dermis. A complete blood cell count may also show neutrophils in the blood (neutrophilia).
The treatment of Sweet syndrome is directed toward the specific symptoms that are apparent in each individual. In some cases, Sweet syndrome may resolve itself with no treatment, although this can take weeks to months. The mainstay of treatment is with systemic corticosteroids. In most cases, treatment with low doses of corticosteroids such as methylprednisolone or prednisone has proven effective in eliminating symptoms, sometimes rapidly resolving symptoms. However, Sweet syndrome often recurs periodically despite therapy. For isolated lesions, local therapy may consist of topical corticosteroids (creams of gels) or directly injecting corticosteroids into the lesion (intralesional corticosteroid).
Other drugs have been used to treat individuals with Sweet syndrome including colchicine, dapsone, and potassium iodide. These drugs are generally used for individuals who cannot tolerate corticosteroids, in whom corticosteroids were ineffective, or when trying to lower the dose of (taper) the corticosteroid. A variety of additional drugs have been used to treat individuals with Sweet syndrome including cyclosporine, indomethacin and clofazimine.
Individuals with Sweet syndrome should receive a thorough clinical examination to detect any possible underlying malignancy or disorder that may be associated with Sweet syndrome, including a complete hematologic evaluation. Usually, treatment of the underlying cancer results in the resolution of symptoms in malignancy-associated Sweet syndrome. However, treatment with corticosteroids as with the classic form is often recommended.
Drug-induced Sweet syndrome usually goes away after the affected individual stops taking the offending medication. Treatment with corticosteroids may also be used to treat this form of Sweet syndrome.
The skin lesions associated with Sweet syndrome usually heal without scars, unless open sores were present (ulceration). The affected area may remain discolored for months after the lesion has resolved.
Although corticosteroids are the mainstay of treatment and often effective in treating Sweet syndrome, there are no standardized treatment protocols for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with Sweet syndrome.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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