Answers

Short answers

1 This patient has Sweet’s syndrome.

2 Sweet’s syndrome is associated with upper respiratory tract infection; gastrointestinal infection; inflammatory bowel disease; pregnancy; malignancy; and certain drugs (for example, growth factors and various antibiotics, antiepileptics, antihypertensives, antipsychotics, contraceptives, diuretics, non-steroidal agents, and retinoids).

3 The "gold standard" treatment option is a tapered dose of systemic corticosteroids (initial dose of 40-60 mg per day) over a period of 4-6 weeks.

Long answers
1 Sweet’s syndrome
Sweet’s syndrome, also known as acute febrile neutrophilic dermatosis, was first described by Dr Robert Douglas Sweet in 1964.¹ The syndrome is characterised by fever, neutrophilia, and tender erythematous papules, nodules, and plaques that typically show an upper dermal infiltrate of mature neutrophils on skin biopsy.² If pustules are present, they tend to surmount the erythematous plaques and nodules. Sweet’s syndrome can be classified on the basis of the clinical setting in which it occurs: that is, classic (or idiopathic); in the presence of malignancy; and drug induced. Although the disorder can occur in the absence of other known diseases, Sweet’s syndrome is a reactive phenomenon and should be considered a cutaneous marker of systemic disease.³ Classic or idiopathic Sweet’s syndrome predominantly affects women and most frequently occurs in those between the ages of 30 and 60 years old.

Clinically, the skin lesions in Sweet’s syndrome appear as tender and erythematous papules, plaques, and nodules, with or without superadded pustules, and show a predilection for the upper extremities, face, and neck. Several extracutaneous manifestations of Sweet’s syndrome have been reported, including fever; arthralgia or arthritis; eye involvement, most frequently conjunctivitis or iridocyclitis; and oral ulceration. Differential diagnosis includes erythema multiforme, erythema nodosum, pyoderma gangrenosum, adverse drug reaction, and urticaria, as well as a number of other systemic and mucocutaneous disorders that may morphologically mimic Sweet’s syndrome.⁴

The pathogenesis of Sweet’s syndrome has yet to be elucidated. The development of Sweet’s syndrome is postulated to be a multifactorial process, involving perhaps a hypersensitivity reaction to a bacterial, viral, or tumour antigen. If deposited in the dermis, cytokines—such as granulocyte colony stimulating factor, interferon gamma, interleukin 1, interleukin 6, and interleukin 8—might contribute to the immunopathological and clinical manifestations of the disease.

From a diagnostic standpoint, studies consistently show peripheral leukocytosis with neutrophilia and an elevated erythrocyte sedimentation rate in patients with Sweet’s syndrome, as well as the classic skin lesions.⁵ Skin biopsy is a useful procedure for confirming the diagnosis of Sweet’s syndrome. In this patient, the diagnosis was made clinically and skin biopsy was not performed.

2 Associations
Malignancy related Sweet’s syndrome occurs as frequently in men as in women and can precede, follow, or appear concurrently with a patient’s neoplasm.⁴ Approximately 20-25% of cases are associated with malignancy, predominantly haematological malignancies and especially acute myelogenous leukaemia.⁶ Sweet’s syndrome is linked to solid tumours—including breast, genitourinary, and gastrointestinal malignancies—in 15% of patients.²

Drug induced Sweet’s syndrome most commonly occurs in patients treated with haematopoietic growth factors, such as granulocyte colony stimulating factor and granulocyte macrophage colony stimulating factor. A number of different types of drug have been associated with Sweet’s syndrome, however, including antibiotics, antiepileptics, antihypertensives, antipsychotics, contraceptives, diuretics, non-steroidal agents, and retinoids.⁴ A few cases of Sweet’s syndrome associated with azathioprine have been reported in the literature.^{7 8}

Our patient demonstrates a rare association of Sweet’s syndrome with Crohn’s disease; only a handful of such cases have been reported in the literature.^{3 9 10 11 12 13} Sweet’s syndrome associated with Crohn’s disease or ulcerative colitis shows a stronger predilection for women than men. Reports also suggest a higher incidence of colonic involvement and extraintestinal features of Sweet’s syndrome in these patients.¹⁴ The rash is generally associated with active Crohn’s disease in most patients but can sometimes precede the onset of intestinal symptoms.¹⁰ This case highlights the importance of being able to recognise and differentiate lesions characteristic of Sweet’s syndrome from other dermatological conditions more frequently associated with inflammatory bowel disease, such as erythema nodosum and pyoderma gangrenosum.

3 Treatment
The "gold standard" treatment option for Sweet’s syndrome is a tapered dose of systemic corticosteroids (initial dose of 40-60 mg per day) over a period of 4-6 weeks¹⁰; however, the disease can clear spontaneously in some patients. Topical and/or intralesional corticosteroids can be effective as either monotherapy or adjuvant therapy.^{2 15} Relapses are common though, particularly when steroids are withdrawn too quickly. Other first line systemic agents that can induce rapid resolution of Sweet’s syndrome include potassium iodide and colchicine. These treatments may be used in patients who have a systemic infection or in whom steroids are contraindicated. Other alternatives to corticosteroid treatment include dapsone, doxycyline, clofazimine, isotretinoin, and cyclosporine.^{15 16} Interestingly, all these drugs influence the migration and function of neutrophils.

Patient outcome
The patient underwent a dermatology review for his skin lesions. Following a clinical diagnosis of Sweet’s syndrome, a course of oral prednisolone 40 mg daily was commenced.

Flexible sigmoidoscopy confirmed a flare of Crohn’s disease, with inflammation from 20 cm to 40 cm and rectal sparing.

The skin lesions responded rapidly to treatment and had almost completely resolved at the time of discharge 2 weeks after admission. The patient has since responded well to infliximab therapy for the inflammatory bowel disease and has, to date, not had a further flare of Crohn’s disease or Sweet’s syndrome.

Cite this as: BMJ 2009;338:b2293