Sweet’s Syndrome

Sweet's syndrome was originally described in 1964 by Dr Robert Douglas Sweet as an 'acute febrile neutrophilic dermatosis'. The syndrome is characterized by pyrexia, elevated neutrophil count, painful red papules, nodules, plaques (which may be recurrent) and an infiltrate consisting predominantly of mature neutrophils that are diffusely distributed in the upper dermis. In addition to skin and mucosal lesions, Sweet's syndrome can also present with extra-cutaneous manifestations. Sweet's syndrome can be classified based upon the clinical setting in which it occurs: classical or idiopathic Sweet's syndrome, malignancy-associated Sweet's syndrome and drug-induced Sweet's syndrome. Systemic corticosteroids have been considered the 'gold standard' for the treatment of patients with Sweet's syndrome; in addition, treatment with topical and/or intralesional corticosteroids may be effective as either monotherapy or adjuvant therapy. However, spontaneous resolution of the symptoms and lesions has occurred in several patients with Sweet's syndrome for whom disease-specific therapeutic intervention was not initiated and in some of the patients with drug-induced Sweet's syndrome after withdrawal of the dermatosis-causing medication. Oral therapy with either potassium iodide or colchicine typically results in rapid resolution of Sweet's syndrome symptoms and lesions; therefore, in patients with Sweet's syndrome who have a potential systemic infection or in whom corticosteroids are contraindicated, it is reasonable to initiate treatment with these agents as a first-line therapy. Indomethacin, clofazimine, dapsone, and cyclosporine have also been effective therapeutic agents for managing Sweet's syndrome. However, indomethacin and clofazimine appear less effective than corticosteroids, potassium iodide, and colchicine. Appropriate initial and follow-up laboratory monitoring is necessary when treating with either dapsone or cyclosporine because of the potential for severe adverse drug-associated effects. Systemic antibacterials with activity against Staphylococcus aureus frequently result in partial improvement of Sweet's syndrome lesions when they are impetiginized or secondarily infected. In some patients with dermatosis-associated bacterial infections, organism-sensitive specific systemic antibacterials have been helpful in the management of their Sweet's syndrome. Although patients with hematologic malignancy-associated Sweet's syndrome often receive cytotoxic chemotherapy agents and antimetabolic drugs for the treatment of their underlying disorder, these agents are seldom used solely for the management of the symptoms and lesions of Sweet's syndrome. The treatment of patients with Sweet's syndrome with either etretinate or interferon-alpha have been reported as single case reports; both patients had improvement of not only their Sweet's syndrome lesions, but also their associated hematologic disorder.     

Sweet's syndrome revisited: a review of disease concepts

Sweet's syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by a constellation of symptoms and findings: fever, neutrophilia, erythematous and tender skin lesions that typically show an upper dermal infiltrate of mature neutrophils, and prompt improvement of both symptoms and lesions after the initiation of treatment with systemic corticosteroids. Hundreds of patients with this dermatosis have been reported. The manifestations of Sweet's syndrome in these individuals have not only confirmed those originally described by Dr Robert Douglas Sweet in 1964, but have also introduced new features that have expanded the clinical and pathologic concepts of this condition. The history, clinical characteristics, laboratory findings, associated diseases, pathology, and treatment options of Sweet's syndrome are reviewed. The evolving and new concepts of this dermatosis that are discussed include: (i) Sweet's syndrome occurring in the clinical setting of a disease-related malignancy, or medication, or both; (ii) detection of additional sites of extracutaneous Sweet's syndrome manifestations; (iii) discovery of additional Sweet's syndrome-associated diseases; (iv) variability of the composition and/or location of the cutaneous inflammatory infiltrate in Sweet's syndrome lesions; and (v) additional efficacious treatments for Sweet's syndrome.     

Lymphocytic infiltrates as a presenting feature of Sweet's syndrome with myelodysplasia and response to cyclophosphamide

Sweet's syndrome has a well-recognized association with malignancies, around half of which have been acute myelogenous leukaemia. There are also numerous reports of Sweet's syndrome in association with myelodysplasia. We report two patients with Sweet's syndrome in whom the classical histological appearances were preceded by dermal lymphocytic infiltrates. A literature search using PubMed indicates that this phenomenon has not been previously reported. The cases demonstrate the chronicity of Sweet's lesions in association with haematological disease and the need for repeat biopsies to make the diagnosis. We also describe successful treatment with cyclophosphamide, which adds to the list of second-line drugs that may be used in Sweet's syndrome.     

Histiocytes in Sweet''s syndrome

The histological features of biopsies from 18 previously unreported cases of Sweet's syndrome are reported. The dermal infiltrate in the majority of the cases contained numerous histiocytes that at first sight appeared to mimic neutrophils. The immunophenotype of these histiocytes was consistent with monocytes that have freshly infiltrated into the lesions. Only two of the cases in this series, associated with leukaemia, displayed the histological features of Sweet's syndrome with a predominant neutrophilic infiltration. We suggest that the initiating mechanisms in Sweet's syndrome are that monocyte/histiocyte-derived cytokines such as the interleukins IL-1 and IL-8, secreted either by infiltrating histiocytes in the non-leukaemia-associated cases of Sweet's syndrome or by tumoural myelomonocytic cells in those associated with leukaemia, are responsible for the systemic manifestations and the infiltration with neutrophils in the skin lesions.     

Sweet's syndrome and non-Hodgkin's lymphoma: the first report of this association

A 58-year-old woman developed Sweet's syndrome one week after a flu-like illness. She was later found to have a centrocytic/centroblastic non-Hodgkins lymphoma. Six courses of chemotherapy were given during which the lesions of Sweet's syndrome resolved completely. As far as we are aware this is the first report of the association of Sweet's syndrome with a lymphoma.     

Secondary syphilis mimicking Sweet''s syndrome

We describe a patient with secondary syphilis and facial skin lesions which resembled Sweet's syndrome clinically and histologically. We suggest serological tests for syphilis in patients with Sweet's syndrome.     

Sweet's syndrome from an Indian perspective: a report of four cases and review of the literature

BACKGROUND: Sweet's syndrome or acute febrile neutrophilic dermatosis is not frequently reported from India. Four patients fulfilling clinico-pathologic criteria for Sweet's syndrome seen during May-August 2002 prompted us to review reports on Indian patients from the indexed literature. METHODS: A PubMed and IndMed search for Sweet's syndrome revealed 11 reports appearing between 1985-2002 documenting 12 patients. The clinico-pathologic features, clinical course and treatment of all these 16 patients (including four new cases) were studied. RESULTS: The study comprised 12 females and four males between 35 days to 57 years of age. There were four children of < 12 years. Ulcerated, crusted lesions in one and typical, erythematous, tender, papulo-nodulo-plaques and targetoid lesions with pseudovesiculation were observed in 13 other patients particularly involving head, neck and upper limbs. Extracutaneous Sweet's syndrome manifesting as gingival hyperplasia and myositis was seen in one patient each. All had simultaneous onset of cutaneous lesions, fever, headache and malaise. Ocular involvement was observed in four patients only. Associated hematoligic disorders recorded were myelodysplasia in three, polycythemia vera in one and leukemia in three patients respectively. Two of these patients had treatment with all-transretinoic acid and low-dose cytosine-arbinoside before onset of Sweet's syndrome. One patient each had symptoms of upper respiratory tract infection and history of minor injury prior to cutaneous lesions. Another patient had pregnancy induced self-limiting Sweet's syndrome. Leukocytosis was present in 11 patients. Three of four new patients had positive tests for antistreptolysin-O and C-reactive protein. Characteristics histologic features were recorded in specimens of all patients. Eleven patients responded to systemic corticosteroids. Colchicin or potassium iodide were effective in one patient each. CONCLUSION: The overall clinico-pathologic and therapeutic spectrum of Sweet's syndrome in Indian patients does not appear to be different from its established picture.     

Acute febrile neutrophilic dermatosis and malignant hematologic diseases: report of a new bullous case and review of the literature

A new case of Sweet's syndrome (acute febrile neutrophilic dermatosis) associated with a malignant hemopathy is presented. The blood disease was a chronic myelomonocytic dysmyelopoiesis which was discovered during the eruption and resulted in the patient's death within a few months, probably through acutization. The skin lesions were atypical, bullous and ulcerated. On this occasion, the international literature concerning all cases of Sweet's syndrome associated with malignant or premalignant hemopathies is reviewed. Several concepts emerge from this study: the association is frequent (about 20 p. 100 of all published cases of Sweet's syndrome); there is a strong predominance of granulocytic hemopathies over lymphoplasmocytic and monocytic hemopathies; the blood disease is revealed by the skin eruption in some 50 p. 100 of the patients; there are frequent chronological relations between Sweet's syndrome and the events that occur in the course of the hemopathy; finally, the association is usually of poor prognosis. A comparison with Sweet's syndrome unassociated with a blood disease showed only three significant points: the frequency of bullous lesions, of the initial anaemia (the most important element) and of extreme figures in leucocyte counts (leucopenia or major hyperleukocytosis). The atypical character of the skin lesions in the patient presented here incites to discuss the nosological relationship between Sweet's syndrome and bullous pyoderma, an entity closely associated with hemopathies. It has recently been suggested by several authors that this anatomico-clinical kinship should be turned into a wide spectrum of acute neutrophilic dermatoses, with typical Sweet's syndrome at one end and Pyoderma gangrenosum at the other end. The interface between this spectrum and haemopathies seems to be maximum at its intermediate stage: the bullous and superficially ulcerated lesions. The aetiology and pathogenesis of this new nosological entity are uncertain. The presence of chemoattractants or of polymorphonuclear cell abnormalities is still open to discussion. The relationship between the entity and leukocytoclastic vasculitis has recently been questioned.     

Bullous Sweet's syndrome in congenital neutropenia: association with pegfilgrastim

Sweet's syndrome is an acute febrile neutrophilic dermatosis marked by attacks of painful, plaque-forming inflammatory papules accompanied by fever, arthralgias, peripheral leukocytosis, a diffuse dermal neutrophilic infiltrate, and prompt resolution of symptoms and lesions with glucocorticoid therapy. There are many reports of drug-induced Sweet's syndrome to various medications including all- trans -retinoic acid, carbamazepine, hydralazine, levonorgestrel/ethinyl estradiol, minocycline, trimethoprim/sulfamethoxazole, and granulocyte colony-stimulating factor. We describe the first known case of Sweet's syndrome induced by pegfilgrastim, a pegylated form of granulocyte colony-stimulating factor with unique pharmacologic properties that may induce Sweet's syndrome in patients with no history of neutrophilic dermatoses associated with granulocyte colony-stimulating factor therapy.     

Myelofibrosis Discovered After Diagnosis of Sweet''s Syndrome

Multiple edematous plaques and nodules suddenly developed on the face and neck of a 26-year-old man whose physical examination was said to be normal Because the patient's condition fulfilled the diagnostic criteria of Sweet's syndrome, a further general medical examination and hematologic evaluation were performed. Extensive myelofibrosis was revealed by bone marrow biopsy. This case supports the belief that Sweet's syndrome is a reactive phenomenon. Because myelofibrosis was discovered in this patient after Sweet's syndrome was diagnosed, the importance of having the diagnostic criteria of Sweet's syndrome is emphasized. Careful systemic evaluation is indicated, especially when cutaneous lesions are severe or hematologic values are abnormal.     

Sweet's syndrome with abscess-like lesions in a patient with acute myelogenous leukemia

We describe a 49-year-old man with acute myelogenous leukemia associated with Sweet's syndrome and abscess-like lesions mimicking an infectious disease. Although blisters may be included in the clinical spectrum, frank non-infectious abscesses have not been reported as far as we know. Clinicians should be familiar with this clinical and histopathologic variant of Sweet's syndrome. It is mandatory to make every effort to find an infectious cause for abscesses before a diagnosis of Sweet's syndrome is made.     

A case of Sweet's syndrome with early gastric cancer

The case of a 49-year-old man with Sweet's syndrome (acute febrile neutrophilic dermatosis) is described, who had coincidently gastric cancer. The therapeutic effectiveness of colchicine is also presented as one treatment for Sweet's syndrome, because rapid regression of the lesions was noticed.     

Elastophagocytosis: a feature of resolving Sweet''s syndrome

We report the case of a patient with atypical Sweet's syndrome characterized by an annular erythema that showed consumption of elastic fibres by giant cells and histiocytes. Although the lesions were found on sun-exposed sites and the first biopsy demonstrated extensive elastophagocytosis, our patient did not have photodamaged skin clinically. A repeat biopsy 5 weeks later demonstrated an abundant collection of neutrophils supporting the diagnosis of Sweet's syndrome. To our knowledge, an elastolytic granulomatous reaction pattern has not been previously reported in Sweet's syndrome.     

Localization of Sweet's syndrome in radiation-induced locus minoris resistentae

Sweet's syndrome is a reactive dermatosis clinically characterized by fever, leukocytosis, and multiple, erythematous, painful plaques. Histopathologically, the lesions show edema of the papillary dermis and a dermal infiltrate mainly composed of neutrophils, without vasculitis. We describe a patient with breast carcinoma and Sweet's syndrome mostly involving previously irradiated skin.     

Sweet's syndrome associated with acute renal failure

We describe two patients with Sweet's syndrome and acute renal failure requiring dialysis. One patient developed end-stage renal disease; the other died from acute renal failure. We recommend that patients with Sweet's syndrome be evaluated for concomitant renal disease and suggest that a common pathogenesis may produce cutaneous and renal lesions in some cases.     

Sweet's syndrome masquerading as facial cellulitis

Sweet's syndrome, or acute febrile neutrophilic dermatosis, is a cutaneous condition that typically occurs as tender red plaques or nodules. However, atypical presentations may occur and, in our case, Sweet's syndrome masqueraded as facial cellulitis and soft tissue infections of the extremities in a sporotrichoid pattern. Despite treatment with broad-spectrum antibiotics, the cutaneous lesions progressed. Results of skin biopsy specimens of the facial plaque and a nodule on the right upper extremity were diagnostic of Sweet's syndrome. Simultaneous to diagnosis, the patient also was found to have acute myelogenous leukemia (AML).     

Acute febrile neutrophilic dermatosis (Sweet's syndrome) in a patient with hairy-cell leukemia

A case of hairy-cell leukemia that started with cutaneous lesions similar to those of acute febrile neutrophilic dermatosis (Sweet's syndrome) is reported. The patient had leukopenia and a recurrent eruption for a year prior to the diagnosis of the hematologic disorder. Bone marrow examination eventually demonstrated characteristic "hairy" cells with tartrate-resistant, acid-phosphatase activity. Biopsy of a cutaneous lesion suggested an abscess showing a dense neutrophilic dermal infiltrate with perivascular predilection. The findings of IgA, IgM, C3, and fibrinogen in vessel walls by immunofluorescence and vascular disruption by electron microscopy contribute additional evidence for an immunologic determinant in this instance of Sweet's syndrome. It is known that neutrophilic infiltrates of Sweet's syndrome may have a variety of clinical presentations. This is the second case of hairy-cell leukemia with which Sweet's syndrome was associated.     

Sweet's syndrome in patients with kidney and liver disorders.

Two patients with Sweet's syndrome are described. In the first patient the disorder was associated with urinary stone disease and in the second with chronic hepatitis. We compared skin lesions in patients with kidney and liver diseases with those in Sweet's syndrome. In both patients all skin manifestations disappeared when the underlying disorders were treated. No corticosteroids were used.     

Acute febrile neutrophilic dermatosis--a marker of malignancy?

A retrospective survey during a 2-year period disclosed 18 patients with acute febrile neutrophilic dermatosis (Sweet's syndrome). An associated lympho- or myeloproliferative malignancy was found in 6 patients. Attacks of Sweet's syndrome preceded the diagnosis of neoplasia in 4 patients (3 months to 6 years). Some differences in symptoms and signs were found in the group of patients with associated malignancy compared with the group without, that is, male predominance, mucosal symptoms, anemia, and frequent recurrence of skin symptoms. The onset of Sweet's syndrome indicates an acute infectious disease, and the patients are frequently referred to departments of internal medicine and infectious diseases. In addition, the skin lesions may mimic those which often accompany a generalized infection (erythema multiforme, erythema nodosum, vasculitis, pustular eruptions and urticaria). Since Sweet's syndrome may precede the possibly associated malignant disease, the initial diagnosis of the syndrome is important and should be made with confidence with increasing awareness of the characteristic symptoms.     

Sweet's syndrome associated with cellulitis

A 38-year-old woman developed an acute, painful cutaneous eruption on her lower legs, neck, chest and fingers while receiving a number of oral and intravenous antibiotics for left leg cellulitis caused by trauma. Clinically and histopathologically, she was diagnosed with Sweet's syndrome with typical pseudovesicular skin changes in conjunction with erythema nodosum-like lesions on her lower legs. She responded quickly to oral prednisolone. We propose Staphylococcal cellulitis as a cause of Sweet's syndrome.