December 2007

Fig.4

Fig.5

Diagnosis: Sweet's syndrome with pulmonary involvement in the setting of myelodysplastic syndrome.

Histopathology: Skin biopsy revealed a dense, predominantly superficial, dermal infiltrate of neutrophils (Figure 4). Stains for organisms, including GMS, AFB and tissue gram, were performed and no fungal, mycobacterial or bacterial organisms were seen.

Bone marrow biopsy showed hypercellularity with trilineage dysplasia and marked megakaryocytic hypoplasia, consistent with myelodysplastic syndrome.

Chest CT (Figure 5) revealed scattered nodular infiltrates in the lungs bilaterally, right significantly greater than left. Infectious work-up was negative and these were felt to represent neutrophilic infiltrates of Sweet's syndrome.

Treatment and course:
The patient was started on prednisone 90mg daily with significant improvement in rash, fever, and weakness, as well as resolution of infiltrates on CXR.

After discharge, the patient was tapered to prednisone 10mg daily. He was hospitalized 2 months later with an exacerbation of Sweet's syndrome consisting of fever and aphthous ulcers, which resolved with another course of prednisone 40mg daily. He developed a disseminated fungal infection and died while awaiting an allogeneic peripheral blood stem cell transplant.

Discussion:
Sweet's syndrome is a rare neutrophilic dermatosis associated with fever, leukocytosis, and erythematous plaques with neutrophilic infiltrates. Cutaneous plaques, papules, and vesicles may be several centimeters in diameter, and may be painful. They can occur anywhere on the body but have a predilection for the face and limbs. Oral lesions occur in up to 30% of patients. Without treatment, lesions last 5-12 weeks, but new lesions will usually continue to form beyond this time period. The rash is preceded by a fever and/or URI in 50-80% of patients. Other systemic symptoms include conjunctivitis, keratitis, headache, nausea, vomiting, arthralgia, myalgia, ARF, alveolitis, and osteomyelitis.

Lung involvement in Sweet's syndome is rare, though it may be more common with hematologic dyscrasias relative to other associated diseases. Symptoms include dyspnea, dry cough, and lung crackles. Chest X-ray reveals unilateral or bilateral interstitial infiltrates and/or pulmonary opacities, representing dense neutrophil infiltration of alveoli. Pleural effusions have also been reported. Pulmonary manifestations usually parallel cutaneous disease and resolve with steroids. However, pulmonary involvement may occur months or years following cutaneous lesions.

Sweet's syndrome is more common in women (2-4:1) between ages 30-70. The pathogenesis of Sweet's syndrome is unknown, with some studies indicating an association with cytokine (interleukins, G-CSF, GM-CSF, and IFN-gamma) dysregulation. Associated medical conditions include malignancy, bacterial and viral infections, autoimmune disease, collagen vascular disease, inflammatory bowel disease, sarcoidosis, pregnancy, and medications (G-CSF, furosemide, hydralazine, oral contraceptives, lithium, carbamazepine, bactrim, minocycline). Approximately 20% of cases are associated with underlying malignancy, most commonly AML and myelodysplastic disease.

MDS represents ~9% of hematologic disorders with associated Sweet's syndrome. Recurrence of Sweet's syndrome is high (up to 70%) when associated with MDS, either due to rapid tapering of corticosteroids or to hematologic relapse or progression to AML. In fact, studies suggest that MDS patients who develop Sweet's syndrome may be more likely to progress to acute leukemia. Due to the underlying hematologic disorder, the absence of pyrexia or neutrophilia does not rule out Sweet's syndrome in patients with MDS or other hematologic malignancies. Dermal lymphocytic infiltrates have even been shown to precede neutrophilic infiltrates in some patients with MDS.

Diagnosis is based on the presence of 2 major criteria and 2 of 4 minor criteria. The 2 major criteria are acute onset of typical rash and histopathology of mature neutrophils in the mid and upper dermis. The histopathology may also include mature neutrophils that migrate transepidermally to create pustules. Vessel walls are classically spared. The 4 minor criteria include 1) antecedent fever or infection, 2) accompanying fever, arthralgia, conjunctivitis, underlying malignancy, 3) leukocytosis, 4) response to corticosteroids but no response to antibiotics.

Treatment of Sweet's syndrome is prednisone 40-60 mg daily for 1 week, tapered over 3-4 weeks. Corticosteroids typically lead to resolution of all symptoms, but recurrence rates have been reported to be as high as 25-70%. Repeated relapses may require steroid-sparing drugs such as NSAIDs, dapsone, colchicine, metronidazole, doxycycline, methotrexate, cyclosporin, and potassium iodide.

References:
1. Astudillo L, Sailler L, Launay F, et al. Pulmonary involvement in Sweet's syndrome: a case report and review of the literature. Int J Dermatol 2006 Jun; 45(6): 677-80.
2. Callen, JP. Neutrophilic dermatoses. Dermatol Clin 2002; 20:409.
3. Cohen, PR, Talpez, M, Kurzrock, R. Malignancy associated Sweet's syndrome. Review of world literature. J Clin Oncol 1988; 6:1887.
4. Kemmett, D, Hunter, JA. Sweet's syndrome: A clinicopathologic review of 29 cases. J Am Acad Dermatol 1990; 23:503.
5. Soppi, E et al. Acute febrile neutrophilic dermatosis (Sweet's syndrome) in association with myelodysplastic syndromes: a report of three cases and a review of the literature. Br J Haematol 1989; 73:43.
6. Su, WP, Liu, HN. Diagnostic criteria for Sweet's syndrome. Cutis 1986; 37:167.
7. Vignon-Pennamen et al. Chronic recurrent lymphocytic Sweet syndrome as a predictive marker of myelodysplasia: a report of 9 cases. Arch Dermatol 2006; 142:1170.
8. Von den Driesch, P. Sweet's syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol 1994; 31:535.

Case presented by Drs. Cheryl Gray, Kara Nunley, and Liana Abramova.
Special thanks to Dr. Kim Crone for histopathology pictures.