Interactive Case Report: Sweet Syndrome Associated With ET Transformation to AML

Rita Raturi, MD
University of South Florida Morsani College of Medicine, Tampa, Florida

Charlotte O’Leary, MD, and Sudeep Gaudi, MD
James A. Haley Veterans’ Hospital, Tampa, Florida

A 62-year-old man presented with new-onset, erythematous lower-extremity skin lesions (Figure 1), which he had discovered after having changed a flat tire on gravel. He had a medical history of JAK2-negative essential thrombocythemia (ET), for which he had been taking hydroxyurea; type 2 diabetes; and thromboembolic disease, for which he was on systemic anticoagulation with warfarin. Of note, he also was being treated for progressively worsening anemia and thrombocytopenia, for which his hydroxyurea had been held as an outpatient.

The patient’s lesions markedly improved with the administration of intravenous broad-spectrum antibiotics (cefepime and vancomycin). He was discharged to home on a 7-day course of minocycline for a suspected diagnosis of localized posttraumatic cellulitis. Minocycline was chosen because of the need for methicillin-resistant Staphylococcus aureus coverage due to its high prevalence in our area. Doxycycline causes increased photosensitivity in 20% of patients compared with minocycline,1 which is noted to rarely cause photosensitivity, thus making it ideal for our patient, who is frequently outdoors.

However, the patient returned 2 days later with similar nodular lesions located diffusely on his body (Figures 2 and 3), as well as worsening fevers of up to 38.9°C.

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Diagnostic tests. Laboratory test results revealed increasing leukocytosis from 11,000 to 20,000 cells/µL with elevated blasts, a decreased hemoglobin from 9.0 to 7.0 g/dL, and a decreased platelet count from 100 × 103/µL to 60 × 103/µL. The C-reactive protein (CRP) level was 1.6 mg/dL, and the erythrocyte sedimentation rate (ESR) was 90 mm/h.

A hematologist was consulted for additional assistance given the patient’s leukocytosis, anemia, and thrombocytopenia. An infectious disease consultant proceeded to monitor the patient without additional antimicrobial coverage, because the condition was likely not infectious.

Results of a peripheral blood smear revealed teardrop cells, nucleated red blood cells, and giant platelets. Results of a workup for disseminated intravascular coagulation were negative. An antinuclear antibody test and complement testing were ordered for further workup of an autoimmune etiology; however, the results were unrevealing. Flow cytometry studies revealed an increased proportion of phenotypically abnormal, immature myeloid blasts and immunophenotypic abnormalities of the myeloid lineage.

A dermatologist was consulted for further recommendations given the widespread cutaneous involvement. The results of a skin biopsy (Figure 4) of one of the lesions showed Sweet syndrome, also known as acute febrile neutrophilic dermatosis. A subsequent bone marrow biopsy confirmed transformation to acute myeloid leukemia (AML) from ET.

Discussion. Classically, the neutrophilic lesions of Sweet syndrome have accompanying papillary edema, as first described by R. Douglas Sweet, MD, in 1964.2 Commonly misdiagnosed as a soft tissue infection, Sweet syndrome is defined by an abrupt onset of painful or erythematous plaques or nodules; pyrexia; histologic evidence of dense neutrophilic infiltrate without vasculitis; a response to corticosteroid therapy; and an association with hematologic or visceral malignancy (in approximately 21% of cases).1 The condition may be preceded by a respiratory or gastrointestinal tract infection or a vaccination.

The diagnostic criteria also include 3 of 4 of the following: an ESR greater than 20 mm/h, an elevated CRP, a white blood cell count above 8000/µL, or a differential cell count showing greater than 70% neutrophils.3 Our patient met all 4 of these diagnostic criteria.

Other underlying disease processes, in addition to hematologic or solid tumor malignancy, include inflammatory bowel disease and pregnancy. Drug-induced Sweet syndrome also has been well documented in the literature and is associated with granulocyte-colony stimulating factor, all-trans retinoic acid, and other miscellaneous drugs in adults.4,5

Systemic corticosteroids are the gold standard treatment, with the ideal prednisone dose being 1 mg/kg daily with a slow taper over 4 to 6 weeks.3 Other pharmacotherapies include anakinra, clofazimine, indomethacin, dapsone, or colchicine if a corticosteroid-sparing agent is needed.3,4 Approximately one-third of patients who develop Sweet syndrome will experience a reoccurrence.3

Outcome of the case. Our patient received 60 mg prednisone once daily for 1 month, which resulted in the complete resolution of the cutaneous symptoms. He began outpatient chemotherapy for AML.

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References:

1. Vassileva SG, Mateev G, Parish LC. Antimicrobial photosensitive reactions. Arch Intern Med.1998;158(18):1993-2000.
2. Sweet RD. An acute febrile neutrophilic dermatosis. Br J Dermatol. 1964;​76(8-9):349-356.
3. Cohen PR. Sweet’s syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34.
4. Kluger N, Gil-Bistes D, Guillot B, Bessis D. Efficacy of anti-interleukin-1 receptor antagonist anakinra (Kineret®) in a case of refractory Sweet’s syndrome. Dermatology. 2011;222(2):123-127.
5. Kim MJ, Choe YH. Eponym: Sweet syndrome. Eur J Pediatr. 2010;169(12):​1439-1444.