Subcutaneous Sweet syndrome as an initial presentation of acute myelogenous leukemia – A case report

Dear Editor, Subcutaneous Sweet syndrome (SSS) is a rare variant of neutrophilic dermatosis characterized by diffuse neutrophilic infiltrates predominantly located in the subcutis. It often showed erythematous painful nodules or plaques on the extremities and trunk, similar to other panniculitis.[1] SSS is commonly associated with hematopoietic disorders, such as leukemia and myelodysplastic syndrome.[1] A 49-year-old woman presented with a 3-week history of painful erythematous nodules on the lower extremities [Figure 1a-c]. She did not have a history of previous systemic disorders. The pathology of a punch biopsy revealed diffuse neutrophilic infiltrates in the deep reticular dermis, fat lobules, and septa. Vasculitis was not observed [Figure 2a-c]. Periodic acid–Schiff and acid-fast stains were negative for infectious organisms. Immunohistochemically, CD34+ or CD117+ immature cells were absent in the inflammatory infiltrates. The initial pathological diagnosis was a neutrophil-predominant septal-lobular panniculitis. Subsequent serum test results showed leukocytosis (11,000/uL) with increased blasts (13%) and an elevated erythrocyte sedimentation rate (118 mm/h). Fever and chills were noted 1 week later. Blood culture was negative. Flow cytometry and bone marrow examination which showed a hypercellular marrow with replaced hematopoiesis confirmed the diagnosis of acute myelogenous leukemia (AML). Induction chemotherapy was administered (idarubicin, 12 mg/m2; cytarabine, 100 mg/m2). No systemic corticosteroids were administered. Her skin lesions gradually disappeared and spontaneously subsided. No new lesions were noted during the following 1 year.Figure 1: (a) Tender erythematous plaques and nodules were observed on the (b) left thigh and (c) lower leg.Figure 2: Pathology of skin biopsy. (a) A dense and diffuse inflammatory cell infiltration was present in the deep dermis with both lobular and septal panniculitis. There was diffuse neutrophil infiltration without vascular damage in the (b) fat septa and (c) fat lobules (original magnification, hematoxylin and eosin; (a) ×2; (b) ×100; (c) ×400).To differentiate SSS from neutrophilic panniculitis, Sutra-Loubet et al. proposed five positive diagnostic criteria: (i) a nodule or plaque as an elementary lesion, (ii) the presence of general symptoms (fever, arthralgia, or malaise), (iii) mostly lobular infiltration of neutrophils in the biopsy specimen, (iv) an association with myelodysplasia, and (v) high responsiveness to systemic corticosteroids. Three negative criteria were also defined: (i) neutrophilic infiltrate not predominating in the septa, (ii) no associated vasculitis, and (iii) other causes of panniculitis excluded.[2] SSS has been reported to be associated with medications and underlying myeloid disorders.[3-5] The associated drugs include BRAF inhibitors, granulocyte colony-stimulating factor, mitoxantrone, and cytarabine. None of them had been used in our patient before the rash. Wang et al. reviewed 16 cases of SSS associated with hematopoietic disorders. Most SSS occurs after the diagnosis of myelodysplastic disorder, myeloproliferative disorders, or leukemia.[3] Our patient presented SSS as an initial presentation of AML was rare. Many previously reported SSS cases showed erythematous nodules on the lower extremities accompanied by fever, similar to erythema nodosum (EN). Histopathologically, SSS shows neutrophilic subcutaneous infiltrates without vasculitis. While a lobular distribution was observed in most cases, infiltrate also involved the septa or both.[3] Therefore, distinguishing SSS from EN, which has been reported in patients with leukemia, may be challenging. Early EN findings may show edema and diffuse neutrophil infiltration in the subcutis. Nevertheless, the infiltration is mostly located in the subcutis septa rather than fat lobules and has a higher change to include lymphohistiocytic components. Another important neutrophil-predominant lobular panniculitis is α1-antitrypsin deficiency panniculitis. Blood tests for α1-antitrypsin level and phenotype or genetic test for SERPINA1 gene are required to establish the diagnosis.[6] However, it is extremely rare to have α1-antitrypsin deficiency panniculitis in leukemic patients. Other differential diagnoses of neutrophilic panniculitis occurring in patients with myeloid disorders include infectious panniculitis or leukemia cutis.[4] In patients with febrile myeloid disorders, tissue stains for fungi and mycobacteria should be performed to exclude infectious panniculitis. Pathological examinations may reveal basophilic necrosis, abscesses, granulomas, neutrophil-lined microcysts, or vasculitis. In leukemia cutis, immature blasts can be found in pathological examinations or immunochemical stains such as CD33, myeloperoxidase, lysozyme, and CD117.[4] In our case, only a minor population of CD117+ cells among the inflammatory tissue were noted. SSS responds well to systemic corticosteroids; however, it is challenging to initiate steroid therapy in patients with febrile acute leukemia because infections are the leading cause, and steroids may exacerbate the infection.[1,2-5] Careful examination and integration of all clinical and laboratory data are important in making a correct diagnosis and determining appropriate therapy. Dapsone is also a treatment option.[1] Agarwal et al. reported administering adalimumab (40 mg every 2nd week) in refractory SSS with resolution.[7] Adalimumab offers a new approach for patients with disease refractory to lower-dose corticosteroid therapy or traditional steroid-sparing agents.[7] Treating the underlying disease of myelodysplastic syndrome with Sweet's syndrome is important.[8] Spontaneous relief of SSS has been reported in several cases.[3,4] Wang et al. reported a case with clinical improvement after starting induction chemotherapy with idarubicin and cytarabine without systemic corticosteroid treatment.[3] SSS is difficult to diagnose pathologically without clinical information. Complete workup of systemic symptoms, correct interpretation of pathology, and exclusion of infection are necessary for diagnosis. Our patient demonstrated SSS can be an initial presentation of AML, and the skin lesions may subside after successful chemotherapy without the use of systemic corticosteroid. Ethical approval This study was approved by MacKay Memorial Hospital IRB (Approval number: 23MMHIS289e). The patient consent was waived by IRB. Data availability statement The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Financial support and sponsorship Nil. Conflicts of interest Dr. Nan-Lin Wu and Dr. Yu-Hung Wu, editorial board members at Dermatologica Sinica, had no roles in the peer review process of or decision to publish this article. The other author declared no conflict of interest in writing this paper.