Corticosteroid-resistant Sweet’s syndrome as the first manifestation of myelodysplastic/ myeloproliferative neoplasm-unclassifiable: a case report : Emergency and Critical Care Medicine

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Case Report

Corticosteroid-resistant Sweet’s syndrome as the first manifestation of myelodysplastic/ myeloproliferative neoplasm-unclassifiable: a case report

Pan, Lina; Zhang, Jingru; Li, Peng; Zhao, Chuanli; Zang, Shaolei; Ji, Min; Lu, Fei; Ye, Jingjing; Zhang, Chunqing; Ji, Chunyan

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Emergency and Critical Care Medicine 2(4):p 233-238, December 2022. | DOI: 10.1097/EC9.0000000000000034
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Sweet’s syndrome (SS) is a rare disease that manifests as an acute febrile neutrophilic dermatosis. The mainstay of treatment for SS is systemic corticosteroids, which induce a rapid and complete response in most cases. Our study provides a rare case of myelodysplastic/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U) related-SS, resistant to systemic corticosteroid therapy. Extremely severe systemic skin lesions were characteristic and the first manifestation in this case. High-dose intravenous immunoglobulin (IVIG) was used to stop corticosteroid-resistant SS progression. MDS/MPN-U mediated immune disorders may be involved in the severe skin presentation and unresponsive to systemic steroid therapy. We present this case as a vivid clinical example of severe SS associated with hematological malignancies, providing a reference for diagnosis and treatment.

Case presentation

A 53-year-old man was admitted to our hospital with a month’s history of raised, painful skin plaques and fever for 20days. In October 2020, a painful rash was found on his nose and scalp, which gradually spread to his face, neck, trunk, and bilateral upper extremities (Fig. 1). Ten days later, he was febrile to 40°C. In another hospital, the complete blood count revealed leukocyte of 4.22 × 109/L, hemoglobin of 69 g/L, platelet of 114 × 109/L. Skin biopsy for histopathology showed papillary dermal edema with a diffuse neutrophilic infiltrate in the reticular dermis, which was diagnosed as SS. The rash and fever continued to progress despite treatment with daily intravenous methylprednisolone (80 mg) for 5days and daily oral prednisolone (75 mg) for SS, as well as biapenem and vancomycin for infection.

Figure 1:
Patient examination findings: skins with pink-violaceous, edematous nodules and plaques at initial presentation.

The patient was diagnosed with SS and moderate anemia was admitted to our hospital in November 2020. Physical examination on admission revealed a temperature of 36.3°C and normal circulation and breathing. No abnormalities were detected on elementary neurological and abdominal examinations. The skin of the back, face, neck, and both arms were covered with erythematous infiltrative lesions. The patient had a medical history of allergic purpura in 1990 and 2010. After admission, laboratory tests revealed a leukocyte count of 5.88 × 109/L, with a differential of 88.80% neutrophils, hemoglobin level of 39 g/L, platelet count of 126 × 109/L, erythrocyte sedimentation rate (ESR) of 66 mm/h, C-reactive protein (CRP) of 132.66 mg/L, interleukin-6 of 87.03 pg/mL, procalciton in level of 0.134 ng/ mL, a ferritin level of 1175 ng/mL, and normal transaminase and creatinine levels. No perinuclear antineutrophil cytoplasmic antibodies, cytoplasmic antineutrophil cytoplasmic antibodies, or antinuclear antibodies were detected in the patient’s serum. No pathogenic bacteria were detected in the blood cultures. The skin secretion cultures were positive for staphylococcus aureus. Computed tomography (CT) showed no pleural effusion but mild splenomegaly.

Bone marrow aspirate results showed dysgranulopoiesis and dyserythropoiesis, morphologically indicative of myelodysplastic syndrome (MDS). Bone marrow biopsy showed few blasts and extremely active myelodysplasia, demonstrating that erythroid and megakaryocytes were hyperplastic with increased atypia, and the proliferation of collagen fibers was also hyperactive (GomoriMF grade 3). Immunohistochemistry of bone marrow showed CD42b (+), CD34 (partly +), CD117 (partly +), CD71 (+). The above data could draw the histological conclusion of MDS and myelofibrosis (MF). Bone marrow flow cytometric immunotyping revealed a normal phenotype. Assessed by next-generation sequencing of acute myeloid leukemia (AML)/MDS/MPN, the mutated genes and the corresponding mutation load included JAK2-V617F (27.40%), SF3B1- K700E (40.90%), and EP300-Y638C (44.88%). The karyotype was 46, XY add (2p). As shown in Fig. 2, histopathology of the punch skin biopsy illustrated that the superficial dermis was infiltrated with dense inflammatory cells dominated by neutrophils, accompanied by nuclear fragmentation, according to the diagnosis of SS. Thus, the patient was diagnosed with (1) MDS/MPN-U (MPN-SAF TSS 24, IPSS Intermediate); (2) SS; and (3) Staphylococcus aureus skin infection.

Figure 2:
Histopathologic findings: beneath the edematous papillary dermis is a sheet-like inflammatory infiltrate that contains abundant mature neutrophils (Hematoxylin eosin stain; original magnification).


In the early stage, the patient was treated with oral prednisolone (1 mg/kg/day) for SS, thalidomide (50 mg/day), and danazol (600 mg/day) for MDS/MPN-U, piperacillin sodium, and tazobactam plus norvancomycin for infection. However, the patient still experienced continuous fever associated with a chilly sensation and rigor, and his rash continued to progress (Fig. 3). Given the lack of response to the above treatment, the patient was switched to continuous intravenous methylprednisolone (500 mg/day for 3 days, then 240 mg/day for 3 days, and then 120 mg/day for 3 days), and antibiotics were changed to meropenem plus daptomycin. However, there was no clinical improvement, and the temperature was sustained up to 38.5°C. At the same time, the skin of his double legs and abdomen was covered with symmetrical petechia, and he was diagnosed with relapsed allergic purpura (Fig. 4). Meanwhile, there were diffuse red papules with pustules at the top. After discussion with dermatologists, we preferred that this patient had corticosteroid-resistant SS complicated with acute generalized exanthematous pustulosis (AGEP), as illustrated in Fig. 5. Eventually, we initiated treatment with IVIG, which led to rapid improvement of the new lesion.

Figure 3:
Patient examination findings: the rash on his face, neck, trunk and bilateral upper extremities continued to progress after oral prednisone therapy.
Figure 4:
The allergic purpura relapsed after 9 days’ intravenous methylprednisolone therapy.
Figure 5:
The acute generalized exanthematous pustulosis appeared after several kinds of antibiotics therapy.

Patient outcome

The inflammation subsided rapidly, and the lesions regressed after high-dose IVIG treatment (Fig. 6). Unfortunately, even though the Janus kinase inhibitor was suggested to treat MDS/MPN-U further, the patient’s family declined more aggressive treatment. The patient died within half a month of discharge.

Figure 6:
The lesions regressed after immunoglobin therapy.


SS is an acute febrile neutrophilic dermatosis that presents with acute onset fever, neutrophilic leukocytosis, and erythematous, tender plaques or nodules with dense neutrophilic infiltration in the dermis. Its pathogenesis is multifactorial and remains unknown. SS most often affects women with the highest incidence between 30 and 60 years. According to Nofal et al. (p. 2), the diagnostic criteria for SS require all 2 major criteria and 2 of the 4 minor criteria (Table 1).[1]

Table 1 - Diagnostic Criteria for Sweet’s Syndrome[1]
Major criteria 1. Sudden onset of tender, erythematous plaques or nodules
2. Dense neutrophilic infiltrate in the upper dermis without evidence of leukocytoclastic vasculitis
Minor criteria 1. Fever (38°C or higher), arthralgia, or malaise
2. Rapid response to systemic corticosteroids
3. Abnormal laboratory values at presentation (3 or more of the following: leukocyte count >8000; >70% neutrophils; elevated C-reactive protein; erythrocyte sedimentation rate >20mm/h)
4. Association with underlying malignancy, inflammatory disease, pregnancy; or preceding infection or vaccination

SS is classified into several types, including classical/idiopathic SS (approximately 70%), malignancy-associated SS (approximately 20%), and drug-induced SS (approximately 7%). The mainstay of treatment for SS is systemic corticosteroids, which in most cases induce a rapid and dramatic improvement within 4 to 6 weeks.[2–5] As summarized by Kaszewski, et al. (p. 51), other systemic drugs are also effective for the treatment of SS as the firstline or second-line therapy (Table 2).[6]

Table 2 - Treatment for Sweet’s Syndrome[2]
First-line therapy Corticosteroids Prednisone 1 mg/kg/day (30-60 mg) p.o. within 4–6 weeks taper dose to 10 mg/day; some patients may require 2–3 months of treatment, methylprednisolone intravenously administered (up to 1000 mg/day, for 3–5 days)
 Potassium iodide 3 times each day 300 mg p.o. (daily dose 900 mg) or as a saturated solution (1 g/mL of water) of potassium iodide (Lugol’s solution)
 Colchicines Orally at dose 0.5 mg 3 times each day (daily dose of 1.5 mg)
Second-line therapy Indomethacin
150 mg/day for 7 days and then 100 mg/day for next 14 days, orally
 Clofazimine 200 mg/day for 4 weeks and then 100 mg/day for next 4 weeks
 Cyclosporine A Initial dose ranges from 2 to 4 mg/kg/day to 10 mg/kg/day orally, from 11th day the dose should be reduced by 2 mg/kg/day every 2 days and stopped on treatment day 21
Others Cyclophosphamide, immunoglobulin, Interferon α, Infliximab, and so on

SS associated with hematological malignancies (SSAHMs) has been reported in approximately 80% of SS cases associated with malignant disorders. The most common causes of SS are AML and MDS.[7] Other hematological malignancies include acute promyelocytic leukemia (APL), chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, multiple myeloma, monoclonal gammopathy of undetermined significance, primary myelofibrosis, and essential thrombocythaemia (ET). In addition, the onset or recurrence of many cases of SSAHMs is related to the development or relapse of hematological malignancies; thus, it was considered as a paraneoplastic syndrome.[7–9] Compared to classic SS, SSAHMs have different clinical characteristics. SS-AHMs tend to present with more severe and atypical manifestations than classic SS.[10] It is known that SS-AHMs have equal frequency in males and females and occur more frequently in older people with a lower mean hemoglobin concentration.[9]

An underlying hematological malignancy should be considered in cases of anemia, subcutaneous involvement, or both in SS,[11] such as periorbital cellulitis and pyoderma gangrenosum.[12,13] These skin lesions must be distinguished from specific leukemic infiltrations, including AML and APL.[14] It is worth noting that many anticancer agents contribute to SS induction. The most commonly reported drug that causes SS is a granulocytecolony stimulating factor (G-CSF).[15,16] Other medications include bortezomib,[17] hypomethylating agents (azacytidine,[18] decatibine[19]), tyrosine kinase inhibitors (imatinib,[20] dasatinib[21]), lenalidomide[22] and all-trans retinoic acid.[23] In some cases, it is necessary to withdraw or temporarily discontinue the anticancer agents.

Patients with SS-AHMs have more severe presentations with multisystem involvement and a greater number of plaques or nodules, leading to a worse prognosis. Genetic analysis reveals an increased incidence of SS in AML patients with poor cytogenetic risk and unfavorable molecular abnormalities. Patients with AML-related SS are more likely to have t(6;9), −5/del(5q), and FLT3 mutations. More myelodysplasia-related features are observed in patients with AML-related SS.[24] It has also been shown that the existence of SS in patients with MDSis an independent indicator of poor prognosis.[25] In MDS cases, refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-t) are likely associated with the onset of SS.[26] For patients with malignancies, treatment of the underlying malignancy may result in the resolution of neutrophilic dermatosis. Patients with malignancy-associated diseases often have pulmonary and multisystem involvement characterized by recurrent episodes, leading to a poor prognosis.[27] In some cases, all symptoms may resolve only with anti-neoplastic treatment.[28,29] Recurrence is an important characteristic of malignancy-associated SS since up to two-thirds of reported cases have recurrences.[10,30]

Intravenous pulse administration of methylprednisolone sodium succinate (≤1000mg/day) over one or more hours, daily for 3–5 days, maybe utilized for patients whose condition is refractory to other therapies.[6] SS-AHMs are more likely to be corticosteroid-resistant, showing that the skin lesions progressed rapidly after routine dose and full course of glucocorticoid treatment. Additional immuno-suppressive agents, including IVIG, should be considered to treat corticosteroid-resistant SS. Successful cancer management contributes to the treatment of SS in patients with malignancies.[16,31,32]

SS-AHMs patients may develop more extracutaneous complications, including pulmonary involvement, renal dysfunction, hepatic dysfunction, cardiac dysfunction, non-infectious shock, and systemic inflammatory response syndrome, leading to a poor prognosis.[27] Moreover, SS may relapse following either spontaneous or therapyinduced remission,[33] which is more common in patients with SS-AHMs.[32] Indeed, the reappearance of lesions may represent a relapse signal of a previously treated malignancy.[25]

AGEP is a severe allergic reaction characterized by an acute onset of small non-follicular pustules on an erythematous base. More than 90% of cases are caused by a small number of drugs, including antibiotics, especially beta-lactams.[34] AGEP is a rare, self-limiting disease that erupts suddenly within 1 or 2 days of drug exposure. Removing the causative drug usually improves clinical manifestations within several days and spontaneous resolution within 2 weeks.[35] A diagnosis of AGEP was made according to clinical features, medical history, and laboratory test results. This case is a reminder that antibiotics should be used in full compliance with requirements in consideration of immune system disorders in patients with SS.

Our study describes a rare case of MDS/MPN-U related- SS that was resistant to systemic corticosteroid therapy. This case is unique because of the extremely severe systemic skin lesions. High-dose IVIG was used to stop corticosteroid-resistant SS progression. MDS/MPN-U mediated immune disorders may be involved in the severe skin presentation and unresponsive to systemic steroid therapy. IVIG may occupy phagocyte receptors and modulate immunoglobulin synthesis, thereby attenuating the immune response and preventing the excessive release of cytokines involved in SS.

More attention should be paid to the clinical presentation of SS-AHMs to ensure effective management. Correct morphological and immunohistochemical interpretation, cytogenetics, and molecular analysis will provide valuable information for SS-AHMs diagnosis and prognosis. Additionally, management guidelines for SS-AHMs have not yet been established. Therefore, future studies are urgently needed to establish management guidelines for malignancy-associated SS and improve patient outcomes.

Conflict of interest statement

The authors declare no conflict of interest.

Author contributions

Pan L designed the figures and wrote the manuscript. Zhang J and Li P interpreted the results and revised the manuscript. Zhao C, Zang S, Ji M, Lu F, and Ye J were involved in patient diagnosis and management. Zhang C and Ji C supervised the study and approved the final manuscript. All the authors approved the final version of the manuscript.


This work was supported by the Shandong Provincial Natural Science Foundation (ZR2020MH119, ZR2020MH118), Distinguished Taishan Scholars in Climbing Plan (tspd20210321), National Nature Science Foundation of China (81400118, 81700143), and the horizontal subject of Shandong University (6010120072).

Ethical approval of studies and informed consent

This study was approved by the ethics committee of Shandong University Qilu Hospital, and written informed consent was obtained from the patient (KYLL-202111-022-1, 29th December 2021). All authors have read the manuscript and approved its submission to your journal. This manuscript has the patient’s written informed consent to use his data and for the publication of the data that appear in this article.


The authors acknowledge all working staff in the Department of Hematology of Qilu Hospital of Shandong University for their constructive discussions and suggestions.


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Case report; Corticosteroid-resistant; Intravenous immunoglobulin; Myelodysplastic/myeloproliferative neoplasm-unclassifiable; Sweet’s syndrome

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