Sweet syndrome induced by FLT3 inhibitors: case report and literature review.

BACKGROUND: Acute febrile neutrophilic dermatosis, also commonly referred to as Sweet syndrome, is often associated with tumors, infections, immune disorders and medications. FLT3 inhibitor-induced Sweet syndrome is a rare complication. METHODS AND RESULTS: We report a patient with relapsed and refractory acute monocytic leukemia harboring high-frequency FLT3-ITD and DNMT3a mutations. The FLT3 inhibitor gilteritinib was administered for reinduction therapy after failure of chemotherapy with a combination of venetoclax, decitabine, aclarubicin, cytarabine and granulocyte colony-stimulating factor. The leukemia patient achieved remission after 1 month of treatment. However, Sweet syndrome induced by gilteritinib, which was confirmed by skin biopsy, developed during induction therapy. Similar cases of Sweet syndrome following FLT3 inhibitor therapy for acute myeloid leukemia were reviewed. CONCLUSION: Attention should be given to this rare complication when FLT3 inhibitors are used for acute myeloid leukemia therapy, and appropriate treatments need to be administered in a timely manner.

Mercaptopurine-induced Sweet's syndrome.

Sweet's syndrome is an acute febrile neutrophilic dermatosis. Drug-induced Sweet's syndrome typically occurs soon after drug administration, with rapid resolution of symptoms with cessation of the offending agent. We report a man in his early 40s who presented with fever and widespread erythematous rash on a background of recently diagnosed mild stricturing ileal Crohn's disease. He was commenced on 6-mercaptopurine 12 days before presentation. Skin biopsy demonstrated diffuse infiltration of neutrophils in the upper dermis, dermal oedema, eosinophils and fibrin deposition. Symptoms rapidly improved with cessation of 6-mercaptopurine without requiring systemic corticosteroids.

Sweet syndrome following the ChAdOx1-S vaccine.

We report a case of vaccine-induced Sweet syndrome in a female patient in her 50s presenting with fevers and a scattered red patchy rash on the lower limbs. Seven days prior, she had received the first dose of AstraZeneca ChAdOx1-S vaccine. A skin biopsy confirmed Sweet syndrome. She did not respond to high doses of prednisolone and required methotrexate therapy to induce remission. This is one of the first reports of Sweet syndrome caused by the ChAdOx1-S vaccine and provides further evidence for vaccine-induced dermatosis. This case demonstrates that methotrexate can induce remission in cases of Sweet syndrome resistant to corticosteroids. This report also describes an approach to the differential diagnosis of patients presenting with a rash, fever and malaise.

Azathioprine hypersensitivity: A Sweet-like syndrome.

INTRODUCTION: Azathioprine hypersensitivity can occasionally present as Sweet-like syndrome, a dose-independent side effect characterized by the unanticipated onset of macules, papules, and pustules. CASE PRESENTATION: A 35-year-old woman with systemic lupus erythematosus presented with complaints of generalized maculopapular rash, facial swelling, and bilateral lower extremity edema with a duration of 4 days and a 2-day history of constitutional symptoms within 2 weeks of the beginning of azathioprine therapy to treat existing lupus nephritis (class 2/3). DISCUSSION: Patients who experience azathioprine hypersensitivity syndrome can present with erythema nodosum, small-vessel vasculitis, acute generalized exanthematous pustulosis, Sweet syndrome, and nonspecific dermatosis. The following signs and symptoms are used as criteria to diagnose drug-induced Sweet syndrome: (a) abrupt onset of painful erythematous plaques, (b) histopathological evidence of dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis, (c) temperature higher than 39.7°C, (d) temporal relationship between drug ingestion and clinical presentation, and (e) temporal resolution of lesions after drug withdrawal. Our patient met three out of five criteria and was diagnosed with Sweet-like syndrome. CONCLUSION: Our case highlights the uncommonly presented azathioprine-induced Sweet-like syndrome that occurs abruptly after the commencement of the offending drug. This diagnosis can be established through basic laboratory workup and skin biopsy findings.

Atypical Sweet syndrome: skin sinus tracts in an acutely febrile patient after lymphoma treatment: a case report.

Sweet syndrome (SS) is an uncommon inflammatory disease that involves painful skin, edematous, red papules, plaques, or nodules often accompanied by fever and leukocytosis. SS has three subtypes, including classical, malignant-tumor associated, and drug-induced SS (DISS). Patients with DISS have clear histories of recent drug exposure. The incidence of SS is high in hematological malignancy but rare in lymphomas. Glucocorticoid treatment is the recommended treatment for all subtypes of SS. This case study describes a male patient who had a history of sALCL(Systemic anaplastic large cell lymphoma) and was treated with multiple cycles of monoclonal-antibody (mAb) therapy. They also received the G-CSF injection at the site where skin lesions later developed. They met the diagnosis criteria for DISS, which was considered to be caused by the G-CSF injection. In addition, BV(Brentuximab vedotin) administration might predispose them to DISS. This case illustrates the first reported SS during the lymphoma treatment, with rare clinical presentations of local crater-like suppurative skin lesions. This case expands the available literature on SS and hematologic neoplasms and reminds clinicians to promptly recognize and diagnose SS to minimize patient morbidity and long-term sequelae.

Adalimumab Biosimilar-Induced Autoimmunity-Related Sweet-Like Neutrophilic Dermatosis.

ABSTRACT: Antitumor necrosis factor therapies have shown to produce a broad range of cutaneous eruptions. We report the case of a patient under adalimumab biosimilar treatment for a punctate inner choroidopathy who developed a cutaneous eruption on sun-exposed areas that showed a diffuse dermal neutrophilic infiltrate consistent with a Sweet-like neutrophilic dermatosis and some features of autoimmunity.

Acute iododerma presenting as cryptococcoid neutrophilic dermatosis: A clinicopathological pitfall and interesting findings gleaned from a review of the literature.

Iododerma is an uncommon dermatosis caused by excessive iodine exposure and is associated with significant morbidity and mortality. Because of its heterogenous clinical presentation and variable histopathological findings, which depend on the time the skin biopsy is performed, the diagnosis of iododerma is often delayed. We report a rare case of acute iododerma in a woman with end-stage diabetic nephropathy with antecedent radioiodine contrast exposure, presenting histopathologically as cryptococcoid neutrophilic dermatosis (CND). We underscore important clinicopathological pitfalls to avoid misdiagnosis with similar overlapping entities such as Sweet syndrome, review all published cases of CND and draw novel insights into its associated entities.

Azathioprine hypersensitivity syndrome manifesting as subcutaneous Sweet syndrome and acute pancreatitis.

Azathioprine (AZA) is a commonly used immunosuppressive therapy that has been implicated in a number of cutaneous and systemic inflammatory reactions. Initiation of AZA has been associated with a hypersensitivity syndrome manifesting as acute pancreatitis and Sweet syndrome. Subcutaneous Sweet syndrome is a rare variant of Sweet syndrome where the dominant localization of inflammation is within the subcutaneous fat; it is commonly associated with underlying myeloproliferative disease. However, it has not been reported in the literature as a cutaneous manifestation of AZA hypersensitivity syndrome. We present a unique case of acute pancreatitis and biopsy-proven subcutaneous Sweet syndrome following the initiation of AZA with resolution upon discontinuation.

A case of filgrastim-induced neutrophilic dermatosis of the dorsal hands in a patient with Felty Syndrome.

Neutrophilic dermatosis of the dorsal hands (NDDH) is a variant of Sweet syndrome that presents with erythematous bullae, papules/plaques, or pustules on the dorsal hands. It is most commonly associated with hematologic and solid organ malignancies, though cases of NDDH associated with inflammatory bowel disease, rheumatologic disorders, and medication exposure have also been described in the literature. Felty syndrome is a rare complication of long-standing rheumatoid arthritis characterized by neuropathy, splenomegaly, and neutropenia. Granulocyte colony stimulating factors (e.g., filgrastim) can be utilized to rescue the neutropenia observed in Felty syndrome, but this treatment may subsequently cause Sweet syndrome. Herein, we present a 64-year-old man with Felty syndrome and a complex medical history who presented with sudden onset, painful blisters located on the dorsal and palmar aspects of his bilateral hands. Given the patient's past medical history, a broad differential diagnosis, including disseminated fungal and viral infection was initially considered. A punch biopsy of the skin lesion disclosed neutrophilic dermatosis, which together with laboratory data satisfied the von den Driesch criteria for Sweet syndrome. As the lesions were localized exclusively on the patient's hands, the qualification of NDDH was also endorsed.

Deep Sweet Syndrome Secondary to Pegfilgrastim.

Sweet syndrome, or acute febrile neutrophilic dermatosis, is a skin condition consisting of erythematous papules and plaques in association with fever, neutrophilia, and a neutrophilic infiltrate that typically involves the papillary dermis. Although development is most commonly idiopathic, medications are also frequently associated with the eruption, notably, the granulocyte colony-stimulating factor (G-CSF), filgrastim. Pegylated G-CSF, despite similar activity, is not commonly reported, with only four published cases. We present a case of drug-induced sweet syndrome with unique histologic features (deep inflammatory infiltrate) in association with the usage of pegfilgrastim in the treatment of invasive ductal carcinoma of the breast. J Drugs Dermatol. 2022;21(4):422-424. doi:10.36849/JDD.4794.

Sweet's syndrome in the setting of newly initiated risankizumab therapy for pre-existing psoriasis.

Sweet's syndrome (acute febrile neutrophilic dermatosis) is a rare disorder of unclear aetiology characterised by painful cutaneous lesions, sometimes accompanied by systemic symptoms. It has been associated with several autoimmune conditions, drugs, malignancies and infections, though many cases are idiopathic. We describe a case of Sweet's syndrome in a 49-year-old man with pre-existing psoriasis following recent initiation of risankizumab therapy. There are very few reported cases of Sweet's syndrome in association with psoriasis and no existing reports in association with an IL-23 inhibiting medication. Further investigation of the potentially overlapping immunologic pathways implicated in cutaneous reactions to biologic agents and autoimmune conditions such as psoriasis may yield insights into the pathogenesis of such conditions and guide advancements in the rapidly evolving field of targeted biologic therapies.

Drug-Induced Histiocytoid Sweet Syndrome: Two Cases With Levofloxacin and Amoxicillin-Clavulanate.

ABSTRACT: Histiocytoid Sweet syndrome (HSS) is an uncommon histologic variant of Sweet syndrome (SS). HSS can be distinguished from the classic SS with an infiltrate of histiocyte-like immature myeloid cells rather than dense neutrophilic infiltration, although the clinical features are similar. Previous studies have shown that the risk of hematologic malignancy is significantly higher in HSS compared with classic SS. To lesser extent, HSS is also associated with infections, inflammatory diseases, and drugs, particularly with antineoplastic agents as well. Here, we report a case of 2 patients with an abrupt onset of erythematous, tender plaques accompanied by fever, with that revealed similar histopathologic and immunohistochemical features, whom had a history of antibiotic use. Clinicopathologic correlation led to diagnosis of drug-induced HSS, associated with the use of levofloxacin and amoxicillin-clavulanate, respectively. Both patients were then successfully treated with systemic corticosteroid therapy, and neither of them had recurrence during the period of 24-month follow-up.

Successful management of tumor necrosis factor-alpha inhibitor-induced Sweet syndrome in a patient with ulcerative colitis: A case report.

Tumor necrosis factor (TNF) α inhibitors are widely used to treat inflammatory bowel disease (IBD); however, some patients have unexpected inflammatory episodes during anti-TNF therapy. The objective of our research was to highlight a paradoxical case of anti-TNF-agent-induced Sweet syndrome compared with Sweet syndrome treated by anti-TNF agents. We describe a 62-year-old male with a history of ulcerative colitis presenting with multiple polymorphic indurated skin macules and plaques after 2 months of adalimumab therapy. Neutrophilic dermatosis was diagnosed based on the clinical presentation and skin biopsy and may have resulted from extraintestinal manifestations of a flare-up of IBD or been induced by adalimumab therapy. We conclude that when facing this dilemma, adalimumab should be discontinued, and the dose of prednisolone should be increased before determining the definitive cause. Based on drug hypersensitivity syndrome (DHS) risk assessment in the 10-D assessment system, this case was classified as grade 1 (no risk). Finally, we review the molecular and cellular mechanisms connecting cytokine dysregulation to Sweet syndrome.

Neutrophilic dermatosis of the dorsal hands related to cocaine abuse

Abstract Neutrophilic dermatoses encompass a wide spectrum of diseases characterized by a dense infiltration mainly composed of neutrophils. Neutrophilic dermatosis of the dorsal hands is currently considered a localized variant of Sweet syndrome. Cocaine abuse has been related to a wide range of mucocutaneous manifestations, including neutrophilic dermatoses such as pyoderma gangrenosum. The authors of this study present a patient with neutrophilic dermatosis of the dorsal hands, in which cocaine abuse was identified as a probable trigger.

Response of autoimmune and inflammatory disorders in myelodysplastic syndromes to 5-azacytidine: report of two cases and literature review.

Paraneoplastic autoimmune and inflammatory disorders are often associated with myelodysplastic syndromes (MDS). The etiopathogenesis of MDS-associated autoimmune and inflammatory disorders is still unclear and treatment options are limited. Patients with MDS are at high risk of infections, which can be increased by the use of steroids. In the present study, we report on two patients with MDS-related autoimmune and inflammatory disorders who were in remission and reduced the steroid dose with 5-azacytidine treatment. The first case was a 67-year-old patient diagnosed with MDS and the whole-body erythroderma was the chief complaint. When the patient was treated with decitabine, steroid treatment was needed to control the erythroderma. When we changed decitabine to 5-azacytidine, both his erythroderma and his dependency on the steroid treatment were resolved. The second patient was a 68-year-old man with MDS who presented with Sweet's syndrome. Sweet's syndrome was completely treated after the first cycle of 5-azacytidine. In addition, Sweet's syndrome can occur as an adverse reaction of 5-azacitidine, so we illustrate that it is important to distinguish whether Sweet's syndrome is MDS-related skin disorders or 5-azacitidine-related skin side-effects.

Midostaurin-induced Sweet syndrome in a patient with FLT3-ITD-positive AML.

Sweet syndrome (SS), also referred as acute febrile neutrophilic dermatosis, is an inflammatory process characterised by the abrupt appearance of erythematous papules or nodules with predominant neutrophilic infiltration in the dermis. Fever and neutrophilia are common presenting features. However, extracellular manifestations, including ocular and musculoskeletal, may occur. SS is divided into three subtypes: classical (or idiopathic), malignancy associated and drug induced. Medication-induced subtype accounts for up to 26% of cases. In recent years, emerging evidence has showed that SS may also occur in neutropenic patients who underwent induction for acute myeloid leukemia (AML). The identification of FMS-like tyrosine kinase 3 (FLT3) gene mutation in approximately 30% of patients with AML has promoted the targeted therapy with FLT3-internal tandem duplication (ITD) inhibitors. Midostaurin, a recently Food and Drug Administration-approved medication for FLT3-ITD-positive AML, was reported once as cause for SS. We report a midostaurin-induced SS with neutropenia in a patient following induction chemotherapy of AML.