Sweet syndrome with peripheral neuropathy in a patient with metastatic clear cell renal cell carcinoma.

A female patient in her 70s with a newly diagnosed clear cell renal cell carcinoma (ccRCC) with osseous metastasis presented with sudden onset erythematous painful blistering skin lesions on the dorsum of both hands, with associated intermittent fever episodes. Blood tests showed elevated inflammatory marker levels (C reactive protein 257.8 mg/dL, leucocytes 17.79×109/L, with 94% neutrophils). Histologically, there was predominately neutrophil dermal infiltrate without leucocytoclastic vasculitis. The diagnostic criteria of Sweet syndrome were fulfilled. A week later, the patient developed abrupt left-hand palsy, which was confirmed as a medial and ulnar sensorimotor axonal peripheral neuropathy of paraneoplastic origin. The patient was prescribed a course of oral high-dose steroids, which significantly improved the skin lesions. The peripheral nerve palsy improved after 3 months. This case describes the two very rare concurrent paraneoplastic manifestations of ccRCC occurring simultaneously, which have been rarely reported.

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 and Neutrophilic Dermatosis of the Dorsal Hands.

Sweet syndrome is a rare cutaneous condition with a broad clinical differential diagnosis. It can be classified into 3 subtypes: classic, malignancy-associated, and drug-induced. There are numerous associated disorders and provoking medications. Uncommonly, it can present as a multiorgan disease and cause significant morbidity. Systemic corticosteroids are the gold standard of treatment and yield rapid improvements in both lesions and symptoms. Nonsteroidal therapies may be effective alternatives, although high-quality comparative data are lacking. Some treatments for Sweet syndrome have paradoxically been implicated in the induction of disease.

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.

A diagnostic challenge-First case of chronic lymphatic leukemia-associated necrotizing sweet syndrome.

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare disorder typically characterized by the clinical triad including a sudden onset of fever, painful skin lesions, and neutrophilia. The histopathological findings are a dense neutrophilic infiltrate and oedema of the dermis and epidermis without evidence of a vasculitis. Besides treatment of the underlying cause, sweet syndrome is typically treated with high-dose corticosteroids leading to a relapse-free response in 70% of patients. However, if left unrecognized or untreated, the condition may lead to serious complications. Here, we report on the case of a 38-year-old patient in whom, under the assumption of the presence of necrotizing fasciitis, exarticulation of the right arm was performed. In the absence of pathogen detection and insufficient response to anti-infective therapies, the diagnosis of a sweet syndrome was assumed and, later, confirmed by an excellent response to high-dose administration of systematic glucocorticoids. The case emphasizes the need to be aware of this rare syndrome, which can be easily misdiagnosed due to its close resemblance to infection and stresses the need of further research to define distinct diagnostic tools.

Sweet Syndrome: Clinical Presentation, Malignancy Association, Autoinflammatory Disorders and Treatment Response in a Cohort of 93 Patients with Long-term Follow-up.

Sweet syndrome is a neutrophilic dermatosis associated with multiple disorders. This retrospective case-series study of patients with Sweet syndrome in a tertiary hospital in Spain from 2001 to 2021, explores clinicopathological characteristics of Sweet syndrome and variables associated with malignancy, presence of autoinflammatory disorders and differences between histological subtypes. A total of 93 patients were identified: 30% idiopathic, 34% malignancy-associated, 29% reactive to infections or drug-associated, and 6% with an autoimmune/inflammatory condition. Acute myeloid leukaemia was the most common malignancy (16/93) followed by myelodysplastic syndrome (7/93). Patients with acute myeloid leukaemia presented isolated flares, marked cytopaenia and rapid response to treatment, whereas myelodysplastic syndrome followed a chronic-recurrent course. The most frequent associated medications and inflammatory  disorders were filgrastim and hydroxyurea (n = 2);  and inflammatory bowel disease (n = 4). In addition, 3 patients were diagnosed with VEXAS syndrome. Male sex (p = 0.006), fever (p = 0.034), increased erythrocyte sedimentation rate (p < 0.001), anaemia (p < 0.001), and thrombocytopaenia (p < 0.001) were associated with malignancy. Histologically, patients were classified as classic (60%), histiocytoid (22.5%) or subcutaneous (15%), with pain (p = 0.011) and nodules (p < 0.001) being associated with subcutaneous-Sweet syndrome. Sweet syndrome in the context of cytopaenia should alert the presence of malignancy. An  acquired autoinflammatory condition should be explored  in relapsing Sweet syndrome with myelodysplastic syndrome. A minimum follow-up of 6 months is recommended.

Periorbital Necrotizing Sweet's Syndrome: A Case Report.

Sweet's syndrome (acute febrile neutrophilic dermatosis) is an uncommon inflammatory condition most often associated with painful skin lesions of the head, neck, and upper extremities. To the authors' knowledge, this case report is the only published record of the necrotizing clinical variant of Sweet's syndrome in the periorbital space. This case follows a 91-year-old female who presented with generalized cutaneous eruptions of tender erythematous plaques, including a necrotic plaque of the left upper eyelid, and pancytopenia. A biopsy of an inner thigh lesion was consistent with Sweet's syndrome. Initially diagnosed with preseptal cellulitis, the patient experienced marked clinical improvement with corticosteroids. This, coupled with the histopathologic findings of her thigh biopsy and the absence of eyelid margins, led to the diagnosis of periorbital necrotizing Sweet's syndrome. Although cases of Sweet's syndrome in the periorbital region are rare, these diagnoses should not be overlooked and may be critical to patient care.

Sweet Syndrome Associated with Active Inflammatory Bowel Disease: A Case Series of a Rare Extra-intestinal Manifestation.

BACKGROUND: Cutaneous extra-intestinal manifestations (EIM) occur in up to 20% of patients with IBD. Information about Sweet syndrome (SS)'s clinical course as a rare cutaneous EIM in IBD is limited to case reports. We present the largest retrospective cohort on the occurrence and management of SS in IBD. STUDY: Electronic medical records and paper charts since 1980 were retrospectively reviewed at a large quaternary medical center to identify all adult IBD patients with histopathology-proven SS. Patient characteristics and clinical outcomes were evaluated. RESULTS: 25 IBD patients with SS were identified; 3 patients were assessed to have AZA-induced SS. The majority of SS patients were female. Median age at diagnosis was 47 years (IQR 33-54 years) and SS appeared at a median of 6.4 years after IBD diagnosis. IBD patients with SS had a high rate of complicated IBD phenotypes (75% extensive colitis in UC and 73% stricturing or penetrating disease in CD, with 100% colonic involvement), as well as frequent co-occurring EIMs (60%). SS correlated with global IBD disease activity. Corticosteroids were an effective therapy for SS in IBD. Recurrence rate of SS was 36%. CONCLUSION: Contrary to previous case reports, SS was a cutaneous EIM occurring late after diagnosis of IBD in our cohort, with occurrences paralleling global IBD disease activity. Although AZA-induced and IBD-associated SS were both effectively treated with corticosteroids, distinguishing them is relevant for future IBD treatment strategies.

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.

Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome: A Systemic Review.

BACKGROUND: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome is a rare, hereditary, autoinflammatory disease. However, there are few cases reported in the literature. Therefore, we conduct this systematic review to summarize current evidence. METHODS: We conducted a systematic search in July 2021 using 11 different electronic databases. The included articles were screened according to our inclusion and exclusion criteria and assessed using an appropriate quality assessment tool. Then, the relevant data were extracted and summarized in tables accordingly. Each step of the previous one was done by 3 independent reviewers, and the conflicts were resolved by discussion and sometimes by counseling a senior member. RESULTS: The final included studies were 18 articles with 34 cases (mean age = 8 years, male/female = 19/15). The most reported symptoms and signs were fever 97.1%, erythematous plaques 76.5%, arthralgia 67.6%, hepatomegaly 61.8%, violaceous hue 61.8%, lipodystrophy in extremities 53.1% in addition to low weight and height. Rare features were reported too. The laboratories were not specific, which may be explained by a systemic inflammatory response. Vasculitis was the dominant feature in the skin biopsy, whereas the calcification in the basal ganglia was a prominent sign in many cases. CONCLUSIONS: Fever, skin lesions, and systemic inflammatory response were the prominent features of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome. The clinical picture is the main guide in addition to the pathological findings. Mutation detection is the confirmatory test. Prednisolone is the most effective reported treatment for acute presentations in the literature.

Sweet Syndrome: A Review of Published Cases.

Sweet syndrome (SS), the prototypical neutrophilic dermatosis, is characterized by abrupt onset of tender plaques and nodules, classically accompanied by fever and leukocytosis. While management mainly relies on systemic corticosteroids, inadequate response can be seen in some patients that necessitates exploring other treatment options. Early diagnosis of malignancy-associated SS (MA-SS) along with detection of concomitant malignancy is crucial for improving patients' outcomes. Data regarding various clinical manifestations, extracutaneous associations, treatment, and outcomes are poorly characterized in the literature. We aimed to review all published case reports and case series to portray clinical features of SS including extracutaneous manifestations. We also describe reported treatment options and their outcomes to draw attention toward unmet therapeutic needs in the management of SS. In addition, for clinical and practical purposes, we attempted to delineate the distinction between MA-SS and nonmalignant subtypes of SS.

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.

Neutrophilic dermatosis of the dorsal hands: A review of 123 cases.

Neutrophilic dermatosis of the dorsal hands (NDDH) is an uncommon localized variant of Sweet syndrome first described in 1995. It is characterized by tender erythematous plaques, pustules, and bullae on the dorsa of the hands. A total of 123 cases of NDDH are included in this review. The mean patient age was 62.1 years, and there was a slight female preponderance. Overall, 78.0% of cases had bilateral involvement, and other sites were affected in almost a third of cases. Underlying disease was found in ∼40% of patients, with the most common associations being hematologic disorders (gammopathies, myelodysplasias, or malignancies), recent infection, solid organ tumors, and inflammatory bowel disease. Systemic or topical corticosteroids or both were employed in the treatment of 88.1% of cases, while dapsone, colchicine, and tetracyclines were the most common steroid-sparing agents used. Improvement was often rapid and complete resolution the norm. Although uncommon, NDDH is frequently misdiagnosed, and thus, its exact prevalence is probably underestimated. Misdiagnosis might have significant implications, including treatment delays or incorrect management. Moreover, recognition of NDDH is important, since a correct diagnosis should trigger a search for underlying diseases and proper treatment with corticosteroids, steroid-sparing agents, or both, which is almost invariably curative.

Identification of a neutrophil-specific PIK3R1 mutation facilitates targeted treatment in a patient with Sweet syndrome.

BackgroundAcute febrile neutrophilic dermatosis (Sweet syndrome) is a potentially fatal multiorgan inflammatory disease characterized by fever, leukocytosis, and a rash with a neutrophilic infiltrate. The disease pathophysiology remains elusive, and current dogma suggests that Sweet syndrome is a process of reactivity to an unknown antigen. Corticosteroids and steroid-sparing agents remain frontline therapies, but refractory cases pose a clinical challenge.MethodsA 51-year-old woman with multiorgan Sweet syndrome developed serious corticosteroid-related side effects and was refractory to steroid-sparing agents. Blood counts, liver enzymes, and skin histopathology supported the diagnosis. Whole-genome sequencing, transcriptomic profiling, and cellular assays of the patient's skin and neutrophils were performed.ResultsWe identified elevated IL-1 signaling in lesional Sweet syndrome skin caused by a PIK3R1 gain-of-function mutation specifically found in neutrophils. This mutation increased neutrophil migration toward IL-1ß and neutrophil respiratory burst. Targeted treatment of the patient with an IL-1 receptor 1 antagonist resulted in a dramatic therapeutic response and enabled a tapering off of corticosteroids.ConclusionDysregulated PI3K/AKT signaling is the first signaling pathway linked to Sweet syndrome and suggests that this syndrome may be caused by acquired mutations that modulate neutrophil function. Moreover, integration of molecular data across multiple levels identified a distinct subtype within a heterogeneous disease that resulted in a rational and successful clinical intervention. Future patients will benefit from efforts to identify potential mutations. The ability to directly interrogate the diseased skin allows this method to be generalizable to other inflammatory diseases and demonstrates a potential personalized medicine approach for patients with clinically challenging disease.Funding SourcesBerstein Foundation, NIH, Veterans Affairs (VA) Administration, Moseley Foundation, and H.T. Leung Foundation.

Neutrophilic Dermatosis of the Hands: A Case Report.

Neutrophilic dermatosis of the hands (NDDH) is a localized variant of Sweet's syndrome which has been recently introduced. Strutton et al.in 1996 and then in Galaria et al. in 2000 reported cases with violaceous papulonodules on the dorsal surfaces of the hands with histopathological findings of a neutrophilic dermatosis in association with leukocytoclasia, but clinically and histologically without true vasculitis findings. Eventually, they proposed the term NDDH for these lesions (1,2). A 46-year-old man was referred to our outpatient dermatology clinic with a painful ulcerative lesion on the dorsal side of the left hand that had been present for one year. Initially, the lesion had appeared as a small purulent papule, which gradually extended to a large ulcer. The patient underwent frequent referrals to several physicians and had taken a variety of topical and systemic antibiotics, meglumine antimoniate (Glucantime), and amphotericin with the clinical diagnosis of cutaneous bacterial or fungal infections, or leishmaniasis. All of these therapeutic regimes were ineffective in eradicating the lesion. Given the history, he denied any trauma to the site of lesion; he also did not report any similar lesions in his family. The physical examination revealed an extensive tender ulcer of 4×7 cm2 in size, with a shallow violaceous border superimposed on an edematous region on the dorsal side of the left hand. Atrophic scars resulting from old similar lesions were visible on the dorsal aspects of the 3rd and 4th proximal and middle metacarpal joints (Figure 1). The examination of the other parts of the body was unremarkable. Laboratory tests showed an impaired white blood cell count and their differentiation, including leukocytosis (white blood cell count of 16.12/mm3) with neutrophilia (neutrophil percent at 65.9%). Additionally, altered liver function tests were remarkable for high serum levels of AST (SGOT) (105 IU/L) and ALT(SGPT) (355 IU/L), while the total bilirubin and alkaline phosphatase were within normal limits. Hemoglobin levels (13.90 g/dL) and platelet count (272/mm3) were within normal range. The other laboratory tests, including serological tests for fasting blood sugar, hemoglobin A1c, creatinine, BUN, and an immunoassay for ruling out vasculitis lesions (anti-MPO (P-ANCA) and anti-PR3 (C-ANCA)) revealed no remarkable results. An erythrocyte sedimentation rate of 16 mm/h was reported. A biopsy was performed. Histologic features demonstrated a dense, diffuse dermal infiltrate comprised almost entirely of neutrophils. The epidermis was slightly acanthotic and showed small foci of spongiosis, but the inflammatory infiltrate remained largely in the dermis. Sheets of neutrophils were present, admixed with karyorrhectic debris. The infiltrate did not appear to be peri-vascular, and most vessels that could be observed clearly appeared to be undamaged. However, some vessels appeared to show some neutrophils infiltrating vessel walls (Figures 2a, b). Based upon histopathologic examination, the diagnosis of neutrophilic dermatosis of the hands (NDDH) was suggested. The work-up findings for ruling out neoplastic diseases were unremarkable. Clinically, patients with NDDH show various morphologic patterns of the lesions on the dorsal aspect of the hands, including violaceous edematous plaques or ulcers with undermined borders, hemorrhagic bullae, necrotic pyoderma-like lesions with pseudovesiculation, and atypical pyoderma gangrenosum-like lesions (1). This disease is more common in women (70%) than in men (3). NDDH has been reported in association with malignancies (such as leukemia and lymphoma), myelodysplasia, inflammatory bowel diseases, seropositive arthritis, sarcoidosis, HCV infection, and medications (such as lenalidomide, thalidomide, vaccinations, fertilizer, etc.) (1). Among them, neoplastic diseases are the most common association, which has been reported in 27% of the cases. It may thus represent a paraneoplastic phenomenon (3). Histopathological study is mandatory for achieving a definite diagnosis of NDDH. Its pathological findings include subepidermal edema, a dense and diffuse dermal infiltration of neutrophils along with leukocytoclastic debris, and extravasated erythrocytes, which are not associated with true vasculitis (1,3). However, the presence or absence of some vasculitic features as a histopathological finding depends on the time of biopsy with regard to the evolutionary phases of the lesion (3). In our case, the diffuse nature of the infiltrate was somewhat indicative against the diagnosis of leukocytoclastic vasculitis. Additionally, the possibility of infection was excluded empirically (due to the ineffectiveness of previous therapies without doing cultures or PCR), and indirectly through biopsy. Cohen (4) and Cohen and Kurzrok (5) explained the presence of vasculitis in Sweet's syndrome and NDDH as an epiphenomenon in which the damaged vessel is as an "innocent bystander" in the background of an inflammatory dermatosis. Eventually, they concluded that the presence or absence of vasculitis has a secondary importance in the diagnosis of NDDH. The following entities should be considered in the differential diagnoses of NDDH: cutaneous infections, vesiculobullous pyoderma gangrenosum (atypical), bullous erythema multiforme, pustular drug reactions, rheumatoid neutrophilic dermatosis, bowel-associated dermatosis-arthritis syndrome, and erythema elevatum diutinum (1-3). In our case, based on the pathological examination, the differential diagnosis included neutrophilic dermatosis such as Sweet's syndrome or neutrophilic dermatosis of the dorsal hands. It is essential to exclude an infectious etiology that might include a bacterial infection, or less likely a fungal or atypical mycobacterial infection, given the lack of any granulomatous component. However, some atypical mycobacterial infections can demonstrate a brisk neutrophilic infiltrate and relatively sparse granulomatous responses (6). For the same reason (lack of significant histiocytes), we thought that palisaded neutrophilic and granulomatous dermatosis associated with connective tissue disease was less likely. The relationship between this disease entity and a superficial variant of pyoderma gangrenosum remains unclear. The treatment of NDDH includes systemic corticosteroids, dapsone, methotrexate, potassium iodide, colchicine, and minocycline (2). NDDH is often misdiagnosed as an infectious condition, which can result in inappropriate antibiotic therapy, surgical debridement, and even amputation (7). Therefore, early diagnosis and initiation of appropriate treatment should be mainstay of its treatment.

Bullous Sweet syndrome as a presentation of chronic myelogenous leukaemia.

A woman in her 40s presented with a 3-month-long history of fever and tender erythematous bullous skin lesions not responsive to antibiotics. There had been no previous gastrointestinal, respiratory or urinary infection, nor did she have any history of autoimmune disease, drug reaction or vasculitis.Histological evaluation of skin biopsy showed diffuse dense neutrophilic infiltrates located in dermis diagnostic of Sweet syndrome. Haematological investigations showed leucocytosis with circulating immature cells, which on further investigations with bone marrow biopsy, were evident of chronic myelogenous leukaemia in the accelerated phase. Sweet syndrome was the presenting characteristic of chronic myelogenous leukaemia in this case, which is a rare association. Investigating unusual skin lesions can aid in the suspicion of underlying cancer, allowing for prompt action.

Rare mucocutaneous manifestations of ulcerative colitis: A case report of pyostomatitis vegetans and Sweet syndrome.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the digestive tract, and they involve systemic inflammatory diseases known as extra-intestinal manifestations (EIMs). Timely and correct diagnosis of mucocutaneous EIMs could assist with detecting and monitoring IBD. We present a case of 52-year-old male patient of ulcerative colitis with 2 rare EMIs together at the same time: pyostomatitis vegetans in the oral cavity and Sweet syndrome on the skin. They presented as multiple small white or yellow pustules on the surface of the hyperemic fragile oral mucosa and abrupt appearance of painful, swollen, and erythematous papules on the skin, respectively. The final diagnosis was made based on clinical manifestations, skin and oral tissue biopsies, and the ulcerative colitis history. This rare case report may remind dentists of rare mucocutaneous EIMs of IBD that might be overlooked. Dentists and dermatologists could contribute to the early diagnosis and management of systematic diseases.