Sweet Syndrome Research Articles

Systemic Lupus Erythematosus presenting as Sweet Syndrome: A Case Report

No abstract available

Reactive Neutrophilic Dermatoses in Adult-Onset Immunodeficiency due to Interferon-Gamma Autoantibody and Their Associated Factors

Background: Adult-onset immunodeficiency (AOID) due to interferon-gamma autoantibody is a rare, acquired immunodeficiency disease. Reactive neutrophilic dermatoses (RND), predominantly Sweet syndrome (SS), and generalized pustular eruption have been reported repeatedly. Objectives: The aims of this study were to describe the cutaneous manifestations in AOID patients and determine the incidence of RND and associated factors using a larger population size than have been previously reported. Methods: A retrospective chart review of all confirmed AOID cases in Chiang Mai University Hospital from January 2006 to June 2020 was conducted. The demographics and characteristics of RND including type, onset, and laboratory information in every episode of cutaneous manifestations were collected. Generalized estimating equations of binary logistic regression were used to determine the indicators of RND. Results: A total of 146 patients with confirmed AOID were identified. Of these, 57 cases (39%) developed at least one episode of RND. Thirteen cases (23%) of the patients experienced RND twice during the follow-up period. All recurrence of RND displayed the same cutaneous phenotype, with the exception of 2 cases who had both SS and generalized pustular eruption. Finally, 49 episodes of SS and 22 episodes of generalized pustular eruption were included in the analysis. All patients with RND had concomitant active opportunistic infections, of which most were non-tuberculous mycobacterium (NTM) infection. NTM infection (prevalence odds ratio [POR] 2.87), lymphadenopathy (POR 3.30) as well as lower serum alkaline phosphatase (ALP) level (POR 0.71 for every 100-unit increment in ALP) were found to be significantly associated with RND occurrence. Conclusions: 39% of our AOID patients experienced RND once during the course of the disease. Notable factors associated with RND occurrence were concomitant NTM infection, lymphadenopathy, and lower level of ALP.

Cutaneous Involvement of Angioimmunoblastic T-cell Lymphoma

A 74-year-old man with chronic lymphocytic leukemia and angioimmunoblastic T-cell lymphoma (AITL) of the right lung was undergoing evaluation for initiation of chemotherapy. Bendamustine and rituximab were previously initiated but stopped after one month due to adverse effects. The patient subsequently completed 7 years of ibrutinib therapy, which was halted 3 weeks prior to presentation due to its ineffectiveness and significant hematologic lab abnormalities. Treatment with CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) was proposed, however the patient had a nodule concerning for cellulitis on the left fifth palmar digit requiring treatment prior to chemotherapy initiation. No improvement was seen after courses of cephalexin and doxycycline. Due to a lack of response to these two antibiotics, dermatology was consulted for further evaluation.
 On physical exam, there was a 1.3-cm red-violaceous crusted nodule on the palmar aspect of the left fifth digit (Figure 1, panel A). Dermoscopy showed central orange-tan pigmentation with loss of normal acral ridge pattern and surrounding irregular vessels (Figure 1, panel B). The differential diagnosis included Sweet syndrome, drug eruption, infection, and malignancy. A punch biopsy was performed and showed an atypical lymphocytic nodular infiltrate with angioinvasive and angiodestructive features, and immunohistochemical stains suggested AITL. The patient’s clinical stage was changed from stage II to stage IV AITL due to skin involvement, and the patient was started on CHOP treatment.
 AITL is a peripheral CD4+ follicular T-helper cell-based lymphoma that presents with B symptoms and generally has a poor prognosis after conventional chemotherapies [1]. Though rare, AITL has been reported to present with skin manifestations in up to 50% of cases, which typically present as macular or papular eruptions on the trunk, similar to toxic erythema of chemotherapy, drug eruptions, or viral exanthems [2]. However, there are multiple case reports of AITL mimicking a variety of systemic dermatologic or oncologic entities, including dermatomyositis, systemic lupus erythematosus, vasculitis, and urticaria [3].
 This case of AITL with cutaneous involvement illustrates an uncommon presentation of this peripheral lymphoma that often has skin manifestations. The presence of skin involvement implies an advanced clinical stage, which confers a poorer prognosis [4]. Due to its variable presentations in the skin, it is often misdiagnosed as a vasculitis or exanthem, particularly when its initial presentation is in the skin without prior diagnosis of internal AITL malignancy [3]. As in this case, most patients are treated for their condition with chemotherapy, starting with anthracycline-based chemotherapy, and often require higher-dose or modified therapy due to the short response duration [4]. Here, we highlight the diagnostic challenge of AITL and the clinical importance of its identification for appropriate staging and treatment of this condition.

Lingual location of Sweet's syndrome: A case report

Context: Sweet's syndrome is a rare acute febrile neutrophilic dermatosis and idiopathic in two-thirds of cases. The pathophysiological mechanisms of Sweet's syndrome are poorly understood. Observation: A 35 yr old female patient has been referred from the Dermatology Department to the Oral and Surgery Department, University Hospital Center of Oran (Algeria), for a lingual nodule. For medical history, the patient had a Sweet's syndrome diagnosed 1 yr ago and a rheumatoid arthritis treated with corticosteroids. An excisional biopsy of the lingual nodule was performed and the anatomopathological result revealed a pyogenic granuloma associated with polymorphonuclear neutrophilic vasculitis in the context of Sweet's syndrome. Discussion and conclusion: Sweet's syndrome is characterized by a constellation of clinical symptoms, biological and histological abnormalities and is manifested by the sudden appearance of painful skin lesions in the form of asymmetric erythematous papules, nodules or plaques. In the context of Sweet's syndrome, faced with an oral with cutaneous lesions a correlation and/or manifestation of neutrophilic dermatosis must be suspected.

Severe anemia and neutrophilic leukocytosis resembling Sweet’s syndrome in a dog

Sweet’s syndrome is a rare inflammatory condition characterized by the presence of neutrophilic infiltrate of the skin. We describe a case of severe anemia and neutrophilia with post-mortem findings resembling Sweet's syndrome in a five-years-old female Labrador Retriever with bilateral epistaxis, hematemesis, hyporexia, pale oral mucosa, and fever. Laboratory analysis evidenced severe unresponsive anemia, thrombocytopenia, and leukocytosis. Biochemistry showed hypoalbuminemia and increased ALT and SAP activities. The patient was transfused and received doxycycline and prednisone for one week without improvement. Two further blood transfusions were administered. Bone marrow analysis showed a mild erythroid hypoplasia, granulocytic hyperplasia, myeloid to erythroid ratio of 6.01:1 (reference: 0.9:1 – 1.76:1) without dysplasia, mild megakaryocytic hyperplasia, and increased iron stores. Macrophages were slightly increased in number with erythrophagocytosis, and immune-mediated anemia was considered. Immunosuppressive treatment was prescribed to reduce red blood cell destruction, but no improvement after one week was observed, and euthanasia was performed. Necroscopic findings resembled those described for the systemic form of Sweet's Syndrome. Bone marrow histopathology showed remarkably increased granulopoiesis and destruction of platelets and erythrocytes. Sweet's syndrome is frequently associated with hematologic malignancy or drug exposure. Leukemia was excluded after bone marrow analysis because no increase in blast population was seen as well as no signs of dysplasia. Previous treatment could be related to the development of Sweet's syndrome, which might be the primary event. Although rare, this syndrome should be considered in the differential diagnosis of dermatosis and leukocytosis when infectious agents are not identified.

Management of coronavirus disease 2019 vaccine-induced cutaneous complications: A comprehensive literature review.

Despite the numerous reports of cutaneous manifestations associated with vaccines for coronavirus disease 2019 (COVID-19), the relationship between COVID-19 vaccines and cutaneous side effects remains unevaluated. In this review, we examine these manifestations and their management. Reported dermatoses included injection-site reaction (early and delayed), type I allergic reaction, morbilliform eruption, pityriasis rosea, Sweet syndrome, lichen planus, psoriasis, herpes zoster reactivation, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN). The most common COVID-19 vaccination-related cutaneous manifestations are delayed local reactions, approximately 66% of which are associated with the Moderna vaccine, and 33% with the Pfizer vaccine. Aside from mild injection-site reactions, severe reactions include anaphylaxis and TEN. Most reactions, except for Stevens-Johnson syndrome and anaphylaxis, though unpredictable and unpreventable are mild and can be treated symptomatically. Findings from this review should allow primary care physicians and dermatologists to reach faster diagnosis and initiate prompt intervention.

Sweet Syndrome Localized to the Face.

Sweet Syndrome Localized to the Face.

Sweet's syndrome

Sweet's syndrome

Anti-glomerular basement membrane disease developing 3years after the development of Sweet syndrome and 1year after the development of anti-neutrophil cytoplasmic antibody-associated vasculitis: a case report.

A 73-year-old Japanese woman, with a history of Sweet syndrome diagnosed 3years earlier and anti-myeloperoxidase (MPO) antibody anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis diagnosed 1year earlier, presented with an episode of rapidly progressive glomerulonephritis (RPGN) with anti-glomerular basement membrane (GBM) disease. At the time of diagnosis of the ANCA-associated vasculitis 1 year earlier, serological testing yielded a negative result for anti-GBM antibody. However, at the present visit, serology for anti-MPO antibody was negative, while that for anti-GBM antibody was positive. This is the first report of anti-GBM disease developing sequentially after Sweet syndrome and ANCA-associated vasculitis. This case may provide clues to the potential immunological links among these three distinct conditions.

Sweet Syndrome: A Rare Skin Disorder in Children

Sweet syndrome (SS) is a rare dermatosis of unknown etiology. It is characterized by fever, neutrophilia, raised and painful plaques on the skin of the face, neck, limbs, and histologically by dermal infiltration of neutrophils. Here, we present a ten-year-old boy who presented with fever and multiple skin lesions for 15 days. On examination, he was febrile and presented with multiple nodular, tender, erythematous rash on face and limbs. Laboratory findings revealed raised inflammatory markers with neutrophilic leukocytosis, skin biopsy showed hyperkeratosis and neutrophilic infiltration of the dermis. Typical history, laboratory investigations including skin biopsy findings were suggestive of diagnosis of SS. Prolonged fever and characteristics skin lesions in any child should be suspected for this rare syndrome. It should be kept in mind as a differential diagnosis in the day-today clinical practice for effective management of this rare disease.
 BANGLADESH J CHILD HEALTH 2021; VOL 45 (3) : 172-174

149 Sweet’s Syndrome: One Center Study of 42 Patients

Sweet’s syndrome (SS) is a rare acute febrile neutrophilic dermatosis characterized by an abrupt onset of fever, arthralgia, neutrophilia, tender erythematous papules, nodules, and plaques. We present a case series of patients seen at the dermatology department of the Ibn Sina University Hospital (Rabat). The goal of our study was to describe the epidemiological, clinical profile and the possible association of the Sweet syndrome in our department. We performed a descriptive retrospective study of 42 Moroccan patients seen between January 2004-January 2020.

Vexas Syndrome: A Complex Necessarily Integrated Diagnosis That Can Benefit from the Help of Deep Learning

Introduction At the end of 2020, a novel entity dubbed VEXAS (for vacuoles, E1 enzyme, X-linked, auto-inflammatory, somatic) was described by Beck et al. (NEJM, 2020). This syndrome is defined molecularly by a mutation of the UBA1 gene that codes for the E1 enzyme, a major actor of ubiquitinylation. From a pathophysiological point of view, UBA1 mutations induce the transcription of a deficient enzyme. Affected cells display an altered ubiquitinylation of misfolded proteins and dysregulated autophagy. This leads in fine to an impairment of several pathways of innate immunity, overproduction of a range of pro-inflammatory cytokines and, more generally, systemic inflammation. Clinical manifestations are pleomorphic and patient-dependent, with reported cases of fever, vasculitis, ophthalmic lesions, chondritis, Sweet syndrome or pulmonary interstitial infiltration. From a hematological point of view, thromboses have also been described as well as several cytologic alterations. The latter include cytopenias of any lineage, myeloid hyperplasia with erythroblastic hypoplasia (M/E) and, notably, the presence of vacuoles essentially in granulocytes and erythroblasts precursors. Some cases are associated to myelodysplastic syndrome (MDS). Here, an in-depth morphological examination of VEXAS and non-VEXAS patients was performed, to delineate and quantify several anomalies. These data were then fed to a deep learning algorithm to evaluate the additional help provided by this artificial intelligence (AI) tool in predicting VEXAS syndrome and orienting further analyses towards the identification of the molecular anomaly. Patients, material and methods To identify diagnostic tools for VEXAS syndrome on blood and bone marrow smears, 4 patient cohorts were analyzed :i) patients with a diagnosis of VEXAS syndrome confirmed by genetic analysis (n=6), ii) MDS patients (n=4), iii) patients with an initial clinical suspicion of VEXAS invalidated by molecular analysis (UBA1 WT: n=3) and iv) 4 healthy controls. For each patient, morphological examination of blood and marrow smears was performed independently by two experts in a blind fashion. In order to guide the diagnosis of the syndrome on the blood smears, a deep learning method was trained in a multilabel classification setting to automatically evaluate the percentages of abnormal polymorphonuclears (PMN). The final dataset was therefore composed of PMN from healthy controls (n=5, 519 images) and from VEXAS syndrome (n=4, 938 images) (DI microscope, Cellavision ®). Results Among the 6 patients with VEXAS syndrome, the main clinical manifestations were: asthenia 100%; fever 83.3%; skin involvement 66.7%; thrombosis 66.7%, chondritis 33.3% and interstitial lung disease 33.3%. The most frequent cytopenia was macrocytic anemia in 66.7% of the patients. Upon morphological examination of blood smears, the following abnormalities were statistically associated with the diagnosis of VEXAS : percentage of pseudo-Pelger PMNs (p=0.003), percentage of PMNs with more than 4 nuclear projections (Barr bodies; p=0.0009), percentage of vacuolated PMNs (p=0.01). On bone marrow smears, compared to the MDS and UBA1 WT cohort, patients with VEXAS syndrome had significantly more PMNs with a pseudo-Pelger aspect (p<0.05), more vacuolization of granular (p<0.05) and erythroblastic (p<0.05) precursors. Different deep learning architectures were tested on blood smear images, with the objectives of distinguishing abnormal PMN from others. The trainings were conducted by cross-validation, and then the algorithm was evaluated on new patients. The metrics used to evaluate algorithm performance were precision, recall, F1-score and Hamming loss. These data allowed to establish a standardized computer aided diagnosis tool. Discussion/conclusion The diagnosis of VEXAS syndrome is complex. This analysis identified cytological features on blood smears leading to the development of a deep learning-based diagnosis algorithm. Promising leads are currently investigated to improve the efficiency and robustness of this deep learning algorithm such as the inclusion of other pathologies in order to train a disease agnostic anomaly detection algorithm, or leveraging data from other modalities as prior knowledge.

Infantile Sweet syndrome following MMRV vaccine.

Sweet syndrome (SS), also called acute febrile neutrophilic dermatosis, is rare in the pediatric population, especially in infants and neonates. We present a case of infantile SS that developed 1 day after the MMRV vaccine; we suggest a possible causal relationship between the MMRV vaccine and SS.

Histiocytoid Sweet Syndrome Presenting in Two Sisters With Deficiency of Deaminase Type 2.

Deficiency of adenosine deaminase type 2 (DADA2) is an autosomal recessive monogenic autoinflammatory syndrome that is classically characterised by polyarteritis nodosa, systemic vasculitis and stroke. The spectrum of disease manifestations has broadened to encompass a range of cutaneous, vascular and haematological manifestations. We report a novel association in two sisters with heterozygous p.R169G/p.M309l mutations in ADA2 with low serum ADA2 activity who both presented similarly with clinical and histological features consistent with histiocytoid Sweet syndrome.

Sweet's Syndrome: An Update.

Sweet's syndrome is a serious dermatological disorder characterized by a rapid onset of tender plaques or nodules, fever, joint pain, headache, and oral and genital lesions. According to the clinical features and underlying causes, Sweet's syndrome is divided into three categories, i.e., classical (or idiopathic), malignancy-associated Sweet's syndrome, and drug-induced Sweet's syndrome. It is multifactorial in etiology, and the exact cause is still undetermined. The diagnosis can be confirmed by the routine histopathologic evaluation of skin biopsy from the lesions. The first-line treatment options are topical and systemic steroids. Multiple databases, like Medline/PubMed, Scopus, and Google, were used to identify resources for this literature review. The relevant information was collected from various case reports, case series, reviews, meta-analyses, and large clinical trials reporting clinical description, etiology, diagnosis, and management of Sweet's syndrome. This narrative review aimed to discuss recent understandings related to Sweet's syndrome, both in terms of clinical presentation and management approach.

WHEN A SWEET RASH LEADS TO A SOUR DIAGNOSIS

<h3>Introduction</h3> Sweet syndrome (SS) is a rare neutrophilic dermatosis with symptoms including fever, neutrophilia and tender erythematous skin lesions. Often preceded by upper respiratory infections, SS classically presents in middle-aged women. Pediatric SS is rare; SS as the presenting feature of chronic granulomatous disease (CGD) has only been described in two case reports previously. We describe a patient presenting with SS, who was found to have CGD. <h3>Case Description</h3> A 12 month-old male presented for evaluation of persistent fevers, lymphadenopathy and pustular rash. It was thought that he had an atypical presentation of Kawasaki Disease, and he was treated with IVIG in addition to doxycycline for empiric coverage of possible infection. Biopsy of the rash confirmed neutrophilic dermatitis, consistent with SS. One week later, he was readmitted for recurrence of fever, anemia, transaminitis and elevated inflammatory markers. Genetic testing for autoinflammatory disorders was completed, and a pathogenic hemizygous mutation in <i>CYBB</i> was found. This prompted dihydrohodamine testing which confirmed abnormal neutrophil respiratory burst. His rash resolved after treatment with corticosteroids which is the mainstay treatment for SS. He was started on antimicrobial prophylaxis and referred for evaluation for hematopoietic stem cell transplant. <h3>Discussion</h3> In children, SS is associated with chronic inflammatory conditions, viral illnesses or malignancy. Immunodeficiency and lupus are also associated with SS, specifically in neonates. This case highlights that immunodeficiency should be considered in cases of SS even in older children. Immunologists play a role in the evaluation of these children.

A CASE OF RECURRENT HISTIOCYTOID SWEET SYNDROME

<h3>Introduction</h3> Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis characterized by abrupt onset of painful plaques, nodules, or papules, which can be associated with malignancies, auto-immune diseases, infections, or drug exposures. Identifying triggers, if any, especially in the context of rare life-threatening histological variants, is crucial for disease management. <h3>Case Description</h3> Ms. S is a 44-year-old woman who presented for evaluation of a 9-year history of erythematous, painful, non-pruritic, indurated plaques on her abdomen and thighs that can last 1-2 months, leaving residual bruising, often associated with fevers, headaches, pleuritic chest pain, dyspnea, and fatigue. Triggers include intense workouts and elevated stress. Lesions initially occurred once every 2 years, but now occur bi-annually. Systemic steroids helped the most, while colchicine and Benadryl provided marginal relief. Rheumatological, immunodeficiency, infectious, malignancy and autoinflammatory disease work-up was unremarkable. Biopsy with direct immunofluorescence revealed histopathologic features consistent with histiocytoid SS. Given infrequency of symptoms, we decided against chronic suppressive therapy with steroids. <h3>Discussion</h3> Histiocytoid SS is a rare histological variant of neutrophilic SS, with dermal infiltrate mainly composed of lymphocytes and histiocytoid myeloperoxidase-positive cells, which may be associated with a higher risk of hematologic malignancy. This case demonstrates the extensive work-up required to evaluate for underlying diseases, as treatment of the underlying condition can often mitigate these lesions. We were unable to identify any triggers, and she presented with a rare histological variant not well described in the literature, making management more challenging. Continued surveillance, particularly for malignancy, is warranted given that this rash can potentially precede cancer.

PAINFUL SKIN LESIONS AFTER STARTING SUBCUTANEOUS IMMUNOGLOBULIN REPLACEMENT

<h3>Introduction</h3> 17-year-old female with history of Behcet's, Sweet's syndrome, Chilblain lupus, inflammatory arthritis and ileitis complains of painful skin lesions of the extremities after initiation of subcutaneous immunoglobulin (SCIg) replacement (Cutaquig). <h3>Case Description</h3> Patient is on multiple immunosuppressants including ustekinumab, canakinumab, and leflunomide managed by Rheumatology. She has received intermittent IVIg at ∼1 g/kg (anti-inflammatory dosing) for joint pain and skin lesions. Due to post-IVIg headaches, SCIg was opted and the patient was started on Cutaquig 15 g weekly. On the 2nd - 3rd Cutaquig infusions, painful red/purplish lesions appeared on fingers and toes bilaterally, which worsened weekly with the infusions. Skin biopsy was considered, but the lesions crusted and resolved over a few weeks shortly after Cutaquig was stopped. Allergy and Immunology (A/I) has been involved in the patient's care for concern for hypogammaglobulinemia with lowest IgG at 469 mg/dL. Past immune evaluation showed normal IgG and appropriate response to Pneumovax two years ago. Genetic testing has been unremarkable so far. Recent evaluation revealed persistently low IgG and gradually down trending IgA at 623 mg/dL and 45 mg/dL, respectively. Additionally, the patient also had a few ear infections; thus, A/I currently trialing Cuvitru at IgG replacement dosing (∼500 mg/kg). <h3>Discussion</h3> Systemic reaction to SCIg infusions are rare and thus well tolerated by patients. In contrast, local reactions with swelling, pain, and bruising on SCIg infusion sites have been well reported. To our knowledge, systemic dermatological adverse reactions due to SCIg have not been reported in the past.

Granuloma Annulare: a Case-control Study of Possible Associated Diseases.

Granuloma annulare (GA) has been reported as associated with multiple diseases, mainly diabetes mellitus (DM), thyroid diseases, and dyslipidemia. However, the high prevalence of some of these illnesses makes it difficult to assess whether the association is real or fortuitous. Our objective was to analyze the clinical features of GA patients and the possible associations. This is a retrospective observational study of 225 patients with biopsy-proven GA diagnosed between 2009 and 2019 in a referral university hospital in Barcelona, Spain. Clinical charts were reviewed to obtain clinical data. As a control group we used a random list of 225 patients diagnosed in the hospital traumatology department in the same period, matched by age and sex. Diabetes was diagnosed in 40 GA patients (18%) (34 in the control group, 15%) and hypothyroidism in 33 (15%) (22 in the control group 9.8%); the differences were not significant. We also did not detect any association with uveitis, sarcoidosis, necrobiosis lipoidica, Sweet syndrome, HIV infection, hepatitis B, or hematological malignancies. We only detected a possible association with hepatitis C (6 GA patients, 2.7%, versus 0 controls, P = 0.03), and hypercholesterolemia (108 GA patients, 48%, versus 79 controls, 35%, P = 0.007). The possible pathogenic explanations for the association with hepatitis C and hypercholesterolemia seem unlikely. We consider that the association of GA with other diseases, including hypercholesterolemia and hepatitis C, is doubtful and that it there is no justification rule out possible associated diseases in patients with GA.

SWEET Syndrome, who was to blame?

SWEET Syndrome, who was to blame?