Giant Cellulitis-Like Sweet Syndrome Masquerading As Cellulitis and Shingles: A Case Report and Literature Review.

Sweet syndrome (SS) is also known as acute febrile neutrophilic dermatoses. Clinically, SS features fever, arthralgias, and the sudden onset of an erythematous rash. The morphologies of skin lesions in SS are heterogenous, varying from papules, plaques, and nodules to hemorrhagic bullae, which sometimes makes the diagnosis of SS more challenging. We report a 62-year-old obese male with a history of chronic myeloid leukemia in remission for 10 years who presented with a rash for five days. The patient reported prodromal flu-like symptoms with subjective fever, malaise, cough, and nasal congestion followed by a sudden onset, painful, non-pruritic rash. The rash was associated with bilateral hip arthralgias and abdominal pain. The patient denied any recent travel, exposure to sick contacts, or the use of any new medications. Physical examination showed a well-demarcated, non-blanching, confluent, erythematous plaque involving the bilateral buttocks and extending to the lower back and flanks with coalescent "juicy"-appearing plaques and flaccid bullae. No oral or mucosal involvement was noted. Laboratory investigations revealed mild leukocytosis, elevated inflammatory markers, and acute kidney injury. The patient was started on antibiotics given the cellulitis-like skin lesions, leukocytosis with neutrophilia, and elevated inflammatory markers. Dermatology was consulted, who attributed the patient's rash to shingles and recommended initiating acyclovir and obtaining a skin biopsy. However, the patient's rash and arthralgias worsened with anti-viral treatment while awaiting pathology results. Antinuclear antibodies, complement, human immunodeficiency virus, hepatitis panel, blood cultures, and tumor markers were all negative. Flow cytometry showed no evidence of hematopoietic neoplasms. The skin punch biopsy revealed dense neutrophilic infiltration in the dermis with no evidence of leukocytoclastic vasculitis, consistent with acute neutrophilic dermatoses. The diagnosis of giant cellulitis-like Sweet syndrome was established, and the patient was started on prednisone 60 milligrams daily. His symptoms improved promptly with steroid treatment. Our case suggests that SS can camouflage a wide spectrum of diseases, including cellulitis, shingles, vasculitis, drug eruptions, leukemia cutis, and sarcoidosis, which emphasizes the importance of keeping a high index of suspicion for SS when assessing the clinical constellations of fever, neutrophilia, and erythematous plaques suggesting atypical cellulitis. Approximately 21% of Sweet syndrome is associated with malignancy. Sweet syndrome can precede, concur with, or follow the onset of malignancy. Due to the lack of a systematic approach to patients with SS, under-investigation and diagnostic delays are common. Therefore, further screening and continuous monitoring in patients with SS becomes especially important in facilitating the early detection of a potential underlying malignancy and assists in initiating adequate therapy.

A contrasting diagnosis: iododerma

An 86-year-old woman presented to the emergency department with acute shortness of breath. She was treated with intravenous furosemide for acute-on-chronic heart failure. Her past medical history included atrial fibrillation, hypertension, diverticulosis and hypothyroidism. Rivaroxaban and levothyroxine were her only long-term medications. On day 5 of hospital admission, she developed painful haemorrhagic and purulent bullae on her dorsal hands, head and neck. These evolved to large suppurative, vegetative plaques over a 72 h period and she developed additional lesions on her trunk, upper back and thighs. The patient had routine blood tests, which showed a raised C-reactive protein at 260 mg L-1, and an acute kidney injury with a glomerular filtration rate of 54 mL-1 min-1. She had a negative COVID-19 swab, and swabs from the lesions for bacterial culture and viral polymerase chain reaction were negative. She had a normal serum protein electrophoresis, immunoglobulin, antinuclear antibody and antineutrophil cytoplasmic antibody. She had computed tomography of her chest 24 h prior to the onset of her lesions, which showed mild bilateral pleural effusions in keeping with fluid overload secondary to heart failure. A biopsy taken from her hand showed orthokeratosis and parakeratosis, and there was bulla formation subepidermally. There was a dense neutrophilic infiltrate with microabscess formation with scattered eosinophils and lymphocytes. There was no evidence of vasculitis. Direct immunofluorescence was negative and a tissue culture for atypical mycobacteria was negative. The patient was commenced on high-dose intravenous methylprednisolone at 500 mg for 3 days followed by 40 mg prednisolone orally for 1 week, but there was a limited response. Our initial differential was Sweet syndrome or pyoderma vegetans;however, the patient had no fevers and no risk factors (malignancy, inflammatory disease, infection, etc.). She also had no response to high-dose oral prednisolone. Given the timing of her CT examination in relation to her acute dermatosis and the use of radioiodine for contrast, we assessed the patient's serum iodine and urine iodine. These were both high at 1.02 mmol L-1 (reference interval 0.32- 0.63) and 3.46 mmol L-1 (reference interval 0.0-2.43), respectively. A diagnosis of iododerma was made. The patient's eruption slowly resolved and at 12 weeks there was evidence of postinflammatory skin changes only. Her urine and serum iodine were rechecked, and both had normalized. In the last 20 years there have been approximately 20 case reports of iododerma. Most have been following iodine contrast use in patients with abnormal kidney function, like our patient. Most describe an acneiform eruption that subsequently evolves to vegetative plaques (Chalela JG, Aguilar L. Iododerma from contrast material. N Engl J Med 2016;374: 2477). Iododerma is largely a diagnosis of exclusion, but histopathology and urine and serum iodine levels can help support diagnosis.

Neutrophilic dermatosis with necrobiotic changes as an unusual manifestation after the first shot of a COVID-19 mRNA vaccine together with a high fever and liver injury

Coronavirus disease 19 (COVID-19) mRNA vaccines sometimes cause various skin rashes. We report an unusual case of erythema nodosum-like nodules with vesicular and pustular papules, which arose after the first shot of a COVID-19 mRNA vaccine. A skin biopsy showed marked neutrophilic infiltration with necrobiotic changes throughout the dermis and subcutis. Immunohistochemically, CD8+ cells were much more common than CD4+ cells in the dense neutrophilic infiltrates. Many CD68+ macrophages were present around the CD8+ cells. No cases of neutrophilic dermatosis with necrobiotic changes have been reported. Thus, our findings should be added to the cutaneous adverse effects of the vaccines.

Autoimmunity-related neutrophilic dermatosis after coronavirus disease 2019 vaccination: A case report and literature review.

Autoimmune diseases triggered by coronavirus disease 2019 (COVID-19) mRNA vaccination have been emerging. Here, we report the case of a 27-year-old Japanese man with autoimmunity-related neutrophilic dermatosis, occurring as an initial cutaneous manifestation of systemic lupus erythematosus with Sjögren syndrome after the second dose of the Pfizer/BioNTech COVID-19 vaccination. The patient presented with urticarial erythema and partially annular erythema on the trunk and extremities with severe pruritus. Histopathological analysis showed vacuolar degeneration at the dermo-epidermal junction and interstitial neutrophil infiltration. We reviewed eight patients, including the aforementioned patient, with exacerbation or new-onset of SLE after COVID-19 vaccination and found the patient had relatively mild symptoms, itchy annular erythema, and positive anti-SS-A/SS-B antibodies. COVID-19 mRNA vaccination can induce the production of type-I interferon, which plays a crucial role in the pathogenesis of SLE and may cause autoimmunity-related neutrophilic dermatosis in susceptible individuals. In the case that itchy annular erythema develops approximately 2 weeks after the vaccination, the possibility of systemic or cutaneous lupus erythematosus should be considered. For an accurate diagnosis, dermatologists should obtain a recent vaccination history and perform complete antibody profiling and skin biopsy for patients presenting with annular or erythema multiforme-like lesions.

Atypical presentation of Sweet syndrome with nodular erythema and oral ulcerations provoked by Ad26.COV2.S SARS-CoV-2 vaccination and review of literature.

The aim of this article is to present the case of acute febrile neutrophilic dermatosis (Sweet syndrome-SS) after Ad26.COV2.S vaccination against SARS-CoV-2. To the best of our knowledge, this is the second case of SS provoked by this specific vaccine. What is more, the mildly symptomatic beginning of the disease, later followed by typical SS manifestation with a variety of symptoms including nodular erythema of the feet and oral ulcerations, made it very challenging to establish the diagnosis. The article focuses on the current literature on the acute febrile neutrophilic dermatosis, along with the coexistence with other neutrophilic dermatoses and anti-SARS-CoV-2 vaccinations as provoking factors. It emphasizes the necessity for sharing the knowledge and experience on the subject of SS's clinical manifestations and underlying causes to facilitate prompt diagnosis and introduction of appropriate treatment.

Neutrophilic dermatosis with necrobiotic changes as an unusual manifestation after the first shot of a COVID ‐19 mRNA vaccine together with a high fever and liver injury

Coronavirus disease 19 (COVID-19) mRNA vaccines sometimes cause various skin rashes. We report an unusual case of erythema nodosum-like nodules with vesicular and pustular papules, which arose after the first shot of a COVID-19 mRNA vaccine. A skin biopsy showed marked neutrophilic infiltration with necrobiotic changes throughout the dermis and subcutis. Immunohistochemically, CD8(+) cells were much more common than CD4(+) cells in the dense neutrophilic infiltrates. Many CD68(+) macrophages were present around the CD8(+) cells. No cases of neutrophilic dermatosis with necrobiotic changes have been reported. Thus, our findings should be added to the cutaneous adverse effects of the vaccines.

LUNG INVOLVEMENT in VEXAS SYNDROME

Background: Vacuoles, E1 enzyme, X-linked, autoinfammatory, somatic (VEXAS) syndrome is a recently identifed disorder caused by somatic mutations in the UBA1 gene of myeloid cells. Various manifestations of pulmonary involvement have been reported, but a detailed description of lung involvement and radiologic fndings is lacking. Objectives: To describe lung involvement in VEXAS syndrome. Methods: A retrospective cohort study was conducted of all patients iden-tifed at the Mayo Clinic with VEXAS syndrome since October 2020. Clinical records and chest high resolution computed tomography (HRCT) scans were reviewed. Results: Our cohort comprised 22 white men with a median age of 69 years (IQR 62-74, range 57-84). Hematologic disorders including multiple myeloma, myelodysplastic syndrome and pancytopenia were present in 10 patients (45%), rheumatologic diseases including granulomatosis with poly-angiitis, IgG4-related disease, polyarteritis nodosa, relapsing polychondritis, and rheumatoid arthritis were found in 10 patients (45%), and 4 patients had dermatologic presentations including Sweet syndrome, Schnitzer-like syndrome or drug rash with eosinophilia skin syndrome (DRESS). VEXAS syndrome-related features included fever (18, 82%), skin lesions (20, 91%), lung infiltrates (12, 55%), chondritis (10, 45%), venous thromboembolism (12, 55%), macrocytic anemia (21, 96%), and bone marrow vacuoles (21, 96%). Other manifestations observed were arthritis, scleritis, hoarseness and hearing loss. Median erythrocyte sedimentation rate (ESR) was 69 mm/1st hour (IQR 34.3-118.8) and median C-reactive protein (CRP) of 55.5 mg/dL (IQR 11.4-98.8). The somatic mutations affecting methionine-41 (p.Met41) in UBA1 gene were: 11 (50%) p.Met41Thr, 7 (32%) p.Met41Val, 2 (9%) p.Met41Leu, and 2 (9%) in the splice site. All patients received glu-cocorticoids (GC) (median duration of treatment was 2.6 years);21 (96%) received conventional immunosuppressive agents (methotrexate, aza-thioprine, mycophenolate, leflunomide, cyclosporin, hydroxychloroquine, tofacitinib, ruxolitinib) and 9 (41%) received biologic agents (rituximab, tocilizumab, infliximab, etanercept, adalimumab, golimumab, abatacept). Respiratory symptoms included dyspnea and cough present in 21 (95%) and 12 (55%), respectively, and were documented prior to VEXAS diagnosis. Most of the patients were non-smokers (14, 64%) and obstructive sleep apnea (OSA) was present in 11 patients (50%). Seven patients (32%) used non-invasive ventilation, 6 used C-PAP, and 1 used Bi-PAP. Bronchoalveolar lavage (BAL) was available in 4 patients, and the findings were compatible with neutrophilic alveolitis in 3. Two patients had lung biopsies (2 transbronchial and 1 surgical) that showed ATTR amyloidosis and organizing pneumonia with lymphoid interstitial pneumonia, respectively. Pulmonary function tests were available in 9 (41%) patients and showed normal results in 5;3 patients had isolated reduction in DLCO and 1 with mild restriction. On chest HRCT, 16 patients (73%) had parenchymal changes including ground-glass opacities in 9, septal thickening in 4, and nodules in 3;pleural effusions were present in 3 patients, air-trapping in 3 patients and tracheomalacia in 1 patient. Follow-up chest HRCT was available for 8 patients (36%), the ground-glass opacities resolved in 5 patients, 3 patients manifested new or increased ground-glass opacities, and 1 patient had increased interlobular septal thickening. After 1 year of follow-up, 4 patients (17%) had died;3 due to pneumonia (2 COVID-19,1 bacterial) and 1 due to heart failure. VEXAS flares occurred in 18 patients (82%), the maximum number of relapses was 7, and they were mainly managed with GC and with changes in the immuno-suppressive regimen. Conclusion: Pulmonary involvement was documented by chest HRCT in most patients with VEXAS syndrome. Respiratory symptoms occurred in over one half of patients and about 20% had PFT abnormalities. The pulmonary manifestations of VEXAS are nonspecifc and characterized predominantly by infamma-tory parenchymal involvement.

SWEET SYNDROME IN ACUTE MYELOGENOUS LEUKEMIA- A CASE REPORT

CASE: Patient is a 63 y/o F with PMH of relapsed AML on treatment with Gilteritinib, Meniere's Disease, asthma, GERD, PRA positive, CKD Stage 3. She was on cycle 1 day + 20 of Gilteritinib when she presented with a neutropenic fever of 101.9. She reported congestion and headache. She was pan cultured and started on empiric Cefepime. Her blood cultures, COVID test and CXR were all negative for sources of infection. Eventually, Cefepime was stopped, and she was transited to PO Cefdinir and Cipro but redeveloped fevers and a maculopapular rash. Repeat pan-cultures were negative. Antibiotics were broadened to Merrem, Linezolid and Cresemba and her fevers improved. However, the rash continued to worsen. There was concern that nodular rash was secondary to infection or possible drug reaction from her antibiotics. Her rash showed no improvement with Benadryl or withholding drugs. She underwent skin punch biopsy before discharge. Biopsy showed florid superficial inflammation with benign ulcer that was highly suggestive of Sweet Syndrome given history of AML. IMPACT/DISCUSSION: Sweet syndrome (SS), or acute febrile neutrophilic dermatosis is a rare inflammatory condition characterized by painful cutaneous nodules and neutrophilic infiltrate in the dermis, in the absence of vasculitis. This syndrome is associated with malignancies with AML and MDS being the most reported. Malignancy associated Sweet Syndrome accounts for 15-20% of cases of SS. The atypical production of both pro-inflammatory cytokines (IL - 6, TNF - alpha) and signaling molecules demonstrated in AML is suspected to affect neutrophil function leasing to dermal clumping of the mature neutrophils. In our patient the fever presented prior to the rash with sudden onset of nodular as it has been commonly reported in literature review. Glucocorticoids, either topical or systemic, together with antibiotics and wound care, represent the mainstays of SS therapy. The rash heals without scarring if no ulcerations are present. The signs and symptoms of Sweet syndrome can mimic infection and be treated inaccurately, thus, it is important to make a correct diagnosis. Our patient's tissue cultures were negative for microorganisms. She was started on glucocorticoid with good response in regards to her rash but did have some scars and hyperpigmentation. Unfortunately due to her aggressive AML and complications patient elected to go to Hospice. CONCLUSION: When SS is established, the physician should keep a high index of suspicion to search underlying malignancies. Sweet Syndrome generally responds promptly to treatment with glucocorticoid.

What to expect when AGEP is induced by terbinafine? Case report and critical review of the literature.

BACKGROUND: Acute Generalised Exanthematous Pustulosis (AGEP) is a rash with multiple sterile intraepidermal or subcorneal non-follicular pustules on edematous papules, with a sudden development and rapid evolution, triggered by drugs, vaccination, insect bites, exposure to mercury, and allergens. OBJECTIVES AND METHODS: We describe a female patient who developed extensive and abnormally prolonged AGEP following exposure to terbinafine and SARS-CoV vaccine. A detailed review of terbinafine-induced-AGEP cases was performed, with the aim of evaluating if the AGEP criteria would follow a different pattern when the disease is triggered by this drug. A PubMed search helped retrieve all terbinafine-induced AGEP case reports. AGEP-specific Sideroff criteria were analysed in terbinafine-induced cases and compared to other trigger causes. CONCLUSIONS: When the AGEP causative drug was terbinafine, a delay in recovery was observed, compared to the existing AGEP criteria when other causes are considered. Terbinafine frequently leads to delayed resolution AGEP probably due to the presence of the drug in the skin for several weeks after exposure, even after discontinuation, and the disease severity may be potentialised by additional factors such as concomitant viral infections or vaccination.

Neutrophilic Dermatosis and Management Strategies for the Inpatient Dermatologist.

Purpose of Review: Neutrophilic dermatoses are a heterogeneous group of disorders with significant overlap in associated conditions, clinical presentation, and histopathologic features. This review provides a structural overview of neutrophilic dermatoses that may present in the inpatient setting along with diagnostic work-up and management strategies. Recent Findings: Sweet's syndrome has been found in patients with coronavirus disease 2019 (COVID-19). Pyoderma gangrenosum (PG) has been shown to be equally associated with ulcerative colitis and Crohn's disease. A clinical trial shows that cyclosporine is equally effective as prednisone in treating PG. Neutrophilic eccrine hidradenitis has been found in the setting of newer antineoplastic medications, such as BRAF inhibitors, as well as in the setting of malignancy without chemotherapy exposure. Summary: Neutrophilic dermatoses are a rare and complex group of dermatoses with varying and overlapping clinical presentations. Physicians should be aware of the growing list of associated diseases in order to build a better differential diagnosis or to potentially investigate for co-existing disease.

Sweet syndrome induced by adenovirus vector CoViD-19 vaccine

Introduction: Sweet syndrome (SS) is a rare skin disease, characterized by rapid onset of plaques or nodules with extensive infiltration of neutrophils into epidermidis and dermis. Three main types of SS are known: classical or idiopathic, malignancy-associated, drug-induced. Case report: A 69 yo woman was admitted because of recent pirexya, painful and asymmetric erythematous plaques on legs and buttock, painful wrist and elbow tenderness for 6 days. History: hypertension and dyslipidemia. Eighteen days before she received Vaxzevria first dose. Physical examination revealed normal findings except of skin lesions. Biohumoral exams showed increased CRP, normal GB count;negative SARS-CoV-2 test, as well as HBV, HCV, CMV, EBV, Quantiferon, ANA, ANCA, LAC. C3 and C4 were normal. Blood and skin coltures were negative. Chest X-ray, ECG, ecocardiography, EGDS, colonscopy, PET TC were all normal. A broad spectrum antibiotic and anti-inflammatory therapy was initially set (vasculitis vs staphylococcus infection). Skin biopsy was performed: it showed a dense interstitial neutrophilic infiltrate of the dermis, according with SS. Corticosteroid therapy caused a prompt improvement of skin lesions. Conclusions: A classical SS induced by SARS-CoV-2 vaccine was diagnosed at the discharge. A vaccine-associated SS is well known: some post CoViD and post mRNA SARS-CoV-2 vaccine SS are described in literature. This is probably the first case of a SS induced by SARS-CoV-2 adenovirus vaccine. An alert was sent to AIFA.