Dermal Neutrophilic Infiltrate Research Articles

A rare case of Acute Febrile Neutrophilc Dermatosis – Sweet’s syndrome

Sweet syndrome is an inflammatory dermatosis characterized by non-itchy, sometimes tender, erythematous plaques and papules most commonly distributed on the arms, upper body, head and neck. Histological findings include a dense dermal neutrophilic infiltrate with oedema. We report a case of 32year old female patient with solitary well defined erythematous edematous plaques with whitish scales at the centre of the lesion present over the extensor aspect of left forearm since 5days with sparing of palms , soles and mucosae. Laboratory investigations and histopathology were suggestive of Neutrophilic dermatoses (Sweet’s syndrome). This case was presented to highlight Atypical presentationof sweet syndrome – annular morphology and localization of lesions only over left forearm Therefore high index of suspicion is needed for its diagnosis in cases of solitary and isolated presentation along with necessary histopathological and laboratory investigations.

Sweet Syndrome in Early Infancy

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an uncommon inflammatory disease in pediatrics. It presents with fever, blood neutrophilia, and painful erythematous plaques with a dermal neutrophilic infiltrate. In general, it is associated with infections, hematologic and solid tumor, immunodeficiency, and certain drugs. It can easily be mistaken for infection and can lead to prescribe antibiotics or antiviral agents. Here, we describe a case of a 6-week-old infant who developed SS following a pulmonary infection. The patient presented with ocular manifestations and fully recovered after 1 week of corticosteroids.

16783 Prompt identification of primary cutaneous nocardiosis utilizing immunohistochemical staining: A case report

A 72-year-old man with a history of renal transplantation (maintained on mycophenolate, tacrolimus, and prednisone) sustained a laceration to the right forearm after a fall onto gravel. Three weeks later, he reported onset of a painful, pustular rash of the right extensor arm. Before admission, he did not respond to outpatient clindamycin or ceftriaxone. HSV/VZV PCR swabs, blood cultures, and tissue fungal stain were negative. Preliminary hematoxylin and eosin evaluation showed extensive dermal neutrophilic infiltrate. Acid-fast bacilli (AFB) culture smear showed 2+ AFB with initial concern for a rapidly growing nontuberculosis mycobacterium. However, tissue gram and acid-fast stains showed rare, equivocal and weakly staining filamentous structures within dermal abscesses, which were highlighted and confirmed by immunohistochemical (IHC) staining. Consequently, the patient was diagnosed with primary cutaneous nocardiosis, and the antimicrobial regimen was altered, resulting in gradual clinical improvement on linezolid and amoxicillin-clavulanate. The presented case demonstrates the diagnostic challenge of distinguishing Nocardia from mycobacteria, as both grow on the same media, show similar colony morphology, and demonstrate acid-fast staining. Unfortunately, features of Nocardia, such as acid-fast staining and filamentous cell morphology, can be equivocal. We utilized a mycobacterium tuberculosis IHC stain with cross-reactivity to Nocardia to rapidly confirm our suspicion. In the current case, the utilization of an IHC stain allowed for prompt presumptive identification of Nocardia (initially thought to be NTM) and subsequent timely alteration of antimicrobials prior to confirmation of Nocardia brasiliensis via culture.

Sweet syndrome as an adverse reaction to tyrosine kinase inhibitors: A review.

Tyrosine kinase inhibitors are a class of targeted anticancer drugs that inhibit cancer cell proliferation by inactivating proteins involved in signal transduction cascades. Various cutaneous adverse events have been observed after tyrosine kinase inhibitor administration, including Sweet syndrome. We queried the PubMed database to identify 14 cases of Sweet syndrome thought to be secondary to tyrosine kinase inhibitors. Tyrosine kinase inhibitor-induced Sweet syndrome had a median of 2 months latency following drug administration. All cases but one had morphologic features classic for Sweet syndrome (erythematous and tender papules, plaques, or nodules). All cases also had classic histopathologic findings (dermal neutrophilic infiltrate without vasculitis or necrosis). Using diagnostic criteria for drug-induced Sweet syndrome and the Naranjo Drug Reaction Probability Scale for a drug-induced cutaneous eruption, we found that six cases favored a drug-induced etiology over malignancy, two cases favored a malignancy-associated Sweet syndrome, and the remaining eight met drug-induced Sweet syndrome criteria but had low Naranjo scores. Nine cases resulted in medication discontinuation, while five cases continued anticancer therapy and were treated only with corticosteroids with quick resolution of skin lesions. Dermatologists should be aware of this adverse cutaneous reaction to tyrosine kinase inhibitors and should treat on a case-by-case basis, though limited evidence in this review suggests that oncologic therapy may safely be continued with prompt corticosteroid treatment.

Contrast Media-Induced Iododerma Around the Eyes

A 62-year-old man who required hemodialysis thrice weekly developed an asymptomatic eyelid rash. Two days before presentation he had undergone computed tomography with iodinated contrast. Scheduled hemodialysis was performed 22 hours later. Examination disclosed several firm eyelid nodules, some of which were hemorrhagic (Fig A), and swelling around the meibomian gland orifices (Fig B). Biopsy evinced a dense dermal infiltrate of neutrophils and histiocytes (Fig C). Iododerma, a hypersensitivity reaction to iodine, was diagnosed; impaired renal clearance of iodine is a known risk factor.

Pyoderma gangrenosum and chronic granulomatous disease treated with adalimumab: Case-based review

BackgroundChronic granulomatous disease (CGD) is a rare immunodeficiency disorder that manifested by recurrent severe bacterial and fungal infection. It may be associated with non-infectious inflammatory complications that affect gastrointestinal tract, lung and skin. Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterizes by painful cutaneous ulceration. The coexistence of PG and CGD is very rare and the treatment is challenging; only few cases have been reported. Aim of the workTo describe the features and management of a challenging case of PG associated with CGD. Case reportA 20-year old male with a long history of recurrent bacterial and fungal infections due to CGD presented to the Rheumatology and Immunology outpatient clinic at Mansoura University hospital with an ulcerative cutaneous lesion with exudation and crusting on the left lateral malleolus. There were elevated inflammatory markers: erythrocyte sedimentation rate (ESR) 130 mm/1st h and C-reactive protein (CRP) 52 mg/dl. Histological examination of the lesion revealed diffuse dermal infiltrate of neutrophils and nuclear dust admixed with some histiocytes, lymphocytes and plasma cells, a picture suggestive of PG. Systemic and musculoskeletal examination were unremarkable except for low grade fever (37.7 °C). Conventional immunosuppressives were not satisfactory and adalimumab (40 mg/2 weeks) was added showing significant improvement of the lesion (ESR 7 mm/h, CRP 3 mg/dl). ConclusionCGD is a rare primary immunodeficiency disorders that can be associated with PG. The coexistence of these two conditions requires judicious use of immunosuppressive agents. However; adalimumab may be an effective and safe treatment option.

363 Systemic sphingosine 1-phosphate receptor 2 (S1PR2) deficiency facilitates dermal neutrophil infiltration against S. aureus infection

Background: Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator generated in the skin when cell membrane or barrier components are damaged. S1P regulates a variety of cell activities via different S1P receptors (S1PR). Keratinocytes express S1PR1-5. We have already reported that, in normal human epidermal keratinocytes, S1PR1 and 2 control neutrophil migration-related proinflammatory cytokine expression and secretion, respectively, in vitro. As a next step, we decided to evaluate the role of S1PR2 in bacterial skin infection in vivo environment. Methods: A mouse model that lack S1PR2 (S1pr2-/- mouse) was used for the study and compared to wild type (WT); S. aureus was applied on the skin and S. aureus bacterial supernatant was injected intradermally; qPCR was used to evaluate cytokine gene expressions; filaggrin2 expression and neutrophil infiltration were evaluated by histologically. Results: Both S. aureus epicutaneous application and S. aureus supernatant intradermal injection on S1pr2-/- mouse skin showed more dermal neutrophil infiltration. S1pr2-/- mouse dermis showed more severe dermal inflammation with higher proinflammatory cytokine expressions. These data were accompanied by an increased skin barrier permeability and a decrease in filaggrin2. These data suggest that, although the lack of S1pr2-/- in the epidermis decreases the proinflammatory cytokines response, the increased barrier permeability drives a strong dermal inflammation due to bacteria penetration. Conclusions: The lack of S1pr2 shows two different activities in the skin, while it decreases the epidermal proinflammatory response to S1P signal, it also increases permeability to pathogens and promotes infections.

Essential role of CCL2-CCR2 axis in the pathogenesis of chronic irritant contact dermatitis

Abstract Chronic irritant contact dermatitis (ICD) including hand eczema is a common skin disorder caused by the repetitive exposure to irritants such as chemical detergents and organic solvents. Products including sodium dodecyl sulfate (SDS), such as soap or shampoo, are the leading cause of occupational ICD. Previous studies have shown that irritants cause epidermal damage which induce the production of proinflammatory mediators, followed by a dermal influx of inflammatory cells. However, the detailed immunological cascades occurring in the chronic ICD remains unclear. Repeated application of SDS, onto murine ear skin induced ear swelling, accompanied by epidermal hyperplasia and barrier dysfunction. Dermal infiltration of neutrophils, eosinophils and monocytes were remarkable in the SDS-applied skin. Our observation described above was consistent with the features of human chronic ICD. Here, we found that CCR2 deficiency or blockade of CCL2, a major ligand for CCR2, significantly attenuated SDS-induced ear swelling as well as inflammatory cell accumulation. Among the differentially expressed genes, which were up-regulated by SDS application, genes related to cell interaction at the vascular wall were significantly affected by CCR2 deficiency. Further, we investigated whether CCR2 on radiosensitive cells or radioresistant cells is critical. Lethally irradiated CCR2−/− mice transplanted with CCR2+/+ bone marrow cells (BMC) exhibited impaired SDS-induced ICD, while CCR2+/+ mice transplanted with CCR2−/− did not. Collectively, our data suggest that CCR2 expression by radioresistant cells plays an essential role in the pathogenesis of chronic ICD.

Afebrile and Leukopenic Sweet's Syndrome Following Partial Ileectomy in an Elderly Woman

Afebrile and Leukopenic Sweet's Syndrome Following Partial Ileectomy in an Elderly Woman

2070 Sweet's Syndrome as the Initial Presentation of Crohn's Disease

INTRODUCTION: The diagnostic criteria for Sweet's syndrome include fever, peripheral neutrophilia, erythematous skin lesions and diffuse neutrophilic dermal infiltrate. Classically, the lesions and symptoms promptly improve with the initiation of systemic corticosteroids. This is a rare case of Sweet’s syndrome as the initial presentation of Crohn’s disease. CASE DESCRIPTION/METHODS: A 23-year-old African-American male with no past medical history presented to our ED with fever and rash. He reported a sudden onset mildly sensitive rash on his bilateral lower extremities, preceded by two weeks of fever, myalgia and headaches. He denied arthralgia but endorsed recent weight loss and sporadic aphthous ulcers. He developed watery, non-bloody diarrhea in the ED. His abdomen was soft and non-tender. Examination of the rash revealed erythematous nodules, some studded with pustules and a few ulcerated nodules. He was febrile to 102.7 ºF with tachycardia. Labs were significant for leukocytosis at 22.5 (68% neutrophils), thrombocytosis at 515, microcytic anemia (Hb 9.6), elevated inflammatory markers (CRP 326 mg/L; ESR >130 mm) and AST:ALT 64:41 U/L. Broad spectrum antibiotics were started due to concerns for sepsis. Blood, wound, and stool cultures, including Clostridium difficile were all negative. Fecal calprotectin was 32. His immunological workup showed ANA, RF and anti-GBM negative; normal IgM, IgG, IgA, C3 and C4. HIV, Hepatitis B and C and QuantiFERON were also negative. ANCA was positive at 1:320, with positive PR3. CT scan of the abdomen showed proctitis and ascending colitis with no lymphadenopathy. Colonoscopy showed mild-moderate inflammation of the left sided colon with skip lesions in the transverse colon, without terminal ileum involvement, with biopsies showing focal acute cryptitis and rare crypt abscesses. Skin biopsy revealed neutrophilic dermatitis and panniculitis without vasculitis. Once infection was ruled out, prednisone 60 mg was started and the rash and fever rapidly improved. DISCUSSION: Sweet’s syndrome is considered part of the family of neutrophilic dermatoses, which also includes pyoderma gangrenosum, and is considered an unusual extra-intestinal manifestation of IBD. Sweet's syndrome is also associated with malignancies, infections, pregnancy and medications. The temporal relationship between Sweet's syndrome and IBD activity is variable, but the majority of cases present after the diagnosis of IBD, with few cases in the literature with Sweet’s syndrome as the presenting symptom for IBD.

Pyoderma gangrenosum: a presenting sign of myelodysplastic syndrome in undiagnosed Fanconi anemia

A 26-year-old man with a history of congenital bilateral microtia, unilateral renal agenesis, left aural atresia, and right external auditory canal occlusion admitted for right rib cartilage graft harvest and left ear re-construction. Following surgery, an ulceration with violaceous borders and a yellow fibrinous base unresponsive to broad-spectrum antibiotics developed at the harvest site. The wound was expanding and not responsive to systemic broad-spectrum antibiotics. Biopsy revealed a dense dermal infiltrate of neutrophils with negative tissue cultures consistent with pyoderma gangrenosum (PG). He was treated with systemic, intralesional, and topical steroids, as well as doxycycline. Three weeks after the diagnosis of PG, he was found to have persistent anemia and leukopenia. Bone marrow aspiration analysis was consistent with hypocellular myelodysplastic syndrome and genetic testing was consistent with Fanconi anemia. There is a well-known association of PG with hematological disorders. Fanconi anemia is a rare genetic hematologic disorder with congenital defects leading to bone marrow failure and malignancy in long-standing disease. In our patient, we consider his development of PG a paraneoplastic sign associated with the onset of his hypocellular myelodysplastic syndrome.

Clinical and histopathological analysis of 313 cases of psoriasis

Objective To analyze clinical manifestations and histopathological features of 6 subtypes of psoriasis presenting mainly as skin manifestations. Methods Clinical and histopathological data were collected from 313 patients with psoriasis in the Department of Dermatology of Xijing Hospital between 2013 and 2017, and analyzed retrospectively. Results Among the 313 patients, there were 31 patients with guttate-type psoriasis mainly induced by upper respiratory tract infections, 60 with plaque psoriasis with the main precipitating factors being upper respiratory tract infections, overexertion, cold weather and so on, 42 with erythrodermic psoriasis induced mainly by the withdrawal of systemic glucocorticoids, 60 with generalized pustular psoriasis with the main precipitating factors being upper respiratory tract infections, pregnancy, drugs and so on, 60 with palmoplantar pustulosis without definite precipitating factors, and 60 with acrodermatitis continua without definite precipitating factors. The 6 subtypes of psoriasis had similar typical pathological manifestations, including parakeratosis, Munro′s microabscess and/or spongiform pustules of Kogoj, thinning or absence of the granular layer, psoriasis-like epidermal hyperplasia, capillary ectasia in the dermal papillae, lymphocytic infiltration and so on. Atypical pathological manifestations were observed in 98 (31%) of the 313 patients, which included 4 with guttate type psoriasis (13%) , 3 with plaque psoriasis (5%) , 12 with erythrodermic psoriasis (29%) , 41 with generalized pustular psoriasis (68%) , 12 with palmoplantar pustulosis (20%) and 26 with acrodermatitis continua (43%) . These atypical pathological manifestations included serous fluid exudation, irregular epidermal hyperplasia, non-neutrophilic spongiosis, keratinocyte necrosis, dermal neutrophilic infiltration and dermal eosinophilic infiltration. Conclusions Different subtypes of psoriasis have different clinical manifestations and similar typical histopathological features. Atypical pathological features can interfere with the diagnosis of psoriasis, and attention should be paid to the differential diagnosis. Key words: Psoriasis; Retrospective studies; Clinical manifestation; Histopathology

Topical delivery of l-theanine ameliorates TPA-induced acute skin inflammation via downregulating endothelial PECAM-1 and neutrophil infiltration and activation

l-theanine, the most abundant free amino acid in tea, has been documented to possess many different bioactive properties through oral or intragastrical delivery. However, little is known about the effect of topical delivery of l-theanine on acute inflammation. In the present study, by using 12-O-tetradecanoylphorbol-13-acetate (TPA, 2.5 μg/ear)-induced ear edema model in mice, we first found that single-dose local pretreatment of l-theanine 30 min before TPA time- and dose-dependently suppressed the increases in both skin thickness and weight. Subsequently l-theanine ameliorated TPA-induced erythema, vascular permeability increase, epidermal and dermal hyperplasia, neutrophil infiltration and activation via downregulating the expression of PECAM-1 (a platelet endothelial adhesion molecule-1) in blood vessels and the production of pro-inflammatory cytokines IL-1β, TNF-α, and mediator cyclooxygenase-2 (COX-2), which is mainly expressed in neutrophils. It highlighted the potential of l-theanine as a locally administrable therapeutic agent for acute cutaneous inflammation.

Schnitzler syndrome, a rare autoinflammatory disease. Complete response to IL-1 blockade.

The Schnitzler syndrome (SCS) is a rare, late-onset acquired autoinflammatory syndrome often underdiagnosed. The diagnosis is based on the Lipsker and recently on validated Strasbourg diagnostic criteria (chronic urticarial rash, monoclonal gammopathy, intermittent fever, arthritis, arthralgia, bone involvement, hepatomegaly, splenomegaly, lymphadenopathy, dermal infiltration of neutrophils and laboratory markers of inflammation). Conventional therapies including anti-histamines, anti-inflammatory drugs, corticosteroids and immunosuppressive drugs that are usually ineffective. Recently the gold standard therapy of SCS are considered IL-1 blocking agents as anakinra, canakinumab, rilonacept that led to a significant control of clinical symptoms, even if a relapse could appear at suspension of the treatment. We report a case of a 63-year-old man with a recent diagnosis of SCS - after 6 years of symptoms of disease - refractory to several conventional immunosuppressive therapies and treated with anakinra, with sustained remission of clinic manifestations during treatment at 24 months of follow up.

Clinical, histological, immunological presentations and outcomes of bullous systemic lupus erythematosus: 10 New cases and a literature review of 118 cases.

Bullous systemic lupus erythematosus (BSLE) is a rare blistering condition associated with systemic lupus erythematosus (SLE). We conducted a multi-center retrospective study and literature review in order to describe the clinical, immunological, and histological presentations and outcomes of BSLE. The skin biopsies were centrally reviewed, and sera obtained during a flare of BSLE were analyzed for identification of circulating anti-basement membrane zone antibodies. Ten patients (all women, median age at SLE diagnosis of 22 years) were included, as well as 118 cases from a systematic review of the literature. Lupus nephritis was associated in 50% of the cases. BSLE presented as tensed bullae on normal or erythematous skin, predominantly localized on the trunk, arms, head, and neck. Urticarial lesions were associated in 31% of the cases, and mucous membrane involvement was seen in 51%. Histological analyses displayed subepidermal detachment, dermal infiltration of polynuclear neutrophils, alignment of these cells at the basal membrane zone and leukocytoclasis. The direct immunofluorescence was polymorphic, showing linear and/or granular deposits of IgG, IgA, IgM, and/or C3. Anti-type VII collagen antibodies were detected in 69% of cases. Dapsone was efficacious in 90% of cases. BSLE is rather an autoimmune neutrophilic blistering disease associated with SLE than a cutaneous manifestation and may be associated with active extra-cutaneous manifestations of SLE. Dapsone is the first-choice option.

Clinico-pathological features of erythema nodosum leprosum: A case-control study at ALERT hospital, Ethiopia.

BackgroundLeprosy reactions are a significant cause of morbidity in leprosy population. Erythema nodosum leprosum (ENL) is an immunological complication affecting approximately 50% of patients with lepromatous leprosy (LL) and 10% of borderline lepromatous (BL) leprosy. ENL is associated with clinical features such as skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. ENL is treated mainly with corticosteroids and corticosteroids are often required for extended periods of time which may lead to serious adverse effects. High mortality rate and increased morbidity associated with corticosteroid treatment of ENL has been reported. For improved and evidence-based treatment of ENL, documenting the systems affected by ENL is important. We report here the clinical features of ENL in a cohort of patients with acute ENL who were recruited for a clinico-pathological study before and after prednisolone treatment.Materials and methodsA case–control study was performed at ALERT hospital, Ethiopia. Forty-six LL patients with ENL and 31 non-reactional LL matched controls were enrolled to the study and followed for 28 weeks. Clinical features were systematically documented at three visits (before, during and after predinsolone treatment of ENL cases) using a specifically designed form. Skin biopsy samples were obtained from each patient before and after treatment and used for histopathological investigations to supplement the clinical data.ResultsPain was the most common symptom reported (98%) by patients with ENL. Eighty percent of them had reported skin pain and more than 70% had nerve and joint pain at enrolment. About 40% of the patients developed chronic ENL. Most individuals 95.7% had nodular skin lesions. Over half of patients with ENL had old nerve function impairment (NFI) while 13% had new NFI at enrolment. Facial and limb oedema were present in 60% patients. Regarding pathological findings before treatment, dermal neutrophilic infiltration was noted in 58.8% of patients with ENL compared to 14.3% in LL controls. Only 14.7% patients with ENL had evidence of vasculitis at enrolment.ConclusionIn our study, painful nodular skin lesions were present in all ENL patients. Only 58% patients had dermal polymorphonuclear cell infiltration showing that not all clinically confirmed ENL cases have neutrophilic infiltration in lesions. Very few patients had histological evidence of vasculitis. Many patients developed chronic ENL and these patients require inpatient corticosteroid treatment for extended periods which challenges the health service facility in resource poor settings, as well as the patient’s quality of life.

Neutrophilic Dermatosis of the Hands: A Review of 17 Cases.

Neutrophilic dermatosis of the hands is an inflammatory skin condition related to Sweet syndrome that responds to corticosteroids. It commonly affects the dorsum of the hand and often mimics infection, with violaceous inflammatory papules and plaques that may ulcerate. The aim of this study was to review the clinical presentation of neutrophilic dermatosis of the hands. A retrospective review was undertaken of all cases of neutrophilic dermatosis of the hands seen at a tertiary hospital in New South Wales, Australia, over a 5-year period. Seventeen cases were identified. The mean time to diagnosis was 9 days after lesion onset. Most cases were older adults (mean age, 71 years). The most common referral diagnoses were infection or a nonhealing wound and 65% of cases reported a history of trauma. The dorsal index finger was the site of involvement in 41% of cases. One case involved the palm.Histopathology reports were available for skin punch biopsy for 14 of 17 cases, which showed dermal neutrophilic infiltrate (93%) and epidermal involvement with necrosis, ulceration, or pustulation (64%). Six cases were treated surgically prior to the correct diagnosis and management being introduced. Neutrophilic dermatosis of the hands was often misdiagnosed as infection. A history of trauma is common and may be misleading. Dermatological consultation and skin punch biopsy are useful in confirming the diagnosis, ideally prior to surgical management. Diagnostic IV.

Calcitriol Treatment Ameliorates Inflammation and Blistering in Mouse Models of Epidermolysis Bullosa Acquisita

A link between hypovitaminosis D and development of autoimmune bullous disorders has been suggested recently, but this association has not been elaborated experimentally. Here, the role of vitamin D was investigated in epidermolysis bullosa acquisita (EBA), an anti-type VII collagen autoantibody-induced blistering skin disease. Oral administration of the hormonally active vitamin D metabolite calcitriol ameliorated clinical disease severity and dermal neutrophil infiltration in both an antibody transfer- and immunization-induced EBA mouse model. Mechanistically, calcitriol hindered immune effector cell activation as evidenced by increased L-selectin expression on Gr-1+ cells in calcitriol-treated mice with antibody transfer-induced EBA, as well assuppressed invitro immune complex-induced reactive oxygen species production in calcitriol-treated murine neutrophils. Additionally, calcitriol administration was associated with an increase of regulatory T(CD4+FoxP3+) and B (CD19+IL10+) cells as well as reduction of pro-inflammatory T helper 17 (CD4+IL-17+) cells in mice with immunization-induced EBA. In line, levels of circulating anti-type VII collagen autoantibodies were lower in mice that received calcitriol compared to solvent-treated animals. Together with the observed state of hypovitaminosis D in most cases of an analyzed EBA patient cohort, the results of this study support the use of vitamin D derivatives or analogs for patients with EBA and related diseases.

Vitamin E isoforms (d α-tocopherol and δ-tocotrienol) promote healing of secondary skin wounds in diabetic rats

l-theanine, the most abundant free amino acid in tea, has been documented to possess many different bioactive properties through oral or intragastrical delivery. However, little is known about the effect of topical delivery of l-theanine on acute inflammation. In the present study, by using 12-O-tetradecanoylphorbol-13-acetate (TPA, 2.5 μg/ear)-induced ear edema model in mice, we first found that single-dose local pretreatment of l-theanine 30 min before TPA time- and dose-dependently suppressed the increases in both skin thickness and weight. Subsequently l-theanine ameliorated TPA-induced erythema, vascular permeability increase, epidermal and dermal hyperplasia, neutrophil infiltration and activation via downregulating the expression of PECAM-1 (a platelet endothelial adhesion molecule-1) in blood vessels and the production of pro-inflammatory cytokines IL-1β, TNF-α, and mediator cyclooxygenase-2 (COX-2), which is mainly expressed in neutrophils. It highlighted the potential of l-theanine as a locally administrable therapeutic agent for acute cutaneous inflammation.

Serum cytokine profile in pediatric Sweet\u2019s syndrome: a case report

BackgroundSweet’s syndrome is characterized by fever, leukocytosis, and tender erythematous papules or nodules. It is a rare condition, particularly in the pediatric population, and has recently been proposed to be an autoinflammatory disease that occurs due to innate immune system dysfunction, involving several cytokines, which causes abnormally increased inflammation. To the best of our knowledge, no report has documented the cytokine profile in a pediatric patient with Sweet’s syndrome.Case presentationA previously healthy 34-month-old Japanese girl was hospitalized because of remittent fever and pain in her right lower extremity with erythematous nodules. A skin biopsy of the eruption revealed dermal perivascular neutrophilic infiltration with no evidence of vasculitis, which led to the diagnosis of Sweet’s syndrome. She was prescribed with orally administered prednisolone and a prompt response was observed; then, the prednisolone dose was tapered. During treatment she developed upper and lower urinary tract infections, after which her cutaneous symptoms failed to improve despite increasing the prednisolone dosage. To avoid long-term use of systemic corticosteroids, orally administered potassium iodide was initiated, but it was unsuccessful. However, orally administered colchicine along with prednisolone effectively ameliorated her symptoms, and prednisolone dosage was reduced again.We analyzed the circulating levels of interleukin-1β, interleukin-6, interleukin-18, neopterin, and soluble tumor necrosis factor receptors I and II, in order to clarify the pathogenesis of Sweet’s syndrome. Of these cytokines, only interleukin-6 levels were elevated prior to orally administered prednisolone therapy. Following therapy, the elevated interleukin-6 levels gradually diminished to almost normal levels; interleukin-1β and interleukin-18 stayed within normal ranges throughout the treatment. Neopterin became marginally elevated after the start of treatment. Both soluble tumor necrosis factor receptor I and soluble tumor necrosis factor receptor II levels increased shortly after the onset of urinary tract infections.ConclusionsThis is the first case report of pediatric Sweet’s syndrome in which serum cytokine levels were investigated. Future studies should gather more evidence to elucidate the pathophysiology of Sweet’s syndrome.