A case of likely acute febrile neutrophilic dermatosis in a 17-year-old male presenting to general paediatrics.

We present the case of a 17-year-old male with a sore throat, tender cervical lymphadenopathy, bilateral erythematous and enlarged tonsils, fever, joint pain, widespread tender purpuric nodules, ulcerative lesions and erythematous pustules. The diagnosis was initially unclear. He had raised neutrophils, erythrocyte sedimentation rate and C-reactive protein. His skin biopsy showed a neutrophilic dermatosis with superficial pustulosis and leukocytoclastic vasculitis. Most likely, the patient suffered from a rare condition called acute febrile neutrophilic dermatosis (AFND). AFND is a very rare disorder of poorly understood aetiology, with only a few hundred reported cases in the literature. The complexity and rarity of this condition, and the difficulty in diagnosing, is an example of the challenge facing paediatricians as the paediatric admission age threshold increases to include older adolescents and young adults up to the age of 25 years, as per the National Health Service (NHS) long-term plan.

Paraneoplastic Dermatoses: A Brief General Review and an Extensive Analysis of Paraneoplastic Pemphigus and Paraneoplastic Dermatomyositis.

Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform an early diagnosis of the underlying neoplasm. Lack of familiarity with cutaneous clues of internal malignancy may delay diagnosis and treatment of cancer. In this review, we described several paraneoplastic dermatoses and discussed extensively two paradigmatic ones, namely paraneoplastic pemphigus and paraneoplastic dermatomyositis.

Sweet's Syndrome: A Classical Presentation of a Rare Disease.

Sweet's syndrome, also known as acute febrile neutrophilic dermatosis, is a rare disorder that typically presents with rapid appearance of tender skin lesions accompanied by fever and leukocytosis with neutrophilia. Its pathogenesis is not fully understood. The syndrome is generally classified into classical, malignancy-associated, and drug-induced categories, each of which has its specific characteristics. In this article, we present a case of classical Sweet's syndrome in a woman who presented with an acute viral illness.

Discriminatory features of acute eosinophilic dermatitis with oedema (Wells-like syndrome) and sterile neutrophilic dermatosis (Sweet's-like syndrome) in dogs.

BACKGROUND: Canine acute eosinophilic dermatitis with oedema (CAEDE) and sterile neutrophilic dermatosis have overlapping clinical and histopathological features. HYPOTHESIS/OBJECTIVES: The objective of this study was to identify features that differentiate these entities. ANIMALS: Forty dogs. METHODS AND MATERIALS: Retrospective case series. Forty cases with diagnoses of either CAEDE and/or sterile neutrophilic dermatosis were included based on histopathological review. Medical records (29 of 40 dogs) were reviewed for clinical findings and historical data. Commercially available immunohistochemical stains for granulocytes and a Luna stain were performed (40 of 40 dogs) to assess the granulocytic infiltrate. RESULTS: Nineteen cases had been previously diagnosed as CAEDE, seven cases had been designated as sterile neutrophilic dermatosis and 14 cases had overlapping features. Based on review and receiver operating characteristic (ROC) curve analysis, 30 cases with >12% eosinophils, enumerated by Luna staining, were diagnosed as eosinophilic dermatitis and oedema. Ten cases were diagnosed as sterile neutrophilic dermatosis. Dogs with CAEDE frequently had gastrointestinal signs (24 of 30;80%) and pruritus (11 of 30;33%). In dogs with sterile neutrophilic dermatosis, five of 10 (50%) had diagnoses of or histories compatible with immune-mediated polyarthropathy. CONCLUSIONS AND CLINICAL IMPORTANCE: In this case series, CAEDE was encountered more frequently than neutrophilic dermatosis and could be distinguished by the eosinophilic infiltrate, aided by a Luna stain. Concurrent arthralgia was more frequently identified with neutrophilic dermatosis. It remains unclear whether CAEDE and sterile neutrophilic dermatosis are separate disease entities or varied manifestations of the same disease.

Síndrome de Sweet en una niña preescolar / Sweet syndrome in a 5-year-old girl

El síndrome de Sweet, también conocido como dermatosis neutrofílica febril, es un trastorno dermatológico poco frecuente en pediatría. Clínicamente, se caracteriza por la aparición de lesiones papulares y/o nodulares de una coloración rojiza-violeta con hipersensibilidad local. Se reporta el caso de una paciente femenina de 5 años, quien consultó por un cuadro clínico de 10 días de evolución de aparición de lesión forunculosa en el arco nasal. Se realizó una biopsia de piel, que reportó dermatitis difusa con predominio de polimorfonucleares neutrófilos, necrosis epidérmica y ausencia de vasculitis. No se identificaron microorganismos. Se consideró el cuadro compatible con síndrome de Sweet. Es importante tener en cuenta este diagnóstico en cuadros clínicos similares y se deben descartar otros diagnósticos más frecuentes primero.

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is an infrequent dermatological disorder in pediatrics. Clinically it is characterized by the development of papular and/or nodular lesions of a reddish-violet coloration with local hypersensitivity. We report the case of a 5-year-old female who consulted 1 month after the appearance of the lesion in the nasal arch. A skin biopsy was performed and it reported diffuse dermatitis with a predominance of neutrophil polymorphonuclear cells, epidermal necrosis and absence of vasculitis. No microorganisms were identified. It was considered compatible with Sweet syndrome. It is important to consider this diagnosis in similar clinical cases and other more frequent diagnoses must be ruled out first.

[Sweet syndrome in a 5-year-old girl]. / Síndrome de Sweet en una niña preescolar.

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is an infrequent dermatological disorder in pediatrics. Clinically it is characterized by the development of papular and/or nodular lesions of a reddish-violet coloration with local hypersensitivity. We report the case of a 5-year-old female who consulted 1 month after the appearance of the lesion in the nasal arch. A skin biopsy was performed and it reported diffuse dermatitis with a predominance of neutrophil polymorphonuclear cells, epidermal necrosis and absence of vasculitis. No microorganisms were identified. It was considered compatible with Sweet syndrome. It is important to consider this diagnosis in similar clinical cases and other more frequent diagnoses must be ruled out first.

El síndrome de Sweet, también conocido como dermatosis neutrofílica febril, es un trastorno dermatológico poco frecuente en pediatría. Clínicamente, se caracteriza por la aparición de lesiones papulares y/o nodulares de una coloración rojiza-violeta con hipersensibilidad local. Se reporta el caso de una paciente femenina de 5 años, quien consultó por un cuadro clínico de 10 días de evolución de aparición de lesión forunculosa en el arco nasal. Se realizó una biopsia de piel, que reportó dermatitis difusa con predominio de polimorfonucleares neutrófilos, necrosis epidérmica y ausencia de vasculitis. No se identificaron microorganismos. Se consideró el cuadro compatible con síndrome de Sweet. Es importante tener en cuenta este diagnóstico en cuadros clínicos similares y se deben descartar otros diagnósticos más frecuentes primero.

Cutaneous hemophagocytosis: Clinicopathologic features of 21 cases.

BACKGROUND: Hemophagocytosis is well known in cytotoxic cutaneous T-cell lymphomas (CTCLs), in which it may represent a sign of hemophagocytic lymphohistiocytosis syndrome (HLHS), and is also typical of cutaneous Rosai-Dorfman disease (cRDD) (without prognostic relevance). Only rarely, has cutaneous hemophagocytosis (CH) been described in other skin conditions. OBJECTIVE: To characterize the clinicopathologic features of CH in skin biopsy specimens from patients with conditions other than CTCL or cRDD. METHODS: Case series analyzing clinicopathologic features and follow-up data on patients presenting with histopathologic signs of CH. RESULTS: Biopsy specimens from 21 patients were included. None of the patients had HLHS. The majority (n = 11) presented with leukocytoclastic vasculitis. Other associated diseases were lupus erythematous (n = 2), arthropod bite reaction (n = 2), erysipelas (n = 1), acne conglobata (n = 1), and Sweet syndrome (n = 1). Three patients had a nonspecific rash concomitant with Chlamydia pneumonia, middle ear infection, and pharyngitis, respectively. LIMITATIONS: This was a single-center, retrospective study. CONCLUSION: Isolated CH in conditions other than CTCL and cRDD is a histopathologic finding related mostly to leukocytoclastic vasculitis. Extensive investigations should be performed only if patients have other signs or symptoms of HLHS.

[Sweet's syndrome, a diagnosis to keep in mind]. / Syndrome de Sweet : un diagnostic à ne pas manquer.

Sweet's syndrome is a rare neutrophilic dermatosis. Typically, patients present with a sudden onset of tender erythematous skin lesions (papules, nodules, and plaques), of asymetrical distribution, located preferentially on the superior limbs, face and neck, associated whith high fever and neutrophilia. Histologicaly, there is a diffuse infiltrate of neutrophils located in the dermis. Most of the time idiopathic, it may be associated with a respiratory or gastro-intestinal infection, with inflammatory bowel disease, pregnancy and vaccination. A drug-induced form and a malignancy-associated form have been described. Based on illustrations and two clinical cases, we wish to focus on the diagnostic strategy and the management of this disease.

Le syndrome de Sweet est une dermatose neutrophilique rare. Les patients présentent classiquement une apparition brutale de lésions cutanées douloureuses sous forme de papules, nodules ou plaques érythémateuses asymétriques localisées préférentiellement sur les extrémités supérieures, le visage et le cou, associées à une fièvre élevée, une neutrophilie et, à l'histologie, un infiltrat diffus de neutrophiles dans le derme. Le plus souvent idiopathique, il peut être en lien avec des infections respiratoires et gastro-intestinales, avec des maladies inflammatoires de l'intestin, avec une grossesse ou une vaccination. Des formes médicamenteuses et paranéoplasiques ont été rapportées. A l'aide d'images cliniques et de deux cas cliniques, nous souhaitons rappeler les points essentiels nécessaires au diagnostic et à la prise en charge de cette maladie.

Drug management of neutrophilic dermatoses.

INTRODUCTION: Neutrophilic dermatoses are a heterogenous group of chronic, cutaneous inflammatory conditions characterized by the accumulation of neutrophils in the skin and by systemic inflammation. Neutrophilic dermatoses can be idiopathic or associated with other inflammatory or systemic diseases, including the group of the hereditary, autoinflammatory syndromes. Clinical management is challenging, due to limited clinical evidence and lack of clinical practice guidelines. Areas covered: This review provides an overview of current therapeutic management of the three prototypical neutrophilic dermatoses, aseptic pustulosis of the folds, Sweet syndrome and pyoderma gangrenosum. In addition, we describe innovative, pathogenesis-oriented treatment approaches, which are based on recent advances in the pathophysiology of neutrophilic dermatoses and autoinflammatory syndromes. The increasing role of the IL-1 cytokine family in initiating neutrophilic inflammation in both idiopathic and syndromic disease opened the way for the use of targeted biological treatment. Another promising treatment strategy is aimed at blocking downstream effector cytokines, such as IL12/23 and IL-17, involved in the autoinflammatory immune cascade. Expert commentary: In chronic-recurrent and syndromic cases of neutrophilic dermatoses, there is an unmet clinical need for long-term, continuous disease control. Future controlled clinical studies will optimize the use of targeted-biological agents in sequential or combination treatment strategies.

T helper type 1-related molecules as well as interleukin-15 are hyperexpressed in the skin lesions of patients with pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare, immune-mediated skin disease classified into the group of neutrophilic dermatoses. Although a number of studies confirmed the central role of innate immunity, only few studies have investigated the possible contributing role of acquired immunity. In particular, no reports concerning T helper type 1 (Th1) and Th2 cells are available as yet. Therefore, 15 patients with PG, five with Sweet's syndrome (SS) and nine skin specimens from healthy controls (HC) were investigated, evaluating the expression of Th1-related markers interleukin (IL)-12, interferon (IFN)-γ, C-X-C motif chemokine receptor 3 (CXCR3) and C-C motif chemokine receptor 5 (CCR5), of the Th2-related molecules IL-4, IL-5, IL-13 and CCR3, of the co-stimulatory axis CD40/CD40 ligand, of IL-15 and the natural killer (NK) cell marker CD56 in skin lesions by immunohistochemistry. Patients with PG and SS showed a higher expression of Th1 markers than HC. Conversely, IL-5- and CCR3-expressing cells were less numerous in PG skin lesions compared to SS (P = 0·0157 and < 0·0001, respectively). Both CD40 and CD40L were expressed more in PG than in SS and HC (P < 0·0001 for both). Finally, the number of IL-15+ and CD56+ cells was higher in the skin of patients with PG than in those of SS and HC (P < 0·0001 for both). Our results suggest that Th2 cells are down-regulated in PG. At the same time, over-expression of the co-stimulatory axis CD40/CD40L amplifies the impairment of the Th1/Th2 balance. Both these findings might explain the most aggressive behaviour of PG in comparison to SS. Moreover, over-expression of IL-15+ and CD56+ cells may suggest a possible role of NK cells in the pathogenesis of the disease.

Histiocytoid Sweet Syndrome Is More Frequently Associated With Myelodysplastic Syndromes Than the Classical Neutrophilic Variant: A Comparative Series of 62 Patients.

Histiocytoid Sweet syndrome (H-SS) is a histological variant of Sweet syndrome (SS) differing from classical neutrophilic SS (N-SS) by a dermal infiltrate mainly composed of lymphocytes and histiocytoid myeloperoxidase-positive cells. We aimed to report a large series of H-SS and compare the frequency and type of hematological malignancies associated to H-SS and N-SS. We included 62 patients with a coding histopathologic diagnosis of SS prospectively registered between 2005 and 2014 in the database of our Department of Pathology. Overall, 22 (35.5%) and 40 (64.5%) patients had a histological diagnosis of H-SS and N-SS, respectively. Median age, sex ratio, and cutaneous lesions were similar in the 2 groups. The frequency of extra-cutaneous manifestations was similar (50% vs 37.5%, P = 0.42). Recurrent forms were significantly more frequent in H-SS than in N-SS patients (21% vs 2.5%, P = 0.01). A hematological malignancy was diagnosed in 22 patients, 12 (55.5%) with H-SS and 10 (25%) with N-SS (P = 0.019). Hematological malignancy was of myeloid origin in 8/22 (36.3%) H-SS and 5/40 (12.5%) N-SS patients (P = 0.02), and of lymphoid origin without myeloid component in 4/22 (18.1%) H-SS and 4/40 (10%) N-SS patients (P = 0.35), respectively. One N-SS patient had a hematological malignancy of mixed (myeloid and lymphoid) phenotype. A myelodysplastic syndrome (MDS) was diagnosed in 7/22 (31.8%) H-SS and 1/40 (2.5%) N-SS patients (P < 0.001). Hematological disease was diagnosed before (in 8 H-SS and 3 N-SS patients) or at the time of the occurrence of the cutaneous lesions (in 1 H-SS and 7 N-SS patients). However, in 3 H-SS patients, all with MDS, cutaneous lesions preceded the hematological disease by ≤6 months. In conclusion, H-SS was associated with MDS in one third of patients but also with lymphoid malignancies, and cutaneous lesions could precede the hematological diagnosis in patients with MDS. A complete hematological assessment is mandatory at diagnosis, and monitoring blood cell counts should be recommended for at least 6 months after the diagnosis of H-SS.

Eosinophil-Rich Acute Febrile Neutrophilic Dermatosis in a Patient With Enteropathy-Associated T-cell Lymphoma, Type 1.

The presence of eosinophils within the neutrophilic infiltrates of acute febrile neutrophilic dermatosis (Sweet syndrome) is documented in the literature. Here, the authors describe a case of eosinophil-rich acute febrile neutrophilic dermatosis in the setting of new onset enteropathy-associated T-cell lymphoma (EATL), type 1. Histopathologic evaluation of the skin biopsies demonstrated a mixed superficial perivascular and inflammatory infiltrate composed of neutrophils, lymphocytes, and abundant eosinophils. EATL, type 1 is an aggressive although rare primary intestinal lymphoma that may be associated with celiac disease. This lymphoma is associated with a poor prognosis due to treatment resistance or bowel perforation. To the authors' knowledge, Sweet syndrome has not been reported in a patient with EATL.

CANDLE syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature-a rare case with a novel mutation.

UNLABELLED: We described herein a patient with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome and a novel mutation in PSMB8 gene. This patient had multiple visceral inflammatory involvements, including rare manifestations, such as Sweet syndrome and pericarditis. A 3-year-old male, Caucasian, was born to consanguineous healthy parents. At the age of 11 months, he presented daily fever (temperature >40 °C), irritability, hepatomegaly, splenomegaly; and tender and itching, erythematous papular and edematous plaque lesions. Echocardiogram showed mild pericarditis. Skin biopsy revealed a neutrophil infiltrate without vasculitis suggesting Sweet syndrome. Mutational screening of PSMB8 gene revealed homozygous c.280G>C, p.A94P mutation. He responded partially to high doses of oral glucorticoid and intravenous methylprednisolone. Colchicine, azathioprine, methotrexate, cyclosporine, and intravenous immunoglobulin were not efficacious. At the age of 3 years and 1 month, tocilizumab was administered resulting in remission of daily fever and irritability. However, there was no improvement of the skin tenderness and itching lesions. CONCLUSION: A new mutation in a CANDLE syndrome patient was reported with pericarditis and mimicking Sweet syndrome. The disease manifestations were refractory to immunosuppressive agents and partially responsive to tocilizumab therapy. WHAT IS KNOWN: • Proteasome-associated autoinflammatory syndromes (PRAAS) include four rare diseases. • Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome was seldom reported. What is New: • We described a Brazilian patient with CANDLE syndrome possessing a novel mutation in the PSMB8 gene. • This patient had multiple visceral inflammatory involvements, including rare manifestations, such as pericarditis and mimicking Sweet syndrome.