[Sweet syndrome manifestations].

Sweet syndrome (SS) exists as classical, malignancy-associated, drug-induced and as the new variants: giant cellulitis-like SS and neutrophilic dermatosis of the hands. SS exhibits different morphologies. Skin manifestations are usually accompanied by fever and neutrocytosis. All variants respond to systemic corticosteroids, but SS can recur. SS may be the first sign of malignancy or recurrence of previous cancer. It is important to be aware of the disease, which may mimic other reactive and febrile diseases, to enable patients to obtain the correct diagnostic set-up and treatment.

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.

A Review and Proposed Approach to the Neutrophilic Dermatoses of Childhood.

Neutrophilic dermatoses (NDs) are inflammatory skin conditions that are not associated with infection. The classification and clinical approach to these conditions in children is poorly described. This review classifies these conditions into five nosological subtypes: Sweet's syndrome, pyoderma gangrenosum, aseptic pustules, neutrophilic urticarial dermatoses, and Marshall's syndrome. In addition, we review the various secondary diseases that need to be excluded in the clinical management of the NDs of childhood, with a focus on the autoinflammatory conditions that the reader may not be familiar with. We propose a practical clinical approach to these disorders.

[Systemic urticaria in 2014]. / Urticaires systémiques en 2014.

Systemic urticaria are defined as urticaria, most often chronic, associated with systemic diseases. At present time, urticarial vasculitis and neutrophilic urticarial dermatosis associated to autoinflammatory syndromes are not considered to be subtypes of chronic spontaneous urticaria due to their distinctly clinical and histological characteristics as well different pathomechanisms. Sometimes, chronic urticaria is associated to thyroid autoimmunity. However, the majority of cases of chronic spontaneous urticaria have no discernible cause and further investigations are not necessary, as already suggested by some authors and French consensus conference more than 10 years ago.

Insight into Sweet's syndrome and associated-malignancy: a review of the current literature.

Sweet's syndrome (acute febrile neutrophilic dermatosis) is an infrequent skin disease characterized by sudden onset of fever, leucocytosis and erythematous plaques or nodules infiltrated by neutrophils. There are three main clinical settings in which Sweet's syndrome has been described: classical or idiopathic Sweet's syndrome, malignancy-associated Sweet's syndrome and drug-induced Sweet's syndrome. Classical Sweet's is often preceded by an upper respiratory tract infection and may be associated with inflammatory bowel disease and pregnancy. Approximately 21% of patients have an associated malignancy, most commonly hematological disease. The syndrome may occur as a paraneoplastic accompaniment to established cancer or may be a first sign of malignancy or its recurrence. The incidence is said to be increasing in recent years due to the frequent use of growth factors in cancer patients. Several anticancer agents including all-trans-retinoic acid proteosome inhibitors, hypomethylating agents, tyrosine kinase inhibitors and lenalidomide are potential harbingers of Sweet's syndrome. Unfortunately, little is known about the pathophysiology of Sweet's syndrome and there are no established guidelines for treatment of malignancy-associated Sweet's syndrome. Systemic corticosteroids are the mainstay of treatment. Sweet's syndrome caused by anticancer agents sometimes involves withdrawal or temporary discontinuation of anticancer agents, use of systemic corticosteroids and/or rechallenge with either with the same anticancer agents or different agents. This report provides insights into the pathophysiology, clinical presentation, diagnostic work, differential diagnosis and management of malignancy-associated Sweet's syndrome published in reported cases.

Autoimmunity-related neutrophilic dermatosis: a newly described entity that is not exclusive of systemic lupus erythematosus.

Neutrophilic dermatoses have long been known to be associated with autoinmune systemic diseases. Recently, a small number of cases of a disorder distinct from Sweet syndrome or bullous lupus erythematosus (LE) have been described as specifically related to systemic LE under diverse terms, including nonbullous neutrophilic dermatosis, nonbullous neutrophilic LE, and Sweet-like neutrophilic dermatosis. We describe 7 patients that developed urticarial lesions in the context of a known or concurrently diagnosed autoimmune connective tissue disease. Of a total of 7 patients, 6 were afflicted by systemic LE and 1 by rheumatoid arthritis and secondary Sjögren syndrome. Histological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, vacuolar alteration along the dermal-edidermal junction, and no vasculitis. Most patients had active systemic disease at the time of the cutaneous eruption. Skin lesions resolved rapidly after the administration of immunomodulating agents. In conclusion, we provide additional evidence of the existence of a recently defined nonbullous neutrophilic dermatosis in the context of autoimmune connective tissue diseases and propose the term autoimmunity-related neutrophilic dermatosis as an appropriate designation. Furthermore, we believe that this entity should prompt physicians to screen the presence of an active systemic disorder in afflicted patients.

Autoinflammatory skin disorders in inflammatory bowel diseases, pyoderma gangrenosum and Sweet's syndrome: a comprehensive review and disease classification criteria.

Pyoderma gangrenosum (PG) and Sweet's syndrome (SS) are skin diseases usually presenting with recurrent ulcers and erythematous plaques, respectively. The accumulation of neutrophils in the skin, characteristic of these conditions, led to coin the term of neutrophilic dermatoses to define them. Recently, neutrophilic dermatoses have been included in the group of autoinflammatory diseases, which classically comprises genetically determined forms due to mutations of genes regulating the innate immune response. Both PG and SS are frequently associated with inflammatory bowel diseases (IBDs); however, IBD patients develop PG in 1-3 % of cases, whereas SS is rarer. Clinically, PG presents with deep erythematous-to-violaceous painful ulcers with well-defined borders; bullous, pustular, and vegetative variants can also occur. SS is characterized by the abrupt onset of fever, peripheral neutrophilia, tender erythematous skin lesions, and a diffuse neutrophilic dermal infiltrate. It is also known as acute febrile neutrophilic dermatosis. Treatment of PG involves a combination of wound care, topical medications, antibiotics for secondary infections, and treatment of the underlying IBD. Topical therapies include corticosteroids and the calcineurin inhibitor tacrolimus. The most frequently used systemic medications are corticosteroids and cyclosporine, in monotherapy or in combination. Dapsone, azathioprine, cyclophosphamide, methotrexate, intravenous immunoglobulins, mycophenolate mofetil, and plasmapheresis are considered second-line agents. Hyperbaric oxygen, as supportive therapy, can be added. Anti-TNF-α agents such as etanercept, infliximab, and adalimumab are used in refractory cases. SS is usually responsive to oral corticosteroids, and the above-mentioned immunosuppressants should be considered in resistant or highly relapsing cases.

Sweet's syndrome: a revisit for hematologists and oncologists.

The diagnosis of Sweet's syndrome rests on a combination of clinical symptoms and characteristic physical and pathologic features. Patients typically have fever and tender erythematous skin lesions (papules, nodules, or plaques). Neutrophilia, high levels of serum inflammatory markers, and diffuse mature neutrophil infiltration localized to the upper dermis are the most important findings. Sweet's syndrome was first described by Robert Sweet in 1964, whose sentinel paper described 8 women with fever, leukocytosis, and erythematous plaques infiltrated by neutrophils. Subsequently, extracutaneous sites were included in the diagnosis. This review of publications between 1964 and April 2012 found 1683 reports of Sweet's syndrome of which only 8 were published between 1964 and 1969, after which the number of the papers grew by decades to 59, 228, 459 and 692. With more articles, there are more reports of malignancy-associated Sweet's syndrome. This may reflect the awareness by physicians of the disease and of the drugs which may cause it. There is considerable overlap in the constitutional findings of Sweet's syndrome and malignant disorders. It is crucial that the possibility of Sweet's syndrome be included in a hematologist or oncologist's differential diagnosis of fever and skin lesions.

[Sweet's syndrome]. / Síndrome de Sweet.

Sweet's syndrome represents the epitome of the neutrophilic dermatosis, a group of reactive cutaneous diseases characterized histopathologically by the existence of an infiltrate composed by neutrophils. Clinically, it is characterized by the abrupt onset of tender or painful plaques accompanied by fever, general malaise, and neutrophilic leukocytosis. Sweet's syndrome is a marker of several internal conditions, especially infections, inflammatory bowel disease, autoimmune disorders, and malignant neoplasm (predominantly of hematological origin). Sweet's syndrome reflects a neutrophilic reaction that affects the skin and sometimes internal organs. For this reason it is important to reach a correct diagnosis and assess appropriately both the triggering factors and the concomitant internal involvement. There are several therapeutic approaches that achieve either the resolution or the satisfactory management of this condition.

Neutrophilic dermatosis of the dorsal hands in a patient treated with chemotherapy for acute myelogenous leukemia.

The proper nomenclature and classification of the group of diseases known as neutrophilic dermatoses is a topic of ongoing interest and study Specifically, the possible relationship between neutrophilic dermatosis of the dorsal hands (NDDH) and Sweet disease (SD), or their existence as separate and discrete entities, has been explored in the literature. We present the case of a 63-year-old woman with acute myelogenous leukemia (AML) who developed NDDH 4 weeks after undergoing chemotherapy. Results from a punch biopsy revealed leukocytoclasia and endothelial swelling around the dermal vessels, with no evidence of fibrinoid necrosis of the vessel walls. This case may lend support to the concept that NDDH is a variant of SD rather than a distinct clinical entity.

[Chronic recurrent neutrophilic dermatosis: a possible variant in the spectrum of neutrophilic dermatoses]. / Dermatosis neutrofílica crónica recurrente: una posible variante en el espectro de las dermatosis neutrofílicas.

Neutrophilic dermatoses constitute a clinically heterogeneous group of diseases that share a common histological substrate, consisting of a dense dermal inflammatory infiltrate of mature polymorphonuclear neutrophils and no evidence of vasculitis. We describe the case of a 56-year-old man with a 6-month history of painful generalized erythematous edematous plaques. Histopathology indicated neutrophilic dermatosis but the patient did not have fever, elevated white blood cell count, or systemic involvement. Tests to rule out possible inflammatory, neoplastic, or infectious processes were negative. We consider the term chronic recurrent annular neutrophilic dermatosis, first used by Christensen et al, to be the most appropriate to define this variant with clinical findings that differ from classic Sweet syndrome.

Histiocytoid neutrophilic dermatoses and panniculitides: variations on a theme.

Requena et al, in their article titled "Histiocytoid Sweet syndrome," in 2005, established that the dermal infiltrate in some patients with Sweet's syndrome is composed of histiocyte-like immature myeloid cells, not polymorphonuclear leukocytes as is the norm. With this premise in mind, we report on 6 cases of inflammatory skin disease in which the common denominator was a dermal and/or subcutaneous infiltrate of histiocytoid myeloid cells in patients with new-onset cutaneous eruptions and systemic symptoms. The cases were diverse clinically and microscopically, fell short of the criteria necessary for a diagnosis of classical Sweet's syndrome, and were difficult to categorize at the outset. The systemic manifestations ranged from malaise alone to a combination of fever, chills, night sweats, and polyarthralgia. The clinical morphology of the cutaneous eruptions varied from being papulovesicular in 1 patient to mainly consisting of erythematous plaques and nodules in the remainder. The dermatologists' differential diagnoses included Sweet's syndrome in 3 cases, a drug eruption in 2, and other entities such as erythema nodosum and Well's syndrome. Biopsies in all cases revealed a dermal and/or subcutaneous infiltrate composed predominantly of mononuclear histiocytoid cells of myeloid origin. With the benefit of detailed clinicopathologic correlation, the cases were classified for the purpose of this report as follows: Sweet's-like neutrophilic dermatosis, histiocytoid (3 cases); subcutaneous Sweet's syndrome, histiocytoid (2 cases); histiocytoid neutrophilic dermatosis, unspecified (1 case). In addition, we describe a further instructive case that exhibited overlap with those in the series but proved ultimately to represent leukemia cutis. The spectrum of observations in this report supports and expands the original concept of histiocytoid Sweet's syndrome.

From acute febrile neutrophilic dermatosis to neutrophilic disease: forty years of clinical research.

In 1964, Sweet described an acute febrile neutrophilic dermatosis. It is now widely accepted that Sweet's syndrome belongs to a group of associated neutrophilic dermatoses. Although clinically dissimilar, Sweet's syndrome, pyoderma gangrenosum, subcorneal pustular dermatosis, erythema elevatum diutinum, and a few other conditions can be considered a part of this same pathologic spectrum of inflammatory disorders because of (1) the existence of transitional and overlap forms; (2) the similar histopathologic feature of an infiltrate by normal polymorphonuclear leukocytes; (3) the possible occurrence of extracutaneous neutrophilic infiltrates, defining the neutrophilic disease; and (4) the frequent association with systemic diseases. According to the localization of the neutrophilic infiltrate, we describe neutrophilic dermatoses en plaques (dermal), superficial (epidermal), and deep (dermal and hypodermal). Almost every organ of the body may be involved by a neutrophilic aseptic inflammation. The main systemic diseases associated with neutrophlic dermatoses are hematologic, gastrointestinal, and rheumatologic diseases. Although the pathophysiology of these conditions is still poorly understood, treatment with systemic anti-inflammatory agents is usually efficacious.