**5.3 Laboratory findings**

Analytic alterations are very frequent and they can have diagnostic significance. The most typical but not constant alteration is leukocytosis with neutrophilia that only in the 50% of the patients exceed by 10.0 x103 cells/mm3. The majority of patients have the acute reactants (erythrocyte sedimentation rate and C-reactive protein) elevated and a third have mild alterations in urinary tests (haematuria, leukocyturia, and/or proteinuria) without affectation of renal function (Ginarte et al, 1997). It is necessary to distinguish the laboratory findings related to SS from the analytic changes due to trigger or associated diseases. For example, the presence of anemia, trombocytosis and/or massive leukocytosis should force us to rule out an haematologic malignancy (Cohen & Kurzrock, 1993).

#### **5.4 Extracutaneous manifestations**

Frequently patients with SS have extracutaneous manifestations that can be caused by two different mechanisms: a) a systemic neutrophilic reaction that affects not only the skin but also internal organs, and b) a disease or trigger condition causing the SS. These two different possibilities make more difficult the management of the patients because it is hard to distinguish by means the clinical and routine complementary tests if an internal disorder is the cause or the consequence of the SS. For example, the existence of respiratory manifestations, pulmonary infiltrates in X-ray chest, fever and leukocytosis with neutrophilia in a patient with SS set the doubt between an infectious pneumonia or a neutrophilic pneumonitis (which has important practical consequences since their treatment is quite different, i.e., antibiotics versus glucocorticoids). Despite of its original denomination as acute febrile neutrophilic dermatosis, the fever is only present in 50 to 72% of the cases (Ginarte et al, 1997). Joint involvement appear in 37 to 51% of the patients, usually as arthralgias or, more rarely, as true arthritis, which is commonly located on knees

Analytic alterations are very frequent and they can have diagnostic significance. The most typical but not constant alteration is leukocytosis with neutrophilia that only in the 50% of the patients exceed by 10.0 x103 cells/mm3. The majority of patients have the acute reactants (erythrocyte sedimentation rate and C-reactive protein) elevated and a third have mild alterations in urinary tests (haematuria, leukocyturia, and/or proteinuria) without affectation of renal function (Ginarte et al, 1997). It is necessary to distinguish the laboratory findings related to SS from the analytic changes due to trigger or associated diseases. For example, the presence of anemia, trombocytosis and/or massive leukocytosis should force

Frequently patients with SS have extracutaneous manifestations that can be caused by two different mechanisms: a) a systemic neutrophilic reaction that affects not only the skin but also internal organs, and b) a disease or trigger condition causing the SS. These two different possibilities make more difficult the management of the patients because it is hard to distinguish by means the clinical and routine complementary tests if an internal disorder is the cause or the consequence of the SS. For example, the existence of respiratory manifestations, pulmonary infiltrates in X-ray chest, fever and leukocytosis with neutrophilia in a patient with SS set the doubt between an infectious pneumonia or a neutrophilic pneumonitis (which has important practical consequences since their treatment is quite different, i.e., antibiotics versus glucocorticoids). Despite of its original denomination as acute febrile neutrophilic dermatosis, the fever is only present in 50 to 72% of the cases (Ginarte et al, 1997). Joint involvement appear in 37 to 51% of the patients, usually as arthralgias or, more rarely, as true arthritis, which is commonly located on knees

Fig. 3. Epiescleritis in a patient with Sweet syndrome

us to rule out an haematologic malignancy (Cohen & Kurzrock, 1993).

**5.3 Laboratory findings** 

**5.4 Extracutaneous manifestations** 

and ankles. Neutrophilic infiltration of internal organs is less frequent. Although the infiltration of the majority of the organs has been reported, the most frequently affected are the lungs (up to 6% of the patient in a serie) (Sitjas et al, 1993). Pulmonary involvement expresses as neutrophilic alveolitis. In the literature there are abundant references about the neutrophilic affectation of internal organs, which may induce to think that it is a frequent event even though it is actually an uncommon fact. This situation is secondary to a bias in reporting the more extreme cases of SS. Nevertheless, the possibility of internal organ involvement in SS patients should always be taken in consideration and it is important distinguish it from other diseases or trigger factors (especially the infectious ones) since their clinical management is quite different. As neutrophilic internal organ involvement is relatively more frequent in paraneoplastic SS than in other subtypes of SS, its presence obligates us to rule out a malignancy (Cohen & Kurzrock, 1993). Table 3 shows the main extracutaneous manifestations of SS.


Table 3. Systemic involvement in Sweet syndrome

Sweet Syndrome 125

The typical cases of SS present very characteristics clinicopathological manifestations so that their diagnosis usually does not represent particular difficulty. Nevertheless, the SS may occasionally show a different clinical picture or it may be associated with other cutaneous signs making difficult to set the diagnosis and/or imply a change in the patient´s management. There is controversy about the need of describing such cases as "atypical" SS

The group of ND represents a *continuum* of diseases that share clinical, histopathological, and causal features. The individualization of each entity is mainly based on clinical criteria. This fact explains that SS occasionally shares clinical characteristics with other ND (overlap), especially with generalized vesiculobullous forms of pyoderma gangrenosum. Other ND such as Behçet disese, bowel bypass syndrome, and neutrophilic eccrine hidradenitis may clinically resemble SS (Mizuashi et al, 2010). Sometimes patients with these features can only be diagnosed generically as suffering a ND, without a more specific denomination. In the same way, there have been reported patients suffering both SS and other ND (either simultaneously or sequentially) (Callen, 1985; Sherertz, 1987; Villanueva et al, 1989; Ginarte

As its denomination indicates, it is a subtype of SS characterized by erythematoedematous plaques with a chronic and recurrent evolution. It has neither extracutaneous signs, nor fever or neutrophilia (Christensen et al, 1989; Romero et al, 1994; Cabanillas et al, 2008).

Frequently, patients with SS have nodular lesions, especially on anterior aspects of the legs. These nodules are the clinical manifestation of the alteration of the subcutaneous fat, which can be originated by two different mechanisms. The first one called subcutaneous SS is characterized by a neutrophilic inflammatory infiltrate located on subcutaneous fat (either exclusively or accompanied by dermal affectation). Such infiltrate is usually located in fat lobules, but occasionally it may be septal or mixed (Cohen & Kurzrock, 2003). In a recent study, subcutaneous SS was shown by 16% of the patients (Abbas et al, 2010). The second possibility of subcutaneous fat involvement in SS is the association between this syndrome and erythema nodosum. This association is relatively frequent (up to 30% of the cases) and can be explained because both entities share several common features: essentially both are reactive dermatoses triggered by similar stimuli and pathogenically mediated by neutrophils. They are also treated with similar treatments (Ginarte et al, 1997; Ginarte & Toribio, 2000; Ginarte & Toribio, 2007). Due to the different significance of subcutaneous SS and erythema nodosum, it is necessary to make a deep biopsy from one of the nodules.

About 16% of SS appears in children (Abbas et al, 2010). Pediatric SS is similar to that in adult population, with only three differences: a) it is associated with immunodeficiency

**7. Clinical variations and associations with other dermatoses** 

or as individualizing them as different entities.

**7.1 Overlap and relationship with other ND** 

**7.2 Chronic recurrent annular neutrophilic dermatosis** 

**7.3 Subcutaneous fat involvement** 

**7.4 Sweet syndrome in infancy** 

et al, 1997).
