**5. Clinical manifestations**

#### **5.1 Skin**

SS begins as an alarming feature for the patient because of its abrupt onset, the presence of general malaise, and the pain or tenderness of the multiple erythematoedematous plaques (Gunawardena et al 1975; Kemmett & Hunter, 1990; Zamora et al 1990; Sitjas et al, 1993; von den Driesch 1994; Chan et al, 1994; Ginarte et al, 1997). The appearance of each individual lesion may be variable: the colour goes from vivid red to violaceus, sometimes with central paleness due to dermal edema. This edema can also be represented by pseudovesicular or true bullous lesions (figure 1). It is relatively frequent to oberve dome like lesions, especially on tenar and hypotenar eminences (in "mountain range") (figure 2). Individual lesions can also be pustular. Up to a third of the lesions have an annular appearance. Plaque´s size is variable but the majority range between 1 and 10 cm. The lesions are distributed bilaterally but asymmetrically. Common locations are face, neck, upper trunk, shoulders, and hands. On pretibial aspect of the legs, the lesions may exhibit a nodular morphology, which may be the clinical manifestation of a typical SS, a subcutaneous Sweet or an erythema nodosum (see forward). Pathergy may be present in up to 8% of the patients.

There is not reliable data regarding the incidence and prevalence of SS in general population. This relies on the fact that SS is an infrequent condition and the available data are based on series´ reports of and patient´s records from hospitals and dermatology departments. Moreover, it is necessary to take into account that the incidence of SS is determined by the incidence of infectious causes in general population (Hommel et al, 1993). With all these limitations, it has been reported that the incidence of SS in Scotland is 2.7

Gender distribution of SS is conditioned by the underlying or trigger disorder. There is a female predominance in parainflammatory and idiopathic cases which disappears in the

The pathogenesis of SS remains to be definitively determined. Three possible pathogenical mechanisms have been considered, but none of them have been consistently demostrated (Requena, 2007): a) a type III hypersensitivity reaction, b) an activation of T cells by antigens or superantigens, and c) a disturbance of neutrophils´ function. It seems that genetic factors play a role since SS has been associated to several HLA, especially to Bw54 (Mizoguchi, 1988). Because of female predominace in parainflammatory and idiopathic cases and both pregnancy and contraconceptive pills implication in some cases of SS, hormonal

Numerous cytokines are involved in the pathogenesis of this condition, including interleukins 1, 2, 3, 6, and 8 and gamma interferon, but the key substance is the granulocytecolony stimulating factor (G-CSF). The administration of G-CSF can result in an outbreak of SS and this substance is elevated in serum of patients with SS and its levels are directly

SS begins as an alarming feature for the patient because of its abrupt onset, the presence of general malaise, and the pain or tenderness of the multiple erythematoedematous plaques (Gunawardena et al 1975; Kemmett & Hunter, 1990; Zamora et al 1990; Sitjas et al, 1993; von den Driesch 1994; Chan et al, 1994; Ginarte et al, 1997). The appearance of each individual lesion may be variable: the colour goes from vivid red to violaceus, sometimes with central paleness due to dermal edema. This edema can also be represented by pseudovesicular or true bullous lesions (figure 1). It is relatively frequent to oberve dome like lesions, especially on tenar and hypotenar eminences (in "mountain range") (figure 2). Individual lesions can also be pustular. Up to a third of the lesions have an annular appearance. Plaque´s size is variable but the majority range between 1 and 10 cm. The lesions are distributed bilaterally but asymmetrically. Common locations are face, neck, upper trunk, shoulders, and hands. On pretibial aspect of the legs, the lesions may exhibit a nodular morphology, which may be the clinical manifestation of a typical SS, a subcutaneous Sweet or an erythema nodosum (see forward). Pathergy may be present in

related with the disease activity (Kawakami et al, 2004; Ginarte & Toribio, 2010).

cases per million inhabitants and year (Kemmett & Hunter, 1990).

infantile and paraneoplastic ones. There is no racial predilection.

background can also be involved in the development of SS.

**3. Epidemiology** 

**4. Pathogenesis** 

**5. Clinical manifestations** 

up to 8% of the patients.

**5.1 Skin** 

Fig. 1. Erythematous plaques with vesicular and bullous appearance due to a intense dermal edema.

Fig. 2. The plaques on tenar and hypotenar skin have frequently a characteristic appearance of "montain range"

#### **5.2 Mucous membranes**

The mucous membranes are frequently involved, especially the ocular as conjunctivitis or epiescleritis (Gottlieb et al, 2008) (figure 3). Less frequent is the affectation of the oral mucosa, usually as aphtous ulcers.

Sweet Syndrome 123

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

ORGAN CLINICAL MANIFESTATIONS REFERENCES

insuficiency, isquemic cardiopathy

urinalysis Christ et al, 1996

Majeed et al, 1989; Marie et al, 1998

Fain et al, 1996

McDermott et al, 2001;

Hisanaga et al, 1999; Nobeyama & Kamide, 2003; Ramos et al, 2003; Hisanaga et al, 2005; Sobol et al, 2009; Watanabe et al, 2009

Muster et al, 1983; Shimizu, 1998; Guia et al, 1999; Dorenkamp et

Kemmett & Hunter, 1990; Zamora et al, 1990; Fett et al, 1995; Ginarte et al, 1997

Cohen & Kurzrock, 1992; Sitjas et al, 1993; Fett et al, 1995; Peters et al, 1998; Astudillo et al,

Attias et al, 1995; Brown et al, 2002

al, 2003

2006

Bones Chronic recurrent osteomyelitis (in children)

Bowel Neutrophilic bowel infiltration, pancolitis

Heart Aortitis, myocarditis, cardiac

Kindney Glomerulonephritis, alterations of

Liver Neutrophilic hepatitis, changes in liver

Lung Neutrophilic alveolitis, pleural effusion;

Muscle Tendosinovitis, myositis, myalgias

Table 3. Systemic involvement in Sweet syndrome

function tests and analysis

radiologic sterile infiltrates

extracutaneous manifestations of SS.

system Neuro-Sweet

Central nervous

Fig. 3. Epiescleritis in a patient with Sweet syndrome
