INTRODUCTION

Sweet syndrome (SS) is a rare neutrophilic dermatosis [1]. It is defined by a distinct combination of clinical manifestations, laboratory findings, and histopathological features [2]. In recent years, the understanding of its clinical spectrum has broadened, yet its etiology remains uncertain. Notably, a possible pathergy phenomenon has been suggested, where skin trauma may precipitate the condition [3]. In this context, we report a new observation of SS potentially triggered by an insect bite, highlighting the need for awareness of this rare but possible association.

CASE REPORT

A 64-year-old male presented to our department with painful and pruritic lesions on the exposed areas (hands, forearms, and neck), which had been evolving for three days. The lesions were preceded by insect bites in the same location. The medical history revealed no associated illness, recent medication use, infection, or vaccination. Interestingly, the patient’s son, who had also been bitten by insects (likely mosquitoes) in the same environment, developed pruritic papules, which resolved spontaneously.

On clinical examination, multiple well-defined, infiltrated, erythematous and violaceous papules and plaques of varying sizes were noted. Some lesions were centered by a small crust and vesicle or pustule (Fig. 1). Despite the febrile state, the patient had a preserved general condition.

Figure 1: Clinical aspects of the lesions prior to treatment initiation: multiple well-defined, infiltrated, erythematous and violaceous papules and plaques of varying sizes on the dorsum of a) the hand, b) palms, and c) neck.

Biological tests revealed an elevated C-reactive protein level (54 mg/L) and an accelerated erythrocyte sedimentation rate (1^st hour = 76 mm; 2^nd hour = 96 mm). The blood count was normal with no leukocytosis or hypereosinophilia. A skin biopsy was performed, showing an edematous dermis with a dense perivascular infiltrate containing neutrophils and numerous lymphocytes. Lesions of leucocytoclasis without vasculitis were described (Fig. 2). Based on these clinico-biological and histopathological findings, a diagnosis of Sweet syndrome with a possible pathergy phenomenon was made. The patient was treated with topical corticosteroids and non-steroidal anti-inflammatory drugs (indomethacin) with complete healing.

Figure 2: a) Histopathological examination showing exocytosis of PNN in the epidermis associated with an abundant dermal infiltrate. b) Higher magnification showing PNN-rich dermal infiltrate with leukocytoclasia.

DISCUSSION

Sweet’s syndrome is a rare inflammatory disorder with predominantly cutaneous expression. It is characterized by its clinical polymorphism, and it is often associated with a wide range of underlying conditions, including malignancies, autoimmune diseases, and infections [2]. Interestingly, our patient did not present any associated conditions, making this case particularly noteworthy.

The pathophysiological mechanisms underlying Sweet syndrome are not well understood [4]. Some authors suggest a hyperreactivity of the immune system, probably mediated by cytokines, leading to an influx of neutrophils activated by IL-1 [1]. Although rare, a pathergy phenomenon also referred to as skin hypersensitivity has been described at sites of cutaneous trauma [1,4]. This includes areas where procedures such as intravenous catheter placements, biopsies, or vaccinations have been performed. Additionally, regions exposed to radiation therapy, sensitizing antigens, or sunburns may also be concerned [1,4].

There have been reports of Sweet’s syndrome lesions occurring at insect bite sites, suggesting that, in some patients, an exaggerated hypersensitivity to insect stings may trigger the condition [3]. Our patient’s presentation aligned with this phenomenon, as the onset of the SS lesions followed shortly after insect bites.

In the literature, we found only one reported case of Sweet syndrome triggered by an insect bite (Table 1) [3,5]. The patient was a 65-year-old Tunisian woman with a medical history of chronic lymphocytic leukemia (stage A of Binet), evolving for five years with no need of specific treatment. She presented a fever at 39°C and multiple deep erythematous and annular plaques with a centrifugal growth and erythematous and edematous margins. The lesions initially appeared on her buttocks, several hours after an insect bite on the same location and progressed to most of her body, including the palms. Laboratory findings were the same as in our patient: an elevated C reactive protein level with no leukocytosis or hypereosinophilia. A histological examination revealed an edematous dermis associated with abundant perivascular and interstitial inflammatory infiltrates. What made the difference in our patient was that this infiltrate was mainly composed of neutrophils yet also numerous eosinophils. Their patient was treated with doxycycline (100 mg/day), which resulted in complete recovery within two weeks [3].

Table 1: Clinical and histological features of Sweet Syndrome cases triggered by an insect bite.

The diagnosis of Sweet syndrome relies on the association of clinical, biological, and histopathological criteria (Table 2). The presence of both major criteria and two minor criteria is required to establish the diagnosis [4]. When those criteria are not fulfilled, the diagnosis of Sweet-like reaction due to arthropod bites should be considered [6]. Arthropods include arachnids, myriapods, and insects. Arthropod bite reactions are typically characterized histopathologically by ‘‘dermal edema with superficial and middle to deep dermal inflammation arranged in a perivascular and wedge-shaped pattern.” The infiltrate composition may vary, including lymphocytes, histiocytes, neutrophils, and eosinophils. A characteristic yet inconstant feature is the prominence of eosinophils within collagen bundles. Indeed, the two cases reported by Battistella et al. [6] lacked the characteristic eosinophil infiltration and demonstrated dermal neutrophilic infiltration, similar to what is observed in Sweet syndrome lesions. Regarding the pathogenesis of arthropod bite reactions, it is thought that insect salivary antigens react with specific immunoglobulins IgE, leading to the local recruitment of eosinophils. Insect saliva also contains chemokines that may be responsible for the recruitment of neutrophils, resulting in the histopathological pattern in both of our patients. Therefore, distinguishing between the two diagnoses may be challenging, and pathologists should be very careful when diagnosing neutrophilic dermatosis.

Table 2: Diagnostic criteria of Sweet syndrome [2].

If untreated, Sweet syndrome lesions may persist for weeks [4]. Treatment options include topical or intralesional corticosteroids for localized lesions, either as monotherapy or combined with other therapies, as in our patient [4]. For extensive lesions, first-line treatments are systemic corticosteroids or colchicine [1]. Systemic corticosteroids (prednisone 0.5–1 mg/kg/day) have a spectacular immediate effect but may be contraindicated in cases of systemic infection. Colchicine is administered orally at a dose of 1 mg/day. As second-line therapy, dapsone 100–200 mg/day or cyclosporin at a dose of 2–5 mg/kg/day are most often used [1]. Indomethacin is also effective, with an oral daily dose of 150 mg for the first seven days, then reduced to 100 mg/day for the following fourteen days [4]. Doxycycline at a dose of 100 mg/day seems to be an interesting therapeutic alternative by modulating cytokine gene expression [3]. Refractory forms could benefit from interleukin 1 receptor antagonists, illustrating the role of IL-1 in its pathophysiology. Anti-tumor necrosis factor (TNF)-α agents have been reported to be effective [1]. Overall, treatment must be continued at least for three weeks and weaned cautiously because relapses and rebounds are common [1].

CONCLUSION

The sudden onset of painful erythematous papular lesions associated with fever should raise the suspicion of Sweet syndrome, even if there is evidence of an insect bite. If the diagnostic criteria are not fulfilled, Sweet-like reactions due to arthropod bites should be considered [6]. Further research is needed to clarify the precise mechanisms linking insect stings to the development of Sweet syndrome.

REFERENCES

1.Lang C, Quenan S. [Sweet’s syndrome:A diagnosis to keep in mind]. Rev Med Suisse. 2017;13:678-83.

2.Bouzidi H, Gallouj S, Amraoui N, Mernissi FZ, Harmouch T. Syndrome de Sweet:étude clinique et anatomopathologique sur 5 ans. Pan Afr Med J. 2015;20:362.

3.Soua M, Korbi M, Boumaiza S, Kooli I, Hadhri R, Soua Y, et al. Sweet syndrome induced by insect bite in a patient with chronic lymphocytic leukemia. WCD. 2019;40.

4.Cohen PR. Sweet’s syndrome:A comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34.

5.Korbi M, Chtiou E, Soua M, Hadhri R, Belhadjali, Youssef M, et al. Eosinophil-rich sweet syndrome:Is it a new entity?Authorea. 2022;13.

6.Battistella M, Bourrat E, Fardet L, Saada V, Janin A, Vignon-Pennamen MD. Sweet-like reaction due to arthropod bites:A histopathologic pitfall. Am J Dermatopathol. 2012;34:442-5.