|Year : 2022 | Volume
| Issue : 2 | Page : 121-126
Sweet's syndrome: A study of 16 cases and review of literature
H Bangaru, KR Raghavendra, Sathish Shankar
Department of Skin and STD, Mysore Medical College and Research Institute, Mysore, Karnataka, India
|Date of Submission||13-Feb-2022|
|Date of Decision||06-May-2022|
|Date of Acceptance||07-May-2022|
|Date of Web Publication||26-Aug-2022|
K R Raghavendra
Room No. 14, Department of Skin and STD, KR Hospital, Mysore Medical College and Research Institute, Mysore, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Sweet's syndrome (SS) is a classical representative of neutrophilic dermatosis characterized by the abrupt onset of fever, erythematous tender plaques and nodules on exposed parts, and histopathological reaction in response to different external and internal stimuli. Objectives: The aim of this study was to assess the clinical, epidemiological, histological features and therapeutic outcomes of SS. Materials and Methods: A retrospective study of all patients diagnosed with SS over a 4-year period (2016–2020) was conducted. Results: Over a period of 4 years, a total number of cases of SS were 16. Female patients were predominant around 13 (81.25%), and male patients were 3 (18.75%). The most common site affected was face in 87.5% (14), followed by upper limb in 50% (8) and lower limb in 25% (4). Among the systemic manifestations, fever was there in all cases. The associated causes were infectious conditions in 6 (37.5%) cases, among which five cases were upper respiratory tract infection, hematological malignancy in three cases, one case with solid tumors, one case was associated with acquired cutis laxa (Marshall' s syndrome), one was drug induced (diclofenac sodium), one case was pregnancy associated, and other three cases were idiopathic. Conclusion: SS can be diagnosed based on clinical and laboratory findings. In all atypical and recurrent SS cases, thorough evaluation for malignancy is essential. Dapsone can be considered a concomitant therapy along with steroids and also a steroid-sparing agent.
Keywords: Marshall's syndrome, non-Hodgkin lymphoma, Sweet's syndrome
|How to cite this article:|
Bangaru H, Raghavendra K R, Shankar S. Sweet's syndrome: A study of 16 cases and review of literature. Clin Dermatol Rev 2022;6:121-6
| Introduction|| |
Sweet's syndrome (SS) (also known as acute febrile neutrophilic dermatosis or Gomm–Button disease) is classically characterized by fever, leukocytosis, tender erythematous plaques and nodules mostly on exposed parts, and a dense dermal neutrophilic infiltrate on histopathology and rapid response to systemic corticosteroids. For the first time in 1964, Robert Douglas Sweet observed eight women with acute fever, leukocytosis, and erythematous plaques inﬁltrated by neutrophils. Later in 1968, Whittle et al. coined the term SS for these constellations of classical features. SS occurs worldwide and there appears to be no racial predilection. The disease is common among women in the age group of 30 and 60 years but is also reported in children., Its etiology is obscure, and various cytokines may play a role in development of SS. The hypersensitivity reaction to various antigens such as bacterial, viral, or tumor antigens may play a vital role in pathogenesis of SS. Depending on its association with various disorders, it can be classified into three groups: classical or idiopathic SS, malignancy-associated or paraneoplastic SS, and drug-induced SS. Approximately 70% of cases are idiopathic and the paraneoplastic form is present in 10%–20% associated predominantly with hematological malignancies such as acute myelogenous leukemia, myelodysplastic syndromes, and lymphoma and extracutaneous variants have also been reported., Most series of SS are limited by a small sample size; the largest series is of 90 cases. The present study assesses the epidemiological, clinical, laboratory, histological findings, and therapeutic responses, as well as triggering factors and disorders associated with SS in our geographical region.
| Materials and Methods|| |
This was a retrospective study of all confirmed cases of SS treated during the study period from 2016 to 2020 at a tertiary care center in South India. The criteria used to diagnose SS were by Su and Liu and revised by von den Driesch [Table 1]. Data collected included age at presentation, gender, distribution and morphology of lesions, triggering factors if any, associated symptoms and disorders, related laboratory abnormalities, histopathological ﬁndings, and outcome to treatment. All the patients were evaluated for possible malignancies. The data were analyzed using percentage and bar diagram.
|Table 1: Diagnostic criteria used to diagnose classical Sweet's syndrome and drug-induced Sweet's syndrome|
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| Results|| |
Over a period of 4 years, a total number of cases were 16 and the annual incidence of SS in our OPD came to around 4 cases per year [Table 2]. Female patients were 13 (81.25%) and males were 3 (18.75%) in our study. Their age ranged from 4 to 60 years, with a mean age of 38.78 years. On excluding the single pediatric cases, the affected age group ranged from 24 to 60 years. The most common site affected was face in 87.5% (14 cases), followed by upper limb in 50% (8), lower limb in 25% (4), trunk in 50%, and neck in 25% of cases. The lesions were generalized in three cases. Among the systemic manifestations, fever was the most common complaint and was there in all cases. Other manifestations were joint pain in 18.75% (3) and malaise in 31.25% (5) of cases, and only in one case, conjunctivitis was there. In laboratory investigation, the total leukocyte counts of more than 8000 were seen in all cases and neutrophilia (>70% leukocytes) was seen in 81.25% (13) of study patients. C-reactive protein was positive in 62.5% (10) of patients. The erythrocyte sedimentation rate (ESR) was more than 20 mm in 62.5% (10) of patients. All the cases had histopathological features consistent with classical features of SS. The associated causes were infectious conditions in 6 (37.5%) cases, among which five cases were upper respiratory tract infection [Figure 1] and one was gastrointestinal infection. Other causes were hematological malignancy in three cases which included two cases of non-Hodgkin lymphoma and one case of acute myeloid lymphoma; among these three cases, one case developed classical SS lesion involving the whole body [Figure 2]a, [Figure 2]b and [Figure 3]a, [Figure 3]b histopathologically features consistent with SS [Figure 4]a and [Figure 4]b, one more case was associated with pleomorphic adenoma, one case was associated with acquired cutis laxa (Marshall's syndrome) [Figure 5], one was induced by diclofenac sodium in which classical SS lesions developed within 24–48 h of ingestion over the face and dorsal aspects of both limbs [Figure 6], one case was associated with pregnancy in which lesions developed over the face and patient also developed erythematous edematous urticarial plaques over the abdomen on stretch marks suggestive of pruritic urticarial papules of pregnancy [Figure 7]a and [Figure 7]b, and other three cases were idiopathic in nature.
|Figure 1: Erythematous edematous nodule to plaque with appearance of pseudovesicular appearance over the back of a female|
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|Figure 2: (a) Skin-colored nodules all over the face with swelling over the submandibular region. (b) Almost clearance of lesions after starting dapsone treatment|
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|Figure 3: (a) Multiple erythematous plaques with erosion and jugular group lymph node enlargement. (b) Erythematous edematous plaque with ulceration|
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|Figure 4: (a) Histopathology showing histologic features of SS with diffuse dermal nodular and perivascular neutrophilic inﬁltrate and edema (H and E, ×10). (b) Histopathology showing diffuse neutrophilic infiltration and edema with few eosinophils (H and E, ×40)|
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|Figure 5: Annular erythematous, infiltrated plaques with pseudovesicle appearance at periphery with central clearing, and wrinkled skin in the center in a 4-year-old patient (Marshall's syndrome)|
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|Figure 6: Multiple erythematous edematous indurated nodule to plaque involving all over the face after diclofenac injection|
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|Figure 7: (a) Multiple erythematous edematous plaques over the cheek, above eyebrow, and pinna of a pregnant female. (b) Multiple erythematous papules over striae gravidarum of a pregnant female|
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| Discussion|| |
The pathogenesis of SS is still unclear, but almost all studies hypothesize it to be a hypersensitivity reaction based on its association with infections, autoimmune and inﬂammatory conditions, malignancies, and drugs., The recent hypothesis suggests an inappropriate regulation of cytokines, among which interleukin (IL)-1, IL-8, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF, and interferon-gamma.
SS is reported all over the world, but its occurrence varies from one region to another. Till now, most of the studies are retrospective. A low incidence of SS (1.18) was reported in Lebanon and a higher incidence (14.6) has been noted in Brazil. The total incidence of SS in our region was around 4 patients per year. SS usually predominates in women compared to men. The reported sex ratios (women to men) vary from 1.1813 to 15. In the present study, the sex ratio was 4.3. Women, in particular in almost all studies, appear to be at risk of idiopathic or drug-induced SS. SS involves all age groups, but its incidence peaks in the ﬁfth and seventh decades. SS is relatively rare among children. The youngest classical SS patient reported was a 7-week-old infant. The earliest cases reported were brothers who developed dermatosis at 10 and 15 days of age.
Clinically, most patients in this study had the typical cutaneous picture of SS which is characterized by the abrupt onset of tender erythematous to violaceous papules or irregularly shaped edematous plaques over the face, upper trunk, and proximal extremities with possible overlying pseudo-vesiculations or pseudo-pustulations. However, other atypical morphological variants are mollascum papuloid-like lesion, only palmoplantar pseudovesicle type, and recurrent symmetrical bullous lesions. The areas primarily affected in classical type of SS are face, neck, chest, back, and upper extremities. In our study, maximum patients developed lesions over the face and lower limb only. The role of UV rays in development of lesions still needs to be evaluated. Almost all parts of the body are involved in malignant and drug-induced variant types.
Clinically, SS presents with fever, malaise, and joint pains, but in other malignancy-associated SS, prodromal symptoms may be absent. Skin lesions usually erupt along with fever and leukocytosis. In some patients, fever precedes the onset of lesions and continues to present till the complete eruption of the lesions. Other symptoms are generalized malaise, headache, and arthralgia. In our study, fever was the most common symptom, but in one case of malignancy-associated SS, fever preceded the onset of lesion and continued till the evolution of lesions. Among laboratory parameters, neutrophilic leukocytosis and increased ESR were the most consistent abnormalities occurring in almost all cases., Leukocytosis, neutrophilia, and increased ESR and positive CRP level were consistent abnormalities in this study, which is in accordance with the data reported in the literature.
However, in SS associated with malignancy eosinophilia was noted. SS may precede or appear concurrently with the underlying malignancy, particularly hematologic malignant disorder, and in general worsens the prognosis. An unusual early onset of the side effects of therapy as a SS in patients with leukemia has also been reported.
In our study, one pediatric case 4-year-old child presented with red raised painful skin lesions on the exposed since 2 months associated with fever. The lesions started as erythematous papules expanded peripherally, forming large round plaque with prominent raised margin. History of similar skin eruptions 1 year back over the forehead, chest, and extremities followed by loose, wrinkled patches in the affected sites. Laboratory parameters show raised leukocyte count, ESR, and neutrophil count, and histopathological reports were consistent with SS in new lesions and cutis laxa in old lesion suggestive of Marshall's syndrome.
SS can occur during pregnancy also, in our study one case developed classical SS lesion and laboratory abnormality.Although exact etiopathogenesis of occurrences of SS during pregnancy is not known, altered levels of estrogen and progesterone causing impairment of immunological response lead to development of SS. SS in pregnancy does not affect the outcome of pregnancy and rapidly responds to corticosteroids.
Several mucocutaneous and systemic disorders can mimic SS whose features morphologically similar to SS. These disorders consist of not only cutaneous conditions and systemic diseases but also infectious and inflammatory disorders, neoplastic conditions, reactive erythemas, and vasculitis. The histologic differential diagnosis of SS includes conditions microscopically characterized by either neutrophilic dermatosis or neutrophilic panniculitis. Sometimes, the culture of lesional tissue for bacteria, fungi, and mycobacteria should be considered to rule out infection since the pathologic changes associated with SS are similar to those observed in an abscess or cellulitis.
The management of SS includes evaluation of the cause and treatment targets, both symptomatic and specific. Some classical SS resolves spontaneously. Drug-induced SS is often occurs and most commonly in females. The diagnosis of drug-induced SS can be made after fulfilling the criteria [[Table 1] part b]. The most common offending drugs are trimethoprim-sulfamethoxazole, minocycline, oral contraceptives, all-trans retinoic acid, granulocyte CSF, furosemide, hydralazine, nitrofurantoin, and rarely diclofenac sodium as observed in our study too. Drug-induced SS responds well when the offending agents were withdrawn.
Surgical intervention is needed in diseases associated with SS such as tonsillitis, solid tumors, or renal failure. In one of our cases which was associated with pleomorphic adenoma, after complete excision of tumor, there was no recurrence of SS lesions.
Various therapeutic options are available for the treatment of SS [Table 3]., Oral, topical, and intralesional steroids are the first-line agents for SS. In our study, a pediatric case diagnosed as Marshall's syndrome was started on oral prednisolone 1 mg/kg, and an excellent response was observed in 1 week, with clearance of almost all the lesions leaving behind hyperpigmented atrophic patches. Prednisolone was tapered over a period of 8 weeks without reappearance of lesions, and the patient was followed up to 1 year, but there was no any recurrence. Almost all other cases were treated with oral steroids only with excellent response. Dapsone can be used as monotherapy and also steroid-sparing agent in the management of SS. In our study, we started dapsone in SS associated with non-Hodgkin lymphoma in two patients 100 mg daily dose, showed dramatic response in 2 weeks and continued for 6 months, no recurrence were noted in the follow-up period of 1 year.
| Conclusion|| |
Thorough clinical knowledge and prompt evaluation will help us to identify the underlying associated conditions and effective management. As in our study, around 80% of cases had underlying conditions. Classical clinical features and histology are most essential in diagnosis of SS. Always in any generalized form of SS, it is mandatory to rule out hematological and other malignancies also. SS can occur during the pregnancy and even without affecting the outcome of the pregnancy. In Marshall's syndrome (acquired cutis laxa) a variant of SS still steroids shows a rapid and excellent response. Dapsone can be considered an alternate therapy in malignancy associated and other variants of SS where steroids cannot be used for long time. Dapsone can also be used along with steroids, but monitoring of side effects should be done.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3]