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| Year : 2014 | Volume
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| Issue : 3 | Page : 401-405 |
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| Sweet's syndrome |
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Piyush G Limdiwala, Shilpa J Parikh, Jigna S Shah
Department of Oral Medicine and Radiology, Government Dental College and Hospital, Ahmedabad, Gujarat, India
Click here for correspondence address and email
| Date of Submission | 04-Oct-2013 |
| Date of Decision | 23-Nov-2013 |
| Date of Acceptance | 19-May-2014 |
| Date of Web Publication | 7-Aug-2014 |
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 Abstract | | |
Acute febrile neutrophilic dermatosis or Sweet's syndrome (SS) is characterized by painful, erythematous plaques of rapid onset accompanied by fever. The etiology of SS is unknown and it may be associated with antecedent infections, malignancies, autoimmune diseases, drugs and vaccines, upper respiratory or gastrointestinal infection, pregnancy, inflammatory bowel disease as well as chemotherapy or idiopathic. The standard therapy for SS is systemic corticosteroids. We report a rare case of 19-year-old young male patient with complaint of severe ill-defined type of pain in both jaws associated with plaques and papules on extensor surfaces of upper and lower extremities with bodyache and myalgia. Histopathological examination suggested perivascular neutrophilic infiltration with scattered eosinophils. Sweet syndrome has rare oral manifestations secondary to hematological changes. It can also present as a paraneoplastic syndrome (malignancy-associated form of condition, which is most commonly related to acute myelogenous leukemia), which leads to poor prognosis and thus it requires careful examination, early diagnosis and long-term follow-up. Keywords: Corticosteroids, cutaneous eruption, granulocyte macrophage - colony stimulating factor, neutrophilic dermatosis, Sweet′s syndrome
How to cite this article:
Limdiwala PG, Parikh SJ, Shah JS. Sweet's syndrome. Indian J Dent Res 2014;25:401-5 |
The Sweet syndrome (SS) was originally described by Dr. Robert Douglas Sweet as in 1964 as an "acute febrile neutrophilic dermatosis"- strange eruption. [1],[2] The etiology of SS is unknown but several features suggest that the dermatosis results from a hypersensitivity reaction to an eliciting antigen; the source of that antigen may be diverse, such as bacterial, viral, or tumoral. SS may be associated with antecedent infections, malignancies, autoimmune diseases, drugs and vaccines, granulocyte-colony stimulating factor as well as chemotherapy or idiopathic (associated with upper respiratory or gastrointestinal infection, viral infections, pregnancy or inflammatory bowel disease). [1],[3],[4],[5],[6] Most commonly it affects women between the ages of 30 and 70 years. However, SS had been reported in children and younger adults. [1],[3] Clinically, it is characterized by acute onset of fever, cutaneous manifestations such as raised painful, erythematous, well-demarcated papules and plaques, which are typically few centimeters in size on the upper extremities, face and neck. Systemic symptoms include malaise, headache, conjunctivitis, arthralgias. However, in some patients with biopsy-confirmed malignancy-associated SS, fever may be absent. Oral, eye (conjunctivitis or episcleritis), alveolitis, sterile osteomyelitis, renal, hepatic, and central nervous system involvement have been frequently reported. [1],[2],[3],[4],[7] Histologically, a dense, perivascular, neutrophilic infiltrate with leukocytoclasis is the hallmark of SS. Mononuclear cells and occasional eosinophils may be interspersed. The inflammatory cells form a band-like infiltrate in papillary dermis. [3],[7] Su and Liu proposed original diagnostic criteria for SS in 1986 and they were modified by von den Driesch in 1994 [6],[8],[9],[10] [Table 1]. It consists of two major and four minor criteria. [1],[5],[6],[10] Both major criteria and two of the four minor criteria are required to establish the diagnosis of classical SS. [1] The standard therapy for SS is systemic corticosteroids. In general prednisolone, given in tapering dose for 2 weeks (40-60 mg/day) is found to be effective. Topical and intralesional steroid administrations have also been used for the primary treatment and in an adjuvant setting. In chronic course of the lesion, steroid sparing drugs are used, such as dapsone, potassium iodide, doxycycline, clofazimine, colchicines, metronidazole, isotretinoin, methotrexate, chlorambucil, cyclosporine, and pulse therapy with methyl prednisolone. [3],[5]
| Case report | |  |
A 19-year-old male Hindu patient referred from skin outpatient department (OPD) to dental OPD, civil hospital with severe, intermittent pain in both right and left posterior buccal vestibular region involving both jaws since 1 month.
Patient was relatively asymptomatic before 2 years. He noticed swelling on lower part of abdomen, followed by fever and headache. For the same, he was admitted to private hospital where only symptomatic treatment was given. Again after a month, he had same complaint and for that he was admitted to private hospital. Investigations were carried out. On blood investigations, Hb was 10.9 g%, white blood cell (WBC) was 7800 cells/cmm and Widal test was positive for Salmonella More Details typhi "O" and "H" having titer of 1:160. Serum creatinine and serum glutamic-pyruvic transaminase were within normal range. Ultrasonography (USG) of abdomen and pelvis showed right inguinal lymphadenopathy. All other organs appeared normal. Patient didn't have further records regarding investigations and treatment taken at private hospital. On symptomatic treatment, patient got temporary relief from abdominal pain. Then after within few months, patient developed skin lesions in form of macules and papules on extensor surfaces of upper and lower extremities which were gradually increasing in size, severity with encrustation along with bodyache and myalgia but without itching and bleeding tendency. On hematologic investigation, it revealed Hb 13 g%, WBC 18300 cells/cmm, Widal test - negative and C-reactive protein (CRP) positive. Venereal disease research laboratory and HIV test were also nonreactive. Gradually skin lesions were increasing in severity, so he was referred to skin OPD, civil hospital.
On extraoral examination, multiple erythematous, tender, ill-defined plaques and papules with crusting were found on middle third of face, extensor surfaces of upper and lower extremities, back and shoulder region [Figure 1], [Figure 2], [Figure 3], [Figure 4]. According to nature of disease, lesion was suspected as Herpes viral infection or erythema mutiforme. Allergy test was performed but it was found nonspecific. Incisional biopsy performed at skin department from lesion on patient's right hand revealed neutrophilic infiltration with scattered eosinophils involving dermal papillae [Figure 5] and it was diagnosed as SS. Patient was admitted for skin lesion at civil hospital and treated with intravenous steroids (inj dexona 1 cc OD for 8 days) followed by oral steroids (tab prednisolone 40 mg/day in tapering dose with 10 mg maintenance dose). Along with tab dapsone 100 mg/day, tab cetrizine, tab paracetamol SOS and multivitamins as a nutritional support was given. Drastic relief was found from symptoms within few days. | Figure 5: Histology of skin biopsy showing neutrophilic infiltration with scattered eosinophils
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Since last 1 month, patient had also developed pain in both jaws. Hence, he was referred to dental OPD, civil hospital for the same. With the presence of skin lesions, intraorally there was palatal erythema on the midline of posterior part of hard and soft palate and on left buccal mucosa [Figure 6]. No vesicles or ulcers on oral mucosa and odontogenic pathology were found for jaw pain. No trigger zones were present on palpation. Panoramic radiograph was taken to rule out any odontogenic foci for pain, but it showed normal bony architecture without any impacted tooth or odontogenic lesion. Hematological investigations were also carried out which showed decreased Hb (9.8 g %), raised erythrocyte sedimentation rate (ESR) (36 mm/h) and elevated WBC count, that is, 9200 cells/cmm of blood. Platelet count was normal in range.
Treatment was continued with steroids and analgesic (tab diclofenac sodium 50 mg BID) SOS was given for jaw pain. On regular follow-up, patient had dramatic relief from jaw pain and healing of skin lesions with pigmentation [Figure 7].
| Discussion and conclusion | | |
Sweet syndrome or Acute febrile neutrophilic dermatosis, which was described by Dr. R.D. Sweet in 1964, is rare immunological mediated condition, characterized by sudden onset of fever, leukocytosis and abrupt onset of tender, painful erythematous well-demarcated papules and plaques containing dense neutrophil infiltrates on histologic examination. [3],[4],[7],[10]
The etiology of SS is unknown, but it is associated with antecedent infections, malignancies, autoimmune diseases, drugs and vaccines as well as chemotherapy. [3],[4],[5],[7] Mostly, it is presumed to be a type of hypersensitivity reaction, which leads to stimulation of a cascade of cytokines that precipitate neutrophils activation and infiltration of T-cell mediated immune response. [7] Human leukocyte antigen (HLA) is presumed to be associated with variable results. In 1988, Mizoguchi described an increased frequency of HLA-Bw54 with a relative risk of 5:1 in Japanese but it was not significantly found in European and Caucasian patients. [7],[11] Some investigators had also reported elevated serum levels of interleukin 1 (IL-1α and β), IL-2 and interferon-γ, but not IL-4 suggest that T H 1 type cytokines expression is involved in pathogenesis of SS. IL-1 is a potent cytokine with multiple immunoregulatory and proinflammatory effects with special effect on neutrophils causing neutrophilic leukocytosis and metabolic activation. [12],[13] Garty et al. suggested a possible role of granulocyte-colony-stimulating factor induced granulopoiesis and granulocyte activation in pathogenesis of SS. [13],[14]
Sweet's syndrome can be associated with upper respiratory tract infection (Streptococcosis), gastrointestinal infections ( Salmonellosis More Details and yersiniosis), inflammatory bowel disease (Crohn's disease, ulcerative colitis), pregnancy, hematological malignancies, solid tumors (mostly of genitourinary tract, breast and gastrointestinal tract [GIT]) and medications related with granulocyte-colony stimulating factor. [15] In our case, patient had initially developed abdominal pain with positive titre of S. typhi and USG of abdomen showed only right inguinal lymphadenopathy, so abdominal pain with GIT infection can be a possible cause. However in majority cases etiology was not specific and onset of pain and other symptoms were sudden in nature as a part of hypersensitivity reaction.
von den Dreisch categorized SS cases into four groups: Classic/idiopathic (71%), para inflammatory (16%), paraneoplastic (11%) and pregnancy- related (2%). [3],[7],[9] The classic/idiopathic form has a significant female predominance whereas the malignant form does not. [7] von den Driesch reviewed seven large series of 176 patients demonstrating an overall female/male ratio of 3.7:1. Atypical presentations of SS occur with equal frequency in both sexes. [3],[5],[9] Mean age of onset of SS is 30-70 years. [1],[2],[3] In presented case, we reported a 19-year-old young male patient with typical findings of SS. In SS, patients have the acute onset of raised painful plaques on the upper extremities, face, and neck. SS include malaise, headache, conjunctivitis, and arthralgias. Fever is common, as is peripheral leukocytosis. Lesions may include vesicles, bullae and ulcers. [2] It is often accompanied by oral signs and symptoms, such as buccal ulcerations, ulcerative stomatitis, recurrent apthous like ulcerations and painful lesions similar to skin eruptions. [13] In SS, laboratory findings are often nonspecific. The ESR is said to be elevated in most of cases. Other include leucocytosis consisting predominantly of neutrophils, anemia, abnormalities in platelet counts (thrombocytosis and thrombocytopenia) and elevated CRP. [1],[5],[7],[15] In this case, patient had all the cardinal signs of classical/idiopathic form (skin lesions, pyrexia, raised ESR, neutrophilia, positive CRP, neutrophilic infiltration) with jaw pain and erythema on hard palate without any ulceration or vesicles at time of reporting.
In drug induced form of SS, neutrophilia is less commonly found. Anemia and elevated alkaline phosphatase are present about half of time. Review suggested that 10-50% of SS may be associated with hematological malignancies or a solid tumor, most commonly acute myelogenous leukemia. [1],[4],[5],[7] The presence of anemia and low platelet count have been associated with an underlying malignancy. [7] In our patient, only increased ESR (>36 mm/h), 18300 cells/cmm WBCs, <10 g% Hb with normal platelet count was found. Other blood reports were also within normal range.
The classic histology finding in SS is a dense diffuse dermal infiltrate of mature neutrophils in the upper and mid-dermis without evidence of vasculitis. The epidermis is usually normal or displays mild reactive changes. Histiocytes and lymphocytes accompanied by leukocytoclasis may predominate the infiltrate in later stages. [5] The inflammatory cells form a band-like infiltrates in the papillary dermis with dermal edema may be seen in neutropenic states. In leukemia associated cases, atypical neutrophilic infiltrates may be seen. [3] In our patient, no such atypical neutrophilic infiltration was found.
Differential diagnosis includes cellulitis, herpes simplex virus infection, leprosy, syphilis, tuberculosis, pyoderma gangrenosum, lymphoma, leucocytoclastic vasculitis, dermatomyositis, and systemic lupus erythematosus, erythema multiforme, erythema nodusum, behchet's syndrome, chronic neutrophilic plaques, bowel bypass syndrome and rheumatoid neutrophilic dermatosis. [2],[5],[7],[10]
Various treatment modalities have been tried with different success rate. The standard therapy for SS is systemic corticosteroids, which usually results in a rapid improvement in symptoms over a course of several hours to days. In general, prednisone or prednisolone in tapering dose (40-60 mg/day) for 2 weeks is effective. However, recurrence is common (25%). In chronic course of the lesion, steroid sparing drugs are used, such as dapsone, potassium iodide, doxycycline, clofazimine, colchicines, metronidazole, isotretinoin, methotrexate, chlorambucil, cyclosporine, and pulse therapy with methyl prednisolone. In chronic recurrent cases an antibiotic such as dapsone or metronidazole is tried first, followed by immunosupressants such as cyclosporine. [3],[5],[7] Pentoxifylline can be given at 400 mg TID, but it proved nonresponsive. [7] The presented case was treated initially with corticosteroid (prednisolone 40 mg) in tapering dose for 2 weeks, followed by dapsone and cetrizine and showed faster response of therapy, but considering the recurrent nature of disease, patient was put on maintenance dose.
In summary, clinical presentation of SS has wide variation in distribution and manifestations depending on form of SS. In this case, a 19-year-old young male patient had been reported with erythema over palatal mucosa and pain in jaws with cutaneous lesions. Occurrence of this disease with oral mucosal lesions is very rare. Review showed that this disease has association with neurological pain and abnormalities along with oral manifestations [3] Furthermore, SS may be associated with malignancy that can lead to poor prognosis. Henceforth oral physician must establish a wide vision toward such type of dermatological lesions with oral manifestations for early diagnosis and better outcome.
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[PUBMED] |
Correspondence Address:
Piyush G Limdiwala
Department of Oral Medicine and Radiology, Government Dental College and Hospital, Ahmedabad, Gujarat
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0970-9290.138358
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1] |
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