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 Table of Contents  
Year : 2016  |  Volume : 5  |  Issue : 3  |  Page : 178-181

Rare occurrence of bortezomib-induced Sweet's syndrome in multiple myeloma

1 Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
2 Department of Hematology, Army Hospital (R and R), New Delhi, India

Date of Web Publication5-Aug-2016

Correspondence Address:
Dr. Chaturbhuj Agrawal
Room No. 210, Rajiv Gandhi Cancer Institute, Sector 5, Rohini, New Delhi - 110 085
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-344X.187832

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Sweet's syndrome (SS) (acute neutrophilic dermatosis) has already been described in cases of acute leukemia. It has been rarely reported in patients receiving bortezomib therapy for multiple myeloma (MM). A 65-year-old male, who was diagnosed as a case of MM 3 years back, initially received lenalidomide- and dexamethasone-based regimen, followed by lenalidomide maintenance, but subsequently had progressive disease with increasing monoclonal M-spike on serum protein electrophoresis, so shifted to bortezomib and dexamethasone along with monthly zoledronic acid-based treatment. He developed itching over face and neck with darkening and thickening of the skin. Examination revealed hyperpigmentation of face along with excoriation and erosions with involvement of "V" of neck with relative sparing of upper eyelid, postauricular area, and nasolabial folds. Histopathological examination of skin biopsy revealed neutrophilic infiltration of dermis suggestive of SS. A wide variety of cutaneous complications has been described in 10-20% of patients receiving bortezomib. However, SS has rarely been described in such patients with only a few case reports reported so far. Our patient developed features of SS while on bortezomib therapy and had shown dramatic response to bortezomib withdrawal and treatment with oral and topical steroids showing temporal association of this rare syndrome with bortezomib therapy.

Keywords: Bortezomib, hyperpigmentation, Sweet′s syndrome

How to cite this article:
Agrawal C, Kapoor R, Saini R. Rare occurrence of bortezomib-induced Sweet's syndrome in multiple myeloma. Int J Health Allied Sci 2016;5:178-81

How to cite this URL:
Agrawal C, Kapoor R, Saini R. Rare occurrence of bortezomib-induced Sweet's syndrome in multiple myeloma. Int J Health Allied Sci [serial online] 2016 [cited 2023 Oct 4];5:178-81. Available from: https://www.ijhas.in/text.asp?2016/5/3/178/187832

  Introduction Top

Sweet's syndrome (SS) was first described in 1964 by Dr. Robert Douglas Sweet. It is etiologically classified as classical (idiopathic SS), malignancy-associated (paraneoplastic SS), and drug-induced SS. [1] Idiopathic SS is the most common accounting for more than 70% of cases. Approximately, 21% cases are associated with malignancy, and 85% of those are seen with underlying hematological malignancy most commonly acute myelogenous leukemia, myelodysplastic syndromes, and lymphoma. [1] Association with multiple myeloma (MM) is very rare with only 14 cases reported in the literature so far. [2] We herein report a 65-year-old patient, who was on bortezomib therapy, developed SS 3 years after being diagnosed with MM.

  Case Report Top

A 65-year-old male patient, a known case of MM (immunoglobulin G [IgG] type) since 3 years (cytogenetic report not available), initially received lenalidomide- and dexamethasone-based therapy (lenalidomide 25 mg OD day 1-21 and dexamethasone 40 mg OD PO on days 1, 8, 15, and 22 of a 28-day cycle for four cycles), followed by lenalidomide maintenance (lenalidomide 10 mg OD PO day 1-21 of 28 days cycle), had disease progression evident by increasing monoclonal M-spike on serum protein electrophoresis, so started on bortezomib- and dexamethasone-based regimen (injection bortezomib 1.3 mg/m 2 intravenously on days 1, 4, 8, and 11 and dexamethasone 40 mg PO day 1-4 and day 9-12 of a 21 day cycle) with intravenous zoledronic acid 4 mg monthly. While on this treatment regimen, he presented with complaints of multiple red raised painful lesions on his face of 3 days duration. Lesions over his face coalesced within 1 day of their appearance and subsequently similar lesions appeared on his extremities. Associated history of fever with vomiting of 3 days duration was present. Fever was moderate to high grade, intermittent, with chills and rigors. Patient also had four to five episodes of nonprojectile vomiting per day.

Dermatological examination revealed multiple erythematous papules and nodules coalescing to form plaques on forehead, malar region, arms, and thighs [Figure 1] and [Figure 2]. Few of his plaques had hemorrhagic crusting on its surface. No mucosal lesions were found. Investigations revealed hemoglobin of 10.8 g/dl, total leukocytes count 4200/mm 3 with a differential count of 78% neutrophils, and 16% lymphocytes. His erythrocyte sedimentation rate (ESR) was 35 mm fall in the 1 st h, and his C-reactive protein was negative. Skin biopsy showed neutrophilic infiltration of superficial dermis [Figure 3]. A diagnosis of SS secondary to bortezomib therapy was made, bortezomib was withheld for a week, and he was managed with a tapering dose of oral prednisolone starting at 40 mg/day (40 mg/day for 3 days rapidly tapered off within 1 week). Topically, he was prescribed 0.05% Fluticasone cream to be applied twice. Patient had an excellent clinical response to oral and topical steroids and his lesions cleared off within 1 week. He became afebrile, and his vomiting also subsided. After 1 week, he was restarted on bortezomib along with his hematinics.
Figure 1: Multiple erythematous papules and nodules coalescing to form plaques on forearm

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Figure 2: Skin biopsy showing neutrophilic infiltration of superficial dermis

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Figure 3: Multiple papular lesions over pinna of left ear

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  Discussion Top

SS is an acute febrile neutrophilic dermatosis. Diagnostic criteria for SS consist of major and minor criteria. Both the major criteria plus two out of four minor criteria are essential to establish the diagnosis. The major criteria include acute onset of typical lesions in skin and histopathological correlation without evidence of vasculitis. Minor criteria include fever >38°C, associations (malignancy, inflammatory disorders, or pregnancy), excellent response to oral corticosteroids, and abnormal laboratory values (ESR >20 mm, leukocytes >8000/mm 3 , neutrophils >70%, and positive C-reactive protein). [3] Our patient fulfilled both the major criteria as well as three minor criteria.

The etiopathogenesis of SS still remains unclear. Theories proposed include trauma, infection, defective neutrophil chemotaxis/phagocytosis, hypersensitivity reaction, and drugs, mainly granulocyte-monocyte colony-stimulating factor (CSF). Interleukin-6 which is found to be elevated in these cases may be responsible for fever, pain, and raised acute-phase reactants. Hypersensitivity reaction leading to cytokine release and subsequent neutrophil activation seems to be the most probable explanation. granulocyte CSF (GCSF), which is a neutrophil growth factor probably, plays a key role in the pathogenesis. Several reports have described the appearance of SS after GCSF administration. [4] Certain studies have revealed increased levels of endogenous GCSF in acute phase of SS. Structural alterations in the long arm of chromosome 3 have also been seen associated with SS. [5]

The secretory status in MM may influence the occurrence of SS. Among 14 associated cases of SS with MM reported in literature, seven cases were IgG, four IgA, one was free kappa, and two had unknown Ig secretion. [2] Our patient expressed the IgG type. SS is probably related to increase in IgG expression in MM though this frequent association may be related to the point that in MM, IgG is the most commonly secreted Ig. IgG plasma cells have been demonstrated to have a unique constellation of adhesion molecules for leukocyte traffic. It has also been found that GCSF increases expression of IgGFc receptors on neutrophils, so patients with IgG MM may be more prone to developing SS. [6]

Several medications have been incriminated in SS, the most common being GCSF. Other causes include all-trans retinoic acid, carbamazepine, celecoxib, diazepam, diclofenac, hydralazine, levonorgestrel/ethinyl estradiol, minocycline, nitrofurantoin, propylthiouracil, and trimethoprim/sulfamethoxazole. [7] Very recently, proton pump inhibitors causing SS in case of metastatic breast cancer have been described. [8] Bortezomib has also been reported to cause SS. Differential diagnoses include mainly erythema multiforme, erythema elevatum diutinum, erythema nodosum, and pyoderma gangrenosum.

Many previously reported cases of Sweet's syndrome were successfully treated with Systemic corticosteroids [Table 1]. The first-line treatment of SS is systemic glucocorticoids. Systemic symptoms and skin manifestations rapidly respond to therapy. Localized lesions may respond to topical or intralesional corticosteroids. [1] Our patient was managed with bortezomib withdrawal for 1 week and treatment with oral and topical corticosteroids with a good response within 1 week. Many other treatments reported to be successful in treating SS include potassium iodide, colchicine, dapsone, indomethacin, cyclosporine, cyclophosphamide, chlorambucil, doxycycline, and clofazimine. [9] Spontaneous resolution may occur but only after several weeks or months. SS requires a high index of suspicion in MM patients on bortezomib therapy.
Table 1: Previous reports of drug-induced Sweet's syndrome reported in literature

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Conflicts of interest

There are no conflicts of interest.[12]

  References Top

Villarreal-Villarreal CD, Ocampo-Candiani J, Villarreal-Martínez A. Sweet syndrome: A review and update. Actas Dermosifiliogr 2016;107:369-78.  Back to cited text no. 1
Bayer-Garner IB, Cottler-Fox M, Smoller BR. Sweet syndrome in multiple myeloma: A series of six cases. J Cutan Pathol 2003;30:261-4.  Back to cited text no. 2
Cohen PR. Sweet′s syndrome - A comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis 2007;2:34.  Back to cited text no. 3
Ozaki S, Funasaka Y, Takubo M, Matayoshi T, Ueno T, Asayama T, et al. Granulocyte colony-stimulating factor-induced granulomatous dermatitis with enlarged histiocytes clinically manifesting as painful edematous nodules with high fever similar to Sweet′s syndrome. J Dermatol 2015;42:414-7.  Back to cited text no. 4
Parsapour K, Reep MD, Gohar K, Shah V, Church A, Shwayder TA. Familial Sweet′s syndrome in 2 brothers, both seen in the first 2 weeks of life. J Am Acad Dermatol 2003;49:132-8.  Back to cited text no. 5
Ohsaka A, Saionji K, Takagi S, Igari J. Increased expression of the high-affinity receptor for IgG (FcRI, CD64) on neutrophils in multiple myeloma. Hematopathol Mol Hematol 1996;10:151-60.  Back to cited text no. 6
Gilmour E, Chalmers RJ, Rowlands DJ. Drug-induced Sweet′s syndrome (acute febrile neutrophilic dermatosis) associated with hydralazine. Br J Dermatol 1995;133:490-1.  Back to cited text no. 7
Cohen PR. Proton pump inhibitor-induced Sweet′s syndrome: Report of acute febrile neutrophilic dermatosis in a woman with recurrent breast cancer. Dermatol Pract Concept 2015;5:113-9.  Back to cited text no. 8
Cohen PR, Kurzrock R. Sweet′s syndrome revisited: A review of disease concepts. Int J Dermatol 2003;42:761-78.  Back to cited text no. 9
Alsaleh K. Sweet′s syndrome with multiple myeloma. J Appl Hematol 2014;5:69-70.  Back to cited text no. 10
  Medknow Journal  
Llamas-Velasco M, Concha-Garzón MJ, Fraga J, Aragüés M. Histiocytoid sweet syndrome related to bortezomib: A mimicker of cutaneous infiltration by myeloma. Indian J Dermatol Venereol Leprol 2015;81:305-6.  Back to cited text no. 11
[PUBMED]  Medknow Journal  
Zobniw CM, Saad SA, Kostoff D, Barthel BG. Bortezomib-induced Sweet′s syndrome confirmed by rechallenge. Pharmacotherapy 2014;34:e18-21.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]

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