Case Presentation: The patient was a 57 year old male with IgG lambda MM (Multiple Myeloma) without remission after autologous hematopoietic stem cell transplant. One month after transplantation, he developed erythematous right flank swelling, high fever, fatigue and anorexia. CT scan revealed inflammatory stranding of right medial gluteal musculature and pre sacral space which was managed with IV antibiotics. His IgG levels were elevated and maintenance treatment with bortezomib and dexamethasone was initiated. However four cycles later, he developed recurrent diffuse erythematous firm swelling, with pain over right thigh. MRI showed large soft tissue defect along anterior proximal right thigh notable for enhancement along superficial fascial planes and deep musculature suggestive of myofascitis. IgG levels at that time were 1544mg/dL. Muscle biopsy was significant for necrotizing myofascitis. He was given a treatment break of 2 months and administered antibiotics. His fasciitis resolved and bortezomib was reinitiated secondary to IgG of 2990 mg/dL. However, after 3 cycles, he presented the third time with a suprapubic indurated tender mass with inflammatory extension to the left medial thigh in association with night sweats and high fevers. ESR and CRP were elevated with low C4 levels. He underwent surgical debridement and pathology was remarkable for focal histiocytic areas with dense neutrophilic infiltrates. He was started on a tapered regimen of high dose prednisone and bortezomib was withheld; leading to excellent response consistent with diagnosis of paraneoplastic Sweet’s Syndrome (SS).

Discussion: SS is a type of acute neutrophilic dermatoses characterized by a heavy dermal infiltrate of neutrophils and variable leukocytoclasis. It lacks cytogenetic specificity and may be secondary to elevated levels of; and enhanced sensitivity to endogenously produced granulocyte colony stimulating factor (G-CSF). High levels of G-CSF lead to increased recruitment of neutrophils; explaining the fever and skin changes. Immunoglobulin secretory status of MM may play a role with prior case reports including ours demonstrating occurrence predominantly in IgG MM. Various drugs have also been implicated in its causation. Though clinical findings mimic autoimmune dermatological conditions like erythema nodusum, erythema multiforme and pyoderma gangrenous, our patient presented atypically with cellulitis and necrotizing fasciitis which were concerning given his immunocompromised status. Salient features in our case including fever, anatomical and chronological multiplicities, antibiotic unresponsiveness, and aggravation after debridement with no proof of infectious disease strongly suggested a case of paraneoplastic atypical Sweet’s Syndrome associated with MM and bortezomib therapy.

Conclusions: Sweet’s syndrome (SS) is a paraneoplastic syndrome characterized by fever, multiple painful erythematous plaques, neutrophilia and a dense dermal neutrophilic infiltration. It is known to have an association with hematologic malignancies such as Acute Myelogenous Leukemia and Myelodysplastic disorders. Paraneoplastic syndromes in MM are rare and physicians should be aware of this complex entity for successful multidisciplinary management.