1. LT Laura Gilbert, MD, Associate CPT Nate Copeland, MD, Associate Catherine F. Decker, MD, Fellow Navy ACP Conference Walter Reed National Military Medical Center October 17, 2014 The Sweet Spot: A Case of Unusual Rash Associated with Cutaneous Trauma

2. Case Presentation 68yF presents with diffuse erythematous, non-pruritic and painful lesions involving face, legs, chest, and back Endorses low grade fever Placed on TMP-SMX post I/D of a left axillary MRSA abscess nine days PTA

3. Past Medical/Surgical History GERD, hyperlipidemia, overactive bladder Hysterectomy Left total knee arthroplasty Jan 2014 – Complicated by post-op MRSA joint infection in Mar 2014 Left axillary MRSA abscess s/p I&D Aug 2014 – Started on TMP-SMX 9 days prior to presentation

4. Social History Non-smoker, rare alcohol, no IV drug use Originally from Thailand No recent travel, sick contacts or tick exposure Swimming in pool 4 days prior to presentation Dog at home, no new pet or animal exposure

5. Medications Outpatient Medications: – Atorvastatin – Aspirin – Esomeprazole – Conjugated Estrogen – Solifenacin Succinate – TMP-SMX Allergies: – Shellfish

6. Physical Exam Vital signs: afebrile HEENT: no conjunctival injection, oral ulcers Extremities: no edema Skin:

10. Complete blood count: – WBC 9.9K, Hgb 11.9 g/dL, Plt 36K (repeat - 22K) Serum chemistry: normal Urinalysis: normal ESR: 43 mm/hr CRP: 9.475 mg/dL Skin biopsy: Laboratory Data

12. Neutrophilic Dermatosis: Differential Diagnosis Infections – Bacterial, Fungal, Mycobacterial Inflammatory diseases – Vasculitis: Polyarteritis nodosa – Erythema nodosum, Pyoderma gangrenosum – Acne fulminans, Psoriasis – Cutaneous Sarcoidosis – Behçet's disease – Sweet Syndrome

13. Sweet Syndrome First described in 1964 – “Acute febrile neutrophilic dermatosis” – Initially called Gomm- Button disease – First reported drug- induced case in 1986 TMP-SMX

14. Characteristics Fever with characteristic rash and pathology – Neutrophilic dermatosis without vasculitis – Rash: painful, raised erythematous papules 3 Major classifications – Classical – Malignancy-associated – Drug-induced

15. Classification Classical – Infections, Inflammatory Bowel Disease, Pregnancy Malignancy-associated Drug-induced – Granulocyte-colony stimulating factor, antibiotics, chemotherapy

16. Clinical Features Cohen PR. Sweet’s syndrome – a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007 Jul; 2:34.

17. Diagnostic Criteria: Drug-induced Sudden onset of painful, erythematous nodules Neutrophilic infiltration of dermis without vasculitis Fever > 38 C Relationship between drug ingestion and symptoms Improvement in symptoms after discontinuation of medication or treatment with steroids

18. Pathophysiology Not well understood Hypersensitivity reaction – Immune reaction to antigen: activation cytokines and PMNs Cytokine dysregulation Genetic susceptibility – HLA B54 linked to Sweet in Japanese women

19. Management Removal of inciting drug if applicable Treatment of underlying condition First line agents: – oral steroids or potassium iodide Second line agents: – Dapsone or Colchicine

20. Hospital Course TMP-SMX and Aspirin were discontinued Dermatology recommendation: no oral steroids Daily CBC – Platelet count recovered to 118K by HD 3 Decrease in erythema Recommended age-appropriate cancer screening TMP-SMX was listed as an allergy

23. Sweet Syndrome and Pathergy Definition: hyper-reactivity of the skin in response to cutaneous trauma Rare association with Sweet syndrome – Case reports associated with burns, radiation, biopsy site, bites, surgical scars First documented case of Sweet syndrome associated with non-acute trauma?

26. Conclusion Sweet syndrome mimics a variety of diseases characterized by rash and a fever Association with malignancy and drugs Biopsy is essential for diagnosis Treatment with oral steroids is gold standard Pathergy is rare clinical manifestation of Sweet syndrome associated with cutaneous trauma

27. References Awan F, Hamadani M, Devine S. Paraneoplastic Sweet’s Syndrome and the pathergy phenomenon. 2007; 86:613-614. Bi XL, Gu J, Yan M, Gao CF. A case of Sweet's syndrome with slack skin and pathergy phenomenon. Int J Dermatol. 2008 Aug; 47(8):842-4. Callen JP. Neutrophilic Dermatosis. Derm Clinics. 2002 Jul; 20:3. Cohen PR. Sweet’s syndrome – a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007 Jul; 2:34. De Moya MA, Wong JT, Kroshinsky D, Robbins GK, Shenoy-Bhangle AS, Gimbel DC. Case records of the Massachusetts General Hospital. Case 28-2012. A 30-year-old woman with shock and abdominal-wall necrosis after cesarean section. N Engl J Med. 2012 Sep 13; 367(11):1046-57. Minocha R, Sebaratnam D, Choi J. Sweet’s Syndrome following surgery: cutaneous trauma as a possible aetiological co-factor in neutrophilic dermatosis. Australias J Derm. Online publication: March 11, 2014. O’Halloran E, Stewart N, Vetrichevvel TP, Rea S, Wood F. Sweet’s syndrome mimicking alkali burn: a clinical conundrum. J Plast Reconstr Aesthet Surg. 2013 Jun; 66(6):867-869. Ramos I, Wiering C, Tebcherani A, Sanchez A. Sweet’s syndrome on surgical scar. An Bras Dermatol. 2006; 81(5):S324-6. Sweet RD. Br J Dermatol. 1964; 76:349-356. Varol A, Seifert O, Anderson C. The skin pathergy test: innately useful? Arch Dermatol Res. 2010; 302:155-168. Walker DC, Cohen PR. Trimethoprim-sulfamethoxazole-associated acute febrile neutrophilic dermatosis: Case report and a review of drug-induced Sweet’s Syndrome. J Am Acad Derm. 1996; 34:918-923.

28. Thank you!